In chronic hepatitis C (CHC) patients, interferon-based treatments showed toxicity, limited efficacy, and psychiatric manifestations. Direct-acting antiviral (DAA) agents appeared safer, though it remains unclear if they may exacerbate or foster mood symptoms in drug-naïve CHC patients. We evaluated 62 CHC patients’ mental status, before and 12 weeks after DAA therapy, by assessment scales and psychometric instruments. We subdivided patients into two groups, CHC patients with (Group A) or without (Group B) a current and/or past psychiatric history. After DAA treatment, Group A patients showed low anxiety and improved depression, no variation in self-report distress, but worse general health perceptions. No significant difference emerged from coping strategies. Depression and anxiety improved in Group B, and no change emerged from total self-reported distress, except for somatization. Moreover, Group B increased problem-focused strategies for suppression of competing activities, and decreased strategies of instrumental social support. Contrarily, Group B reduced significantly emotion-focused strategies, such as acceptance and mental disengagement, and improved vitality, physical and social role functioning. DAA therapy is safe and free of hepatological and psychiatric side effects in CHC patients, regardless of current and/or past psychiatric history. In particular, patients without a psychiatric history also remarkably improved their quality of life.

Increased screen time during the COVID-19 pandemic and the accelerated incorporation of technology into daily practices have directly contributed to the increased prevalence of eye disease. The human eye is not built for continual technological use and must adjust to exposure to digital screens. Overexposure to technology can result in eye strain and an increased risk of eye diseases such as myopia with complications later in life, including retinal tears, cataracts, and macular degeneration. As vision and ocular diseases become more prevalent, the study of eye diseases, including their causes and treatments, is especially relevant. There is a need to prevent ocular diseases before they become a burden to individuals, their families, and their communities by better understanding the pathophysiology of ocular diseases. Several ocular diseases are thought to be caused by imbalances in reactive oxygen species (ROS) and autophagy. ROS refers to a class of highly reactive oxygen-containing molecules that can undergo damaging reactions with other molecules in the cell. Autophagy is a cellular process of self-eating whereby damaged, harmful, or dead material in cells is broken down to maintain cellular homeostasis. This paper discusses the role of ROS and autophagy in the pathogenesis of computer vision syndrome (CVS), digital eye strain (DES), myopia, cataracts, glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve crush injury (OCN), optic nerve gliomas, and retinoblastoma. Lifestyle changes such as limiting screen time, ensuring adequate exposure to evening sunlight, and using blue light protection measures or protective eyewear are important in the prevention of eye disease. Nutrition also contributes significantly to eye health. A balanced diet rich in vitamins and antioxidants may help to prevent ROS and autophagy imbalance-induced eye disease. Medical and surgical treatments become necessary when preventative measures fail. This paper also addresses how government measures to decrease the onset of eye disease, including targeted programs to increase access to fresh vegetables and fruits in food deserts, are a critical macro-level avenue to reduce eye disease prevalence in the US, which according to the National Eye Institute, costs $139 billion yearly.

Background: Angelica gigas Nakai, Korean dang-gui, has long been widely used in traditional treatment methods. There have been a number of studies of the health effects of A. gigas and related compounds, but studies addressing effects on blood triglycerides (TG) are lacking. To investigate the effects of A. gigas Nakai extract (AGNE) on TG in Korean subjects, we carried out a 12-week, randomized, double-blind, placebo-controlled clinical trial. Methods: Subjects who met the inclusion criterion (130 mg/dL ≤ fasting blood TG ≤ 200 mg/dL) were recruited for this study. One hundred subjects were assigned to the AGNE group (n=50) or the placebo group (n=50), who were given 1g/day of AGNE (as a gigas Nakai extract 200mg/d) in capsules, and the control group for 12 weeks. Outcomes were efficacy TG, lipid profiles, atherogenic index, and safety parameters were assessed initially for a baseline measurement and after 12 weeks. Results: After 12 weeks of supplementation, TG and very low-density lipoprotein cholesterol (VLDL-C) concentration and TG/HDL-C ratio in the AGNE group were significantly reduced compared to the placebo group (p <0.05). No significant changes in any safety parameter were observed. Conclusions: These results suggest that ingestion of AGNE may improve TG and be useful to manage or prevent hypertriglyceridemia.

The emergence of chemoresistance in neoplastic cells is one of the major obstacles in cancer therapy. Autophagy was recently reported as one of the mechanisms that promote chemoresistance in cancer cells by protecting from apoptosis and driving senescence. Thus, understanding the role of autophagy and its underlying signaling pathways is crucial for the development of new therapeutic strategies to overcome chemoresistance. We have previously reported that PKCη is a stress-induced kinase that confers resistance in breast cancer cells against chemotherapy by inducing senescence. Here we show that PKCη promotes autophagy induced by ER and oxidative stress and facilitates the transition from autophagy to senescence. We demonstrate that PKCη knockdown reduces both the autophagic flux and markers of senescence. Additionally, using autophagy inhibitors, such as chloroquine and 3-methyladenine, we show that PKCη and autophagy are required for establishing senescence in MCF-7 in response to oxidative stress. Different drugs used in the clinic are known to induce autophagy and senescence in breast cancer cells. Our study proposes PKCη as a target for therapeutic intervention, acting in synergy with autophagy-inducing drugs, to overcome resistance and enhance cell death in breast cancer.

SCARED-C instrument (the child version, 41 items) is used for screening anxiety in children between 8 to 18 years old and has been first introduced by Birmaher & collab. in 1995, with good psychometric data - internal consistency from α =.74 to .93 - and good discriminative validity indices in the original versions (1997, 1999). Since then, many countries have adopted the scale, for its utility in identifying five subsets of anxiety disorders (subscales): somatic/panic disorder, generalized anxiety, separation anxiety, social phobia, and school avoidance. The present study contains the first Romanian translated and adapted version of the SCARED-C instrument on a community sample of 477 children (8-18 years old) from Mureș county schools. The instrument showed moderate to good internal consistency (α Cronbach from to .63 to .91 for the total scale) and good test-retest reliability (.70) on a subset of 85 children sample. A confirmatory factorial analysis (CFA) was conducted to test the factor structure of the Romanian version of SCARED-C; results showed that SCARED-C has good psychometric properties to be used for screening anxiety in Romanian children and adolescents. The implications for using SCARED-C in dental practice are discussed. Future studies need to be conducted for exploring convergent and discriminative validity of the instrument and the sensitivity to current DSM-V criteria. Application on a dental pediatric sample is also required.

This comprehensive analysis thoroughly examines the topic of adversarial attacks in artificial intelligence (AI), providing a detailed overview of the various methods used to compromise machine learning models. It explores different attack techniques, ranging from the simple Fast Gradient Sign Method (FGSM) to the intricate Carlini and Wagner Attack (C&W), emphasising the wide range of adversarial approaches and their intended goals. The discussion also distinguishes between targeted and non-targeted attacks, highlighting the adaptability and versatility of these malicious efforts. Additionally, the study delves into the realm of black-box attacks, revealing the capability of adversarial strategies to compromise models even with limited knowledge. Real-life examples illustrate the tangible consequences and potential dangers of adversarial attacks in various fields such as self-driving cars, multimedia, and voice assistants. These cases highlight the difficulties in ensuring the legitimacy and dependability of AI-powered technologies and programs. The article stresses the importance of ongoing research and innovation to address the growing difficulties posed by advanced methods like deepfakes and disguised voice commands in preserving the security of AI systems. This study provides valuable insights on how different adversarial strategies and defence mechanisms interact within AI. The results emphasise the urgent need for stronger and more secure AI models to combat the increasing number of adversarial threats in today's AI landscape. These findings can guide future research and innovations in developing more resilient AI technologies that can better withstand various adversarial vulnerabilities and challenges.

Acute myeloid leukaemia (AML) is characterized by the accumulation of undifferentiated blast cells in the bone marrow and blood. In most AMLs, relapse frequently occurs due to resistance to chemotherapy. Compelling research results indicate that drug resistance in cancer cells is highly dependent on the intracellular levels of reactive oxygen species (ROS). Modulating ROS levels is therefore a valuable strategy to overcome the chemotherapy resistance of leukemic cells. In this study, we evaluated the efficiency of diphenyleneiodonium (DPI), a well-known inhibitor of ROS production, in targeting AML cells. Results showed that although inhibiting cytoplasmic ROS production, DPI triggered an increase in the mitochondrial ROS levels caused by the disruption of the mitochondrial respiratory chain. We also demonstrated that DPI blocks the mitochondrial oxidative respiration (OxPhos) in a dose-dependent manner and that AML cells with high OxPhos status were highly sensitive to treatment with DPI, which synergizes with the chemotherapeutic agent cytarabine (Ara-C). Thus, our results suggest that targeting mitochondrial function by DPI might be exploited to target AML cells with high OxPhos status.

Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with a low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology ranging from clinical activity to genealogical reconstruction of families/populations along the centuries, creation of databases, and molecular/genetic research, has been modelled on the characteristics of the Calabrian population for more than three decades. This methodology allows to the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, in this population it has been reported a higher prevalence of several hereditary neurodegenerative diseases such as Alzheimer’s disease, Frontotemporal dementia, Parkinson’s disease, Niemann Pick type C disease, Spino-cerebellar ataxia, Creutzfeldt–Jakob disease and Gerstmann Straussler Scheincker disease. Thus, Calabria constitutes a model for the study of neurodegenerative diseases, a sort of "outdoor laboratory" useful for the advancement of knowledge in this field. Here, we summarize and discuss some results of research data supporting the view that Calabria is a genetic isolate and could represent a useful model for the study and characterization of neurodegenerative diseases.

I propose a new strategy to suppress human cancer completely with two entirely new drug compounds exploiting cancer's Warburg effect characterized by a defective mitochondrial aerobic respiration, substituted for by cytosolic aerobic fermentation/glycolysis of D-(+)-glucose into L-(+)-lactic acid. The two essentially new drugs compound 1 [P(op)T(est)162] and compound 3 (PT167) represent new highly symmetric, four-bladed propeller-shaped polyammonium cations. The in vitro antineoplastic highly efficacious drug compound 3 represents a covalent combination of compound 1 and compound 2 (PT166). The intermediate drug compound 2 is an entirely new colchic(in)oid derivative synthesized from colchicine. Compound 2's structure was determined by X-ray crystallography. Compound 1 and compound 3 were active in vitro versus 60 human cancer cell lines of the National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) 60-cancer cell testing. Compound 1 and compound 3 both not only stop the growth of cancer cells to ±0% (cancerostatic effect), but completely kill nearly all 60 cancer cells to a level of almost −100% (tumoricidal effect). Compound 1 and compound 3 induce mitochondrial apoptosis (under cytochrome c release) in all cancer cells tested by (re)activating (in most cancers impaired) p53 function which results in a decrease of cancer's dysregulated cyclin D1 and an induction of the cell cycle-halting cyclin-dependent kinase inhibitor p21^Waf1/p21^Cip1.

Cellular Vehicle-to-Everything (C-V2X) is a communication technology that supports various safety, mobility, and environmental applications given its higher reliability properties compared to other communication technologies. The performance of these C-V2X-enabled Intelligent Transportation System (ITS) applications is affected by the performance of the C-V2X communication technology (mainly packet loss). Similarly, the performance of the C-V2X communication is dependent on the vehicular traffic density which is affected by the traffic mobility patterns, and vehicle routing strategies. Consequently, it is critical to develop a tool that can simulate, analyze, and evaluate the mutual interactions of the transportation and communication systems at the application level and to the evaluate the benefits of the C-V2X enabled ITS applications. In this paper, we demonstrate the benefits gained when using C-V2X Vehicle-to-Infrastructure (V2I) communication technology in an energy-efficient dynamic routing application. Specifically, we develop a Connected Energy-Efficient Dynamic Routing (C-EEDR) application using C-V2X as a communication medium in an integrated vehicular traffic and communication simulator (INTEGRATION). The results demonstrate that the C-EEDR application achieves fuel savings of up to 16.6% and 14.7% in the IDEAL and C-V2X communication cases, respectively for a peak hour demand on the downtown Los Angeles network considering a 50% level of market penetration of connected vehicles. The results demonstrate that the fuel savings increase with increasing levels of market penetration at lower traffic demand levels (25% and 50% the peak demand). At higher traffic demand levels (75% and 100%) the fuel savings increase with increasing levels of market penetration with maximum benefits at a 50% market penetration rate. Although the communication system is affected by the high density of vehicles at the high traffic demand levels (75% and 100% the peak demand), the C-EEDR application manages to perform reliably producing system-wide fuel consumption savings.The C-EEDR application achieves fuel savings of 15.2% and 11.7% for the IDEAL communication and 14% and 9% for the C-V2X communication at the 75% and 100% market penetration rates, respectively. Finally, the paper demonstrates that the C-V2X communication constraints only affect the performance of the C-EEDR application at the full demand level when the market penetration of connected vehicles exceeds 25%. This degradation, however is minimal (less than a 2.5% reduction in fuel savings).

The treatment of the bulky Rind-based dibromosilanes, (Rind)2SiBr2 (2) [Rind = 1,1,7,7-tetra-R1-3,3,5,5-tetra-R2-s-hydrindacen-4-yl: EMind (a: R1 = Et, R2 = Me) and Eind (b: R1 = R2 = Et)], with two equivalents of tBuLi in Et2O at low temperatures resulted in the formation of blue solutions derived from the diarylsilylenes, (Rind)2Si: (3). Upon warming the solutions above −20 °C, the blue color gradually faded, accompanying the decomposition of 3 and yielding the cyclic hydrosilanes (4) via intramolecular C−H bond insertion at the Si(II) center. The molecular structures of the bulky Eind-based 3b and 4b were confirmed by X-ray crystallography. Thus, at −20 °C, blue crystals were formed (Crystal-A), which were identified as mixed crystals of 3b and 4b. Additionally, colorless crystals of 4b as a singular component were isolated (Crystal-B), whose structure was also determined by an X-ray diffraction analysis. Although the isolation of 3 was difficult due to their thermally-labile nature, their structural characteristics and electronic properties were discussed based on the experimental findings complemented by computational results. We also examined the hydrolysis of 3b to afford the silanol, (Eind)2SiH(OH) (5b).

The demand for dietary supplements containing collagen has been growing for years. The speciality and uniqueness of the dietary supplement (DS) examined in our study is the presence of L-arginine and hyaluronic acid alongside collagen and vitamin C. The individual mechanisms of action and physiological role of these compounds are understood, but they have not yet been tested in the combination and amounts of the dietary supplement used in this study. In this study, we investigated the effectiveness of the DS in elderly patients with musculoskeletal complaints. Somatometric, body composition, physiotherapy and laboratory tests were performed at the beginning and at the end of the study. The two-month study involved 30 people, randomly divided into two groups: a control group (CG) and an experimental group (EG). All subjects consumed 25 ml DS per day and EG members also participated in physiotherapy 3 times a week. Alongside the DS, blood lipid levels changed: LDL decreased, HDL increased, LDL/HDL ratio significantly decreased in both groups. For EG, the results improved more markedly. In 3 items of the body composition test, there was a significant improvement in both groups, which was attributed to the use of the dietary supplement. For the EG, there were significant changes in 5 additional test items, which we attribute to the addition of regular physical activity. Knee and hip joint range of motion (ROM) showed significant improvements in the study group, while in the CG the DS can cause significant improvements in joint range of motion in a passive condition as well.

Type 2 diabetes mellitus may be complicated with chronic complications including diabetic neuropathy (DN). Timely diagnosis is crucial in treatment and maybe reversal of this complication. C reactive protein to albumin ratio (CAR) is considered as a marker of inflammation in various diseases that characterized with acute or chronic inflammation. Since diabetic neuropathy and type 2 diabetes mellitus are also associated with chronic, low grade inflammation, we aimed to study CAR levels of type 2 diabetic subjects with diabetic neuropathy and to compare to those in patients without diabetic neuropathy. Type 2 diabetic patients presented to our institutional outpatient clinics were divided into two according to the presence of DN. Subjects with DN were listed as DN group and others were as non-DN group. Characteristics and laboratory data, including CAR, in DN and non-DN groups were compared. Median CAR of the DN and non-DN groups were 2,19 (0,2-49)% and 0,56 (0,02-5,8)%, respectively (p&lt;0.001). CAR was significantly and positively correlated with age (r=0.15, p&lt;0.001), weight (r=0.19, p=0.01), BMI (r=0.11, p=0.03), waist circumference (r=0.10, p=0.046), fasting plasma glucose (r=0.14, p=0.004), serum creatinine (r=0.25, p&lt;0.001), triglyceride (r=0.17, p&lt;0.001), and LDL-cholesterol (r=0.13, p=0.001) levels. Moreover, CAR was inversely correlated with eGFR levels (r=-0.16, p&lt;0.001). The sensitivity and specificity of CAR (when higher than 1,02%) in predicting diabetic neuropathy were 78% and 73%, respectively (AUC: 0.84, p&lt;0.001, 95% CI: 0,82-0,87). Moreover, high CAR level was an independent risk factor of diabetic neuropathy (p&lt;0.001, OR: 1.34, 95% CI: 0.48-1.62). In conclusion, elevated CAR levels could be considered as a marker of diabetic neuropathy.

COVID-19 infection in the pediatric population usually leads to a mild illness, however, a rare but serious complication of MIS-C has been seen in children. MIS-C usually presents 2-4 weeks after COVID-19 infection or exposure, and rare reports have been documented in neonates. Vaccinations for COVID-19 have been approved for children 6 months and above in the United States, and recent reports suggest significantly low prevalence and risk of complications of MIS-C in vaccinated children compared to unvaccinated children. Vaccinations for COVID-19 are safe and recommended during pregnancy and prevent severe maternal morbidity and adverse birth outcomes. Evidence from other vaccine-preventable diseases suggests that through passive transplacental antibody transfer, maternal vaccinations are protective against infections in infants during the first 6 months of life. Various studies have demonstrated that maternal COVID-19 vaccination is associated with the presence of anti-spike protein antibodies in infants, persisting even at 6 months of age. Further, completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy is associated with reduced risk for COVID-19–associated hospitalization among infants aged 6 months or less. Therefore, it can be hypothesized that maternal COVID-19 vaccination can reduce the risk of and severity of MIS-C in infants. In this article, we review the literature to support this hypothesis.

The symmetries of a Riemann surface $\Sigma \setminus \{a_i\}$ with $n$ punctures $a_i$ are encoded in its fundamental group $\pi_1(\Sigma)$. Further structure may be described through representations (homomorphisms) of $\pi_1$ over a Lie group $G$ as globalized by the character variety $\mathcal{C}=\mbox{Hom} (\pi_1,G)/G$. Guided by our previous work in the context of topological quantum computing (TQC) and genetics, we specialize on the $4$-punctured Riemann sphere $\Sigma=S_2^{(4)}$ and the \lq space-time-spin' group $G=SL_2(\mathbb{C})$. In such a situation, $\mathcal{C}$ possesses remarkable properties (i) a representation is described by a $3$-dimensional cubic surface $V_{a,b,c,d}(x,y,z)$ with $3$ variables and $4$ parameters, (ii) the automorphisms of the surface satisfy the dynamical (non linear and transcendental) Painlev\'e VI equation (or $P_{VI}$), (iii) there exists a finite set of $1$ (\mbox{Cayley-Picard})+$3$ (\mbox{continuous platonic})+$45$ (\mbox{icosahedral}) solutions of $P_{VI}$. In this paper we feature on the parametric representation of some solutions of $P_{VI}$, (a) solutions corresponding to algebraic surfaces such as the Klein quartic and (b) icosahedral solutions. Applications to the character variety of finitely generated groups $f_p$ encountered in TQC or DNA/RNA sequences are proposed.

A hydrothermal technique with microwave heating (200 °C, 2 hours, 2 magnetrons, 2.45 GHz) was modified to obtain UV-C luminescent LaPO4: Pr3+ colloidal nanorods for the potential use in X-ray cancer theranostics. For further possible biofunctionalization, a compound of tartaric acid formed under basic conditions was used as a coating and stabilizing agent to provide colloidal properties to the surface of nanoparticles in basic to neutral aqueous media, which was confirmed by zeta potential measurements. In addition, the colloidal properties and clustering processes of synthesized LaPO4:Pr3+ nanorods in aqueous solutions with different pH values were studied in real time using a highly sensitive laser ultramicroscope operating according to the “light-sheet” scheme. A comparative analysis of the transmission electron microscopy, X-ray powder diffraction and high-energy spectroscopy showed the different effects of synthesis parameters on the morphological, crystalline and luminescent properties of the obtained nanorods. Through optimization of the synthesis parameters, stable aqueous solutions of m-LaPO4:Pr3+ nanorods with sizes less than 30 nm and an intensity of UV-C luminescence equal to 5-10% of the unmodified nanofibers were obtained.

The effect of the antioxidant vitamin C in cancer has been studied for over 30 years with conflict-ing results ranging from total absence of effect, to possible protective effect, to potential therapeutic effect when administered in high doses. The aim of the study was to define the effect of vitamin C in breast cancer and the possible involvement of sphingomyelin metabolism. Therefore, the effect of low and high dose of vitamin C on cells reproducing luminal A type (MCF7) and triple negative type (MB231) of breast cancer was analyzed. The results showed that high dose of vitamin C produced effects only in MCF7 cells such as decreased cell viability, modulation of cell cycle re-lated genes, unexpected change in cell phenotype due to estrogen receptor downregulation, catabo-lism of sphingomyelin with a large increase in ceramide. In conclusion, we demonstrated that high doses of VitC on the one hand reduce the growth of lu-minal A type breast cancer cells and on the other hand induce their phenotypic change towards hormone therapy resistant cells. The effect of vitamin C on therapeutic treatment failure of luminal A breast cancer and the possible involvement of high ceramide levels were discussed.

Prostate cancer (PC) is the most frequently diagnosed non-skin cancer in the world. Previous studies showed that genomic alterations represent the most common mechanism for molecular alterations that cause the development and progression of PC. Great efforts have been done to identify common protein-coding genetic variations; however, the impact of non-coding variations including regulatory genetic variants is not still well understood. To gain an understanding of the functional impact of genetic variants, particularly, regulatory variants in PC, we developed an integrative pipeline (AGV) that used whole genome/exome sequences, GWAS SNPs, chromosome conformation capture data, and ChIP-Seq signals to investigate the potential impact of genomic variants on the underlying target genes in PC. We identified 646 putative regulatory variants, of which 30 of them significantly altered the expression of at least one protein-coding gene. Our analysis of chromatin interactions data (Hi-C) revealed that the 30 putative regulatory variants may affect 131 coding and non-coding genes. Interestingly, our study showed the 131 protein-coding genes are involved in disease-related pathways including Reactome and MSigDB in which for most of them targeted treatment options are currently available. Together, our results provide a comprehensive map of genomic variants in PC and revealed their potential contribution to prostate cancer progression and development.

Blackcurrant juice (Ribes nigrum L.) was subjected to supercritical carbon dioxide (SCCD) at 10, 30 and 60 MPa for 10 min at 45°C as well as thermally treated at 45°C and 85°C for 10 min to determine the stability, antioxidant capacity (AC) and bioaccessibility (BAc) of vitamin C, total anthocyanins and their individual monomers. An in vitro gastrointestinal digestion model completed with dialysis was used to assess BAc. The use of SCCD at each of the pressures applied improved the stability of vitamin C, total anthocyanins, and AC before in vitro digestion. As a result of digestion, L-ascorbic acid was oxidized to L-dehydroascorbic acid, and finally, the total content of vitamin C, anthocyanins, and AC decreased. SCCD did not significantly improve the BAc of vitamin C and total anthocyanins. The highest BAc of vitamin C was noted in fresh juice (FJ) (40%) and after mild heat treatment at 45°C (T45) (46%). The highest BAc of total anthocyanins was also noted in the FJ (4.4%). The positive effect of the application of SCCD on the BAc of the delphinidin-3-O-glycosides was observed compared to T45 and thermal pasteurization at 85°C (T85). Moreover, cyanidins were generally more bioaccessible than delphinidins in all samples. AC after digestion was higher in SCCD samples compared to thermally treated measured using ABTS+• and DPPH• assays, whereas in dialysate similar trends were observed only for AC measured using the ABTS+• assay. This phenomenon was justified by the formation of individual metabolites detected by UPLC-PDA-MS / MS in the model experiment with delphinidin-3-O-rutinoside. The protocatechuic acid which is well known as a strong antioxidant was detected in the model experiment after digestion. Further research is needed to better understand the metabolic pathway of anthocyanins and the possible uses of SCCD to improve the health properties of fruit products.

Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras expressing or transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Oncogenes induce replication stress, re-sulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment cause toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overex-pressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but interestingly not by nucleoside supplementation. This suggest that cancer selectivity is unrelated oncogene-induced replication stress. We conclude that the molecular toxi-cological mechanisms how TH588 and TH1579 kill c-Myc overexpressing cells have several com-ponents and involves MTH1-independent proteosomal degradation of c-Myc itself, c-Myc driven transcription and CDK activation, and is likely unrelated to oncogene-induced replication stress.

Coastal resources in Lian, Batangas, have undergone significant degradation due to a combination of human activities and natural factors, including sea-level rise, changes in sea-surface temperature, fluctuations in rainfall, increased storm frequency, and sedimentation. This has led to adverse effects on key ecosystems such as corals, mangroves, and seagrasses. To assess the extent of climate change hazards on these coastal resources, a Vulnerability Assessment was conducted in the municipality of Lian, Batangas. The assessment employed a combination of the Coastal Integrity Vulnerability Assessment Toolkit (CIVAT) and Integrated Coastal Sensitivity, Exposure, and Adaptive Capacity to Climate Change (ICSEA-C) guidelines. Additionally, the analysis incorporated detailed mapping using Light Detection and Ranging (LiDAR) data for mangroves and LandSat 8 imagery for corals and seagrasses. The findings at the municipal scale revealed that a staggering 90% of mangroves in Lian, Batangas, were highly vulnerable. This vulnerability was attributed to a high score in intrinsic characteristics and a low adaptive capacity. Similarly, a majority of seagrasses in the area were classified as medium and highly vulnerable at the municipal level. Only 10–20% of seagrasses received low to medium vulnerability scores. Shockingly, almost 100% of the coral reefs in Lian, Batangas, were deemed highly vulnerable, indicating a critical threat to this crucial marine ecosystem.

We study C*-algebraic versions of following conjectures/theorems: (1) Bieberbach conjecture (de Branges theorem) (2) Robertson conjecture (3) Lebedev-Milin conjecture (4) Zalcman conjecture (5) Krzyz conjecture (6) Corona conjecture (Carleson theorem). We prove that the C*-algebraic Bieberbach Conjecture for invertible coefficients is true for second degree C*-algebraic polynomials.

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique at-tributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two preg-nancies, which occurred 4 years apart, without evidence of human immunodeficiency virus or hepatitis C virus infection. The second pregnancy was complicated by congenital heart disease. A high level of HPgV infection was detected in maternal blood from different trimesters by RT-PCR and identified as HPgV type 1 genotype 2 in both pregnancies. In the second pregnancy, the decidua and intervillous tissue of the placenta were positive for HPgV by PCR but not the chorion or cord blood (from both pregnancies), suggesting no vertical transmission despite high levels of viremia. The HPgV genome sequence was remarkably conserved over the 4 years. Using VirScan, sera antibodies for HPgV were detected in the first trimester of both pregnancies. We observed the same anti-HPgV antibodies against the non-structural NS5 protein in both pregnancies, suggesting a similar non-E2 protein humoral immune response over time. To the best of our knowledge, this is the first report of persistent HPgV infection involving placental tissues with no evidence of vertical transmission. Our results reveal a more elaborate viral-host interaction than previously reported, expand our knowledge about tropism, and opens avenues for exploring the replication sites of this virus.

This paper investigates whether currency risk is priced differently in the different sectors (industrial, financial, and basic materials) of equity markets in a sample of developed United States of America (USA) and developing economies (Brazil, India, Poland, and South Africa). The paper makes use of the following techniques: (i) Univariate Autoregressive Fractionally Integrated Moving Average and Exponential General Autoregressive Conditional Heteroskedastic (ARFIMA-EGARCH), (ii) the Markov-Switching method (MS), and (iii) the Canonical Vine Copulas (C-Vine) techniques. Using a sample of daily data made of the foreign exchange rate against the domestic currency and equity market sectors; our findings show that there is an asymmetry effect between equities markets and the foreign exchange rate: there is a heterogeneous, strong, and positive dependence between the two. Higher equities prices are associated with depreciation of local currencies, according to US dollar (USD) exchange rates. In addition, we find that the selected emerging economies are pricing a positive and considerable currency risk. The pricing of currency risk has a varied effect in both regimes representing the states of the economy. In fact, when currency risk pricing has a beneficial impact on certain sectors of the economy, investors predict better returns.

Steel slag is a co-product of the steelmaking industry, this material is rarely used as a binder due to its low cementitious properties. Thus, it´s believed that the alkaline activation of steel slag can enable its use as a cementitious material. This work has the objective of making a systematic bibliographic review on the theme "slag melt as a precursor in activated alkali binders". To this end, the ProKnow-C method was used for the selection and analysis of relevant research on the topic. The portfolio resulted in 71 texts, mostly journals paper. Bibliometrics showed that the country with the most publications is China and the journal with the most publications is Construction and Building Materials. The critical analysis concluded that the XRD, XRF, and compressive strength tests are the most used for the characterization of the material. It is possible to establish that there are some knowledge gaps on the subject, such as better mechanical characterization and greater production of works with dosing by the one-part method.

G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs, however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of Class C GPCRs and speculate on their corresponding therapeutic potential.

The efficiency and performance of Proton Exchange Membrane Fuel Cells (PEMFCs) are primarily influenced by ORR electrocatalysts. In recent years, atomically dispersed met-al-nitrogen-carbon (M-N-C) catalysts have gained significant attention due to their high active center density, high atomic utilization, and high activity. These catalysts are now considered the preferred alternative to traditional noble metal electrocatalysts. The unique properties of M-N-C catalysts are anticipated to enhance the energy conversion efficiency and lower the manufac-turing cost of the entire system, thereby facilitating the commercialization and widespread ap-plication of fuel cell technology. This article initially delves into the origin of performance and degradation mechanisms of Fe-N-C catalysts from both experimental and theoretical perspectives. Building on this foundation, the focus shifts to strategies aimed at enhancing the activity and durability of atomically dispersed Fe-N-C catalysts. These strategies encompass the use of bi-metallic atoms, atomic clusters, heteroatoms (B, S, and P), and morphology regulation to optimize catalytic active sites. The article concludes by detailing the current challenges and future pro-spects of atomically dispersed Fe-N-C catalysts.

In Southeast Asia, the incidence of Leukemia, a malignant blood cancer originating from hema-topoietic progenitor cells, is on the rise, marked by a concerning 54% mortality rate. This study focuses on enhancing early-stage prediction to improve patient recovery prospects significantly. Leveraging Machine Learning and Data Science, we employ protein sequential data from frequently mutated genes such as BCL2, HSP90, PARP, and RB to predict Chronic Myeloid Leukemia (CML). Our approach relies on robust feature extraction techniques, namely Di-peptide Composition (DPC), Amino Acid Composition (AAC), and Pseudo amino acid composition (Pse-AAC), with prior attention to addressing outliers and validating feature selection through the Pearson Corre-lation Coefficient. Data augmentation ensures a well-rounded dataset for analysis. Employing a range of Machine Learning models, including Support Vector Machine (SVM), XGBoost, Random Forest (RF), K Nearest Neighbor (KNN), Decision Tree (DT), and Logistic Regression (LR), we achieve accuracy rates spanning from 66% to 94%. These classifiers undergo comprehensive as-sessment using performance metrics such as accuracy, sensitivity, specificity, F1-score, and the confusion matrix. Our proposed solution, encompassing a user-friendly web application dashboard, presents an invaluable tool for early CML diagnosis with profound implications for practitioners, offering a deploy-able asset within healthcare institutions and hospitals.

CRISPR-Cas allows us to introduce desired genome editing, including mutations, epitopes, and deletions with unprecedented efficiency. The development of CRISPR-Cas has progressed to such an extent that it is now applicable in various fields with the help of model organisms. C. elegans is one of the pioneering animals in which numerous CRISPR-Cas strategies have been rapidly es-tablished over the past decade. Ironically, the emergence of numerous methods makes the right choice of method difficult. Choosing an appropriate selection or screening approach is the first step in planning a genome modification. This report summarizes the key features and applications of CRISPR-Cas methods using C. elegans and illustrates key strategies. Our overview of significant advances in CRISPR-Cas will help readers to understand current advances in genome editing and navigate various methods of CRISPR-Cas genome editing.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

In the multicenter, non-randomized, exploratory C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) 3-9 d after onset of STEMI symptoms and quantified by myocardial infarct size (IS; %), left ventricular ejection fraction (LVEF; %), circumferential strain (CS) and longitudinal strain (LS) Compared with the control group (n=34), cardiac damage was significantly lower in the apheresis group (n=32). These findings suggested improved wound healing due to CRP apheresis already within few days after the STEMI event. In the current supplementary data analysis of CAMI-1, we have tested by a follow-up CMR (CMR2) after an average of 88 (65-177) d whether the effect of CRP apheresis is clinically maintained. After this time period wound healing in STEMI is considered complete. Whereas patients with low CRP production and a CRP gradient cut off of &lt;0.6 mg/L/h in the hours after STEMI (9 of 32 patients in the CRP apheresis group) did not significantly benefit from CRP apheresis in CMR2, patients with high CRP production and a CRP gradient cut off of &gt;0.6 mg/L/h (23 of 32 patients in the CRP apheresis group) showed significant treatment benefit. In the latter patients, CMR2 revealed a lower IS (-5.4%; p=0.05), a better LVEF (+6.4%; p=0.03), and an improved CS (-6.1%; p=0.005). No significant improvement, however, was observed for LS (-2.9%; p=0.1). These data suggest a sustained positive effect of CRP apheresis on the heart physiology in STEMI patients with high CRP production well beyond the period of its application. The data demonstrate the sustainability of the CRP removal from plasma which is associated with less scar tissue.

Prolonged fatigue is associated with non-pathological causes, and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve® Response) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue Severity Scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stressed conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months supplementation in healthy subjects with mild prolonged fatigue.

The visual appearance of humans derives significantly from our skin and hair color. While melanin from epidermal melanocytes protects our skin from the damaging effects of ultraviolet radiation, the biological value of pigmentation in the hair follicle, particularly in the scalp, is less clear. In this study, we explore the heterogeneity of pigment cells in the human scalp anagen hair follicle bulb, a site conventionally viewed to be focused solely on pigment production for transfer to the hair shaft. Using c-KIT/CD117 microbeads, we isolated bulbar c-KIT-positive and c-KIT-negative melanocytes. While both subpopulations expressed MITF, only the c-KIT-positive fraction expressed SOX10. We further localized bulbar melanocyte subpopulations (expressing c-KIT, SOX10, MITF, and DCT) that exhibited distinct/variable expression of downstream differentiation-associated melanosome markers (e.g., gp100 and Melan-A). Localization of a second ‘immature’ SOX10 negative melanocyte population, which was c-KIT/MITF double positive, was identified outside of the melanogenic zone in the most peripheral/proximal matrix. These studies describe an approach to purifying human scalp anagen hair bulb melanocytes, allowing us to identify unexpected levels of melanocyte heterogeneity. The function of the more immature melanocytes in this part of the hair follicle remains to be elucidated. Could they be in-transit migratory cells destined to synthesize mela-nin ultimately or could they contribute to the hair follicle in non-melanogenic ways.

Background and Aim: Spontaneous bacterial peritonitis is a common infection in liver cirrhosis. This systematic review and meta-analysis provides detailed information on the prevalence of SBP among HBV and HCV-related liver cirrhosis globally. Methods: A systematic search for articles describing the prevalence of SBP in HBV, and HCV related cirrhosis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Our search returned ten (10) eligible articles involving 1,713 viral cirrhosis cases representing eight (8) countries. A meta-analysis was performed on our eligible studies using the random effect model. A protocol was registered with PROSPERO (CRD42022321790). Results: The pooled prevalence of SBP in HBV associated cirrhosis had the highest estimate [8.0% (95% CI, 2.7 – 21.0%; I2= 96.13%; p < 0.001)], followed by SBP in HCV associated liver cirrhosis [4.0% (95% CI, 1.3% – 11.5%; I2 = 88.99%; p < 0.001)]. China (61.8%, CI: 57.1 – 66.3%), the USA (50.0%, CI: 34.6 – 65.4%), and Holland (31.1%, CI: 21.6 – 42.5%) had the highest estimate for SBP in HBV associated liver cirrhosis, SBP in HCV associated liver cirrhosis and SBP in HBV+HCV associated liver cirrhosis respectively. There was a significant difference in the prevalence of SBP in viral hepatitis-associated liver cirrhosis with the year of sampling and method of SBP detection at P<0.001. There was an increase in SBP incidence at the beginning of 2016 across the liver cirrhosis in this study. Conclusion: The findings of this review revealed an increase in the incidence of SBP in viral hepatitis over the last decade, the latter could be due to the global increase in Bacterial resistance. This indicates a possible future rise in the global prevalence of SBP among HBV, and HCV-related liver cirrhosis.

We recently proposed that topological quantum computing might be based on $SL(2,\mathbb{C})$ representations of the fundamental group $\pi_1(S^3\setminus K)$ for the complement of a link $K$ in the $3$-sphere. The restriction to links whose associated $SL(2,\mathbb{C})$ character variety $\mathcal{V}$ contains a Fricke surface $\kappa_d=xyz -x^2-y^2-z^2+d$ is desirable due to the connection of Fricke spaces to elementary topology. Taking $K$ as the Hopf link $L2a1$, one of the three arithmetic two-bridge links [the Whitehead link $5_1^2$, the Berge link $6_2^2$, the double-eight link $6_3^2$] or the link $7_3^2$, the $\mathcal{V}$ for those links contains the reducible component $\kappa_4$, the so-called Cayley cubic. In addition, the $\mathcal{V}$ for the later two links contains the irreducible component $\kappa_3$, or $\kappa_2$, respectively. Taking $\rho$ to be a representation with character $\kappa_d$ ($d<4$), with $|x|,|y|,|z| \le 2$, then $\rho(\pi_1)$ fixes a unique point in the hyperbolic space $\mathcal{H}_3$ and is conjugate to a $SU(2)$ representation (a qubit). Even though details on the physical implementation remain open, more generally, we show that topological quantum computing may be developed from the point of view of three-bridge links, the topology of the $4$-punctured sphere and Painlev\'e VI equation. The $0$-surgery on the $3$ circles of the Borromean rings L6a4 is taken as an example.

INTRODUCTION: The purpose of the study was to determine (a) the overall preclinical character; (b) the cumulative cutoff values and the risk ratio, and (c) the factors associated with severity by a unidimensional and multidimensional analysis on 2173 Sars-Cov2 patients. METHODS: The machine learning study population consisted of 2173 patients (1587 mild and non symptoms patients, 377 moderate patients, 209 severe patients). The status of the patients was recorded from September 2021 to March 2022. RESULTS: The Covid19 Severity directly links with a significant correlation to Age, Score index of the chest X-ray, percentage and quantity of neutrophils, Albumin, C reactive protein, and ratio of Lymphocytes. Their important cut off values (from regression analysis) respectively are: 77.56 years old (the mild-moderate group), 5.53 (the mild-moderate group) and 10.51 (the moderate-severe group), 84.80% (the mild-moderate group) and 87.74%(the moderate-severe group), 11.77G/L (the moderate-severe group), 29.73g/L (the moderate-severe group), 7.46mg/dL (the mild-moderate group), 6.32% (the moderate-severe group). Their significant (p<0.0001) R score correlation with the severity of Covid19, are: 0.44, 0.52 and 0.52, 0.33 and 0.44, 0.42, -0.43, 0.40, -0.41. Their significant risk ratio (p<0.00001) from the meta-analysis, respectively are: 4.19 [3.58-4.95], 3.29 [2.76-3.92] and 3.03 [2.4023;3.8314], 3.18 [2.73-3.70] and 3.32 [2.6480;4.1529], 3.15 [2.6153;3.8025], 3.4[2.91-3.97], 0.46 [0.3650;0.5752] (p<0.00001), 0.34 [0.2743;0.4210]. The pair ALT – Leucocytes and Transferrin – Anion Chloride get the most important correlation shift. ALT – Leucocytes show the important negative link (R=-1, p<0.00001) in the mild group to the significant positive correlation in the moderate group (R=1, p<0.00001). Transferrin–anion Chloride has an important positive association (R=1, p<0.00001) in the mild group with a significant negative correlation in the moderate group (R=-0.59, p<0.00001). The network map and HCA show that in the mild-moderate group, the closest neighbors with the Covid19 severity are ferritins, Age. Then there is C-reactive protein, SI of X-ray, Albumin, and Lactate dehydrogenase, which are the next close neighbors of these three factors. In the moderate-severe group, the closest neighbors with the Covid19 severity are Ferritin, Fibrinogen, Albumin, the quantity of Lymphocytes, SI of X-ray, white blood cells count, Lactate dehydrogenase, and quantity of neutrophils. CONCLUSIONS: Complete multidimensional study in 2173 Covid19 patients in Vietnam shows the whole picture of all the preclinical factors, which may become the clinical reference marker for surveillance and diagnostic management

Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A correlation was found between IL-10 and IL-6 concentrations and age group; lymphocyte subpopulations and nutritional status and steroid use; IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.

This study assesses the feasibility of hepatitis B and C elimination, using an analysis of trends of epidemiology data (1990-2019) from the global burden of disease. Joinpoint regression analysis was used to identify significant changing points in trends of Age-standardizes Prevalence Rate (ASPR) and Age-standardizes Mortality Rate (ASMR) and to estimate the annual percentage changes (APC) and the average annual percentage changes (AAPC) for the period. Sociodemographic Index (SDI) was used to analyze trends between countries. The total percentage change of the ASPR (2019/1990) was -31.4% and -12.8% for HBV and HCV worldwide respectively, the rate ratio (HBV/HCV) was 2.5. Mortality has decreased for HBV but not for HCV. The total percentage change for the ASMR (2019/1990) was -26.7% and 10.0%, for HBV and HCV respectively. While ASMR of HBV decreased, HCV increased during this period. The percentage change in ASMR of HBV was highest in countries with high-middle SDI and lowest in countries with high SDI. For HCV, the percentage change in ASMR was highest in countries with High SDI (increase) and only in countries with low SDI decreased. The global HBV and HCV rates have fallen with different AAPC associated with the SDI. Despite the advances, there is still a long way forward to achieve the 2030 elimination goals. An important challenge is related to finding a way to speed up the yearly rate at which the decline is happening.

Methane (CH4) has attracted attention as not only synthetic natural gas, but also one of the hy-drogen carriers in terms of energy density. On the other hand, there exist bacterial ecosystems in nature that can decompose organic compounds to produce CH4 and CO2. In this study, Clostridi-um cellulovorans was first cultivated with pig manure (PM) as an unused biomass. Regarding the measurement of organic acids by high-performance liquid chromatography (HPLC), acetate and butyrate were increased in the C. cellulovorans medium containing 0.5% PM, while formate and lactate were decreased in it. Next, in comparison with carbon sources such as glucose, cellobiose, and acetate, cocultivation of C. cellulovorans and Methanosarcina mazei or microbial flora of me-thane production (MFMP) was performed in the C. cellulovorans medium. These results revealed that 0.5% acetate as the sole carbon source produced CH4 only by cocultivating C. cellulovorans and MFMP. Furthermore, MFMP was only cultivated with 1% acetate or 1% methane as a carbon source after precultivated with 0.5% glucose medium for 12 h. As a result, methane productivity of MFMP with 1% methanol medium was approximately eight times higher than that with 1% acetate medium. Finally, next-generation sequencing (NGS) analysis of MFMP after cultivation with 1% acetate or 1% methane was carried out. Interestingly, Methanofollis (0.211%) belonging to H2/CO2 -using methanogens (CO2 reduction pathway) was dominant in the 1% acetate medium for 72 h cultivation, whereas Methanosarcina siciliae (1.178%), M. barkeri (0.571%), and Methano-follis (0.490%) were major species in 1% methanol medium for 72 h cultivation. Since Methano-sarcina spp. are belonging to acetoclasts (acetoclastic pathway), methanol could promote to grow Methanosarcina spp. rather than acetate. Therefore, it seemed Methanosarcina spp. may play a key methanogenesis in MFMP. Thus, these results will provide important information for low cost biomethane production.

Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicat-ed in several neurological disorders, including Parkinson’s disease (PD). Here, we report results of an RNAi screen of genes differentially regulated in adr-2 mutants, normally encoding the only catalytically active ADAR in Caenorhabditis elegans, ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegenera-tion, two PD pathologies, reveal that reduced expression of xdh-1, the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegenera-tion. Further RNAi experiments show that WHT-2, the worm ortholog of the human ABCG2 transporter and a predicted interactor of XDH-1, is the rate-limiting factor in the ADR-2, XDH-1, WHT-2 system for dopaminergic neuroprotection. Proteomic analysis indicates that the editing of one nucleotide in wht-2 RNA leads to the substitution of threonine with alanine at residue 124 in the WHT-2 protein, changing its structure. Thus, we propose a model where wht-2, is edited by ADR-2 which promotes optimal export of uric acid, a known substrate of WHT-2 and a product of XDH-1 activity. In the absence of editing, uric acid export is limited provoking a reduction in xdh-1 transcription to limit uric acid production and maintain cellular homeostasis. In turn, ele-vation of uric acid is protective against dopaminergic neuronal cell death. These data indicate that modifying specific targets of RNA editing may represent a promising therapeutic strategy for PD.

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is commonly enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer causing viruses.

The study aimed to determine the relationship between glucose, C-peptide, BDNF, and leptin between mother and fetus and neonatal weight. Methods: In the prospective observational cohort study, we included 66 women with T1DM. According to the z-score for neonatal weight, patients were divided into Healthy weight neonates (n=42) and Overweight neonates (n=24). The maternal blood samples were taken during pregnancy and cesarean section when the umbilical vein blood sample was also withdrawn. The maternal vein sera were analyzed for fasting glucose, CRP, leptin, BDNF, TSH, FT3, and FT4. The umbilical vein sera were analyzed for glucose, C-peptide, leptin, TSH, FT3, FT4, and BDNF concentration. The neonatologist measured the skinfold thickness on the third day of neonatal life. Results: A strong correlation was confirmed between maternal and umbilical vein glucose concentration and maternal glucose and C-peptide in umbilical vein blood. A negative correlation was found between the concentration of BDNF in the umbilical vein and glucose in maternal blood. A strong correlation was seen between BMI and maternal blood leptin concentration, neonatal fat body mass, and umbilical vein blood leptin concentration. Increased odds for Overweight neonates were BMI, BDNF, and TSH in the first trimester of pregnancy. Maternal leptin concentration decreased the odds of Overweight neonates. Conclusions: Maternal glucose concentrations affect the fetus’s glucose, C-peptide, and BDNF concentrations. Leptin levels increase in maternal blood due to increased body mass index, and in the neonate, its fat body mass is responsible for increased leptin concentrations.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with hyperactivation of Smad3 and elevated expression of the proapoptotic protein caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries, and a switch of aortic VSMCs from the ‘contractile’ to the ‘synthetic’ phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

Increasing the loading density of nanoparticles on carbon support is essential for making Pt-alloy/C catalysts practical in H2-air fuel cells. The challenge lies in increasing the load-ing while suppressing the sintering of Pt-alloy nanoparticles. This work presents a 40% Pt-weighted sub-3 nm PtCo/C alloy catalysts via a simple incipient wetness impregnation method. By carefully optimizing the synthetic conditions such as Pt/Co ratios, calcination temperature and time, the size of supported PtCo alloy nanoparticles is successfully con-trolled below 3 nm, and a high electrochemical surface area achieves of 94 m2/g is achieved, which is 2.8 times of commercial PtCo/C-TKK catalysts. Demonstrated by elec-trochemical oxygen reduction reaction, PtCo/C alloy catalysts present an enhanced mass activity of 0.45 A/mg at 0.9 V vs. RHE, which is 1.7 times that of PtCo/C-TKK catalyst. Therefore, the developed PtCo/C alloy catalyst can potentially be a highly practical cata-lyst for H2-air fuel cells.

Radiation therapy is employed in treating various cancer types. However, depending on the type and stage of cancer, its benefits can be limited, and it may cause serious side effects that detrimentally affect the quality of life (QOL) for the patient. Preventing the side effects of radiation therapy can enhance the response to cancer treatment and improve the patient’s QOL. Independently, vitamin C and hydrogen have demonstrated potential in reducing the side effects of anticancer drugs and radiation therapy. Furthermore, both have been postulated to possess direct anticancer properties. However, the effects of their combined therapy remain underexplored. This study investigates the hypothesis that combining vitamin C and hydrogen efficiently prevents radiation-induced injuries. Survival rates were investigated in cancer cell lines (MDA-MB231 and GL261) and normal cells (HUVEC) treated with hydrogen, vitamin C and irradiation. Apoptosis was assessed using the FLICA test, and EMT gene expression was elucidated via the qPCR technique. In the normal cell line, the introduction of vitamin C and hydrogen to the culture medium boosted survival rates, exhibiting a radioprotective effect upon irradiation. In contrast, cancer cells showed a decreased survival rate with the introduction of vitamin C and hydrogen, which was further diminished with irradiation. Treated cancer cells showed signs of apoptosis. Caspase activity in viable cells was reduced by the combination treatment with vitamin C and hydrogen. Additionally, glioblastoma cells treated with this combination showed reduced EMT gene expression. This study reveals that a combined therapy of hydrogen and vitamin C offers radioprotective effects on normal cells and exerts direct anticancer effects on cancer cells, while also amplifying the anticancer effects of radiation. Importantly, this combined therapy attenuated the radiation-induced EMT signature in the GL261 murine glioma cell line, suggesting potential in diminishing treatment resistance and tumor invasion.

pH is the major factor that makes producers in aquaponics frustrated, since the main three organisms (aquatic animal, plant, and microbes) in the system with different preferences. Yet, amending the growing environment with additional C is a potential method to improve the growth of shrimp and plants as well as the establishment of microbe. A detailed study of the effects of pH and additional C on aquaponics under saline conditions has not been investigated. In this study, the effect of pH and additional C on the growth performance of shrimp (Litopenaeus vannamei) and five edible plants in marine aquaponic systems using the nutrient film technique (NFT) was evaluated. The results indicated that at both pH 6.5 treatments, plants grew better; nevertheless, the growth performance of plants in pH 7.5 with additional C was improved and showed a similar yield to lower pH treatments. On the other hand, shrimp growth was little affected by pH and additional C. A higher impact of imbalanced ionic composition on shrimp performance may have contributed to this trend. Hence, we suggest that only if the ionic composition is managed can make RO water a suitable source of water for shrimp-based aquaponic. In spite of this, more research is required.

Apis cerana and Apis mellifera, are very important honey species for agriculture in Asian countries. In recent decades, A. cerana populations have sharply declined in all Asian countries as a result of Sacbrood Virus infection and have now recovered to their original size. It can change the genetic structure of local populations of A. cerana. We used the nuclear gene Vitellogenin VG to assess the genetic structure of local populations of A. cerana and the signature of adaptive selection. We performed a population genetic analysis of the honey bees A. cerana from South Korea in comparison with A. cerana samples from Russia, Japan, Nepal, and China. The sequences of the gene VG of a closely related honey bee species, A. mellifera, from India and Poland were used as outgroup samples. A comparative analysis of northern and southern A. cerana populations was performed. The signatures of positive adaptive selection were found in the local population of A. cerana. We performed the Tajima's neutrality D test for A. cerana populations from different local populations based on the gene VG exon sequences. All A. cerana populations showed signs of population size expansion following the possible recent decline in population sizes. The local populations of A. c. koreana were subdivided according to their geographical distribution into southern, northern, and central Korean clusters. The gene VG exon sequences can be used as informative markers for monitoring the changes in genetic structure and adaptation to the environment processes in A. cerana populations.

Motivated from the theory of Hilbert-Schmidt morphisms between Hilbert C*-modules over commutative C*-algebras by Stern and van Suijlekom [J. Funct. Anal., 2021], we introduce the notion of p-absolutely summing morphisms between Hilbert C*-modules over commutative C*-algebras. We show that an adjointable morphism between Hilbert C*-modules over monotone closed commutative C*-algebra is 2-absolutely summing if and only if it is Hilbert-Schmidt. We formulate version of Pietsch factorization problem for p-absolutely summing morphisms and solve partially.

This study investigates the stress corrosion cracking (SCC) behavior of type 316L stainless steel (SS316L) produced with sinter-based material extrusion additive manufacturing (AM). This technology has been shown to produce SS316L with microstructures and mechanical properties comparable to its wrought counterpart in the annealed condition. However, despite plenty of research on SCC of SS316L, little is known about SCC in sinter-based AM SS316L. This study focuses on the influence of sintered microstructures on susceptibility to SCC initiation and crack-branching. Custom-made C-rings were exposed to different stress levels in acidic chloride solutions at various temperatures. To better understand the SCC behavior of SS316L, solution-annealed (SA) and cold-drawn (CD) wrought SS316L were tested for comparison. Results showed that sinter-based AM SS316L was more susceptible to SCC initiation than SA wrought SS316L but more resistant than CD wrought SS316L. Moreover, sinter-based AM SS316L showed noticeably better resistance to crack-branching than both wrought SS316L counterparts. The investigation was supported by comprehensive pre- and post-test microanalysis using light optical microscopy (LOM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and micro-computed tomography (micro-CT)

Cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) are endemic threats to cassava production. To fill the existing gaps in the understanding of the epidemiology of these diseases in Côte d’Ivoire, nationwide field surveys were conducted in 2016, 2017 and 2020. The leaf samples collected were analysed by PCR. CBSD was not detected in all fields visited. However, an increase of CMD incidence was observed from 45.95% in 2016 to 51.37% in 2020 while CMD severity remained moderate over the years with a mean value of 2.29. Low whiteflies number was observed in field and decreasing over the years. Molecular analysis allowed detection of East African cassava mosaic Cameroon virus (EACMCMV) in single as well as in mixed infection with African cassava mosaic virus (ACMV). Single EACMCMV infection, which was detected only in three agroecological zones of the eastern Côte d’Ivoire in 2016, spread throughout the country in 2017 and became more widespread in 2020 with a preponderance in the central and southern zones, whereas the ACMV+EACMCMV coinfection has spread to the entire zones studied. Knowing the dynamics of the evolution of these viruses across the country, better disease management strategies could be adopted to control the disease.

In the production of grafted vines, losses are caused by fungal pathogens during callus forming or after planting in the soil. To control or reduce natural fungal infections in nurseries, certain applications were conducted in sapling cultivation stage to analyse the efficacy of cyprodinil + fludioxonil, floupyram + tebuconazole active substances and Trichoderma harzianum biological preparation. 1103 Paulsen rootstock and Vitis viniferea L. Sultana cultivars were stored in fungicide suspensions for 60 minutes before and after grafting in the study. After grafting, the seedlings were divided into i) cutting + sawdust ii) cutting + sawdust + soil application groups and transferred to the callus room. Fungicides were applied 1 to 7 days after the callus development to wet the seedling roots 1 to 7 days after they were planted. After nine months in the nursery, the plants were uprooted, classified as diseased or healthy, and analysed for morphological and molecular diagnosis of fungal species, isolation incidence, and seedling quality and yield. After callus development, Fusarium solani was most frequently isolated pathogen in the roots (21.5%), cyprodinil + fludioxonil reduced the Ilyonectria sp. isolation rate in both shoots and roots. Botryosphaeria obtusa and I. liriodendri pathogens were not detected in sick and healthy cyprodinil + fludioxonil-treated saplings. The highest seedling yield was observed with fludioxonil + cyprodinil, cutting + sawdust + soil (78.75%) and cutting + sawdust (70.68%) applications. According to the results of this study, it was found that fungicide applications before and after grafting prevented soil-borne pathogen infections and improved sapling quality.

The nematode Angiostrongylus cantonensis has been reported worldwide, however, some basic questions remain unanswered about the presence of A. cantonensis in Ecua-dor: 1) Was the invasion of A. cantonensis in Ecuador unique, or did it occur in different waves? 2) Was this invasion as recent as historical records suggest? 3) Did this inva-sion come from other regions of South America or elsewhere? To address these issues, we assessed the genetic diversity of MT-CO1 gene sequences from isolates obtained in eleven of Ecuador's 24 provinces. Our Bayesian inference phylogenetic tree recovered A. cantonensis as a well-supported monophyletic group. All eleven sequences from Ec-uador were identical and identified as AC17a. The haplotype AC17a, found in Ecuador and the USA, formed a cluster with AC17b (USA); AC13 (Thailand); and AC12a-b (Cambodia). It is notable that all the samples, obtained in different geographic and climatic regions of different Ecuadorian provinces, had no genetic difference between them. Despite the lack of genetic information on A. cantonensis in Latin America, ex-cept in Brazil, our finding differs from previous studies by its absence of genetic diver-sity in Ecuador. We concluded that the invasion of A. cantonensis in Ecuador may have occurred: 1) as a one-time event, 2) recently, and 3) from Asia via the USA. Further re-search should include samples from countries neighboring Ecuador to delve deeper in-to this.

Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for the c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards the c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.

We suggest a new solution to the strong CP problem. The solution is based on the proper use of the boundary conditions for the QCD generating functional integral. It obeys the principle of renormalizability of Quantum Field Theory and does not involve new particles like axions.

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

Côte d’Ivoire has substantially neglected crop residues from farms in rural areas. This study aims to provide strategies for the sustainable conversion of crop residues to hydrogen. Using existing data and theoretical approaches, up to 16,801,306 tons of crop residues of 11 crop types were available in Côte d’Ivoire in 2019. A theoretical hydrogen potential of 1,296,424.84 tons was estimated from the crop residues. Technically, 907,497.39 tons of hydrogen is expected annually. Three scenarios of hydrogen project implementation developed indicated that the Ivorian industries can be supplied with 9,026,635 gigajoules of heat. Moreover, 17,910 cars and 4,732 buses can be supported in the transport sector. It is estimated that 817,293.95 tons of green ammonia for farmers can be supplied. Five million, seven hundred twenty-seven thousand, nine hundred ninety-two (5,727,992) households are expected to have access to 1,718.40 gigawatts of electricity. Due to these changes in transport, energy, industry, and agricultural sectors, a reduction of 1,644,722.08 tons of carbon dioxide per year can be achieved theoretically. With the scenarios, some 263,276.87 tons of hydrogen are exportable to other countries. Conversion of crop residues to hydrogen is a promising opportunity with environmental and socio-economic impact. Therefore, this study requires further extensive research.

Background and objectives: Since 2013, highly effective direct-acting (DAA) chronic hepatitis C (CHC) antiviral therapy became available, which has cure rates of over 95%. For choice of optimal CHC treatment, assessment of hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage are necessary. Information about distribution of these parameters among CHC patients in Baltic states and especially in Ukraine is scarce. This study was performed to obtain epidemiological data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (Baltic states) and lower-middle income (Ukraine) countries. Materials and Methods: This was an epidemiological, retrospective, cross-sectional study that included 1451 CHC patients. Demographic and disease information from medical charts was collected for each patient during a single visit. Results: Most frequent suspected mode of viral transmission was blood transfusions (17.8%), followed by injection drug use (15.7%); however, in 50.9% of patients exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%) transmission by the injection drug use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1 - 66.4%; GT3 - 28.1; and GT2 - 4.1%. The prevalence of GT1 was the highest in Latvia (84%), and the lowest in Ukraine (63%, p<0.001). Liver fibrosis stages were distributed as follows: F0 - 12.2%, F1 - 26.3%, F2 - 23.5%, F3 – 17.1% and F4 - 20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p <0.001). Conclusions: This study contributes to the knowledge of epidemiological characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

Background: Macrophage inflammatory protein-1 alpha (MIP-1α) and C-reactive protein (CRP) are pro-inflammatory biomarkers that quantify clinical and subclinical inflammation in cardiac ischemia in cardiac inflammation and disease. Adiponectin is an anti-inflammatory marker associated with good health. The susceptibility of periodontitis patients to cardiovascular events needs to be evaluated. Objective: This study aims to assess the levels of biomarkers in periodontitis patients with and without acute myocardial infarction (AMI) compared to controls. Material and methods: Pro-inflammatory and anti-inflammatory analytes were examined by collecting unstimulated saliva from three groups (n = 20/each): healthy individuals, individuals with stage III periodontitis, and post-myocardial infarction patients with stage III periodontitis. The samples were collected within 48 hours of AMI. Results: Adiponectin levels were significantly lower in patients with periodontitis with and without AMI compared to controls, while CRP and MIP-1α were significantly higher in patients with periodontitis with and without AMI compared to controls. The highest titers for MIP-1α and CRP were detected among patients with periodontitis with and AMI. Conclusion: Our study provides evidence of the association between periodontitis and salivary analytes that occur in tandem with cardiovascular disease. The lower levels of Adiponectin and higher levels of CRP and MIP-1α in patients with periodontitis indicate that this condition is a potential risk factor for cardiovascular disease. The findings emphasize the importance of early detection and intervention for periodontitis patients to prevent cardiovascular events.

In the Czech Republic, the Universal Soil Loss Equation provides the basis for defining the soil protection strategy. Field rainfall simulators were used to define the actual cover-management factor values of the most extensively seeded crops in the Czech Republic. More than 380 simulations between 2016 and 2021 provided data. The methodology focused on multi-seasonal measurements to cover the most important phenological phases. A comparison with the original USDA values for maize showed that it is desirable to redefine the C-factor. 71 fallow plot experiments showed that the rainfall-runoff relation is much easier to replicate than the actual sediment transport. For 30-minute intensive rainfall, the runoff ratio reached 62%, and the coefficient of variation was 25%. On saturated soil, the runoff ratio reached 81% and the coefficient of variation dropped to 12%. Soil protection techniques have a significant effect on runoff reduction. Maize seeded after cover crops and combined with reduced tillage or direct seeding can reduce the runoff ratio to 10-20% for ‘dry’ conditions and to 12-40% for ‘saturated’ conditions. Concerning soil loss, the variations are greater, with the coefficient of variation reaching 42% during fallow plot experiments. The reader should consider associated uncertainties.

The involvement of NK and other cytotoxic cells is considered the first defense' line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells, the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers, some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin and the combination of both drugs. Possible correlations were estimated with Pearson's correlation analysis. Despite having demonstrated multiple correlations, it should be noted that immaturity/activation markers were related to these cells' activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02-restricted CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope exclusively restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

Estrogens play a protective role during early life stages. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression in low-grade inflammatory conditions like established atherosclerosis. Our single-center cohort study assessed sex-specific associations of gonadal hormones with oxidative stress, inflammation, and myocardial injury markers in 111 patients (37% women) diagnosed with acute myocardial infarction (MI) between July 2011 and December 2013. Blood samples were collected within 48 hours of symptom onset, and we measured sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitive C-reactive protein (CRP), white blood cell counts (WBC), and cardiac enzymes (creatine kinase [CK], the CK Muscle-Brain fraction [CK-MB], and high-sensitive troponin T [hsTnT]). The SYNTAX score gauged coronary disease severity from coronary angiography results. In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels (OR 1.011, p=0.047 - CK; OR 1.018, p=0.013 - CK- MB; OR 1.019, p=0.005 - TnT), peak WBC count (OR 1.487, p=0.015 - CK ; OR 1,709, p=0,005 - CK- MB; OR 1.391, p=0.012 - TnT), and peak CRP plasma levels (OR 1.040, p=0.033 - CK; OR 1.024, p=0.029 - CK-MB; OR 1.063, p=0.006 - TnT). T levels and E2/T ratio were associated with post-PCI CRP in these men (OR 0.980, p = 0.024 - T, OR 1.010, p = 0.076 - CRP). For women, peak WBC was a marker of highest testosterone (OR 1.348, p = 0.062), and only WBC was a significant indicator of myocardial injury extent (OR 1.426, p=0.039 - CK; OR 1.384, p=0.036 - CK-MB; OR 1.299, p=0.048 - TnT). During acute MI, elevated endogenous estradiol levels correlate with myocardial necrosis severity in men, while in women, increased leukocyte levels indicate acute myocardial damage. Elevated plasma T is associated with increased WBC in women. In men, post-PCI plasma CRP specifically indicates endogenous T levels and E2/T ratio during the acute phase.

A change in biological properties of the SARS-CoV-2 virus can enhance its transmissibility and virulence, complicate the disease course, and reduce the effectiveness of anti-viral therapy and vaccination. We have studied 16 genetic lineages of the Omicron variant. The viral reproduction course was analyzed based on plaque morphology in the agar layer and the maximum titer in Vero E6 cells. BALB/c mice and Syrian hamsters were used as animal models. Viral load and infectious SARS-CoV-2 titer were determined in the nasal tissue and lungs. The severity of infectious process was assessed using histological methods. An increased plug size was observed in CH.1.1 and BQ.1.2.1 strains after six passages. This was due to substitutions D614G, H655Y, and N764K in the coronavirus S protein. The same changes in gene variants Gamma and BA.1 were caused by the substitution R682W, which is not present in lineages CH.1.1 and BQ.1.2.1. A similar substitution, namely R682P, was observed in the BA.5.1 strain. We characterized BA.1 (as a reference), BA.5.2, and XBB.3 strains in vivo as representatives of the main circulating genetic lineages. For the BA.1 strain, ID50 was 1.3 and 14 TCD50 in Syrian hamsters and BALB/c mice, respectively. An insignificant increase in the BA.5.2 virulence compared to that of BA.1 was noted (ID50 was 07. and 10 TCD50, respectively). The XBB.3 pathogenicity in laboratory animals is similar to that of BA.1 (ID50 was 1.8 and 15 TCD50, respectively). Experiments showed a consistent decrease in the virulence of Omicron strains compared to previously circulating SARS-CoV-2 variants. A co-evolutionary change in amino acid sequences, affecting the conformation of the coronavirus S protein and its surface epitopes in representatives of different genetic lineages, was noted. The emergence of potential proteolysis sites and alterations of the furin cleavage site have been observed in numerous Omicron coronavirus variants.

SORL1 gene encodes LR11/SorLA, a protein that binds -amyloid precursor protein (bAPP) and drives its intracellular trafficking. SORL1 mutations occurring frequently in a subset of familial cases of Alzheimer’s disease (AD) have been documented but their pathogenic potential is not yet clear and questions remain concerning their putative influence on the physiopathological processing of bAPP. We have assessed the influence of three SORL1 mutations that were described as likely disease-causing and that were associated with either benign (SorLA924) or severe (SorLA141 and SorLA511) AD phenotypes. We examined the influence of wild-type and mutants SorLA in transiently transfected HEK293 cells expressing either wild-type or Swedish mutated bAPP on bAPP expression, secreted Ab and sAPPa levels, intracellular Ab40 and Ab42 peptides, APP-CTFs (C99 and C83) expressions, a-, b- and g-secretases expressions and activities as well as Ab and CTFs-degrading enzymes. These paradigms were studied in control conditions or after pharmacological proteasomal modulation. We also established stably transfected CHO cells expressing wild-type SorLA and established the colocalization of wild-type SorLA and bAPP. Overall, although we mostly confirmed previous data concerning the influence of wild-type SorLA on bAPP processing, we were unable to evidence significant alterations triggered by our set of SorLA mutants, whatever the cells or pharmacological conditions examined. Our study however does not rule out the possibility that other AD-linked SORL1 mutations could indeed affect bAPP processing and that pathogenic mutations examined in the present study could interfere with other cellular pathways/triggers in AD.

Due to the widespread application of (hetero)arylazoles, the development of straightforward functional group-tolerant synthetic methods that enable selective heteroaromatic elaboration under mild conditions aroused considerable attention. Over the last years we were interested in studies aimed to broaden the substrate scope of the direct functionalization of azoles and, in particular, to develop efficient synthetic protocols for the carbon-carbon bond forming reaction by selective palladium-catalyzed Csp2-H bond activation of imidazole derivatives. During these studies, we discovered that the outcome of the Pd-catalyzed arylation of imidazoles with aryl bromides is deeply influenced by the nature of the reaction solvent. Specifically, it is well known that the Pd-catalyzed direct arylation of imidazoles with aromatic halides selectively leads to C-5 monoarylation products when polar aprotic solvents such as DMF (or DMA) are used as a reaction medium, but these solvents are coded as dangerous according to EHS (Environmental, Health, Safety) parameters. Instead, the use of aromatic solvents as the reaction medium for direct arylations, although some of them show good EHS values, is poorly reported, probably due to their low solvent power against reagents and their potential involvement in undesired side reactions. So, with the intention of filling this gap, in this paper, we have developed a selective C-5 arylation procedure in anisole as the solvent, discovering also the unprecedented role of benzoic acid as a promoter of the coupling.

Fluorinated compounds and co-enzymes are being widely researched and employed throughout research community because of their versatile physical, chemical and biological properties. In this work, we synthesized NiS-NiO/S-g-C3N4, a highly effective photocatalyst for C(sp3)-F bond activation and the regeneration of coenzyme (1,4-NADH) employing a new and ecologically acceptable route. The obtained photocatalyst exhibited important photocatalytic properties, such as good solar light harvesting ability, suitability of the optical band-gap, and facilitating efficient charge migrations. As a result, the newly designed NiS-NiO/S-g-C3N4 photocatalyst shows the excellent yield for regenerations of 1,4-NADH (51%). Further, a method of combining C(sp3)-F bond activation with photocatalysis has been demonstrated that represents a very powerful and sustainable approach, that can be a major breakthrough for the field of pharmaceutical.

Low-lying coastal communities are often threatened by compound flooding (CF), which can be determined through the joint occurrence of storm surges, rainfall and river discharge either successively or in close succession. The trivariate distribution can demonstrate the risk of the compound phenomenon more realistically rather than considering each contributing factor independently or in a pairwise dependency. Recently vine copula has been recognized as the highly flexible approach to constructing a higher dimensional joint density framework. In such construction, parametric class copula with parametric univariate marginal distributions is often involved. Such incorporation can lack flexibility due to parametric functions with prior distribution assumptions about their univariate marginal and/or copula joint density. This study introduces the vine copula approach in a nonparametric setting by introducing Bernstein and Beta kernel copula density in establishing trivariate flood dependence. The proposed model is applied to 46 years of flood characteristics collected on the west coast of Canada. The univariate flood marginal distribution is modelled using nonparametric kernel density estimation (KDE). The 2-D Bernstein estimator and Beta kernel copulas estimator are tested independently in capturing pairwise dependencies to establish D-vine structure in a stage-wise nesting approach in three alternative ways, each by permutating the location of the conditioning variable. The best-fitted vine structure is selected using goodness-of-fit (GOF) test statistics. The performance of the nonparametric vine approach is also compared with the vine constructed in the parametric and semiparametric fitting procedure. Investigation reveals that the D-vine constructed using Bernstein copula with normal KDE marginals nonparametrically performed well in capturing dependence of the compound events. Finally, the derived nonparametric model is used in the estimation of trivariate OR- and AND-joint return periods, further employed in estimating failure probability (FP) statistics. The trivariate return periods for the AND-joint case are higher than for the OR-joint case for the same flood combination. Also, the trivariate flood hazard results in a high-value FP than bivariate and univariate events. Ignoring the trivariate dependence could result in the underestimation of FP

Pruning is an important part in controlling the branching, good fruit size, and prodctivity of fruit trees. and consequently, ‘Valencia’ orange trees were grown many years ago, the trees were suffering from a decline in productivity in the newly reclaimed lands after certain years of plantation. This study elucidated the effect of pruning severity on growth, yield and fruit quality of ‘Valencia’ orange trees. Four levels of pruning were applied on 35 years old ‘Valencia’ orange trees as follows: T1: Control (un-pruned), T2: Light pruning ( 25% of main branches were removed); T3: Moderate pruning (50% of main branches were removed) and T4: Heavy pruning: 75% of main branches were removed. The treatments were done in February 15th (for each season). The results indicated that pruning severity increased vegetative growth paraments such as shoot length and leaf area and decreased canopy volume of Valencia orange trees in comparison to control. Maximum yield was gained from 75% followed by 50% and 25% pruning severity treatment. The pruning treatments improve in fruit weight, size, firmness, juice content, TSS%, TSS/acid ratio and vitamin C content. In addition, pruning produced an increasing in fruit yield per tree as well as yield increasing %. Hence, it might be concluded that pruning at different severity applied in February can be used effectively on ‘Valencia’ orange trees to improve vegetative growth, fruit physical and chemical properties. Besides, increasing fruit yield by nearly 20% in comparison to control.

The catalytically inactive caspase-8-homologous protein, c-FLIP, is a potent antiapoptotic protein highly expressed in various types of cancers. c-FLIP competes with caspase-8 for binding to the adaptor protein FADD (Fas-Associated Death Domain) following Death Receptors (DRs) activation by the ligands of the TNF-R family. As a consequence, the extrinsic apoptotic signaling pathway involving DRs is inhibited. Inhibition of c-FLIP activity in tumor cells might enhance DR-mediated apoptosis and overcome immune and anticancer drug resistance. Based on an in silico approach, the aim of this work was to identify, new small inhibitory molecules able to bind selectively to c-FLIP and block its anti-apoptotic activity. Using a homology 3D model of c-FLIP, an in silico screening of 1880 compounds from the NCI database (National Cancer Institute) was performed. Nine molecules were selected for in vitro assays, based on their binding affinity to c-FLIP and their high selectivity compared to caspase-8. These compounds selectively bind to the Death Effector Domain 2 (DED2) of c-FLIP. We have tested in vitro the inhibitory effect of these 9 molecules using the human lung cancer cell line H1703 overexpressing c-FLIP. Our results showed that 6 of these newly identified compounds efficiently prevent FADD/c-FLIP interactions in a molecular pull-down assay, as well as in a DISC Immunoprecipitation assay. Overexpression of c-FLIP in H1703 prevents TRAIL-mediated apoptosis, however, combination of TRAIL with these selected molecules signifi-cantly restored TRAIL-induced cell death by rescuing caspase cleavage and activation. Altogether, our findings indicate that new inhibitory chemical compounds efficiently prevent c-FLIP recruit-ment into the DISC complex, thus restoring caspase-8 dependent apoptotic cascade. These results pave the way to design new c-FLIP inhibitory compounds that may serve as anticancer agents in tumors overexpressing c-FLIP.

Using the nematode C. elegans germline as a model system, we previously reported that PUF-8 (a PUF RNA-binding protein) and LIP-1 (a dual-specificity phosphatase) repress sperm fate at 20°C and the dedifferentiation of spermatocytes into mitotic cells (termed "spermatocyte dedifferentiation") at 25°C. Thus, double mutants lacking both PUF-8 and LIP-1 produce excess sperm at 20°C, and their spermatocytes return to mitotically dividing cells via dedifferentiation at 25°C, resulting in germline tumors. To gain insight into the molecular competence for spermatocyte dedifferentiation, we compared the germline phenotypes of three mutant strains – fem-3(q20gf), puf-8(q725; fem-3(q20gf), and puf-8(q725); lip-1(zh15). Both fem-3(q20gf) and puf-8(q725); fem-3(q20gf) mutants produced excess sperm like puf-8(q725); lip-1(zh15) double mutants. Our results show that spermatocyte dedifferentiation was not observed in fem-3(q20gf) mutants, but it was more aggressive in puf-8(q725); lip-1(zh15) than in puf-8(q725); fem-3(q20gf) mutants. These results suggest that MPK-1 (the C. elegans ERK1/2 MAPK ortholog) activation by removing the function of LIP-1 in the absence of PUF-8 promotes spermatocyte dedifferentiation. This idea was confirmed using Resveratrol (RSV), a potential activator of MPK-1 and ERK1/2 in C. elegans and human cells. Notably, spermatocyte dedifferentiation was significantly enhanced by RSV treatment, and its effect was blocked by mpk-1 RNAi. We, therefore, conclude that PUF-8 and MPK-1 are normally required to inhibit spermatocyte dedifferentiation and tumorigenesis. Since these regulators are broadly conserved, we suggest that similar regulatory circuitry may control cellular dedifferentiation and tumorigenesis in other organisms, including humans.

It is widely reported that the mitochondrial membrane potential, ∆Ψm, is reduced in aging animals. It was recently suggested that the lower ∆Ψm in aged animals modulate mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in C. elegans increased lifespan. Here I review, critically, studies that reported reduction of ∆Ψm in aged animals, including worms, and conclude that many of these observations are best interpreted as evidence that the fraction of depolarized mitochondria is increased in aged cells because of the enhanced activation of the mitochondrial Permeability Transition Pore, mPTP. Activation of the voltage-gated mPTP depolarizes the mitochondria, inhibits oxidative phosphorylation, releases large amounts of calcium and mROS, and depletes cellular NAD+, thus accelerating degenerative diseases and aging. Since the inhibition of mPTP was shown to restore ∆Ψm and retard aging, the reported lifespan extension by artificially generated ∆Ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP. Similarly, the reported activation of the mitochondrial Unfolded Protein Response by reduction of ∆Ψm, and the reported preservation of ∆Ψm in dietary restriction treatment in C. elegans are best explained as a resulting from activation or inhibition of the voltage-gated mPTP, respectively.

Revealing the time structure of physical or biological objects is usually performed thanks to the tools of signal processing like the fast Fourier transform, Ramanujan sum signal processing and many other techniques. For space-time topological objects in physics and biology, we propose a type of algebraic processing based on schemes in which the discrimination of singularities within objects is based on the space-time-spin group SL(2,C). Such topological objects possess an homotopy structure encoded in their fundamental group and the related SL(2,C) multivariate polynomial character variety contains a plethora of singularities somehow analogous to the frequency spectrum in time structures. Our approach is applied to an Akbulut cork in exotic R4, to an hyperbolic model of topological quantum computing based on algebraic surfaces and to microRNAs in genetics. Such diverse topics reveal the manifold of possibilities of using the concept of a scheme spectrum.

Cervical cancer is caused by a persistent and high-grade infection, caused by the Human Papilloma Virus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 - is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. Knowing that L-Asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers, due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50ºC, resistance to surfactants and metallic ions, and an increase in enzymatic activity was also noted with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells, and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from Aspergillus niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Abstract: Background: Viral hepatitis B and C (HBV and HCV) pose significant public health challenges globally, particularly in Nigeria, where access to healthcare and treatment affordability are major concerns. This study aims to identify sociodemographic and clinical predictors of health insurance coverage among patients with HBV and HCV in Nigeria. Methods: A cross-sectional facility-based study was conducted at two secondary hospitals in Nasarawa State, Nigeria. Par-ticipants included patients diagnosed with HBV, HCV, or both and are > 18 years old. Data were collected using a structured questionnaire covering sociodemographic and clinical information, health insurance details, and economic impact. Logistic multivariate regression analysis was used to analyze the relationship between sociodemographic/clinical variables and health insurance status. Results: Out of 295 participants included in the final analysis, 67.1% had health insur-ance, primarily covering hepatitis screening and vaccination. Being aged 31-45 years (adjusted Odds Ratio [aOR]: 5.72, 95% Confidence Interval [CI]: 1.4 - 23.28, p = 0.02), having post-secondary education (aOR: 11.73, CI: 4.09 - 33.66, p < 0.001), and being HIV-positive (aOR: 2.86, CI: 1.02 - 8.02, p = 0.046) were significant predictors of health insurance coverage. Being unemployed significantly reduced the likelihood of having health insurance (aOR: 0.04, CI: 0.01 - 0.11, p < 0.001).Conclusions: This study reveals high insurance coverage among patients seeking viral hepatitis services in Nasarawa state, Nigeria and provides critical insights into the sociodemo-graphic predictors of health insurance coverage. It also highlights the need for the expansion health insurance benefit package that covers for viral hepatitis diagnosis and treatment, espe-cially for the younger adults, unemployed and less educated populations. This should be followed with adequate budgeting and policy implementation monitoring efforts, which are crucial for Nigeria's journey towards universal health coverage and elimination of viral hepatitis.

Towards better understanding of factors controlling carbon (C) exchange between inland waters and atmosphere, we addressed inorganic carbon cycle in semi-arid lakes of Central Eurasia, subjected to strong impact of on-going climate change. For this, we assessed the hydrochemical vari-ability and quantified its control on formation of authigenic carbonate minerals, occurring within the upper layer of sediments in 43 semiarid lakes located in the southwest of Western Siberia (Central Eurasia). Based on measurements of pH, total dissolved solids (TDS), cationic and anionic composition, dissolved organic and inorganic C, as well as textural and mineralogical characterization of bottom sediments using X-ray diffraction and scanning electron microscopy, we demonstrate that lake water pH and TDS are primarily controlled by both lithological and climatic context of the lake watershed. We have not revealed any direct relationships between lake morphology and water chemistry. The most common authigenic carbonates scavenging atmospheric CO2 in the form of insoluble minerals in lake sediments were calcite, aragonite, Mg-calcite, dolomite and hydro-magnesite. The calcite was the most common component, aragonite mainly appears in lakes with sediments enriched in gastropod shells or artemia cysts, while hydromagnesite was most common in lakes with high Mg/Ca molar ratios, as well at high DIC concentrations. The relationships between mineral formation and water chemistry established in this study can be generalized to a wide suite of arid and semi-arid lakes in order to characterize current status of inorganic C cycle and predict its possible modification under on-going climate warming such as water temperature rise and change of hydrological connectivity, primary productivity and nutrient regime.

Background: SARS-CoV-2 continues to impact human health globally, with airborne transmission being a significant mode for transmission. In addition to tools like vaccination and testing, counter-measures that reduce viral spread in indoor settings are critical. This study aims to assess the efficacy of UV-C light, utilizing the Violett sterilization device, as a countermeasure against airborne transmission of SARS-CoV-2 in the highly susceptible Golden Syrian hamster model. Methods: Two cohorts of naïve hamsters were subjected to airborne transmission from experimentally infected hamsters; one cohort was exposed to air treated with UV-C sterilization, while the other cohort was exposed to un-treated air. Results: Treatment of air with UV-C light prevented the airborne transmission of SARS-CoV-2 from experimentally exposed hamster to naïve hamsters. Notably, this protection was sustained over a muti-day exposure period during peak viral shedding from hamsters. Conclusion: These findings demonstrate the efficacy of the UV-C light to mitigate airborne SARS-CoV-2 transmission. As variants continue to emerge, UV-C light holds promise as a tool to reduce infections in diverse indoor settings, ranging from healthcare facilities to households. This study reinforces the urgency of implementing innovative methods to reduce airborne disease transmission and safeguard public health against emerging biological threats.

Background: Acute pancreatitis is a common emergency. Morbidity control requires early detection of disease severity. METHODS: A total of 131 AP patients were analyzed retrospectively. Patients were divided into two groups mild AP (MAP: Ranson score <3) and severe AP (SAP: Ranson score ≥3), according to Ranson’s criteria. Demographic data, hospitalization duration, PNI, CRP, and RDW levels were compared. Any p-value below 0.05 (p<0.05) was accepted as statistically significant. RESULTS: Study included 67 (51.15%) males and 64 (48.85%) females. The age average was 59.74 (19-90) years. 95 (72.52%) patients had MAP, and 36 (27.48%) patients had SAP. Mean hospitalization time, PNI, and CRP differed significantly between the two groups (p=0.010, p<0.05, p<0.05, respectively). The RDW (p=0.380) level difference was insignificant. For SAP prediction; the sensitivity, specificity and cut-off value according to Ranson code cut-off point for PNI were determined as 80.0% (95% CI:54.8-85.8), %72.2 (95% CI:70.5-87.5) and ≤45.6 (gr/L) + (mm3), respectively, and 94.7% (95% CI:57.8-87.9), %75.0 (95% CI:88.1-98.3) and >105,1 mg/L, respectively for CRP. CONCLUSION: PNI and CRP values (but not RDW values) were compatible with the disease severity determined by the Ranson criteria.

The integration of deep learning methods, especially Convolutional Neural Networks (CNN), and Synthetic Aperture Radar Automatic Target Recognition (SAR ATR) has been widely deployed in the field of radar signal processing. Nevertheless, these methods are frequently regarded as black-box models due to the limited visual interpretation of their internal feature representation and parameter organization. In this paper, we propose an innovative approach named C-RISE, which builds upon the RISE algorithm to provide a post-hoc interpretation technique for black-box models used in SAR Images Target Recognition. C-RISE generates saliency maps that effectively visualize the significance of each pixel. Our algorithm outperforms RISE by clustering masks that capture similar fusion features into distinct groups, enabling more appropriate weight distribution and increased focus on the target area. Furthermore, we employ Gaussian blur to process the masked area, preserving the original image structure with optimal consistency and integrity. C-RISE has been extensively evaluated through experiments, and the results demonstrate superior performance over other interpretation methods based on perturbation when applied to neural networks for SAR image target recognition. Furthermore, our approach is highly robust and transferable compared to other interpretable algorithms, including white-box methods.

A twelve-week feeding trial was conducted to investigate the effect of dietary supplementation of a functional immunostimulant mixture (FIM; nucleotides, β-glucan and vitamins C and E) on growth, feed utilization, innate immunity, digestive enzyme activity, hematological parameters, intestinal morphology and inflammatory gene expression of olive flounder, Paralichthys olivaceus. A fish meal-based basal diet (control) was formulated and three other diets were prepared by incorporating 0.5, 1.0 and 1.5% FIM into the basal diet (HB0.5, HB1.0 and HB1.5, respectively). Five replicate groups of fish (26.3 ± 0.1 g) were fed one of the experimental diets. Inclusion of 1.5% FIM in the diet significantly enhanced growth and feed utilization. Significantly higher plasma hemoglobin, hematocrit, total protein levels and lower plasma glucose level were observed in HB1.5 group. Total immunoglobulin content, lysozyme, nitroblue tetrazolium, myeloperoxidase, superoxide dismutase, glutathione peroxidase and catalase activities and immune-related gene expressions of toll-like receptor and perforin were significantly increased at highest inclusion level. FIM supplementation significantly increased villus height and goblet cell counts. Anti-inflammatory gene expression was significantly upregulated at a 1.5% level. Dietary supplementation of 1.5% of FIM could improve growth and feed utilization, immune, hematological and histomorphological parameters of olive flounder.

Recently, the Third Generation Partnership Project (3GPP) introduced the New Radio (NR) technology for Vehicle-to-everything (V2X) communication to enable delay-sensitive and bandwidth-hungry applications in vehicular communication. The NR system is strategically crafted to complement the existing Long Term Evolution (LTE) Cellular-Vehicle-to-Everything (C-V2X) infrastructure, particularly to support advanced services such as the operation of automated vehicles. It is widely anticipated that the 5th generation (5G) NR system will surpass LTE C-V2X in terms of achieving superior performance in scenarios characterized by high throughput, low latency, and enhanced reliability, especially in the context of congested traffic conditions and a diverse range of vehicular applications. This article will provide a comprehensive literature review on vehicular communications from Dedicated Short Range Communication (DSRC) to NR V2X. Subsequently, it delves into a detailed examination of the challenges and opportunities inherent in NR V2X technology. Finally, we proceed to elucidate the process of creating and analyzing an open-source 5G NR V2X module in network simulation-3 (ns-3) and then demonstrate the NR V2X performance in terms of different key performance indicators implemented through diverse operational scenarios.

Background: Constipation is one of the chronic gastrointestinal functional diseases that affects the quality of life. While Qi Lang Formula (QLF) has demonstrated effectiveness in alleviating constipation symptoms, its precise mechanism remains elusive. Methods: QLF was analyzed using UPLC-MS/MS. Targets for QLF were collected from SwissADME, Herb, ITCM databases, and FC-related targets from scRNA-seq and Genecards databases. Overlapping targets suggested potential QLF therapy targets for FC. Enrichment analysis used the KOBAS database. A "drug-ingredient-target" network was constructed with Cytoscape, and AutoDock verified active component binding. H&E staining assessed colonic mucosa changes, TEM examined ICC structural changes. ELISA measured neurotransmitter levels, and western blot verified QLF's effect on target proteins. ICC proliferation was observed through immunofluorescence. Results: We identified 89 targets of QLF associated with ICC-related FC, with c-Kit emerging as the pivotal target. Molecular docking studies revealed that Atractylenolide Ⅲ, Apigenin, Formononetin, Isorhamnetin, Naringenin, and Ononin exhibited strong binding affinities for the c-Kit structural domain. QLF significantly enhanced first stool passage time, fecal frequency, fecal moisture content, and intestinal propulsion rate. Further analysis unveiled that QLF not only restored neurotransmitter levels but also mitigated colon muscular fiber ruptures. ICC ultrastructure exhibited partial recovery, while RT-qPCR and western blot confirmed upregulated c-Kit expression and downstream targets. Immunofluorescence results indicated ICC proliferation post QLF treatment in rat colon. Conclusion: Our findings suggest that QLF may promote ICC proliferation by targeting SCF/c-Kit and its downstream signaling pathway, thereby regulating intestinal motility.

Nowadays, digitalization and automation in both industrial and research activities is a driving force for innovations. In recent years, Machine Learning (ML) techniques - the subset of Artificial Intelligence - have been widely applied as a key tool to automize and digitalize numerous in-dustrial processes. ML models can predict specific features, like materials' lifetime in a heating device, based on recently trained algorithms with applied input data. The results of ML algorithms are easy to interpret and can significantly decrease the time of research and decision-making, thus, substituting the trial-error approach. This work presents the state of the art in the application of Machine Learning in the investigation of MgO-C refractories for the steel industry. Also, the work presents an overview of the most commonly used ML algorithms in refractory engineering. So far published results confirm the high performance of ML, e.g., for prediction of oxidation behaviour, optimum graphite content and wear rate of MgO-C refractories, or for clustering materials based on various fused and sintered MgO sources into groups with similar corrosion resistance, thus, permitting to reduce expensive fused raw materials content. Most of the presented works were positively validated via experiment.

Background: Recommended CKD first-line diagnostics is based on GFR-determination by Creatinine. Cystatin C-use may provide better assessment. Methods: We compared creatinine- and cystatin C-derived eGFR determination in first-line di-agnostic of 112 hospital patients aged >60 years (median=76 years). Patients were judged kid-ney-sane according to first-line diagnostic recommendations (N=61, eGFR (CKD-EPI) ≥60ml/min/m2, total urine protein <150mg/g creatinine, urinary red and white blood cells not increased) or classified at-risk for kidney insufficiency due to aortic valve dysfunction (N=51). Plausibility of eGFR-values was evaluated retrospectively by final case diagnoses. Results: eGFR (CAPA) was found linearly correlated to eGFR (CKD-EPI) (R2=0.5, slope=0.69, p<0.0001). In 93/112 (>80%) cases, eGFR (CAPA) yielded lower values (on average ≈20%). In 55/112 (49%) cases CKD-stage decreased. CKD-reclassification from kidney-sane to kid-ney-insufficient state (i.e. CKD1/2 to CKD3a/b or 4) or reclassification to more severe kidney in-sufficiency (i.e. CKD3a3b/4 or 3b4) was found in 41/112 (37%) cases. Worsening of CKD-classification (kidney-sanekidney-insufficient) based on eGFR (CAPA) was in 30% of cases plausible in the light of final case-diagnoses. Conclusion: In elderly patients (>60 years), renal function appears systematically overestimated by creatinine-based eGFR (CKD-EPI) heralding for this group employment of cystatin C-based eGFR (CAPA) as first-line diagnostic.

Powerful emitters of the ultraviolet C (UVC) light in the wavelength range of 230-280nm are necessary for the development of effective and safe optical disinfection technologies, high-sensitive optical spectroscopy and non-line-of-sight optical communication. This review considers such UVC-emitters with electron-beam pumping of heterostructures with quantum wells in the (Al,Ga)N material system. The important advantages of these emitters include the absence of the critical problem of p-type doping and the possibility of achieving record (up to several tens of watts for peak values) output optical power values in the UVC range. The review consistently considers about a decade of world experience in the implementation of various UV emitters with various types of thermionic, field-emission, and plasma-cathode electron guns (sources) used to excite various designs of active (light-emitting) regions in heterostructures with quantum wells AlxGa1-xN/AlyGa1-yN (x = 0 − 0.5, y = 0.6 − 1) fabricated either by metal-organic chemical vapor deposition or by plasma-activated molecular beam epitaxy. Special attention is paid to the production of heterostructures with multiple quantum wells/two-dimensional(2D) quantum disks GaN/AlN with a monolayer (1ML ~ 0.25nm) thickness, which ensures a high internal quantum efficiency of radiative recombination in the UVC range, low elastic stresses in heterostructures, and a high output UVC-optical powers.

Analytics have become increasingly popular among sports in recent years, providing valuable information regarding physical and mental health. Many athletes have found that analytics during training can help to improve their performance, reduce the risk of injury, and enhance their overall well-being. This paper aims to improve the results of handball players by applying a method for measuring the influence of different trials on aggregate performance calculated per each athlete in order to qualify for the Olympic Games. By separating the isolated action of each trial, the result is an additional influence caused by the interaction of factors or the simultaneous action. That might explain why the neuromuscular feedback loop is utterly necessary to perform handball motor actions. Further on, the ML analysis can help identify areas for improvement, optimize training programs, and enhance overall team performance.

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to interrogate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations and the possible extent of these additional requirements. The relevant data were extracted from the NHANES 2017-2018 datasets, the final cohort of which comprised 2828 non-supplementing adult males and females (aged 18 – 80+ years) with both vitamin C serum concentrations and dietary intake data available. The data was subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: &gt;3.0, 1.36 – 3.0, ≤1.35), weight tertiles (≤72, 72-91, ≥91 kg), BMI tertiles (≤26, 26-32, ≥32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach ‘adequate’ serum concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heaver weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes &gt; 75 mg/day, at intakes &lt; 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population must consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach the same vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

Biological neural network (BNN) is the core brain for creature to accomplish its intelligent behaviors through unique network structure and mechanisms. It also inspires controlling human-designed autonomous agents including robots to generate more advanced intelligent behaviors by mimicking the neural control mechanism of creatures at a deeper and more interactive level. Here, we constructed a whole-brain neural network model of Caenorhabditis elegans (C. elegans), which characterizes the electrochemical processes at the level of cellular synapse. The neural network simulation integrates computational programming and visualization of neurons and synapse connections of C. elegans, containing the specific controllable circuits summarization with their dynamic characteristics within the whole network. To illustrate its particular intelligent control capability in terms of robotics, we introduce the first innovative methodology for applying the BNN model to a 12-legged robot’s movement control based on the established numerical simulation platforms. We accomplished and designed two methods and corresponding encoding processes, one involving orientation control and the other involving locomotion generation, to demonstrate the intelligent control performance of BNN. Both simulation and experiment results indicate that the robot exhibits stronger autonomy and more intelligent moving performance under the control of BNN. We then summarized the contributions for digitalizing the C. elegans’ whole-brain neural network in real-time and utilizing it to control robot in a closed loop to validate its advanced intelligence control ability in terms of a scientific robot.

Nonalcoholic fatty liver disease (NAFLD) is a liver metabolism-associated steatohepatitis caused by non-alcoholic factors. NAFLD is currently the most prevalent liver disease in the world, affecting one-fourth of the world's population, and its prevalence increases with age. There are no approved drugs specifically for the treatment of NAFLD, and one important reason hindering drug development is the lack of effective biomarkers. C-reactive protein (CRP), a marker of inflammation, has been linked to NAFLD and aging in recent studies. Coincidentally, hepatocytes are responsible for the major CRP production, and the levels of CRP increase with age. Therefore, CRP is not only a potential marker, but also acts as a key factor driving liver aging and NAFLD. Herein, we reviewed the biological function and production mechanism of CRP and the relationship between CRP and NAFLD. We also comprehensively described the potential molecular mechanisms of CRP-mediated signaling in aging-associated NAFLD. Finally, we proposed possible therapeutic approaches based on the mechanism of CRP signaling in the pathogenesis of NAFLD. We hope this study can provide new insights into the development of aging associated NAFLD biomarkers and suggest that modulation of CRP signaling is a potential therapeutic target.

Background: We previously reported that human keratinocytes express protease-activated receptor (PAR)-2 and play an important role in activated protein C (APC)-induced cutaneous wound healing. This study investigated the involvement of PAR-2 in the production of gelatinolytic matrix metalloproteinases (MMP)-2 and -9 by APC during cutaneous wound healing. Methods: Full-thickness excisional wounds were made on the dorsum of male C57BL/6 mice. Wounds were treated with APC on days 1, 2, and 3 post-wounding. Cultured neonatal foreskin keratinocytes were treated with APC with or without intact PAR-2 signalling to examine the effects on MMP-2 and MMP-9 production. Murine dermal fibroblasts from PAR2 knock-out (KO) mice were also assessed. MMP-2 and -9 were measured by gelatin zymography, fluorometric assay, and immunohistochemistry. Results: APC accelerated wound healing in WT mice, but had negligible effect in PAR-2 KO mice. APC stimulated murine cutaneous wound healing was associated with differential 0temporal production of MMP-2 and MMP-9, with the latter peaking on Day 1 and the former on Day 6. In-hibition of PAR-2 in human keratinocytes reduced APC-induced MMP-2 activity 25~50, but had little effect on MMP-9. Similarly, APC-induced MMP-2 activation was reduced by 40% in cultured dermal fibroblasts derived from PAR-2 KO mice. Conclusion: This study shows for the first time that PAR-2 is essential for APC-induced MMP-2 production. Considering the important role of MMP-2 in wound healing, this work helps explain the underlying mechanisms of action of APC to promote wound healing through PAR2.

Vaginal ecosystem is a unique environment where, in physiological conditions, lactobacilli dominate. However, also pathogenic microbial species, responsible of vaginitis and vaginosis, can harbor vaginal microbiota. To extend the data published by De Seta and Larsen in Pathogens (2021), here we analyzed both the anti-Candida and anti-inflammatory properties of the vaginal gel formulation, Respecta® Balance Gel (RBG), commercialized as an adjuvant to treat vaginitis and vaginosis. We evaluated its activity by an in vitro model where a monolayer of A-431 vaginal epithelial cells was infected by Candida albicans in the presence of RBG or the placebo formulation (pRBG). Specifically, we tested the RBG capacity to counteract C. albicans virulence factors as well as their anti-inflammatory properties. Our results show that, unlike the placebo, RBG reduces ,reduces, C. albicans adhesion, its capacity to form hyphae and C. albicans-induced vaginal cell damage. Interestingly, both RBG and pRBG reduce LPS-induced IL-8 secretion (being RBG the most effective) demonstrating that also the placebo retains anti-inflammatory properties. By our experimental approach we highlight the possible role of farnesol on such effects, but we would like to point out that lactic acid, polydextrose and glycogen too must be relevant in the actual application. Taken together, our results show that RBG impairs C. albicans virulence and is able to reduce the inflammation in the vaginal environment, ultimately allowing the establishment of a balanced vaginal ecosystem.

Background: this study aimed to describe the distribution of the genotype and allele frequencies of GJB2 variants in the Chinese population of the Dongfeng Tongji cohort and to analyze the features of the hearing phenotype. Methods: we used data from 9910 participants in the Dongfeng Tongji cohort in 2013 and selected nine GJB2 variants. Pure-tone audiometry was employed to measure hearing. Differences in genotype and allele frequencies were analyzed by chi-squared test or Fisher's exact test. Results: of the 9910 participants, 5742 had hearing loss. The genotype frequency of the GJB2 variant p.V37I was statistically significantly distributed between the normal and impaired hearing groups, but not for the variant c.235delC. A higher frequency of the p.V37I homozygous genotype was found in the hearing loss group (0.5%) than in the normal hearing group (0.1%). Patients with p.V37I and c.235delC homozygous mutations exhibited varying degrees of hearing loss, mainly presenting sloping and flat audiogram shapes. Conclusions: a significant difference was found in the genotype frequency of the GJB2 variant p.V37I between the case and control groups, but not for the variant c.235delC. Different degrees of hearing loss and various audiogram shapes were observed in patients with p.V37I and c.235delC homozygous mutations.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

Vasculitis diseases include Kawasaki Disease (KD), Kawasaki Disease Shock Syndrome (KDSS), Multisystem Inflammatory Syndromes (MIS), Henoch-Schönlein purpura (HS) or IgA Vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than adults. These diseases have been extensively studied, but understanding of the disease etiology remains to be established. Many studies have failed to demonstrate an association between these vasculitis diseases and vaccination. Here, the Vaccine Adverse Event Reporting System (VAERS) is used to demonstrate that, in certain rare cases, the number of cases of KD, MIS, and HS is higher than background following vaccination. These rare cases are predicted to occur in individuals with genetic risk factors who produce antibody titer levels above primary immune response level. Herein, the model of humoral immune response antibodies bound to antigens (pathogen or vaccine) creating immune complexes is proposed. These immune complexes are proposed to bind Fc receptors on immune cells and platelets resulting in cell activation and release of inflammatory molecules including histamine and serotonin. Immune complexes and inflammatory molecules including serotonin and histamine likely trigger vasculitis. Elevated serotonin and likely histamine drive initial vasoconstrictions disrupting blood flow. Increased blood flow pressure from cardiac capillary vasoconstrictions is predicted to trigger coronary artery aneurysms in some patients. For KDSS and MIS patients, these cardiac capillary vasoconstrictions are predicted to result in ischemia followed by ventricular dysfunction. Ongoing ischemia can result in long-term cardiac damage. Cases associated with pathogens are likely to have persistent infections triggering disease onset.

Background: One of the main diseases of worldwide concern is non–insulin dependent Diabetes mellitus. 90-95% of patients with diabetes suffers from Type II diabetes, a metabolic diabetes whose prevalence is increasing in the world.Given the current prevalence of diabetes type II in society, research of natural compounds able to regulate glycaemia and insulin–resistance is nowadays covering importance, as alternative or co–adjuvant treatment to existing hypoglycaemic medicines. In pre–clinical steps of research, C. elegans is considered a promising in vivo model for the study of the molecular mechanism of glucose as part of anti–diabetic bioactivity.Most of the studies of insulin resistance with this in vivo model are carried out by using mutant strains such as daf-2 and the effects of the compounds are attributed a posteriori, after a physiological response of the worms rather than directly measuring preservation of activity inside the worm. Methods: The in vitro α-glucosidase inhibition of two oral formulations with Origanum vulgare extract before and after a simulated process of gastrointestinal digestion was evaluated. After confirming the in vitro activity, the α-glucosidase inhibition was tested in vivo through the new method proposed. Results: The crude extract showed an IC50 value similar to acarbose (positive control), before and after the gastrointestinal digestion. The encapsulated extract (111.86±1.25 µg/mL) did not present statistical differences with the positive control (110.10±1.15 µg/mL) after digestion. However, the powder formulation showed the highest hypoglycaemic activity (59.55±0.85 µg/mL).In vivo, the IC50 values showed similar profile than in vitro. Conclusion: A new simple and reliable method has been developed to determine pharmacological activities inside in vivo model C. elegans.The method has been evaluated with a hydroalcoholic extract of O. vulgare. The method is accurate and valid for the quantification of the inhibition of in vivo, allowing the direct attribution of this in vivo hypoglycaemic activity to the treatment. In addition, it opens the door to further research into in vitro pharmacological activities that require an in vivo counterpart.

: Cardiac surgery (CS) with extracorporeal circulation (ECC), induces oxidative stress and systemic inflammatory response, which may seriously affect postoperative lung function. We aimed to test if high parenteral (200mg/kg/24h) perioperative (48h) doses of Vitamin C (VitC) may reduce the incidence and severity of postoperative pulmonary complications (PPC) in selected CS patients. Single centered, prospective, randomized, single-blinded, interventional study included 150 patients, assigned to control group A (n=75) and interventional group B (n=75). Group B intraoperatively received 1/4 of the planned daily Vit C dose (200mg/kg/24h), diluted in 10 ml of normal saline, divided into three parts, while Group A received an equal volume of normal saline at the same time frames. After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 200 mg/kg/24h - 30 min i.v. infusion of VitC in 50 ml of normal saline, every 6h, for the next 48h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 hours, for the next 48h. Modified Kroenke’s score was used to determine the incidence and severity of PPC. The overall incidence of PPC was 36.7% and was significantly lower in Group B (13.3% v.s. 60.0%, p&lt;0.001). The severity of PPC was also significantly lower in Group B [1(1) v.s. 3(2), p&lt;0.001]. Besides, patients from Group B had significantly less damaged lungs and better postoperative renal function, shorter ICU stay, fewer ICU re-admissions, and lower hospital mortality. High parenteral daily VitC doses (200mg/kg/24h) given to selected CS patients for 48h after CS are safe and effective in reducing the incidence and severity of PPC. Further multicenter RCT is needed to confirm these results.

Considering the relevance of the pathogenesis research of different liver diseases, in our study we investigated the possible activity of IL-23/IL-17 axis on the im-munohepatotoxicity of two etiologically different CLD. A total of patients with CHC infection, 19 with NASH and 20 healthy controls (CG) were recruited. After histological verification from liver tissue obtain by liver biopsy, patients with CHC were divided into two groups: CHC-NSF (F0/F1/F2)-non-significant fibrosis, 20 patients, and CHC-SF (F3/F4)-significant fibrosis/cirrhosis, 16 patients. All anthropometric, biochemical, immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed accordance to standard procedure. The plasma levels of IL-6, Il-17A and IL-23 were significantly higher in CHC-SF and NASH in compared with CG. Also, plasma levels of IL-23/IL-17A were significantly higher in NASH in compared to CHC-SF. In CHC-SF we had significantly lowest IL-10 level in compared with all three groups. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in compared with NASH. IN CHC-SF and NASH, IL17-A and IL-23 in liver tissue were significantly higher in compare to plasma levels. In conclusan, proinflammatory response of IL-23/17A axis is dominant in plasma and liver tissue in CHC with higher levels of liver fibrosis and in NASH patients.

Recent years have experienced an increase in construction and demolition waste (C&amp;DW), which is the most significant solid waste stream. C&amp;DW is contributing to exceeding all planetary boundaries and presents a range of other issues. In order to better understand the existing research on C&amp;DW, a global bibliographic analysis was undertaken through seven groups of keyword searches and the results visualised using VOCviewer. The results show that C&amp;DW receives only a modest research attention compared to other areas of waste, and this is despite an exponential increase in C&amp;DW research since 2016. The analyses also show that concrete is the most researched material in terms of C&amp;DW, and that reuse, recycling, and circular economy are so far attracting only proportionally modest research attention. This signals a need for further acceleration of the C&amp;DW research, and specifically for more research on reuse, recycling, and circular economy for materials other than concrete.