ObjectiveTo explore the role and potential mechanism of circulating glutamate in enhancing insulin sensitivity by aerobic exercise. This research may provide a novel strategy for preventing metabolic diseases through precise exercise interventions. MethodsTo investigate the effects of elevated circulating glutamate on insulin sensitivity and its potential mechanisms, 18 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into 3 groups: a control group (C), a group receiving 500 mg/kg glutamate supplementation (M), and a group receiving 1 000 mg/kg glutamate supplementation (H). The intervention lasted for 12 weeks, with treatments administered 6 d per week. Following the intervention, an insulin tolerance test (ITT) and a glucose tolerance test (GTT) were conducted. Circulating glutamate levels were measured using a commercial kit, and the activity of the skeletal muscle InsR/IRS1/PI3K/AKT signaling pathway was analyzed via Western blot. To further investigate the role of circulating glutamate in enhancing insulin sensitivity through aerobic exercise, 30 male C57BL/6 mice were randomly assigned to 3 groups: a control group (CS), an exercise intervention group (ES), and an exercise combined with glutamate supplementation group (EG). The ES group underwent treadmill-based aerobic exercise, while the EG group received glutamate supplementation at a dosage of 1 000 mg/kg in addition to aerobic exercise. The intervention lasted for 10 weeks, with sessions occurring 6 d per week, and the same procedures were followed afterward. To further elucidate the mechanism by which glutamate modulates the InsR/IRS1/PI3K/AKT signaling pathway, C2C12 myotubes were initially subjected to graded glutamate treatment (0, 0.5, 1, 3, 5, 10 mmol/L) to determine the optimal concentration for cellular intervention. Subsequently, the cells were divided into 3 groups: a control group (C), a glutamate intervention group (G), and a glutamate combined with MK801 (an NMDA receptor antagonist) intervention group (GK). The G group was treated with 5 mmol/L glutamate, while the GK group received 50 μmol/L MK801 in addition to 5 mmol/L glutamate. After 24 h of intervention, the activity of the InsR/IRS1/PI3K/AKT signaling pathway was analyzed using Western blot. ResultsCompared to the mice in group C, the circulating glutamate levels, the area under curve (AUC) of ITT, and the AUC of GTT in the mice of group H were significantly increased. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle were significantly downregulated. Compared to the mice in group CS, the circulating glutamate levels, the AUC of ITT, and the AUC of GTT in the mice of group ES were significantly reduced. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle of group ES mice were significantly upregulated. There were no significant changes observed in the mice of group EG. Compared to the cells in group 0 mmol/L, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in cells of group 5 mmol/L were significantly downregulated. Compared to the cells in group C, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in the cells of group G were significantly downregulated. No significant changes were observed in the cells of group GK. ConclusionLong-term aerobic exercise can improve insulin sensitivity by lowering circulating levels of glutamate. This effect may be associated with the upregulation of the InsR/IRS1/AKT signaling pathway activity in skeletal muscle. Furthermore, glutamate can weaken the activity of the InsR/IRS1/PI3K/AKT signaling pathway in skeletal muscle, potentially by binding to NMDAR expressed in skeletal muscle.

ObjectiveThe primary objective of this study was to investigate the effects of carbohydrate intake order on post-exercise recovery and metabolic regulation under heat stress, particularly in models of exercise induced fatigue. Given the increasing significance of optimizing nutritional strategies to support performance in extreme environmental conditions, this study aimed to provide experimental evidence that contributes to a better understanding of how the sequence in which carbohydrates are consumed impacts exercise recovery, metabolic homeostasis, and fatigue alleviation in a high-temperature environment. MethodsA mouse model of exercise-induced fatigue was established under high-temperature (35°C) to simulate heat stress. The subjects were divided into 3 distinct groups based on their carbohydrate intake order: the “mixed intake” group (HOT_MIX), where all macronutrients (carbohydrates, proteins, and fats) were consumed in a balanced ratio; the “carbohydrate-first intake” group (HOT_CHO), where carbohydrates were consumed first followed by other macronutrients; the “carbohydrate-later intake” group (HOT_PRO), where proteins and fats were consumed prior to carbohydrates. Each group underwent a 7 d intervention period with daily intake according to their designated group. Exercise performance was assessed using rotarod retention time test, and biomarkers of muscle damage, such as lactate dehydrogenase (LDH), creatine kinase (CK), lactate (LD), alanine aminotransferase (ALT), and non-esterified fatty acids (NEFA), were measured. Furthermore, targeted metabolomics analyses were conducted to investigate metabolic shifts in response to different dietary strategies, and KEGG pathway enrichment analysis was employed to explore the biological mechanisms underlying these changes. ResultsThe findings demonstrated that the HOT_PRO group exhibited a significantly improved performance in the rotarod test, with a longer retention time compared to both the HOT_MIX and HOT_CHO groups (P<0.05). Additionally, this group showed significantly reduced levels of muscle damage markers such as LDH and CK, indicating that the carbohydrate-later intake strategy helped alleviate exercise-induced muscle injury. Metabolomic profiling of the HOT_PRO group showed marked increases in alanine, creatine, and flavin adenine dinucleotide (FAD), indicating shifts in amino acid metabolism and oxidative metabolism. Conversely, metabolites such as spermidine, cholesterol sulfate, cholesterol, and serine were significantly reduced in the HOT_PRO group, pointing to alterations in lipid and sterol metabolism. Further analysis of the differential metabolites revealed that these changes were primarily associated with key metabolic pathways, including glycine-serine-threonine metabolism, primary bile acid biosynthesis, taurine and hypotaurine metabolism, and steroid hormone biosynthesis. These pathways are essential for energy production, antioxidant defense, and muscle recovery, suggesting that the carbohydrate-later feeding strategy may promote metabolic homeostasis and improve exercise recovery by enhancing these critical metabolic processes. ConclusionThe results of this study support the hypothesis that consuming carbohydrates after proteins and fats during exercise recovery enhances metabolic homeostasis and accelerates recovery under heat stress. This strategy effectively modulates energy, amino acid, and lipid-related pathways, which are crucial for improving endurance performance and mitigating fatigue in high-temperature environments. The findings suggest that carbohydrate-later intake could be a promising nutritional strategy for athletes and individuals exposed to heat during physical activity. Furthermore, the study provides valuable insights into how different nutrient timing strategies can impact exercise recovery and metabolic regulation, paving the way for more personalized and effective nutritional interventions in extreme environmental conditions.

The two core causes of obesity in modern lifestyle are high-fat diet (HFD) and insufficient physical activity. HFD can lead to disruption of gut microbiota and abnormal lipid metabolism, further exacerbating the process of obesity. The small intestine, as the “first checkpoint” for the digestion and absorption of dietary lipids into the body, plays a pivotal role in lipid metabolism. The small intestine is involved in the digestion, absorption, transport, and synthesis of dietary lipids. The absorption of lipids in the small intestine is a crucial step, as overactive absorption leads to a large amount of lipids entering the bloodstream, which affects the occurrence of obesity. HFD can lead to insulin resistance, disruption of gut microbiota, and inflammatory response in the body, which can further induce lipid absorption and metabolism disorders in the small intestine, thereby promoting the occurrence of chronic metabolic diseases such as obesity. Long term HFD can accelerate pathological structural remodeling and lipid absorption dysfunction of the small intestine: after high-fat diet, the small intestine becomes longer and heavier, with excessive villi elongation and microvilli elongation, thereby increasing the surface area of lipid absorption and causing lipid overload in the small intestine. In addition, overexpression of small intestine uptake transporters, intestinal mucosal damage induced “intestinal leakage”, dysbiosis of intestinal microbiota, ultimately leading to abnormal lipid absorption and chronic inflammation, accelerating lipid accumulation and obesity. Exercise, as one of the important means of simple, economical, and effective proactive health interventions, has always been highly regarded for its role in improving lipid metabolism homeostasis. The effect of exercise on small intestine lipid absorption shows a dose-dependent effect. Moderate to low-intensity aerobic exercise can improve the intestinal microenvironment, regulate the structure and lipid absorption function of the small intestine, promote lipid metabolism and health, while vigorous exercise, excessive exercise, and long-term high-intensity training can cause intestinal discomfort, leading to the destruction of intestinal structure and related symptoms, affecting lipid absorption. Long term regular exercise can regulate the diversity of intestinal microbiota, inhibit inflammatory signal transduction such as NF-κB, enhance intestinal mucosal barrier function, and improve intestinal lipid metabolism disorders, further enhancing the process of small intestinal lipid absorption. Exercise also participates in the remodeling process of small intestinal epithelial cells, regulating epithelial structural homeostasis by activating cell proliferation related pathways such as Wnt/β-catenin. Exercise can regulate the expression of lipid transport proteins CD36, FATP, and NPC1L1, and regulate the function of small intestine lipid absorption. However, the research on the effects of long-term exercise on small intestine structure, villus structure, absorption surface area, and lipid absorption related proteins is not systematic enough, the results are inconsistent, and the relevant mechanisms are not clear. In the future, experimental research can be conducted on the dose-response relationship of different intensities and forms of exercise, exploring the mechanisms of exercise improving small intestine lipid absorption and providing theoretical reference for scientific weight loss. It should be noted that the intestine is an organ that is sensitive to exercise response. How to determine the appropriate range, threshold, and form of exercise intensity to ensure beneficial regulation of intestinal lipid metabolism induced by exercise should become an important research direction in the future.

ObjectiveTo systematically review the modeling methods and analyzes the model alignment with clinical features of primary dysmenorrhea （PD） in both traditional Chinese medicine （TCM） and western medicine， providing theoretical and practical guidance for establishing the animal models of PD that better reflect the diagnostic and therapeutic characteristics of both TCM and western medicine. MethodsThe literature on PD animal models was searched against domestic and international databases such as PubMed， CNKI， and Wanfang Data. According to the diagnostic criteria of TCM and western medicine， the modeling methods in the literature were summarized， evaluated for strengths and weaknesses， and systematically assessed for clinical concordance rates to identify suitable reference models. ResultsThe available animal models of PD showed the average clinical concordance rates of 43.64% and 61.27% with the clinical features in TCM and western medicine， respectively. Commonly used modeling methods included estrogen administration， physical stimulation， and surgical intervention， with the estrogen combined with oxytocin model and the ice-water bath model being the most studied. The model of Qi stagnation and blood stasis syndrome that was established with the comprehensive stimulation method demonstrated the highest clinical concordance rate. ConclusionCurrent PD animal models primarily replicate dysmenorrhea and simulate menstruation， but they differ from human menstruation to some extent and cannot fully reflect the pathogenesis and physiological characteristics of PD. Moreover， except the cold coagulation and dampness stagnation syndrome and Qi stagnation and blood stasis syndrome， no animal models for other TCM syndromes have been reported， which limits comprehensive TCM research on this disease to a certain extent.

ObjectiveTo systematically review the modeling methods and analyzes the model alignment with clinical features of primary dysmenorrhea （PD） in both traditional Chinese medicine （TCM） and western medicine， providing theoretical and practical guidance for establishing the animal models of PD that better reflect the diagnostic and therapeutic characteristics of both TCM and western medicine. MethodsThe literature on PD animal models was searched against domestic and international databases such as PubMed， CNKI， and Wanfang Data. According to the diagnostic criteria of TCM and western medicine， the modeling methods in the literature were summarized， evaluated for strengths and weaknesses， and systematically assessed for clinical concordance rates to identify suitable reference models. ResultsThe available animal models of PD showed the average clinical concordance rates of 43.64% and 61.27% with the clinical features in TCM and western medicine， respectively. Commonly used modeling methods included estrogen administration， physical stimulation， and surgical intervention， with the estrogen combined with oxytocin model and the ice-water bath model being the most studied. The model of Qi stagnation and blood stasis syndrome that was established with the comprehensive stimulation method demonstrated the highest clinical concordance rate. ConclusionCurrent PD animal models primarily replicate dysmenorrhea and simulate menstruation， but they differ from human menstruation to some extent and cannot fully reflect the pathogenesis and physiological characteristics of PD. Moreover， except the cold coagulation and dampness stagnation syndrome and Qi stagnation and blood stasis syndrome， no animal models for other TCM syndromes have been reported， which limits comprehensive TCM research on this disease to a certain extent.

Metaflammation is a crucial mechanism in the onset and advancement of metabolic disorders, primarily defined by the activation of immune cells and increased concentrations of pro-inflammatory substances. The function of brain-derived neurotrophic factor (BDNF) in modulating immune and metabolic processes has garnered heightened interest, as BDNF suppresses glial cell activation and orchestrates inflammatory responses in the central nervous system via its receptor tyrosine kinase receptor B (TrkB), while also diminishing local inflammation in peripheral tissues by influencing macrophage polarization. Exercise, as a non-pharmacological intervention, is extensively employed to enhance metabolic disorders. A crucial mechanism underlying its efficacy is the significant induction of BDNF expression in central (hypothalamus, hippocampus, prefrontal cortex, and brainstem) and peripheral (liver, adipose tissue, intestines, and skeletal muscle) tissues and organs. This induction subsequently regulates inflammatory responses, ameliorates metabolic conditions, and decelerates disease progression. Consequently, BDNF is considered a pivotal molecule in the motor-metabolic regulation axis. Despite prior suggestions that BDNF may have a role in the regulation of exercise-induced inflammation, systematic data remains inadequate. Since that time, the field continues to lack structured descriptions and conversations pertinent to it. As exercise physiology research has advanced, the academic community has increasingly recognized that exercise is a multifaceted activity regulated by various systems, with its effects contingent upon the interplay of elements such as type, intensity, and frequency of exercise. Consequently, it is imperative to transcend the prior study paradigm that concentrated solely on localized effects and singular mechanisms and transition towards a comprehensive understanding of the systemic advantages of exercise. A multitude of investigations has validated that exercise confers health advantages for individuals with metabolic disorders, encompassing youngsters, adolescents, middle-aged individuals, and older persons, and typically enhances health via BDNF secretion. However, exercise is a double-edged sword; the relationship between exercise and health is not linearly positive. Insufficient exercise is ineffective, while excessive exercise can be detrimental to health. Consequently, it is crucial to scientifically develop exercise prescriptions, define appropriate exercise loads, and optimize health benefits to regulate bodily metabolism. BDNF mitigates metaflammation via many pathways during exercise. Initially, BDNF suppresses pro-inflammatory factors and facilitates the production of anti-inflammatory factors by modulating bidirectional transmission between neural and immune cells, therefore diminishing the inflammatory response. Secondly, exercise stimulates the PI3K/Akt, AMPK, and other signaling pathways via BDNF, enhancing insulin sensitivity, reducing lipotoxicity, and fostering mitochondrial production, so further optimizing the body’s metabolic condition. Moreover, exercise-induced BDNF contributes to the attenuation of systemic inflammation by collaborating with several organs, enhancing hepatic antioxidant capacity, regulating immunological response, and optimizing “gut-brain” axis functionality. These processes underscore the efficacy of exercise as a non-pharmacological intervention for enhancing anti-inflammatory and metabolic health. Despite substantial experimental evidence demonstrating the efficacy of exercise in mitigating inflammation and enhancing BDNF levels, numerous limitations persist in the existing studies. Primarily, the majority of studies have concentrated on molecular biology and lack causal experimental evidence that explicitly confirms BDNF as a crucial mediator in the exercise regulation of metaflammation. Furthermore, the outcomes of current molecular investigations are inadequately applicable to clinical practice, and a definitive pathway of “exercise-BDNF-metaflammation” remains unestablished. Moreover, the existing research methodology, reliant on animal models or limited human subject samples, constrains the broad dissemination of the findings. Future research should progressively transition from investigating isolated and localized pathways to a comprehensive multilevel and multidimensional framework that incorporates systems biology and exercise physiology. Practically, there is an immediate necessity to undertake extensive, double-blind, randomized controlled longitudinal human studies utilizing multi-omics technologies (e.g., transcriptomics, proteomics, and metabolomics) to investigate the principal signaling pathways of BDNF-mediated metaflammation and to elucidate the causal relationships and molecular mechanisms involved. Establishing a more comprehensive scientific evidence system aims to furnish a robust theoretical framework and practical guidance for the mechanistic interpretation, clinical application, and pharmaceutical development of exercise in the prevention and treatment of metabolic diseases.

OBJECTIVE: Asthma imposes a significant global health burden. This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios. METHODS: Using data from the Global Burden of Disease 2021 study, we analyzed asthma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled. Temporal trends in age-standardized incidence, prevalence, mortality, and DALY rates were explored using Annual Percent Change. RESULTS: In 2021, the age-standardized rates for asthma incidence, prevalence, mortality, and DALYs in China were 364.17 per 100,000 (95% uncertainty interval [ UI]: 283.22-494.10), 1,956.49 per 100,000 (95% UI: 1,566.68-2,491.87), 1.47 per 100,000 (95% UI: 1.15-1.79), and 103.76 per 100,000 (95% UI: 72.50-145.46), respectively. A higher disease burden was observed among Chinese men and individuals aged 70 years or older. Compared to the current trend, a combined scenario involving improvements in environmental factors, behavioral and metabolic health, child nutrition, and vaccination resulted in a greater reduction in the disease burden caused by asthma. CONCLUSION Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
Humans ; Asthma/mortality* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Child ; Adolescent ; Global Burden of Disease/trends* ; Child, Preschool ; Young Adult ; Infant ; Cost of Illness ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Infant, Newborn ; Aged, 80 and over ; Risk Factors

The cutaneous resident memory T cells(TRM)are important immune surveillance cells in skin tissue and are highly heterogeneous.The TRM achieve residency in skin by expressing residency markers such as CD69 and CD103,and their development and survival are regulated by several molecules such as interleukin-15(IL-15).In addition to their roles in infection and tumors,the TRM,especially CD8+TRM,play an important role in the development and recurrence of autoimmune skin diseases such as vitiligo.Under the continuous stimulation of melanocyte antigens,melanocyte-specific CD49a+TRM1 can directly kill the melanocytes by expressing the interferon-γ(IFN-γ),granzyme B and perforin and they also recruit circulating memory CD8+T cells through the IFN-γ-Janus kinase(JAK)-signal transducer and activator of transcription(STAT)(IFN-γ-JAK-STAT)signaling pathway to collectively kill the melanocytes,which promotes vitiligo development and recurrence.Combined with the research progress at home and abroad,this article now summarizes the source,function and biological properties of cutaneous TRM,provides an overview of the research on TRM in vitiligo development and recurrence,and elaborates on the strategy of intervening in the recurrence of vitiligo by targeting TRM,aiming to provide the new ideas for the pathogenesis research and precise treatment of vitiligo.

Iodine speciations in aquatic environments are affected by dissolved oxygen,redox potential,microbial activity,organic matter decomposition,light reaction,etc.Accurate quantification of iodine speciation can not only help to understand the geochemical cycle of iodine,but also help to trace and study environmental processes.Based on the combination of ion chromatography(IC)and inductively coupled plasma mass spectrometry(ICP-MS),a rapid and sensitive method was established for determining the speciations of iodine in environmental water samples including seawater,river water,lake water,rainwater,groundwater,etc.The results presented here showed that IO3?and I?in seawater were quickly separated and measured within 120 s when using guard column AG22 and 8 mmol/L(NH4)2CO3 as the mobile phase.While for lake water,river water and precipitation samples with high soluble organically bond iodine(SOI),an AS22 separation column(250 mm×4 mm)connected with a guard column and using 50 mmol/L(NH4)2CO3 as mobile phase could effectively separate unknown SOI from IO3? to achieve accurate quantification of IO3?.For accurate correction of iodine measurement signal fluctuations,133Cs was directly added to the(NH4)2CO3 mobile phase as an internal standard.The SOI content was calculated by the total iodine concentrations minus the sum of IO3?and I?.The precision of the established iodine speciation analytical method was better than 3.5%,and the standard addition experiment showed that the analytical method was accurate.When the injection volume was 25 μL,the detection limits were 0.011?0.025 μg/L for IO3? and 0.023?0.031 μg/L for I?,respectively.The method was successfully used to analyze IO3?,SOI and I? in environmental water samples,such as seawater,river water,rainwater and groundwater.

Ferric oxide/nitrogen-doped carbon nanomaterials(Fe2O3/N-C)with high oxidase-like activity were successfully synthesized via the wet chemistry and pyrolysis method using pyrrole and 1,2,3,4-butanetetracarboxylic acid as raw materials and ferric chloride as the oxidant.The structure and morphology of Fe2O3/N-C were characterized by the techniques including scanning electron microscopy,surface scanning elemental analysis,X-ray diffraction,X-ray photoelectron spectroscopy,and Fourier transform infrared spectroscopy.It was revealed that Fe2O3/N-C could efficiently catalyze the conversion of colorless 3,3',5,5'-tetramethylbenzidine(TMB)into blue-colored oxidized TMB(oxTMB).Based on the principle that ascorbic acid(AA)could inhibit the catalytic color-development reaction of Fe2O3/N-C on TMB,resulting in a paler color and a reduction in the absorbance of the system,a colorimetric sensor for sensitive and accurate detection of AA was constructed.The linear range of the sensor for AA detection was 0.25-30.0 μmol/L,and the detection limit was 0.1 μmol/L.Moreover,it was successfully applied to determination of AA in beverage and tablet samples with satisfactory results.