This study investigates the molecular responses to heatstroke in young and old patients by comparing whole-genome transcriptomes between age groups. We analyzed transcriptomic profiles from patients categorized into two age-defined cohorts: young (mean age = 44.9 ± 6 yr) and old (mean age = 66.1 ± 4 yr). Control subjects, exposed to similar environmental heat conditions but without developing heatstroke, were also included in the analysis to provide a baseline for comparison. Despite uniform heatstroke severity at admission, as indicated by core body temperature, consciousness level, and organ damage markers, notable gene expression differences emerged. Old patients showed 37% fewer differentially expressed genes compared with young patients at admission, with a shift toward gene upregulation, deviating from the usual downregulation seen in heat stress responses. Both age groups exhibited increased heat shock protein gene expression, activated the heat stress, and unfolded protein responses indicating comparable proteotoxic stress. Nonetheless, age-specific differences were evident in critical regulatory pathways like Sirtuin, mTOR, and p53 signaling, along with key pathways related to proteostasis, energy metabolism, oxidative stress, and immune responses. Following cooling, older adults exhibited a decline in the heat stress response and a cessation of the unfolded protein response, in contrast to the sustained responses seen in younger individuals. This pattern suggests an age-related adaptability or a diminished protective response capacity with aging. These findings provide insights into the biological mechanisms that may contribute to age-specific vulnerabilities to heat. Our study reveals distinct molecular responses to heatstroke across age groups, with older adults showing fewer differentially expressed genes and an atypical pattern of gene upregulation, contrasting with the downregulation in usual heat stress responses. It also uncovers a reduced heat stress response and an abbreviated unfolded protein response in older adults, likely impairing their cellular repair mechanisms. This contributes to increased vulnerability during severe heat waves, underscoring the urgent need for age-specific interventions.

We examined the effects of a 20-wk exercise intervention on whole blood genome-wide DNA methylation signature and its association with the exercise-induced changes in gene expression profiles in boys and girls with overweight/obesity (OW/OB). Twenty-three children (10.05 ± 1.39 yr, 56% girls) with OW/OB were randomized to either a 20-wk exercise intervention [exercise group (EG); = 10; 4 boys/6 girls] or to usual lifestyle [control group (CG); = 13; 6 boys/7 girls]. Whole blood genome-wide methylome (CpG sites) analysis using Infinium Methylation EPIC array and transcriptome analysis using RNA-seq (STRT2 protocol) were performed. Exercise-induced modifications in DNA methylation at 485 and 386 CpGs sites in boys and girls, respectively. These CpG sites are mapped to loci enriched in distinct gene pathways related to metabolic diseases, fatty acid metabolism, and immune function. In boys, changes in the DNA methylation of 87 CpG sites (18% of the 485 CpGs sites altered by exercise) were associated with changes in the gene expression levels of 51 genes also regulated by exercise. Among girls, changes in DNA methylation at 46 CpG sites (12% of the initial 386 significant CpGs) were associated with changes in the expression levels of 30 exercise-affected genes. Genes affected by exercise that were associated with DNA methylation are related to obesity, metabolic syndrome, and inflammation. Multiomics analysis of whole blood samples from children with OW/OB suggests that gene expression response to exercise may be modulated by DNA methylation and involve gene pathways related to metabolism and immune functions. This study pioneers the exploration into the effects of exercise on whole blood genome-wide DNA methylation patterns and its association with changes in transcriptome profiles in children with overweight/obesity. Exercise potentially impacts molecular pathways involved in metabolism and immune functions in children with overweight/obesity (sex-specific responses) through the modification of epigenetic and transcriptomic profiles. Our preliminary results provide initial steps to understand better the molecular mechanisms underlying cardiometabolic benefits of exercise in children with overweight/obesity.

The regulation of oxygen homeostasis is critical in physiology and disease pathogenesis. High-altitude environment or hypoxia (lack of oxygen) can lead to adverse health conditions such as high-altitude pulmonary edema (HAPE) despite initial adaptive physiological responses. Studying genetic, hematological and biochemical, and the physiological outcomes of hypoxia together could yield a comprehensive understanding and potentially uncover valuable biomarkers for predicting responses. To this end, healthy individuals ( = 51) were recruited and exposed to graded normobaric hypoxia. Physiological parameters such as heart rate (HR), heart rate variability (HRV), oxygen saturation (Spo), and blood pressure (BP) were constantly monitored, and a blood sample was collected before and after the hypoxia exposure for the hematological and gene-expression profiles. HR was elevated, and Spo and HRV were significantly reduced in a fraction of inspired oxygen ([Formula: see text])-dependent manner. After exposure to hypoxia, there was a minimal decrease in HCT, red blood cell distribution width (RDW)-coefficient of variation (CV), mean platelet volume (MPV), platelet distribution width, plateletcrit, eosinophils, lymphocytes, and HDL cholesterol. Additionally, there was a marginal increase observed in neutrophils. The effect of hypoxia was further assessed at the genome-wide expression level in a subset of individuals. Eighty-two genes significantly differed after hypoxia exposure, with 46 upregulated genes and 36 downregulated genes ( ≤ 0.05 and log-fold change greater than ±0.5). We also conducted an integrative analysis of global gene expression profiles linked with physiological parameters, and we uncovered numerous reliable gene signatures associated with BP, Spo, HR, and HRV in response to graded normobaric hypoxia. Our study delves into the multifaceted response to hypoxia, integrating gene expression and hematological, biochemical, and physiological assessments. Hypoxia, crucial in both physiology and pathology, prompts varied responses, necessitating a thorough systemic understanding. Examining healthy subjects exposed to graded normobaric hypoxia, we observed significant shifts in heart rate, oxygen saturation, and heart rate variability. Moreover, genomic analysis unveiled distinct gene signatures associated with physiological parameters, offering insights into molecular perturbations and adaptations to oxygen deprivation.

Guillain-Barré syndrome (GBS) and cardiovascular diseases (CVDs) have been observed to have a potential association, with GBS potentially leading to cardiovascular complications. However, these observational studies may be influenced by confounding factors. This study aimed to assess the causal relationship between GBS and CVDs, including heart failure (HF), atrial fibrillation (AF), and coronary artery disease (CAD), using a two-sample bidirectional Mendelian randomization (MR) analysis. We analyzed four datasets from the UK Biobank, selecting only datasets of European origin according to predetermined criteria to avoid population stratification bias. Datasets for GBS and CVDs were retrieved from the UK Biobank and analyzed using selected instrumental variables (IVs) related to genetic variations. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the reliability of the selected IVs. The analysis results were then visualized to illustrate the causal relationships. The study identified genetic variants as IVs for both GBS and CVDs. MR analysis revealed a significant causal effect of GBS on the increased risk of HF [inverse-variance weighted (IVW), < 0.05], but no significant causal relationship was found between GBS and AF or CAD. Similarly, no causal effect of CVDs on the occurrence of GBS was observed. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy, supporting the robustness of the results. These findings underscore the importance of considering cardiovascular complications, particularly HF, in the clinical management of patients with GBS in European populations. This study utilizes bidirectional Mendelian randomization to analyze the causal relationships between Guillain-Barré syndrome (GBS) and cardiovascular diseases (CVDs). It uniquely demonstrates a significant causal link from GBS to an increased risk of heart failure (HF), without similar effects on atrial fibrillation (AF) or coronary artery disease (CAD). No reverse causality from CVDs to GBS was found, highlighting the need for targeted cardiovascular management in patients with GBS.

The purpose of this study was to elucidate the skeletal muscle transcriptomic response unique to rest duration during high-intensity interval exercise. Thoroughbred horses performed three 1-min bouts of exercise at their maximal oxygen uptake (10.7-12.5 m/s), separated by 15 min (long) or 2 min (short) walking at 1.7 m/s. Gluteus medius muscle was collected before and at 4 h after the exercise and used for RNA sequencing. We identified 1,756 and 1,421 differentially expressed genes in response to the long and short protocols, respectively, using DEseq2 analysis [false discovery rate (FDR) cutoff = 0.05, minimal fold change = 1.5]. The overall transcriptional response was partially aligned, with 43% ( = 949) of genes altered in both protocols, whereas no discordant directional changes were observed. K-means clustering and gene set enrichment analyses based on Gene Ontology biological process terms showed that genes associated with muscle adaptation and development were upregulated regardless of exercise conditions; genes related to immune and cytokine responses were more upregulated following the long protocol, and protein folding and temperature response were highly expressed after the short protocol. We found that 11 genes were upregulated to a greater extent by the short protocol and one was by the long protocol, with , , , and identified as potential candidates for skeletal muscle remodeling. Our results suggest that altered metabolic fluctuations dependent on the intermittent pattern of interval exercise modulate skeletal muscle gene expression, and therefore, rest interval length could be an important consideration in optimizing skeletal muscle adaptation. This is the first study to address the comparison of transcriptional responses to high-intensity interval exercise with two different rest periods in skeletal muscle. The expression of genes related to metabolic adaptations altered in both conditions, while genes associated with immune and cytokine responses and protein folding and temperature response were varied with the length of the rest period. These results provide evidence for rest duration-specific transcriptional response to high-intensity interval training.

"Jiedutongluo Tiaoying Formula" (JDTLTYF) TCM prescriptions can effectively treat hyperthyroidism and effectively improve the condition of patients. The main active ingredients of JDTLTYF were collected from the TCMSP database and the target was predicted. Genes related to hyperthyroidism were identified using DisGeNET, GeneCards and OMIM databases. Protein-protein interaction (PPI) network and interaction network of "formula-herb-active ingredient-target genes" was constructed. Mass spectrometry was used to identify the components. The binding of key components to the target was verified by molecular docking and molecular dynamics (MD) simulations. A hyperthyroidism mouse model was established using levothyroxine sodium tablets, and the hormone and expression levels of inflammatory factorswere examined by ELISA and western blot. The key genes of JDTLTYF in the treatment of hyperthyroidism were TNF and AKT1. The results of mass spectrometry also showed that quercetin was one of the main components. The results of molecular docking and MD simulation showed that the binding free energy between AKT1 and quercetin was the lowest and the binding was stable. experimental results showed that gastric lavage with JDTLTYF could target AKT1 and TNF-α, effectively alleviate the pathological features of hyperthyroidism in mice and reduce inflammation response. This study elucidated the key small molecule compounds and their action targets of JDTLTYF in the treatment of hyperthyroidism. It provides a direction for the development of new drugs for clinical hyperthyroidism.

Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy with an incidence rate of up to 8% worldwide. However, the complete pathogenesis is still unknown. Obesity increases the risk of developing PE three-fold. To better understand the relationship of maternal risk factors, the BPH/5 mouse was described as a model of superimposed PE. Previous research demonstrated that adult BPH/5 female mice have an adverse cardiometabolic phenotype characterized by hypertension, obesity with increased white adipose tissue and dyslipidemia, exaggerated by pregnancy. We hypothesize that BPH/5 mice have gut dysbiosis characterized by changes in alpha and beta diversity of bacterial community structure as well as perturbed short chain fatty acids (SCFA) compared to controls in pregnancy. Fecal samples were used for Illumina sequencing of 16S v4 rRNA amplicons. Microbial community composition of the pregnant BPH/5 compared to C57 controls was different using PERMANOVA with Bray-Curtis dissimilarity. Alpha diversity was increased in pregnant BPH/5 dams compared to controls. and were increased while , and were decreased compared to controls. Fecal SCFAs were not different between groups, but BPH/5 serum acetic and butyric acid were decreased while isobutyric and isovaleric acid were increased specifically in pregnancy. BPH/5 pregnant colons had decreased expression of free fatty acid receptor, . In conclusion, the BPH/5 maternal fecal microbiome demonstrates microbial dysbiosis characterized by community structure and diversity changes before and after the onset of pregnancy. Gut dysbiosis may be a key mechanism linking SCFA signaling and obesity to the BPH/5 PE-like phenotype.

Aspirin (ASA) is a proven chemoprotective agent for colorectal cancer (CRC), though inter-individual responses and cellular mechanisms are not well characterized. Human organoids are ideal to study treatment responses across individuals. Here, colonic organoids from African-Americans (AA) and European-Americans (EA)were used to profile genomic and cellular ASA responses. Colonic organoids from 67 participants, 33 AA and 34 EA, were treated with 3mM ASA or vehicle control for 24h. Gene expression was assessed by RNA-seq, and differentially responsive genes analyzed by condition, population and for gene set enrichment. Top differentially responsive genes were assessed by time and ASA doses in independent organoids. Expression quantitative trait loci (eQTL) mapping was performed to identify variants associated with condition-specific responses. Proliferation, apoptosis and necrosis assays were performed, and apoptosis gene expression measured in organoids. Overall, 8343 genes were differentially responsive to ASA with differences between AA and EA. Significant enrichment for fatty acid oxidation (FAO) and PPAR signaling was found. Significant treatment eQTLs were identified for relevant genes involved in FAO, apoptosis and prostaglandin metabolism. ASA-induced apoptosis and secondary necrosis were confirmed with identification of significant differential responses of apoptotic genes to ASA. Results demonstrate large transcriptional responses to ASA treatment with differences in responses between individuals. Genomic and cellular results suggest that ASA effects on the mitochondria are key mechanisms of action that could underlie clinical effects. These results could be used to assess clinical treatment responses for chemoprevention in the future.

The study aimed to verify the physiological and metabolic parameters associated with the time to task failure (TTF) during cycling exercise performed within the severe-intensity domain. Forty-five healthy and physically active males participated in two independent experiments. In experiment 1, after a graded exercise test, participants underwent constant work rate cycling efforts (CWR) at 115% of peak power output to assess neuromuscular function (Potentiated twitch) pre- and post-exercise. Experiment 2 was similarl to experiment 1, but with physiological (respiratory parameters, energetic pathway contribution) and metabolic parameters in the blood (gasometry and blood lactate responses) and vastus lateralis muscle tissue (target metabolomic analysis, glycogen content, muscle pH and buffering capacity in vitro) measured instead of neuromuscular function. Experiment 1 evidenced a significant decrease in muscle force with instauration of peripheral fatigability indices and no change in central fatigue indices. Severe-intensity domain exercise in Experiment 2 was accompanied by changes in physiological and metabolic parameters and in blood and muscle parameters. However, the TTF was associated with oxidative contribution (r=0.811, p<0.001), as well as anaerobic capacity (r=0.554, p=0.027), muscle buffering capacity (r=0.792, p=0.035), phosphagen energy contribution (r=0.583, p=0.017), and carnitine changes (r=0.855, p=0.016), but no correlated with electromyographic response, blood acid-base balance, and muscular glycogen content and pH. TTF during CWR exercise within the severe-intensity domain is likely explained by a combination of interacting mechanisms, with oxidative and phosphagen contributions, and muscle buffering capacity suggested as the main peripherals limiting factors to exercise within this exercise intensity domain.

This research explored the effect of high-fiber diet based on gut microbiota on chronic heart failure (HF) patients. Chronic HF patients, who had undergone a dietary survey indicating a daily dietary fiber intake of less than 15g/d were divided into the control and study groups (n = 50). In addition to conventional heart failure treatment, the study group received dietary guidance, while the control group did not receive any dietary guidance and maintained their usual low-fiber dietary habits. After one year intervention, the daily dietary fiber intake, abundance of gut microbiota, plasma trimethylamine N-oxide (TMAO), albumin (ALB), prealbumin (PA), transferrin (TF), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), left ventricular ejection fraction (LVEF), left ventricular end-diastolic index (LVEDVI), and left ventricular end-systolic volume index (LVESVI), Barthel index (BI), and 6 min walking distance (6 MWD) were compared. After intervention, in both groups, the daily dietary fiber intake increased, abundance of decreased and that of increased; the plasma TMAO decreased; serum ALB, PA, and TF levels increased; serum CRP, TNF-α, IL-6, and IL-8 levels decreased, and the change was greater in the study group; LVEF elevated, LVEDVI and LVESVI reduced, and the differences between both groups were not significant; BI and 6 MWD elevated, and the study group was higher than the control group. High-fiber diet positively regulates the composition of gut microbiota, nutritional status and microinflammatory level in chronic HF patients, thereby improving patients' quality of life.

The etiology of fetal growth restriction (FGR) is multifactorial, although many cases often involve placental insufficiency. Placental insufficiency is associated with inadequate trophoblast invasion, resulting in high resistance to blood flow, decreased availability of nutrients, and increased hypoxia. We have developed a nonviral, polymer-based nanoparticle that facilitates delivery and transient gene expression of human insulin-like 1 growth factor () in placental trophoblast for the treatment of placenta insufficiency and FGR. Using the established guinea pig maternal nutrient restriction (MNR) model of placental insufficiency and FGR, the aim of the study was to identify novel pathways in the subplacenta/decidua that provide insight into the underlying mechanism driving placental insufficiency and may be corrected with nanoparticle treatment. Pregnant guinea pigs underwent ultrasound-guided sham or nanoparticle treatment at midpregnancy, and subplacenta/decidua tissue was collected 5 days later. Transcriptome analysis was performed using RNA Sequencing on the Illumina platform. The MNR subplacenta/decidua demonstrated fewer maternal spiral arteries lined by trophoblast, shallower trophoblast invasion, and downregulation of genelists involved in the regulation of cell migration. nanoparticle treatment resulted in marked changes to transporter activity in the MNR + subplacenta/decidua when compared with sham MNR. Under normal growth conditions however, nanoparticle treatment decreased genelists enriched for kinase signaling pathways and increased genelists enriched for proteolysis, indicative of homeostasis. Overall, this study identified changes to the subplacenta/decidua transcriptome that likely result in inadequate trophoblast invasion and increases our understanding of pathways that nanoparticle treatment acts on to restore or maintain appropriate placenta function. Placental insufficiency at midpregnancy, established through moderate maternal nutrient restriction, is characterized with fewer maternal spiral arteries lined by trophoblast, shallower trophoblast invasion, and downregulation of genelists involved in the regulation of cell migration. Treatment of placenta insufficiency with a nanoparticle results in marked changes to transporter activity and increases our mechanistic understanding of how therapies designed to improve fetal growth may impact the placenta.

Decades of artificial selection have markedly enhanced egg production efficiency, yet the epigenetic underpinnings, notably DNA methylation dynamics in the gut, remain largely unexplored. Here, we investigate how breeds and developmental stages influence DNA methylation profiles in laying hens, and their potential relationship to laying performance and gut health. We compared two highly selected laying hen strains, Lohmann Brown-Classic (LB) and Lohmann LSL-Classic (LSL), which exhibited similar egg production but divergent physiological, metabolic, and immunological characteristics. Our sampling encompassed key developmental stages: the pullet stage (10 and 16 weeks old), peak production (24 and 30 weeks old), and later stage (60 weeks old) (n=99; 10 per group), allowing us to elucidate the temporal dynamics of epigenetic regulation. Our findings highlight a crucial window of epigenetic modulation during the pre-laying period, characterized by stage-specific methylation alterations and the involvement of predicted transcription factor motifs within methylated regions. This observation was consistent with the expression patterns of DNA methyltransferases (DNMTs), including DNMT1, DNMT3a, and DNMT3b. In addition, a higher methylation level was observed in specific loci or regions in the LSL compared to the LB strain. Notably, we uncover strain-specific differences in methylation levels, particularly pronounced in genomic regions associated with intestinal integrity, inflammation, and energy homeostasis. Our research contributes to the multidisciplinary framework of epigenetics and egg laying performance, offering valuable implications for poultry production and welfare.

The elusive function of myosin light chain 9 (MYL9) in cancer is an area ripe for further investigation. Bioinformatics was used to compare the expression levels of MYL9 in non-small-cell lung cancer (NSCLC) and normal tissues. Gene set enrichment analysis was used to investigate the pathways associated with MYL9. The BioGRID database was used to screen for potential targets of MYL9. The expression of MYL9 and myosin 19 (MYO19) mRNA was quantified using quantitative reverse transcriptase PCR. Cell migration was assessed using a scratch wound healing assay. The protein levels of MYL9, MYO19, and epithelial-mesenchymal transition (EMT) biomarkers were examined using Western blot (WB). Epithelial cell adhesion molecule (EpCAM) expression in different cell groups was profiled using flow cytometry analysis. Coimmunoprecipitation assays were performed to determine the binding affinity between MYL9 and MYO19. In addition, the direct protein interaction between MYL9 and MYO19 was explored using a glutathione-S-transferase (GST) pull-down assay. In NSCLC patients, MYL9 was significantly downregulated both in vivo and in cell cultures and had a high enrichment score in the EMT pathway. Scratch assays pointed to its inhibitory effect on cancer cell migration. WB showed that MYL9 could suppress EMT marker protein expression in NSCLC cells. Flow cytometry found that MYL9 greatly reduced the distribution of EpCAM on the cell surface. MYO19 was pinpointed as a potential target of MYL9, as confirmed by coimmunoprecipitation and GST pull-down assays. Rescue experiments confirmed that MYO19 could enhance cell migration, promote the expression of EMT markers, and increase EpCAM levels on the cell surface, but these effects were reserved by MYL9 overexpression. MYL9 impedes the migration and EMT in NSCLC cells by binding to MYO19. Myosin light chain 9 (MYL9) is downregulated in non-small-cell lung cancer (NSCLC). MYL9 suppresses epithelial-mesenchymal transition (EMT) in NSCLC cells. MYL9 binds to myosin 19 (MYO19). MYL9/MYO19 signaling inhibits EMT in NSCLC.

Low carbohydrate availability during recovery from aerobic exercise alters skeletal muscle microRNA (miRNA) profiles, which may mechanistically regulate exercise recovery. However, its impact on circulating miRNA (c-miRNA) profiles remains unclear. This study aimed to determine the effects of low versus adequate carbohydrate availability on c-miRNA profiles during recovery from aerobic exercise. Nine males (22±4yrs, 1.81±0.09m, 83.9±11.9kg, 25.7±2.3kg/m, mean±SD) completed this randomized, crossover study consisting of two glycogen depletion trials, followed by 24 hours of isocaloric refeeding to induce low (LOW; 1.5 g/kg carbohydrate, 3.0 g/kg fat) or adequate (AD; 6.0 g/kg carbohydrate, 1.0 g/kg fat) carbohydrate availability. Total c-miRNA were extracted from serum 24 hours following glycogen depletion exercise. Data were log transformed and analyzed as fold change relative to AD. Bioinformatics were conducted on significant c-miRNA and associated pathways (miRTarBase/KEGG). Follow-up transfection of miR-375-3p mimic or inhibitor into C2C12 cells assessed metabolic, inflammatory, and catabolic pathways at the gene and protein levels. Of the 84 miRNA assessed, miR-335-5p (-0.49±0.60; P=0.04) and miR-375-3p (-1.57±1.25; P=0.01) were significantly lower, and miR-214-3p (1.76±1.85; P=0.02) was significantly higher in AD versus LOW. experiments indicated that miR-375-3p regulates catabolic pathways at the gene and protein level. Low carbohydrate availability alters c-miRNA profiles, particularly miR-375-3p, which targets proteostasis and metabolism 24 hours into recovery from aerobic exercise. These findings identify unique c-miRNA targets as potential biomarkers for the mechanistic effects of low carbohydrate availability on exercise recovery.

Cancer remains a leading cause of death worldwide and although prognosis and survivorship after therapy have improved significantly, current cancer treatments have long-term health consequences. For decades telomerase-mediated telomere maintenance has been an attractive anti-cancer therapeutic target due to its abundance and role in telomere maintenance, pathogenesis, and growth in neoplasms. Telomere maintenance-specific cancer therapies, however, are marred by off-target side effects that must be addressed before they reach clinical practice. Regular exercise training is associated with telomerase-mediated telomere maintenance in normal cells, which is associated with healthy aging. A single bout of endurance exercise training dynamically, but temporarily, increases mRNA and telomerase activity, as well as several molecules that control genomic stability and telomere length (i.e., shelterin and TERRA). Considering the epidemiological findings and accumulating research highlighting that exercise significantly reduces the risk of many types of cancers and the anti-carcinogenic effects of exercise on tumor growth , investigating the governing molecular mechanisms of telomerase control in context with exercise and cancer may provide important new insights to explain these findings. Specifically, the molecular mechanisms controlling telomerase in both healthy cells and tumors after exercise could reveal novel therapeutic targets for tumor-specific telomere maintenance and offer important evidence that may refine current physical activity and exercise guidelines for all stages of cancer care.

This study intended to analyze the effects of body weight control by the diet, training adaptation, and gut microbiota metabolites of wrestlers in the week leading up to competition. According to the weight difference of wrestlers from the target weight 1 wk before the competition, those whose weight control effectiveness is less than 2 kg were classified as the CW group, whereas more than 2 kg were classified as the CnW group. The body weight, body composition, and diet of wrestlers were recorded; urine samples were taken for standard urine testing, and stool samples were collected for the analysis of gut microbiota and metabolites. The data showed that the relative values of carbohydrate and fat energy in the CnW group were significantly higher than those of the CW group, but the relative values of protein energy were significantly lower. The white blood cells, occult blood, and protein appeared in urine in the CnW group. The microbiota with higher abundance values in the CnW group were positively correlated with the relative value of carbohydrate energy, while the abundance value of was negatively correlated, and the functional prediction of differential bacteria was related to riboflavin and selencompound metabolism. The differential metabolites of CW/CnW group were functionally enriched in the processes of lipid and amino acid metabolism. Overall, the extent of weight control in wrestlers was correlated with sensible dietary patterns, adaptability to training load, and distinct gut microbiota and metabolites. The purpose of this study is to observe the differences in precompetition diet structure, adaptability to training, gut microbiota, and metabolites of wrestlers with different weight control effects and analyze the correlation between them, aiming to provide scientific guidance and advice on weight control for wrestlers.

Glioblastoma multiforme (GBM) is one of the most common and aggressive type of malignant glioma with an average survival time of 12-18 mo. Despite the utilization of extensive surgical resections using cutting-edge neuroimaging, and advanced chemotherapy and radiotherapy, the prognosis remains unfavorable. The heterogeneity of GBM and the presence of the blood-brain barrier further complicate the therapeutic process. It is crucial to adopt a multifaceted approach in GBM research to understand its biology and advance toward effective treatments. In particular, omics research, which primarily includes genomics, transcriptomics, proteomics, and epigenomics, helps us understand how GBM develops, finds biomarkers, and discovers new therapeutic targets. The availability of large-scale multiomics data requires the development of computational models to infer valuable biological insights for the implementation of precision medicine. Artificial intelligence (AI) refers to a host of computational algorithms that is becoming a major tool capable of integrating large omics databases. Although the application of AI tools in GBM-omics is currently in its early stages, a thorough exploration of AI utilization to uncover different aspects of GBM (subtype classification, prognosis, and survival) would have a significant impact on both researchers and clinicians. Here, we aim to review and provide database resources of different AI-based techniques that have been used to study GBM pathogenesis using multiomics data over the past decade. We summarize different types of GBM-related omics resources that can be used to develop AI models. Furthermore, we explore various AI tools that have been developed using either individual or integrated multiomics data, highlighting their applications and limitations in the context of advancing GBM research and treatment.

We aimed to determine the peripheral blood mononuclear cell (PBMC) immune profiles of mid- and late-stage pregnant women to establish a foundation for studying pregnancy-related diseases. Peripheral blood samples were collected from three women each during mid- and late-stage pregnancy, and PBMCs were extracted for single-cell RNA sequencing (scRNA-seq). Peripheral blood samples were also collected for flow cytometry analysis to validate the analytical results. HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells significantly differed in quantitative ratio and gene transcript level between women at mid- and late-stage pregnancy. In late pregnancy, cell-to-cell communication was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," exhibited high expression, a gene that may be involved in the regulation of immune-related gene transcription and translation, and insulin signaling pathway, during pregnancy. Monocytes exhibited significant proinflammatory and metabolic properties in mid- and late-stage pregnancy, respectively. Natural killer (NK) cells were mainly involved in T- and B-cell-mediated signaling pathways, and in T cell differentiation, in mid-pregnancy. Enhanced innate immunity of NK cells was observed. Moreover, NK cells expressed genes associated with diabetes-related pathways in late-stage pregnancy. To conclude, we present detailed changes in the immune response occurring in pregnant women from mid- to late-stage gestation, revealing significant differences in PBMC subtypes and molecular properties. These findings provide insights into the physiopathological mechanisms of chronic hepatitis B infection, systemic lupus erythematosus, and gestational diabetes mellitus underlying systemic immune responses during mid- and late-stage pregnancy. There are significant differences in three subtypes of memory/effector T cells (HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells) between mid- and late pregnancy. In late pregnancy, intercellular interaction was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," may be involved in the regulation of immune-related gene transcription and translation with a strong female bias.

This study aimed to examine the protective effect of celastrol on testicular dysfunction in diabetic rats and the potential underlying mechanisms. All rats included in the study were divided into four groups: a control group treated with sodium citrate buffer and vehicle), a celastrol-treated control group, a streptozotocin (STZ)-induced diabetic group following insulin resistance, and a celastrol-treated diabetic group. Serum glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, interleukin (IL)-1β, tumor necrosis factor-alpha, and testosterone levels were measured. In addition, the levels of testicular homogenate superoxide dismutase and malondialdehyde were assessed. Furthermore, testicular tissue relative , , and expression were quantitatively measured using polymerase chain reaction. Histopathological and immunohistochemical studies were also conducted. The results revealed that treatment with celastrol significantly reduced , , expressions and the levels of inflammatory mediators such as tumor necrosis factor-alpha and IL-1β in the testicular tissue of treated rats. These findings suggest has the potential to be effective in the treatment of diabetes-induced testicular injury by inhibiting testicular inflammation, apoptosis, and oxidative stress.

Hypertension affects 1 in 2 U.S. adults and hypertension prevalence increases with aging. Both hypertension and aging can cause arterial remodeling. We investigated the hypothesis that aortic remodeling contributes to age-dependent hypertension in male Sprague Dawley (SD) rats. Compared to young 3-month-old rats 16-month-old male SD rats developed age-dependent hypertension that associated with increased sympathetic tone to the vasculature, elastin disarray and blood pressure variability. Our quantitative proteomic/phosphoproteomic workflow of the aorta identified 2366 proteins and 226 phosphoproteins, from which 58 proteins and 39 phosphoproteins were differentially expressed or phosphorylated respectively between young normotensive controls and aged hypertensive animals. Analysis of the proteome highlighted significant changes in the extracellular matrix, actin cytoskeleton and inflammatory pathways. Analysis of the differential phosphoproteome revealed significant differences in synapse and neuron projection and vascular smooth muscle cell (VSMC) function including actin remodeling and focal adhesions. STRING hypertension network analysis identified 13 differentially expressed and 10 differentially phosphorylated proteins associated with hypertension. Within the STRING analysis we observed 2 major areas of correlation of alterations in the aorta proteome with increased hypertension risk score - vascular inflammation and VSMC function. The majority of the identified phosphorylation sites (78.57%) in hypertension-relevant hyperphosphorylated proteins were located at serine residues. Collectively, we report that arterial remodeling in age-dependent hypertension is associated with an altered extracellular matrix and actin cytoskeleton and modulation of VSMC focal adhesion networks and neuron/synapse interactions.