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.

The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.

The article presents comparative results from 5 categories of animals (4 samples originating from pigs, 2 from cows, 1 from chicken, 1 from ostriches, 1 from horses, samples quantified with A, B, C, D, E, F, G, H, I). These samples were collected from large, medium and small (family) farms. The results were validated by the biogas production generated by the respective samples, using the Automatic Methane Potential Test System (AMPTS II) bio-processor. The largest amounts of biogas (2,464.5 Nml, 2,262.0 Nml) were recorded for the samples from pig farms (Sample B and Sample D), whereas the lowest values were obtained in the case of Sample A (414.1 Nml) and Sample C (558.3 Nml). The heavy metals analyzed in the article are Zn, Cu, Fe, Mn, Ca, K, As. The results corroborate that the C/N ratio can also vary to values lower than 20-30, without affecting the biogas production process, and the heavy metal content must be known especially for the full management of the wastes. All final data presented in the article are based on repeated, triplicate experiments, with less as 2% deviation between data.

Background and Objective: Although whole body-electromyostimulation (WB-EMS) has been shown to favorably improve body composition in several research studies, it has not been confirmed how it affects adipose tissue-derived biomarkers and circumferences of the abdomen and thighs. Materials and Methods: Twenty participants of obese elderly women were randomly classified into an EMS group (EMSG; n = 10) or a non-EMS group (CON; n = 10). The WB-EMS suits used in this study enabled the simultaneous activation of 8 muscle groups with selectable intensities for each phase. Stimulation frequency was selected at 85 Hz, impulse-width at 350 μ seconds, and impulse-rise as a rectangular application. Impulse duration was 6 seconds with a 4-second break between impulses. The EMS sessions were combined with aerobic dancing 3 times a week for 12 weeks. Both groups received the same program; however, the CON did not receive electrical stimuli. Biomarkers and body composition including circumferences of the abdomen and thighs were measured on Week 0 and Week 12. Results: Compared with the CON, 1) a significant effect of the EMS-intervention concerning decreased body weight (p = 0.032) and increased basal metabolic rate (p = 0.029) were evident. The thigh subcutaneous fat and total fat of EMSG were not significantly changed, but those of CON were significantly increased after 12 weeks. 2) The biomarkers of CON either increased or showed no change, although the interleukin (IL)-6 was significantly (p = 0.028) decreased in EMSG. Specifically, C-reactive protein (CRP; p = 0.005) and alpha-fetoprotein (p = 0.050) of CON were significantly increased after 12 weeks. In addition, the IL-6 (p = 0.034), CRP (p = 0.001), carcinoembryonic antigen (p = 0.017), and low density lipoprotein (p = 0.005) of EMSG were lower than those of CON in the end of experiment. 3) Conclusions: The results indicate that EMS intervention improved body composition and reduced negative biomarkers, thus highlighting its effectiveness.

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.

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce risk of end-stage liver diseases to the level observed in patients that have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to accumulation of arginine and upregulates proline oxidase with a concomitant decrease in proline concentrations. Addition of exogenous proline moderately suppressed viral replication. HCV upregulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism.

In an attempt to correct misunderstandings this article brings together the observations on Calcium, Myosin Binding Protein-C and Hypertrophic Cardiomyopathy in the basic function of cardiac muscle. A finding of many years ago is reiterated in a novel enzyme kinetic format with defined rate limiting step which makes CaATP the apparent substrate of the actomyosin cross-bridge. The relationship of these kinetics to recent observations on disruption of myosin binding protein-C is described along with how this bears on the understanding of the related cardiomyopathies.

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.

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs known as SINE-VNTR-Alu (SVA) demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), however the exact mechanism has yet to be identified. In this study we used whole genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Center ALS Consortium, to elucidate the influence of reference SVA elements on gene expression genome-wide within central nervous system (CNS) tissues. To investigate this, we applied matrix expression quantitative trait loci analysis and demonstrated that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position, and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative disease. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.

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.

I have recently reiterated that the cross-bridge is a calcium ATPase that is inhibited by magnesium and this arises because in normal hearts Myosin binding Protein-C prevents the use of MgATP as rate limiting substrate ensuring that Ca²⁺ replaces Mg²⁺ in the excitation pathway. Here I revisit the studies on [Ca²⁺] dependency of ATPase and tension under diastolic stretch with a different conclusion on Hill coefficients. This reveals the underlying mechanisms of the Frank-Starling Law and Hypertrophic myopathy are not the same, the former being kinase controlled.

In this paper, several two-dimensional clustering scenarios are given. In those scenarios, soft partitioning clustering algorithms (Fuzzy C-means (FCM) and Possibilistic c-means (PCM)) are applied. Afterward, VAT is used to investigate the clustering tendency visually, and then in order of checking cluster validation, three types of indices (e.g., PC, DI, and DBI) were used. After observing the clustering algorithms, it was evident that each of them has its limitations; however, PCM is more robust to noise than FCM as in case of FCM a noise point has to be considered as a member of any of the cluster.

Adenoviruses are associated with respiratory tract, gastrointestinal or, less frequently, other involvement. Epidemics of adenovirus infections occur globally, in communities and in closed or crowded settings. In our institution, an outbreak of Adenovirus infection in infants and children was recently observed. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n=67, cough n=44; tonsillar exudate n=17; other respiratory signs n=4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n=26, vomiting n=8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN and platelets, while CRP level approached statistical significance (p=0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, possible association between level of CRP and presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had significantly more often tonsillar exudate and diarrhea, while those in the lower tertile had a 4.4 days duration of fever, vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p=0.006). Duration of hospitalization was not associated with the CRP level. The median time from the receipt of positive adenovirus PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of adenovirus detected by PCR ranged between 47 million and 15/L. Falling in the highest terzile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception of a significantly higher leukocyte count. Rapid turn-around of results of molecular testing of adenovirus genome on pharyngeal swab allowed us to rapidly diagnose adenovirus infection, allowing stopping antibiotic therapy and immediate discharge, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of adenovirus from pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing preferential use of qualitative rather than quantitaive assay.

Abstract: Carbohydrates form the major source of energy in Asian diets. A lower carbohydrate diet became the recommended golden standard for healthy lifestyle. However, the effects of low-carbohydrates diet on health in apparently healthy individuals have been poorly studied, especially in relation to insulin resistance syndrome (IRS). A total of 120 healthy weight participants with no previous history of a major medical condition and an average BMI of ≤ 25kg/m2 were recruited. Self-reported dietary intake and objective physical activity by accelerometry were tracked for seven days. Participants were divided into three categories according to their dietary intake of carbohydrates. Blood samples were collected for metabolic markers analysis. HOMA of insulin resistance (HOMA-IR), β-cell function (HOMA-B) and C-peptide were used to evaluate glucose homeostasis. The consumption of low carbohydrates (less than 45% of total energy) significantly correlated with higher HOMA-IR, Lower HOMA-β % compared to moderate carbohydrate intake (between 45% to 65%). However, only the HOMA-β % was significantly influenced by carbohydrates intake. Moreover, low carbohydrates intake was significantly associated with elevated C-peptide secretion. The substitution of carbohydrates with other macronutrients, such as fat and proteins in the Atkins/ketogenic diet, resulted in a pronounced induction of IRS-related inflammatory markers; FGF2, IP-10, IL-6, IL-17A, MDC and reduction of IL-13. Overall, the presented data highlight, for the first time, that low carbohydrate intake results in significant glucose homeostasis imbalance that may be driven by a heightened state of inflammatory response.

Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine-deaminases (ADARs) on dsRNAs. Although a considerable fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicate changes in A-to-I RNA editing frequencies following exposure to several stress types. However, the overall effect of stress on the expression of ADAR targets is not fully understood. Here, we performed high-throughput RNA sequencing of wild-type and ADAR mutant C. elegans worms after heat-shock to analyze the effect of heat-shock stress on the expression pattern of genes. We found that ADAR regulation following heat-shock does not directly involve heat-shock related genes. Our analysis also revealed that lncRNAs and pseudogenes, which have a tendency for secondary RNA structures, are enriched among upregulated genes following heat-shock in ADAR mutant worms. The same group of genes is downregulated in ADAR mutant worms under permissive conditions, which is likely, considering that A-to-I editing protects endogenous dsRNA from RNA-interference (RNAi). Therefore, temperature increases may destabilize dsRNA structures and protect them from RNAi degradation, despite the lack of ADAR function. These findings shed new light on the dynamics of gene expression under heat-shock in relation to ADAR function.

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those involving costly resource reallocation, and exhibiting endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

The mechanistic target of rapamycin (mTOR) kinase is one of the top drug targets for promoting health and lifespan extension. Besides rapamycin, only a few other mTOR inhibitors have been developed and shown their ability to slow aging. We used machine learning to predict novel small molecules targeting mTOR. We selected one small molecule, TKA001, based on in-silico predictions of a high on-target probability, low toxicity, favorable physicochemical properties, and preferable ADMET profile. We confirmed TKA001 binding in silico by molecular docking. TKA001 potently inhibits both TOR complex 1 and 2 downstream signaling in vitro. Furthermore, TKA001 inhibits human cancer cell proliferation in vitro and extended the lifespan of C. elegans, suggesting that TKA001 can slow aging in vivo.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Standard evolutionary theory, supported by mathematical modelling of outbred, dispersed populations predicts that ageing is not an adaptation. We recently argued that in clonal, viscous populations, programmed organismal death could promote fitness through social benefits and has, in some organisms (e.g. Caenorhabditis elegans), evolved to shorten lifespan. Here we review previous adaptive death theory, including consumer sacrifice, biomass sacrifice, and defensive sacrifice types of altruistic adaptive death. In addition we discuss possible adaptive death in semelparous fish, coevolution of reproductive and adaptive death, and adaptive reproductive senescence in C. elegans. We also describe findings from recent tests for the existence of adaptive death in C. elegans using computer modelling. Such models have provided new insights into how trade-offs between fitness at the individual and colony levels mean that senescent changes can be selected traits. Exploring further the relationship between adaptive death and social interactions, we consider examples where adaptive death results more from action of kin than from self-destructive mechanisms and, to describe this, introduce the term adaptive killing of kin.

Ready-to-eat fresh fruit have an increasing presence in international markets due to its convenience and health benefits. However, these produces are highly perishable and efficient technologies to increase their shelf life are needed. In the present research, different citrus fruit species and cultivars from organic farming were assayed to obtain enzymatically citrus segments. The best results in terms of segment quality were observed for ‘Hernandina’ clementine which was chosen to make a new ready-to-eat produce based on peeled citrus segments packaged in glass jars with slight syrup made on citrus juice and organic sugar cane. The most appreciated syrup was those containing 50-50 (v/v) of ‘Fino’ lemon juice and ‘Hernandina’ clementine based on the sensory scores given by the panellists. In addition, different pasteurization treatments were assayed to preserve the new produce safety and nutritional and sensory quality properties during storage at cold temperature. Results showed that pasteurization treatment at 50 °C for 45 min could be enough to avoid microbial contamination with mesophilic and psychrophilic aerobic bacteria or yeast and mould and to maintain sensory properties until five weeks of storage at 4 °C. In addition, only a 10 % reduction of vitamin C was observed from fresh segments or syrup until the end of storage period, showing that the new ready-to-eat produce would conserve high bioactive compound content and health benefits after pasteurization and prolonged cold storage.

Umbu is a tropical fruit with high content of bioactive compounds. However, maturation causes significant losses on nutrient density reducing the nutritional value of this highly appreciated fruit. Thus, the objective of the present work was to encapsulate the Umbu fruit bioactive compounds using spray drying and identify the variables affecting the biomolecules preservation. A Box-Behnken experimental design with 3 factors was set varying inlet temperature, atomization flow rate, and maltodextrin concentration for process otimization. Then the powder physicochemical and chemical properties were characterized, and results were modeled using a polynomial equation. Results revealed that the droplet size and maltodextrin concentration had a significant influence on the conservation of the biomolecules. Drying kinetics favoring fast formation of a particle crust increases encapsulation efficiency. Bioactive compounds retention was achieved by increasing maltodextrin even at high temperatures, where a matrix is formed hindering chemical degradation. Process optimization was validated and revealed low inlet temperatures (122ºC), high atomization flow rate (5kg/h) and high maltodextrin concentration (20%) to be the most desirable conditions for bioactive compounds retention.

Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents which targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents which target multiple components of the host’s response to an infectious agent will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.

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.

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.

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2’-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino acid residues from the hypervariable E region of the capsid in the cultured viruses provided no support for the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4-0.6 µM, TI 21; 2CMC EC50, 2.7-5.3 µM, TI >18; NITD-008, 0.5 to 0.9 µM, TI >111. Investigation of these antivirals for treatment of FCV-VSD is warranted.

Febrile infections are a common cause of presentation to the emergency department (ED) in chil-dren. While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; the better understanding of immunochemical pathways has nowadays led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models combining them for serious bacterial infections (SBI) diagnosis in febrile children. Litera-ture analysis showed that inflammatory response is a complex mechanism in which many bio-chemical and immunological factors contribute to host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined and for this reason it is reasonable to take them both into consideration in the evaluation of a febrile children. The potential of machine learning tools, who represent a real novelty in medical practice, in conjunction with routine clinical and biological in-formation, may improve accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pe-diatric precision medicine still uncertain. More data from further researches are needed to improve clinical practice and decision making using these new technologies.

An undescribed diterpene, stellerterpenoid A (1) and two undescribed sesquiterpenoids, stellerterpenoids B and C (2-3), together with six known compounds, were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic data (1D, 2D NMR, IR, UV and HR-ESI-MS). The absolute configuration of 1-3 were elucidated based on ECD calculation. Among of them, stellerterpenoid A was a rare 13, 14 - seco nortigliane diterpenoid and stellerterpenoid B was a guaiacane type sesquiterpenoid with an unusual 1, 2-diketone moiety. The known stelleraguaianone B (5) exhibited moderate activity to suppress NO production in LPS - simulated macrophages with an IC50 value of 24.76 ± 0.4 μM. None of the compounds showed inhibitory influenza virus and tumor activity.

The Ramazzottius varieornatus tardigrade is an extremotolerant terrestrial invertebrate belonging to the phylum of Tardigrada. At a length of 0.1-1.0 mm, tardigrades are small animals with an exceptional tolerance to extreme conditions such as high pressure, chemicals and irradia-tion. These properties have been attributed to the recently-discovered Dsup protein. Dsup is a nucleosome-binding protein that prevents DNA damage against X-ray and oxidative stress without impairing cell life, also in Dsup-transfected animal and plant cells. However, the precise “protective” role of this protein is still under study. We performed experiments on human cells and shows that, as compared to control cells, Dsup+ cells are more resistant to UV-C exposure and H2O2. Real-time PCR identified different expression patterns of endogenous genes involved in apoptosis, cell survival and DNA damage repair in Dsup+ cells in response to H2O2 and UV-C. While H2O2 treatment in Dsup+ cells only marginally involved the activation of pathways responsible for DNA repair reinforcing the idea of a direct protective effect of the protein on DNA, in UV-C exposed cells, Dsup efficiently upregulates DNA damage repair genes. In conclusion, our data may help to delineate the different mechanisms by which the Dsup protein operates in response to different insults.

Arthrospira platensis is the widely available source of spirulina and contains distinctive natural pigments including carotenoids and C-phycocyanin (C-PC). In this study, the major carotenoid and C-PC contents were determined in seven commercially available spirulina powder products and laboratory-prepared A. platensis trichomes (AP-1) by an LC-DAD method and a UV-Visible spectrometry, respectively. The correlation of these two pigment content levels with Hunter color coordinates and antioxidant activity was also evaluated. The L* value failed to show a significant correlation with pigment content, but a positive correlation was observed between a* values and the contents of total carotenoid and C-PC. As b* values decreased, the total carotenoid and C-PC contents increased. AP-1 exhibited the highest content of total carotenoids, chlorophyll a and C-PC, and antioxidant activities among the samples. This observation could be related to degradation of these pigments during the mass production process. The carotenoid profiles suggested that the commercial spirulina powders originated from two different sources, A. platensis and A. maxima. Total carotenoid and C-PC content exhibited positive significant correlations with antioxidant activities measured by DPPH and ABTS assays. These results provide a strong scientific foundation for the establishment of standards for the commercial distribution of quality spirulina products.

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.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

In this paper, the computational fluid dynamics (CFD) method has been used to simulate the gas flow and the catalytic hydrogenation process of the C-2 hydrogenation adiabatic reactor in a practical ethylene production unit of a chemical plant. The laminar finite-rate model was used for the chemical reaction model. The standard two-equation model was used for the turbulence model. The exponent-function kinetic model was used for the reaction dynamics model. The simulation results were in good agreement with the actual industrial data obtained from the C-2 hydrogenation reactor, and the distributions of reaction parameters such as temperature and component concentrations in the reactor were further analyzed. Based on the validated CFD models, the structure and operating conditions of the reactor, as well as hydrogen load distribution ratios, are simulated for comparing the comprehensive performance metrics of ethylene selectivity and acetylene conversion rate; as a result, we can obtain the optimal temperature of 312 K, the optimal hydrogen/acetylene ratio of 0.10 as well as the optimal hydrogen load distribution ratio of 4:4:2, and the diameter/height ratio exerts a marginal effect on the selectivity, conversion rate and harmonic mean of the reactor.

Aim. The purpose of the work was the development of a machine learning model for diagnosing the stage of liver fibrosis in patients with chronic viral hepatitis C according to the data of routine clinical examination. Materials and methods. A total of 1240 patients with chronic viral hepatitis C was examined. A set of data obtained from 689 patients balancing by the stage of liver fibrosis was used for developing and testing machine learning models. 9 routine clinical parameters were selected as the most important predictors for determining the likelihood of liver fibrosis the 3–4 stages presence: age, height, weight and body mass index of the patient, the number of platelets in the clinical blood test, levels of alanine transaminase, aspartate transaminase, gamma-glutamyltransferase, and total bilirubin in a biochemical blood test. Results. The accuracy of the developed method for determining the 3–4 stages of liver fibrosis in patients with chronic viral hepatitis C in comparison with the «gold standard» of diagnosis (liver biopsy) was 80.56% (95% CI: 69.53–88.94%), sensitivity — 66.67%, specificity — 94.44%. Conclusion. The developed method is an alternative to more expensive and geographically inaccessible studies. The method does not require the purchase of additional equipment or software, as well as additional laboratory tests, when used in real clinical practice. The introduction of the method into clinical practice can help to solve the problem of low material and territorial availability of diagnostic tests and allow determining the stage of liver fibrosis in patients with chronic viral hepatitis C.

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

Dengue is one the most significant mosquito-borne viral diseases globally, with its prevalence extending across tropical and subtropical regions, exerting a considerable financial strain on health systems. Despite decades of research leading to the development of a vaccine implemented in endemic countries, its usage remains restricted to a fraction of the population at risk of contracting dengue. Due to these limitations, there is a growing focus on research aimed at unraveling the cellular mechanisms crucial for Dengue virus (DENV) infection to pinpoint potential host targets. Multiple studies propose a pivotal role of cytoskeletal remodeling in DENV infection. Specifically, DENV alters the organization of actin to facilitate viral entry, replication, and release. In this study, we investigated the involvement of the protein c-Abl, a kinase crucial in actin dynamics, in the context of DENV infection. Our findings suggest that either silencing or pharmacological inhibition of the kinase c-Abl leads to accumulation of dengue ENV protein in vitro, associated with actin remodeling. These results illuminate cellular mechanisms that could serve as potential therapeutic alternatives for dengue management.

CD8+ cytotoxic T lymphocytes (CTLs) play a crucial role in anti-tumor immunity. In a previous study, we identified a subset of murine effector CTLs expressing the hepatocyte growth factor (HGF) receptor c-Met (c-Met+ CTLs) that are endowed with enhanced cytolytic capacity. HGF directly inhibited the cytolytic function of c-Met+ CTLs, both in 2D in vitro assays and in vivo, leading to reduced T cell responses against metastatic melanoma. To further investigate the role of c-Met+ CTLs in a three-dimensional (3D) setting, we studied their function within B16 melanoma spheroids and examined the impact of cell-cell contact on the modulation of inhibitory checkpoint molecules expression such as KLRG1, PD-1 and CTLA-4. Additionally, we evaluated the cytolytic capacity of human CTLs clones expressing c-Met (c-Met+) and compared it to c-Met− CTLs clones. Our results indicated that, similar to their murine counterparts, c-Met+ human CTLs clones exhibited increased cytolytic activity compared to c-Met− CTLs clones, and this enhanced function was negatively regulated by the presence of HGF. Taken together, our findings highlight the potential of targeting the HGF/c-Met pathway to modulate CTL-mediated anti-tumor immunity. This research holds promises for developing strategies to enhance the effectiveness of CTL-based immunotherapies against cancer.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions and biomarkers, such as c-reactive protein (CRP) and adiponectin. Recently, marine algal biomaterials have been investigated extensively due to their health benefits. We report on associations between metabolic markers and bioactive nutrients from diet and Sujiaonori algal biomaterial (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of ulvan-rich fiber, in a sample of Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m² [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

Cordia dichotoma Forst. (F. Boraginaceae) has been traditionally used for the management of a variety of human ailments. In our earlier work, the antidiabetic activity of methanolic bark extract of C. dichotoma (MECD) has been reported. In this paper, two flavonoid molecules were isolated (by column chromatography) and identified (by IR, NMR and Mass spectroscopy/spectrometry) from the MECD with an aim to investigate their antidiabetic effectiveness. Molecular docking and ADMET studies were carried out using AutoDock Vina software and Swiss ADME online tool, respectively. The isolated flavonoids were identified as 3,5,7,3’,4’-tetrahydroxy-4-methoxyflavanone-3-O-L-rhamnopyranoside and 5,7,3’-trihydroxy-4-methoxyflavanone-7-O-L-rhamnopyranoside (quercitrin). Docking and ADMET studies revealed the promising binding affinity of flavonoid molecules for human lysosomal alpha-glucosidase and human pancreatic alpha-amylase with acceptable ADMET properties. Based on computational studies, our study reports the antidiabetic potential of the isolated flavonoids with predictive pharmacokinetics profile.

We describe the innate and adaptive immune system trajectory in Multi-system inflammatory syndrome of childhood (MIS-C), at acute(within 72 hours of hospitalization), resolution (at clinical improvement) and convalescent phase. In our cohort, in the acute phase, 68% of the children were SARS-CoV-2 seropositive, with hypercytokinenemia (high interleukin(IL)-1beta,IL-6,IL-8,IL-10,IL-17, interferon gamma), procoagulant state, myocardial dysfunction, activated neutrophils and monocytes; differential T and B cell subset lymphopenia; activated chemokine receptor type-7 positive and gamma-delta T cell subsets; antigen presenting cells had reduced HLA-DR expression; and B-cell class-switch responses occurred with illness resolution. MIS-C is an immunopathogenic illness associated with SARS-CoV-2 infections in children.

Background: Inflammation is an important mechanism in atherosclerosis and plaque formation. C-reactive protein (CRP) is a common inflammatory biomarker associated with the risk of coro-nary heart disease. We investigated the relationship of CRP with findings from myocardial per-fusion imaging (MPI). Methods: In this retrospective study, 102 consecutive patients (mean age 71 years, 68% males) that underwent MPI (for diagnostic reasons or quantification of myocardial ischemia) and CRP determination (upper limit: 6mg/L) within 1 month from MPI, were included. Patients had no infection or recent acute coronary syndrome. Results: the median CRP level was 4mg/L (2,10) among the study population. Patients with raised CRP had higher summed stress score (SSS) (P = 0.006) and summed rest score (SRS) (P = 0.001) and higher risk for SSS > 3 (OR 9.25, 95% CI 2.03-42.13, P = 0.001) compared to those with low CRP. The association of SSS and SRS with CRP levels was more evident in patients over 70 years (P = 0.027 and P = 0.005 respectively). No significant difference in summed difference score was shown. The two groups had no difference in other risk factors (p > 0.05 for all comparisons). Conclusion: A high level of CRP was associated with the presence and extent of stress-induced myocardial ischemia in MPI.

Background: Polycystic ovary syndrome is a common reproductive and endocrinological disease characterized by ovulatory dysfunction, polycystic ovaries, and hyperandrogenism. Adipokines are believed to contribute to developing polycystic ovary syndrome and its accompanying metabolic complications such as dyslipidemia, insulin resistance, and cardiovascular diseases. Oncostatin M, a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to polycystic ovary syndrome pathogenesis and its related metabolic problems. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the polycystic ovary syndrome (n = 32) or the control group (n = 32). Blood samples were obtained between the third and fifth days of the menstrual cycle. Serum levels of fasting glucose, insulin, C-reactive protein, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin, estradiol, homeostasis model assessment of insulin resistance and oncostatin M were analyzed. Results: Oncostatin M levels were significantly lower, but C-reactive protein levels were substantially higher in the polycystic ovary syndrome group than in the control group (p = 0.002, p = 0.001, respectively). Oncostatin M was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = -0.329, p =0 .017; ρ = -0.386, p = 0.005; ρ = -0.440, p = 0.001; ρ = -0.316, p = 0.023, respectively). Conversely, there was no correlation between oncostatin M and total testosterone level (ρ = 0.220; p = 0.118). In the context of inflammation and metabolic parameters, oncostatin M was inversely correlated with C-reactive protein, homeostatic model assessment for insulin resistance score, and low-density lipoprotein cholesterol (ρ = -0.353, p = 0.019; ρ = -0.275, p = 0.048; ρ = -0.470, p &lt; 0.001, respectively). The diagnostic performance of oncostatin M, C-reactive protein, homeostasis model assessment of insulin resistance, and non-high-density lipoprotein cholesterol for polycystic ovary syndrome is as follows: Oncostatin M, sensitivity: 50%, specificity: 75%, Accuracy: 63%, p = 0.009; C-reactive protein, sensitivity: 84%, specificity: 61%, Accuracy: 74%, p = 0.004; homeostasis model assessment of insulin resistance, sensitivity: 72%, specificity: 81%, Accuracy: 77%, p &lt; 0.001; and non-high-density lipoprotein cholesterol; sensitivity: 72%, specificity: 75%, accuracy: 73%, p &lt; 0.001. Conclusions: Plasma oncostatin M levels were considerably lower in patients with polycystic ovary syndrome than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of polycystic ovary syndrome. Thus, oncostatin M may be a novel therapeutic target for polycystic ovary syndrome and its metabolic complications.

Aims TRAIL is a promising anticancer agent that has the potential to sensitize a wide variety of cancer or transformed cells by inducing apoptosis. However, resistance to TRAIL is a growing concern. Current manuscript aimed to employing combination treatment to investigate resveratrol induced TRAIL sensitization in NSCLC. Method A549 and HCC-15 cells were used in experimental design. Cell viability was determined by morphological image, crystal violet staining and MTT assay. Apoptosis was evaluated by LDH assay, Annexin V and DAPI staining. Autophagy and apoptosis indicator protein were examined by western blotting. TEM and puncta assay were carried out to evaluate the autophagy. MTP and ROS activity were evaluated by JC-1 and H₂DCFDA staining. Findings Resveratrol is a polyphenolic compound capable of activation of tumor suppressor p53 and its pro-apoptotic modulator PUMA. Herein, we showed the p53-independent apoptosis by decrease the expression of phosphorylated Akt-mediated suppression of NF-κB that is also substantiated with the downregulation of anti-apoptotic factors Bcl-2 and Bcl-xl in NSCLC, resulting in an attenuation of TRAIL resistance in combined treatment. Furthermore, apoptosis was induced in TRAIL-resistant lung cancer cells with a co-treatment of resveratrol and TRAIL assessed by the loss of MMP, ROS generations which resulting the translocation of cytochrome c from the mitochondria into the cytosol due to mitochondrial dysfunction. Moreover, autophagy flux was not affected by resveratrol-induced TRAIL-mediated apoptosis in NSCLC. Significance Overall, targeting the NF-κB (p65) pathway via resveratrol attenuates TRAIL resistance and induces TRAIL-mediated apoptosis which could be the effective TRAIL-based cancer therapy regimen.

This study develops a vitamin C controlled-release system trackable via color changes as a function of vitamin C release. The system is composed of coaxial microfibers prepared via coaxial electrospinning, with a core of poly(ethylene oxide) (PEO) incorporating vitamin C, and a shell composed of polycaprolactone (PCL) containing polydiacetylene (PDA) as the color-changing material. The shell thickness was controlled by adjusting the amount of PCL ejected during electrospinning, allowing the regulation of the release rate of vitamin C. When vitamin C added to PEO penetrated the PCL layer, the color of PDA changed from blue to red, indicating a color change. The results of this study can be applied to devices that require immediate detection of vitamin C release levels.

Various implementations of the Move with Interleaving transform are discussed in this paper, with the transformation itself explained briefly at first. The transform has an expected time complexity of O(n), where n represents the length of the sequence being transformed. The importance of implementation also grows as the sequences become longer. The paper explains three different implementations: the first uses the standard vector, the second employs a lookup table, and the third utilises a dynamic linked list with a pool of released records. The experiments were conducted on 32 greyscale raster images of various contexts and sizes. All three solutions were implemented in both C++ and Java, and then executed on three different platforms: a personal computer running MS Windows and Linux, and a Raspberry Pi 2 with Linux. The implementation based on the dynamic linked list was the fastest, and outperformed the vector-based implementation by more than 1800%. While direct comparisons between results on the Raspberry Pi and those on the modern personal computer may not be straightforward, a consistent pattern prevails: the dynamic linked list implementation outperformed the other two consistently, and the C++ code was faster than the code written in Java. The difference was most evident on the Raspberry Pi.

Using a safe subset of C++ is a promising direction for increasing the safety of the programming language while maintaining its performance and productivity. In this paper, we examine how close existing C/C++ code is to conforming to a safe subset of C++. We examine the rules presented in existing safe C++ standards and safe C++ subsets. We analyze the code characteristics of 5.8 million code samples from the Exebench benchmark suite and 5 modern C++ applications using a static analysis tool. We find that raw pointers, unsafe casts, and unsafe library functions are used in both C++ code at large and modern C++ applications. In general, C++ code at large does not differ much from modern C++ code, and continued work will be required to transition from existing C/C++ code to a safe subset of C++.

Osteoclasts (OCs) are the multinucleated, bone-resorbing giant cells originally differentiated from a monocyte/macrophage lineage. OC differentiation and maturation, also called osteoclastogenesis, are strictly regulated by a variety of signaling pathways primarily induced by the interactions of two prerequisite cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-κB ligand (RANKL) to their respective surface receptors, c-fms and RANK, in OC precursors (pre-OCs). Rab11 has emerged as the spatiotemporal regulators of intracellular vesicular transport in the endosomal recycling system; however, how it regulates osteoclastogenesis is incompletely understood. OC-triggered bone resorption is best characterized to be immensely dependent upon lysosomal function, the intracellular acidic organelles containing more than 50 acid hydrolases secreted into bone matrix microenvironment (BME). On the contrary, it is little known about the lysosomal function on modulating the turnover of c-fms and RANK surface receptors via Rab GTPase-mediated vesicular transport, thereby dictating osteoclastogenesis. In this review, I briefly describe the mechanism underlying lysosome-induced osteoclastogenesis via the Rab11-mediated modulation of the surface receptors in OCs.

Liposome-mediated delivery is a possible means to overcome several shortcomings with C. elegans as a model for identifying and testing drugs that retard aging. These include interactions between drugs and the nematodes’ bacterial food source, and failure of drugs to be taken up into nematode tissues. To explore this, we have tested liposome-mediated delivery of a range of fluorescent dyes and drugs in C. elegans. Liposome encapsulation led to enhanced effects on lifespan, using smaller quantities of compound, and enhanced uptake of three dyes into the gut lumen. However, one dye (Texas red) did not cross into nematode tissues, indicating that liposomes cannot ensure uptake of any compound. Of six compounds previously reported to extend lifespan (vitamin C, N-acetylcysteine, glutathione (GSH), trimethadione, thioflavin T (ThT) and rapamycin), this effect was reproduced for the latter four in a condition-dependent manner. For GSH and ThT, antibiotics abrogated life extension, implying a bacterially-mediated effect. With GSH, this was attributable to reduced early death from pharyngeal infection, and associated with alterations of mitochondrial morphology in a manner suggesting a possible innate immune training effect. By contrast, ThT exhibited antibiotic effects. For rapamycin, significant increases in lifespan were only seen when bacterial proliferation was prevented. These results document the utility and limitations of liposome-mediated drug delivery for C. elegans. They also show how nematode-bacteria interactions can determine the effects of compounds on C. elegans lifespan in a variety of ways.

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.

This study aimed to investigate the efficacy of DìRelaxTM, a nutraceutical formulated to reduce anxiety in dogs. The CBARQ questionnaire, some clinical investigations, and the impossible task test were performed in dogs before and after the treatment. Results showed an ameliorative effect on the performances of treated dogs during the solvable phases, with a significant decrease of the time needed to solve the task. No behavioral difference was found between treated and untreated anxious dogs during the unsolvable phase. According to the results from the C-BARQ questionnaire, some of the behaviors appear improved. In general, this study suggests that DiRelaxTM can be safely administered with no adverse effects and can exercise a beneficial effect on anxious dogs by enhancing their cognitive abilities.

We reelaborate on the basic properties of PT symmetry from a geometrical Perspective. The transfer matrix associated with these systems induces a Möbius transformation in the complex plane. The trace of this matrix classifies the actions into three types that represent rotations, translations, and parallel displacements. We find that a PT invariant system can be pictured as a complex conjugation followed by an inversion in a circle. We elucidate the physical meaning of these geometrical operations and link them with measurable properties of the system.

In this work the influence of the structure forming agent on the composition, morphology and oxygen reduction reaction (ORR) activity of Fe-N-C catalysts was investigated. As structure forming agent (SFA), dicyandiamide (DCDA) (nitrogen source) or oxalic acid (oxygen source) or mixtures thereof were used. For characterization, cyclic voltammetry and rotating disc electrode (RDE) experiments were performed in 0.1 M H2SO4. In addition to this, N2 sorption measurements and Raman spectroscopy were performed for the structural characterization. The role of metal, nitrogen and carbon sources within the synthesis of Fe-N-C catalysts has been pointed out before. Here, we show that the optimum in terms of ORR activity is achieved if both N- and O-containing SFAs are used in almost similar fractions. All catalysts display a redox couple, whereat its position depends on the fractions of SFAs. The SFA has also a strong impact on the morphology: Catalysts that were prepared with a larger fraction of N-containing SFA revealed a higher order in graphitization, indicated by bands in the 2nd order range of the Raman spectra. Nevertheless, the optimum in terms of ORR activity is obtained for the catalyst with highest D/G band ratio. Therefore, the results indicate that the presence of an additional oxygen-containing SFA is beneficial within the preparation.

Increased construction activities in Australia have led to the generation of a massive volume of construction and demolition (C&D) waste annually. Management of this volume of waste requires an effective waste framework. The literature reported that the current Australian waste framework does not meet expectations and needs immediate improvements. This study was therefore conducted to seek the key C&D stakeholders' opinion about various issues identified in this waste stream. The specific objectives of this study are identification of the main barriers to effective C&D waste management, the impact of current regulations and opportunities to enhance the current C&D waste management system. A survey was conducted in 2019 to capture the stakeholders' perception. 132 participants from various industries and government agencies based in various Australian jurisdictions took part in the survey. The key results showed that the main barriers towards an effective management system are "overregulation, tough acceptance criteria, and increased testing requirements", "lack of local market" and "culture, poor education and low acceptance". Furthermore, a low number of participants indicated that the current legislation encourages waste recovery activities. The main areas of improvements included "providing a guideline that determines the accepted level of contamination for reusing C&D waste”, "preparation of guidelines on requirements of using recycled C&D materials in different industries" and "setting target for reduction, reusing, and recycling C&D waste". The results can inform policy development and be used as evidence for a broader discussion to solve lasting issues in C&D waste management.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions, c-reactive protein (CRP) and adiponectin. We report on associations between targeted metabolic markers and active nutrients from diet and Sujiaonori algal supplement (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of bioactive ulvan-rich fiber, in Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m2 [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

Introduction: Dental health care workers, particularly dental medicine students (DMS), are at an increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The aim of our study was to assess the level of knowledge on HBV and HCV, estimate needlestick injury (NSI) prevalence and reporting practice in DMS at the University of Zagreb and analyze how enrolment in obligatory and supplemental courses affects knowledge and needlestick injury reporting practice. Materials and methods: The knowledge was assessed by our questionnaires based on Centers for Disease Control general handouts. Additional information was collected to examine the prevalence and reporting practice of NSI. Data was analyzed by descriptive statistical analysis, independent-samples t-tests, proportion analyses and combined factor analyses of categorical and quantitative variables in SPSS and R. Results: In total, 206 students participated. The overall level of HBV and HCV-related knowledge was poor with average scores being 61.90% and 51.35% respectively. Moreover, students enrolled in the first year demonstrated significantly lower levels of knowledge in comparison with their older peers. Of all participants 18.2% sustained a needlestick injury, and majority of them (78.95%) never reported the injury. Conclusion: In conclusion, DMS have low levels of knowledge on important occupational pathogens and poor NSI reporting practice. Moreover, formal education in the current form failed to significantly improve competence of students and theoretical knowledge translates poorly into more conscientious injury reporting practice. We should look for a better way to increase student awareness and level of knowledge on this topic.

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.

C-C motif chemokine ligand 2 (CCL2), also called monocyte chemoattractant protein-1 (MCP-1) is a key β-chemokine involved in the migration of monocytes and macrophages, playing a significant role in the inflammatory responses in the airways. We aimed to assess the serum levels of MCP-1/CCL2 in a pilot cross-sectional study of Bulgarian children with bronchial asthma (BA) and cystic fibrosis (CF). Forty-two children were recruited to the study as follows: twenty with BA, twelve with CF and ten healthy children. Serum MCP-1/CCL2 levels were measured using ELISA. We found higher serum level of MCP-1/CCL2 in children with BA (191.09±64.96 pg/ml) and CF (258.51±76.45 pg/ml) compared to healthy children (70.30±64.30 pg/ml, p=0.022, and p=0.068, respectively). Younger patients with BA had higher levels of MCP-1/CCL2, as well as children with CF, with levels decreasing gradually with age. We observed also higher levels of MCP-1/CCL2 in children with moderate to severe BA compared to mild BA. We documented the significantly higher level of MCP-1/CCL2 in children with these chronic pulmonary diseases than in healthy controls, which suggesting that investigation of serum MCP-1/CCL2 levels could turn out to be beneficial for the severity of the disease.

Recently, the medical image processing is extensively used in several areas. In earlier detection and treatment of these diseases is very helpful to find out the abnormality issues in that image. Here there are number of methods available for segmentation to detect the lung nodule of computer tomography (CT) image. The main result of this paper, the earlier detection of lung nodules using Pre-processing techniques of top-hat transform, median and adaptive bilateral filter was compared both filtering methods and proved the adaptive bilateral filter is suitable method for CT images. The proposed segmentation technique uses novel strip method and the image is split into number of strips 3, 4, 5 and 6. A marker- watershed method based on PSO and Fuzzy C-mean Clustering method was proposed method. Firstly, the input image was reduced noise reduction and smoothing and the filter image is using strips method and then the image is segmented by marker watershed method. Secondly, the enhanced PSO technique was used to locate the better accurate value of the clustering centers of Fuzzy C-mean Clustering. Final stage, with the accurate value of centers and the enhanced target function and the small region of the segmented object was clustered by Fuzzy C-mean. In segmentation algorithm presented in this paper gives 95% of accuracy rate to detect lung nodules when strip count is 5.

(1) Background: P-cadherin (CDH3) is a transmembrane protein that plays a crucial role in maintaining the structural integrity of epithelial tissue and homeostasis. Its role in carcinogenesis remains a subject of debate, as its behavior can vary depending on the molecular context and the specific tumor cell model under study. In this study, we explored the role of P-cadherin in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its function. (2) Methods: We analyzed P-cadherin expression in HNSCC patients using The Cancer Genome Atlas (TCGA) database. For in vitro functional analysis, we conducted proliferation, migration, invasion, and western blot assays after either suppressing or overexpressing P-cadherin. For in vivo functional analysis, we utilized mouse xenograft models. (3) Results: P-cadherin was significantly overex-pressed in tumor samples compared to normal samples in the TCGA-HNSCC cohort. P-cadherin knockdown resulted in decreased proliferation, migration, and invasion compared to control cells, while P-cadherin overexpression increased cell proliferation and migration in HNSCC cells. We discovered that c-Met functioned as an upstream regulator of P-cadherin. Surprisingly, we found that P-cadherin knockdown increased the phosphorylation of c-Met and STAT3. Combining P-cadherin siRNA with the c-Met inhibitor SU11274 resulted in a more effective reduction in HNSCC cell growth, both in vitro and in vivo, compared to either treatment alone. (4) Conclusions: Our study uncovered a previously unknown aspect of P-cadherin-mediated c-Met regulation. The enhanced activation of c-Met/STAT3 following P-cadherin inhibition could be responsible for the survival of resistant tumor cells. Therefore, dual inhibition of P-cadherin and c-Met may be a potentially effective approach for treating HNSCC.

Methylation of cytosines at CpG sites in DNA, carried out by de novo by DNA methyltransferase Dnmt3a, is a basic epigenetic modification involved in gene regulation and genome stability. Aberrant CpG methylation in gene promoters leads to oncogenesis. In oncogene promoters, CpG sites often colocalize with guanine-rich sequences capable of folding into G-quadruplexes (G4s). Our in vitro study aimed to investigate how parallel G4s formed by a sequence derived from the c-MYC oncogene promoter region affect the activity of the Dnmt3a catalytic domain (Dnmt3a-CD). For this purpose, we designed synthetic oligonucleotide constructs: c-MYC G4-forming oligonucleotide and linear double-stranded DNA containing an embedded stable extrahelical c-MYC G4. The topology and thermal stability of G4 structures in these DNA models were analyzed by physicochemical techniques. We showed that Dnmt3a-CD specifically binds to an oligonucleotide containing c-MYC G4, resulting in inhibition of its methylation activity. c-MYC G4 formation in a double-stranded context significantly reduce Dnmt3a-CD-induced methylation of a CpG site located in close proximity to the quadruplex structure; this effect depends on the distance between the non-canonical structure and the specific CpG site. One would expect DNA hypomethylation near the G4 structure, while regions distant from this non-canonical form would maintain a regular pattern of high methylation levels. We hypothesize that the G4 structure sequesters the Dnmt3a-CD and impedes its proper binding to B-DNA, resulting in hypomethylation and activation of c-MYC transcription.

Background: Schizophrenia is a mental disorder associated with inflammatory and oxidative stress markers such as lactate; in addition, the rate of physical inactivity in this population is very high, which leads to physical and metabolic alterations. Aims: This study measured the effect of assisted physical exercise over lactate levels in schizophrenia. Methods: Stable outpatients with schizophrenia and a group of Healthy controls received two different programs of Physical exercise (Aerobic and Functional) in a clinical trial. Results: Patients had higher lactate compared to healthy controls before and after intervention, and had higher rate of lactate increase after activity. The finding of increased lactate in schizophrenia detected before and after physical exercise deserve further attention in biomarker studies and in the development of physical rehabilitation in schizophrenia, suggesting different profile of oxidative metabolism after physical exercise. Basal increased lactate may reflect mitochondrial dysfunction or metabolic dysregulation, and the higher rate of increase may reflect a different metabolic and oxidative process. Conclusion: The finding is in line with recent studies as surrogate of mitochondrial dysfunction in schizophrenia and points to the need of additional studies on mitochondrial activity in schizophrenia, and to additional care in the design of physical interventions in schizophrenia.

Nickel based superalloys finds extensive usage in manufacturing of intricate part shapes in gas turbine, aircraft, submarine, and chemical industries owing their excellent mechanical property and heat resistant abilities. However, machining of such difficult-to-machine alloys up to the desired accuracy and preciseness is a complex task owing to a rapid tool wear and failure. In view of this, present work proposes an experimental investigation and optimization of process parameters of the cryogenic assisted turning process during machining of Nimonic C-263 super alloy with a multilayer CVD insert. Taguchi’s L-27 orthogonal array is used plan the experiments. Effect of input parameters viz. cutting speed (N), cutting feed (f), depth of cut (d) are studied on responses viz. surface roughness (SR), nose wear (NW) and cutting forces (F) under hybrid cryogenic (direct+indirect) machining environment. A scanning electron microscope (SEM) analysis is carried out to explore the post-machining outcomes on the performance measures. The multiple responses are converted in to single response and ranked according to Taguchi based gray relational grade (TGRG). Feed rate (f) is found to be the most influential parameter from the analysis of variance of GRG. The means of GRG for each level of process parameters are used to improve the optimal process parameters further. Finally, the confirmative experiment is performed with these optimal set of process parameters which showed an improvement of 9.34% in the value of GRG. The proposed work can be beneficial to choose ideal process conditions to enhance the performance of turning operation.

EIT-MESHER (https://github.com/EIT-team/Mesher) is C++ software, based on the CGAL library, which generates high quality Finite Element Model tetrahedral meshes from binary masks of 3D volume segmentations. Originally developed for biomedical applications in Electrical Impedance Tomography (EIT) to address the need for custom, non-linear refinement in certain areas (e.g. around electrodes), EIT-MESHER can also be used in other fields where custom FEM refinement is required, such as Diffuse Optical Tomography (DOT).

The objective of this investigation was to enhance the sensory appeal of Cerasus humilis (C. humilis) juice and ascertain potential interactions among bioactive compounds within a functional juice matrix. Sensory attributes, color, antioxidant potential, polyphenol and vitamin C (VC) concentrations, and sugar levels were assessed. Diverse dosage combinations were examined to determine their impact on the quality of both C. humilis and Green grape juices. Among the formulations, CG5 exhibited elevated antioxidant activit y and polyphenol content (455.02 mg TE/100 ml and 173.1 mg/100 ml, respectively), coupled with favorable consumer preference. Notable variations in compound content were observed across the seven analyzed juices. In the blended juices (CG1–CG5), interactions between distinct juices influenced VC and sugar levels, with other bioactives contributing to beneficial modifications, displaying a progressive rise. This study innovatively crafted delectable and convenient C. humilis juice, upholding its intrinsic high antioxidant activity, thereby presenting a novel avenue for marketable functional juice offerings.

Polymethyl methacrylate (PMMA) polymer is widely used in various fields today. In order to thoroughly reveal the structural impact performance of PMMA materials, this paper is based on the comprehensive Johnson-Cook constitutive model and damage failure model, and accurately confirm the J-C constitutive and damage failure model parameters of PMMA through material test data, The dynamic process of steel bullet impacting PMMA plate structure is analyzed by finite element software ABAQUS. The calculation results show that the numerical simulation results in this paper are in good agreement with the experimental test data. Therefore, the feasibility and accuracy of the impact analysis of PMMA structures based on J-C constitutive and damage failure models in this paper are studied. Finally, based on the J-C constitutive model and damage failure model, the variation of the residual velocity of the bullet with the PMMA plate thickness is analyzed in depth, that is, the results show that the residual velocity of the bullet has a certain linear relationship with the plate thickness.

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms have generated the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN-, then IFN-α plus ribavirin (IFN-RBV); then, pegylated-IFN--RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing the patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced SVR (&gt; 90%); the compounds were able to inhibit HCV replication without significant side effects, even in pediatric populations. The management of coinfected patients HBV-HCV and HCV-HIV has also improved based on DAA and PEG-IFNα-RBV (HBV-HCV). CD4 cells are crucial for an effective antiviral response. IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research focuses on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection to different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.

C-peptide is used as a measure of endogenous insulin production. Given that insulin and C-peptide are produced in equal amounts, C-peptide is typically used to differentiate between external and endogenously produced insulin in insulin-treated type 1 diabetes mellitus (T1DM). In a clinical setting, a decline in C-peptide is regarded as a loss of beta cell function. However, physiological conditions may also be associated with low C-peptide levels. The authors of this paper use a low-carbohydrate diet, the so-called paleolithic ketogenic diet (PKD), in the treatment of various conditions and observed that C-peptide is typically low on this diet. In order to characterize C-peptide levels on this diet, we designed a study to retrospectively assess C-peptide levels in 100 non-T1DM subjects. We found that 55% of the subjects had a C-peptide level below the standard reference range. C-peptide levels correlated with glucose levels. A significant correlation was found between C-peptide and age, with younger subjects having lower C-peptide levels. Males also showed lower C-peptide levels than females. Given the increasing number of patients using low-carbohydrate diets worldwide, physicians should be aware of laboratory correlates of low-carbohydrate diets, including low C-peptide levels, most importantly to prevent incorrect T1DM diagnosis.

Variations in liver metabolism as a result of hepatitis C virus have been established by numerous clinical trials. The use of antioxidants supplements has been reported to minimize the implication of this disease. In this regard, we examined the suitability of Solanum fruit juice, a natural source of vitamin C and citrus flavoniod as a precursor for the treatment of patients with chronic hepatitis C. Forty adult patients who were diagnosed with chronic hepatitis C and were under antiviral therapy were divided into two equal groups. Group 1 patients received their antiviral therapy with normal food and water and served as the control group while patients in group 2 were supplemented with Solanum fruit juice for eight consecutive weeks. Measurements for Anthropometric data, C reactive protein (CRP), atherogenic indices, biochemical parameters and activities of liver marker enzymes were recorded before and after eight weeks. No alterations were found in waist circumference, body mass and body fat following regular use of Solanum fruit juice. The serum levels of oxidative stress markers, LDL-cholesterol, total cholesterol, CRP and atherogenic indices decreased in the Solanum fruit juice group when compared to the control group. Moreover, the activities of the liver marker enzyme AST decreased in those who had high levels before the intervention. These results underscore the benefits of Solanum fruit juice in the diet of patients with HCV as a result of decreased cholesterol in blood serum, decreased inflammation, and increase in antioxidant capacity as well as maintaining body mass index. This clinical trial is registered at Pan African Clinical Trial Registry (www.pactr.org) with unique identification number PACTR201802003092138.

The Koka gold deposit is located in the Elababu shear zone between the Nakfa terrane and the Adobha Abiy terrane, NW Eritrea. Based on the paragenetic study two main stages of gold mineralization were identified in the Koka gold deposit: 1) an early stage of pyrite-chalcopyrite-sphalerite-galena-gold-quartz vein; and 2) a second stage of pyrite-quartz veins. NaCl-aqueous inclusions, CO2-rich inclusions, and three-phase CO₂-H₂O inclusions occur in the quartz veins at Koka. The ore-bearing quartz veins formed at 268℃, from NaCl-CO₂-H₂O(-CH₄) fluids averaging 5 wt% NaCl eq. The ore-forming mechanisms include fluid immiscibility during stage I, and mixing with meteoric water during stage II. Oxygen, hydrogen and carbon isotopes suggest that the ore-forming fluids originated as mixtures of metamorphic water, meteoric water and magmatic water, whereas sulfur isotope suggest an igneous origin. Features of geology and ore-forming fluid at Koka deposit are similar to those of orogenic gold deposits, suggesting the Koka deposit might be an orogenic gold deposit related to granite.

Investments in wind and solar power are driven by the aim to maximize the utilization of renewable energy (RE). This results in an increased concentration of wind farms at locations with higher average wind speeds and of solar panel installations at sites with higher average solar insolation. This is unfavourable for energy suppliers and for the overall economy when large power output fluctuations occur. Thus, when evaluating investment options for spatially distributed RE systems, it is necessary to model resource fluctuations and power output correlations between locations. In this paper, we propose a methodology for analyzing the spatial dependence, accurate modeling, and forecasting of wind power systems with special consideration to spatial dispersion of installation sites. We combine vine-copulas with the Kumaraswamy distribution to improve accuracy in forecasting wind power from spatially dispersed wind turbines and to model solar power generated at each location. We then integrate these methods to formulate an optimization model for allocating wind turbines and solar panels spatially, with an end goal of maximizing overall power generation while minimizing the variability in power output. A case study of wind and solar power systems in Central Ontario, Canada is also presented.

Polymer-derived ceramic (PDC) based coatings like Si-C-N and their derivatives are gaining importance day by day in N/MEMS and aerospace due to their thermos-mechanical stability and conductivity. The crystallized, amorphous, and near amorphous morphology of SiCN nanocomposite coatings based on deposition conditions requires thorough investigation for appropriate utilization as they lead to differences in mechanical properties (quantified using nanoindentation in this case). A 4-stage model was proposed based on Raman spectroscopy due to the N₂-Ar pressure variations during the deposition process of SiCN coatings by magnetron sputtering. The integral intensity of the G (graphitic), disorder (D), and tetrahedral (T) peaks namely I_G, I_D, and I_T were calculated after the deconvolution of the spectra. The sp² domain size and defect parameters were evaluated and correlated with the hardness and different bond formation involving Si, C, and N. Image analysis revealed the atomic migration involved during the growth process leading to crystallization along with the formation of voids and defects. The observations were supported by FTIR and TEM-SAED analysis. The outcomes provide a foundation causing an urge to develop similar models with further elemental additions and correlate with various physical properties.

Continuous Distributed Constraint Optimization Problem (C-DCOPs) are a powerful framework to model problems with continuous variables in multi-agent systems. Previous works about C-DCOP algorithms mainly use pseudo-trees to guarantee the anytime property or are without anytime property guarantees. However, there is a risk of privacy leakage in the pseudo-tree due to utility passing between agents. Therefore, based on the basic constraint graph instead of the pseudo-tree, we (i) extend the Maximum Gain Message (MGM) algorithm by combining the local search strategy to solve C-DCOPs, named Continuous MGM (C-MGM), and it’s able to guarantee the monotonicity of the solution quality; (ii) propose a Parallel C-MGM (C-PMGM) algorithm to improve the solution quality through parallel random search; and (iii) introduce the differential search into C-PMGM to design a Parallel Differential Search C-MGM (C-PDSM) algorithm, which constructs a heuristic method to speed up convergence and improve solution quality. Compared to other anytime C-DCOP algorithms using pseudo-trees, the proposed three algorithms can exhibit better performance in avoiding privacy violations. We theoretically prove that the proposed algorithms are the anytime algorithms and empirically demonstrate that our algorithms outperform the state-of-the-art C-DCOP algorithms.

Background and Objectives: Obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis resistant obese individuals. Materials and Methods: Thirty-nine, periodontally healthy subjects were enrolled. Based on BMI scores, 20 subjects were categorized as lean and 19 as obese. A comprehensive periodontal examination was performed. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were assessed for interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A) and CRP. Results: GCF CRP levels were significantly higher in obese than lean individuals. No statistically significant differences were noted between the two groups in both GCF and blood on any of the inflammatory cytokine levels. IL-17A was not detected in GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, the association tended to be stronger in obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels positively associated with multiple GCF inflammatory cytokines (e.g., IL-1β, IL-6, IL-8 and TNF-α) in all subjects, the associations tended to be weaker in obese individuals (e.g., IL-1β, IL-6, TNF-α). Furthermore, the levels of GCF inflammatory cytokines IL-6 and TNF-α were depressed in obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a dysregulated inflammatory cytokine response in the gingival tissues of obese individuals.

The purpose of this study was to determine the income, costs and revenue of the Gontor Putri 3 bakery. Want to know the efficiency of the bakery business in Karangbanyu Regency. The method used in this research is analytical descriptive by conducting a survey. The data used in this research is primary data. Data collection techniques use observation, interviews and documentation, while the process of analysis is quantitative descriptive. Using the R/C ratio, a value of 1.72 per month is obtained. This value indicates that the bakery factory in Karangbanyu is efficient because the value is more than one.

Amyotrophic Lateral Sclerosis (ALS) stands as a debilitating neurodegenerative condition characterized by the progressive degeneration of motor neurons. Despite extensive research in various model animals, the cellular signal mechanisms of ALS remain elusive, impeding the development of efficacious treatments. Among these models, a well-characterized and diminutive organism, Caenorhabditis elegans (C. elegans), has arisen as a potent tool for investigating the molecular and cellular dimensions of ALS pathogenesis. This review summarizes the contributions of C. elegans models to our comprehension of ALS, emphasizing pivotal findings pertaining to genetics, protein aggregation, cellular pathways, and potential therapeutic strategies. We analyze both the merits and constraints of C. elegans system in the realm of ALS research, and point towards future investigations that could bridge the chasm between C. elegans foundational discoveries and clinical applications.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

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.

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.

A clear relationship between the tau assemblies and toxicity has still to be established. To correlate the tau conformation with its proteotoxic effect in vivo we developed an innovative cell-worm-based approach. HEK293 cells expressing tau P301L under a tetracycline-inducible system (HEK T-Rex) were employed to produce different tau assemblies whose proteotoxic potential was evaluated using C. elegans. Lysates from cells induced for five days, significantly reduced the worm’s locomotor activity. This toxic effect was not related to the total amount of tau produced by cells or to its phosphorylation state but was related to the formation of multimeric tau assemblies, particularly tetrameric ones. We investigated the applicability of this approach for testing compounds acting against oligomeric tau toxicity, using doxycycline (Doxy) as prototype drug. Doxy affected the tau solubility and promoted the disassembly of already formed toxic aggregates in lysates of cells induced for five days. These effects translated into a dose-dependent protective action in C. elegans. These findings confirm the validity of the combined HEK T-Rex cells and C. elegans-based approach as a platform for pharmacological screening.

In this work, a tool for estimating the contact angle from the molecular dynamics simulations is developed and presented. The tool (Achilles) can detect water droplet on hydrophobic and hydrophilic surfaces. The tool can reconstruct the droplets broken across the periodic boundaries. Further a neighbor density based accurate filter is used to find the droplet liquid vapor interface and a circle is fitted using it after removing the dense layers of water next to solid surface. This fitted circle is solved for contact angle and results are outputted in the form of graphical images and text. The entire content of the internal computations of the tool is broken down into 4 phases and users can monitor the outcomes at every phase through output images. The tool is tested using sample molecular dynamics results of water droplet on hydrophobic and hydrophilic surfaces. We believe this tool can be a good addition to the molecular dynamics simulation community who work on the interfacial physics, droplet evaporation, super hydrophobic surfaces, and wettability etc.

Background & Aims: The covid19 is a world changing challenge. Furthermore, this disease challenges our capacities to change our point of view in the domain of infectiology, immunology and global public health. Many trials try some drug such as antiviral (lopinavir, remdesivir) interferon, and the chloroquine. Unfortunately, all approach is not really convincing at this time. We are proposing another approach on this issue. In infectiology there are two protagonists : the host and its immune system versus pathogens and its virulence. Our approach focuses on an intervention on the host’s immune system and how stimulate and modulate its reactions. Methods: We searched on PubMed and Google Scholar databases for French and English-language studies, without a limit of date of publications, for randomized clinical trials, meta-analyses, reviews, systematic reviews, observational studies, case report. We performed a review on the field of immunology enhancements by nutrients use. Results: We identified groups of vitamins (D and C), oligo-elements (magnesium, zinc, selenium) and nutrition advice which enhance immune system response. Indeed, these supplements have some proved properties in modulating and stimulating the immune system. For example, a recent study demonstrates that vitamin D deficiency is linked with the severity of covid19. Majority of the population has a deficiency in these elements. According to this, we propose a therapeutic protocol using these elements to reach an efficient therapy against covid19 by enhancing host’s immune system. Conclusion: Due to this serious pandemic, any solutions must not be disregarded. The nutrition way is an entire part of the solution.

During analysis of kiwifruit derived from hybrids between the high AsA species Actinidia eriantha and A. chinensis var chinensis, we observed bimodal segregation of fruit AsA concentration suggesting major gene segregation. To test this hypothesis we performed whole-genome sequencing on pools of high and low AsA fruit from tetraploid A. chinensis var. deliciosa x A. eriantha backcross families. Pool-GWAS revealed a single QTL spanning more than 5 Mbp on chromosome 26, which we denote as qAsA26.1. A co-dominant PCR marker was used to validate this association in four diploid (A. chinensis x A. eriantha) x A. chinensis backcross families, showing that the eriantha allele at this locus increases fruit AsA levels by 250 mg/100 g fresh weight. Inspection of genome composition and recombination in other A. chinensis genetic maps confirmed that the qAsA26.1 region bears hallmarks of suppressed recombination. The molecular fingerprint of this locus was examined in leaves of backcross validation families by RNASEQ. This confirmed strong allelic expression bias across this region as well as differential expression of transcripts on other chromosomes. This evidence suggests that the region harboring qAsA26.1 constitutes a supergene, which may condition multiple pleiotropic effects on metabolism.

Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed by transient elastography No patient had cirrhosis at baseline (LSM≥12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected by HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR)=1.14; p=0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM≥5 kPa) [adjusted odds ratio (aOR)=2.37; p=0.029], and greater than 7 kPa (ΔLSM≥7 kPa) [aOR=3.24; p=0.032], after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR=2.18; p=0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.

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.

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.

Heterosis plays a significant role in enhancing variety, boosting yield, and raising economic value, but the molecular mechanism is still unclear. We analyzed the transcriptomes and 3D genomes of hybrid (F1) and its parents (w30 and 082). Analysis of the expression revealed a total of 485 specially expressed genes (SEGs), 173 differentially expressed genes (DEGs) above parental expression level, more actively expressed genes and up-regulated DEGs in F1. Further study revealed that the DEGs detected in F1 and its parents were mainly involved in response to auxin, plant hormone signal transduction, DNA metabolic process, Purine metabolism, starch and sucrose metabolism, which suggested that these biological processes may play a crucial role in the heterosis of B. rapa. The analysis of 3D genome data revealed that hybrid F1 tend to contain more transcriptionally active A compartments after hybridization. Additionally, F1 had a smaller TAD (topologically associated domain) genome length, but the number was the highest, and the expression change of activated TAD was higher than repressed TAD. More specific TAD boundaries were detected between parents and F1. Subsequently, 140 DEGs with genomic structural variants were selected as potential candidate genes. Among them, we found two DEGs with consistent expression changes in A/B compartments and TADs. Our findings suggest that genomic structural variants, such as TADs and A/B compartments, may affect gene expression and contribute to heterosis in B. rapa. This study provides further insight into the molecular mechanism of heterosis in B. rapa.

A enantioselective tandem transformation concerning asymmetric allylic decarboxylative addition and cyclization of N-nosylimines with vinylethylene carbonates (VECs) in the presence of [Rh(C2H4)2Cl]2, chiral sulfoxide-N-olefin tridentate ligand has been developed. The reaction of VECs with various substituted N-nosylimines proceeded smoothly under mild conditions, giving highly functionalized oxazolidine frameworks in good to high yields with good to excellent enantioselectivity.

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.

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.

In this paper we investigate in different scenarios the feasibility of using massive multiple-input multiple-output (mMIMO) with Reconfigurable Intelligent Surfaces (RISs) to boost the throughput and coverage performances with high energy efficiency, considering sub-6 GHz, mmWave and THz bands. With that objective, a centralized radio access network (C-RAN) suitable for beyond fifth generation (B5G) systems is considered, where we integrate the base stations (BSs) with multiple RISs and devices or user equipment. RISs with a large number of quasi-passive reflecting elements constitute a low-cost approach capable of shaping the radio wave propagation and improve wireless connectivity. We consider a scenario where multiple RISs are combined with mMIMO in the uplink in order to provide connectivity to Smart City (thousands of active low power devices) wirelessly, in the 3.6GHz and 28GHz bands. We also address a scenario where RISs are adopted with mMIMO in the downlink so as to offer connectivity to a Stadium with Pitch, (thousands of active user equipment) in the 28GHz band. Finally, we have also studied the connectivity at 100GHz of a Factory where several RIS panels replacing most of the BSs equipped with mMIMO assure improved throughput and coverage. We concluded that RISs are capable of improving the performance in any of these analyzed scenarios at the different frequency bands, justifying that they are a key enabling technology for 6G.

Evidence indicates that the long noncoding RNAs are involved in the metformin-mediated anti-cancer processes. However, the potential effects of the long noncoding RNAs in metformin-mediated anti-tumor processes in esophageal squamous cell carcinomas (ESCC) are still elusive. This study uncovered that metformin decreases the level of long noncoding RNAs CCAT1 and SPRY4-IT1 thereby contributing to the down-regulation of c-Myc and vimentin. Also, the RNA level test of human ESCC tissue confirmed the positive correlation between CCAT1 and c-Myc. These findings demonstrated that metformin facilitated anti-cancer effects by targeting the 2 long noncoding RNAs (CCAT1 and SPRY4-IT1) and their consequential targets c-Myc and vimentin. Therefore, the CCAT1 and SPRY4-IT1 might act as novel molecular targets that mediate the anti-tumor effects in esophageal squamous cell carcinoma. This helps in predicting the treatment response of metformin in patients diagnosed with esophageal squamous cell carcinoma.

In this paper, Fe-Cr-C-N-Al-Y wear-resistant surfacing alloy was prepared by open arc surfacing with self-shielded flux-cored wire. The wear properties of the surfacing alloy were analyzed by MLS-23 rubber wheel wet sand wear tester. The phase composition and microstructure of the surfacing alloy were analyzed by XRD, SEM, EBSD and TEM, and the strengthening mechanism and wear mechanism of the alloy were discussed. The results show that the microstructure of Fe-Cr-C-N-Al-Y surfacing alloy is composed of M + γ-Fe + M7C3 + AlN. When the content of nano-Y2O3 is 0.456wt. %, the formability of the surfacing alloy is the best and the wetting angle is the smallest, which is 50.8°, AlN and M7C3 precipitate the most, and the microstructure grain is the smallest. At this time, the hardness value of the surfacing alloy is up to 62.3 HRC, which is 11.8 % higher than that of the unmodified surfacing alloy. The minimum wear weight loss is 0.125 g, and the wear resistance is increased by 41.86 %. The wear mechanism of surfacing alloy is mainly plastic deformation mechanism, and the material removal process is micro cutting and furrow wear.

Worldwide, the prevalence of surgery under general anaesthesia has increased significantly, on one hand because of modern anaesthetic and pain control techniques, and on the other hand because of better diagnosis and increased complexity of surgical technique. Together with the development of new concepts in the surgical field, the attention of researchers and clinicians turned to minimizing the impact of surgical trauma and offering minimal invasive procedures. This fact is due to the recent discoveries in the field of cellular and molecular mechanisms, that have revealed a systemic inflammatory and pro-oxidative impact that not only lasts in the perioperative period, but also impacts the long term, contributing to more difficult recovery, increased morbidity, and mortality, and finally a negative financial impact. Detailed molecular and cellular analysis have shown an overproduction of inflammatory and pro-oxidative species, that are responsible for an augmentation of the systemic inflammatory status and more difficult postoperative recovery. Moreover, it was shown that there are a series of changes in certain epigenetic structures, the most important being the microRNAs. Based on these findings, a series of modern, targeted therapeutic approaches have been proposed, with the final goal of blocking these mechanisms and reducing the redox state. Recent studies carried out had a positive clinical impact regarding antioxidant therapy and have shown that it can be used in the perioperative period with beneficial clinical impact. This review describes and details the most important molecular and cellular mechanisms that impact the surgical patient undergoing general anaesthesia, and it presents a series of antioxidant therapies that can reduce systemic inflammation.

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.

Concept Knowledge (C-K) theory has been used in engineering and science-based research for more than a decade. Design of an Information Technology (IT) artefact is mostly pragmatic in nature. Design Science Research (DSR) methodology applied and studied in many Information Systems (IS) research. Many sub design decisions involved through the design of an IT artefact from a concept (idea) to a working prototype. A DSR artefact is based on a combination of decisions made during several sub-design stages. Artefacts are built based on the selection of elements in each sub-design space. Recording the design decisions on each sub-design space would be beneficial for future researchers. By knowing the design decisions on each sub-design space, researchers would be able to try different combinations of the design. C-K theory provides the ability to capture the design processes’ several sub-design spaces. In this paper, we discuss the DSR research methodology by looking at the stages proposed in the literature, and the application of C-K theory in an IT-based DSR. This paper also proposed a C-K theory-based protocol called Concept Tree for tracking and reporting artefact design steps. The application of C-K theory in DSR is exhibited using the implementation of the Concept Tree for a prototype design IT artefact.

HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing HLA-E monomeric heavy chain (HC) (Open Conformers, OCs). Two of the mAbs (TFL-006 and TFL-007) bound to the HC’s coated on a solid matrix. The binding was inhibited by a peptide 117AYDGKDY123, present in all alleles of the six HLA-I isoforms but masked by 2-microglobulin -m) in intact HLA-I trimers (Closed Conformers, CCs). Identical HLA-I polyreactivity is observed in IVIg administered to lower anti-HLA antibodies (Abs) in HLA-sensitized patients, but the mechanism is unknown. We hypothesized that the mAbs that mimic IVIg HLA-I polyreactivity might mimic the immunomodulatory functions of IVIg. We tested the relative binding affinity of the mAbs and IVIg for both OCs- and CCs and compared their effects on (a) the phytohemagglutinin (PHA)-activation T-cells, (b) the production of anti-HLA-II antibody (Ab) by B-memory cells, and anti-HLA-I Ab by immortalized B-cells, and (c) the upregulation of CD4+, CD25+, and Fox P3+ T-regs. The mAbs bound only to OCs, whereas IVIg is bound to both CCs and OCs. The mAbs suppressed blastogenesis and proliferation of PHA-activated T-cells, anti-HLA Ab production by B-cells and expanded the T-regs, better than IVIg. We conclude that a humanized version of the TFL-mAbs could be an ideal therapeutic IVIg-mimetic.

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM), and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided in two groups: group A, with PROM ≥ 18 hours and group B, with PROM < 18 hours. Both groups were further split into subgroups: proven sepsis, probable sepsis and no sepsis. Descriptive statistics, ANOVA analysis, and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cells count from the first (p = 0.005) and third day (p = 0.028), and high CRP values from the first day (p = 0.004). Procalcitonin (area under the curve - AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early onset neonatal sepsis. (4) Conclusions: Further studies are needed to explore other bi-omarkers of sepsis in both pregnant women and newborns to better predict EOS.

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

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.

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.