Keywords: methylmercury, ApoE, epididymal white fat, metabolomics, dyslipidemia, oxidative stress, liver steatosis.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

Introduction: Type 1 diabetes mellitus is a chronic disease of autoimmune etiology that is highly prevalent in childhood. In the last decade, the possibility of using the Bacillus Calmette-Guérin vaccine for the treatment of this disease has been studied thanks to its immunomodulatory action . Objectives: The objective of this work is to carry out a systematic review of the available scientific evidence on the relationship between the tuberculosis vaccine and the treatment of diabetes in childhood. Secondarily, the aim is to study the incidence of Type 1 Diabetes Mellitus in a cohort of children from the Basque Country according to whether or not they have received the vaccine. Methods: An exhaustive bibliographic search has been carried out on the evidence available to date. For the epidemiological study in Euskadi, a comparison of accumulated incidences between vaccinated and unvaccinated population groups was made. Results: According to the literature analyzed, There is more and more evidence about the possible use of the tuberculosis vaccine in Type 1 Diabetes Mellitus. The results of our study were not conclusive, but we believe that it is necessary to continue with long-term studies to eliminate biases. Conclusions: The Bacillus Calmette-Guérin vaccine could be used for the treatment of autoimmune, allergic, infectious or oncological processes, although more studies are still necessary in this regard.

Lipoprotein (a) is a highly atherogenic, lipid particle whose concentration is genetically determined, and represents an independent risk factor for cardiovascular disease. On the other hand, metabolic syndrome represents a cluster of interconnected cardiovascular risk factors (obesity, insulin resistance, arterial hypertension, dyslipidemia) that are a direct consequence of an unhealthy lifestyle. Some evidence suggests a connection between each component of metabolic syndrome and high levels of lipoprotein (a). Still, the exact mechanisms are not fully understood and may involve complex interactions between various metabolic pathways. High levels of lp(a) are associated with insulin resistance, a key feature of type 2 diabetes mellitus and obesity. Although there is no significant association between lp(a) and other lipid levels (LDL-C, HDL-C, triglycerides), studies have shown a strong synergistic effect of genetically elevated LDL-C and Lp (a) on the development of cardiovascular events. Also, there is supporting evidence that hypertensive patients with high levels of lp(a) have higher cardiovascular risk, there is no direct association between hypertension and lp (a). Treatment of metabolic syndrome is often long-term and challenging but very important to reduce the overall cardiovascular risk, especially in individuals with higher levels of Lp (a), in whom the risk of developing cardiovascular disease is much higher.

Background and Objectives: Mycobacterium bovis Bacillus Calmette–Guérin (BCG) vaccine administration has been suggested to prevent glucose metabolism abnormalities and fatty liver in genetically obese ob/ob mice; however, it is not clear whether the beneficial effects of BCG are also observed in the progression of glucose intolerance induced by a high-fat diet (HFD). Therefore, the effects of BCG vaccination on changes in glucose tolerance and insulin response were investigated in HFD-fed C57BL/6 mice. Materials and Methods: We used the BCG Tokyo 172 strain to determine its effects on abnormalities in glucose metabolism. For vaccination, five-week-old male mice were injected intraperitoneally with BCG and maintained on an HFD three weeks later. The mice were regularly subjected to intraperitoneal glucose tolerance and insulin tolerance tests (IGTT and ITT). These tests were also performed in mice transplanted with bone marrow cells from BCG-vaccinated donor mice. Results: Significant effects of BCG vaccination on blood glucose levels in IGTT and ITT were observed from week 12 of the experiment. BCG vaccination significantly improved changes in fasting glucose and insulin levels, insulin resistance indexes, and glucagon-to-insulin ratios by HFD at the end of the experiment. Significant inhibitory effects in IGTT and ITT on glucose intolerance were also observed by transplantation with bone marrow cells derived from BCG-vaccinated donor mice. Conclusions: BCG vaccination significantly delayed glucose intolerance progression, suggesting a beneficial effect of BCG on the pathogenesis of type 2 diabetes. It has also been demonstrated that the effects of BCG vaccination may be at least partially due to an immune memory (trained immunity) for hematopoietic stem and progenitor cells of the bone marrow.

Metabolic syndrome (MS), a complex pathology with features like abnormal body fat distribution, insulin resistance, and dyslipidaemia, contributes to higher cardiovascular (CV) risk. A cross-sectional study including 87 individuals, assessed CV risk in elderly patients with type 2 diabetes and MS in Algarve, Portugal. The 10-year CV risk was estimated using the ADVANCE risk score calculator. The reductions in CV risk were estimated by adjusting the data inputted on the online tool to achieve systolic blood pressure (SBP) <130 or <120 mmHg, and LDL-cholesterol <70 mg/dL. Beyond waist circumference, the mean number of clinical features of MS was 3.14±0.84, without significant sex differences. The mean CV risk was 22.5% (CI: 20.3-24.7). Sex-specific analysis showed higher risk in males (24.2%, CI: 21.3-27.0) vs. females (19.7%, CI: 16.2-23.3; p=0.028). Hypothetical risk reductions show that lowering SBP to <130 mmHg could significantly lower the risk by an average of 9.2% (CI: 7.7-10.7), whereas 34.5% of the participants would be out of the diagnostic criteria for MS. When comparing each potential intervention with current risk, all interventions significantly reduce the 10-years CV risk. The study highlights the potential of blood pressure control in reducing CV risk and the importance of multifaceted risk reduction strategies.

Drug-induced liver injury (DILI) stands as a significant cause of drug attrition. To mitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2, HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in drug-induced liver injury marker expressions. In cytotoxicity assays, HepG2 cells exhibited heightened sensitivity to amiodarone HCl, while HepaRG cells showed greater sensitivity to acetaminophen. Generally, 2D cultures were more responsive to drugs than 3D cultures. Consistency was observed between cytotoxicity assays and liver injury markers AST and ALT. Variations were also noted in liver cell marker secretion, with albumin and urea concentrations declining post-drug treatment, particularly with higher baseline expression in HepaRG cells and 3D cultures. Additionally, mRNA expression levels of CYP enzymes involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not expressed in HepG2 cells. On the other hand, CYP3A4 was expressed higher in 3D culture than in 2D culture. HepaRG cells exhibited significantly increased expression of all three enzymes post-treatment. Notably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

p-type Ag-N dual acceptor doped ZnO thin films with long electrical stability were deposited by DC magnetron reactive co-sputtering technique. After deposition, the films were annealed at 400 °C for one hour in a nitrogen-controlled atmosphere. The deposited films were amorphous. However, after annealing they crystallize in the typical hexagonal wurtzite structure of ZnO. The Ag-N dual acceptors were incorporated substitutionally in the structure of zinc oxide and achieving that the three samples presented the p-type conductivity in the ZnO. Initial electrical properties showed a low resistivity of from 1 to10^{−3} Ω.cm, Hall mobility of tens cm2/V.s and a hole concentration from 10^{17} to 10^{19} cm^{−3}. The electrical stability analysis reveals that the p-type conductivity of the ZnO:Ag,N films is very stable and does not revert to n-type, even after 36 months of aging. These results reveal the feasibility of using these films for applications in short-wavelength or transparent optoelectronic devices.

Gilbert's syndrome (GS) is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism. This review, based on data from peer-reviewed articles and journals spanning from 1977 to January 2024, provides a comprehensive overview of over four decades of research on GS. Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome, laying the foundation for subsequent investigations. More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase, which has significantly enhanced our understanding of the pathogenesis of GS. Furthermore, recent studies have shed light on the clinical implications of GS, including its association with non-alcoholic fatty liver disease and mortality risk, highlighting the complex interplay between genetic factors, bilirubin metabolism, and clinical outcomes. Despite its generally benign nature, thorough research is essential to fully understand the impact of GS on patients' lives. This review emphasizes the importance of ongoing research to deepen our understanding of GS and its broader implications.

Neurofibromatosis type 2 (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2-deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2-deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

The increased prevalence of obesity worldwide has been implicated for the alarming rise of the incidence of gestational diabetes and preeclampsia as well, both considered as threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF and VEGF-receptor all known to be involved in pregnancy complications aiming to identify possible predisposing risk factors in pregnancies with obesity. G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and to those developed preeclampsia it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptor. We conclude that the genetic profile of the obese pregnant woman shares a common background with that of a pre-existing type 2 diabetes mellitus and therefore predisposes to complications in pregnancy.

Background This study aimed to identify the prominent risk factors that may trigger danger signals of early onset of vascular deregulation in T1D. The risk factors we have identified may serve as dual-purpose biomarkers of rapid diagnosis that offer prospective tailor-made resolution therapeutics. Methods The healthy control (HC) was compared with individuals diagnosed with T1D for the risk factors of vascular deregulation in published research studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, which is relevant to clinical subjects. A random effect model for continuous data was followed and analysed by RevMan 5.4 and GraphPad Prism software. Results 80 relevant case-control studies having 5293 HC and 7492 T1D patients were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of all age groups were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Conclusions Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-C, and AI% which the clinicians could evaluate using a simple blood test or non-invasive techniques. (Protocol registered at https://www.crd.york.ac.uk/prospero/ CRD42022384636).

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curable for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists or/and to downstage patients who are beyond Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine Kinase Inhibitors (TKIs) can be used as a bridging systemic therapy to LT in patients with contraindication to locoregional liver-directed therapies. Immune Checkpoint Inhibitors (ICIs) treatment can be utilized either as a monotherapy or as a combination therapy with Bevacizumab or TKIs prior to LT. Acute rejection post liver transplantation is a concern in the context of ICIs treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients.

Background and Objectives: To investigate the relationship between the SII index and the micro-macro complications and death that develop in the first year and the following 3 years, following the calculation of the index in type 2 diabetic retinopathy patients. Materials and Methods: This study was performed retrospectively with 523 type 2 diabetic retinopathy patients admitted to the endocrinology outpatient clinic of our hospital between January 2019 and December 2019. The demographic, and clinical characteristics of the patients were evaluated using descriptive statistics. Shapiro-Wilk test was used for the normal distribution of quantitative data; Mann-Whitney U, Mc Nemar Chi-square, and Cochran's Q tests were used to analyze SII values between groups and complication rates by years; sensitivity and specificity were determined by ROC analysis and considered statistically significant with a significance level of P

Rapidly digestible starch can be obtained by gelatinization (cooking), cooking extrusion, use of small granule starch, breaking down starch granules, or by hydrolysis to maltodextrins. Resistant starch includes five groups: the first group is physically encapsulated starch within a food/polymer matrix, the second one is some native starch, the third one is recrystallized starch, the fourth one is chemically modified starch, and the fifth one is starch-lipid complexes. Starch digestion in the human body is also influenced by the degree of chewing, activity of α-amylase in the intestine, and transit time through the stomach and small intestine. Resistant starch or dietary fiber (DF) enriches specific bacterial groups located in the large intes-tine. They produce short chain fatty acids (SCFAs) and gases, causes the lowering of the pH, and inhibits pathogens. SCFAs are considered endogenous signaling molecules, acting through their free fatty-acid receptors 2 and 3 which can trigger the secretion of glucagon-like peptide-1 and peptide PYY, being released together following a meal to mediate postprandial satiety. A sufficient intake of DF reduces the risk of cardiovascular disease, coronary heart disease, stroke, hyperten-sion, colorectal cancer, and type 2 diabetes. Gluten matrix or phenolic compounds can lead to a low digestion rate of starch.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

(1) Background: Learning and training in variable conditions favors adapting to unstable or changing environments. The aim of the study was to test the effect of variable practice on the accuracy of the forehand net approach shot in tennis.; (2) Methods: Thirty (n=30) first-class national players (12.9 ± 1.1 years old) participated, divided into three groups: i) induced variability training (n=10) (varying court surfaces and balls), ii) specific training (n=10) and iii) usual training -control group- (n=10). All groups trained for a month: 12 sessions of 20 minutes -3 per week-. The accuracy of the shots were analyzed through a 2D capture and digitization process of the ball bounce on the court; (3) Results: The variability group presented better accuracy values after the period without practice than the stable training group (p = 0.041; ES= 0.51).; (4) Conclusions: the application of variability in the game conditions during tennis training seems to have a favorable effect on the retention of accuracy in the forehand down the line approach to the net.

This study investigates the effects of subclinical hypothyroidism and BDNF on telomere length in T1DM mothers and their neonates. Methods: In this prospective cohort study, 70 pregnant women with T1DM were enrolled. Subclinical hypothyroidism during the first trimester was characterized by elevated thyroid-stimulating hormone (TSH) levels ranging from 2.5 to 5.0mIU/L alongside normal free thyroxine (FT4) concentrations. Participants were stratified into two groups based on TSH levels: a maternal subclinical hypothyroid group (SHG, n=35) and a maternal euthyroid group (ETG, n=35). Leukocyte telomere length (LTL) measurements were conducted using whole blood samples from the mothers and umbilical veins. Results: The maternal LTL mean was 1.7 (SD=1.1), which was significantly shorter than the neonatal telomeres, with a mean of 2.3 SD (1.2). A significant correlation was observed between maternal and neonatal LTL (r=0.750, p&lt;0.001). A positive association was found between neonatal LTL and BDNF levels in maternal circulation [β=0.421 (95% CI 0.536; 1.873; p=0.001)]. Neonatal LTL was negatively associated with gestational weight gain [β=-0.266 (95% CI-0.138; -0.009)], and with TSH in the first trimester [β=-0.237; (95% CI -0.493; - 0.010)]. Notably, neonates in the SHG exhibited shorter LTL, with a mean of 2.1 (1.0), compared to those in the ETG, who had a mean LTL of 2.7 (1.4). A positive association was found between maternal LTL and BDNF levels in maternal circulation [β=0.523 (95% CI 0.790; 1.950; P&lt;0.001)]. Maternal LTL was negatively associated with gestational weight gain [β=-0.259 (95% CI -0.122; -0.010)], and with TSH in the first trimester [β=-0.231; (95% CI -0.422; - 0.015)]. Conclusions: Genetic factors affect neonatal LTL. Maternal subclinical hypothyroidism reduces neonatal LTL. The link between maternal and neonatal LTL and BDNF reveals the complex endocrine-neurotrophic interaction in T1DM telomere dynamics.

Nuclear DNA mutations, mitochondrial DNA mutations, combined nuclear and mitochondrial DNA defects, and random occurrences are the main causes of mitochondrial disease. Black pigmentation loss is a major sign of Parkinsonism. Because of the loss of dopaminergic neurons in the substantia nigra, it drops to less than 80%. The degree of motor impairment was correlated with the amount of black pigmentation loss. After RNA extraction, reverse transcription is carried out because reverse transcriptase was used to create cDNA. One microliter of total RNA supplemented with IORT Buffer, dNTPs, random hexamers, Multi-Scribe Reverse Transcriptase, and nuclease-free was used to create cDNA. The following was how the reaction was carried out in a thermal cycler: 10 minutes at 25°C, 120 minutes at 37°C, 5 seconds at 85°C, and lastly 4°C. The data was expressed as a v-value, which shows how much the target gene is enriched in comparison to the reference gene. Earlier research using mice injected with functional HtrA2/Omi protease activity revealed similar outcomes, including induced up-regulation of CHOP, decreased mitochondrial function, and early brain cell aging because of an increase in mtDNA deletions. The cell viability of the genotypes exhibits a dmg concentration-dependent effect in these results, suggesting that high content ratios of drug treatment with 6-OHDA may be the cause of cellular content depletion. After 6-OHDA neurotoxin treatment, CHOP is up-regulated. Prior in vitro research has shown that treatment with a model based on 6-OHDA neurotoxin causes the activation of mitochondrial stress pathways, which in turn promotes the death of neurons. 6-OHDA reversibly inhibited complexes I and IV's activities in rat brain cells, which led to dopaminergic neurodegeneration, a defining feature of PD pathogens. As a result, the number of living cells will directly correlate with the dmg concentration, supporting the results of the current study. Real-time PCR can generally demonstrate that the removal of HtrA 2 results in a significant up-regulation of Hsp60 expression when compared to WT cells. This could be linked to a decreased threshold for mitochondrial stress in HtrA2 KO cells, which would explain why, following ADEP4 and ACP5 treatment, Hsp60 is significantly up-regulated in HtrA2 KO cells compared to WT cells.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, conspicuously during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to human, despite their secondary role for proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules, and CLPX on multi-enzyme condensates, near the inner mitochondrial membrane, as first-aid system. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, in mitochondrial RNA granules and nucleoids, and in D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination, and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, like peptidases MPP at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.

Maternal unbalanced diets cause adverse metabolic programming and affect the offspring's liver microRNA profile. The liver is a site of β-carotene (BC) metabolism and a target of BC action. We studied the interaction of maternal Western diet (WD) and early-life BC supplementation on the epigenetic remodeling of offspring’s liver microRNAs. Mouse offspring of WD-fed mothers were given daily a placebo (controls) or BC during suckling. The liver miRNAome was analyzed in recently weaned animals by microarray hybridization. BC impacted the liver miRNAome differently in male and female offspring, with no overlap in differentially expressed (DE) miRNAs between sexes and more impact in females. Bioinformatic analysis of DE miRNA predicted target genes revealed enrichment in biological processes/pathways related to metabolic processes, regulation of developmental growth and circadian rhythm, liver homeostasis and metabolism, insulin resistance, and neurodegeneration, among others, with differences between sexes. Fifty five percent of the overlapping target genes in both sexes identified were targeted by DE miRNAs changed in opposite directions in males and females. The results identify sex-dependent responses of the liver miRNA expression profile to BC supplementation during suckling and may sustain further investigations regarding the long-term impact of early postnatal life BC supplementation on top of an unbalanced maternal diet.

Dietary fibers regulate intestinal barrier function; however, the precise mechanisms remain unclear. This study investigated the effects of psyllium fibers on antimicrobial protein expression, focusing on the type II immunity and tuft cell-group 2 innate lymphoid cell (ILC2) circuit in the small intestine of the mouse. Supplemental psyllium fiber upregulated antimicrobial proteins, such as small proline-rich protein 2A (SPRR2A) and resistin-like beta (RELMβ), in mouse small intestine, evidently affecting cecal microbiota composition. Psyllium fibers also increased the RNA and protein expression of molecules related to ILC2 and tuft cells, such as IL-13, IL-25, DCLK1, Gfi-1b, SH2 domain-containing protein 3C, and Spi-B. In addition, ILC2 inhibitor (disulfiram) and bitter taste receptor blocker administration reduced psyllium-induced SPRR2A and RELMβ expression. Collectively, psyllium supplementation upregulates antimicrobial proteins such as SPRR2A and RELMß via the type II immune response and tuft cell-ILC2 circuit in the mouse small intestine.

Let a,b,c be positive integers such that a²+b²=c², 2|b,gcd(a,b)=1. In 1956, Jesmanowicz conjectured that for any positive integer w, the only solution of (aw)^x+(bw)^y=(cw)^z in positive integers is (x, y, z) = (2, 2, 2). In this paper, based on Gaussian integer ring, we show that Je$\acute{s}$manowicz' conjecture is true for any positive integer

Let BT4l denotes a subclass of bounded turning functions connected with a four-leaf-type domain. The goal of the study is to probe into coefficients of |b6|, |b7|, |b8|, the bounds of the logarithmic coefficients and the third-order determinants of H3,1, H3,2, H3,3 for functions in this class.

Aims: This study aims to evaluate the impact of family-centered empowerment on Jordanian adolescents with type 1 diabetes (T1DM), focusing on their HbA1c levels, self-efficacy, and quality of life (QOL). Background: Poor glycemic management in adolescents with type 1 diabetes increases complications. Improved control is linked to various variables, but few studies focus on Middle Eastern populations. Methods: An experimental study involved 68 adolescents with T1DM visiting Jordanian Royal Medical Services' clinics. Two sets of participants were created: control (n = 34) and intervention (n = 34). Data was collected through face-to-face interviews and medical records. Results: The study found significant differences in self-efficacy scores between the intervention and control groups, with the intervention group experiencing a significant decrease in HbA1c readings and a significant difference in QOL between pre-program and post-program phases. Discussion: Family empowerment can significantly improve the lives of Jordanian teenagers with type 1 diabetes. This strategy leads to improved glycemic management, increased self-efficacy, and improved quality of life. Future treatments and health policies should recognize and value the critical role families play in the care of this population. Conclusion: The study suggests that patients with T1DM should receive continuous care education sessions, including self-care training, to improve their health. Nurses should also incorporate these training into treatment plans and educational programs for adolescents to enhance their QOL.

In the context of the minimally extended varying speed of light (meVSL) model, both the absolute magnitude and the luminosity distance of type Ia supernovae (SNe Ia) differ from those predicted by general relativity (GR). Utilizing the Pantheon+ data, we examine the plausibility of various dark energy models under meVSL. Both ωCDM and CPL parameterization dark energy (DE) models exhibit indications of cosmic variations in the speed of light at the 1-σ level. For Ωm0=0.30,0.31, and 0.32 with (ω0,ωa)=(−1,0), the 1-σ range of c˜˙0/c˜0(10−13yr−1) is (-8.76 , -0.89), (-11.8 , 3.93), and (-14.8 , -6.98), respectively. Meanwhile, the 1-σ range of c˜˙0/c˜0(10−12yr−1) for CPL dark energy models with −1.05≤ω0≤−0.95 and 0.28≤Ωm0≤0.32, is (-6.31 , -2.98). The value of c˜ at z=3 can exceed that of the present by 0.2∼3 % for ωCDM models and 5∼13 % for CPL models. Additionally, for viable models except for the CPL model with Ωm0=0.28, we find −25.6≤G˜˙0/G˜0(10−12yr−1)≤−0.36. For this particular model, we obtain an increasing rate of the gravitational constant within the range 1.65≤G˜˙0/G˜0(10−12yr−1)≤3.79.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

Buildings’ thermal energy needs are inherently linked to climate conditions. Consequently, it is crucial to evaluate how climate changes affect these energy demands. Despite extensive analysis, a comprehensive assessment involving a diverse range of building types has not been consistently conducted. The primary objective of this research is to perform a coherent evaluation of the influence of climate changes, construction element properties, and the Heating, Ventilation, and Air Conditioning (HVAC) system type of control on the energy requirements of six buildings (residential, services, and commercial). The buildings are considered located in a temperate Mediterranean climate. Our focus is on the year 2070, considering three distinct climatic scenarios: (i) maintaining the current climate without further changes, (ii) moderate climate changes, and (iii) extreme climate changes. The buildings are distributed across three different locations, each characterized by unique climatic conditions. Buildings’ envelope features a traditional External Thermal Insulation Composite System (ETICS) and expanded polystyrene (EPS) serves as thermal insulation material. Two critical design factors are explored: EPS thickness ranging from 0 (no insulation) to 12 cm; and horizontal external fixed shading elements varying lengths from 0 (absence) to 150 cm. Six alternative setpoint ranges are assessed for the HVAC system control: three based on the Predicted Mean Vote (PMV) and three based on indoor air temperature (Tair). Results were obtained with a validated in-home software tool. They show that, even under extreme climate conditions, the application of thermal insulation remains energetically favorable, however its relative importance diminishes as climate severity increases. Then, proper insulation design remains important for energy efficiency. The use of external shading elements for glazing (e.g., overhangs, louvers) proves beneficial in specific cases. As climate changes intensify, the significance of shading elements grows. Thus, strategic placement and design are necessary for good results. The HVAC system’s energy consumption depends on the level of thermal comfort requirements, on the climate characteristics and on the building’s type of use. As climate change severity intensifies, energy demands for cooling increase, while energy needs for heating decrease. However, it’s essential to recognize that the impact of climate changes on HVAC system energy consumption significantly depends on the type of building.

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

We have now identified two thermodynamically distinct types (A and B) of energetic processes naturally occurring on Earth. Type A energy processes such as the classical heat engines, apparently well follow the second law of thermodynamics; Type B energy processes, such as the newly discovered thermotrophic function that isothermally utilizes environmental heat energy to do useful work in driving ATP synthesis, which follows the first law of thermodynamics (conservation of mass and energy) but does not have to be constrained by the second law, owing to their special asymmetric functions. Several Type-B energy processes such as asymmetric-function-gated isothermal electricity and epicatalysis have been created through human efforts. The innovative efforts on Type-B processes to enable isothermally utilizing endless environmental heat energy could help to liberate all peoples from their dependence on fossil fuel energy, thus helping to reduce greenhouse gas CO2 emissions and control climate change towards a sustainable future for the humanity on Earth.

Chronic conditions like type 2 diabetes mellitus (T2DM), arterial hypertension (HTN), and obesity are major global health issues, causing significant morbidity and mortality. In Latin America, these conditions contribute to millions of premature deaths annually, posing challenges exacerbated by limited healthcare access and poor primary care quality, particularly in Mexico. Complementary medicine presents a potential solution, offering minimally invasive techniques to improve physical, mental, and spiritual well-being. Effective treatment adherence, crucial for positive outcomes, is influenced by self-efficacy, the ability to manage one's behavior in response to medical conditions. However, treatment adherence rates remain low, indicating a pressing public health concern. This study aimed to explore how perception of complementary medicine and treatment adherence predict self-efficacy among individuals with chronic conditions in Mexico. Analyzing data from 113 participants revealed significant correlations between variables, with treatment adherence positively associated with self-efficacy and perception of holistic medicine negatively correlated with self-efficacy. Regression analysis showed that incorporating perception of complementary medicine and treatment adherence significantly explained self-efficacy levels, suggesting the potential of complementary therapies in holistic healthcare approaches. However, collinearity between variables highlights the need for further research to better understand these relationships and their implications for improving healthcare outcomes in Mexico. Integrating complementary therapies with conventional treatments could enhance overall well-being and treatment adherence, offering promising avenues for addressing chronic conditions in the region. These findings underscore the importance of comprehensive healthcare approaches that integrate both conventional and complementary modalities to optimize health outcomes and quality of life for individuals with chronic conditions in Mexico and beyond.

Mothers of children with a specific clinical condition such as type 1 diabetes mellitus (T1DM) may experience higher levels of stress predisposing them to a poorer perception of quality of life and alterations in nutritional status. The aim of this research was to evaluate the relationship between nutritional status and quality of life perception of mothers caring for children with Type 1 Diabetes Mellitus. This research was conducted from July to September 2022, with mothers of children aged 5 to 10 years with diabetes. Data were collected through an online questionnaire including soci-oeconomic information, anthropometric data, clinical data of the children, and the WHO-QOL-abbreviated quality of life questionnaire. For statistical analysis, Statistical Package for Social Science 24 was used. Fifty-five mothers of children with diabetes were evaluated. Over 33% of the mothers were overweight and reported a regular perception of quality of life. Higher BMI was associated with poorer perception of quality of life in the psychological and self-assessment domains, and longer diagnosis time was associated with better perception of quality of life in the physical, psychological, and environmental domains. Therefore, it is understood that actions aimed at improving the quality of life of these mothers are necessary.

Existing research indicates that mineralization of Carlin-type gold deposit is related to geological structures, but current studies mostly focus on the qualitative association, and lack quantitative analysis of the relationship between mineralization and structural features, which limits the potential for predictive mineral exploration. In this study, the Nibao Carlin-type gold deposit was selected as the research area to conduct three-dimensional geological modeling, spatial analysis, and three-dimensional prospectivity modeling. Spatial analysis revealed that the majority of gold ore bodies are situated near the main fault, with gold mineralization primarily occurring within a spatial range of approximately -80 meters to 20 meters from the main fault plane. This spatial distribution predominantly aligns in a SW-NE direction. Spatial characteristic extraction of fault slope indicators suggests that the slope angles are conducive to the migration and accumulation of ore-forming hydrothermal fluids, with ore body metal content rapidly increasing within an angle range of approximately 20° to 60°. The shape analysis of the mainfault indicates that the principal spaces of mineralization enrichment are within -10m to 20m of the fault plane undulations, where gold resources are concentrated in a relatively flat area. However, the degree of mineralization is more pronounced in the protruding sections than in the depressed areas. The areas with significant dip changes in faults display higher variations in orebody attitudes, with mineralization noticeably weaker in areas where the fault steepness changes markedly. Ore-bearing units exhibit significantly higher grades within the -17° to 3° interval of fault steepness transition. This interval also sees a rapid accumulation of gold resources. The Nibao gold mine's mineralization is derived from deep, ore-bearing hydrothermal fluids ascending along major fractures, precipitating, and accumulating in favorable ore-hosting spaces (faults, anticline cores) and lithological combinations (sedimentary tuffs, tuffs). Three deep potential gold targets were identified, highlighting the deep western edge of the F1 fault and the deep southeast-trending lower plate as prospective areas for future exploration. This study underscores the effectiveness of 3D prospective modeling as an indispensable tool for elucidating the spatial distribution of fault-controlled Carlin-type gold deposits and their tectonic determinants.

Tunicate orthologs in the human genome comprise just 84 genes of the 19,872 protein-coding genes, yet they stand at the base of the Olfactores clade - which radiated to generate thousands of tunicate and vertebrate species. What were the powerful drivers among the 84 that enabled this process? Many of these orthologs are present in gene families. We discuss the biological role of each family and the orthologs’ quantitative contribution to the family. Most important was the evolution of a second type of cadherin. This, a Type II cadherin, had the property of detaching the cell containing that cadherin from cells that expressed the Type I class. The set of such Type II cadherins could now detach and move away from their Type I neighbours, a process which would eventually evolve into the formation of the neural crest, “ the fourth germ layer”, providing a wide range of possibilities for further evolutionary invention. A second important contribution were key additions to the broad development of the muscle and nerve protein and visual perception tool-kits. These developments in mobility and vision provided the basis for the development of the efficient predatory capabilities of the Vertebrata.

A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.

Background: Progression of metabolic dysfunction associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis. MASH can lead to cirrhosis and hepatocellular carcinoma. We showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASLD-induced liver fibrosis and tumorigenesis. Methods: Using mice fed MASH diet for 24-52 weeks, we examined MASLD in mice with hepatocyte specific Nrf1, Nrf2, or combined deletion, and compared this to control. In a separate study, mice received weekly injections of carbon tetrachloride to induce liver fibrosis. From week 16-24, mice were treated with Nrf2 activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and groups were compared to control. Results: Hepatocyte Nrf2 deficiency had no effect. Hepatocyte Nrf1 and combined deficiency caused MASH but only hepatocyte Nrf1 deficiency in male mice increased tumor number. Bardoxolone reduced liver steatosis, fibrosis, inflammation, and proliferation, and this effect when combined with hNRF1 was greater than bardoxolone alone. Conclusion: Physiologic Nrf1 delays MASLD progression, Nrf2-induction alleviates MASH, and combined enhancement synergistically protects against steatosis.

In Indonesia, types of meat are still identified manually due to increasing prices for beef and buf-falo ahead of Idul Fitri. Traders mix beef with pork to thwart the beef scam. Haar wavelet and GLCM, GLCM with angles of 0°, 45°, 90°, and 135°, as well as matrices using contrast, correlation, energy, homogeneity, and entropy, are used in feature extraction. The following are the results of meat image classification testing using k-NN, Haar wavelet, and GLCM: The k-NN algorithm shows superiority in identifying fresh (99%), frozen (99%), and rotten (96%) meat texture images with the most fantastic accuracy results in every situation. Meanwhile, GLCM routinely provides good results, especially regarding the texture image of fresh meat (183.21) and rotten meat (115.79). However, despite delivering less throughput than k-NN and GLCM, Haar wavelets are still helpful, especially when dealing with fresh meat texture images (89,96).

The liver diseases are posing serious threat to human health associated with abusive use of allopathy medicines, especially in developing economies like Pakistan. The strengthening of detoxification system using natural products might be a suitable option to minimize the liver problems. In this current research, Zingiber officinale and Azadirachta indica were evaluated for their hepatoprotective role. For the purpose, 20 Sprague Dawley rats were equally divided into four groups i.e., negative control, paracetamol positive control, 2.5% ginger and 2% neem powder, respectively. During 42 days study, the levels of bilirubin and liver enzymes significantly elevated due to liver damage. Although, the values dropped (20-25%) in treatment group. Serum glucose and serum lipid profile increased in positive control group, but reduced (5-10%) in both ginger and neem groups. The serum protein profile declined in liver damage group, however, improved (~5%) in treatment groups. The hematological parameters slightly declined in liver damage group, but increased in ginger and neem groups. Moreover, the white blood cells differential count and renal parameters showed abnormal values in liver damage group, but improved after treatment. This study is promising and highlighted the hepato-protective role of neem and ginger that may open several avenues of research.

Lipid droplet (LD) accumulation in hepatocytes is one of the major symptoms associated with fatty liver disease. Mitochondria play a key role in catabolizing fatty acids for energy production through β-oxidation. The interplay between mitochondria and LD assumes a crucial role in lipid metabolism, while it is obscure how mitochondrial morphology affects systemic lipid metabolism in the liver. We previously reported that cilnidipine, an already existing anti-hypertensive drug, has potency to prevent pathological mitochondrial fission by inhibiting protein-protein interaction between dynamin-related protein 1 (Drp1) and filamin, an actin-binding protein. Here, we found that cilnidipine and its new dihydropyridine (DHP) derivative, 1,4-DHP, which lacks Ca2+ channel blocking action of cilnidipine, prevent the palmitic ac-id-induced Drp1-filamin interaction, LD accumulation and cytotoxicity of human hepatic HepG2 cells. Cilnidipine and 1,4-DHP also suppressed the LD accumulation accompanied by reducing mitochondrial contact with LD in obese model and high fat diet-fed mouse livers. These results propose that targeting Drp1-filimin interaction becomes a new strategy for the prevention or treatment of fatty liver disease.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play vital roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and potential therapeutic targets in this area.

Breast cancer, when advancing to a metastatic stage, involves the liver, impacting over 50% of cases and significantly diminishing survival rates. Presently, a lack of tailored therapeutic protocols for Breast Cancer Liver Metastasis (BCLM) underscores the need for a deeper understanding of molecular patterns governing this complication. Therefore, by analyzing differentially expressed genes (DEGs) between primary breast tumors and BCLM lesions, it aimed to shed light on the diversities of this process. This research investigates Breast cancer liver metastasis relapse by employing a comprehensive approach that integrates data filtering, Gene Ontology and KEGG Pathway Analysis, Overall Survival analysis, identification of the Alteration in the DEGs, Visualization of Protein-Protein Interaction Network, Signor 2.0, identification of positively correlated genes, screening results of the function of hub genes, immune cell infiltration analysis, genetic alternation analysis, Copy number variant analysis, Gene to mRNA interaction, transcription factor analysis , autodocking and identification of Potential Treatment Target. This study’s integrative approach unveils metabolic reprogramming, suggesting altered PCK1 and LPL expression as key in breast cancer metastasis recurrence.

Fiber-rich green river Aonori alga is mass-cultivated in Japan; it has been reported to reduce inflammation and improve metabolic health in humans. Peroxisome proliferation-activated receptor (PPARs) are associated with metabolic disorders such as obesity and type 2 diabetes (T2DM). We evaluated the effects of supplementation with NBF2, a formula made of algal and junos citrus biomaterials, on metabolic markers in obese and diabetic rats. An experimental study was performed using 18 obese and hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats randomly assigned to high dose NBF2 (20mg/kg; n=6), low dose (10mg/kg; n=6) NBF2 drink for 6 weeks, whereas OLETF control rats received similar amount of tap water (vehicle; n=6). LETO rats were used as normal controls (n=8). Biospecimens were taken for ELISA and real-time PCR. Both high dose and low dose NBF2 increased brown adipose tissue (BAT) mass and adiponectin (APN), improved insulin sensitivity, and significantly improved glycemic and lipid (TG, LDL-c) profiles in NBF2-supplemented OLETF rats after a 6-week supplementation with NBF2 (vs. OLETF controls), as well as LDL-c (p<0.05). During the glucose tolerance test (OGTT), both NBF2 groups and LETO rats had normal glycemia by 90-minute time-point (vs. OLETF controls; p<0.01). Furthermore, intake of NBF2 up-regulated PPARa/g-mRNA and Sirt2-mRNA gene expressions in BAT, and improved blood pressure profile in OLETF rats. Findings from this research suggest that intake of NBF2 formula induces dual PPAR-a/g and Sirt2 activation, providing insights on beneficial prophylactic and therapeutic effects of this NB2 formula on dyslipidemia and hyperglycemia in T2DM.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

It is essential to have a thorough knowledge of the genetic variation among different strains of Xanthomonas citri pv. citri (Xcc), which is responsible for causing citrus bacterial canker. This understanding is important for studying the disease’s characteristics, population structure, and evolution, and ultimately for developing sustainable methods of control. A total of 48 strains, obtained from citrus production areas in Burkina Faso in 2012, 2020, and 2021, were subjected to polymerase chain reaction (PCR) tests using specific primers. The aim was to examine the distribution of type 3 effectors (T3E) and determine the geographical origins of the strains. The examination of the distribution of type 3 non-transcription activate like effectors (TALE) indicates a broader range in strains obtained in 2020 and 2021 compared to those obtained in 2012. However, all strains possess a shared set of three genes, specifically XopE2, XopN, and AvrBs2. Furthermore, all examined effectors were observed in the Bobo-Dioulasso region. Regarding the characterization of TALEs, two profiles containing two to three TALEs were discovered. Profile 1, consisting of two TALEs, was found in 37 Xcc strains, whereas Profile 2, comprising three TALEs, was detected in 11 strains. Out of the three TALEs (A, B, and C) that were identified, TALEs B and C were present in all strains. The correlation matrix indicated a positive association between the T3E content of strains and the duration of their isolation. Principal component analysis revealed a limited organization of the strains under investigation

We report a novel dual-band barrier infrared detector (DBIRD) design using type-II superlattices (T2SLs). The DBIRD structure consists of back-to-back barrier diodes: a "blue channel" (BC) diode which has an nBp architecture, an n-type layer of larger bandgap for absorbing blue band infrared/barrier/p-type layer, and a "red channel" (RC) diode which has an pBn architecture, a p-type layer of smaller bandgap for absorbing red band infrared/barrier/n-type layer. Each has a unipolar barrier using a T2SL lattice matched to a GaSb substrate to impede the flow of majority carriers from the absorbing layer. Each channel in the DBIRD can be independently accessed with a low bias voltage, as is preferable for high-speed thermal imaging. Device modeling of DBIRDs and simulation results of the current-voltage characteristics under dark and illuminated conditions are also presented. They predict that dual-band operation of the DBIRD will produce low dark currents and 27-33% quantum efficiencies for the in-band photons in the BC with λc=5.58 μm, and a nearly-constant 33% in the RC with λc=8.05 μm. The spectral quantum efficiency of the BC for 500 K blackbody radiation is approximately 20% over the range of λ=3 − 4.2 μm, while that of the RC has a peak of 42% at 5.7 μm. The DBIRD may provide improved high-speed dual-band imaging in comparison with NBn dual-band detectors.

Abstract: Background: Irreversible electroporation (IRE) is a form of non-thermal ablation that delivers pulses of high voltage electrical current between electrodes. The role of IRE in the treatment of colorectal hepatic metastases is unestablished. This study is an international ques-tionnaire survey of the use of IRE for colorectal hepatic metastases. Methods: A questionnaire addressing views on the use of IRE for colorectal liver metastases was circulated to clinicians with an interest and/or expertise in this technique. Results: 64 clinicians from 17 different countries replied to the questionnaire. Thirty-six (56%) had experience of treating patients with colorectal liver metastases with IRE. The preferred mode of delivery of IRE was percutaneous treatment under CT guidance. Thirty-three (70% respondents) used IRE exclusively for lesions in proximity to inflow or outflow structures. Twenty (43% respondents) used IRE as their sole ablative treat-ment whilst 19 (40% respondents) used IRE in combination with thermal ablation. The maximum number of lesions that could be treated by IRE was two and preferred size of lesion was

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in early predicting CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on November 12th, 2023, using the MeSH terms “Children”, “CPB”, “L-FABP”, and “Acute Kidney Injury”. Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher’s exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) were susceptible to HBV, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.

The Upper Hunter Valley is a major coal mining area in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. The early part of this study identified two air quality subregions in the valley. This paper aims to provide a holistic summarisation of the relationships between elevated PM10 pollution in two subregions and the local- and synoptic-scale meteorological conditions for spring and summer, when PM10 pollution is relatively high. A catalogue of twelve synoptic types and a set of six local meteorological patterns have been quantitatively derived and linked to each other using the self-organising map (SOM) technique. The complex meteorology-air pollution relationships have been visualised/interpretated on the SOM planes for two representative locations. It was found that the influence of local meteorological patterns differed significantly for mean PM10 levels vs the occurrence of elevated pollution events and between air quality subregions. In contrast, synoptic types showed generally similar relationships with mean vs elevated PM10 pollution in the valley. Two local meteorological patterns, the hot-dry-northwesterly wind conditions and the hot-dry-calm conditions, were found most PM10 pollution conducive in the valley when combined with a set of synoptic counterparts. These synoptic types are featured with the influence of eastward migrating continental high pressure system and westerly troughs, or a ridge extending northwest towards coastal northern NSW or southern Queensland from the Tasman Sea. The method and results can be used in air quality research for other locations of NSW, or similar regions elsewhere.

A comprehensive understanding of the genetic diversity among strains of Xanthomonas citri pv. citri (Xcc), the causative agent of citrus bacterial canker, is crucial for unraveling the pathological nature, structure, and evolution of populations, thereby facilitating the adoption of sustainable control measures. In a collection of 48 strains isolated in 2012, 2020, and 2021 from citrus production areas in Burkina Faso, polymerase chain reaction (PCR) tests utilizing specific primers were conducted to investigate the distribution of type 3 effectors (T3E) and the structuring of strains based on their geographical origins. The analysis of the distribution of type 3 non-transcription activate like effectors (TALE) reveals a more extensive repertoire in strains isolated in 2020 and 2021 compared to those isolated in 2012. Nevertheless, all strains share a common repertoire of three genes, namely XopE2, XopN, and AvrBs2. Additionally, all screened effectors were observed in the Bobo-Dioulasso locality. Concerning the characterization of TALEs, two profiles consisting of two to three TALEs were identified. Profile 1, with two TALEs, was present in 37 Xcc strains, while Profile 2, with three TALEs, was identified in 11 strains. Among the three TALEs (A, B, and C) identified, TALEs B and C were common to all strains. The correlation matrix revealed a positive correlation between the T3E content of strains and the years of their isolation. Multiple component analysis indicated a weak structuring of the tested strains.

Drugs are known to cause substantial liver injury, with hepatotoxicity ranging from asymptomatic increase of liver enzymes to hepatic failure. HIV/AIDS patients, with compromised immune systems, are especially vulnerable to opportunistic infections such as tuberculosis (TB). Patients with co-infection frequently get combined antiretroviral (ART) and antitubercular (ATD) regimens, which can cause hepatotoxicity. Hepatotoxicity has been linked to commonly administered antiretroviral drug regimens as well as first-line antitubercular agents such isoniazid, rifampin, and pyrazinamide, which are required for the treatment of both drug-sensitive and drug-resistant tuberculosis. As a result, there is an urgent need to investigate treatments based from traditional herbs known for their hepatoprotective abilities against ART and ATD-induced liver injury. Many researchers have investigated the effectiveness of medicinal plants in treating chemically caused hepatotoxicity. Medicinal plants are high in phytochemicals and secondary metabolites, both of which have a variety of medicinal benefits. Currently, there is a lack of specific therapeutic regimens to address this adverse effect, and management often relies on symptomatic treatment or therapy withdrawal. Traditional medicinal plants may have the potential to restore normal liver function, enzyme activity, and cellular structure in response to ART and ATD-induced hepatotoxicity. This review aims to examine the scientific evidence supporting the use of medicinal plants as hepatoprotective agents against liver damage induced by ART and ATDs.

Abstract: The study used whole-genome sequencing (WGS) and bioinformatics analysis for the genomic characterization of 60 isolates of Listeria monocytogenes isolated from cattle farms, cattle abattoirs, and retail outlets in Gauteng province, South Africa. The isolates' sequence types (STs), clonal complexes (CCs), and lineages were determined using in silico multilocus sequence typing (MLST). We used BLAST-based analyses to identify virulence and antimicrobial genes, plasmids, proviruses, and the CRISPR-Cas system. The study investigated any association of the detected genes to the origin in the beef production chain of the L. monocytogenes isolates. Overall, in 60 isolates of Listeria monocytogenes, there were 7 STs, 6 CCs, 44 putative virulence factors, 2 resistance genes, 1 plasmid with AMR genes and 3 with conjugative genes, 1 CRISPR gene, and all 60 isolates were positive for proviruses. Among the 7 STs detected, ST204 (46.7%) and ST2 (21.7%) were the most prominent, with ST frequency varying significantly (p&lt;0.001). The predominant CC detected were CC2 (21.7%) and CC204 (46.7%) in lineages I and II, respectively. Of the 44 virulence factors detected, 26 (across Listeria Pathogenicity Islands, LIPIs) were present in all the isolates. The difference in the detection frequency varied significantly (P&lt;0.001). The two AMR genes (fosX and vga(G)) detected were present in all 60 (100%) isolates of L. monocytogenes. The only plasmid, NF033156, was present in 3 (5%) isolates. A CRISPR-Cas system was detected in 6 (10%), and all the isolates carried proviruses. Significant differences were detected in the frequencies of STs and virulence factors regarding the source and sample type of the L. monocytogenes isolates. The presence of both fosX and vga(G) genes in all the isolates from the three industries (cattle farms, abattoirs, and retail outlets) can potentially cause therapeutic implications. Our study, which characterized L. monocytogenes recovered from the three levels in the beef production chain in the country, provides the first evidence of the distribution of the pathogen with potential food safety and therapeutic implications.

The sexual reproduction of ascomycetes is controlled by the mating-type(MAT) locus. (Pseudo)homothallic reproduction has been hypothesized based on genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis). In this study, the differential occurrence of the mating-type genes in the MAT1-1 and MAT1-2 idiomorphs, which constitute the genetic control of O. sinensis reproduction, was analyzed in 237 strains and 5 genomes of H. sinensis. The mating-type genes were differentially transcribed in H. sinensis Strain L0106, and the MAT1-2-1 transcript in H. sinensis Strain 1229 was alternatively spliced, with an unspliced intron I containing stop codons; these findings constitute O. sinensis reproduction controls at the transcriptional and coupled transcriptional-translational levels. The occurrence of the mating-type genes and a-/α-pheromone receptor genes differed among the 5 H. sinensis genomes. The differential occurrence and transcription of these genes are inconsistent with self-fertilization under (pseudo)homothallism but suggest self-sterility of H. sinensis, which therefore needs a mating partner to achieve sexual outcrossing under heterothallism or hybridization. Consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis, but these findings are insufficient to determine the reproduction mode(s) because of the co-occurrence of >90 fungal species and multiple genomically independent genotypes of O. sinensis. The mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in the N-terminus or middle-truncated proteins, with changes in hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction.

Graft injury affects over 50% of liver transplant (LT) recipients, but non-invasive biomarkers to diagnose and guide treatment are currently limited. We aimed to develop a biomarker of graft injury by integrating serum metabolomic profiles with clinical variables. Serum from 55 LT recipients with biopsy confirmed metabolic-dysfunction associated steatohepatitis (MASH), T-cell mediated rejection (TCMR) and biliary complications was collected and processed using a combination of LC-MS/MS assay. The metabolomic profiles were integrated with clinical information using a multi-class Machine Learning (ML) classifier. The efficacy of the model was assessed through the evaluation of the Out-of-Bag (OOB) error estimate. Our ML model yielded an overall accuracy of 79.66% with an OOB estimate of the error rate at 19.75%. The model exhibited a maximum ability to distinguish MASH, with an OOB error estimate of 7.4% compared to 22.2% for biliary and 29.6% for TCMR. The metabolites serine and serotonin emerged as the topmost predictors. When predicting binary outcomes using 3 models: Biliary (biliary vs. rest), MASH (MASH vs. rest) and TCMR (TCMR vs. rest), the AUCs were 0.882, 0.972 and 0.96 respectively. Our ML tool integrating serum metabolites with clinical variables shows promise as a non-invasive, multi-class serum biomarker of graft pathology.

Patients with predominantly antibody deficiencies (PAD) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate their possible contribution to PAD clinical phenotype. Eight CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474) which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD, in order to identify patients with a higher risk for liver disease.

This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes asso-ciated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity and their association with non-alcoholic fatty liver disease (MAFLD). We did not observe a significant association between the investigated SNPs and COVID-19 severity. While the IFNAR2 rs2236757 A allele correlated with higher creatinine levels upon admission and the G allele with lower band neu-trophils upon discharge, these findings require further investigation. The distribution of OAS gene polymorphisms (rs10774671, rs10735079 did not differ between MAFLD and non-MAFLD patients. Our study population's distribution of ACE2 rs2074192 genotypes and alleles differed from the European reference population. Overall, our findings suggest that these specific SNPs may not be major contributors to COVID-19 severity in our patient population, highlighting the potential role of other genetic factors and environmental influences.

Rhodotorula mucilaginosa fungaemia is rare and highly resistance to antifungal therapy. We herein report a case involving a 31-year-old male admitted after a high-velocity road traffic accident. He sustained a grade IV liver injury with right hepatic vein thrombosis, necessitated an urgent laparotomy. Post-operatively, repeated imaging of the abdomen revealed presence of biloma. Percutaneous subdiaphragmatic drainage was done but appeared ineffective, prompting second surgery for a urgent hemi-hepatectomy. Patient then was nursed in the intensive care unit (ICU) however during his stay in the ICU he became more sepsis evident by worsening ventilatory support and rise in septic parameters from the biochemistry parameters. Despite on intravenous piperacillin-tazobactam and fluconazole, his septic parameters did not improve and a full septic workup was done and was found to be positive for Rhodotorula mucilaginosa from the blood cultures. After discussion with the infectious disease physicians and clinical microbiologist, it was decided to initiate a course of intravenous meropenem and amphotericin B based on minimum inhibitory concentration (MIC) values, considering the patient's extended ICU stay and catheter use. Eventually, successful weaning off mechanical ventilation was discharge from ICU care. This case underscores the necessity of individualized approaches, combining timely imaging, appropriate drainage techniques, and tailored treatments to optimize outcomes for such intricate post-traumatic complications.

The microscopic pore structure of tight sandstone reservoir significantly influences the characteris-tics of CO2 flooding after water flooding. The research was conducted using various techniques such as casting thin sections, high pressure mercury injection, scanning electron microscopy, Nu-clear magnetic resonance (NMR) testing, and a self-designed high-temperatures and high-pressures microscopic visualization displacement system. Three type cores with different pore structures were selected for the flooding experiments and the microscopic visualization displace-ment experiments, including CO2 immiscible flooding, near-miscible flooding, and miscible flood-ing after the conventional water flooding. The characteristics of CO2 flooding and the residual oil distribution after water flooding were quantitatively analyzed and evaluated. The results show that: (1) During the water flooding process, the oil produced from type I and type III samples mainly comes from large and some medium pores. Oil utilization of all pores is significant for type II samples. The physical properties and pore types have a greater impact on water flooding. Type I and II samples are more suitable for near-miscible flooding after water flooding. Type III samples are more suitable for miscible flooding after water flooding. (2) In the CO2 flooding, oil recovery increases gradually with increasing pressure for all three types of samples. Type II core samples have the highest recovery. Before miscibility, the oil recovered from type I and type II samples was primarily from large pores, however, the oil recovery mainly comes from medium pores when reaching miscibility. As for the type III samples, the oil produced in the immiscible state mainly comes from large and medium pores, and the enhanced oil recovery mainly comes from medium and small pores after reaching the near-miscible phase. (3) It can be seen from the microscopic re-sidual oil distribution that oil recovery will increase as the petrophysical properties of the rock model improve. The oil recovery of near-miscible flooding after water flooding regarding the type II model is up to 68.11%. The oil recovery of miscible flooding after water flooding about type III model is the highest at 74.57%. With increasing pressure, the proportion of flake residual oil grad-ually decreases, while the proportion of droplet-like and film-like residual oil gradually increases. Type II samples have a relatively large percentage of reticulated residual oil in the near-miscible stage.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

This is growing recognition of early onset gastrointestinal (GI) malignancies in young adults

Regulatory T cells are key immune cells to initiate tolerable immune responses. TGFβ is the key cytokine of regulatory T cells. TGFβ is also the master cytokine to stimulate tissue fibrosis. Systemic sclerosis is an autoimmune disease related to overt organ fibrosis. Thus, systemic sclerosis is a disease related to regulatory T cell over-representation. Besides, many end stage organ failures including heart failure, liver cirrhosis, uremia, and pulmonary fibrosis also related to tissue fibrosis. Thus, TGFβ producing regulatory T cells are also involved in the pathogenesis of these end stage organ failure. Once we know the significance of TGFβ and it induced tolerable immune reactions in the pathophysiology of end organ failure, we can develop better prevention or therapeutic strategies to combat these detrimental disorders.

The late diagnosis of Type 2 Diabetes Mellitus can occur due to lack of access to the primary health care system and the non-manifestation of symptoms. Faced with this problem, this work presents the creation of a mobile application, called DiabetesCheck, for predicting the risk of Type 2 Diabetes Mellitus. A mathematical model is used, which classifies the risk of Type 2 Diabetes Mellitus for a group of patients with intervention and for a comparative group, using Fuzzy Classification and Decision Trees. The proposed application allows the health professional to monitor patients through the history stored in a database, allowing a representation of the evolution of patients and indication of medications. Therefore, this proposal aims to carry out the diagnosis in the initial phase of the disease and help in the prescription of more effective treatments and in the proposition of public policy strategies in epidemiology and screening.

The gastrointestinal tract is inhabited by the gut microbiota. The main phyla are Firmicutes and Bacteroidetes. In non-alcoholic fatty liver disease, now renamed metabolic dysfunction-associated fatty liver disease (MAFLD), an increase in Firmicutes and Bacteroidetes abundance promotes its pathogenesis and evolution into non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma. For this reason, an early treatment is necessary to disfavor its progression. The aim of the present narrative review is to evaluate the different therapeutic approaches to MAFLD. The most important treatment for MAFLD is lifestyle changes. In this regard, the Mediterranean diet could be considered the gold standard in the prevention and treatment of MAFLD. In contrast, a Western diet should be discouraged. Probiotics and fecal microbiota transplantation seem to be valid, safe, and effective alternatives for MAFLD treatment. However, more studies with a longer follow up and with a larger cohort of patients are needed to underline the more effective ap-proaches to contrasting MAFLD.

The structural, elastic, and electronic properties of orthorhombic Cd2SiO4 and Hg2GeO4 were examined under varying pressure conditions using first-principles calculations based on densi-ty-functional theory employing the projector augmented wave method. The obtained cell pa-rameters at 0 GPa were found to align well with existing experimental data. We delved into the pressure-dependence of normalized lattice parameters and elastic constants. In Cd2SiO4, all lat-tice constants decreased as pressure increased, whereas in Hg2GeO4, parameters a and b de-creased while parameter c increased under pressure. Employing the Hill average method, we calculated the elastic moduli and Poisson’s ratio up to 10 GPa, noting an increase with pressure. Evaluation of ductility/brittleness under pressure indicated both compounds remained ductile throughout. We also estimated elastic anisotropy and Debye temperature under varying pres-sures. Cd2SiO4 and Hg2GeO4 were identified as indirect band gap insulators, with estimated band gaps of 3.34 eV and 2.09 eV, respectively. Interestingly, Cd2SiO4 exhibited a significant increase in band gap with increasing pressure, whereas the band gap of Hg2GeO4 decreased under pres-sure, revealing distinct structural and electronic responses despite their similar structures.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

The three-pronged sliding universal coupling is a new kind of three-pronged coupling. To study its kinematic and dynamic characteristics, directional cosine matrices are utilized as tools to analyze the coordinate systems by establishing simplified geometric models and corresponding motions. Through the analysis of the motions of the input and output shafts and employing the method of single-force element, a set of equilibrium equations for the forces acting on the output shaft and the input shaft are formulated for solution analysis. The research indicates that during the rotation process, there exists a small angular difference between the input shaft and the intermediate shaft, demonstrating the quasi-constant angular velocity characteristics of the new tripod sliding universal coupling. The curves of the forces and torques acting on each component of the coupling approximate sinusoidal curves. The optimal operating angle range for the new tripod universal coupling is at angle , during which the system exhibits good transmission and mechanical performance.

Among the many Lysosomal Storage Disorders (LSDs) that would benefit from the establish-ment of novel cell models, either patient-derived or genetically engineered, is Mucopolysaccha-ridosis type II (MPS II). In fact, even though a specific therapeutic approach does exist for this disorder (Enzyme Replacement Therapy, ERT, with recombinant human IDS) and haematopoiet-ic stem cell transplantation (HSCT) may also hold promise whenever the disorder is diagnosed soon enough, both approaches have their own drawbacks. Here we present our results on the establishment and characterization of two MPS II pa-tient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population is isolated from LSD patient samples obtained from the oral cavity. Taking into account our results on the molecular and biochemical characterization of those cells and our first insights on their subcellular MPS phenotype, we consider these cells will be a valuable tool for both pathophysiological assessments and drugs screenings. Ultimately, we believe patient-derived dental pulp stem cells (DPSC) may represent a feasible alternative to induced pluripotent stem cells (iPSC) in many labs with standard cell culture con-ditions and limited (human and economic) resources.

A sedentary lifestyle associated with unregulated diets rich in high-calorie foods have contributed to the great prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) latterly, with up to 60% in high-risk population and 25% in the general population. The absence of specific pharmacological strategies for this syndrome represents one of the major problems in the management of MASLD patients. Lifestyle interventions and adherence to a healthy diet are the main cornerstones of current therapies. The identification of nutraceuticals useful in the treatment of MASLD appears to be one of the most promising strategies for the development of new effective and safe treatments for this disease. The onion, one of the most widely studied foods in the field of nutraceuticals, serves as an inexhaustible reservoir of potent compounds with various beneficial effects. The following preliminary study analyses, mediating in silico studies, the iteration of a library of typical onion compounds with 3-hydroxy-3-methylglutaryl-coenzyme A reductase, Liver receptors X α and β as well as Peroxisome proliferator-activated receptors α and γ. In this study fort the first time promising smart molecules from the onion that could have a beneficial action in MASLD patients were identified.

Systemic lupus erythematosus (SLE) is a prevalent autoimmune condition, yet its alignment with a specific host immunological pathway remains unclear. The THαβ host immunological pathway, recognized for its defense against viruses and prions, has recently emerged as a response to DNA, RNA, and protein pathogens. SLE patients often produce anti-double strand DNA antibodies and anti-nuclear antibodies, suggesting a potential association with the THαβ host immune reaction. Throughout the course of SLE, elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 are commonly observed. These cytokines and antibody isotypes are indicative of the THαβ host immunological pathway. Similarly, Myasthenia gravis, Grave’s disease, Graft versus host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjogren’s syndrome are also linked to THαβ-related type 2 hypersensitivities. Considering the potential association of these diseases with dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferons α/β could be explored to manage these disorders effectively.

Chronic diseases, such as type 2 diabetes (T2D), are difficult to manage because they demand continuous therapeutic review and monitoring. Beyond achieving the target HbA1c, new guidelines for the therapy of T2D have been introduced with the new groups of antidiabetics (GLP-1ra and SGLT2-in). Despite new guidelines, clinical inertia, that can be caused by physicians, patients or healthcare system, results in T2D not being effectively managed. This opinion paper explores the shift in T2D treatment, challenging assumptions and evidence-based recommendations, particularly for family physicians, considering the patient's overall situation in decision-making. We looked for the possible reasons of clinical inertia and poor application of guidelines in the management of T2D. Guidelines for antidiabetic drugs should be more precise, providing case studies and clinical examples to define clinical contexts and contraindications. Knowledge communication can improve confidence and should include clear statements on areas of decision-making not supported by evidence. Precision medicine initiative in diabetes aims to identify subcategories of T2D patients (including frail patients) using clustering techniques from data science applications, focusing on CV and poor treatment outcomes. Clear, unconditional recommendations for personalized T2D management may encourage drug prescription, especially for family physicians dealing with diverse patient contexts and clinical settings.

The process of sexual reproduction in eukaryotes starts when gametes from two different sexes encounter each other. Paramecium, a unicellular eukaryote, undergoes conjugation and uses a gametic nucleus to enter the sexual reproductive process. The molecules responsible for recognizing mating partners, hypothetically called mating-type substances, are still unclear. We have identified an O3-type mating substance polypeptide and its gene sequence using protein chemistry, molecular genetics, immunofluorescence, RNA inter-ference, and microinjection. The O3-type substance is a polypeptide found in the ciliary membranes, located from the head to the ventral side of cells. The O3-type substance has a kinase-like domain in its N-terminal part located outside the cell and four EF-hand motifs that bind calcium ions in its C-terminal part located inside the cell. RNA interference and immunofluorescence revealed that this polypeptide positively correlated with the expression of mating reactivity. Microinjection of an expression vector incorporating the O3Pc-MSP gene induced additional O3 mating type in the recipient clones of different mating types or syngen. Phylogenetic analysis indicates this gene is widely present in eukaryotes and exhibits high homology among closely related species. The O3Pc-MSP gene had nine silent mutations compared to the complementary mating type of the E3 homologue gene.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent world-wide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBP) is a family of secreted proteins involved in senescence and scarring mainly synthetized in the liver. Here we aimed to study the association of IGFBP and its induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: 16 weeks old male C57BL/6 mice weighing 23 ± 3 g were fed either Methionine-Choline Deficient or control diet for 2, 8 or 12 weeks. Blood and liver samples were collected; histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in liver and serum. Data was expressed as Mean ± SD and analyzed by one-way ANOVA followed Tukey’s test. Lineal regression models were applied for NAFLD and fibrosis progression. p

Photovoltaic materials convert light into electrical voltages. So far, most research in the field are focused on how to refine/improve the existing or standard photovoltaic cells to yield more efficient electricity, to reduce weight, to make more flexible shape, or to minimize costs under standard and uniform sunlight illuminations. In this project, we explore and demonstrate a hypothesis that non-uniform light illumination photovoltages can also be generated due to photo doping induced mobile charge carrier density gradient between light and dark areas in either p-type or n-type photo doping semiconductors. The term non-uniform light illumination was coined to refer to subjecting our photo sensing thin film devices to areas of high and low intensities of light illumination simultaneously, with an intention of creating a charge density gradient and therefore a voltage. Specifically, a polymeric composite thin film composed of P3HT (p-type photo doping semiconductor) and PCBM (photo doping electron acceptor and trap) at varying p-doping levels were studied. We observed that the fabricated photovoltaic cells with about 80% PCBM doped P3HT thin film devices exhibited 0.5-1.2 volts photovoltages under non-uniform light illuminations.

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3-D structure which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC, about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK’s clinical performance was also studied in HCC patients with viral and non-viral cirrhosis including cirrhosis caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84 while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK has significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71%-91% of HCC patients with false-negative AFP test results in viral associated HCC and non-viral associated HCC.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-i in T1D HF management, alongside the emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk, through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests SGLT2-i significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-i into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-i and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim at clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.

The Standard Model is not a complete description of reality; it omits the existence of dark matter, dark energy, and an explanation as to why no CP violation has been observed. However, some of these phenomena could be explained through a new force mediated by a new boson. If such a boson were massless it would result in a power law potential and if massive the interaction would be Yukawa-like. A previous experiment employing a micro-mechanical oscillator and a spherical test mass interactions was successful in placing the best limits on a mass-mass Yukawa-like interaction, but the data was never analyzed in the context of a power law. Here that data is analyzed considering a power law for powers n = 1-5 where n is the number of boson exchanges. The results show that the limits obtained through power law analysis of this data are not better than the currently accepted limits. A discussion of an experiment design capable of producing better limits on power law extensions to the Standard Model is presented, and suggests micro mechanical oscillators based experiment remains capable of improving the limits by at least one order of magnitude.

Background: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well-documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia. Methods: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates diagnosed at Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia, between October 5, 2020, and November 5, 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. Results: The total sample size was 181. The average age of patients was 34 years (SD=6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25-1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38-2.19), LBW (aOR = 1.32, 95% CI: 1.06-1.66), and RDS (aOR = 1.57, 95% CI: 1.28-1.93) were significantly higher among neonates born to mothers with MDM. Types of DM were statistically significant with some neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). Conclusion: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. Early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population.

In vitro glucose uptake in yeast cell facilitated by Abelmoschus esculentus L. (okra seed) for management of type 2 diabetes was studied. Plant material was collected, identified, processed, and stored for further use. 80% methanol was employed for extraction and sonicated to release antidiabetic-bioactive component in solution and was filtered, concentrated, freeze-dried, and fractionated using standard techniques. Glucose uptake at an initial concentration of 5mM/L and 10mM/L by the crude extract was consistent to that of the known standard drug while at 25mM/L glucose concentration was equivalent with the crude extract. Also, at 0.625 mg/mL the linear equations, and R2 demonstrations that the crude extract was higher in dose predictability than the standard drug as presented by the equation; y = 35.754x - 57.822, and R² = 0.9502 (95%). The extract-fractions were employed to evaluate the ability of yeast cell line culture to take up glucose from the system through DPPH, FRAP, lipid peroxidation and anti-diabetes effect of extract-fraction assays. Extract-fractions were found to poses antioxidant activity high enough to inhibit stress-related diseases. The extract fractions were active as drug candidates both at low and high concentrations and were better compared with the standard drug and standard antioxidant was comparable. The high bioactive extract fractions require encapsulation with a nanoparticle as a drug candidate for type 2 diabetes patients. And an animal trial of the drug candidate may be necessary to monitor the in vivo performances of the extract fractions and subsequent human volunteered trial.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent data highlight similarities between neurodegenerative diseases including PD and type 2 diabetes mellitus (T2DM) suggesting a crucial interplay between the gut–brain axis. GLP-1R agonists, known for their use in T2DM treatment, are currently extensively studied as novel PD modifying agents. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles and clinical trials regarding GLP-1R agonists and PD, published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Our research was conducted between February 2023 and February 2024. We used the terms “GLP-1”, “GLP-1 receptor”, “GLP-1R agonists”, “PD”, “T2DM”, “insulin”, “neurodegenerative disease”, “glucose”, “animal models”, “clinical trials” in different combinations. Many data on animal models and preclinical studies show that GLP1-R agonists can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration and alleviate motor and non-motor features of PD. Evidence from clinical studies are also very promising enhancing the possibility of adding GLP1-R agonists in the current armamentarium of drugs available for PD treatment.

We explore the relationship between the exact renormalization group (RG) equation and quantum mechanics. The central idea is to rewrite the exact Wilsonian RG equation as a Schrödinger-type equation, opening avenues for analysis. By introducing a functional transformation, the RG equation takes on a form analogous to a quantum mechanical Schrödinger equation. The study investigates solutions to this equation and draws parallels with quantum mechanics, paving the way for understanding the infrared behavior of quantum field theories. Furthermore, we extends its insights to a one-dimensional toy model, providing illustrative examples. The discussion encompasses the implications of these findings in multiple dimensions and quantum field theory, with a brief exploration of their relevance in the context of inflationary cosmology.

Deep learning (DL) algorithms used for DOTATATE PET lesion detection typically require large, well-annotated training datasets. These are difficult to obtain due to low incidence of gastroenteopancreatic neuroendocrine tumors (GEP-NETs), and the high cost of manual annotation. Furthermore, networks trained and tested with data acquired from site specific PET/CT instrumentation, acquisition and processing protocols have reduced performance when tested with offsite data. This lack of generalizability requires even larger, more diverse training datasets. The objective of this study is to investigate the feasibility of improving DL algorithm performance by better matching the background noise in training datasets to higher noise, out-of-domain testing datasets. 68Ga-DOTATATE PET/CT datasets were obtained from two scanners: Scanner1, a state-of-the-art digital PET/CT (GE DMI PET/CT; n=83 subjects), and Scanner2, an older-generation analog PET/CT (GE STE; n=123 subjects). Set1, the data set from Scanner1 was reconstructed with standard clinical parameters (5 minutes; Q.Clear) and list-mode reconstructions (VPFXS 2, 3, 4, and 5-minutes). Set2, data from Scanner2, representing out-of-domain clinical scans, used standard iterative reconstruction (5 minutes; OSEM). Reconstructed datasets were divided into training, validation, and testing datasets in a 60%, 20%, 20% proportion, and a deep neural network was trained with each: Network1 for Scanner1 and Network2 for Scanner2. DL performance (Network1) was tested with out-of-domain test data (Set2). To evaluate the effect of training sample size, we tested DL model performance using a fraction (25%, 50%, and 75%) of Set1 for training. Scanner1, list-mode 2-minute reconstructed data demonstrated the most similar noise level compared that of Set2, resulting in the best performance (F1=0.713). This was not significantly different compared to the highest performance, upper-bound limit using in-domain training for Network2 (F1=0.755; p-value=0.103). Regarding sample size, the F1 score significantly increased from 25% training data (F1=0.478) to 100% training data (F1=0.713; p&lt;0.001). List-mode data from modern PET scanners can be reconstructed to better match the noise properties of older scanners. Using existing data and their associated annotations dramatically reduces the cost and effort in generating these datasets, and significantly improves the performance of existing DL algorithms. List-mode reconstructions can provide an efficient, low-cost method to improve DL algorithm generalizability.

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer became the leading cause of death in several countries. Our objective was the determination of whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study is a nationwide analysis performed in Hungary. Study population was divided into a group with type 2 diabetes mellitus and into a non-diabetic group. The primary outcome was the risk related to overall cancer incidence. A key secondary outcome was the overall incidence of cancer in distinct study years. Further outcomes were the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, P&lt;0.0001) in patients with diabetes as related to controls. The odds ratio was higher in males than in females. The highest risk was found in the 18-39-year-old subgroup. The annual cancer incidence rate declined in controls, but not in patients with diabetes. Several types of cancer showed a decreasing tendency in non-diabetic controls.; (4) Conclusions: type 2 diabetes is associated with a higher risk of cancer. High risk in young patients with type 2 diabetes suggests that these young individuals should be considered as a risk group.

Nanocrystalline silicon oxide (nc-SiOx:H) is a multipurpose material with its varied application in solar cells as a transparent front contact, intermediate reflector, back reflector layer and even tunnel layer for passivating contacts, owing to easy tailoring of its optical properties. In this work, we systematically investigate the influence of gas mixture (SiH4, CO2, PH3 and H2), RF power and process pressure on the optical, structural and passivation properties of thin n-type nc-SiOx:H films prepared in an industrial, high throughput, plasma-enhanced chemical vapor deposition (PECVD) reactor. We provide a detailed description of the n-type nc-SiOx:H material develop-ment using various characterization techniques (SEM, EDX, Raman spectroscopy, and spectro-scopic ellipsometry) with a focus on the relationship between the material properties and the pas-sivation they provide to n-type c-Si wafers characterized by their effective carrier lifetime (τeff). Further, we also outline the parameters to be kept in mind while developing different n-type nc-SiOx:H layers for different solar cell applications. We report a tunable optical gap (1.8 – 2.3 eV) for our n-type nc-SiOx:H films as well as excellent passivation properties with τeff up to 3.5 ms (iVoc ~ 715 mV) before annealing. Oxygen content plays an important role in determining the crystallinity and hence passivation quality of the deposited nanocrystalline silicon oxide films.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. Summarizing, incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. The incident T2DM and diabetes free Hungarian population were included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p&lt;0.0001. The risk of having cancer was age-dependent, having the highest odd in the age group 18-39. The incidence of cancer was declining in the non-diabetic but was unchanged in T2DM population. The average lag time of diagnosing a cancer after the detection of T2DM was 3.86 months.; (4) Conclusions: Iincident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Commuting is a vital travel channel for college students throughout their higher education career; nevertheless, excessive commute time negatively impacts students’ school satisfaction, academic achievement, health, and quality of life. Meanwhile, few studies have explored students’ commute time, covering a large population and scope. Therefore, this study analyzes the dwelling type that influences college and graduate students’ school commute times in the Seoul Metropolitan Area, using data from the 2016 Household Travel Diary Survey. This study uses spatial data on housing development to classify five dwelling types (i.e., new town, housing site development, Seoul, Incheon, and Gyeonggi-do). A multiple linear regression model empirically analyses students’ household and personal characteristics. The results reveal that dwelling type significantly affects students’ commute time. Specifically, Students living in Seoul have a shorter commute to school than those living in new towns. Socioeconomic characteristics have less effect on college and graduate students' school commute time. This study discusses the problem of excessive commuting of college and graduate students in new towns.

Many metabolic processes at the molecular level support both viral attack strategies and human defenses during Covid-19. This knowledge is of vital importance in the design of antiviral drugs. In this study, we extracted 18 articles (2021-2023) from PubMed reporting the discovery of hub-nodes specific for the liver during covid-19, identifying 142 hub-nodes. They are highly connected proteins from which to get deep functional information on viral strategies when used as functional seeds. Therefore, we evaluated the functional and structural significance of each of them to endorse their reliable use as seeds. After filtering, the remaining 111 hubs were used to get by STRING an enriched interactome of 1111 nodes (13,494 interactions). It shows the viral strategy in the liver is to attack the entire cytoplasmic translational system, including ribosomes, to take control of protein bio-synthesis. We used the SARS2-Human-Proteome Interaction Database (33,791 interactions), de-signed by us with BioGRID data to implement a reverse-engineering process that identified human proteins actively interacting with viral proteins. The results show 57% of human liver proteins di-rectly involved in Covid, a strong impairment of the ribosome and spliceosome, an antiviral defense mechanism against cellular stress of the p53 system, and, surprisingly, a viral capacity for multiple protein attacks against single human proteins that reveal underlying evolutionary-topological molecular mechanisms. Viral behavior over time suggests different molecular strategies for different organs.

Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive. In this study, hindlimb postural asymmetry (HL-PA) development in rats subjected to focal TBI was investigated to explore the potential roles of laminin and collagen IV within the ECM of selected hindlimb muscles in the emergence of motor deficits following TBI. A focal TBI was induced by ablating the left sensorimotor cortex in rats and motor deficits were assessed by measuring HL-PA. The expression of laminin and collagen IV in eight selected muscles on each side of the hindlimbs from both TBI and sham-operated rats were studied using immunohistochemistry and semi-quantitatively analyzed. Results indicated that the TBI rats exhibited HL-PA, characterized by flexion of the contralateral (right) hindlimb. In the sham-operated rats the immunoreactive components of laminin and collagen IV were evenly and smoothly distributed along the border of the muscle fibers in all the investigated muscles. In contrast, in the TBI rats the pattern was broken into aggregated granule-like immunoreactive components. Such a labeling pattern was detected in all the investigated muscles both from the contra-and ipsilateral side of the TBI rats. However, in TBI rats most of the muscles from the contralateral hindlimb showed a significant increased expression of these two proteins in comparison with those from the ipsilateral hindlimb. In comparison to sham-operated rats, there was a significant increase in laminin and collagen IV expression in various contralateral hindlimb muscles in the TBI rats. These findings suggest potential implications of laminin and collagen IV in the development of motor deficits following a focal TBI.

In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.

The detection of Fasciola eggs in ruminant fecal samples typically occurs around 15 weeks post-infection during patent infections. The recent introduction of coproantigen ELISA (cELISA) diagnostics, which capture antigenic enzymes in fecal material, holds promise for monitoring Fasciola fecal egg count (FFEC) to implement control programs, particularly targeted treatments. This study compared two study groups, those with positive FFEC (FFEC+ve) and negative FFEC (FFEC-ve), to assess the sensitivity of Flukefinder sedimentation and a cELISA kit. This study reports that the coproantigen ELISA detection limit was 4.5 eggs per gram (epg) for a 100% positivity rate. Additionally, a moderate, statistically significant positive correlation (r²=0.716, p-value < 0.01) and an odds ratio of 1.96 (p-value < 0.01) were observed between FFEC and Fasciola coproantigen from cELISA. This implies that for every single unit increase in FFEC, there is a 96% likelihood of obtaining a higher optical density (OD) reading from the cELISA test. The results suggest that cELISA can complement fecal sedimentation tests, serving as a valuable tool for detecting cattle with high FFEC. This capability facilitates targeted treatment strategies, thereby aiding in the control and prevention of the spread of fasciolosis within the studied area.

Liver is structurally organized into zonation where LSECs endothelial cells play a crucial role during chronic liver injury and early stages of fibrosis. Fibrosis can be reversed if diagnosed early at molecular level in zonation before progressing to advanced stages like bridging fibrosis. This study identified zonation marker genes using scRNA-seq and spatial transcriptomics molecular profiling technologies in normal and diseased fibrotic human liver. DGE analysis is performed over LSECs and identified the top 20 expressed genes in periportal, perivenous, and intermediate acinar zones. Multi-omics and scRNA-seq analysis over Visium images and ECs liver cells figured out OIT3, DNASE1L3, CLEC4G, LYVE1, FCN2, CRHBP as commonly expressed mid-lobular zonation-specific genes. Also, this study detected STAB2, F8, AQP1, TEK, TIMP3, TIE1, CTSL genes as expressed in DILI and NASH ECs populations. The connection between LSECs marker genes in zone 2 and liver fibrosis holds significant promise for advancing our understanding in developing new therapeutic strategies for fibrosis reversal and designing computational molecular biomarkers in NASH and DILI fibrotic liver diseases.