Physical activity (PA) is an important non-pharmacological intervention that can slow the progression of Chronic Obstructive Pulmonary Disease (COPD). Unfortunately, PA levels in older adults with COP Show more
Physical activity (PA) is an important non-pharmacological intervention that can slow the progression of Chronic Obstructive Pulmonary Disease (COPD). Unfortunately, PA levels in older adults with COPD remain low, and there is substantial heterogeneity within this population. Therefore, identifying potential subgroups is essential for developing targeted interventions. The purpose of this study is to identify latent profiles of PA, and explore the associated factors to inform personalized interventions for this population. This multicenter cross-sectional study was conducted from November 2024 to March 2025 at a tertiary hospital and four community health service centers in the Changning District of Shanghai. The revised International Physical Activity Questionnaire-Long (IPAQ-L) was utilized to assess PA and sedentary behavior. Latent profile analysis (LPA) was employed to classify the subgroups, followed by multinomial logistic regression to explore influencing factors. A total of 423 older adults with COPD (male N = 383; aged 60-89) were included in this study. LPA identified three distinct PA profiles, named the "moderate activity-moderate sedentary-low barrier (C1) group", the "low activity-high sedentary-high barrier (C2) group", and the "high activity-low sedentary-moderate barrier (C3) group". The factors were significantly associated with PA, including Body Mass Index (BMI), disease duration, number of hospitalizations, GOLD stage, COPD Assessment Test (CAT) score, exercise self-efficacy, and exercise social support (p < 0.05). LPA identified three subgroups of PA in older adults with COPD. The results of this research will facilitate targeted interventions for each of the identified subgroups with distinct characteristics, thereby enhancing the management of COPD and reducing healthcare burdens. Show less
Atherosclerotic plaque instability is a direct cause of cardiovascular and cerebrovascular events. In this study, a mitochondria-targeted liposome (LIP), modified with triphenylphosphonium (TPP) to en Show more
Atherosclerotic plaque instability is a direct cause of cardiovascular and cerebrovascular events. In this study, a mitochondria-targeted liposome (LIP), modified with triphenylphosphonium (TPP) to enable specific mitochondrial delivery, was innovatively constructed to encapsulate a PCSK9 inhibitor (TPP-LIP@PCSK9). The aim was to explore a novel strategy for stabilizing plaques by restoring mitochondrial function in endothelial cells. Characterization results showed that TPP-LIP@PCSK9 possesses favorable nano-characteristics, and its targeting capability was confirmed through mitochondrial co-localization experiments. In an Apoe Show less
Endometrial carcinoma (EC) is a common malignancy of the female reproductive system. Rab35 is widely recognized as an oncogenic driver and has been implicated in the progression of various malignant t Show more
Endometrial carcinoma (EC) is a common malignancy of the female reproductive system. Rab35 is widely recognized as an oncogenic driver and has been implicated in the progression of various malignant tumors. However, its regulatory mechanism and pathobiological roles in EC remain unclear. Rab35 expression in EC was systematically profiled via integrative analysis of clinical endometrial specimens and multi-omics databases (CPTAC and GEO). The association between clinical prognosis and Rab35 expression was examined using Kaplan-Meier analysis. Mechanistic investigations included transwell assays, western blotting, and immunofluorescence in Rab35-overexpressing and CRISPR/Cas9-mediated Rab35-knockout EC cells. A mouse xenograft tumor model was established to confirm the effects of Rab35 in vivo. The Rab35 content increased gradually from normal endometrium to atypical hyperplastic endometrium to EC. Moreover, the findings indicated that elevated Rab35 expression was significantly associated with advanced disease characteristics and poor overall survival in patients with EC. In addition, Rab35 enhanced the migratory and invasive nature of EC cells. The expression of Rab35 was inversely linked to that of the β-catenin destruction complex-related proteins Axin-1 and GSK3β, leading to the increased nuclear translocation of β-catenin in EC cells. Animal experiments further verified that Rab35 augmented EC progression by regulating the nuclear translocation of β-catenin. The study revealed that high expression of Rab35 was strongly correlated with EC progression and a poor clinical outcome. Furthermore, Rab35 promoted EC cell metastasis by accelerating the nuclear translocation of β-catenin. These findings suggest that Rab35 serves as a valuable biomarker and therapeutic target for EC. Show less
Conversion of cholesterol into bile acids is a central pathway for cholesterol disposal, which was mainly controlled by cholesterol 7alpha-hydroxylase (Cyp7a1). In present study, we aimed to investiga Show more
Conversion of cholesterol into bile acids is a central pathway for cholesterol disposal, which was mainly controlled by cholesterol 7alpha-hydroxylase (Cyp7a1). In present study, we aimed to investigate the effect and the potential underlying mechanism of microRNA-96 (miR-96) on atherosclerosis development. The anti-atherosclerosis effects of a miR-96 inhibitor (miR-96i) were evaluated using ApoE KO mice fed a high-fat diet, which was treated with miR-96i for 8 weeks. The regulatory mechanism was revealed and validated by RNA-seq transcriptomics, quantitative PCR and western blotting analyses in hepatic cells. The authors identified that miR-96i significantly decreased serum cholesterol and bile acid levels and attenuated arterial plaque in mice. We further revealed that miR-96 regulated Cyp7a1 via a FOXO1-involved indirect pathway, in which miR-96 directly modulated FOXO1 in a posttranscriptional manner. A coordinated regulatory effect of miR-96 and miR-185 on FOXO1 was also observed. The full spectrum of mechanisms underlying the antiatherosclerotic activity beside miR-96-FOXO1-CYP7A1 axis remains to be elucidated. This study provides convincing evidence for the pivotal role of miR-96 in FOXO1 modulation and CYP7A1-involved cholesterol-bile acid metabolism, suggesting that miR-96 is a novel therapeutic target for the discovery and development of drugs against ACVD. Show less
Atherosclerosis presents a persistent health challenge, with limited therapies addressing residual cardiovascular risk. Gualou Xiebai Banxia Decoction (GXBD), a classical Chinese herbal formula tradit Show more
Atherosclerosis presents a persistent health challenge, with limited therapies addressing residual cardiovascular risk. Gualou Xiebai Banxia Decoction (GXBD), a classical Chinese herbal formula traditionally used for chest obstruction syndromes, was evaluated as a dietary-style intervention in ApoE Show less
While active ingredients from compound Chinese herbal medicines (CCHMs) have demonstrated potential in alleviating symptoms of polycystic ovary syndrome (PCOS), their mechanisms of action remain insuf Show more
While active ingredients from compound Chinese herbal medicines (CCHMs) have demonstrated potential in alleviating symptoms of polycystic ovary syndrome (PCOS), their mechanisms of action remain insufficiently understood. This study aimed to identify key active ingredients and gene targets in Xiaochaihu Decoction, Sijunzi Decoction, and Shensiwei that contribute to their efficacy against PCOS. Transcriptomic data of PCOS were obtained from public databases. Information on gut microbiota metabolite-related targets and active ingredients of CCHMs was retrieved from relevant databases. Key gene targets and active ingredients were identified using Graph-based Bioactive Network Analysis (GraphBAN) and toxicological assessments. Molecular docking and dynamic simulations were conducted to validate interactions. Functional enrichment and regulatory network analysis were performed. LCT, FADS1, and CYP11A1 were identified as key genes associated with α-β T cell activation, immune receptor signaling, and adaptive immune responses. LCT and FADS1 were targeted by linolenic acid, while CYP11A1 was regulated by mandenol, EIC, and linolenic acid. Three microRNAs (hsa-miR-320a-3p, hsa-miR-4487, hsa-miR-6090) co-regulated these genes. Molecular docking and dynamics simulations confirmed stable binding between key genes and active ingredients, with binding energies < -5.0 kcal/mol. The findings indicate that CCHMs exert therapeutic effects on PCOS by multi-target regulation of key genes involved in androgen synthesis, metabolic regulation, and immune-inflammatory activation. The observed strong binding affinities provide a structural basis for these interactions. This study identified three key genes and three core active ingredients in CCHMs for PCOS treatment, laying a theoretical foundation for developing multi-target therapeutics. Show less
Alport syndrome (AS) is the most common inherited glomerular disease among patients with chronic kidney disease. With exome sequencing now widely used in clinical practice, pathogenic variants in Alpo Show more
Alport syndrome (AS) is the most common inherited glomerular disease among patients with chronic kidney disease. With exome sequencing now widely used in clinical practice, pathogenic variants in Alport-related genes (COL4A3/COL4A4/COL4A5) are increasingly identified in patients with diverse phenotypes, including proteinuria‑predominant disease and kidney failure of unknown etiology. Diagnostic complexity further increases when COL4A3/COL4A4/COL4A5 variants are co‑inherited with pathogenic variants associated with other genetic kidney disorders. We reported a 31‑year‑old male presenting with kidney failure, significant proteinuria, familial hematuria and hyperlipidemia. Whole‑exome sequencing (WES) identified two pathogenic variants: a hemizygous COL4A5 variant (c.2105G > A; p.Gly702Asp) and a heterozygous APOE Kyoto variant (c.127C > T; p.Arg43Cys). Given the potential dual diagnosis of AS and lipoprotein glomerulopathy (LPG), a kidney biopsy was performed. Histologic examination revealed uneven thickness of the glomerular basement membrane consistent with the diagnosis of AS, but no LPG-related lesions were observed, indicating incomplete penetrance of APOE Kyoto variant. Cascade family screening detected APOE Kyoto variant in the patient's father and elder sister, both of whom lacked proteinuria until follow-up period. This case highlights the complementary role of kidney biopsy alongside WES in AS with complex genetic mechanisms. It also illustrates the incomplete penetrance of APOE Kyoto, common among Chinese carriers. Show less
C-reactive protein (CRP) is a liver-derived soluble marker of inflammation whose levels can predict the risk of atherosclerotic cardiovascular disease and therapeutic efficacy of statins. Intriguingly Show more
C-reactive protein (CRP) is a liver-derived soluble marker of inflammation whose levels can predict the risk of atherosclerotic cardiovascular disease and therapeutic efficacy of statins. Intriguingly, however, CRP is not considered as a mediator of atherosclerosis based primarily on studies examining chow diet (CD)-fed mice. The aim of this study is to investigate the role of CRP in high-fat diet (HFD)-induced atherosclerosis, which models a more prevalent scenario in the real world, and to clarify its impact on Atorvastatin treatment. Apoe-sufficient or -deficient mice with or without Crp knockout were fed with CD, HFD, or methionine- and choline-deficient diet, or subjected to carotid artery ligation or Atorvastatin treatment. Hepatic, vascular, and metabolic indexes were then analyzed. The effects of CRP on lipid droplet formation were examined by cellular assays. Knockout of Crp in Apoe-deficient mice does not affect the progression of atherosclerosis under CD feeding, but significantly reduces plaque burden under HFD feeding. The pro-atherosclerotic effects of Crp are not due to direct modulation of vascular inflammation, but appear to be the result of enhanced lipid accumulation in the liver and the ensuing aggravation of hyperlipidemia. Mechanistically, Crp enhances hepatic lipid accumulation by upregulating Cidea to promote the formation of enlarged lipid droplets in hepatocytes. We further show that the therapeutic efficacy of Atorvastatin on HFD-induced atherosclerosis in Apoe-deficient mice is largely dependent on Crp. Our findings identify a previously unrecognized role of CRP in enhancing hepatic lipid accumulation under stresses induced by dietary or genetic factors, which underlies its secondary impact on atherosclerosis and determines the therapeutic efficacy of Atorvastatin. Show less
Hypertrophic cardiomyopathy (HCM) arises from genetic mutations in sarcomere proteins, resulting in major structural abnormalities and limited treatment options. Patients with HCM had reduced expressi Show more
Hypertrophic cardiomyopathy (HCM) arises from genetic mutations in sarcomere proteins, resulting in major structural abnormalities and limited treatment options. Patients with HCM had reduced expression of the FGF12 (fibroblast growth factor 12), but its precise functional role remains unclear. To explore FGF12's function and interactions, we utilized clustered regularly interspaced short palindromic repeats-Cas9 technology in cardiomyocytes derived from human induced pluripotent stem cells-induced cardiomyocytes, as well as in other cell lines and mouse models (MYH7 First, we observed a decrease in FGF12 expression and a difference in its subcellular localization in patients with HCM compared with healthy volunteers. In hypertrophic mouse models, injecting adeno-associated virus 9 reduced myocardial hypertrophy. FGF12 binds to calmodulin and inhibits its phosphorylation. This interaction also suppresses the expression and phosphorylation of downstream proteins, including CaMKII, ERK1/2, CREB1, and MCU. The nuclear-localization FGF12 binds to the promoter region of CREB1. FGF12 inhibits the expression of the CREB1-MCU axis expression, leading to reductions in both mitochondrial Ca This study reveals a pathological mechanism associated with HCM linked to FGF12. FGF12, located outside the nucleus, suppresses the expression of metabolism-related genes by reducing the phosphorylation levels within the calmodulin-ERK1/2-CREB1-MCU axis. In contrast, the nuclear localization of FGF12 facilitates its binding to the promoter regions of CREB1, inhibiting CREB1 expression. This dual action maintains cardiomyocyte function and mitochondrial homeostasis. Our findings position FGF12 as a promising therapeutic target for HCM. Show less
Li Zhang, Yuting Wang, Wei Min Gao+8 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
Coronary restenosis remains a major challenge following percutaneous coronary intervention (PCI), necessitating the development of effective stent-eluting drugs. Previous studies indicate that scutell Show more
Coronary restenosis remains a major challenge following percutaneous coronary intervention (PCI), necessitating the development of effective stent-eluting drugs. Previous studies indicate that scutellarin protects vascular endothelial cells and exhibits anti-thrombotic and anti-platelet effects. Notably, our prior research demonstrated that scutellarin specifically counteracts oxidative stress-driven endothelial dysfunction, a key initiating event in restenosis. This combined evidence strongly suggests its potential against in-stent restenosis (ISR). Therefore, this study explores the efficacy of scutellarin in preventing ISR after PCI. We investigated scutellarin, derived from Erigeron breviscapus, for its potential to prevent ISR following PCI. The efficacy and mechanism of scutellarin were evaluated using both in vivo and in vitro models. An experimental atherosclerosis model was established in APOE In APOE This study establishes the efficacy of scutellarin in mitigating ISR using two complementary in vivo models. Scutellarin-eluting stents in atherosclerotic minipigs overcome translational barriers through full interventional simulation. Furthermore, scutellarin inhibits VSMCs proliferation, migration and promotes autophagy-coordinated apoptosis by the coordinated downregulation of both the Pl3K/AKT and lKKs/NF-κB cascades.These findings highlight scutellarin as a promising candidate for next-generation bioactive stent coatings, bridging phytopharmacology and precision interventional cardiology. Show less
Neuroplasticity is the core process by which the brain responds to aging, learning, and injury. Reporting positive non-pharmacological intervention approaches to promote neural plasticity is a core fo Show more
Neuroplasticity is the core process by which the brain responds to aging, learning, and injury. Reporting positive non-pharmacological intervention approaches to promote neural plasticity is a core focus of contemporary neuroscience and rehabilitation medicine. Tai Chi (TC), as a traditional Chinese physical and mental practice that deeply combines soothing body movements, breathing regulation, and spiritual focus, is increasingly attracting attention from the scientific community for its role in facilitating brain health. Our review seeks to combine recent evidence, elucidate how TC promotes neural plasticity via multi-level mechanisms, discuss its advantages in promoting cognitive, motor, and emotional functions, and investigate its clinical utilization prospects and future research challenges in neurorehabilitation. According to reviewing recent literature, we combined evidence from cross-sectional studies, randomized controlled trials, systematic reviews, and meta-analyses, with a center on citing research findings utilizing multimodal neuroimaging techniques (such as fMRI, fNIRS, EEG) and molecular biology techniques to construct a complete chain of evidence from molecules to systems. TC drives multi-level neural plasticity modifications via its unique physical and mental combination properties. At the macro level, it can enhance the gray matter volume of the hippocampus and prefrontal cortex, and promote the organizational effectiveness of large-scale functional networks in the brain. At the micro molecular level, TC establishes a favorable microenvironment for neuronal survival, synaptic plasticity, and neural repair by upregulating BDNF, increasing endogenous antioxidant defense, modulating inflammatory balance, and improving mitochondrial energy metabolism. These structural, functional, and molecular level changes collectively form the neurobiological basis for TC to promote memory and executive function, increase balance and motor management, and promote emotional regulation ability. Our review further assesses the clinical effectiveness of TC in the rehabilitation of neurological diseases, such as Parkinson's disease (PD), stroke, and mild cognitive impairment, determining that it not only decreases symptoms, but may also have the possible role to decrease disease development. Ultimately, our review delve into the challenges and future perspectives experienced by this range in the context of standardization of research paradigms, causal reasoning of mechanisms, and individualized interventions. Show less
The formation and retrieval of reward memories within the hippocampus are critical mechanisms underlying the development of substance use disorder. Nitrous oxide (N
Diabetic peripheral neuropathy (DPN), a severe complication of diabetes, is a key risk factor for diabetic foot (DF) that contributes highly to amputation and mortality. The pathogenesis of DPN remain Show more
Diabetic peripheral neuropathy (DPN), a severe complication of diabetes, is a key risk factor for diabetic foot (DF) that contributes highly to amputation and mortality. The pathogenesis of DPN remains unclear and complex, with no effective treatments currently available. Monoamine oxidase (MAO), a flavin adenine dinucleotide (FAD)-dependent enzyme, catalyzes the oxidative deamination of critical biogenic amines. The MAO family comprises two subtypes, MAOA and MAOB, which play distinct roles in pathophysiology. In this study, we identified that MAOB but not MAOA is pathologically upregulated in the sciatic nerve (SN) tissues of DPN patients and in the SN/dorsal root ganglion (DRG) tissues of DPN model mice. Notably, the selective MAOB inhibitor Khellin (Khe) effectively alleviated DPN-like pathology in mice. To explore the mechanistic role of MAOB in DPN, we performed proteomic profiling of DRG tissues from DPN mice and validated the findings using a MAOB-specific knockdown DPN mice model treated with adeno-associated virus (AAV) 8-MAOB-RNAi. Our results demonstrate that Khe targets MAOB to mitigate DPN pathology through HIF-1α/BACE1/Aβ/NLRP3/tau pathway, mediated by Schwann cell/DRG neuron crosstalk. All findings suggest that selective MAOB inhibition represents a promising therapeutic strategy for DPN, with Khe as a potential candidate for clinical translation against this disease. Show less
Atherosclerosis (AS) is a prevalent typical chronic inflammation disease characterised by lipid deposition, immune cell infiltration and inflammatory response in the arterial intima. The long-term tre Show more
Atherosclerosis (AS) is a prevalent typical chronic inflammation disease characterised by lipid deposition, immune cell infiltration and inflammatory response in the arterial intima. The long-term treatments of the existing drugs suffered safety concerns. Show less
This study aims to evaluate the association between multiple lipid indices and coronary collateral circulation (CCC) in patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI) Show more
This study aims to evaluate the association between multiple lipid indices and coronary collateral circulation (CCC) in patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI). This was a cross-sectional retrospective study involving 421 patients with STEMI who underwent coronary angiography between January 2022 and December 2024. Participants were categorized into a poor CCC group (Rentrop grade 0-1) and a good CCC group (Rentrop grade 2-3) according to Rentrop grading criteria. The following lipid parameters were evaluated as both continuous and categorical variables: total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (ApoB), apolipoprotein A-I (ApoA-I), non-HDL-C/HDL-C, ApoB/ApoA-I, atherogenic index of plasma (AIP), and lipoprotein composite index (LCI). The associations between these lipid indices and CCC status were assessed using multivariate logistic regression and receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression analysis revealed that higher HDL-C quartiles were significantly associated with reduced odds of poor CCC (odds ratio [OR]: 0.544, 95% confidence interval [CI]: 0.351-0.771, P < 0.05), whereas elevated LDL-C (OR: 29.299, 95% CI: 3.562-240.976, P < 0.05), non-HDL-C (OR: 50.140, 95% CI: 5.408-464.834, P < 0.01), and non-HDL-C/HDL-C (OR: 4.510, 95% CI: 1.186-25.368, P < 0.05) quartiles were significantly associated with increased odds of poor CCC. Receiver operating characteristic (ROC) curve analysis demonstrated that LDL-C (cutoff: 3.265, AUC: 0.647, 95% CI: 0.573-0.721, P < 0.001), non-HDL-C (cutoff: 2.735, AUC: 0.752, 95% CI: 0.688-0.816, P < 0.001), and non-HDL-C/HDL-C (cutoff: 2.393, AUC: 0.686, 95% CI: 0.611-0.761, P < 0.001) exhibited favorable predictive performance for poor CCC. Stratification analysis showed that the highest prevalence of poor CCC was observed in patients with concurrently elevated levels of LDL-C, non-HDL-C, and non-HDL-C/HDL-C. Several lipid indices-including LDL-C, non-HDL-C, and the non-HDL-C/HDL-C ratio-are significantly associated with impaired CCC in patients with STEMI. Notably, non-HDL-C exhibits the strongest association with CCC dyscrasia and therefore warrants early clinical attention. Show less
Xi-Yu Zhao, Zhen-Qi Wu, Tian-Yu Zhang+4 more · 2026 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
Attention deficit hyperactivity disorder(ADHD), a common neurodevelopmental disorder in children, is characterized by inattention, hyperactivity, and impulsivity. Epidemiological surveys show that the Show more
Attention deficit hyperactivity disorder(ADHD), a common neurodevelopmental disorder in children, is characterized by inattention, hyperactivity, and impulsivity. Epidemiological surveys show that the prevalence of ADHD in children is gradually increasing worldwide, and it is the most common childhood mental disorder in China. Because of the complex clinical symptoms, multiple co-morbidities, and unknown etiology, ADHD has far-reaching negative impacts on individuals, families, and the society. Behavioral interventions, as a pillar in the management of ADHD, play a targeted role in improving children's social functioning, with significant benefits supported by evidence. However, they are constrained by uneven resources, poor compliance, and insufficient continuity, Western medicine has multiple adverse effects and unclear long-term effects in the treatment of ADHD despite the definite efficacy. Accordingly, there is an urgent need to find safe and effective therapies suitable for children. With a holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has significant advantages in treating ADHD via multiple targets, which involves dopamine(DA), norepinephrine(NE), 5-hydroxytryptamine(5-HT), cyclic adenosine monophosphate(cAMP), brain-derived neurotrophic factor(BDNF) and other signaling pathways. Through these pathways, TCM can treat ADHD through the regulation of neurotransmitters, enhancement of prefrontal and striatal functions, enhancement of neuronal protection, attenuation of neuroinflammation, and reduction of neuronal apoptosis. However, a systematic study remains to be conducted. This paper summarizes the signaling pathways related to the treatment of ADHD by TCM in the past two decades, aiming to provide reference for delving into the mechanism and exploring effective TCM prescriptions for ADHD in children and to give full play to the advantages of the efficacy and characteristics of TCM. Show less
Phytate (phytic acid, or InsP6), the primary phosphorus storage compound in plants, plays essential roles in nutrient homeostasis and cellular signaling. However, its strong metal-chelating properties Show more
Phytate (phytic acid, or InsP6), the primary phosphorus storage compound in plants, plays essential roles in nutrient homeostasis and cellular signaling. However, its strong metal-chelating properties make cytosolic accumulation cytotoxic, necessitating its sequestration into vacuoles for safe storage. Here, we present the cryo-EM structures of the rice vacuolar phytate transporter, OsMRP5, captured in distinct functional states. These structures reveal the molecular basis of OsMRP5 function as an ATP-binding cassette (ABC) transporter. OsMRP5 employs a specialized substrate-recognition mechanism, uniquely adapted to bind the fully hydrophilic InsP6 through extensive electrostatic and hydrogen-bonding interactions within two distinct, highly polar binding sites in its central cavity. A distinctive electropositive tunnel, positioned above the central cavity, forms a continuous pathway connecting the InsP6-binding pocket to the vacuolar export site. This tunnel likely generates an electrostatic attraction that facilitates the movement of the highly anionic InsP6 through the transporter. By mapping mutations from low-phytic acid (lpa) crop variants onto the OsMRP5 structures, we pinpoint their conserved locations critical for transporter function and validate their impact experimentally. These results reveal how OsMRP5 recognizes and transports the highly charged InsP6 molecules into vacuoles, providing a molecular framework for targeted manipulation of this agriculturally important transporter. Show less
Validate the clinical utility of exosome cargo (miRNAs/proteins) and NLRP3/BDNF as key regulatory molecules for acupuncture-mediated spinal cord injury (SCI) recovery. From the establishment of the da Show more
Validate the clinical utility of exosome cargo (miRNAs/proteins) and NLRP3/BDNF as key regulatory molecules for acupuncture-mediated spinal cord injury (SCI) recovery. From the establishment of the database to May 2025, a literature search was conducted on PubMed, and Embase, using keywords ["exosome cargo" or "exosome"], ["acupuncture" or "acupuncture and moxibustion" or "electroacupuncture" or "EA"], ["spinal cord injury" or "SCI"], ["immune regulation"], ["inflammatory reaction"], ["neuroregeneration" or "nerve"]. Including peer-reviewed studies on human/animal models, articles that do not meet the requirements are excluded. Preclinically, MSC-exosomal miR-145-5p suppressed TLR4/NF-κB signaling, reducing spinal IL-1β by 47% in SD rats. Schwann cell-exosomal MFG-E8 activated SOCS3/STAT3, increasing M2 macrophage CD206 by 63% and raising rat BBB scores by 3.8 points; Treg-exosomal miR-2861 upregulated tight junction proteins (occludin/ZO-1) to repair the blood-spinal cord barrier. Acupuncture (EA at GV14/GV4) upregulated spinal BDNF by 72% and NGF by 58% via Wnt/β-catenin, while EA at GV6/GV9 downregulated NLRP3 by 42-58% and TNF-α by 35-47%. Clinically, EA at EX-B2 increased ASIA scores by 3.2±1.1 points (Guo et al). Besides, 5x/week EA improved ASIA vs 3x/week (+6.4 points). EA+exercise reduced MAS by 1.6-2.9 points, with outcomes correlated to peripheral NLRP3 reduction, BDNF elevation, and MBI/WISCIII increases. Exosome cargo (miR-145-5p/MFG-E8) and NLRP3/BDNF are key regulatory molecules underlying acupuncture-mediated SCI recovery. However, limitations (small RCT samples, heterogeneous acupuncture protocols, unstandardized exosome isolation) hinder translation. Future work should focus on standardized biomarker detection, exosome engineering, and large-scale clinical trials. Show less
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of cancer-related deaths. Immune checkpoint inhibitors (ICIs) of programmed death-1 (PD-1)/programmed de Show more
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of cancer-related deaths. Immune checkpoint inhibitors (ICIs) of programmed death-1 (PD-1)/programmed death ligand-1 signaling induce tumor regression in some patients with NSCLC, but most patients with NSCLC exhibit resistance to ICIs therapy. NSCLC shapes the potent tumor immunosuppressive microenvironment (TIME) that underlies tumor immune tolerance and acquired resistance. Therefore, elucidating the cellular and molecular mechanisms by which NSCLC establishes and sustains the TIME is essential for developing novel strategies to overcome immune resistance and enhance the clinical benefit of ICIs. The correlation between sterile alpha motif domain and histidine-aspartate domain-containing protein 1 (SAMHD1) expression and ICIs was analyzed via immunohistochemistry. Cell migration assay was performed to assess the effect of SAMHD1 on macrophage recruitment. Multicolor flow cytometry was performed to analyze the effect of SAMHD1 knockdown on the tumor microenvironment. SAMHD1 regulation of the dual specificity phosphatase 6-extracellular regulated protein kinases 1/2 (DUSP6-ERK1/2) pathway was verified by RNA sequencing and western blotting. Here, we identify the SAMHD1 as a potential therapeutic target and a major determinant of poor response to ICIs in patients with NSCLC. Tumors with high SAMHD1 expression show resistance to anti-PD-1 antibody (αPD-1) treatment, whereas tumors with low SAMHD1 expression are highly sensitive. SAMHD1-dependent resistance to αPD-1 is characterized by increased tumor-associated macrophages (TAMs) infiltration and reduced CD8+T cell numbers. Mechanistically, SAMHD1 regulates the expression of macrophage-associated chemokines by influencing the activation of the DUSP6-ERK1/2 pathway, which contributes to TAMs aggregation within NSCLC tumors to shape an immunosuppressive microenvironment. The HIV accessory protein viral protein-x (VPX) specifically degrades SAMHD1 to promote HIV replication. Similarly, the vpx-engineered oncolytic adenovirus (oAd-vpx) targets SAMDH1 degradation to enhance oncolytic adenovirus replication and weaken the hostile immune microenvironment shaped by TAMs, thereby triggering a CD8+T-cell-dependent antitumor immune response. The combination of oAd-vpx and αPD-1 inhibits tumor growth and enhances sensitivity to ICIs in both mouse and human NSCLC. This research identifies a key mechanism of SAMHD1-driven immunosuppression and highlights its important role in oncolytic adenovirus therapy. This study provides a theoretical basis for targeting SAMHD1 as a drug therapy strategy in patients with NSCLC. Show less
To elucidate the molecular mechanism by which ginsenoside Rg3 (G-Rg3) protects human bronchial epithelial (HBE) cells against lipopolysaccharide (LPS)-induced injury, focusing on its regulation of aut Show more
To elucidate the molecular mechanism by which ginsenoside Rg3 (G-Rg3) protects human bronchial epithelial (HBE) cells against lipopolysaccharide (LPS)-induced injury, focusing on its regulation of autophagic flux and the TLR4/NF-κB-mediated inflammatory pathway. HBE cells were treated with LPS (1-100 ng/mL) to induce autophagy dysregulation and inflammation. G-Rg3 (2-16 μM) was administered to evaluate its protective effects. Western blotting was used to detect autophagy-related proteins (ATG4B, ATG7, PIK3C3, LC3B, p62) and TLR4/NF-κB signaling molecules; ELISA quantified proinflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6, IL-8); PI staining and flow cytometry analyzed cell death and apoptosis. LPS dose-dependently upregulated the expression of autophagy-related proteins (ATG4B, ATG7, PIK3C3, p62, LC3B-II), with accumulated p62 and LC3B-II indicating impaired clearance of autophagic substrates. Additionally, G-Rg3 inhibited LPS-induced TLR4/NF-κB activation, suppressed proinflammatory cytokine secretion, and attenuated HBE cell apoptosis/necrosis. G-Rg3 mitigates LPS-induced HBE cell injury by dual mechanisms: restoring impaired autophagic flux and inhibiting the TLR4/NF-κB inflammatory cascade. These findings identify G-Rg3 as a promising therapeutic agent targeting the crosstalk between autophagy and inflammation in respiratory diseases such as COPD and acute lung injury. Show less
In vitro maturation (IVM) is highly susceptible to influences of the culture environment, which can lead to increased intracellular reactive oxygen species (ROS) levels and thereby induce a stress res Show more
In vitro maturation (IVM) is highly susceptible to influences of the culture environment, which can lead to increased intracellular reactive oxygen species (ROS) levels and thereby induce a stress response in oocytes, ultimately reducing the developmental potential of early embryos. Brain-derived neurotrophic factor (BDNF) is an ovarian endocrine factor that can enhance the function of follicular granulosa cells and promote oocyte maturation, but the specific pathways remain unclear. We supplemented IVM cultures of sheep oocytes with BDNF and examined aspects of oocyte nuclear and cytoplasmic maturation. The addition of 50 ng/mL BDNF promoted the expansion of cumulus cells and increased the rates of first polar body extrusion, cleavage, and blastocyst formation. Compared with untreated controls, BDNF-treated oocytes had improved Ca Show less
Digital technology is frequently regarded as a tool to alleviate loneliness and enhance mental health among older adults, yet its effectiveness remains contested. This study explores whether digital e Show more
Digital technology is frequently regarded as a tool to alleviate loneliness and enhance mental health among older adults, yet its effectiveness remains contested. This study explores whether digital exclusion moderates the association between loneliness and depressive, and examines symptom structure and depressive subtypes. Drawing on data form the 2018 and 2020 waves of the CHARLS (N = 13,719), we employed fixed-effect and mixed-effect models to assess the effect of loneliness on depressive and the moderating role of digital exclusion. Latent profile analysis (LPA) was used to identify symptoms subtypes, while symptom network analysis assessed centrality and network stability. Loneliness significantly predicted depressive symptoms across multiple models, demonstrating robust effects. Digital exclusion was positively associated with depressive symptoms but did not exhibit a statistically significant moderating effect on the loneliness-depression relationship (p > 0.05, Δβ ≈ 0.011). LPA identified six psychologically meaningful subtypes of depression. Symptom network analysis revealed that emotional and motivational symptoms occupied central positions within the network structure, whereas loneliness, despite its strong connections, exhibited relatively low centrality. The overall network structure remained stable over two years, with the digital access group exhibiting stronger network connectivity. This study emphasizes that digital access alone is not a universal remedy for alleviating loneliness. The psychological benefits of digital technology depend on the alignment between individual motivations, usage patterns, and broader social contexts. Future research should focus on digital usage quality and contextual adaptability of interventions, promoting a shift from customization in digital mental health intervention strategies. Show less
Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat faci Show more
Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat facial paralysis clinically, yet its neuroprotective mechanisms remain unclear. This study aims to evaluate the therapeutic effects of QZP on FNI and potential underlying mechanisms. A FNI model was established in male C57BL/6 mice by performing facial nerve crush surgery. QZP (3.51 g/kg) was administered orally once daily for 14 days post-surgery. Facial function was assessed behaviorally. Tissue samples were collected on day 21 for histological evaluation, qPCR and Western blotting. Liver and kidney safety were also assessed via H&E staining and serum biochemical markers. QZP significantly improved facial motor function from day 7 post-injury. Additionally, QZP treatment mitigated neuronal loss in the facial motor nucleus, attenuated buccinator muscle atrophy, and enhanced myelin regeneration, as evidenced by increased MPZ and MBP expression. These were consistent with the increace of the BDNF, TrkB, and QZP promotes structural and functional recovery of facial nerve following injury, likely through activation of the BDNF/TrkB/CREB axis, and demonstrates a favorable safety profile. These findings support its potential as a therapeutic adjunct in peripheral nerve repair. Show less
Cancer-associated fibroblasts (CAF) are abundant stromal cells in the tumor microenvironment (TME) that play a vital role in promoting tumor progression and drug resistance. The mechanisms regulating Show more
Cancer-associated fibroblasts (CAF) are abundant stromal cells in the tumor microenvironment (TME) that play a vital role in promoting tumor progression and drug resistance. The mechanisms regulating heterogeneity of CAFs in renal cell carcinoma (RCC) could represent potential targets for reprogramming the TME. In this study, we conducted single-cell RNA sequence and flow cytometry analyses that identified a CAF subset overexpressing apolipoprotein E (ApoE), which was correlated with poor survival in patients with RCC. Mechanistically, NRF1 activation in CAFs induced formation of ApoEhigh CAFs and secretion of NRG1. ApoEhigh CAFs potentiated stemness properties in the surrounding RCC cells by secreting NRG1 and subsequently activating the HER2/NF-κB pathway. Interfering with NRG1 expression or inhibiting NF-κB signaling reduced ApoEhigh CAF-induced stemness of RCC cells. Furthermore, neutralizing NRG1 enhanced the efficacy of sunitinib in RCC models in vivo. Together, these findings highlight targeting the tumor-promoting functions of ApoEhigh CAFs as a promising approach for treating advanced RCC. NRF1 drives formation of ApoEhigh cancer-associated fibroblasts that secrete NRG1 to stimulate stemness of renal cell carcinoma, revealing a stromal-mediated mechanism that can be inhibited to improve treatment of advanced kidney cancer. Show less
ObjectiveTo evaluate the effects of a combined psychological and functional exercise intervention on emotion, quality of life, and brain-derived neurotrophic factor (BDNF) levels in patients with Park Show more
ObjectiveTo evaluate the effects of a combined psychological and functional exercise intervention on emotion, quality of life, and brain-derived neurotrophic factor (BDNF) levels in patients with Parkinson's disease (PD).MethodsIn this randomized controlled trial, 172 patients with PD were randomly assigned into 2 groups with 86 patients in each group. The control group received routine care, while the intervention group received a 12-week intervention combining psychological support with functional exercise in addition to routine care. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Parkinson's Disease Questionnaire-39 (PDQ-39), Barthel Index, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and serum BDNF levels were assessed before and after the intervention. Adherence rates were also determined for each group. Spearman correlation analysis was used to examine associations between changes in BDNF (ΔBDNF) and changes in HAMA (ΔHAMA) and HAMD (ΔHAMD) scores.ResultsAt the end of the 12-week clinical trial, the intervention group demonstrated significantly lower HAMA, HAMD, PDQ-39, and MDS-UPDRS scores ( Show less
Coronary heart disease (CHD) remains a leading cause of morbidity and mortality worldwide. Mitochondria-associated endoplasmic reticulum membranes (MAMs) have recently emerged as critical mediators in Show more
Coronary heart disease (CHD) remains a leading cause of morbidity and mortality worldwide. Mitochondria-associated endoplasmic reticulum membranes (MAMs) have recently emerged as critical mediators in cardiovascular pathophysiology; however, their specific contributions to CHD pathogenesis remain largely unexplored. This study aimed to identify and validate MAM-related biomarkers in CHD through integrated analysis of transcriptomic sequencing data and Mendelian randomization, and to elucidate their underlying mechanisms. We analyzed two gene expression microarray datasets (GSE113079 and GSE42148) and one genome-wide association study (GWAS) dataset (ukb-d-I9_CHD) to identify differentially expressed genes (DEGs) associated with CHD. MAM-related DEGs were filtered using weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis, Mendelian randomization, and machine learning algorithms were employed to identify biomarkers with direct causal relationships to CHD. A diagnostic model was constructed to evaluate the clinical utility of the identified biomarkers. Additionally, we validated the two hub genes in peripheral blood samples from CHD patients and normal controls, as well as in aortic tissue samples from a low-density lipoprotein receptor-deficient (LDLR-/-) atherosclerosis mouse model. We identified 4174 DEGs, from which 3326 MAM-related DEGs (DE-MRGs) were further filtered. Mendelian randomization analysis coupled with machine learning identified two biomarkers, DHX36 and GPR68, demonstrating direct causal relationships with CHD. These biomarkers exhibited excellent diagnostic performance with areas under the receiver operating characteristic (ROC) curve exceeding 0.9. A molecular interaction network was constructed to reveal the biological pathways and molecular mechanisms involving these biomarkers. Furthermore, validation using peripheral blood from CHD patients and aortic tissues from the Ldlr-/- atherosclerosis mouse model corroborated these findings. This study provides evidence supporting a mechanistic link between MAM dysfunction and CHD pathogenesis, identifying candidate biomarkers that have the potential to serve as diagnostic tools and therapeutic targets for CHD. While the validated biomarkers offer valuable insights into the molecular pathways underlying disease development, additional studies are needed to confirm their clinical relevance and therapeutic potential in larger, independent cohorts. Show less
Clinical application of mesenchymal stem cells for endometrial repair has been hampered by variability in cell quality, large-scale production, and uncertainty regarding the optimal delivery route. In Show more
Clinical application of mesenchymal stem cells for endometrial repair has been hampered by variability in cell quality, large-scale production, and uncertainty regarding the optimal delivery route. In this study, we investigated the therapeutic potential of clinical-grade human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) for treating refractory moderate-to-severe intrauterine adhesion (IUA). In a rabbit IUA model, sub-endometrial injection of IMRCs significantly reduced fibrosis and enhanced endometrial angiogenesis, outperforming uterine perfusion. Transcriptomic analysis revealed distinct pro-angiogenic gene expression profiles between the two delivery routes. In vitro, IMRCs co-cultured with endometrial stromal cells (ESCs) markedly enhanced angiogenic potential compared to either cell type alone. Protein array analysis of the co-culture supernatant showed elevated levels of angiogenic factors, with functional assays confirming that inhibition of ANGPTL4, a non-canonical pro-angiogenic mediator, impaired angiogenesis. In a first-in-human, single-center, phase 1 dose-escalation trial involving 18 patients with refractory IUA, high-dose sub-endometrial IMRC injection promoted angiogenesis, reduced uterine scarring, and improved pregnancy outcomes, with no safety concerns observed over 3 years of follow-up. These findings highlight the translational promise of IMRCs as a novel therapeutic strategy for endometrial regeneration in severe IUA. Show less
Neurodegenerative and psychiatric disorders share overlapping molecular mechanisms, including neuroinflammation, oxidative stress, and neurotransmitter dysregulation. Essential oils from Lavandula ang Show more
Neurodegenerative and psychiatric disorders share overlapping molecular mechanisms, including neuroinflammation, oxidative stress, and neurotransmitter dysregulation. Essential oils from Lavandula angustifolia (TLEO) and Rosa rugosa (PREO) contain neuroactive compounds with therapeutic potential, but their mechanisms remain poorly defined. This study aimed to elucidate the shared and distinct molecular targets and pathways of TLEO and PREO using a multi-scale computational strategy. Compounds identified by GC-MS were evaluated through ADMET profiling, target prediction, and disease-target intersection analysis. Enrichment, network, docking, and dynamics analyses were performed on shared protein-coding targets between essential oils and twelve brain disorders, including seven neurodegenerative conditions (Alzheimer's disease, amyotrophic lateral sclerosis, Friedreich ataxia, Huntington's disease, Lewy body disease, Parkinson's disease, spinal muscular atrophy) and five psychiatric disorders (autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia). A total of 110 compounds yielded 252 common targets, with CHRM2 (GPCR) and NR1H3 (non-GPCR) identified as key hubs. Docking suggested strong binding affinities for caryophyllene oxide at CHRM2 (-7.3 kcal/mol) and α-himachalene at NR1H3 (-8.5 kcal/mol). Molecular dynamics simulations confirmed stable, compact complexes with low RMSD and SASA values. MM/PBSA free energy calculations quantitatively validated these interactions, revealing favorable binding energetics driven predominantly by van der Waals and hydrophobic contributions, consistent with the terpenoid chemical profiles. Functional enrichment highlighted involvement in cholinergic signaling, lipid metabolism, and inflammatory regulation. This study demonstrates that PREO and TLEO can modulate multiple targets relevant to brain disorders through both GPCR and non-GPCR mechanisms. These findings provide a computationally inferred mechanistic framework for the potential neuroprotective synergy of these oils and highlight essential oil-derived compounds as promising leads for further experimental investigation. Show less