Staphylococcus aureus is a significant pathogen that poses a threat to both human and animal health. Its pathogenicity in humans has been extensively studied, however, the signaling pathways and key g Show more
Staphylococcus aureus is a significant pathogen that poses a threat to both human and animal health. Its pathogenicity in humans has been extensively studied, however, the signaling pathways and key genes in Koi Carp responding to S. aureus from human rhinitis remain unclear. In this study, we established an intraperitoneal infection model in koi carp (Cyprinus carpio) using an S. aureus isolate from patients with rhinitis and integrated RNA-seq, qPCR, and ELISA to dissect the host response. Our findings reveal a dual-module immune evasion strategy employed by S. aureus in koi carp. Module I: The pathogen down-regulated the entire complement coagulation cascade (C3, C9, CFH, F7/9/10) and apolipoprotein-mediated opsonins (APOA1, APOB, APOC1/2), thereby crippling innate clearance. Module II: The host mounted a restricted but potent counter-response, characterized by type I IFN signalling (gvin1, MHC-I), NK/T-cell co-stimulation (CD244, SLAMF5), and the selective induction of IL-8 and IL-1β, while IL-6, IL-10, and TNF-α remained unchanged. Functionally, serum superoxide dismutase (SOD), catalase (CAT), and lysozyme (LZM) activities surged, confirming an oxidative burst, whereas splenic CD22R protein decreased, indicating B-cell disinhibition. These results establish a molecular basis for understanding the interaction between human-derived S. aureus and the immune system of aquatic organisms. Show less
Given the potential of polyphenols to mitigate neurodegenerative diseases (NDDs), this meta-analysis investigated whether clinical evidence supports the use of polyphenols for neuroprotection and as n Show more
Given the potential of polyphenols to mitigate neurodegenerative diseases (NDDs), this meta-analysis investigated whether clinical evidence supports the use of polyphenols for neuroprotection and as nutritional strategies in NDDs. We analyzed different polyphenol types across seven NDDs, 13 studies involving 849 participants were included. Prespecified outcomes comprised global cognition (Mini-Mental State Examination, MMSE), domain-specific cognition (Alzheimer's Disease Cooperative Study-Cognitive Subscale, ADCS-Cog), activities of daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living, ADCS-ADL), neuropsychiatric symptoms (Neuropsychiatric Inventory, NPI), and selected biomarkers (plasma amyloid-β40 and brain-derived neurotrophic factor, BDNF). Reporting followed PRISMA 2020 guidelines, methods conformed to the Cochrane Handbook, and certainty of evidence was assessed using GRADE. Overall, polyphenol supplementation was associated with improved global cognition (pooled MD in MMSE = 2.06; 95% CI 0.62-3.49). In subgroup analyses, flavonoids were associated with a modest but significant improvement in MMSE scores, whereas stilbenes produced a significant benefit in daily functioning (ADCS-ADL) without clear gains in MMSE or ADCS-Cog and no consistent effects on NPI. Anthocyanidins, phenolic acids, and lignans did not significantly affect cognitive outcomes (MMSE or ADCS-Cog), and polyphenol subclasses did not yield robust or consistent changes in NPI or biomarker endpoints (Aβ40 and BDNF). Specific polyphenol subclasses therefore appear to confer selective cognitive and functional benefits, with stilbenes primarily supporting functional outcomes and flavonoids potentially enhancing global cognition. Show less
This study aimed to assess the childbirth readiness of women in their third trimester of pregnancy and to identify distinct readiness profiles using latent profile analysis (LPA). Additionally, it exp Show more
This study aimed to assess the childbirth readiness of women in their third trimester of pregnancy and to identify distinct readiness profiles using latent profile analysis (LPA). Additionally, it explored the factors influencing childbirth readiness in order to guide targeted interventions for improved maternal and neonatal outcomes. A cross-sectional study was conducted among women in their third trimester of pregnancy between May and November 2024. Eligible participants completed a general information questionnaire, the Childbirth Readiness Scale (CRS), the Childbirth Attitude Questionnaire (CAQ), and the Perceived Social Support Scale (PSSS). LPA identified three groups with distinct childbirth readiness levels: "Low Readiness - Childbirth Knowledge Deficit" (37.9%), "Moderate Readiness - Good Lifestyle Habits" (47.9%), and "High Readiness - Rich Health Knowledge" (14.2%). In addition, gestational age, previous childbirth history, adverse pregnancy outcomes, childbirth attitudes, and social support had different influences on women in different latent profiles of childbirth readiness. There was significant heterogeneity in childbirth readiness among women in their third trimester. Women with lower readiness-especially in childbirth knowledge-would greatly benefit from targeted educational programs, whereas those with moderate readiness levels would find enhanced emotional and psychological support most advantageous. These findings support the implementation of profile-based, personalized prenatal care strategies to improve childbirth preparedness and optimize maternal and neonatal outcomes. Show less
Recent evidence has shown that bone marrow mesenchymal stem cells (BMSCs) have multiple biological applications and play an important role in improving cognitive dysfunction. However, it is still uncl Show more
Recent evidence has shown that bone marrow mesenchymal stem cells (BMSCs) have multiple biological applications and play an important role in improving cognitive dysfunction. However, it is still unclear whether BMSCs play a role in cognitive impairment induced by chronic pain. This study aimed to evaluate the therapeutic effect of BMSCs on neuropathic pain-induced cognitive dysfunction and explore its potential mechanisms. A mouse chronic constriction injury (CCI) model was established, and the new object recognition task and fear conditioning were used to detect cognitive function; the expression of CXCL12/CXCR4 in blood and hippocampus was detected. After intravenous injection of BMSCs, changes in cognitive function and expression of the CXCL12/CXCR4 pathway, dentate gyrus neurogenesis, and excitability of hippocampal neurons were detected. In addition, induction of cognitive impairment in normal mice by CXCL12 recombinant protein was used to clarify whether the CXCL12/CXCR4 pathway mediates the cognitive function improvement effect of BMSCs. Our results found CCI mice showed significant cognitive impairment 21 days after surgery, with significantly increased expression of CXCL12/CXCR4 in blood and hippocampus. Intravenous injection of BMSCs significantly improved cognitive function, inhibited expression of CXCL12/CXCR4 in blood and hippocampus, promoted neurogenesis in dentate gyrus of CCI mice, and increased expression of BDNF and c-Fos in the hippocampus. In addition, BMSCs alleviate cognitive impairment induced by intravenous injection of CXCL12 recombinant protein in mice. In summary, BMSCs improve chronic neuropathic pain-induced cognitive dysfunction through peripheral blood CXCL12/CXCR4, and BMSCs may develop into therapeutic targets for chronic pain induced cognitive impairment. Show less
Executive function (EF) deficits are a core cognitive feature of autism spectrum disorder (ASD) and are closely associated with social responsiveness. Previous research has primarily focused on childr Show more
Executive function (EF) deficits are a core cognitive feature of autism spectrum disorder (ASD) and are closely associated with social responsiveness. Previous research has primarily focused on children with ASD, whereas how specific executive components relate to social functioning in adults remains less clear. This study examined whether patterns of association between EF and social responsiveness differ between children and adults with and without ASD. Data were obtained from the Autism Brain Imaging Data Exchange II (ABIDE II), including 423 participants aged 8-23 years (ASD = 184; controls = 239). EF was evaluated using the Behavior Rating Inventory of Executive Function (BRIEF/BRIEF-A), and social responsiveness was assessed with the Social Responsiveness Scale (SRS). Covariates of age, sex, and full-scale IQ (FIQ) were controlled using entropy balancing in children and multiple regression in adults. Hierarchical regression, moderated mediation analysis, and latent profile analysis (LPA) were conducted to examine the moderation, mediation, and heterogeneity effects, respectively. Across both child and adult samples, individuals with ASD exhibited significantly higher T-scores than controls on nearly all BRIEF and SRS subdomains after covariate adjustment (all adjusted p < 0.01), indicating widespread EF and social responsiveness impairments. Moderation analyses revealed no significant age group × EF interaction, indicating that the association between EF and social responsiveness was consistent across development. Mediation analysis revealed age-specific pathways, with EF broadly mediating social responsiveness in adults but showing more selective mediation in children. LPA identified four distinct subtypes, which were independent of age, sex, and FIQ. EF-social responsiveness associations were evident across development, but the functional contribution of specific executive components became more differentiated with age. Working memory showed greater relative prominence in adulthood. Latent profile analysis revealed heterogeneity in how executive difficulties align with social challenges, supporting developmentally informed assessment and clinical interpretation rather than direct treatment recommendations. Show less
Cognitive reserve (CR) refers to differences in the adaptability of cognitive processes that modify the impact of Alzheimer's disease (AD) pathology on cognitive performance. Currently there are no es Show more
Cognitive reserve (CR) refers to differences in the adaptability of cognitive processes that modify the impact of Alzheimer's disease (AD) pathology on cognitive performance. Currently there are no established blood-based biomarkers of CR in prodromal AD. In this study, we operationalize CR as memory reserve, defined as moderation (attenuation) of the CSF pTau181-memory association. DNA methylation (DNAm) integrates genetic and environmental influences and may capture biological processes that mitigate the impact of AD pathology on memory. We aimed to identify blood DNAm loci that moderate the association between cerebrospinal fluid (CSF) phosphorylated tau (pTau181) and memory in mild cognitive impairment (MCI). We also sought to determine if a DNAm-based signature of memory reserve predicts future memory decline. We analyzed 92 amyloid positive MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with blood DNAm, CSF pTau181, and memory scores (PHC_MEM) collected at the same visit. We first regressed memory scores on covariates (age, sex, number of After removing CpGs with low variability, we identified 6 CpGs with suggestive significance for DNAm×pTau181 interaction ( Blood DNAm patterns that moderate the pTau-memory relationship capture biology underlying memory reserve involving synaptic, vascular, immune, and metabolic pathways, and can be summarized into an MRS that predicts longitudinal memory trajectories in MCI. These findings support blood DNAm as a promising, non-invasive biomarker of cognitive resilience to AD pathology. Show less
Human embryonic stem cell (hESC)-derived hepatocytes (hEHs) display functional deficits, particularly impaired albumin secretion and ammonia metabolism, compared to primary human hepatocytes (PHHs). H Show more
Human embryonic stem cell (hESC)-derived hepatocytes (hEHs) display functional deficits, particularly impaired albumin secretion and ammonia metabolism, compared to primary human hepatocytes (PHHs). Here, we investigated the regulatory role of CCAAT/enhancer-binding protein beta (C/EBPβ) in hepatocyte maturation. Forced C/EBPβ expression enhanced hepatocyte functionality and upregulated hepatocyte-specific genes, while suppressing epithelial-mesenchymal transition (EMT) via downregulating canonical EMT markers. Mechanistically, CUT&Tag and luciferase reporter assays confirmed C/EBPβ directly binds to the promoter regions of CDH1 (E-cadherin) and CPS1 (carbamoyl phosphate synthetase 1). Co-immunoprecipitation identified an interaction between C/EBPβ and the MAPK pathway. RNA interference combined with Western blot analysis revealed that MAPK1-mediated phosphorylation of C/EBPβ at Thr-235 augmented its transactivation activity, accelerating hepatocyte maturation. Our findings establish C/EBPβ as a master regulator that coordinates transcriptional networks and post-translational modifications during hEHs maturation, providing novel insights for generating mature hepatocytes for disease modeling and regenerative medicine applications. The transcriptional activity of C/EBPβ is regulated by MAPK1 protein within the ERK/MAPK signaling pathway. MAPK1 moves from the cytoplasm into the nucleus and transfers phosphate groups to C/EBPβ. This process reverses the "self-inhibition" state of C/EBPβ and enhances its transcriptional activity on downstream target genes. Show less
Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. T Show more
Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. This study aimed to observe the mechanism of EA as an adjunct therapy to escitalopram oxalate (EO) on depressed patients. This study was designed as a single-blinded, double-dummy randomized controlled trial. 61 participants were diagnosed with mild-to-moderate depression according to the International Classification of Diseases 10th Edition (ICD-10, F32) were randomly allocated to receive EA + EO placebo, EO + sham EA, or EA + EO for six weeks treatment. The clinical assessment including depression severity, quality of life (QOL) and clinical safety. Biological indicators of immune-inflammation, the brain-derived neurotrophic factor and glucocorticoid inducible genes in peripheral blood of participants were measured by using enzyme linked immunosorbent assay and real-time polymerase chain reaction respectively before and after treatment. Three interventions improved the depression severity and QOL (P < 0.05), and no inter-group difference was found in the 6th week (P > 0.05). Anxiety psychic and somatic general symptoms in the EA + EO group were improved significantly than those of the other two groups (P < 0.05). After six-week treatment of EA + EO, blood SGK1 mRNA, GILZ mRNA, and BDNF levels were increased significantly ( 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
Angiopoietin-like protein 8 (ANGPTL8), a member of the angiopoietin-like protein (ANGPTL) family, is a physiological inhibitor of lipoprotein lipase (LPL), and plays a critical role in lipoprotein and Show more
Angiopoietin-like protein 8 (ANGPTL8), a member of the angiopoietin-like protein (ANGPTL) family, is a physiological inhibitor of lipoprotein lipase (LPL), and plays a critical role in lipoprotein and triglyceride metabolism in response to nutritional cues. ANGPTL8 is implicated in a wide range of systemic and cellular processes and is closely associated with metabolic and cardiovascular diseases (CVD). Circulating ANGPTL8 is primarily secreted by the liver, with adipose tissue as a secondary source. Its expression is regulated by multiple transcription factors and microRNAs, and is responsive to fasting/refeeding states, hormonal signals, and stress conditions. In lipid metabolism, ANGPTL8 forms complexes with ANGPTL3 and ANGPTL4 to modulate LPL activity under fasting and feeding conditions. In glucose metabolism, ANGPTL8 plays a complex role. While some studies suggest it may improve glucose tolerance and insulin resistance, others indicate it could exacerbate glucose metabolism disorders and diabetes, or have no effect. Cardiovascular diseases are intricately linked to metabolic disorders and diseases. Increasing evidence also links ANGPTL8 to various cardiovascular pathologies, including atherosclerosis, hypertension, cardiomyopathy, cardiac hypertrophy, aortic aneurysm, and dissection. Given the strong interplay between metabolic dysregulation and CVDs, elucidating the role of ANGPTL8 in these processes is of significant interest. This review provides a balanced assessment of ANGPTL8's roles in key pathophysiological processes, highlighting its established functions in metabolism alongside its emerging involvement in CVDs. Understanding the diverse functions of ANGPTL8 in various tissues and metabolic states will lead to new opportunities for therapeutic intervention in cardiometabolic disorders. Show less
Post-cardiac surgery anxiety or depression (PCPAD) is a common neuropsychiatric complication following cardiovascular interventional procedures, which significantly increases the risk of adverse cardi Show more
Post-cardiac surgery anxiety or depression (PCPAD) is a common neuropsychiatric complication following cardiovascular interventional procedures, which significantly increases the risk of adverse cardiovascular events and long-term mortality. Existing treatment strategies have limitations, and clinical needs remain unmet. The gut-brain axis (GBA) serves as a core network regulating neuroimmune and endocrine responses, and its imbalance involves key links such as intestinal flora dysbiosis and neuroimmune crosstalk disorders. It is closely related to the pathogenesis of this complication, providing a novel perspective for targeted interventions. This review aims to systematically clarify the mechanism of GBA in PCPAD, comprehensively explore therapeutic strategies targeting this axis, and focus on the intervention value and application potential of natural products. The study was designed and conducted in strict accordance with the PRISMA 2020 guidelines. Relevant literatures were searched from PubMed, Web of Science Core Collection, ScienceDirect, Embase, Cochrane Library, and CNKI databases from their inception to December 2025. Literatures focusing on GBA-related mechanisms of PCPAD or investigating the mechanisms and clinical applications of natural products targeting GBA for PCPAD treatment were included. Conference abstracts, case reports, duplicate publications, and other ineligible literatures were excluded. Through quality control strategies including double independent screening and verification, priority inclusion of high-credibility evidence, and data cross-validation, 168 eligible literatures were finally included. The composition and functions of GBA, its imbalance mechanisms, and the basic and clinical evidence of natural product-based interventions were systematically analyzed. Studies have shown that GBA imbalance is the core pathogenesis of PCPAD, among which the inflammatory cascade initiated by intestinal flora dysbiosis, abnormal activation of the neuroendocrine axis, disorder of immune-nerve crosstalk, and abnormal gene and epigenetic regulation are key pathological links. In summary, GBA imbalance, especially gut microbiota dysbiosis and neuroimmune interactions, plays a critical role in the pathogenesis of PCPAD. Natural products (including traditional Chinese medicine (TCM) monomers, TCM compound prescriptions, patented TCM drugs, and natural products from other plant sources worldwide) can exert therapeutic effects by synergistically regulating GBA homeostasis through multiple targets. Specifically, they include increasing the abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus, promoting the production of anti-inflammatory metabolites such as short-chain fatty acids, repairing intestinal barrier function, inhibiting pro-inflammatory pathways such as NF-κB and NLRP3 inflammasome, and regulating the levels of neurotransmitters and neurotrophic factors such as 5-HT and BDNF. Basic and clinical studies have confirmed that these natural products have high biocompatibility and low toxic side effects, and are compatible with the safe medication needs of patients during the organ function recovery period after cardiac surgery. Several natural products have been proven to modulate GBA dysfunction, with potential for clinical therapeutic application. This review systematically elucidates a new paradigm of precise intervention for PCPAD via natural products that regulate GBA through multiple targets, addressing the limitation of traditional single-target therapies and providing a low-cost, easily promotable solution for clinical translation. Additionally, natural product-based interventions offer a novel approach for treating post-cardiac surgery complications. In the future, it is necessary to further conduct large-sample, multicenter clinical trials to clarify their mechanisms of action and standardized dosage regimens, strengthen toxicological research, facilitate the translation from basic research to clinical practice, and provide more precise therapeutic strategies for patients. Show less
DUSP6, a dual-specificity phosphatase, has become a focal point in understanding the pathogenesis of various liver disorders. This study aims to investigate the role of DUSP6 in liver fibrosis and exp Show more
DUSP6, a dual-specificity phosphatase, has become a focal point in understanding the pathogenesis of various liver disorders. This study aims to investigate the role of DUSP6 in liver fibrosis and explore the underlying mechanism. Using a CCL4-induced mouse model, the consistent upregulation of DUSP6 expression was observed. Notably, when Dusp6 was knocked down, liver fibrosis showed significant improvement, revealing a protective effect intricately linked to the ERK pathway. This was accompanied by an increase in ferroptosis-related proteins SLC7A11 and GPX4, underscoring the role of ferroptosis, an iron-dependent form of regulated cell death, in this process. Transcriptomic analysis further revealed a crucial downregulation of Cyp2e1 following Dusp6 knockdown. In vitro, DUSP6 knockdown not only promoted ERK phosphorylation but also suppressed CYP2E1 expression, enhancing cell proliferation, bolstering hepatocyte resistance to ferroptosis, and alleviating hepatocyte injury. Importantly, inhibiting CYP2E1 in mouse models of liver fibrosis effectively slowed the progression. These findings illuminate a critical regulatory mechanism that DUSP6 regulates liver fibrosis via targeting ferroptosis, offering new a direction for therapeutic strategies in liver disease. Show less
Chronic obstructive pulmonary disease (COPD) frequently coexists with extrapulmonary comorbidities, most notably cardiovascular diseases (CVD). However, the mechanisms linking COPD to CVD, particularl Show more
Chronic obstructive pulmonary disease (COPD) frequently coexists with extrapulmonary comorbidities, most notably cardiovascular diseases (CVD). However, the mechanisms linking COPD to CVD, particularly atherosclerotic CVD, remain poorly understood. Extracellular vesicles (EVs), as key mediators of inter-organ communication, may participate in this pathological connection. This study aims to determine whether EVs derived from airway epithelial cells (AECs) of individuals with COPD contribute to endothelial dysfunction and atherosclerosis. EVs were isolated from primary airway epithelial cells of COPD patients and matched controls. Their effects on endothelial cell function were assessed in vitro by evaluating inflammation, apoptosis, and monocyte adhesion. ApoE-/- mice were intravenously injected with these EVs to examine their impact on atherosclerotic lesion development. Differentially expressed microRNAs were identified, and the regulatory relationship between miR-141-3p and PDCD4 was validated through molecular assays. Additionally, miR-141-3p supplementation was performed to determine its therapeutic potential in mitigating endothelial injury and atherosclerosis. COPD AECs-derived EVs markedly increased endothelial inflammation, apoptosis, and monocyte adhesion compared with control EVs. In ApoE-/- mice, COPD-derived EVs accelerated the formation of atherosclerotic plaques. Mechanistic analyses revealed that miR-141-3p was significantly downregulated in COPD EVs and directly targeted the 3' untranslated region of PDCD4 to regulate its transcription, leading to dysregulation of PDCD4/NF-κB signaling in endothelial cells. Restoration of miR-141-3p levels in COPD-derived EVs alleviated endothelial injury and reduced atherosclerotic lesion progression both in vitro and in vivo. This study identifies a previously unrecognized mechanism by which COPD AECs-derived EVs may promote atherosclerotic CVD via miR-141-3p-mediated regulation of PDCD4 and subsequent activation of NF-κB signaling. These findings highlight miR-141-3p as a promising therapeutic target to reduce vascular complications in COPD. Show less
Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable s Show more
Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable strategies for Show less
Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson' Show more
Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson's disease (PD). However, no study has investigated peripheral BDNF levels and BDNF Val66Met polymorphism in the prodromal stage of PD and their relationship with disease conversion. In total, 120 patients with video-polysomnography confirmed isolated REM sleep behavior disorder (iRBD) and 120 healthy controls (HCs) were enrolled. Genetic analyses were performed, and plasma levels of BDNF were measured. All patients with iRBD underwent comprehensive clinical testing, and 107 iRBD patients were prospectively followed up. Plasma BDNF levels were significantly lower in the iRBD group than in HCs (18,878.85 pg/mL vs. 24,649.85 pg/mL, p = 0.002), but no differences were observed in BDNF Val66Met carrier rates between the two groups. Plasma BDNF levels did not differ significantly between BDNF Val66Met carriers and noncarriers. Notably, higher plasma BDNF levels were associated with an increased risk of short-term disease conversion (hazard ratio = 3.418, 95% CI: 1.520-7.684, p = 0.003), whereas BDNF Val66Met carrier rates showed no such association. Our findings suggest that plasma BDNF is significantly associated with iRBD and may likely serve as a prognostic biomarker for the development of neurodegenerative disease. However, the BDNF Val66Met polymorphism may not be involved in the pathogenesis of iRBD as well as phenoconversion in the studied population. Show less
Spinal cord injury (SCI) represents significant central nervous system trauma and has consistently been a focal point of research in the domain of neural regeneration and repair. Currently, there is n Show more
Spinal cord injury (SCI) represents significant central nervous system trauma and has consistently been a focal point of research in the domain of neural regeneration and repair. Currently, there is no effective treatment available. Various modalities of magnetic stimulation have emerged for recovery from spinal cord injuries; however, the underlying mechanisms remain unclear, significantly hindering the application of magnetic stimulation technologies in treating such injuries. This study aims to elucidate these relevant mechanisms by establishing a simulated closed-loop magnetic stimulation system. In this study, we established a right hemisection model at T8 in mice and administered continuous simulated closed-loop magnetic stimulation targeting the left motor cortex and right L5 nerve root over six weeks. We subsequently utilized a spinal cord dorsal hemisection model to examine regeneration of the corticospinal tract (CST). Motor-evoked potential assessments and calcium imaging techniques were employed to explore neural circuit repair. Additionally, we integrated transcriptomics, proteomics, and metabolomics approaches to investigate related mechanisms. The findings indicate that simulated closed-loop magnetic stimulation effectively restores motor function in the hind limbs, promotes the regeneration of corticospinal tracts in mice with spinal cord injuries, and facilitates the reconstruction of sensorimotor circuits and functions within the spinal cord. Simulated closed-loop magnetic stimulation significantly enhances axonal regeneration of the CST following SCI. This effect may be mediated through the activation of the AMPK-CREB-BDNF signaling pathway, which promotes neurotrophic factor secretion and subsequently induces nerve axon regeneration. This study suggests that simulated closed-loop magnetic stimulation represents a promising therapeutic approach for the treatment for impaired gait following SCI. Show less
Immune checkpoint inhibitors (ICIs) have prolonged cancer survival but exacerbated atherosclerotic cardiovascular disease (ASCVD). This research aims to interrogate the underlying mechanism of ICIs-re Show more
Immune checkpoint inhibitors (ICIs) have prolonged cancer survival but exacerbated atherosclerotic cardiovascular disease (ASCVD). This research aims to interrogate the underlying mechanism of ICIs-related atherosclerotic progression and the potential protective effect of Red Yeast Rice (RYR) on it. A tumor-bearing atherosclerotic (TB-AS) mouse model was established by subcutaneously injecting MC38 cells in male ApoE Show less
Chronic stress, a key contributor to neurological disorders, is mechanistically linked to hypothalamic-pituitary-adrenal (HPA) axis dysregulation, neuroinflammation, and hippocampal neuronal apoptosis Show more
Chronic stress, a key contributor to neurological disorders, is mechanistically linked to hypothalamic-pituitary-adrenal (HPA) axis dysregulation, neuroinflammation, and hippocampal neuronal apoptosis. Current therapeutic approaches remain limited in efficacy and safety. Schisandrol A, a neuroactive lignan from Show less
This study investigated the impact of This retrospective case-control study involved 628 CAD patients and 628 matched controls without CAD. ApoE genotyping was conducted using PCR-chip technology, and Show more
This study investigated the impact of This retrospective case-control study involved 628 CAD patients and 628 matched controls without CAD. ApoE genotyping was conducted using PCR-chip technology, and genotype and allele frequencies were compared between groups. Multivariate logistic regression analyzed the link between ApoE polymorphisms and CAD risk in populations at middle and high altitudes. The data revealed significant differences in These findings validated that the Show less
To assess the predictive value of serum lipoprotein(a) [Lp(a)] for contrast-induced nephropathy in patients with type 2 diabetes mellitus (T2DM). Consecutive T2DM patients who underwent coronary angio Show more
To assess the predictive value of serum lipoprotein(a) [Lp(a)] for contrast-induced nephropathy in patients with type 2 diabetes mellitus (T2DM). Consecutive T2DM patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI) between January 2019 and December 2021 were enrolled. Baseline Lp(a) was measured before the operation. CIN was defined as an increase in serum creatinine of more than 25% or 44 μmol within 72 h of contrast administration. The relationship between Lp(a) and CIN risk was analyzed. A total of 928 T2DM patients were included. CIN developed in 11.1% (103/928) of patients. The Lp(a) level was significantly higher in patients with CIN than in non-CIN patients (311.12 ± 278.66 vs. 254.19 ± 274.56 mg/L, A higher serum Lp(a) level indicates an increased risk of CIN in T2DM patients undergoing CAG or PCI and can serve as an independent predictor of CIN in this population. This study's findings will aid in the clinical prevention and treatment of contrast agent-induced kidney disease. 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
Abnormalities in protein tyrosine kinases (PTKs) are one of the primary drivers of cancer. As a receptor subfamily, fibroblast growth factor receptors (FGFRs) comprise four subtypes-FGFR1 to FGFR4. Th Show more
Abnormalities in protein tyrosine kinases (PTKs) are one of the primary drivers of cancer. As a receptor subfamily, fibroblast growth factor receptors (FGFRs) comprise four subtypes-FGFR1 to FGFR4. Their abnormal intracellular expression is a significant cause of tumorigenesis, making FGFRs key therapeutic targets in cancer treatment. This paper primarily summarizes the latest research advances in FGFR inhibitors, aiming to provide insights for future design and synthesis studies of FGFR inhibitors. Show less
High-dose methotrexate for pediatric cancer treatment is frequently associated with mucositis, which can lead to delayed or discontinued treatment and impact survival. While individual genetic variant Show more
High-dose methotrexate for pediatric cancer treatment is frequently associated with mucositis, which can lead to delayed or discontinued treatment and impact survival. While individual genetic variants have been implicated, the cumulative impact of genetic variation within relevant biological pathways remains unexplored. We evaluated single nucleotide polymorphisms across 18 pathways previously identified as relevant to mucositis in 278 pediatric patients with acute lymphoblastic leukemia from six academic health centers across Canada. Pathway enrichment was assessed using the Joint Association of Genetic variants tool, and a predictive model was developed using XGBoost, a supervised machine learning algorithm based on gradient-boosted decision trees. Pathway enrichment identified significant associations in IL6 (P = 0.04) and WNT/β-catenin (P = 0.048) signaling pathways. The predictive model (area under the curve [AUC] = 0.76) highlighted single nucleotide polymorphisms associated with inflammation- and mucosa-related genes, including PRKCD, IL17B, MAST3, and CAPN9, with both risk and protective effects. Model performance dropped by 0.15 in AUC (from 0.76 to 0.61) after removing single nucleotide polymorphism features, underscoring their predictive value. This pathway-informed approach identifies genetic contributors to methotrexate-induced mucositis and supports polygenic risk prediction. Our findings provide a foundation for individualized toxicity risk profiling and suggest potential therapeutic targets to mitigate treatment-limiting mucositis in pediatric oncology. Show less
This study aimed to analyze the clinical features, genetic basis, and management of late-onset carbamoyl phosphate synthetase 1 deficiency (CPS1D) through a pediatric case report and literature review Show more
This study aimed to analyze the clinical features, genetic basis, and management of late-onset carbamoyl phosphate synthetase 1 deficiency (CPS1D) through a pediatric case report and literature review, highlighting diagnostic challenges and therapeutic strategies. We present a 19-year-old female with recurrent neurological symptoms since age 8. She underwent comprehensive metabolic screening, neuroimaging, and whole-exome sequencing of theCPS1gene. Identified variants were assessed for pathogenicity using multiple orthogonalin silicoprediction tools. The patient's initial hyperammonemic crisis at age 8 was misdiagnosed as encephalitis. Workup at age 13 confirmed hyperammonemia (peak 168 µmol/L), hypocitrullinemia, and elevated glutamine. Genetic analysis identified compound heterozygousCPS1variants: a novel c.1058 T > C (p.F353S) and known pathogenic c.1145C > T (p.P382L). A self-selected low-protein diet controlled acute crises but led to severe growth failure (height 145 cm, weight 30 kg). Late-onset CPS1D's nonspecific neurological symptoms often lead to misdiagnosis. Diagnosis requires a high index of suspicion, integrating metabolic profiling with genetic confirmation. This case expands the pathogenic genotypic spectrum of CPS1D. It crucially highlights that while dietary management is life-saving, it requires expert multidisciplinary oversight to prevent devastating consequences like growth failure, especially in resource-limited settings. Routine ammonia testing in unexplained encephalopathy is paramount. Show less
Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of ph Show more
Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of phenylacetylglutamine (PAGln), a novel gut microbiota metabolite, in Dox-induced cardiotoxicity (DIC). DIC models were established in vivo and in vitro, and a series of experiments were performed to verify the cardioprotective effect of PAGln. RNA sequencing (RNA-seq) was employed to explore the mechanism of PAGln in DIC. Subsequently, the differentially expressed genes (DEGs) were subjected to comprehensive analysis using diverse public databases, and RT-PCR was used to confirm the expression levels of the candidate genes. Finally, molecular docking techniques were used for validation. PAGln effectively prevented both in vivo and in vitro Dox-induced myocardial injury and cell apoptosis. RNA-seq results showed that 40 genes were up-regulated and 54 down-regulated in the Dox group compared to the Con group, displaying opposite changes in the Dox + PAGln group. Enrichment analysis highlighted several mechanisms by which PAGln alleviated Dox-induced cardiotoxicity, including the lipid metabolic process, calcium-mediated signaling, positive regulation of store-operated calcium channel activity, and hypertrophic cardiomyopathy. In vitro and in vivo experiments confirmed that PAGln treatment could reverse the changes in the expression levels of Klb, Ece2, Nmnat2, Casq1, Pak1, and Apob in Dox. Molecular docking results showed that these genes had good binding activity with PAGln. PAGln shows potential in alleviating Dox-induced cardiotoxicity, with Ece2 identified as key regulatory molecules related to endothelial dysfunction. Show less
Vascular smooth muscle cell senescence contributes critically to vascular remodeling and atherosclerosis, with mitochondrial dysfunction and impaired mitophagy recognized as major contributors. SRC, a Show more
Vascular smooth muscle cell senescence contributes critically to vascular remodeling and atherosclerosis, with mitochondrial dysfunction and impaired mitophagy recognized as major contributors. SRC, a stress-responsive tyrosine kinase, has been linked to aging, yet its role in vascular aging remains unclear. Here, we examined the role of SRC in regulating autophagy/mitophagy using in vitro and in vivo models. An accelerated vascular aging model was established using a high-fat diet and streptozotocin injection in ApoE Show less
To develop and validate a prediction model for in-hospital cardiogenic shock (CS) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) based on machine lea Show more
To develop and validate a prediction model for in-hospital cardiogenic shock (CS) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) based on machine learning (ML) algorithms. A total of 1608 AMI patients admitted to the First Hospital of Lanzhou University during 2023 and 2024 were retrospectively enrolled in this study. The 851 patients from 2023 were randomly divided into a training set ( LASSO regression initially identified 13 candidate features, while the random forest (RF) model demonstrated the best predictive performance in the training set. Following Boruta refinement, seven key features were retained, leading to the construction of an updated RF model. This model achieved an AUROC of 0.906, an accuracy of 0.977, a precision of 0.900, a sensitivity of 0.643, a specificity of 0.996, and a F1 score of 0.750 on the internal validation set. Temporal external validation at the same center showed an AUROC of 0.988, an accuracy of 0.967, a precision of 0.701, a sensitivity of 0.904, a specificity of 0.972, and a F1 score of 0.790. Furthermore, the model demonstrated excellent calibration, with a Brier score of 0.023 and 0.027. The SHAP analysis ranked feature importance as Killip class, D-dimer (DD), creatinine (Crea), alanine aminotransferase (ALT), apolipoprotein B/A (APOB/A), diastolic blood pressure (DBP) and lactate (Lac). We developed and validated a RF model based on seven key variables—Killip class, DD, Crea, ALT, APOB/A, DBP and Lac—that serves as a predictive tool for identifying the risk of in-hospital CS in AMI patients post-PCI. Additionally, we created an online prediction application using Streamlit, which facilitates the implementation of this model into clinical practice. Show less