Male infertility remains a major global health concern. Conventional semen analysis offers limited explanatory power, with most cases remaining idiopathic, underscoring the urgent need for novel biomarkers and mechanisms. Exosomes, 30–150 nm extracellular vesicles that transfer proteins, RNAs, and bioactive molecules, have emerged as pivotal regulators of male reproductive function. Epididymosomes promote sperm maturation and capacitation by delivering proteins and antioxidants. Prostasomes act post-ejaculation, supporting capacitation, the acrosome reaction, and immune protection within the female reproductive tract. Testicular exosomes regulate early spermatogenesis, particularly by modulating spermatogonial stem-cell proliferation and differentiation. Seminal-vesicle exosomes influence motility and fertilization, while bulbourethral exosomes may modulate seminal pH, ion balance, and viscosity. Dysregulation of these exosomal pathways has been linked to oligozoospermia, asthenozoospermia, and teratozoospermia. This review integrates mechanistic and translational evidence across seminal plasma exosome subtypes, emphasizes their reproductive functions, and highlights their diagnostic and therapeutic potential, offering a foundation for exosome-based precision medicine in male infertility.

To evaluate the efficacy and safety of Linggui Yangyuan Paste (LG) in treating male infertility caused by asthenozoospermia (AZS) and oligoasthenozoospermia (OAZS) associated with the Chinese medicine (CM) pattern of Shen (Kidney) deficiency and blood stasis. This randomized, double-blind, double-dummy, parallel-group, multicenter clinical trial enrolled 162 male infertility patients at 5 hospitals in China from June 2023 to February 2024. Using block randomization within strata, participants were assigned (1:1) to LG + Wuzi Yanzong Oral Solution (WZ) placebo or WZ + LG placebo for 12 weeks (each LG 1 sachet and WZ 1 vial, twice daily), with a 12-week follow-up. The primary outcome was the change in total progressive motile sperm count (TPMSC) from baseline to week 12. Secondary outcomes included pregnancy rate, CM symptom score (CMSS), and semen parameters including semen volume (SV), sperm concentration (SC), total sperm count (TSC), progressive motility (PR), and PR + non-progressive motility (NP). Prespecified subgroup analyses on cumulative pregnancy rate and semen parameters were performed for participants with AZS and OAZS. Safety was monitored throughout the trial. Of 162 randomized participants, 145 completed the trial (75 in the LG group and 70 in the WZ group) and were included in the per-protocol analysis. At week 12, the LG group showed significantly greater improvement in TPMSC compared to the WZ group, with an adjusted between-group difference of 8.81 × 106 sperm (P<0.05, 95

Objective:To systematically identify medications potentially causing male infertility or sperm abnormalities and provide risk alerts for clinical practice. Methods:A pharmacovigilance study was conducted using the FAERS database (Q1 2004-Q2 2025) and EudraVigilance (EV) database (January 2002-October 2025). Adverse events related to male reproductive toxicity were screened using the MedDRA dictionary. Drug safety signals were detected using ROR, PRR, IC, and EBGM, with reliability enhanced through cross-database validation and dechallenge/rechallenge analyses. Results:The study included 1,955 FAERS cases and 1,384 from EV, with a median patient age of 35 years and 37% being reproductive-age males (18-44 years). The median time to event onset was 132 days, consistent with the spermatogenic cycle. Cross-validation identified 19 high-risk drugs, including hormonal agents (finasteride, dutasteride, testosterone), antineoplastic drugs (bleomycin, vinblastine, hydroxycarbamide), and antidepressants (citalopram, paroxetine). Finasteride satisfied both dechallenge and rechallenge criteria, providing strong evidence for causality. Signals concentrated in three major categories: genitourinary and sex hormones, dermatological preparations, and antineoplastic agents. Stratified analysis showed that both consumer and healthcare professional reports identified 13 high-risk drugs, with high consistency for major drugs (finasteride, testosterone), confirming result robustness. Conclusion:This pharmacovigilance study identified 19 high-risk drugs for male infertility across hormonal agents, antineoplastic drugs, and antidepressants. These findings underscore pre-prescription, risk-stratified fertility counseling for reproductive-age males, prioritizing sperm cryopreservation before chemotherapy and considering it selectively for 5α-reductase inhibitors, testosterone, or antidepressants.

GenX (HFPO-DA), a short-chain per- and polyfluoroalkyl substance (PFAS) substitute, is implicated in testicular toxicity. GenX-related genes were intersected with aging-associated genes to construct a GenX-Aging gene set. Single-cell RNA sequencing (scRNA-seq) data from human testicular aging (GSE254315) were analyzed to evaluate cell-type-specific aging sensitivity and intercellular communication dynamics. Male infertility transcriptomic datasets (GSE45885/GSE45887) were integrated, and least absolute shrinkage and selection operator (LASSO) regression combined with support vector machine recursive feature elimination (SVM-RFE) were applied to identify hub genes, which were validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in GenX-exposed rat testicular tissues. Spermatids exhibited the highest aging sensitivity, with progressive decline in intercellular communication. Four hub genes-SOD1, XRCC5, FOXO3, and POLB-demonstrated diagnostic value for male infertility. RT-qPCR confirmed computational predictions: SOD1, XRCC5, and FOXO3 were upregulated, while POLB was downregulated. Functional enrichment implicated FoxO signaling, cellular senescence, and DNA repair pathways. Molecular docking confirmed favorable GenX-protein binding interactions. SOD1, XRCC5, FOXO3, and POLB are candidate biomarkers for GenX-induced reproductive toxicity, with oxidative stress and genome maintenance as key pathological mechanisms.

This study aimed to establish Diagnostic criteria for kidney Yang deficiency syndrome in male infertility(referred to as &quot;this criteria&quot;). A preliminary questionnaire item pool was constructed through literature retrieval, in combination with male infertility-related textbooks, existing national standards, guidelines, and expert consensus documents, as well as expert interviews and group discussions. Two rounds of questionnaire surveys were conducted using the Delphi method to standardize the diagnostic criteria item pool and complete item supplementation and screening. Expert questionnaires were collected using the analytic hierarchy process(AHP) to statistically determine item weights and diagnostic thresholds. Finally, a diagnostic test was conducted by enrolling 105 participants to evaluate the diagnostic criteria, with sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio used as indicators of diagnostic efficacy at the established threshold. Based on the results of expert discussions, this criteria was established. After systematic literature screening, 66 articles were included. By incorporating textbooks, national standards, and consensus documents, all items were summarized, merged, and classified, resulting in an initial diagnostic criteria item pool of 39 items. The first round of the Delphi method retained 29 important items, and the second round retained 18 important items. AHP identified three levels of item weights, i.e., high, medium, and low. The primary symptoms for diagnosing kidney Yang deficiency syndrome in MI were finally determined as aversion to cold, soreness and weakness of the lower back and knees, a pale and swollen tongue, and a thin white tongue coating. The secondary symptoms were decreased libido, cold sensation in the lower abdomen or genital region, increased nocturnal urination, and a deep and weak pulse or a deep and slow pulse. Patients presenting all primary symptoms were diagnosed with this syndrome; patients presenting two primary symptoms together with any two manifestations from the secondary symptoms, physical signs, or pulse conditions were also diagnosed with this syndrome. After establishment of this criteria, 105 MI patients from the Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences were enrolled. Eligible participants were diagnosed using both the evaluated this criteria and the reference diagnostic criteria. The diagnostic efficacy of this criteria showed a sensitivity of 0.91, specificity of 0.88, and accuracy of 0.89. This study established Diagnostic criteria for kidney Yang deficiency syndrome in male infertility and completed clinical validation, providing a reference basis for the clinical diagnosis of MI with kidney Yang deficiency syndrome.

With rapid industrialization and urbanization, environmental pollutants have emerged as a major threat to male reproductive health, and declining semen quality and rising rates of male infertility have now become a global public health concern. Owing to its high energetic demand and specialized cellular organization, the testis is especially vulnerable to pollutants, with mitochondria serving as a principal target because they coordinate energy metabolism and apoptotic control. Here we synthesize evidence on how heavy metals, air pollutants, organic pollutants, endocrine-disrupting chemicals, micro(nano)plastics, pesticides, and mycotoxins injure testicular mitochondria and the mechanisms involved. Current evidence indicates that these pollutants compromise spermatogenesis and androgen production via convergent mitochondrial pathways, including oxidative stress, metabolic disruption, mitochondria-dependent apoptosis, imbalance of mitochondrial dynamics, suppressed biogenesis, and dysregulated mitophagy. Importantly, these mechanisms are not independent, since individual pathways may dominate under specific exposure scenarios, yet they can also intersect and mutually reinforce one another to generate a multistep cascading network that culminates in reproductive injury. Therefore, mitochondrial dysfunction represents a central convergent node through which pollutants drive male reproductive toxicity. Future work should prioritize low-dose, long-term, and mixture exposure models, integrate multi-omics approaches with testicular organoid platforms, define key regulatory pathways, identify early biomarkers, and evaluate mitochondria-targeted interventions to support environmental risk assessment and prevention of male reproductive injury.

Objective: To evaluate the association between di(2-ethylhexyl) phthalate (DEHP) exposure and testosterone deficiency in adult men, and to explore molecular changes and candidate compounds related to DEHP-associated male reproductive toxicity. Methods: We used a multi-level integrative strategy. Computational toxicology predicted DEHP endocrine-disrupting potential. In NHANES 2013–2016 adult males, survey-weighted logistic regression and restricted cubic splines assessed associations between urinary DEHP metabolites and testosterone deficiency. Male Sprague-Dawley rats were exposed to DEHP to evaluate sex hormones, testicular/epididymal histopathology, oxidative stress, inflammation, and CD68⁺ macrophage infiltration. Integrated infertility transcriptomes with ensemble machine learning identified hub genes, which were mapped in testicular single-cell RNA-seq with virtual knockout–based network inference. Connectivity Map screening plus molecular docking and molecular dynamics prioritized candidate compounds. Results: In NHANES, oxidative DEHP metabolites (MEHHP, MEOHP, and MECPP) were associated with increased odds of testosterone deficiency and showed monotonic dose-response increases. Rat experiments showed that DEHP reduced testosterone accompanied by decreased FSH/LH levels, disrupted testicular structure and spermatogenesis, and increased oxidative stress, inflammatory markers, and macrophage infiltration. Hub genes (NNT, ACSS1, NANOG, S100A16, and CELF4) were mainly involved in mitochondrial energy metabolism and redox homeostasis. CMap screening and in silico analyses prioritized ursolic acid as a candidate compound, with the predicted ursolic acid–ACSS1 complex showing relative stability in molecular dynamics simulation. Conclusion: DEHP exposure was associated with testosterone deficiency in men and induced reproductive toxicity in rats. Integrated analyses highlighted candidate metabolic, redox, inflammatory, and Sertoli cell-related network alterations. Ursolic acid was computationally prioritized as a candidate compound, but experimental validation is required.

Microplastics (MPs) are pervasive environmental contaminants detected across air, water, soil, and food chains. Their presence in human reproductive tissues has raised concern that MP exposure may contribute to the global decline in male reproductive health. This review summarizes recent progress in animal models used to investigate MP-induced male reproductive toxicity, with particular attention to key design variables, including animal strain and age, polymer type, particle size, dose, exposure route, and exposure duration, as well as the rationale for their selection. We also summarize the major mechanisms implicated in MP-associated reproductive toxicity, including oxidative stress, inflammation, endocrine disruption, programmed cell death, mitochondrial dysfunction, and epigenetic alterations. Current models remain highly heterogeneous, often rely on exposure doses with limited environmental relevance, and provide incomplete mechanistic resolution. Future work should prioritize standardized model design, multi-omics integration, and improved monitoring of human MP exposure and epidemiological surveillance of male reproductive outcomes. Collectively, this review aims to support the refinement of animal models and provide an integrated mechanistic framework for toxicological assessment of MPs.

ETHNOPHARMACOLOGICAL RELEVANCE:Didang Tang (DDT), a classic traditional Chinese medicine formula, possesses the effects of activating blood circulation, resolving stasis, reducing swelling, and alleviating pain. It has demonstrated significant therapeutic efficacy in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), effectively relieving clinical symptoms and improving remission rates. However, its underlying molecular mechanisms remain incompletely elucidated. AIM OF THE STUDY:The present study aimed to investigate the therapeutic effects of DDT on CP/CPPS and to elucidate the potential mechanisms by which it ameliorates prostatic tissue injury. MATERIALS AND METHODS:A CFA-induced CP/CPPS-like prostatitis rat model was established by intra-prostatic injection of Freund's complete adjuvant in male Sprague-Dawley (SD) rats. DDT was administered by oral gavage to evaluate its therapeutic efficacy. Following tissue collection, proteomic and transcriptomic analyses were performed to explore the molecular mechanisms of DDT action. Single-cell RNA sequencing (scRNA-seq) was employed to investigate the causal relationship between necroptosis and CP/CPPS, thereby laying the foundation for clarifying the complex pathogenesis of this disease. Histological changes in prostatic tissue, levels of necroptosis, NETs formation, and expression of the RIPK3/MLKL signaling pathway were assessed using hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), immunofluorescence (IF), Western blot. RESULTS:DDT effectively reduced the level of necroptosis, decreased NETs formation, and improved histopathological injury in the CFA-induced CP/CPPS-like rat model. Proteomic and transcriptomic analyses further suggested that the protective effects of DDT in this prostatitis-like inflammatory injury model may be associated with the regulation of necroptosis-related pathways and NETs formation. CONCLUSIONS:This study provides initial experimental evidence showing that representative necroptosis-related pathway markers and NETs-associated markers are upregulated in a CFA-induced CP/CPPS-like animal model. DDT treatment dose-dependently attenuated the expression of these markers and improved prostatitis-like histopathological injury. These findings suggest that suppression of necroptosis-associated HMGB1 release and NETs formation may represent one possible mechanism by which DDT exerts its protective effects in prostatitis-like inflammatory injury. This study provides supportive evidence for the potential application of traditional Chinese medicine in prostatitis-like inflammatory conditions and offers a basis for further mechanistic and therapeutic studies.

AbstractEthnopharmacological relevanceDidang Tang (DDT), a classic traditional Chinese medicine formula, possesses the effects of activating blood circulation, resolving stasis, reducing swelling, and alleviating pain. It has demonstrated significant therapeutic efficacy in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), effectively relieving clinical symptoms and improving remission rates. However, its underlying molecular mechanisms remain incompletely elucidated.Objective: The present study aimed to investigate the therapeutic effects of DDT on CP/CPPS and to elucidate the potential mechanisms by which it ameliorates prostatic tissue injury.Materials and Methods: A CP/CPPS rat model was established by intra-prostatic injection of Freund’s complete adjuvant in male Sprague-Dawley (SD) rats. DDT was administered by oral gavage to evaluate its therapeutic efficacy. Following tissue collection, proteomic and transcriptomic analyses were performed to explore the molecular mechanisms of DDT action. Single-cell RNA sequencing (scRNA-seq) was employed to investigate the causal relationship between necroptosis and CP/CPPS, thereby laying the foundation for clarifying the complex pathogenesis of this disease. Histological changes in prostatic tissue, levels of necroptosis, NETs formation, and expression of the RIPK3/MLKL signaling pathway were assessed using hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), immunofluorescence (IF), Western blot, and quantitative real-time PCR (qRT-PCR).Results: DDT effectively reduced the level of necroptosis, decreased NETs formation, and improved histopathological scores in the CP/CPPS rat model. Proteomic and transcriptomic analyses revealed that the therapeutic effects of DDT on CP/CPPS are closely associated with the regulation of necroptosis and NETs production.Conclusion: This study is the first to validate the critical roles of necroptosis and NETs formation in CP/CPPS. The findings provide experimental evidence supporting the use of traditional Chinese medicine for CP/CPPS and lay a foundation for further research and development of novel therapeutic strategies.

Varicocele is a common cause of male infertility, but the mechanisms by which it disrupts testicular homeostasis and impairs spermatogenesis remain incompletely elucidated. This article reviews current evidence on the multifactorial disturbances in the testicular microenvironment induced by varicocele, with a focus on hemodynamic, biochemical, and structural abnormalities. Anatomical predisposition, venous valve incompetence, and impaired venous return collectively lead to chronic venous hypertension, causing progressive dilation of the pampiniform plexus and severe hemodynamic dysregulation. These primary vascular abnormalities subsequently establish a foundation for downstream cellular damage, including testicular hyperthermia, hypoxia, and metabolic stress. Among these pathological processes, oxidative stress is widely recognized as a central mediator of testicular injury. Excessive reactive oxygen species overwhelm intrinsic antioxidant defenses, disrupt mitochondrial function, damage germ cell DNA, and impair epididymal sperm maturation, ultimately leading to reduced sperm concentration, motility, and viability. Simultaneously, elevated inflammatory cytokines and immune dysregulation further compromise Sertoli and Leydig cell function, activate inflammasome signaling and amplify inflammatory injury. These inflammatory signals also synergize with oxidative damage to disrupt the blood–testis barrier, resulting in increased permeability, autoimmune activation, and accelerated loss of germ cells. Structural impairment of the seminiferous epithelium, mitochondrial dysfunction, and the activation of intrinsic and extrinsic apoptotic pathways further exacerbate spermatogenic failure. Ultimately, varicocele induces a multifaceted and sustained cycle of testicular microenvironment disruption, impairing spermatogenesis at multiple levels—from Sertoli cell function and blood–testis barrier integrity to germ cell survival and sperm DNA stability.

Floods are severe natural disasters threatening the world, and their long-term evolution patterns are crucial for regional security and sustainable development. Based on the hydrological model HYDROTREND, combined with the Generalized Extreme Value (GEV) analysis and scenario simulation experiments, this study reconstructs annual peak flow over the past 2000 years in the Yalu River and quantitatively analyzes the differential impacts of climate change and human activities on floods of different intensities. The GEV analysis provides long-term baseline estimates of return-period flood magnitudes, allowing the relative responses of floods with different intensities to climate change and human activities to be evaluated. Scenario simulations indicate that the impacts of human activities (reservoir regulation and changes in forest coverage) on floods decrease with increasing flood intensity, whereas the opposite applies to climate change: small-to-medium floods are more significantly influenced by human activities (both reservoir and forest effects >23%), while extreme floods are more sensitive to climate change (>27.06%). Comparison with the long-term evolution of large-scale climate modes suggests that variations in flood intensity in the Yalu River Basin are broadly consistent with the Pacific Decadal Oscillation (PDO), and tend to strengthen (weaken) during El Niño (La Niña) events. This study quantifies the differential impacts of climate change and human activities on floods of varying intensities in the Yalu River basin, and provides a scientific basis for basin-scale flood risk assessment and management under changing climatic and human activity conditions.

The incidence of obesity and male infertility continues to rise, and a complex pathophysiological association exists between the two. However, the comorbid molecular mechanisms remain incompletely elucidated. In this study, bioinformatics and machine learning methods were integrated to systematically explore the shared mechanisms of obesity and male infertility, and to predict natural compounds and TCMs with therapeutic potential based on multi-omics data. Datasets of male infertility and obesity were obtained from the GEO database, and 43 intersecting genes were identified through differential expression analysis. Using three machine learning algorithms, including random forest, least absolute shrinkage and selection operator(LASSO) regression, and support vector machine(SVM), five Hub genes(MAP4K4, GPT2, ADSSL1, PAIP2, and GINS3) were screened. The combined diagnostic model achieved an area under the curve(AUC) greater than 0.8, indicating good diagnostic performance. Functional enrichment analysis revealed that these genes are mainly involved in key biological processes such as amino acid metabolism, cell migration, and DNA replication. Immune infiltration analysis showed a significant upregulation of central memory CD4~+ T cells in both diseases, suggesting that chronic immune activation is an important basis for their comorbidity. Single-cell sequencing and pseudotime analyses demonstrated disordered cell differentiation trajectories in the adipose tissue of obese patients and the testicular tissue of infertile patients. Based on the connectivity map(CMap) database, ten natural compounds, including berberine, curcumin, and ginsenosides, were predicted and further validated by molecular docking to have strong binding affinities with the Hub genes. Integration with the traditional Chinese medicine systems pharmacology(TCMSP) platform enabled the construction of a &quot;target-natural compound-herbal medicine&quot; interaction network, identifying 38 corresponding herbal medicines. Property and meridian analysis indicated a predominance of warm nature, sweet flavor, and liver meridian tropism, consistent with the TCM therapeutic principles of &quot;resolving phlegm and dampness, strengthening the spleen, and tonifying the kidney&quot;. This study reveals, at the molecular level, the comorbid mechanisms of obesity and male infertility in immune-inflammatory regulation and cell differentiation dysfunction, providing a theoretical basis and potential drug targets for precise TCM intervention in obesity-related male infertility.

Abstract Ornidazole (ORN) can induce male reproductive toxicity, but its pathological features and metabolic mechanisms remain incompletely defined. In this study, approved by the Institutional Animal Care and Use Committee of Xiyuan Hospital (No. 2021XLC051), 96 six-week-old male Sprague–Dawley rats were randomly assigned to eight groups, including six ORN-treated groups and two vehicle controls. ORN was administered orally at 200, 400, or 800 mg/kg/day for 14 or 28 days. The 14-day regimen evaluated early epididymal sperm effects, whereas the 28-day regimen assessed broader spermatogenic injury. Body weight, reproductive organ indices, sperm parameters, sex hormones, histopathology, ultrastructure, and targeted energy metabolomics of testicular and epididymal tissues were examined. No obvious reproductive toxicity was observed after 14 days of exposure or after 28 days at 200 mg/kg. However, 400 mg/kg for 28 days significantly reduced sperm motility with minimal histopathological changes, increased luteinizing hormone (LH), and decreased testosterone (T), consistent with asthenozoospermia. In contrast, 800 mg/kg for 28 days markedly decreased sperm concentration and motility, caused prominent testicular and epididymal injury, increased follicle-stimulating hormone (FSH) and LH, and reduced T, consistent with oligoasthenozoospermia. Metabolomic analysis showed that ORN disrupted glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway in reproductive tissues, accompanied by altered energy-related metabolites and reduced ATP levels. These findings demonstrate dose-dependent ORN-induced male reproductive toxicity and suggest that perturbation of energy metabolism contributes to impaired sperm motility and spermatogenesis, providing experimental models and mechanistic insight for drug-induced male reproductive injury and future toxicological risk assessment studies.

Rivers are increasingly affected by dams and reservoirs, which impact the source and transport of riverine particulate organic carbon (POC), and by extreme events, which present an important climatic stressor for river ecosystems. How and to what extent water regulation and extreme events affect POC lability, however, remain poorly constrained. By studying the POC characteristics within the Yangtze River Basin in normal and extreme drought-heatwave years, we find that during a normal year water storage by the Three Gorges Reservoir increases the proportion of algae-derived POC (by 26 +/- 4%) compared to water drainage, leading to a higher proportion of labile POC and younger POC age. During the extreme drought-heatwave year, the drought-heatwave event increases proportions of algae-derived POC and labile POC (by 19 +/- 11% and 18 +/- 8%, respectively) in the whole Yangtze River Basin, with a greater increase in the Three Gorges Reservoir (by 34 +/- 7% and 29 +/- 3%, respectively; compared with the non-Three Gorges Reservoir areas, P < 0.01), whilst resulting in a 29 +/- 6% reduction in export POC flux to the East China Sea. We use our findings from the Yangtze River Basin to assess the global impact of dams and reservoirs, and estimate that the global riverine export POC flux has decreased from pre-dam 190 +/- 5 Tg C/yr to post-dam 97 +/- 48 Tg C/yr. We also posit that the additional increase in POC lability and decrease in export POC flux during an extreme drought-heatwave event in the Yangtze River Basin occurs in other major river systems as well. Combined we assert that more frequent extreme drought-heatwave events will compound the effects of damming, resulting in an increasingly labile and thus more readily remineralized riverine POC source and a decreasing export POC flux into the near-shore environment. Our results provide critical insights into assessing and mitigating the effects of combined damming and extreme drought-heatwave events on the organic carbon cycle in river systems.

Rivers are crucial to biogeochemical cycles, connecting terrestrial, oceanic, and atmospheric systems. However, their ecosystems are increasingly threatened by extreme weather events. Here we used the environmental DNA approach to assess the impact of extreme drought-heatwave events on the aquatic plankton communities of the Yangtze River. We showed that an extreme drought-heatwave event reduced the alpha diversity of communities, increased their beta diversity, and simultaneously simplified and destabilized community network structure. This event also shifted the dominant algae taxa from Bacillariophyta to Cyanobacteria, accompanied by increases in organic carbon and labile organic carbon contents. Globally, temperature rises during this extreme drought-heatwave event are more pronounced in high-latitude regions, likely amplifying impacts on river ecosystem biodiversity and stability. Our findings highlight the vulnerability of river ecosystems to extreme events and underscore the need to mitigate climate change's effects on river ecosystems.

Climate warming is increasingly influencing oceanic physical processes and biogeochemistry. Among these processes, the offshore transport of nearshore terrestrial materials significantly impacts the ecological environment of shelf seas. Due to the widespread presence and high activity of shelf fronts, the instability of the mixing layer implies that the offshore transport of nearshore materials is a common phenomenon. However, the impact of offshore transport on primary production (PP) in the outer continental shelf remains unclear. Here, we investigated the offshore transport processes of terrestrial materials in the South Yellow Sea (SYS), particularly under the influence of climate warming, and assessed its impact on phytoplankton PP. By analyzing sedimentary records and satellite data (2003-2022), and employing methods such as machine learning with long short-term memory (LSTM) neural networks, we discovered that over the past two centuries, warming in the Western Pacific has possible resulted in a significant increase in both offshore transport flux (28.5 %) and biogenic silica (51.7 %). Our research indicates that over the last 20 years, marine PP outside the front has shown an increasing trend (7.9 %), positively correlated with enhanced offshore transport flux and increased front intensity (horizontal temperature gradient). Furthermore, the offshore transport process during the spring phytoplankton blooms (SPB) appears to play a critical role in this trend. These findings highlight that the often-neglected offshore transport flux has a significant impact on ocean marine PP and demonstrates sensitivity to climate change.

Atherosclerosis, a metabolic disease characterized by the formation of plaques consisting of a combination of cholesterol, calcium, fibrin, and other impurities in blood vessels, is a key risk factor for the development of a variety of cardiovascular and cerebrovascular diseases and a global health problem that needs to be addressed urgently. Vascular smooth muscle cells(VSMCs) are the main cell type in atherosclerotic plaques, and many studies have confirmed that the proliferation, migration, and phenotypic transformation of VSMCs are important driving factors for the development of atherosclerosis. VSMCs have a high degree of plasticity, and in the physiological state, VSMCs are responsible for maintaining vasoconstriction and vasodilation and supporting the normal physiological structure of the blood vessels. In case of tissue injury, abnormal lipid metabolism, and abnormal infiltration of inflammation, VSMCs can be de-differentiated into the synthetic type and possess abnormal proliferation and migration capabilities, which will lead to luminal stenosis, plaque accumulation and even rupture. The multi-target and multi-pathway holistic treatment of traditional Chinese medicine(TCM) is consistent with the complexity of this pathological process. Therefore, the intervention of TCM targeting VSMCs may be a new breakthrough. Based on the existing evidence, this study systematically reviewed the research progress of TCM targeting VSMCs proliferation, migration, and phenotypic transformation to intervene in atherosclerosis, with a view to providing evidence support for the clinical diagnosis and treatment of atherosclerosis with TCM and the exploration of the biological basis of atherosclerosis.

Background:Lycii Fructus (dried goji berry), the dried ripe fruit of Lycium barbarum L., has long been used in traditional Chinese medicine for its functions of tonifying the kidney, nourishing essence, soothing the liver, and improving vision. It has been widely applied to enhance male reproductive function. In recent years, modern pharmacological studies have revealed that Lycii Fructus is rich in various bioactive metabolites, particularly Lycium barbarum polysaccharides, betaine, carotenoids, and flavonoids, which exhibit antioxidant, anti-apoptotic, and hormone-regulating effects. This review aims to systematically summarize existing clinical and mechanistic studies on the protective effects of Lycii Fructus and its key metabolites on male infertility. Methods:A literature survey was conducted on studies reporting the effects of Lycii Fructus and its bioactive metabolites on male reproductive parameters, including spermatogenesis, hormone regulation, testicular structure, and molecular signaling pathways. Results:Evidence suggests that Lycii Fructus and its metabolites can improve male reproductive function and sperm quality by modulating the hypothalamic-pituitary-gonadal axis, alleviating oxidative stress, inhibiting testicular cell apoptosis, suppressing pro-inflammatory factors, reducing testicular fibrosis, and regulating autophagy. Animal studies have shown that these effects may be mediated through key signaling pathways such as PI3K/Akt, SIRT1/Nrf2, and AMPK/PGC-1α, thereby enhancing testicular steroidogenesis and antioxidant capacity, among other benefits, and mitigating reproductive damage induced by diabetes, obesity, radiation, and environmental toxins. Although clinical evidence supporting the use of Lycii Fructus alone to improve male infertility is still lacking, traditional Chinese medicine compound formulas containing Lycii Fructus have demonstrated good efficacy and safety in treating oligoasthenozoospermia. Given the increasing attention to the safety and preventive health potential of natural botanical medicines, Lycii Fructus is emerging as a promising natural therapeutic agent for the treatment of male infertility. Conclusion:Lycii Fructus and its metabolites show promising therapeutic potential for male infertility by improving sperm quality, protecting testicular structure and function, and mitigating damage induced by various stressors.