마황 (규제)

Systemic lupus erythematosus(SLE) is a chronic multi-organ autoimmune disorder. Tripterygium wilfordii, a medicinal herb, possesses immunomodulatory and anti-inflammatory properties. Tripterygium glycosides(TG), as the active ingredients, are widely used in the treatment of autoimmune diseases such as SLE and rheumatoid arthritis(RA) due to their definite efficacy and are prepared into tablets for easy administration. Following the PRISMA and PRIO-Harm guidelines, this study employs a prospective registration protocol(CRD420251023354), umbrella review, and network pharmacology, molecular docking, and molecular dynamics simulation to systematically evaluate the efficacy, safety, and potential molecular mechanism of TG in the treatment of SLE. Eight databases were systematically searched. Four Meta-analyses evaluating TG combined with chemotherapy in the treatment of SLE were obtained, and their methodological quality(AMSTAR2), risk of bias(ROBIS-2), and evidence certainty(GRADE) were evaluated. At the same time, network pharmacology was employed to predict the mechanism of TG and evaluate the binding of active ingredients to targets. The results of umbrella review showed that TG significantly ameliorated SLE in terms of the renal function, immune indexes, blood parameters, and disease activity, reduced adverse reactions such as nausea, vomiting, and rash, increased the risk of irregular menstruation, and caused no significant difference in other infection risks. The methodological quality assessment found that the four systematic reviews had serious deficiencies(75% of the non-pre-registered programs and 50% of the non-exclusion lists). ROBIS-2 confirmed that all studies had a high risk of bias. GRADE classification showed that 50% of the evidence had moderate or low quality. Network pharmacology identified potential targets of TG, such as TNF and TP53, which were involved in PD-L1 expression and PD-1 checkpoint pathway in cancer and other signaling pathways. Molecular docking and kinetic simulation showed that TG might play a role by stabilizing the binding of triptoditerpenic acid B to EGFR and HIF1A. In summary, TG can significantly improve multi-system indica

BACKGROUND: Ankylosing spondylitis (AS) is a chronic autoimmune disorder, accompanied by a notably high disability rate and limited treatment options. White peony root is a classic nourishing Chinese medicinal herb with immune-modulating effects. Its glycoside components-Total glucosides of paeony (TGP), a natural compound, exhibits anti-inflammatory and immunomodulatory effects. However, little is currently known about the efficacy and safety of TGP therapy for treating AS. PURPOSE: This study aimed to provide evidence-based support for the efficacy and safety of TGP in treating ankylosing spondylitis and to explore the potential mechanisms underlying TGP therapy for this disease. METHODS: A search strategy combining keywords and free-text terms was employed to retrieve studies from eight databases: CBM, CNKI, VIP, Wanfang, Embase, PubMed, Cochrane Library, and Web of Science. Statistical analysis was conducted using RevMan 5.4 software, with evidence quality assessed via the GRADE system. Additionally, network pharmacology, molecular docking, and molecular dynamics simulations (constant pressure for 100 ns) were utilized to further analyze the potential targets and pathways involved in TGP's therapeutic effects on AS. RESULTS: The meta-analysis ultimately included 28 studies involving 2,130 patients, with results indicating that the TGP combination therapy group significantly improved spinal function in AS patients, reduced inflammatory responses, enhanced quality of life, and played a crucial role in anti-inflammatory and immune modulation with favorable safety profiles. The therapeutic targets of TGP in AS include TLR4, NFKB1, HSP90AA1, HIF1A, MTOR, ITGB1, and CXCR4, with its mechanism of action linked to TLR and NF-κB pathways. Molecular docking and MD simulations revealed benzoylpaeoniflorin exhibits the strongest binding affinity, suggesting TGP may regulate AS pathogenesis by interacting with TLR4. CONCLUSION: TGP demonstrates favorable clinical efficacy in treating AS, with a multi-targeted intervention mechanism that holds therapeutic promise. SYSTEMATIC REVIEW REGISTRATION: The study was prospectively registered in PROSPERO (Registration No. CRD: 4202

OBJECTIVE: The application of Traditional Chinese Medicine (TCM) in managing metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted growing interest in the academic community. However, a comprehensive quantitative analysis of its therapeutic effects on MASLD remains lacking. This research seeks to analyze the current landscape and research trends in TCM treatment for MASLD from 2000 to 2025, thereby offering insights and guidance for future investigations. METHODS: We extracted relevant literature published from 2000 to 2025 from the Web of Science and Scopus databases. The collected data were then processed, analyzed, and graphically represented using Origin, R software, VOSviewer, and CiteSpace. RESULTS: A total of 889 articles (from Web of Science) and 983 articles (from Scopus) were included in the study. From 2000 to 2025, the number of publications demonstrated a consistent upward trend, with particularly significant growth occurring between 2019 and 2022, followed by a slight decline in 2023. China is the leading country in publication output and holds a pivotal position in fostering international research collaboration. The Journal of Ethnopharmacology is the most productive journal in this area. Current research hotspots primarily center on exploring the potential mechanisms of TCM interventions for MASLD, their clinical applications, and the identification and utilization of bioactive components. Mechanistic studies mainly focus on "regulating lipid metabolism," "anti-inflammatory and anti-fibrotic effects," and "reversing gut dysbiosis." Notably, the biotransformation role of gut microbiota is gradually emerging as a key research area. CONCLUSION: As a traditional medical system with multi-target effects and holistic regulatory advantages, TCM is gaining increasing attention in the management and prevention of MASLD. This study provides a comprehensive overview and evaluation of current research on TCM in the treatment of MASLD, providing valuable insights for future studies in this field.

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and constitutes a leading cause of end-stage renal disease (ESRD). Panax notoginseng is a widely utilized traditional Chinese medicinal herb with diverse pharmacological properties, including antioxidant, antithrombotic, and glucolipid metabolism-regulating activities. Preclinical studies have demonstrated the renoprotective effects of Panax notoginseng in DN animal models. However, a comprehensive meta-analysis of these studies is currently lacking, and the dose-time-response relationship remains unexplored. OBJECTIVE: This study aimed to systematically evaluate the efficacy of Panax notoginseng in animal models of DN and, for the first time, to explore its dose-time-response relationship. Additionally, we sought to summarize the potential mechanisms underlying its therapeutic effects on DN. METHODS: A systematic search was conducted across seven databases: PubMed, Web of Science, Embase, Chinese Biomedical Database (CBM), CNKI, WanFang, and VIP. The methodological quality of the included studies was assessed using SYRCLE's risk of bias tool. Statistical analyses were performed using STATA 14.0 software. Primary outcomes included fasting blood glucose (FBG), serum creatinine (SCr), blood urea nitrogen (BUN), 24-h urinary protein (24 h UPro), and kidney index (KI). Secondary outcomes encompassed indicators related to inflammatory response, oxidative stress, glucose and lipid metabolism, and fibrosis. Where substantial heterogeneity was present, sensitivity and subgroup analyses were conducted to explore its sources. Publication bias was assessed via Egger's test and funnel plots. The dose-time-response relationship of Panax notoginseng for DN was evaluated using a three-dimensional surface plot analysis. RESULTS: A total of 37 studies were included in the final meta-analysis. The results demonstrated that Panax notoginseng significantly ameliorated FBG, SCr, BUN, 24 h UPro, and KI levels. Furthermore, Panax notoginseng significantly modulated key inflammatory markers, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoat

BACKGROUND: The mammalian target of rapamycin (mTOR) plays a pivotal role in regulating neuronal survival and synaptic plasticity, both of which are crucial for the progression of Alzheimer's disease (AD). This study aims to delineate the research trends concerning mTOR and AD through bibliometric analysis. METHODS: A systematic search was conducted in the Web of Science Core Collection database to retrieve publications relevant to mTOR and AD from 2003 to 2025. Subsequently, bibliometric analysis and visualization were performed utilizing VOSviewer, CiteSpace, and the R package "Bibliometrix." RESULTS: A total of 1,025 articles were included in the analysis. The annual publication growth rate reached 21.22%, peaking in 2022. The three most cited articles addressed topics such as autophagy induction and clearance in neurons related to AD pathology, mTOR in microglial metabolic fitness, and mTOR inhibition against cognitive deficits. China led in publication volume, followed by the USA. The University of Texas System, Egyptian Knowledge Bank, and University of Texas Health Science Center at San Antonio emerged as the top 3 institutions. Oddo Salvatore ranked as the top author by H-index. Keyword analysis revealed four prominent clusters: cellular signaling and neuroplasticity, molecular mechanisms, neuroprotective effects of mTOR inhibition, and roles of mTOR in AD pathogenesis. Burst analysis identified "target," "neuroinflammation," "stress," "kinase," and "clearance" as the latest hotspots in the field. CONCLUSION: This bibliometric analysis provides a comprehensive overview of publication trends related to mTOR and AD. Future research is anticipated to focus on refining mTOR inhibitors as a therapeutic strategy and further exploring the underlying mechanisms of AD. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Update of Res Sq. 2025 Feb 17:rs.3.rs-6025759. doi: 10.21203/rs.3.rs-6025759/v1. Gene-environment interactions may enhance our understanding of blood pressure (BP) biology. We conducted a meta-analysis of multi-population genome-wide association studies (GWASs) of BP traits accounting for gene-depressive symptomatology (DEPR) interactions. Our study included 564,680 adults from 67 cohorts and four population backgrounds: African (5%), Asian (7%), European (85%), and Hispanic (3%). We discovered seven previously unreported BP loci showing gene-DEPR interaction. These loci mapped to genes implicated in neurogenesis (TGFA and CASP3), lipid metabolism (ACSL1), neuronal apoptosis (CASP3), and synaptic activity (CNTN6 and DBI). We also showed evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between mood disturbance and BP regulation. Of the 16 identified loci, 11 were derived from non-European populations. Post-GWAS analyses prioritized 36 genes, including genes involved in synaptic functions (DOCK4 and MAGI2) and neuronal signaling (CCK, UGDH, and SLC01A2). Integrative druggability analyses identified 11 druggable candidate gene targets linked to pathways involved in mood disorders as well as known anti-hypertensive drugs. Our findings emphasize the importance of considering gene-DEPR interactions on BP, particularly in non-European populations. Our prioritized genes and druggable targets highlight biological pathways connecting mood disorders and hypertension and suggest opportunities for BP drug repurposing and risk factor prevention, especially in individuals with DEPR.

BACKGROUND: With advances in detection technologies and the trend of interdisciplinary integration, mechanical stress in biomechanics has been shown to exert broad effects on organisms. It influences multiple cellular processes, including proliferation, migration, and differentiation, and also plays a critical regulatory role in both immune cell function and the organismal immune-inflammatory response. Thus, an emerging interdisciplinary field-mechanoimmunology-has emerged. However, the specific mechanisms underlying this field remain incompletely elucidated. Herein, this study aims to identify the latest research hotspots and provide a thorough analysis of the current research status in this domain. METHODS: A total of 1,901 articles were retrieved from the Web of Science Core Collection (WOSCC) and 2,954 articles from Scopus. These selected articles were imported into bibliometric analysis software for preliminary data processing, followed by further visual analysis using multiple graphing tools. Finally, specific analyses were conducted based on various categories, including journals, authors, geographical distribution, citations, and keywords. RESULTS: The United States and China are the two leading research hubs in this field, with the University of California System currently standing as the most influential institution. A surge in research on mechanoimmunology has been observed since 2021. During the "Research Explosion Phase" post-2021, several new keyword clusters emerged, including "T cells," "macrophage polarization," and "ion channels," alongside clusters related to emerging fields such as "wound healing," "gut microbiota," and "bone remodeling." The mechanosensitive ion channel protein Piezo1 and the YAP/TAZ transcription complex in the Hippo pathway have emerged as key targets in recent studies. CONCLUSION: This study identifies the ongoing research surge in the field of mechanoimmunology while comprehensively delineating the current research landscape. Additionally, through keyword clustering across different phases, it uncovers the latest research hotspots and potential future research directions focused on novel mechanosensitive targets for immu

The size and angle of the vulva are economically important traits in pig production. Gilts with small or upward-tilted vulva are typically culled directly. Selective breeding aimed at improving vulva traits can enhance the retention rate of replacement gilts. This study aimed to systematically explore the key quantitative trait loci (QTL) and genes influencing vulva traits in Large White pigs using genome-wide association studies (GWAS) and meta-analysis techniques. Data on vulva length (VL), vulva width (VW), and vulva angle scores (VAS) were collected from 2,197 Large White gilts across three distinct populations (313 from PIC, 1,169 from Topigs, and 715 from Canada), with genotyping performed using a 50K single-nucleotide polymorphism (SNP) array. The SNP-chip data were imputed to the whole-genome sequencing (iWGS) level. This study used iWGS data to conduct GWAS, identifying a genomic region (SSC5: 103.04-103.34 Mb) significantly associated with VAS in both the Topigs and Canadian Large White pig populations. The significance of this region was further strengthened through multi-population meta-analysis. The most significant SNP (rs3470833446), identified on chromosome 14 and associated with VW in PIC Large White pigs, explained 16.98% of the phenotypic variation (PVE). Multi-population meta-analysis identified novel significant SNPs associated with VL on SSC4, VW on SSC1, SSC4, and SSC6, and VAS on SSC2 and SSC5. Furthermore, a significant potential pleiotropic QTL (SSC4: 36.42-41.24 Mb) regulating both VL and VW was identified. Bayes fine mapping was employed to determine the confidence intervals for these novel QTLs, with the most refined confidence interval narrowed down to 30 kb (SSC4: 38.73-38.76 Mb for VW, and SSC5: 103.20-103.23 Mb for VAS). Based on the biological functions of the genes, the following were identified as novel regulatory candidate genes for vulva traits: VIP, NAV3, and ESR1. These findings reveal potential key genes and genetic mechanisms influencing vulva traits in pigs, providing a crucial molecular genetic basis for improving pig breeding and reproductive performance. Plain Language Summary: The reproductive performance of pigs i

OBJECTIVE: There are meta-analyses about the correlation between non-coding RNA and the prognosis of gastric cancer, which are focus on a single or a particular type of non-coding RNA. This study aims to verify the correlation between various non-coding RNAs and the prognosis of gastric cancer through meta-analysis. METHODS: The studies documenting the association between non-coding RNAs and the prognosis of gastric cancer up until September 2023 were extracted. The outcomes of the univariate and multivariate analyses were combined for each noncoding RNA. Sources of heterogeneity were determined by meta-regression analysis, and publication bias was assessed using the Egger test. RESULTS: Fifty-five studies were included in meta-analysis, of which 40 reported miRNAs and 14 reported lncRNAs. The up-regulation of miR-17-5p, miR-21, miR-214, miR-20a, lnc-CECR7, lnc-SNHG15, lnc-Sox2ot, lnc-ANRIL, lnc-DSCR8, lnc-ZEB1-AS1 and lnc-NEAT1 were associated with an unfavorable OS in gastric cancer. Elevated level of lnc-PVT1 correlated with an adverse DFS in gastric cancer. A diminished expression of miR-133a, miR-141, miR-206, and miR-1236-3p predicted a poor OS of gastric cancer. CONCLUSIONS: Various non-coding RNAs are associated with the prognosis of gastric cancer based on new evidence-based medical evidence, which provides a potential value for clinical diagnosis and treatment.

Schizophrenia is a severe mental illness with high heritability, but its underlying mechanisms are poorly understood. We meta-analyzed large-scale brain transcriptomic data from mice harboring individual loss-of-function mutations in seven schizophrenia risk genes (Akap11, Dagla, Gria3, Grin2a, Sp4, Srrm2, Zmym2). While all studied brain regions were affected, the striatum and the thalamus emerged as key brain regions of convergence. Striatum showed downregulation of synapse- and oxidative phosphorylation-related gene sets in all models. In the thalamus, mutants separated into two groups based on transcriptomic phenotype: synapse-related gene sets were upregulated in mutants with only schizophrenia and bipolar association, and were downregulated in mutants that are associated with developmental delay/intellectual disability in addition to schizophrenia. Overall, our meta-analysis reveals convergence and divergence in brain transcriptomic phenotype in these schizophrenia genetic models, supports the involvement of striatal disturbance and synapse dysfunction in schizophrenia, and points to a key role of the thalamus. © 2025. The Author(s).

BACKGROUND: Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias. METHODS: We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation. RESULTS: Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred. CONCLUSIONS: In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0650

BACKGROUND: Maternal microbiota during pregnancy plays a crucial role in establishing the neonatal gut microbiota, which is essential for infant health. This study aimed to trace maternal microbial sources contributing to early neonatal gut colonization and assess the effect of prenatal probiotic supplementation on maternal-to-neonatal microbial transmission. METHODS: A total of 26 mother-neonate pairs undergoing full-term vaginal delivery were enrolled. From gestational week 32 until delivery, the intervention group received a probiotic supplement containing Bifidobacterium longum, Lactobacillus delbrueckii bulgaricus, and Streptococcus thermophilus twice daily, while the control group received no supplementation. Maternal fecal, vaginal, and placental samples were collected at full term, and neonatal fecal samples were collected longitudinally at Days 1, 3, 14, and 6 months postpartum. Microbial community profiling was performed using 16 S rRNA gene sequencing. Microbial source attribution was conducted using the FEAST algorithm. RESULTS: Alpha and beta diversity analyses showed that prenatal probiotics transiently altered the composition of neonatal meconium microbiota, with no significant differences observed at later time points. Volatility analysis revealed enhanced microbial stability in the probiotic group during Days 1 to 3 (P < 0.001). FEAST source-tracking indicated that maternal gut and placenta were the major contributors to neonatal meconium colonization, with gut-derived input increasing over time and vaginal contributions remaining minimal throughout. Probiotic supplementation significantly increased the placental contribution to meconium microbiota (P = 0.02), with a sustained but non-significant elevation observed through later stages. Meanwhile, gut-derived and vaginal-derived inputs were consistently reduced in the probiotic group, though these differences did not reach statistical significance. CONCLUSION: This study highlights the dynamic nature of maternal-to-neonatal microbial transmission and demonstrates that prenatal probiotic supplementation can transiently reshape early colonization patterns by modulating source contributions. TRIAL

BACKGROUND: TSLP, a cytokine derived from epithelial cells at barrier surfaces, has been extensively studied as a pivotal regulator of type 2 and non-type-2 immune responses, implicated in inflammatory airway diseases. Although mAb therapy targeting TSLP has shown significant therapeutic effects, there is still no approved TSLP-targeting inhaled formulation. OBJECTIVES: Leveraging the distinct advantages of nanobodies (Nbs) in maintaining efficacy during storage and administration, our objective is to develop a novel inhalable TSLP Nb for effectively treating airway inflammation. METHODS: Four TSLP-immunized Nb libraries were screened to generate specific and functional TSLP Nbs. LQ043, a bivalent Nb comprising 2 humanized Nb13 units, was constructed. The efficacy, pharmacokinetics, and safety of inhaled LQ043 were evaluated in mice and nonhuman primates, followed by a randomized, double-blind phase I clinical study. The clinical trial was registered with the Chinese Clinical Trial Registry (CTR20230092). RESULTS: LQ043 exhibited high affinity and specificity for human TSLP, coupled with a favorable inhibitory effect on TSLP/TSLP receptor interaction. Furthermore, inhaled LQ043 significantly attenuated ovalbumin-induced allergic inflammation in mice and demonstrated excellent safety, pharmacokinetic characteristics, and tissue distribution in nonhuman primate models, with high concentrations observed in the respiratory system. Notably, phase I clinical trial results demonstrated dose-proportional pharmacokinetics, safety, and good tolerability for LQ043. In addition, LQ043 can be produced on a large scale at low cost in yeast cells, thereby substantially alleviating the economic burden associated with inhaled biopharmaceuticals. CONCLUSION: These preclinical and clinical studies robustly establish the safety and efficacy of inhaled LQ043, underscoring its potential as a pioneering inhalation therapy for airway inflammation.

OBJECTIVE: To observe the clinical efficacy of acupoint thread-embedding for overweight and obese young adults with phlegm-dampness constitution. METHODS: A total of 66 young adults with overweight and obesity of phlegm-dampness constitution were randomly divided into an observation group (33 cases, 2 cases dropped out, 1 case was discontinued) and a control group (33 cases, 3 cases dropped out). Health education guidance was adopted in the control group. On the basis of the intervention in the control group, acupoint thread-embedding was applied in the observation group, two groups of acupoints were used alternately, i.e. bilateral Tianshu (ST25), Daheng (SP15), Daimai (GB26), Shuidao (ST28), Huaroumen (ST24), Fenglong (ST40) and bilateral Feishu (BL13), Geshu (BL17), Weiwanxiashu (EX-B3), Pishu (BL20), Shenshu (BL23), Dachangshu (BL25), once a week. Treatment of 8 weeks was required in the two groups. Before treatment, after 4 weeks and 8 weeks of treatment, the body weight, body fat rate, waist circumference and hip circumference were measured, and the body mass index (BMI) was calculated in the two groups; before and after treatment, the phlegm-dampness constitution score and the heart rate variability (HRV) related indexes (total power [TP], low frequency [LF], high frequency [HF], LF/HF, standard deviation of the normal to normal inter beat intervals [SDNN], root mean square of the successive differences [RMSSD], percentage of normal RR intervals with duration [PNN50]) were observed, and the clinical efficacy and constitution improvement rate were compared in the two groups. Six months after the treatment completion, the body weight of patients with effective clinical efficacy was observed, and the body weight rebound rate was compared in the two groups. RESULTS: After 4 weeks of treatment, the body weight, BMI, body fat rate, waist circumference and hip circumference were decreased compared with those before treatment in the two groups (P<0.05); after 8 weeks of treatment, the body weight, BMI, body fat rate, waist circumference and hip circumference were decreased compared with those before treatment and after 4 weeks of treatment in the observation grou

The multi-center randomized phase III NHL-004 study compared etoposide, dexamethasone and pegaspargase (ESA) versus the methotrexate, etoposide, dexamethasone and pegaspargase (MESA) regimen, combined with sandwiched radiotherapy, in newly diagnosed early-stage nasal natural killer / T-cell lymphoma (NKTCL). Here we report the long-term outcomes (median follow-up, 64 months) and biomarker analysis. A total of 256 eligible patients aged 14-70 years were randomly assigned (1:1) to the ESA or the MESA arm. The 5-year progression-free survival (PFS) rates were 80.3% and 74.9% in the ESA and MESA arms (hazard ratio [HR]=0.78 [95% CI: 0.46-1.33], P=0.371), and the 5-year overall survival (OS) rates were 85.1% and 80.9% (HR=0.74 [95% CI: 0.40-1.37], P=0.332), respectively. No new safety signals related to treatments were observed. Interim plasma Epstein-Barr virus (EBV) DNA positivity and stable disease / progressive disease response were independent predictors of inferior PFS and OS. No prognostic significance was observed according to molecular subtypes. Interim EBV DNA positivity correlated with up-regulated chromatin remodeling alterations, immune escape-related genes, and decreased infiltrating monocytes / M1 macrophages. With low toxicity, non-intravenous administration, and an outpatient design, ESA with sandwiched radiotherapy achieved long-term durable response in patients with newly diagnosed early-stage NKTCL. Dynamic monitoring of plasma EBV DNA provided a clinical rationale for future mechanism-based therapy in NKTCL.

AIMS: This study aimed to assess the effects of Low-to-Moderate Intensity Continuous Training (LMICT), Moderate-Intensity Interval Training (MIIT), and Reduced-Exertion High-Intensity Training (REHIT) on blood glucose regulation, functional recovery, and lipid levels in individuals who have experienced a stroke and are diagnosed with Type 2 Diabetes Mellitus (T2DM). METHODS: Forty-two T2DM stroke patients were randomly allocated to four groups: LMICT, MIIT, REHIT, and a control group (CON). Participants continuously monitored their blood glucose levels throughout the intervention using continuous glucose monitoring (CGM) devices. The study comprised two exercise intervention cycles: the first lasting from Day 3 to Day 14 and the second from Day 15 to Day 28, with the initial two days serving as contrasting periods. Primary outcomes encompassed CGM-derived blood glucose measurements, the Barthel Index (BI), Fugl-Meyer Assessment lower-extremity subscale (FMA-LE), and alterations in triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). RESULTS: Compared with the CON, the MIIT group showed significant improvements in mean glucose (MG), glucose standard deviation (SD), time above range (TAR), and time in range (TIR). The REHIT group exhibited significantly reduced time below range (TBR), glucose SD, and coefficient of variation (CV). Regarding lipid levels, although the REHIT group achieved a significant reduction in TG levels compared with the CON, the overall effects of LMICT, MIIT, and REHIT on lipid profiles were relatively modest. Concerning functional recovery, the REHIT group significantly improved the BI and FMA-LE. CONCLUSION: Although the short-term quantitative impact of exercise on lipid levels may be limited, both REHIT and MIIT significantly improved glycemic management and reduced glucose variability in post-stroke patients with Type 2 Diabetes Mellitus. Additionally, REHIT notably enhanced functional recovery.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death in both developed and many developing countries. Exercise training is a fundamental component of cardiac rehabilitation programs for patients with CHD. This study aims to investigate the effects of a Tai Chi rehabilitation program, which is provided through a hybrid online and offline mode, on oxidative stress and inflammatory responses in patients with CHD. METHODS: A total of 34 patients with coronary heart disease were randomly assigned to two groups: an experiment group (n = 14, age 62.07 ± 9.076 years) and a control group (n = 20, age 61.90 ± 9.700 years). The experiment group underwent a 12-week Tai Chi cardiac rehabilitation program (TCCRP), while the control group followed a conventional exercise rehabilitation program (CERP) consisting of 1-h sessions, 3 times per week, for a total of 36 sessions. Participants were studied at baseline and post-intervention. The main assessments include the levels of Malondialdehyde (MDA), Superoxide dismutase (SOD), Tumor necrosis factor (TNF-α) and Interleukin-10 (IL - 10) in blood samples. Pearson correlation analysis was used, and the differences between the two groups were subsequently tested using two-way repeated ANOVA. Statistical significance was defined as a two-sided p-value of <0.05. RESULTS: The key finding of the study reveals that MDA was significantly reduced by 1.027 nmoL/mL. Additionally, the TCCRP showed significant improvements in SOD and IL-10, with values of 10.110 U/mL and 2.441 pg./mL, respectively. Notably, a significant positive correlation was found between SOD and IL-10 (r = 0.689, p = 0.006), while MDA showed a significant positive correlation with TNF-a (r = 0.542, p = 0.045). In contrast, the ECRP group only showed a significant improvement in SOD. CONCLUSION: The study conducted a 12-week program on TCCRP, which utilized a hybrid online and offline model for individuals with coronary heart disease. The program showed promising results in alleviating oxidative stress and inflammation, possibly by regulating the balance between oxidative and antioxidative factors, as well as pro-inflammatory and anti-inflammatory factors.

OBJECTIVES: The study was designed to identify the potential peripheral processes of circulating exosome in response to Tai Chi (TC) exercise and the possibility of its loaded cargos in mediating the effects of TC training on cognitive function among older adults with amnestic mild cognitive impairment (aMCI). DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter randomized controlled trial. One hundred community-dwelling old adults with aMCI were randomly assigned (1:1) to experimental (n = 50) and control groups (n = 50). INTERVENTION: The experimental group participated in TC exercise 5 times/week, with each session lasting 60 minutes for 12 weeks. Both experimental and control groups received health education every 4 weeks. MEASUREMENTS: The primary outcome was global cognitive function. Neurocognitive assessments, MRI examination, and large-scale proteomics analysis of peripheric exosome were conducted at baseline and after 12-week training. Outcome assessors and statisticians were blinded to group allocation. RESULTS: A total of 96 participants (96%) completed all outcome measurements. TC training improved global cognitive function (adjusted mean difference [MD] = 1.9, 95%CI 0.93-2.87, p <0.001) and memory (adjusted MD = 6.42, 95%CI 2.09-10.74, p = 0.004), increased right hippocampus volume (adjusted MD = 88.52, 95%CI 13.63-163.4, p = 0.021), and enhanced rest state functional connectivity (rsFC) between hippocampus and cuneus, which mediated the group effect on global cognitive function (bootstrapping CIs: [0.0208, 1.2826], [0.0689, 1.2211]) and verbal delay recall (bootstrapping CI: [0.0002, 0.6277]). Simultaneously, 24 differentially expressed exosomal proteins were detected in tandem mass tag-labelling proteomic analysis. Of which, the candidate protein low-density lipoprotein receptor-related protein 1 (LRP1) was further confirmed by parallel reaction monitoring and ELISA. Moreover, the up-regulated LRP1 was both positively associated with verbal delay recall and rsFC (left hippocampus-right cuneus). CONCLUSION: TC promotes LRP1 release via exosome, which was associated with enhanced memory function and hippocampus plasticity in aMCI patients. Our

Numerous studies have demonstrated an intimate relationship between circadian rhythm disorders and the development and prevention of depression. The biological clock genes, which constitute the molecular basis of endogenous circadian rhythms, hold promising prospects for depression treatment. Based on an extensive review of recent domestic and international research, this article presents a comprehensive analysis of how traditional Chinese medicine (TCM) intervenes in depression by regulating circadian rhythms. The findings indicate that TCM exerts its antidepressant effects by targeting specific biological clock genes such as Bmal1, clock, Arntl, Per1, Per2, Per3, Nr1d1, Cry2, and Dbp, as well as regulating circadian rhythms of hormone secretion. However, most current research is still confined to basic experimental studies, lacking clinical double-blind control trials to further validate these viewpoints. Furthermore, there is insufficient research on the signal transduction pathway between biological clock genes and pathological changes in depression. Additionally, further clarification is needed regarding the specific targets of TCM on the biological clock genes.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8+ T cells than the placebo group at 3 (2.300,P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8+ T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).

To investigate the main drivers of rhizosphere soil microbial community structure and diversity in Camellia reticulata, this study collected rhizosphere soil samples from six regions at two soil depths (0-30 cm and 30-60 cm). Using high-throughput sequencing, we systematically analyzed the effects of soil environmental factors on microbial communities. The results showed that the dominant bacterial phyla were Proteobacteria, Acidobacteriota, Chloroflexi, Actinobacteriota, and Bacteroidota, while the dominant fungal phyla were Ascomycota, Basidiomycota, and Mortierellomycota. Alpha diversity of both bacterial and fungal communities was higher in surface soils (0-30 cm) than in deeper layers (30-60 cm), although the differences were not statistically significant (p > 0.05). Soil pH, potassium content (K), and catalase activity (S-CAT) were identified as the main environmental factors significantly correlated with microbial community structure. Network analysis identified Acidobacteriota and Ascomycota as highly connected taxa within microbial networks, suggesting their potential importance in maintaining network structure. This study reveals the vertical differentiation characteristics of rhizosphere microbial communities in C. reticulata and their responses to environmental factors, providing a theoretical basis for cultivation management and rhizosphere microecological regulation.

Bi2O2Se is an emerging oxyselenide semiconductor, noted for its promising thermoelectric properties and excellent chemical stability, and it is often regarded as an n-type counterpart to p-type BiCuSeO. However, its intrinsic thermoelectric figure of merit (zT) is severely limited by low electron concentration and high thermal conductivity. In this work, we employed Cl element as donator dopant to substantially enhance the carrier concentration. The room-temperature carrier concentration of Bi2O2Se0.98Cl0.02 thereby reached 2.70 × 1020 cm-3, representing an improvement of two orders of magnitude compared to that of pristine Bi2O2Se. Subsequently, multiple hot-pressing cycles were applied to the optimized composition Bi2O2Se0.98Cl0.02. The process induced significant grain refinement, and the resulting high density of grain boundaries effectively suppressed the lattice thermal conductivity, reducing it to 0.95 W·m-1·K-1 at 823 K. Eventually, a maximum zT of 0.24 was achieved at 823 K for the three-time hot-pressed Bi2O2Se0.98Cl0.02 sample, representing a 71% improvement compared with the pristine Bi2O2Se sample prepared by single hot-pressing (zT = 0.14 at 823 K). This work provides a new strategy for enhancing the thermoelectric performance of oxyselenide through the synergistic regulation of doping and microstructure.

The low absolute strength and insufficient room-temperature ductility remain key bottlenecks that restrict the engineering application of magnesium alloys in high-end industrial fields. In the present study, 1 vol.% carbon nanotubes (CNTs)-reinforced Mg-xAl (x = 0, 1, and 1.5 wt.%) composites were synthesized via a powder metallurgy route coupled with hot extrusion-rolling processing to realize a simultaneous improvement in mechanical properties. The hot extrusion-rolling processed 1 vol.% CNTs/Mg-1Al composite exhibits an ultimate tensile strength of 300 MPa and an elongation to failure of 9%, showing an excellent strength-ductility synergy. Microstructural characterization reveals a well-bonded interface between CNTs and the Mg matrix. Deformation incompatibility between CNTs and the magnesium matrix during hot extrusion-rolling induces a high density of dislocations, providing an important strengthening contribution. Moreover, an increased proportion of low-angle grain boundaries and the development of a bimodal texture promote significant grain refinement and effectively activate non-basal slip systems, thereby alleviating plastic deformation constraints. The synergistic effects of interfacial strengthening, dislocation strengthening, grain boundary strengthening, and texture regulation together contribute to the simultaneous improvement of strength and ductility in CNTs-reinforced Mg-Al composites.

Kopi Luwak (civet coffee), produced from coffee beans recovered from the feces of the Asian palm civet, is among the most expensive specialty coffees worldwide for its unique sensory characteristics. In this study, a multi-omics strategy was employed to elucidate the impact of drying on the microbial community structure and metabolic profiles of Typica Kopi Luwak beans. Drying induced pronounced shifts in the microbial composition, with a significant enrichment of Sphingobacterium and depletion of Streptococcus at the genus level. Concurrently, drying resulted in substantial metabolic remodeling, characterized by increased levels of prenol lipids, fatty acyls, carboxylic acids and derivatives, steroids and steroid derivatives, and organooxygen compounds, accompanied by a marked reduction in flavonoids. KEGG pathway analysis indicated that both altered microbial taxa and metabolites were associated with lipid metabolism, carbohydrate metabolism, amino acid metabolism, and the biosynthesis of other secondary metabolites. Correlation network analysis further revealed the associations between key microbial genera and specific classes of differential metabolites. Collectively, these findings suggest the potential role of post-excretion sun-drying in shaping the microbiome and metabolome of Typica Kopi Luwak beans, offering a scientific basis for controlled or in vitro fermentation strategies to produce coffees with reproducible quality attributes.

Immune-mediated inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus, impose a severe and growing global health burden, where current therapies are limited by poor specificity and significant side effects. The peptidylarginine deiminase (PAD)/citrullination axis, in which protein citrullination catalyzed by PADs drives autoantigen generation and sustains inflammation, has emerged as a critical therapeutic target. This review outlines a comprehensive strategy for targeting this axis using natural products. We first detail the established role of natural compounds as direct PAD inhibitors, covering their chemical diversity, inhibitory mechanisms, and therapeutic applications in disease models. Subsequently, the discussion extends to their broader, indirect modulatory functions, highlighting how these compounds can suppress pathogenic citrullination by regulating upstream processes like NETosis and inflammatory signaling. Furthermore, the review introduces the innovative substrate-centric intervention strategy, which represents a paradigm shift toward shielding key arginine residues on autoantigens, thereby preventing the formation of immunogenic neoepitopes. The translational challenges and future directions for each of these avenues are outlined, addressing persistent obstacles including achieving isoform selectivity and biomarker validation. By integrating these multifaceted strategies, from direct inhibition and indirect modulation to substrate protection, this work provides a strategic roadmap for advancing the next generation of more precise, effective, and safe anti-citrullination therapies, ultimately moving beyond conventional enzyme inhibition toward targeted immunomodulation in immune-mediated inflammatory diseases.

Mitochondrial dysfunction drives persistent inflammation in severe asthma, yet its upstream metabolic regulation remains unclear. Induced sputum from patients with severe asthma was analyzed and integrated with transcriptomic datasets from independent cohorts. Two mouse models (C57BL/6J) were used for in vivo validation with multi-omics profiling, and mechanistic studies were performed in air-liquid interface-cultured primary human airway epithelial cells. Glutathione reduced form (GSHr) was markedly depleted in sputum and associated with poor disease control and mixed granulocytic inflammation in patients with severe asthma. Multi-omics analyses revealed coordinated disruption of glutathione (GSH) metabolism, including oxidized GSH accumulation, reduced synthesis and glutathione-S-transferase activity, and impaired mitochondrial GSH transport. GSH supplementation alleviated airway inflammation, oxidative stress, and mitochondrial dysfunction, whereas pharmacological inhibition of GST exacerbated these effects. Mitochondrial analyses identified suppressed SLC25A39 expression as a key mediator of defective GSH transport and redox imbalance. Transcriptomic profiling of airway biopsies showed upregulation of Neuropilin-1 (Nrp1), closely associated with altered glutathione pathways. Targeting the Nrp1 b1 domain restored mitochondrial GSH metabolism and attenuated airway inflammation. These findings identify an Nrp-centered metabolic pathway that disrupts mitochondrial homeostasis and drives inflammatory amplification, highlighting mitochondria-targeted therapeutic strategies for severe asthma.

High salinity causes severe osmotic and oxidative stress to Zygosaccharomyces rouxii, a crucial yeast in soy sauce manufacturing. We used DIA-based quantitative proteomics to investigate whether a functional protein (casein containing astaxanthin) alters the salt-stress proteome of Z. rouxii CGMCC 3791 at 120 g/L NaCl. Multivariate analysis revealed a clear distinction between the NaCl-only and supplemented groups, with excellent repeatability. A total of 267 differently expressed proteins were discovered (52 up-regulated and 215 down-regulated; |FC| ≥ 1.5, p < 0.05), showing significant proteome remodeling. GO and KEGG/InterPro enrichment identified oxidative stress response, membrane lipid handling, vesicle/vacuolar autophagic regulation, ribosome-associated processes, and oxidative phosphorylation. Protein-protein interaction research identified hub modules centered on the ribosome and mitochondria. Taken together, these results suggest that functional protein supplementation is associated with coordinated changes in redox-related, membrane-associated, proteostasis-related, and energy-metabolism pathways in Z. rouxii under high-salt conditions, which may contribute to the observed improvement in survival. Dabupi decoction mitigates fluorouracil-induced intestinal mucositis via farnesoid X receptor activation and dihydropyrimidine dehydrogenase upregulation. Wang S(1), Li Y(2), Ma J(1), Li J(1), Huang D(1), Wa X(1), Zhou Y(1), Liu Y(3). Author information: (1)Key Laboratory of Dun Huang Medical and Transformation, Ministry of Education of the People's Republic of China, Gansu University of Chinese Medicine, 730000, Lanzhou, China. (2)Key Laboratory of Dun Huang Medical and Transformation, Ministry of Education of the People's Republic of China, Gansu University of Chinese Medicine, 730000, Lanzhou, China; Gansu University Key Laboratory for Molecular Medicine & Chinese Medicine Prevention and Treatment of Major Diseases, Gansu University of Chinese Medicine, 730000, Lanzhou, China. (3)Key Laboratory of Dun Huang Medical and Transformation, Ministry of Education of the People's Republic of China, Gansu University of Chinese Medicine, 730000, Lanzhou, China;

14. J Ethnopharmacol. 2026 Apr 30;367:121742. doi: 10.1016/j.jep.2026.121742. Online ahead of print. Dabupi decoction mitigates fluorouracil-induced intestinal mucositis via farnesoid X receptor activation and dihydropyrimidine dehydrogenase upregulation. Wang S(1), Li Y(2), Ma J(1), Li J(1), H

Update of bioRxiv. 2025 Jul 23:2025.07.08.663739. doi: 10.1101/2025.07.08.663739. BCL-2 has been implicated in prostate cancer (PCa) progression and development of castration-resistant disease (CRPC); however, it remains unclear how the BCL-2- and AR-expressing PCa cell populations evolve across the PCa continuum, how AR molecularly regulates BCL-2 and whether BCL-2 represents a common therapeutic target in heterogeneous CRPC. Here we first show the selective induction of BCL-2 by AR pathway inhibitors (ARPIs). Vectra-based quantitative multiplex immunofluorescence (qmIF) and image mass cytometry (IMC) analyses with single-cell resolution in patient PCa and xenograft models reveal markedly increased BCL-2+ (AR+ or AR-) PCa cells in CRPC. Mechanistically, AR represses BCL-2 transcription through several AR binding sites and ARPIs relieve this repression. Therapeutic studies in cells, organoids and xenografts support BCL-2 as a shared vulnerability across diverse CRPC subtypes. A Phase Ib clinical trial (NCT03751436) combining enzalutamide and BCL-2 inhibitor venetoclax demonstrated reduced circulating tumor cells in responding patients. In summary, by integrating high-content single-cell level imaging analyses with mechanistic studies, extensive preclinical therapeutic experiments and a Phase Ib clinical trial, our studies herein elucidate the AR+/-BCL-2+/- PCa cell subpopulation dynamics and credentials BCL-2 as a vital therapeutic target in heterogeneous CRPC. © 2026. The Author(s).

BACKGROUND: Brain-gut interaction disorders, such as functional dyspepsia (FD) comorbid with depression, are highly prevalent and severely affect patients' quality of life; however, the underlying mechanisms remain incompletely understood, and effective therapeutic options are still limited. Zuojin Pill (ZJP), a classic Chinese herbal formula, has shown potential in treating both gastrointestinal disorders and depressive symptoms, but its role in FD-depression comorbidity and underlying mechanisms remain unclear. PURPOSE: This investigation aimed to evaluate the therapeutic potential of ZJP and delineate its mechanistic pathways in alleviating comorbid depressive symptoms and Gastrointestinal (GI) impairments. STUDY DESIGN: A combined clinical observational study and preclinical experimental study was conducted to integrate human and animal data for mechanistic validation. METHODS: Baseline assessments were conducted in healthy controls and patients with functional dyspepsia (FD)-depression comorbidity, including evaluations of gut microbiota composition, metabolite profiles, inflammatory cytokines, gastrointestinal hormones, and serotonin (5-HT) levels. An animal model using mice was developed to assess the efficacy of ZJP in addressing depression-related phenotypes and GI functional deficits. Furthermore, Parabacteroides distasonis was used to induce pathological features in mice, and the intervention effects of ZJP were systematically assessed. RESULTS: Patients with FD-depression comorbidity exhibited gut microbiota dysbiosis, characterized by a significant increase in P. distasonis abundance. Metabolomic analysis highlighted tryptophan metabolism as a key altered pathway. In model mice, ZJP administration alleviated depression-like behaviors and gastrointestinal dysfunction. Mechanistically, ZJP targeted P. distasonis, regulated tryptophan-derived metabolites, enhanced anti-inflammatory cytokine expression, improved synaptic plasticity, and restored intestinal mucosal barrier integrity. CONCLUSIONS: ZJP ameliorates depression with gastrointestinal dysfunction by modulating P. distasonis and its associated tryptophan metabolic pathway, thereby restoring gut-