Search Results (8,895)

Background/Objectives: Masters athletes are adults aged ≥40 who compete in sport, exhibiting superior physical function and healthier aging than their sedentary peers. However, even highly trained masters athletes experience age-related performance declines. Women masters athletes represent a growing yet understudied population who may face unique physiological challenges. This scoping review synthesizes literature from 1984 to 2024, examining the impact of age and menopause on determinants of endurance performance in women masters athletes. Methods: Following JBI scoping review methodology, six databases were searched (Medline, Embase, Central, CINAHL, SPORTdiscus, Scopus). Studies were evaluated for population characteristics, methodological approaches, and physiological determinants of performance (i.e., aerobic capacity, lactate kinetics, and exercise economy). Results: Twenty-nine studies were included. Most (n = 28) assessed aerobic capacity, reporting declines between 0.36 and 0.84 mL·kg⁻¹·min⁻¹·year⁻¹ (0.5–2.4%·year⁻¹). These reductions were primarily associated with decreased cardiac output followed by changes in body composition. Training volume emerged as a predictor of aerobic capacity, but the effects of menopause were unclear. Findings on lactate kinetics and exercise economy were mixed but preliminary research indicated that lactate threshold relative to VO₂max generally increased, peak lactate remained stable and energy cost increased with age. Fitness and health characteristics among women athletes differed from sedentary populations, emphasizing the need for athlete-specific data to support training and health decisions. Conclusions: Aging is associated with decreased aerobic capacity and variable changes in lactate kinetics and exercise economy. While training volume may attenuate performance decrements, the impact of menopause remains uncertain, underscoring the need for longitudinal research to better support this growing segment of the population. Full article

Breast cancer (BRCA) is the most common cancer worldwide, with an incidence exceeding that of lung cancer. Protein lactylation, a newly identified post-translational modification involving the binding of lactic acid to lysine residues, plays an important role in BRCA. However, its role in BRCA progression remains largely unexplored. This study aims to identify and characterize the lactylation-related genes involved in BRCA biology. Transcriptomic and clinical data of BRCA and normal breast tissues were obtained from TCGA and GEO. Lactylation-related genes were curated from literature and intersected with BRCA datasets to identify candidates. A prognostic risk model was constructed using LASSO and Cox regression. Functional enrichment was performed using KEGG, GSVA, and GSEA. Immune correlations were evaluated by ESTIMATE, CIBERSORT. Single-cell RNA-seq data were integrated to assess gene expression heterogeneity across tumor and immune compartments. In vitro, MDA-MB-231 cells were treated with sodium L-lactate and lactylation-inducing agents, and gene expression was validated by Western blot and RT-qPCR, while EdU and wound healing assays evaluated proliferation and migration. We identified six hub genes associated with the immune microenvironment. Notably, S100A4 is significantly underexpressed, suggesting their potential regulatory roles in BRCA. Further analysis demonstrated that lactylation-related genes are closely linked to immune regulation in BRCA, indicating a possible crosstalk between metabolic modification and tumor immunity. Additionally, we found that lactylation significantly influences gene expression patterns and immune infiltration in BRCA. Importantly, lactic acid ions were shown to upregulate lactylation levels in BRCA cells, underscoring the functional impact of metabolic signals on post-translational modifications in tumorigenesis. Our findings indicate a potential mechanism wherein lactylation affects BRCA progression via lactic acid-driven regulation of the immune microenvironment; they also highlight the possible involvement of S100A4 in this process and offer new insights that could contribute to the diagnosis and treatment of BRCA. Full article

Background/Objectives: Lung cancer (LC) remains the leading cause of cancer-related death worldwide, despite advances in systemic and targeted therapies. A mechanism of survival of tumor cells is metabolic reprogramming, characterized by increased glucose uptake, aerobic glycolysis, and alterations in mitochondrial function. These adaptations seem to support tumor growth, immune evasion, and therapeutic resistance. In parallel, supportive care and specifically nutritional interventions have become essential components of modern oncology. The interplay between metabolic reprogramming and targeted nutritional strategies represents a promising area of investigation that bridges tumor biology with supportive care, aiming to enhance both therapeutic efficacy and patient quality of life. Methods: This narrative review explores the biological and pathophysiological rationale for the ketogenic diet (KD) as a possible complementary intervention in LC management and summarizes the published preclinical and clinical data supporting this rationale. Results: We discuss key aspects of tumor metabolism, including the Warburg effect, glucose dependency, oxidative stress regulation, fatty acid metabolism, lactate cycling and tumor microenvironment interactions, with particular emphasis on how carbohydrate restriction and ketosis may exacerbate mitochondrial dysfunction in cancer cells and modulate inflammatory pathways. Furthermore, we summarize available preclinical and clinical evidence evaluating the KD in oncology and, more specifically, in LC, focusing on feasibility, safety, metabolic effects, and potential synergy with chemotherapy, radiotherapy, and immunotherapy. Conclusions: While preclinical models suggest enhanced treatment efficacy, clinical data remain limited and heterogeneous, with patient adherence representing a major challenge. Further well-designed longitudinal studies are required to clarify the therapeutic role of the ketogenic diet in lung cancer. Full article

The development of selective and sustainable catalysts is essential to enable the chemical recycling of mixed plastic waste. In this work, calcium-modified biochars derived from cocoa pod husk (CPH) and palm kernel shell (PKS) were prepared for treating a mixture of poly(ethylene terephthalate) (PET) and poly(lactic acid) (PLA). The aim was to separate the mixture through the PLA methanolysis, while maintaining the PET unreacted for a potential physical recycling. Biochar was ex situ modified with calcium precursor using a value-added concentrate recovered from the hydrothermal treatment of Jatropha fruit husk. Subsequently, a pyrolysis step was further applied to convert the calcium species into CaO, which is the active phase for the methanolysis reaction. Structural, microscopic, and spectroscopic analyses revealed that the carbon matrix strongly influences the evolution and stabilization of calcium phases during pyrolysis and post-treatment. CPH-derived biochars promoted the formation of highly dispersed CaO, whereas PKS favored the growth of larger, less reactive Ca(OH)₂ domains. As a result, the CPH_Ca10 (i.e., 10% desired calcium loading based on CPH-biochar mass) catalyst exhibited superior basicity and catalytic activity, achieving near-complete PLA conversion under mild conditions (90–110 °C) depending on the system with only 2 wt.% catalyst. Importantly, under these mild conditions, PET remained chemically intact, demonstrating the process’s high selectivity and applicability to mixed bioplastic–fossil plastic streams. This study highlights a circular, low-carbon route to producing effective Ca-based catalysts from agricultural residues. It establishes a promising strategy for selective depolymerization and separation in complex plastic waste systems. Full article

Background: Idiopathic inflammatory myopathies (IIMs), characterized by muscle weakness and chronic inflammation, currently lack highly effective therapies. This study investigated the therapeutic potential and underlying mechanism of (5R)-5-hydroxytriptolide (LLDT-8), a triptolide derivative with reduced toxicity, using an experimental autoimmune myositis (EAM) mouse model and in vitro assays. Methods: Forty female BALB/c mice were randomly assigned to five groups: normal, vehicle, methylprednisolone (MP), LLDT-8 (0.0625 mg/kg), and LLDT-8 (0.125 mg/kg). EAM mice were treated with LLDT-8 (0.0625 or 0.125 mg/kg) or methylprednisolone as a positive control. Cellular experiments and molecular docking were performed to investigate potential mechanisms of LLDT-8. Results: LLDT-8 significantly attenuated clinicopathological features, including muscle weakness and pain sensitivity, while reducing serum levels of aspartate aminotransferase and lactate dehydrogenase. Histological analysis revealed that LLDT-8 reduced inflammatory cell infiltration and the presence of CD4⁺ and CD8⁺ T cells in muscle tissues. Mechanistically, LLDT-8 inhibited the expression of nucleotide-binding oligomerization domain receptor caspase recruitment domain 5 (NLRC5), a key transcriptional regulator of major histocompatibility complex-I (MHC-I). This suppression extended to downstream antigen presentation-related molecules, including the transporter associated with antigen processing and proteasome 20S subunit beta. Molecular docking further confirmed the high binding affinity of LLDT-8 to both NLRC5 and MHC-I. Conclusions: LLDT-8 alleviates inflammatory muscle injury by targeting the NLRC5/MHC-I signaling axis, suggesting it may be a promising therapeutic candidate for IIMs. Full article

Objectives: The Impella 5.5 (J&J MedTech, USA) is increasingly used for refractory cardiogenic shock (CS), yet early predictors of mortality and recovery remain unclear. This study aimed to evaluate early patient characteristics and device-related parameters in relation to clinical outcomes; to compare outcome-based phenotypic groups (native heart recovery (NHR), heart replacement therapy (HRT), and death on the device (DEC)); and to analyze P-level impact on hemolysis and acute kidney injury. Methods: This retrospective single-center study included 28 CS patients supported with Impella 5.5 between May 2023 and August 2024. Data included intensive care unit (ICU) hemodynamics, vasoactive-inotropic score (VIS), lab markers, and pump parameters. Primary analysis evaluated early (first 24 h) parameters as potential indicators associated with mortality on the device and recovery, while secondary analyses compared hemodynamic and pump performance parameters across outcome groups, evaluated the association between P-level and hemolysis, and assessed the impact of shock etiology on clinical outcomes. Results: Among 28 patients (mean age 56 years, 10.7% female, body mass index (BMI) 27.7 kg/m²), NHR occurred in 39.3% and bridged to HRT in 42.9%. Non-survivors (17.8%) had significantly higher lactate (3.1 vs. NHR: 1.9 vs. HRT: 1.4 mmol/L, p < 0.001) and VIS (307.0 vs. NHR: 18.8 vs. HRT: 12.6, p < 0.001) at implantation. Higher VIS values (>69) were strongly associated with mortality on the device, with 100% sensitivity and 77% specificity (area under the curve (AUC) = 0.86); VIS < 9.9 was related to NHR (AUC = 0.63, 94% sensitivity, 45% specificity). P-levels were not linked to hemolysis index (r = −0.03, p = 0.64) or lactate dehydrogenase (r = −0.06, p = 0.37). Conclusions: Early vasoactive burden was associated with clinical outcomes in Impella 5.5-supported patients. No association between P-levels and the analyzed hemolysis surrogates was detected in this cohort. Distinct phenotypes across recovery outcomes may guide personalized management, but prospective validation of this exploratory and hypothesis-generating analysis is needed. Full article

Two-dimensional Ti₃C₂O₂ MXene has emerged as a promising electrode material for non-enzymatic glucose sensing due to its metallic conductivity and biocompatibility. However, the atomic-scale sensing mechanism remains unclear. This DFT study uses the PBE functional with the D3(BJ) dispersion correction to elucidate glucose–MXene interactions under idealized vacuum conditions. Pristine Ti₃C₂O₂ shows metallic behavior with a density of states of about 8.2 states per electron volt at the Fermi level, dominated by Ti 3d states. β-d-glucose adsorbs onto the surface through hydrogen bonding, with an adsorption energy of −0.82 eV at a separation distance of 2.8 angstroms. Bader analysis indicates a transfer of about 0.15 electrons from MXene to glucose, resulting in a Fermi level shift of about −0.15 eV and an 18% reduction in the density of states at the Fermi level. These changes correspond to an estimated sensitivity of approximately 0.6 μA mM⁻¹ cm⁻² and a detection limit of about 17 µM, consistent with reported experimental performance of MXene-based sensors. Comparative adsorption calculations for common sweat interferents yield −0.45 eV for lactate and −0.25 eV for urea, indicating weaker interfacial affinity than glucose; these values reflect thermodynamic binding strength and possible surface occupation rather than definitive electrochemical selectivity, which additionally depends on redox potential, electron-transfer kinetics, and operating bias. We acknowledge three main limitations: first, the model considers only pure oxygen termination rather than mixed oxygen, hydroxyl, and fluorine terminations; second, the calculations are performed under vacuum rather than in aqueous conditions; third, the study is based on static zero kelvin structures rather than finite temperature dynamics. Despite these idealizations, the results provide baseline mechanistic insights to support rational design of MXene-based glucose sensors. Full article

We previously demonstrated that HBV promotes liver fibrosis through the enhanced production of pyruvate. Pyruvate kinase M2 (PKM2), a key enzyme in pyruvate metabolism, plays an important role in liver fibrogenesis. Recently, lactylation of PKM2 has been identified, which contributes to stabilize its catalytically active tetrameric conformation. Therefore, we hypothesize that PKM2 lactylation is involved in the regulation of HBV-induced liver fibrosis. In this study, we found that sera lactate levels were increased in CHB patients and HBV-Tg mice. Moreover, the lysine lactylation levels of proteins in liver tissues were significantly increased in the HBV-Tg mice. In LX2 cells, we found that pyruvate treatment significantly increased the profibrotic gene expression and lactylation level of PKM2, which promoted its tetramer-to-dimer transition, inhibited its pyruvate kinase activity, and facilitated its nuclear distribution. Through immunoprecipitation, we identified that pyruvate induced PKM2 lactylation at the K206 site. PKM2 knockdown or K206 mutation reduced PKM2 lactylation and abrogated the induction of profibrotic gene expression by pyruvate. Collectively, our findings indicate that HBV infection stimulated pyruvate production, which increased PKM2 lactylation at K206 to promote the expression of profibrogenic genes in HSCs, leading to liver fibrogenesis. Full article

Objectives: The mechanism of action of genes related to lactate metabolism in papillary thyroid carcinoma (PTC) is still unclear. In this study, key genes that play a role in PTC were selected from the known genes related to lactate metabolism, and their roles in promoting lactate metabolism in PTC cells were investigated. Methods: Through bioinformatics analysis and cell experiments, the roles of the relevant genes in lactate metabolism and their roles in the occurrence and development of PTC were verified. Results: Through bioinformatics analysis, 12 candidate genes were obtained. Through qRT-PCR experiments, it was confirmed that the expressions of TIMP1 and DPP4 were higher in thyroid papillary carcinoma than in normal PTC cells. By inhibiting the expression of TIMP1 and DPP4 using siRNA, the invasion and proliferation abilities of PTC could be reduced. Compared with normal thyroid cells, the contents of lactic acid and LDHA in PTC cells were higher. Knocking down the expression of TIMP1 and DPP4 would reduce the lactate production ability of PTC cells, and TIMP1 and DPP4 promoted the accumulation of lactate in PTC cells.Conclusions: In this study, by screening the differentially expressed lactate metabolism genes in PTC, different prognostic subtypes were constructed based on the molecular expression patterns. Multi-group student’s t-tests were conducted on the differential signaling pathways and tumor immune regulation of the prognostic subtypes, and a PTC prognosis prediction model was constructed. It was further confirmed that the lactate metabolism genes TIMP1 and DPP4 are highly expressed in PTC and can regulate the proliferation, invasion, metastasis and lactate metabolism of PTC cells. Full article

Background and Objectives: Pulmonary hypertension (PH) is a major contributor to morbidity and mortality in sickle cell disease (SCD), yet reliable and accessible biomarkers for cardiopulmonary risk stratification remain limited. This study aimed to evaluate whether the platelet-to-neutrophil ratio (PNR) is independently associated with echo-estimated PH (ePH) in adolescents and adults with SCD and to compare its predictive value with hemoglobin composition and genotype. Materials and Methods: A retrospective cohort study was conducted at King Fahd Hospital of the University, Al Khobar, Saudi Arabia (January 2019–January 2025). Clinical, laboratory, and echocardiographic data from 114 patients with confirmed SCD who underwent transthoracic echocardiography (TTE) were analyzed. ePH was defined as tricuspid regurgitant velocity (TRV) ≥ 2.5 m/s or pulmonary artery acceleration time (PAAT) ≤ 105 ms. Multivariable logistic and linear regression models were used to assess associations between PNR, hemoglobin fractions, genotype, and pulmonary pressure estimates. Results: Overall, 43% of patients met the criteria for ePH. PNR was not independently associated with ePH or TRV in adjusted analyses. In contrast, higher fetal hemoglobin (HbF) levels were independently associated with lower odds of ePH (adjusted OR 0.92 per 1% increase, 95% CI 0.86–0.98) and lower TRV values. The HbS/β⁰ genotype was significantly associated with increased odds of ePH (adjusted OR 5.44, 95% CI 1.37–24.0). Exploratory analyses demonstrated an inverse association between PNR and lactate dehydrogenase, suggesting that PNR reflects hemolytic activity rather than pulmonary vascular involvement. Conclusions: In this retrospective cohort of patients with SCD, PNR was not independently associated with ePH or TRV after multivariable adjustment. In contrast, hemoglobin composition and genotype, particularly higher HbF and the HbS/β⁰ genotype, were significantly associated with pulmonary pressure estimates. Full article

Heat stress is a major environmental stressor in poultry production that reduces growth performance and induces oxidative stress, inflammatory responses, and lung tissue injury. This study investigated the protective effects of dietary supplementation with Ginkgo biloba extract and tea polyphenols against heat stress-induced lung injury in broilers. A total of 320 one-day-old broilers were reared under standard management conditions until 21 days of age. Subsequently, 300 birds with similar body weight were selected and randomly allocated into six groups: a thermoneutral control group, a heat stress group, a heat stress group supplemented with 300 mg/kg tea polyphenols, and three heat stress groups receiving 300 mg/kg tea polyphenols combined with 100, 300, or 600 mg/kg Ginkgo biloba extract. The analysis of the results showed that heat stress significantly reduced the average daily gain and feed intake while increasing the feed conversion ratio. It also markedly increased serum lactate dehydrogenase activity and malondialdehyde levels, while decreasing antioxidant-related indicators, indicating the occurrence of oxidative stress and inflammatory responses. Histological examination revealed lung injury characterized by alveolar wall thickening, epithelial cell shedding, and disruption of the endothelial barrier, accompanied by upregulated expression of heat shock proteins and inflammation-related signaling genes. Supplementation with tea polyphenols alone partially alleviated these changes. Notably, the combined supplementation of Ginkgo biloba extract and tea polyphenols exerted more pronounced protective effects, significantly enhancing antioxidant capacity, attenuating inflammatory responses, and maintaining pulmonary barrier integrity. Among the tested levels, the groups receiving 300 mg/kg Ginkgo biloba extract in combination with tea polyphenols showed the most evident improvements. These findings suggest that the combined use of these plant-derived extracts effectively mitigates heat stress-induced lung injury in broilers. Full article

Background: Maternal vitamin D deficiency (VDD) compromises fetal skeletal development. The impact of postnatal vitamin D supplementation on osteocalcin (OC) carboxylation, converting undercarboxylated (ucOC) to carboxylated osteocalcin (cOC), in offspring remains unclear, given conflicting reports on the correlation between serum 25-hydroxyvitamin D (25(OH)D) and specific OC forms. This study investigated OC profile recovery in a mouse model of maternal VDD. Methods: Female C57BL/6J mice were fed a VDD diet from four weeks pre-conception through lactation. Weaned offspring were maintained on the VDD diet and randomized to three groups: control (saline), standard-dose (1500 IU/kg), or high-dose (4500 IU/kg) vitamin D supplementation. Serum 25(OH)D, cOC, and ucOC were quantified via ELISA at 1, 2, and 4 weeks post-intervention. Results: Controls remained vitamin D-deficient (<13 ng/mL). Supplementation dose-dependently increased serum 25(OH)D (p < 0.05). Crucially, while absolute ucOC levels remained stable across all groups, supplementation significantly upregulated cOC and total osteocalcin at all time points (p < 0.05). Consequently, the ucOC/cOC ratio significantly decreased in supplemented groups. Partial correlation analysis revealed a strong positive correlation between 25(OH)D and cOC (r_partial = 0.718) and a negative correlation with the ucOC/cOC ratio (r_partial = −0.433), but no correlation with ucOC (r_partial = −0.102). Conclusions: In offspring affected by maternal VDD, vitamin D supplementation improves the osteocalcin carboxylation profile primarily by driving carboxylated osteocalcin synthesis rather than reducing the undercarboxylated pool. Serum cOC and the ucOC/cOC ratio serve as superior functional biomarkers to ucOC for monitoring therapeutic efficacy in this early-life developmental model. Full article

Enterotoxigenic Escherichia coli (ETEC) causes severe intestinal infections in animals and threatens public health under the One Health framework. Most conventional studies focus on acute short-term ETEC infection, while natural persistent colonization oftern induces chronic intestinal mucosal compensatory remodeling in hosts. This study evaluated the protective effects of giant panda-derived Weissella confusa BSP201703 against chronic ETEC-induced intestinal damage using a giant panda fecal microbiota-associated (GPF) mouse model. Seventy-two Kunming mice were divided into six groups: blank control (C1), GPF control (C2), ETEC control (C3), and three W. confusa BSP201703 groups at low (1.0 × 10⁷ cfu/mL, W1), medium (1.0 × 10⁸ cfu/mL, W2), and high (1.0 × 10⁹ cfu/mL, W3) doses. Mice were first subjected to continuous ETEC challenge for 5 days to establish stable chronic intestinal injury, followed by a subsequent 5-day intervention with probiotic or sterile PBS for repairing existing damage. Growth performance, histopathology, serum D-lactate, SIgA, tight junction genes (ZO-1, Occludin, Claudin-1), and gut microbiota were analyzed. Histomorphologically, the chronic ETEC challenge induced compensatory increases in ileal villus height and crypt depth, which differed from typical acute necrotic atrophy. W. confusa BSP201703 mitigated ETEC-induced damage, reduced serum D-lactate (p < 0.05), increased SIgA, and upregulated tight junctions (p < 0.05). Microbial results demonstrated that medium-dose W2 maximized microbial diversity, while W1/W3 selectively enriched beneficial Bacteroidetes, Clostridium cluster IV, and Clostridium cluster XIVa taxa, confirming that moderate doses yielded optimal protection. In conclusion, W. confusa BSP201703 relieves ETEC injury by enhancing intestinal barrier function and regulating gut microbiota, highlighting its potential as a wildlife probiotic for One Health applications. Full article

Myocardial ischemia–reperfusion injury (MIRI) significantly limits the clinical benefits of reperfusion therapy, underscoring a pressing need for effective interventions. This study examines the cardioprotective effects and underlying mechanisms of the natural amide alkaloid N-p-trans-Coumaroyltyramine (p-CT). Using hypoxia/reoxygenation (H/R) models in neonatal rat cardiomyocytes and in vivo rat MIRI models, we assessed p-CT pretreatment on cell viability, cardiac function, serum injury markers (lactate dehydrogenase, creatine kinase-MB, cardiac troponin T, and myoglobin), myocardial histopathology, ultrastructural alterations, and infarct size. The systematic screening and validation of potential targets were conducted via label-free quantitative proteomics, molecular docking, and Western blot. The results demonstrated that p-CT pretreatment dose-dependently mitigated H/R-induced cellular injury, improved cardiac function in MIRI rats, reduced serum markers of myocardial damage, alleviated pathological and ultrastructural injury in myocardial tissue, and significantly diminished infarct size. Proteomic analysis revealed 19 differentially expressed proteins specifically reversed by p-CT, with Titin-cap (Tcap) exhibiting the most pronounced downregulation in the MIRI model—a change effectively restored by p-CT pretreatment. Molecular docking indicated strong binding affinity between p-CT and Tcap protein. In summary, p-CT represents a promising cardioprotective agent, likely exerting its effects by targeting Tcap protein and upregulating its expression, thereby helping preserve cardiomyocyte structural and functional integrity. Full article

This study evaluates the biological effectiveness of camel compound feeds produced using an optimized drying–grinding–extrusion technology and enriched with Artemisia lerchiana (wormwood). Building on a previously published process optimization study, the present work focuses on the effects of the developed feeds on milk productivity and quality in lactating camels. Eighteen lactating dromedary camels were randomly assigned to three dietary treatments (n = 6): a control diet without wormwood and experimental diets containing 10% and 15% wormwood (dry matter basis). The feeding trial lasted 45 days, including a 15-day adaptation period and a 30-day measurement period. Milk yield was recorded daily, and milk composition was analyzed weekly. Statistical analysis was performed using one-way and repeated-measures ANOVA (p < 0.05). Wormwood supplementation resulted in higher milk yield and significantly increased milk fat and protein content, with the strongest effects observed at the 15% inclusion level. No adverse effects on lactose content, physicochemical properties, or milk hygienic quality were detected. The results confirm that combining extrusion-based processing with phytogenic supplementation is an effective strategy for improving camel milk productivity. Full article