Journal of the International Society of Sports NutritionClaire Buechel, Kate Pumpa, Naroa Etxebarria, Luke Ashton, Michelle Minehan
BACKGROUND: Resting Metabolic Rate (RMR) is measured in sport settings for health monitoring and nutrition planning; however, interpreting repeated measures requires an understanding of typical day-to-day variability under habitual, free-living conditions. This study quantified intra-individual variability in RMR among weight-stable strength-trained athletes, examined the impact of data processing approaches, and established protocol-specific least significant change (LSC) thresholds under ecological conditions. METHODS: A repeated-measures design was used to quantify intra-individual variability in RMR in 13 weight-stable strength-trained athletes (8 male, 5 female). RMR was measured on five consecutive mornings using the Parvo Medics TrueOne 2400 metabolic cart with a Hans Rudolph mouthpiece under standardized conditions. Breath-by-breath data were processed using multiple cleaning approaches to evaluate their impact on RMR estimates, with the most reliable method retained for analysis. Intra-individual variability was quantified and used to derive protocol-specific LSC thresholds. RESULTS: Session averaging produced the lowest intra-individual variability in RMR (CV: 3.4 ± 1.4%) compared with alternative data cleaning approaches. Mean RMR was 26.9 ± 1.4 and 29.1 ± 1.7 kcal·kgFFM-1·day-1 in males and females, respectively. The group-level LSC was 2.9 ± 1.2 kcal·kgFFM-1·day-1 (10.4 ± 4.2%), representing the magnitude of change required to exceed expected within-subject variability under the conditions of this protocol. Fat-free mass (FFM) was positively associated with both absolute RMR and day-to-day variability, whereas prior-day training load and protein intake showed no clear association with RMR variability. CONCLUSIONS: Notable intra-individual variability occurs in repeated RMR measurements in strength-trained athletes under applied conditions. Meaningful interpretation of change requires protocol-specific reliability estimates to distinguish true physiological change from expected day-to-day variation. Session averaging improves measurement consistency and is recommended for mouthpiece-based indirect calorimetry systems. RMR should be interpreted relative to individual and context-specific variability rather than universal thresholds.
Myasthenia gravis (MG) is a complex autoimmune neuromuscular disorder, and the role of lipid metabolism dysregulation in MG pathogenesis remains unclear. This study aimed to investigate the molecular mechanisms of lipid metabolism regulation in myasthenia gravis development by integrating single-cell and bulk transcriptomic data. This study analyzed bulk RNA sequencing data from the GSE85452 dataset (13 MG patients and 12 healthy controls) and single-cell RNA sequencing data from the GSE227835 dataset (10 MG patients and 10 healthy controls). Differential expression analysis was performed, and weighted gene co-expression network analysis (WGCNA) was conducted to identify disease-related modules. Key genes were screened through the intersection of differentially expressed genes (DEGs), WGCNA hub genes, and lipid metabolism-related genes. Functional enrichment analysis, protein‒protein interaction (PPI) network construction, immune infiltration analysis, and regulatory network analysis were performed. Single-cell analysis was used to characterize cellular heterogeneity and intercellular communication features. A nomogram prediction model was constructed and internally validated using leave-one-out cross-validation (LOOCV). Potential therapeutic compounds were identified through drug prediction and molecular docking analysis. Furthermore, key genes were validated by RT-qPCR in an independent cohort of 5 MG patients and 5 healthy controls. A total of 823 DEGs and 13 co-expression modules were identified, of which 4 modules were significantly associated with MG. Twenty-one candidate genes were screened, and 2 key genes (IRS2 and ALDH2) were ultimately determined. IRS2 was significantly downregulated while ALDH2 was significantly upregulated in MG patients. The nomogram model based on key genes demonstrated excellent predictive performance (AUC = 0.897). Immune infiltration analysis showed increased regulatory T cells (Tregs) and decreased CD4+ memory activated T cells in MG patients. Single-cell analysis identified 10 major cell types. Cell‒cell communication analysis revealed dense interactions among CD4+ T cells, B cells, and CD14+ monocytes. Drug prediction identified metformin and cyclophosphamide as potential therapeutic candidates, and molecular docking confirmed favorable binding affinities. This integrative study generated the hypothesis that lipid metabolism dysregulation, potentially mediated by IRS2 and ALDH2, may contribute to immune dysfunction in MG pathogenesis. These findings provide preliminary insights into the molecular mechanisms underlying MG development and suggest potential diagnostic biomarkers and therapeutic targets. However, these results are hypothesis-generating, and clinical translation is contingent upon rigorous mechanistic validation through functional experiments, animal models, and larger multicenter clinical cohorts.
Gut microbesYan Cheng, Zhanxuan E Wu, Ruoyue Huang, Qingmei Li, Dongmei Yan, Yuqi Chen, WeiFeng Zhu, Fei Li
Ulcerative colitis (UC) is a systemic disease that can involve multiple organs, and hepatobiliary diseases in UC patients are frequently observed. However, the pathogenesis of UC and its associated hepatobiliary complications remains elusive, and limited therapeutic options are available. This study revealed that disrupted hepatic lipid metabolism plays a pivotal role in driving the progression of UC and its extraintestinal hepatobiliary manifestations. Mechanistically, colitis-elevated circulating endogenous corticosterone (CORT) mediates the downregulation of hepatic LXRα-SCD1 signaling, resulting in diminished monounsaturated fatty acid (MUFA), reduced unsaturated lysophospholipids, and the accumulation of alkyl lysophospholipids, ceramide and hexosylceramide. These alterations contribute to liver lipotoxicity and, in turn, exacerbate colitis. A similar lipid profile is observed in UC patients. Importantly, pristimerin, a natural compound structurally similar to the star molecule celastrol, has been demonstrated to alleviate UC and concomitant liver injury by remodeling hepatic lipid metabolism in a microbiota-dependent manner. The gut commensal Lactobacillus johnsonii mediates the effects of PSM by activating hepatic LXRα-SCD1 signaling and increasing the potential anti-inflammation lipid species LPC20:2 and LPC20:3. This investigation suggests a novel therapeutic strategy for UC and associated liver injury based on the L. johnsonii-hepatic LXRα-SCD1 axis. This study also opens new avenues for mechanistic exploration of systemic diseases and therapeutic strategies of multi-organ comorbidity.
The membrane receptor MerTK is critical for the resolution of inflammation and thus is of pharmacological interest. MerTK function is inhibited by the proteolytic cleavage of its extracellular domain leading to the formation of soluble Mer (sMer). We describe here the NANOBODY molecule A0445046C08 and its half-life-extended version A044500050. Both bound selectively to MerTK and blocked lipopolysaccharide-induced MerTK cleavage in primary macrophages without influencing ligand binding or kinase activity of MerTK. A044500050 reduced Zymosan-induced sMer levels in the peritoneal lavage fluid of a mouse model with sterile peritonitis. The study demonstrates that NANOBODY molecules can be generated that selectively inhibit ectodomain shedding and outlines a novel pharmacological approach for targeting membrane proteins where aberrant cleavage plays a pathogenic role.
The aging male : the official journal of the International Society for the Study of the Aging MaleMingshun Zuo, Yuanjian Liao, Qiang Xu, Ailing Su, Ni Fu, Chenghong Zou
BACKGROUND: Observational studies link hyperthyroidism to increased prostate cancer (PCa) risk, but causality and mechanisms remain unclear. Graves' disease (GD), the primary cause of hyperthyroidism, involves chronic immune dysregulation that may influence PCa through shared immune pathways. METHODS: We performed bidirectional two-sample Mendelian randomization (MR) using IEU Open GWAS data, then integrated differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning on Gene Expression Omnibus (GEO) datasets to identify shared gene, validated by ROC curves, and analyzed immune profilesusing ssGSEA. RESULTS: MR analysis indicated that genetic predisposition to GD significantly reduced PCa risk (OR = 0.997, 95% CI = 0.996-0.999, p = 0.004), with consistentsensitivity and no reverse causality. Four key genes (BTG2, JUN, JUNB, FOS) were identified as robust shared genes with high predictive accuracy in external validation. Immune profiles analysis revealed disease-specific associations of these genes: BTG2 and JUNB correlated with memory CD8 T cells in GD, whereas all four genes correlated with dendritic cells, mast cells and NK cells in PCa. CONCLUSION: This study provided novel insights into the protective effect of GD against PCa and identified shared genes and immune mechanisms, offering a deeper understanding of the common mechanisms between GD and PCa.
Drug deliveryGabriela Koutná, Jan Kotouček, Jan Macků, Kateřina Kubová, Martina Urbanová, Larisa Janisová, Ivana Šeděnková, Jan Muselík, Jakub Vysloužil, Josef Mašek, Elišk…
Self-microemulsifying drug delivery systems (SMEDDS) containing volatile phytotherapeutics such as thymol (T), carvacrol (C), and eugenol (E) present significant formulation challenges, even when solidified. Their instability and interactions with coatings often hinder intestinal delivery. To address these limitations, we developed solid SMEDDS consisting of pellets (microcrystalline cellulose/magnesium aluminometasilicate/chitosan) and enteric capsules (CEC) for enhanced intestinal delivery. Based on solubility and pseudo-ternary phase diagrams, SMEDDS formulations (SES1-3) differing in component ratios (glycerol monooleate/caprylocaproyl macrogol-8 glycerides/diethylene glycol monoethyl ether) with 5% w/w of each drug were identified, demonstrating nano-scale droplet sizes (PDI <0.4) and showing no phase separation over 6 months. Thermodynamic stability and liquid-state NMR revealed particle size variations with preserved structural integrity. The lead formulation SES1 exhibited superior ex-vivo intestinal permeation (T-SES1). CECs filled with T-, C-, and E-loaded SES1 pellets, respectively, prepared via extrusion/spheronization, exhibited in-vitro gastro-resistant release, and achieved > 85% drug release within 120 min after a pH change to 6.8 during a one-year stability study (25 °C; 60% RH). FTIR-ATR analysis of the CEC internal surface confirmed the temperature-dependent restructuring of hypromellose and E sorption, a phenomenon not observed with C or T, which is likely attributable to physicochemical distinctions. Oral administration of CEC with T-SES1-pellets (0.5 mg/kg) in piglets demonstrated a delayed peak plasma concentration (Cmax 11.67 ng/mL at 9 h) and sustained systemic exposure (AUC 119.8 ng·h/mL). These in-vivo findings substantiate the gastro-protective effect and enhanced intestinal absorption, positioning the pellet/CEC system as a promising strategy for the application of volatile phytotherapeutics in current pharmacotherapy.
Ribosomes are essential nanomachines responsible for synthesizing all cellular proteins. Their production, known as ribosome biogenesis, is a highly complex and energy-intensive process that requires the coordinated action of hundreds of proteins and RNA-based trans-acting factors to assemble and mature the functional ribosomal components. Ribosome biogenesis is increasingly recognized as a key contributor to human disease: excessive ribosome production can fuel tumorigenesis, while insufficient or defective ribosome production is observed in a group of tissue-specific disorders known as ribosomopathies. Although the basis of this tissue specificity remains poorly understood, the most commonly affected systems are the blood, brain, and bones. Recent advances in structural biology have yielded high-resolution snapshots of precursor (pre-)ribosomes at various stages of maturation, offering new insights into how pathogenic variants of ribosomal proteins or assembly factors disrupt critical molecular interactions. In this review, we highlight selected examples where structural information is beginning to illuminate the molecular basis of ribosomopathies.
Gut microbesGillian N F Larik, Emanuel E Canfora, Evert M van Schothorst, Ellen E Blaak
The gut microbiota‒host metabolism axis is a critical determinant of metabolic health, yet its functional activity remains difficult to monitor in vivo. The gut microbiota ferments undigested food components such as dietary fibers and proteins, yielding various important metabolites and gases that impact human metabolism. This review synthesizes current evidence on intestinal gases, primarily hydrogen (H2), methane (CH4) and hydrogen sulfide (H2S), as non-invasive markers of the trade-off between saccharolytic and proteolytic fermentation. Within the current review, we evaluate the concentrations of important gut metabolites and gases and techniques to measure intestinal gases, including stable isotope breath tests, volatile organic compound (VOC) profiling, and respiration chambers. Crucially, we highlight that these gases may function not only as metabolic byproducts and biomarkers of microbial activity but as active signaling molecules influencing gastrointestinal transit, satiety, and systemic inflammation. This review concludes that real-time gas monitoring provides a unique opportunity to study real-time gut microbial fermentation. We propose a framework for phenotyping individual or subgroup-based fermentation patterns to guide personalized nutritional interventions for obesity and type 2 diabetes.
Drought-induced reduction in crop yield is becoming a serious threat worldwide, especially in arid to semiarid regions. The introduction of medicinal plants into cropping patterns in arid regions is a suitable alternative to conventional crops because of their high demand and market value. Keeping in view the situation, an experiment was planned under natural arid conditions to screen out the best psyllium varieties in less time for cultivation in arid regions. The experiment included three psyllium varieties (V1 = Gujrat isabgol-2, V2 = Vallabh isabgol and V3 = Jawahar isabgol-4) and three irrigation regimes (control = CK, partial rootzone drying = PRD and deficit irrigation = DI) and was carried out in a completely randomized design with eight replications. The results of our experiment revealed that although cell stress indicators (electrolyte leakage, relative cell injury, methylglyoxal, malondialdehyde, and hydrogen peroxide contents) were less and photosynthesis, water relationships, and membrane stability were greater in the control irrigation, the activities of enzymatic and nonenzymatic antioxidants were greater in the PRD and DI regimes. Among the water deficit treatments, more water potential, proline contents, ascorbic acid contents, membrane stability index, and yield were recorded in the PRD than in the DI. Among the varieties, V3 performed the best under water deficit conditions, whereas variety V2 presented the lowest values. It was concluded that under less water availability, the combination of the PRD with the variety V3 optimized physiological and yield outcomes by sustained higher relative water contents (77.10%), mesophyll conductance (0.67 mol CO2 m-2 s-1 bar-1), photosynthesis (15.10 µmol of CO2 m-2s-1), and membrane stability index (78.80%). Consequently, maximized water use efficiency (0.21 g L-1) and antioxidant activities, leading to higher yield (0.76 g plant-1). Future research should focus on integrating PRD with other water management techniques like mulching, osmoprotectants spray to enhance its efficacy under water deficit conditions.
OncoimmunologyShuhang Xu, Yaorong Su, Senmin Zhang, Dongye Huang, Song Wu, Cailu Song, Wenhuan Zhong, Lan Xie, Wenkuan Chen
Metastasis is a major determinant of treatment failure and mortality in thyroid cancer, yet the interplay between malignant evolution and the immune microenvironment remains poorly characterized. Immunotherapy offers promise, but its efficacy requires a deeper understanding of tumor-associated immune infiltration and checkpoint regulation. In this study, we constructed a high-resolution transcriptomic atlas of the thyroid cancer ecosystem by analyzing 55,005 single cells from paired primary tumors and lymph node metastases. By integrating chromosomal copy number variation (CNV) inference with consensus nonnegative matrix factorization (cNMF), we deciphered the intrinsic heterogeneity of malignant epithelial cells, revealing distinct transcriptional programs and developmental trajectories driving the metastatic cascade. The metastatic niche exhibited significant reprogramming of the immunosuppressive landscape, characterized by the enrichment of FOXP3⁺ regulatory T (Treg) cells, LAMP3⁺ dendritic cells (DCs), and CCL18⁺ M2-like macrophages. Notably, while canonical checkpoints PD-1 and PD-L1/2 showed minimal expression, ligand-receptor interaction analysis identified the LAG3-LGALS3 axes as dominant immune evasion pathways mediating the crosstalk between CD8⁺ T cells and the tumor stroma. In conclusion, this study comprehensively maps the coevolution of malignant thyrocyte plasticity and the immunosuppressive metastatic niche. By uncovering the specific role of LAMP3⁺ DCs and identifying LAG3/TIGIT as critical alternative checkpoints, our findings challenge the utility of conventional PD-1 blockade in this context and provide a robust molecular rationale for developing next-generation immunotherapeutic strategies tailored to thyroid cancer. Although limited by a modest sample size, these findings provide a foundation for further investigation of the metastatic immune landscape in thyroid cancer.
Gynecological endocrinology : the official journal of the International Society of Gynecological EndocrinologyQiu-Feng Xiao, Xiao-Hong Xie, Chong-Zhi Wen, Zhou-Lan Li
OBJECTIVE: To explore the relationship between the C-reactive protein-triglyceride-glucose index (CTI) and the risk of type 2 diabetes mellitus (T2DM) in women with prior gestational diabetes mellitus (GDM). METHODS: Logistic regression and restricted cubic spline (RCS) analyses were used to explore the relationship between CTI and the risk of T2DM. Subgroup and interaction analyses were conducted to examine the sensitivity of CTI to T2DM risk and its interaction with confounding factors, respectively. Machine learning algorithms were employed to rank variable importance in T2DM. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were employed to investigate the clinical value of CTI. RESULTS: CTI showed a significant positive linear association with T2DM, influenced by hyperlipidemia and BMI. CTI was related to T2DM risk among individuals with low-density lipoprotein cholesterol (LDL-C) >130 mg/dL. CTI ranked as the top predictor of T2DM risk. The area under the curve (AUC) of CTI was 0.767 in predicting T2DM. CTI provided a clinical net benefit for predicting T2DM when the threshold probability ranged from 0.18 to 0.64. CONCLUSION: CTI is associated with future T2DM in women with prior GDM, showing a continuous dose-response relationship. Elevated LDL-C may enhance CTI's predictive power.
Gut microbesRimi Chowdhury, Erick M Bosire, Lindsay R Wolverton, Paulina D Pavinski Bitar, Katherine E Bell, Ivan Keresztes, Rory C Chien, Craig Altier
Successful colonization by enteric pathogens requires overcoming colonization resistance of the native microbiota while tightly regulating the expression of energetically-expensive virulence factors. Here we describe a feedback mechanism by which the enteric pathogen Salmonella orchestrates this balance through environmental manipulation. We show that Salmonella-induced oxidative stress can stimulate the colonic resident Stenotrophomonas maltophilia to enhance the secretion of the diffusible signal factor cis-2-hexadecenoic acid (c2-HDA), a potent repressor of Salmonella virulence. By sensing this metabolite, Salmonella can attenuate its own virulence program to favor proliferation and colonic colonization. In murine models, Salmonella colonization was significantly enhanced in the colon, and inflammation reduced, in the presence of c2-HDA produced by S. maltophilia. Moreover, the ability of Salmonella to recognize c2-HDA within the murine colon was crucial for its successful colonization. These findings reveal a pathogen-commensal signaling axis through which pathogen-driven inflammatory cues reshape the metabolic output of the microbiota, generating regulatory signals that are co-opted to optimize pathogen fitness in the gut.
Gut microbesEui Jeong Han, Da-Hye Kim, Jeong Jae Lee, Hea-Jong Chung
The gut microbiome is a key regulator of host physiology, yet its effects remain difficult to predict across individuals and contexts. Similar microbial compositions frequently give rise to divergent and delayed phenotypic outcomes, indicating that models based solely on signal strength or steady-state responses are insufficient to explain microbiome-driven host function. In this review, we propose a conceptual perspective in which microbiome-associated variability is shaped by the capacity of host cells to maintain mitochondrial function under persistent metabolic and immune stress. Microbiome-derived metabolites and immune activity define the metabolic and redox environments that constrain mitochondrial performance, thereby influencing how effectively cells recover from repeated stress. When mitochondrial membrane potential, redox balance, and energy production are not fully restored, mitochondria may show increased engagement of quality-control pathways. Over repeated stress-recovery cycles, this pattern may be associated with reduced functional reserve despite preserved baseline activity. This testable perspective may help explain why microbiome-associated phenotypes are delayed, variable, and context-dependent, and it highlights mitochondrial recovery capacity as a potential determinant of disease vulnerability and host-microbiome interactions.
Gut microbesKhashayar Shahin, Liang Wang, Zihan He, Bomin Lv, Arya Van Alin, Richard Lo-Man, Hao Wu, Philippe Sansonetti, Jean-Marc Collard
Prokaryote-prokaryote symbiotic relationships influence interactions within microbial communities, affecting colonization, survival, and organization. Unlike competition, consortium species facilitate growth via metabolite cross-feeding. This study explored interactions between two early human gut colonizers: partially aerotolerant Bifidobacterium spp. and strict anaerobic Bacteroides spp., using omics techniques. Promotion of Bacteroides spp. growth by Bifidobacterium animalis subsp. lactis was demonstrated through co-culture experiments in anaerobic conditions. Metabolomic analysis revealed over 150 unique metabolites present in B. animalis subsp. lactis supernatants are absent in other Bifidobacterium species, including 3-hydroxycapric acid, D-alanyl-D-alanine, 2-isopropylmalic acid, and D-glucose 2-phosphate. These compounds served as nutritional substrates, including carbon and nitrogen sources, significantly enhancing Bacteroides spp. growth. In murine models, early colonization by B. animalis subsp. lactis consolidated Bacteroides fragilis colonization (1.7 × 104 to 9.7 × 106 copy number/g fecal sample) by providing these metabolites as a niche. These findings highlight B. animalis subsp. lactis plays a critical role in gut colonization of Bacteroides spp. via its exclusive metabolic profile, offering insights into partitioned metabolic activity within gut communities and emphasizing the importance of specific metabolites in early microbial establishment.
Cancer biology & therapyMengting Luo, Feng Shen, Wanli Xu, Christopher Corpe, Jin Wang
Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive human malignancies and has an extremely poor prognosis. Its progression is largely driven by a highly complex and immunosuppressive tumor microenvironment (TME), highlighting the urgent need for a deeper understanding of its molecular mechanisms. Recent advances in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have provided unprecedented opportunities to dissect cellular heterogeneity, spatial organization, and gene expression dynamics within the TME. In this review, we summarize the major scRNA-seq and ST technologies and their unique strengths in cancer research and highlight their integrated applications in revealing PDAC heterogeneity, stromal-immune interactions, and mechanisms of therapeutic resistance. We further discuss how these approaches can inform biomarker discovery and guide the development of novel therapeutic strategies. Together, these findings suggest that integrated single-cell and spatial transcriptomics offers transformative potential to advance precision oncology and improve outcomes for patients with pancreatic cancer.
Gut microbesDominik Awad, Holly Attebury, Ryan Hong, Kwi Kim, Li Zhang, Allison Bischoff, Sajan Achi, Aaron denDekker, Nick Lesniak, Stephanie The, Joseph A Nieto Carrion,…
Pancreatic ductal adenocarcinoma has a unique tumor microbiome, and the depletion of gut bacteria or fungi using antibiotic/antifungal cocktails has been shown to decrease pancreatic tumor burden in mice. However, functional studies evaluating the role of tumor-associated microbes are few due to the limited availability of clinically relevant microbiota. Here, we describe in detail an effective workflow for the isolation of bacteria and fungi from the duodenum and tumor of pancreatic cancer patients, specifically optimized for cryopreserved, low biomass samples. Using this workflow we also isolated microbiota from normal pancreatic tissue and duodenum from organ donors, and we confirmed the presence of bacteria and fungi isolated from tissue samples with 16S and ITS sequencing analysis. Isolation and sequencing results show distinct similarities between the pancreatic and duodenal microbiomes and highlight unique bacterial strains that survive in the tumor microenvironment. As a proof of concept, we characterized a select Klebsiella oxytoca strain (UMKO1) isolated from a pancreatic tumor, using whole genome sequencing, metabolomics, and ex- vivo tumor cultures to determine its potential impact on the pancreatic tumor microenvironment. In summary, this optimized workflow allows for the isolation of a variety of bacteria and fungi from low biomass, cryopreserved pancreatic and duodenal tissues, which can then be used for functional studies characterizing clinically relevant tumor-associated microbiota.
Plant signaling & behaviorHina Firdous, Abbas Shoukat, Muhammad Mubashar Zafar, Huma Saleem, Rabia Faridi, Arfan Ali, Waseem Hassan, Sezai Ercisli, Rafiuddin Rafiuddin, Muhammad Fuad An…
Combined drought and heat stress (DS+HS) represents one of the most devastating multi-factorial constraints on global wheat (Triticum aestivum L.) production, imposing synergistic physiological and molecular damage that far exceeds the effects of each stress applied individually. Emerging evidence suggests that selenium nanoparticles (Se NPs) and biochar independently confer abiotic stress tolerance in cereal crops; however, their combined soil application under concurrent DS+HS in wheat has not been previously investigated. The present study was conducted at the wire house facility of the Four Brothers Group (FBG), Lahore, Pakistan, using soil collected from Faisalabad, to evaluate the individual and combined effects of soil-applied Se NPs (50 mg kg-1) and wheat straw biochar (2% w/w) on wheat cv. FBG-1800 subjected to drought (30% field capacity) and heat stress (42 °C, 6 h d-1) in a completely randomized design with three replications. Combined DS+HS severely impaired growth, photosynthetic function, and grain yield, while markedly elevating oxidative damage markers and disrupting ionic homeostasis. Notably, combined Se NPs + biochar application produced superior synergistic amelioration relative to either amendment alone, restoring net photosynthetic rate and grain yield to approximately 89%-90% and 88% of control values, respectively, alongside significant reductions in oxidative stress indicators. Gene expression analysis confirmed marked upregulation of key stress-responsive genes (TaSOD1, TaDREB2, TaHSP70, TaNHX1) and coordinated antioxidant enzyme activation. These findings establish that soil co-application of Se NPs and biochar is an effective, agronomically feasible strategy to sustain wheat productivity under the increasingly prevalent combined DS+HS conditions in Pakistan's irrigated cropping systems.
Gut microbesSweta Ghosh, Zachary Matthew Vanwinkle, Kanchan Sinha Roy, Miroslav Stýblo, Mayukh Banerjee, James Collins, Venkatakrishna Rao Jala
Chronic exposure to inorganic arsenic (iAs) remains a major environmental health concern and is associated with significant gastrointestinal (GI) disorders, including gastroenteritis, diarrhea, and inflammatory bowel disease-like symptoms. Gut microbiota plays a critical role in mitigating arsenic toxicity, as germ-free or antibiotic-treated mice exhibit reduced fecal arsenic excretion and greater tissue accumulation. We previously showed that the microbial metabolite Urolithin A (UroA) protects against iAs-induced cytotoxicity, apoptosis, oxidative stress, and ROS production in vitro. In this study, using humanized AS3MT mice (mouse arsenic methyltransferase gene (As3mt)replaced with human AS3MT, hAS3MT), we evaluated the in vivo effects of iAs and UroA on gut barrier function. Long-term iAs exposure (100 ppb for 28 weeks) significantly reduced expression of tight junction proteins, indicating compromised intestinal barrier integrity. UroA treatment protected hAS3MT mice from iAs-induced gut permeability, inflammation, colon shortening, and elevated colon weight/length ratio. UroA also reduced iAs-induced inflammatory cytokines, myeloperoxidase (MPO) activity and preserved intestinal epithelial cell tight junction protein expression. Further, microbiome and metabolomic analysis suggested that UroA treatment protected from iAs-induced gut microbial dysbiosis, especially restored several beneficial bacterial strains and short chain fatty acids (e.g., acetate and butyrate) and led to gut homeostasis. Together, these findings demonstrate that UroA mitigates iAs-induced gut toxicity and restores microbiota homeostasis.
Journal of the International Society of Sports NutritionNagham Sannan, Hassan Younes, Nour El Helou
BACKGROUND: A longitudinal controlled intervention study aimed to assess the impact of a nutrition education program on Lebanese athletes' nutritional knowledge, eating habits, body composition and performance. METHODS: A sample of 198 athletes was divided into an intervention group (IG) and a control group (CG). The intervention group followed a 4-month intensive nutrition education program set to ensure sufficient time for meaningful learning and behavior change, while remaining short enough to maintain participant engagement and minimize dropout. The athletes' nutritional status and performance were assessed before and after the intervention using a validated food frequency questionnaire, knowledge and eating habits questionnaires, four 24-h recalls, a beep test to estimate VO2 max and one-repetition maximum tests to measure muscle strength. Paired-sample t-tests, McNemar's test and Mixed Factorial Anova test were conducted to examine the effects of the nutritional education program on nutrition knowledge, hydration status, eating habits and performance within both groups. RESULTS: The nutritional knowledge score increased in both groups after the intervention, with a significantly greater improvement of 23% observed in the IG (from 62.6% to 77.1%; p < 0.001). The IG also demonstrated a notable improvement in eating habits compared to the CG (p < 0.001). Following the intervention, body fat percentage decreased from 21.3% ± 6.0% to 18.8% ± 6.0% (p < 0.001), and waist circumference significantly decreased in the IG (p < 0.001). The IG increased their consumption of vegetables (p < 0.001) and yogurt (p = 0.002) and decreased their intake of sugars (p < 0.001) and sunflower oil (p = 0.002). Improvements in both aerobic and strength performance were observed in the IG (p < 0.001). CONCLUSIONS: The nutrition education program led to significant improvements in athletes' nutritional knowledge and eating habits, which consequently resulted in enhanced performance.
The aging male : the official journal of the International Society for the Study of the Aging MaleAmar Mann, Richard C Strange, Carola S König, Geoffrey Hackett, Ahmad Haider, Karim Sultan Haider, Peter Desnerck, Michael Zitzmann, Farid Saad, Mruga M Dhebar…
BACKGROUND: Using the Gompertz-Makeham model, we describe associations between age and the probability of mortality in men with adult-onset testosterone deficiency (TD), stratified by testosterone undecanoate (TU) treatment and type 2 diabetes (T2DM). METHODS: We analyzed a registry of 737 men (353 and 384 men on/not on TU, respectively) with adult-onset TD with nearly 9 years of follow-up. We compared associations between age and mortality using nonparametric and logistic regression models (estimating individual mortality probability) in men stratified by TU treatment and T2DM. RESULTS: Mortality was lower (p < 0.001) in men on TU compared to men opting against TU. In the men on TU, age was associated with mortality (odds ratio (OR): 1.26, 95% confidence interval (CI): 1.13-1.40) in the nonlinear pattern expected in the Gompertz‒Makeham model. However, age was not associated with mortality in men not on TU (OR: 1.03, 95% CI: 0.98-1.08). T2DM status did not affect these associations. CONCLUSION: The association between age and mortality differed between men on TU and those opting against treatment. In untreated men, features of metabolic syndrome worsened, which perhaps minimized the relationship between age and mortality. In men on TU, these metabolic risk factors improved, perhaps restoring the association between age and mortality.