Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related mortality worldwide due to its high aggressive potential and drug resistance. Previous studies have revealed an impor Show more
Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related mortality worldwide due to its high aggressive potential and drug resistance. Previous studies have revealed an important function of HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 5 (HERC5) in cancer. Six GEO gene microarrays identified HERC5 as a significant upregulated gene in OSCC tissues or cells (log2 Fold change > 1 and adj.p < 0.05). This study aimed to explore the role and underlying mechanisms of HERC5 in OSCC development. High HERC5 expression in OSCC tissues was confirmed by our hospital validation cohort and positively correlated with primary tumor stages. Subsequent functional studies demonstrated that knockdown of HERC5 inhibited the migratory and invasive capabilities with decrease of Vimentin and increase of E-cadherin in OSCC cells. In cisplatin treatment, cell survival rates were significantly reduced in HERC5-silencing OSCC cells, accompanied by the increase in cytotoxicity, DNA damage and apoptosis. OSCC cell-derived tumor xenograft displayed that HERC5 depletion inhibited pulmonary metastasis as well as restored the cisplatin-induced tumor burden. In line with this, overexpression of HERC5 yielded the opposite alterations both in vivo and in vitro. Mechanistically, UDP-glucose 6-dehydrogenase (UGDH) was identified as a HERC5-binding protein. Cysteine residue at position 994 in the HECT domain of HERC5 catalyzed the conjugation of ubiquitin-like protein Interferon-induced 15 kDa protein (ISG15) to UGDH (ISGylation of UGDH) and facilitated its phosphorylation, therefore enhancing SNAI1 mRNA stability. SNAI1 depletion inhibited HERC5 overexpression-triggered invasion and cisplatin resistance of OSCC cells. Our study indicates that HERC5 may be a promising therapeutic target for OSCC. Show less
Ischemic stroke (IS) treatment remains a significant challenge. This study aimed to identify potential druggable genes for IS using a systematic druggable genome-wide Mendelian Randomization (MR) anal Show more
Ischemic stroke (IS) treatment remains a significant challenge. This study aimed to identify potential druggable genes for IS using a systematic druggable genome-wide Mendelian Randomization (MR) analysis. Two-sample MR analysis was conducted to identify the causal association between potential druggable genes and IS. This involved integrating data from the druggable genome, expression quantitative trait loci (eQTL), protein quantitative trait loci (pQTL), and genome-wide association study summary data of IS. Sensitivity and Bayesian colocalization analyses were used to validate the causal relationships. In addition, phenome-wide MR analysis was used to evaluate the side effects or other indications of the identified druggable genes, and their functions were explored using the Metascape database. Our MR analysis identified 16 potential druggable genes significantly associated with IS, three of which were significant in the two QTL datasets. Colocalization analysis revealed six druggable genes (two in the blood eQTL [CALCRL, KCNJ11], two in the brain eQTL [NEK3, THSD1], one in the blood pQTL [MMP12], and one in the brain pQTL [HSD17B12]) had a PP.H4 greater than 0.75. Phenome-wide MR analysis indicated that CALCRL is correlated with benign breast neoplasms, and HSD17B12 is associated with essential hypertension and hypertension. This study identified six potential druggable genes (CALCRL, KCNJ11, NEK3, THSD1, MMP12, and HSD17B12) associated with IS risk. Further research is required to explore the specific roles of these druggable genes in the onset and progression of IS. Show less
This study aimed to comprehensively evaluate the clinical effectiveness and safety of acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) in treating post-stroke cognitive im Show more
This study aimed to comprehensively evaluate the clinical effectiveness and safety of acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) in treating post-stroke cognitive impairment (PSCI) through meta-analysis and trial sequential analysis (TSA), moreover to provide an evidence-based basis for the treatment of PSCI in clinical practice. The study conducted a comprehensive search of eight major domestic and international databases, including PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP and China Biology Medicine (CBM). Four English and four Chinese databases of randomized controlled trials of acupuncture combined with rTMS for the treatment of PSCI from inception until July 2025. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan5.4 and Stata/MP 18.0, and trial sequential analyses were performed by TSA 0.9. Sixteen RCTs involving 1,058 patients were included, including 532 patients in the experimental group and 526 patients in the control group. Meta-analysis results showed that the experimental group had a higher clinical effectiveness rate in treating patients with PSCI compared to the control group [RR = 1.29, 95% CI (1.08, 1.55), Acupuncture combined with rTMS can improve cognitive function, regulate daily living ability, and regulate neurotransmitter levels in patients with PSCI, which is worthy recommended in the clinic. However, due to limitations in sample size, inclusion quality and incomplete reporting, it is worth noting that more rigorously designed and high-quality studies are needed to further validate these conclusions. Show less
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) is a highly prevalent female malignancy. As the epigenomic characteristics of immune cells and cancer cells can serve as predict Show more
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) is a highly prevalent female malignancy. As the epigenomic characteristics of immune cells and cancer cells can serve as predictive indicators for the response to cancer immunotherapy, analysis of epigenetically modified genes (EpiGenes) could contribute to CESC treatment. The ssGSEA algorithm was employed to compute EpiGenes scores. Core genes that exhibited significant module association and a close correlation with EpiGenes scores were identified via the WGCNA package. Univariate Cox proportional hazards regression was performed on the core genes using the survival package, followed by gene set reduction via LASSO Cox regression. Ultimately, key genes were determined through multivariate Cox regression to establish a RiskScore model. Further, the optimal risk cutoff was determined using the survminer package to stratify CESC patients into high- and low-risk subgroups. For enrichment analysis, clusterProfiler and GSEA were utilized. Immune infiltration across risk groups was evaluated via ssGSEA, the MCPcounter algorithm, and the ESTIMATE algorithm. TIDE was employed to compare immunotherapeutic responses between the risk groups, while the pRRophetic software was utilized to predict patients' chemotherapeutic drug sensitivity. The biomarkers identified were validated by performing in vitro experiments. CEP78, DOCK7, DPY19L4, and POM121 were identified by computational analyses as the key genes for CESC and further validated through in vitro experiments. Pathway enrichment analysis revealed predominant enrichment in immune-related pathways in the high-risk group, whereas the low-risk group was more enriched in energy and metabolic pathways. A significant negative correlation was observed between CD8+ T cell abundance and RiskScore, with higher ESTIMATEScores and StromalScores in high-risk patients. Notably, the high-risk group also demonstrated lower potential sensitivity to immunotherapy but more active responsiveness to a broader spectrum of chemotherapeutic agents. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that module genes are significantly enriched in cell cycle regulatory pathways, and these genes, in conjunction with Human Papillomavirus (HPV) infection-induced cell cycle dysregulation, jointly participate in CESC pathogenesis, providing a mechanistic basis for understanding the disease. This study provided novel theoretical evidence for immunotherapy and chemotherapy selection in the management of CESC. Show less
To investigate the clinical and pathological characteristics of patients with non-small cell lung cancer exhibiting coexistence of Clinical data, as well as histopathological, immunohistochemical, and Show more
To investigate the clinical and pathological characteristics of patients with non-small cell lung cancer exhibiting coexistence of Clinical data, as well as histopathological, immunohistochemical, and molecular pathological characteristics, of two patients harboring both Both patients were women aged 57 and 66 years. The two cases were diagnosed as invasive lung adenocarcinoma, and immunohistochemical staining showed that all tumor cells expressed CK7, Napsin A, TTF-1, and PD-L1. In Case 1, an Show less
Cardiovascular diseases from abnormal lipid metabolism significantly increase mortality in systemic lupus erythematosus (SLE). The causal link between dyslipidemia and SLE is unclear. Lipid metabolism Show more
Cardiovascular diseases from abnormal lipid metabolism significantly increase mortality in systemic lupus erythematosus (SLE). The causal link between dyslipidemia and SLE is unclear. Lipid metabolism in patients with SLE was evaluated based on clinical data from 511 patients with SLE and 706 healthy individuals. Bidirectional Mendelian randomization (MR) was employed to assess causal links between 179 plasma lipid metabolites, lipid-lowering drug targets, and SLE risk. Genetic instruments from GWAS and eQTL data were used to evaluate CETP and APOA4 effects. Peripheral blood CETP and apolipoprotein levels in SLE patients were validated via ELISA. SLE patients exhibited reduced HDL-C (P < 0.0001), APOA1 (P < 0.0001), and APOA4 (P < 0.0001), alongside elevated triglycerides (TG, P < 0.0001), APOC3, APOD, and APOF. MR identified three lipid metabolites-PC(18:2₂₀:4), TG(56:6), and TG(58:7)-as causal factors for SLE (P < 2.79E-5). CETP inhibition significantly reduced SLE risk via HDL-C modulation (OR = 0.72, P = 3.38E-08) and influenced LDL-C, TG, and apolipoproteins. Clinical validation confirmed elevated CETP and reduced APOA4 in SLE, correlating with disease activity. APOA4 activation showed protective effects, while PCSK9 inhibition lacked relevance. Bidirectional Mendelian randomization analyses confirmed dyslipidemia as a causal antecedent to SLE, with no evidence of reverse causation. A variety of MR analyses and clinical validation indicated that targeting HDL-C regulation offers significant advantages for managing dyslipidemia in patients with SLE, with CETP identified as the optimal pharmacological target. Show less
The efficacy and mechanism of Fufang Danshen dripping pills (FFDS) in the secondary prevention of stable coronary heart disease (SCHD) is currently undetermined. This study aims to investigate the eff Show more
The efficacy and mechanism of Fufang Danshen dripping pills (FFDS) in the secondary prevention of stable coronary heart disease (SCHD) is currently undetermined. This study aims to investigate the efficacy and preliminary mechanism by which FFDS may impact the progression of SCHD. Based on randomization, we administered oral FFDS to 30 patients with SCHD in addition to conventional treatment for 30 days. After treatment, three-months major adverse cardiovascular events (MACE) were assessed as the primary outcome. Additionally, we evaluated the patients' Seattle Angina Questionnaire score, blood pressure, circulating levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, platelets, alanine aminotransferase, aspartate aminotransferase, serum creatinine, and fasting blood glucose as the secondary outcomes. Furthermore, we utilized mass spectrometry analysis, network pharmacology, and lipidomics to predict the potential mechanisms of FFDS in the treatment of SCHD. Following treatment, FFDS demonstrated significant improvements in serum triglyceride levels ( In individuals with SCHD, the administration of FFDS has been shown to effectively reduce circulating triglyceride levels and decrease the frequency of angina episodes. This therapeutic effect is likely due to the active components of FFDS targeting key proteins: LPL, CD36, FABPpm, L-FABP, LCAT, and CEPT. https://www.chictr.org.cn/, identifier (ChiCTR2400080149). Show less
Yu Zhang, Gang Jiang, Wenrong Feng+4 more · 2025 · Comparative biochemistry and physiology. Part A, Molecular & integrative physiology · Elsevier · added 2026-04-24
The effects of starvation and re-feeding on Jian carp (Cyprinus carpio var. Jian) remain incompletely understood. This study investigated changes in growth performance, liver antioxidant capacity, int Show more
The effects of starvation and re-feeding on Jian carp (Cyprinus carpio var. Jian) remain incompletely understood. This study investigated changes in growth performance, liver antioxidant capacity, intestinal morphology, fatty acid profile, and expression of genes related to lipid metabolism. Juvenile C. carpio var. Jian, with initial body weight of 29.50 ± 2.00 g, were reared in 15 cylindrical culture barrels (200L) at a stocking density of 10 fish per barrel. These fish were subjected to five feeding regimes: a continuous feeding group (control group, treatment A), complete fasting (treatment B), 1, 2, and 3 days starvation within one week, followed by re-feeding 6 days (treatment C), 5 days (treatment D), and 4 days (treatment E). The results indicated significantly lower growth performance in C. carpio var. Jian in treatments B and E compared to the control and treatment C (P < 0.05). Intestinal length (only 627 ± 13.14 μm in treatment B) was significantly reduced, and an increase in vacuoles was observed in C. carpio var. Jian with the prolonged starvation. Antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly (P < 0.05) improved in treatment C when compared with treatments B, D and E.. In contrast, malondialdehyde (MDA) value was lowest (12.62 ± 0.60 nmol/mL) in treatment B. Furthermore, continuous starvation significantly decreased the total lipid and fatty acids contents in the muscle (P < 0.05). Compared with the control group, the reduction of total lipid and fatty acids contents was 31.53 % and 4.57 %, respectively, particularly affecting n3PUFA and n6PUFA. However, after one-day re-feeding, these contents resumed. Lipid metabolism is closely related to fish health, while in the current study, the genes related to lipid metabolism including lipoprotein lipase (LPL), 6-phosphogluconate dehydrogenase (G6PD), and peroxisome proliferator-activated receptor alpha (PPARα) did not differ significantly in treatment C compared to the control group (P > 0.05). In contrast, expressions in treatments B, D, and E were significantly reduced (P < 0.05). Taken together, prolonged starvation (>one day per week) not only affected the growth, which may further disrupt the intestinal structure, weaken antioxidant capacity, but also attenuate lipid deposition. Show less
The prognosis for colorectal cancer (CRC) patients with liver metastasis remains poor, and the molecular mechanisms driving CRC liver metastasis are not fully understood. Tumor-derived hypoxia-induced Show more
The prognosis for colorectal cancer (CRC) patients with liver metastasis remains poor, and the molecular mechanisms driving CRC liver metastasis are not fully understood. Tumor-derived hypoxia-induced extracellular vesicles have emerged as key players in inducing angiogenesis by transferring noncoding RNAs. However, the specific role of CRC-derived hypoxic extracellular vesicles (H-EVs) in regulating premetastatic microenvironment (PMN) formation by inducing angiogenesis remains unclear. Our study demonstrates that H-EVs induce angiogenesis and liver metastasis. Through microRNA microarray analysis, we identified a reduction in miR-6084 levels within H-EVs. We found that miR-6084 inhibited angiogenesis by being transferred to endothelial cells via EVs. In endothelial cells, miR-6084 directly targeted angiopoietin like 4 (ANGPTL4) mRNA, thereby suppressing angiogenesis through the ANGPTL4-mediated JAK2/STAT3 pathway. Furthermore, we uncovered that specificity protein 1 (SP1) acted as a transcription factor regulating miR-6084 transcription, while hypoxia-inducible factor 1A (HIF1A) decreased miR-6084 expression by promoting SP1 protein dephosphorylation and facilitating ubiquitin-proteasome degradation in SW620 cells. In clinical samples, we observed low expression of miR-6084 in plasma-derived EVs from CRC patients with liver metastasis. In summary, our findings suggest that CRC-derived H-EVs promote angiogenesis and liver metastasis through the HIF1A/SP1/miR-6084/ANGPTL4 axis. Additionally, miR-6084 holds promise as a diagnostic and prognostic biomarker for CRC liver metastasis. Show less
Growth traits are among the most important economic phenotypes targeted in the genetic improvement of beef cattle. To understand the genetic basis of growth traits in Huaxi cattle, we performed a geno Show more
Growth traits are among the most important economic phenotypes targeted in the genetic improvement of beef cattle. To understand the genetic basis of growth traits in Huaxi cattle, we performed a genome-wide association study (GWAS) on body weight, eye muscle area, and back fat thickness across five developmental stages in a population of 202 Huaxi cattle. Additionally, publicly available RNA-seq data from the longissimus dorsi muscle of both young and adult cattle were analyzed to identify key genes and genetic markers associated with growth in Huaxi cattle. In total, 7.19 million high-quality variant loci (SNPs and INDELs) were identified across all samples. In the GWAS, the three multilocus models (FarmCPU, MLMM, and BLINK) outperformed the conventional single-locus models (CMLM, GLM, and MLM). Consequently, GWAS analysis was conducted using multilocus models, which identified 99 variant loci significantly associated with growth traits and annotated a total of 83 candidate genes (CDGs). Additionally, 23 of the 83 CDGs overlapped with significantly differentially expressed genes identified from public RNA-seq datasets of longissimus dorsi muscle between young and adult cattle. Furthermore, gene functional enrichment (KEGG and GO) analyses revealed that over 30% of the pathways and GO terms were associated with muscle development and fat deposition, crucial factors for beef production. Specifically, key genes identified included Show less
To investigate the regulatory role of MACF1 and its upstream transcriptional control in focal adhesion remodeling and tumor progression in lung adenocarcinoma (LUAD). We employed in vitro loss- and ga Show more
To investigate the regulatory role of MACF1 and its upstream transcriptional control in focal adhesion remodeling and tumor progression in lung adenocarcinoma (LUAD). We employed in vitro loss- and gain-of-function assays using shRNA-mediated knockdown and ectopic overexpression of MACF1 and NR2F1 in LUAD cell lines (H1299 and Calu-3). Cell proliferation, adhesion, and migration were assessed by CCK-8, EdU, crystal violet, and Transwell assays. In vivo tumor growth and metastasis were evaluated using subcutaneous and tail vein xenograft models in nude mice. RNA-seq and GSEA were performed to identify MACF1-regulated pathways, followed by nuclear-cytoplasmic fractionation, dual-luciferase reporter assays, and immunofluorescence to assess WNT/β-catenin activity. ChIP-qPCR and ChIP-seq data from ENCODE were used to validate NR2F1 binding to the MACF1 promoter. MACF1 knockdown significantly suppressed LUAD cell proliferation, DNA replication, adhesion, and migration, and reduced tumor burden and lung metastases in vivo. Mechanistically, MACF1 activated WNT/β-catenin signaling by promoting CTNNB1 nuclear translocation, which upregulated focal adhesion genes (Paxillin, FAK, ITGB1). CTNNB1 agonist TWS119 restored focal adhesion in MACF1-deficient cells. Bioinformatic prediction and ChIP validation identified NR2F1 as a transcription factor directly targeting the MACF1 promoter. NR2F1 deficiency reduced MACF1 expression and phenocopied its functional loss, while MACF1 overexpression rescued the impaired phenotype. Our study uncovers a previously unrecognized NR2F1-MACF1-WNT axis that drives focal adhesion formation and LUAD progression. Targeting this regulatory circuit may offer new avenues for anti-metastatic therapy in lung adenocarcinoma. 1. NR2F1 is identified as a direct upstream transcription factor that activates MACF1 expression in LUAD. 2. MACF1 promotes LUAD cell proliferation, adhesion, and migration by enhancing focal adhesion assembly. 3. MACF1 activates the WNT/CTNNB1 signaling cascade, facilitating CTNNB1 nuclear translocation and downstream target expression. 4. Loss of MACF1 impairs focal adhesion formation and metastatic potential both in vitro and in xenograft and tail vein models. 5. The NR2F1-MACF1-WNT axis represents a novel regulatory circuit driving LUAD metastasis and offers potential therapeutic targets. Show less
Lipid metabolism may be linked to chronic gastritis, but its causal role remains unclear. While current research emphasizes inflammation, mucosal changes, immune regulation, genetics, and the gut micr Show more
Lipid metabolism may be linked to chronic gastritis, but its causal role remains unclear. While current research emphasizes inflammation, mucosal changes, immune regulation, genetics, and the gut microbiota, the contribution of lipid metabolism is understudied. This study aims to evaluate the impact of serum lipids and the mechanistic roles of lipid-lowering drug targets in chronic gastritis. We conducted a cross-sectional study using data from real world. Multivariable logistic regression was performed to assess the association between serum lipid profiles and gastritis. Mendelian randomization (MR) analyses based on genome-wide association study (GWAS) datasets were performed to detect the causal relationship of serum lipids, plasma lipid species, and lipid-lowering drug targets. Experimental validation was conducted using high-fat diet (HFD)-fed mice and chemically induced CAG rat models. Four thousand sixty one person, including 1,023 patients with chronic atrophic gastritis (CAG), 1,742 with non-atrophic gastritis (NAG), and 1,296 as healthy population were included in the analysis. Through covariates adjustment, TC, ApoA1, and HDL-C showed to be associated with an increased risk of chronic gastritis, whereas TG exhibited a protective effect. MR analysis confirmed a significant inverse causal relationship between TG and gastritis (OR = 0.889, 95% CI: 0.825-0.958). Ten plasma lipid species and lipid-lowering gene targets, including LPL and APOC3, were identified as causally associated with disease risk. Mediation analysis revealed six plasma lipid species as potential intermediaries linking genetic variation to gastritis. In vivo experiments demonstrated progressive hepatic steatosis and mild gastric mucosal changes in HFD-fed mice. Immunohistochemical analysis further revealed a significant reduction in LPL and APOC3 expression in gastric tissue (P < 0.05). In the CAG rat model, histological analysis revealed hepatocyte disarray, edema, and gastric mucosal atrophy. Elevated levels of TNF-α, IL-6, IL-1β and decreased levels of GAS-17 and PG I/II were also observed (P < 0.05). Western blot analyses further confirmed the downregulation of LPL and APOC3 expression in gastric tissue (P < 0.05). This study provides genetic and experimental evidence, supporting a causal role of lipid metabolism in chronic gastritis. LPL and APOC3 are implicated in its pathogenesis, highlighting potential lipid-targeted strategies for prevention and treatment. Show less
Atherosclerosis (AS) is a vascular disorder characterized by lipid accumulation and chronic inflammation, with pathogenesis closely linked to genetic factors and immune regulatory mechanisms. This stu Show more
Atherosclerosis (AS) is a vascular disorder characterized by lipid accumulation and chronic inflammation, with pathogenesis closely linked to genetic factors and immune regulatory mechanisms. This study comprehensively identified ASassociated genes by integrating data from the Gene Expression Omnibus (GEO) database and expression quantitative trait locus (eQTL) analyses, complemented by Mendelian randomization (MR) analysis, followed by experimental validation of their functional roles. Results indicated significant upregulation of CLEC5A and ISG20 in patients with AS, with MR analysis revealing positive causal relationships between both genes and AS risk (CLEC5A: OR = 1.001, P = 0.047; ISG20: OR = 1.001, P = 0.030), while HOXA2 showed a negative causal association. Functional enrichment analysis highlighted CLEC5A and ISG20's involvement in immune responses, inflammatory pathways, and lipid metabolism regulation. Experimental validation in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages and apolipoprotein E-deficient (ApoE This study represents the first to elucidate the molecular mechanism by which ISG20 promotes AS progression through macrophage lipid accumulation and inflammatory responses, positioning it as a potential novel therapeutic target for AS. Show less
Adipogenic differentiation of adipose-derived stem cells (ADSCs) is fundamental to both adipose tissue homeostasis and clinical applications, particularly fat grafting. However, the global and stage-s Show more
Adipogenic differentiation of adipose-derived stem cells (ADSCs) is fundamental to both adipose tissue homeostasis and clinical applications, particularly fat grafting. However, the global and stage-specific transcriptional regulatory networks underlying ADSC adipogenesis remain incompletely elucidated. In this study, we integrated bulk and single-cell RNA-seq datasets across multiple time points of ADSC adipogenesis to identify core regulators of differentiation and maturation. A total of 41 genes were consistently upregulated during early differentiation, among which eight hub genes (FABP4, FASN, FABP5, ADIPOQ, PLIN1, LPL, CIDEC, and ACSL1) formed a tightly connected protein-protein interaction (PPI) module associated with lipid metabolism, lipid droplet formation, and adipocyte maturation. Further integration of differentially expressed lncRNAs and miRNAs led to the construction of a ceRNA network involving 7 mRNAs, 9 miRNAs, and 4 lncRNAs, comprising 34 predicted lncRNA-miRNA-mRNA regulatory axes. To identify temporal transcriptional regulators, we defined five genes (TTC14, MBNL2, UBR3, ABCD2, and SORT1) as early-stage inducers of adipogenesis, and four genes (UQCR11, NDUFB4, S100A10, and PRDX3) as late-stage regulators involved in maintaining the mature phenotype. These stage-specific regulators showed distinct temporal expression patterns and were validated by qPCR. GeneMANIA network analysis further revealed that early-stage regulators were enriched in lipid transport and lipase activity regulation, while late-stage regulators were associated with mitochondrial electron transport and energy metabolism. These findings highlight the stage-dependent transcriptional landscape of ADSC adipogenesis and provide candidate regulatory targets for modulating adipocyte differentiation and stability. Show less
Chronic stress disrupts neuroendocrine regulation, neurotransmitter balance, and neuronal redox homeostasis, thereby contributing to the development of anxiety-related neuropathology. Arecoline, the p Show more
Chronic stress disrupts neuroendocrine regulation, neurotransmitter balance, and neuronal redox homeostasis, thereby contributing to the development of anxiety-related neuropathology. Arecoline, the predominant alkaloid of Show less
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) ameliorate motor deficits in cerebral palsy (CP), but the effect of injection frequency remains unclear. Moreover, most studies have focu Show more
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) ameliorate motor deficits in cerebral palsy (CP), but the effect of injection frequency remains unclear. Moreover, most studies have focused on mild CP models (unilateral carotid artery occlusion [UCAO] model). This study explored the effect and mechanism of hUC-MSCs in a rat model of moderate-to-severe CP (bilateral carotid artery occlusion [BCAO] model). On postnatal Day 4 (P4), Wistar rat pups underwent BCAO induction. Subsequently, they received either a single intrathecal injection of hUC-MSCs on P21 or repeated injections on P21, P28, P35, and P42. Motor performance was assessed using the rotarod and front-limb suspension tests, while neuronal regeneration and inflammation were evaluated via biomarkers including neuronal nuclear antigen (NeuN), ionized calcium-binding adapter molecule-1 (Iba-1), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and brain-derived neurotrophic factor (BDNF). P18 model screening confirmed that the BCAO model resulted in more severe brain damage and motor impairment than the UCAO model. After injection of lentivirally transfected hUC-MSCs, it was found that hUC-MSCs could nest in the damaged area and survive for at least 3 days. Administration of hUC-MSCs following BCAO modeling led to notable improvements in both behavioral performance and histological outcomes. Furthermore, repeated injections offered greater therapeutic benefits compared to single injection. It indicated that the efficacy of repeated injections of hUC-MSCs in the treatment of moderate-to-severe CP was superior to that of single injection. Its mechanism was related to the improvement of damaged myelin structure, reduced immunoinflammatory responses, and increased neurotrophic support. Show less
Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disorder characterized by left ventricular hypertrophy and an elevated risk of sudden cardiac death. Cardiac myosin binding protein C ( Show more
Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disorder characterized by left ventricular hypertrophy and an elevated risk of sudden cardiac death. Cardiac myosin binding protein C (MYBPC3) is the most frequently mutated gene leading to HCM. In this study, peripheral blood mononuclear cells isolated from an HCM patient harboring a heterozygous MYBPC3 missense mutation (c.3072C > A; p.S1024R) were reprogrammed via Sendai virus vectors to generate a patient-specific induced pluripotent stem cell (iPSC) line. The iPSC line exhibits normal morphology and karyotype, alongside definitive hallmarks of pluripotency, including trilineage differentiation potential. Show less
Cadmium (Cd) contamination in plants and soil poses significant risks to livestock, particularly sheep. Cd exposure often leads to severe gastrointestinal diseases in sheep that are difficult to treat Show more
Cadmium (Cd) contamination in plants and soil poses significant risks to livestock, particularly sheep. Cd exposure often leads to severe gastrointestinal diseases in sheep that are difficult to treat. Milk-derived exosomes, particularly those from sheep milk (SM-Exo), have shown potential in treating gastrointestinal disorders, though their efficacy in Cd-induced colitis remains unclear. In this study, we investigated the therapeutic potential of SM-Exo in a Cd-induced colitis model. Hu sheep were exposed to Cd, and their fecal microbiota were collected to prepare bacterial solutions for fecal microbiota transplantation (FMT) in mice. The changes in gut microbiota and gene expression were analyzed through microbiome and transcriptomics. Our results showed that prior to treatment, harmful bacteria (e.g., Show less
Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that was discovered in 2000 by three independent laboratories. In the ensuing two and a half decades, extensive work has been conducted to dete Show more
Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that was discovered in 2000 by three independent laboratories. In the ensuing two and a half decades, extensive work has been conducted to determine its physiological and pathological functions. ANGPTL4 has been shown to be involved in many biological processes, including glucose and lipid metabolism, angiogenesis, and wound healing, with implications in diseases such as type 2 diabetes, cardiovascular (e.g., atherosclerosis) and renal diseases, and cancer. For instance, ANGPTL4 is upregulated in several cancers, including renal cell carcinoma, breast cancer, and colorectal cancer. Interestingly, ANGPTL4 has been shown to exhibit both pro-tumor-promoting tumor growth, cell survival, angiogenesis and metastasis-as well as anti-tumor activities, underscoring its complex roles in cancer biology. This review examines the comprehensive biological functions of ANGPTL4 and its contributions to disease mechanisms with a specific emphasis on cancer, as well as its potential as a therapeutic target across different types of human cancers. Show less
This study aimed to identify heterogeneous patterns of medical coping modes (MCM) and to examine the moderating role of social support in the relationship between these patterns and social disability Show more
This study aimed to identify heterogeneous patterns of medical coping modes (MCM) and to examine the moderating role of social support in the relationship between these patterns and social disability in young and middle-aged patients after percutaneous coronary intervention (PCI). A cross-sectional study was conducted among 129 post-PCI patients from a single center in China. Participants completed the Medical Coping Modes Questionnaire (MCMQ), the Social Support Rating Scale (SSRS), and the Social Disability Screening Schedule (SDSS). Latent profile analysis (LPA) was used to identify distinct coping patterns. The moderation effect of social support was tested using the Johnson-Neyman technique. Two distinct coping profiles were identified via LPA: "Adaptive Copers" (55.1%), characterized by higher confrontation and lower avoidance/resignation, and "Maladaptive Copers" (44.9%), showing the opposite pattern. A counterintuitive finding emerged, with the Maladaptive Copers reporting significantly lower social disability scores. Furthermore, beyond this profile differentiation, social support demonstrated a significant U-shaped moderating effect in the coping-disability relationship. Its moderating role was statistically significant only at very low (<39.884) and very high (>52.924) levels of support. This study reveals two key findings: first, post-PCI patients are heterogeneous in coping, comprising adaptive and maladaptive subgroups; second, the impact of these coping styles on social disability is non-linearly moderated by social support. Clinicians should assess both coping profiles and social support levels to tailor interventions effectively. Show less
Individuals with type 2 diabetes mellitus have an increased risk of developing Alzheimer's disease (AD). GLP-1 receptor agonists (GLP-1RAs) are used for glycemic control in diabetes and show potential Show more
Individuals with type 2 diabetes mellitus have an increased risk of developing Alzheimer's disease (AD). GLP-1 receptor agonists (GLP-1RAs) are used for glycemic control in diabetes and show potential neuroprotective properties, but their effects on AD and the underlying mechanisms are not well understood. Here we demonstrate that GLP-1RAs can alleviate AD-related phenotypes by activating 5' AMP-activated protein kinase (AMPK) signaling. We found that plasma GLP-1 levels were decreased in AD model mice and negatively correlated with amyloid-beta (Aβ) load in patients with AD. Enhancing GLP-1 signaling through GLP-1RAs increased CaMKK2-AMPK signaling, which subsequently reduced BACE1-mediated cleavage of amyloid precursor protein (APP) and Aβ generation. GLP-1RAs also increased AMPK activity in microglia, inhibiting neuroinflammation and promoting Aβ phagocytosis. Consequently, GLP-1RAs inhibited plaque formation and improved memory deficits in AD model mice. Our findings indicate that AMPK activation mediates the effects of GLP-1RAs on AD, highlighting the therapeutic potential of GLP-1RAs for the treatment of AD. Show less
The gut microbiota influences host immunity and metabolism, and changes in its composition and function have been implicated in several non-communicable diseases. Here, comparing germ-free (GF) and sp Show more
The gut microbiota influences host immunity and metabolism, and changes in its composition and function have been implicated in several non-communicable diseases. Here, comparing germ-free (GF) and specific pathogen-free (SPF) mice using spatial transcriptomics, single-cell RNA sequencing, and targeted bile acid metabolomics across multiple organs, we systematically assessed how the gut microbiota's absence affected organ morphology, immune homeostasis, bile acid, and lipid metabolism. Through integrated analysis, we detect marked aberration in B, myeloid, and T/natural killer cells, altered mucosal zonation and nutrient uptake, and significant shifts in bile acid profiles in feces, liver, and circulation, with the alternate synthesis pathway predominant in GF mice and pronounced changes in bile acid enterohepatic circulation. Particularly, autophagy-driven lipid droplet breakdown in ileum epithelium and the liver's zinc finger and BTB domain-containing protein (ZBTB20)-Lipoprotein lipase (LPL) (ZBTB20-LPL) axis are key to plasma lipid homeostasis in GF mice. Our results unveil the complexity of microbiota-host interactions in the crosstalk between commensal gut bacteria and the host. Show less
The association between obesity and cholelithiasis has been identified. However, the causal relationship between age-specific childhood obesity and adult cholelithiasis remains unclear. In addition, t Show more
The association between obesity and cholelithiasis has been identified. However, the causal relationship between age-specific childhood obesity and adult cholelithiasis remains unclear. In addition, the biological basis for the association between childhood obesity and adult cholelithiasis is poorly understood, which poses a challenge for preventing adult cholelithiasis in specific biological pathways. Summary statistics of genome-wide association studies (GWASs) of childhood age-specific body mass index (BMI) at 12 time points and adult cholelithiasis derived from FinnGen were used in this study, with the former covering data from birth to 8 years. Linkage disequilibrium score regression (LDSC) analyses were used to assess the genetic correlations of age-specific childhood BMI to cholelithiasis. Two-sample Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) analyses were utilized to explore the causal associations. As downstream analyses, summary-based Mendelian randomization (SMR) analyses, transcriptome-wide association studies (TWAS), and Bayesian colocalization were conducted to discover the shared transcriptomic signals. The GWAS summary statistics of cholelithiasis from the UK Biobank were used for sensitivity analyses. LDSC analyses revealed significant genetic correlations between 11 age-specific childhood BMIs and adult cholelithiasis (except for birth BMI). Two-sample MR and MVMR analyses indicated causal relationships between birth BMI and BMI at 8 months, 1.5 years, 7 years, and 8 years after birth and adult cholelithiasis. SMR, TWAS, and colocalization analyses identified MLXIPL as the strongest overlapping signal between age-specific BMI and adult cholelithiasis. This study provides new evidence on the relationships between childhood obesity and adult cholelithiasis, highlighting the role of early intervention for obesity in childhood at key time points. MLXIPL gene expression was identified as a potential biological pathway, suggesting potential therapeutic targets and precise intervention strategies for childhood obesity and adult cholelithiasis. Show less
Many patients are suffering from atherosclerosis without typical risk factors, which can cause severe cardiovascular complications. Trimethylamine N-oxide (TMAO), derived from gut microbes, is a key u Show more
Many patients are suffering from atherosclerosis without typical risk factors, which can cause severe cardiovascular complications. Trimethylamine N-oxide (TMAO), derived from gut microbes, is a key unconventional contributor to the development of atherosclerosis. Here we present a strategy performed by orally administered nano-functionalized probiotics (PDMF@LGG) to inhibit TMAO through the gut microbiota-trimethylamine (TMA)-TMAO axis. PDMF@LGG, composed of polydopamine-coated Lacticaseibacillus rhamnosus GG and nanoparticles based on a reactive oxygen species (ROS)-responsive polymeric prodrug of fluoromethylcholine (FMC), can promote the retention of probiotics and nanoparticles in the intestine to persistently scavenge elevated ROS and release drugs. This process suppresses TMA production and absorption, lowering plasma TMAO levels. The therapeutic effects on male ApoE Show less
Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is marked by cognitive deterioration and heightened neuroinflammation. The influence of Insulin-like Growth Factor 1 Receptor (IGF1R Show more
Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is marked by cognitive deterioration and heightened neuroinflammation. The influence of Insulin-like Growth Factor 1 Receptor (IGF1R) and its post-translational modifications, especially sumoylation, is crucial in understanding the progression of AD and exploring novel therapeutic avenues. This study investigates the impact of exercise on the sumoylation of IGF1R and its role in ameliorating AD symptoms in APP/PS1 mice, with a specific focus on neuroinflammation and innovative therapeutic strategies. APP/PS1 mice were subjected to a regimen of moderate-intensity exercise. The investigation encompassed assessments of cognitive functions, alterations in hippocampal protein expressions, neuroinflammatory markers, and the effects of exercise on IGF1R and SUMO1 nuclear translocation. Additionally, the study evaluated the efficacy of KPT-330, a nuclear export inhibitor, as an alternative to exercise. Exercise notably enhanced cognitive functions in AD mice, possibly through modulations in hippocampal proteins, including Bcl-2 and BACE1. A decrease in neuroinflammatory markers such as IL-1β, IL-6, and TNF-α was observed, indicative of reduced neuroinflammation. Exercise modulated the nuclear translocation of SUMO1 and IGF1R in the hippocampus, thereby facilitating neuronal regeneration. Mutant IGF1R (MT IGF1R), lacking SUMO1 modification sites, showed reduced SUMOylation, leading to diminished expression of pro-inflammatory cytokines and apoptosis. KPT-330 impeded the formation of the IGF1R/RanBP2/SUMO1 complex, thereby limiting IGF1R nuclear translocation, inflammation, and neuronal apoptosis, while enhancing cognitive functions and neuron proliferation. Moderate-intensity exercise effectively mitigates AD symptoms in mice, primarily by diminishing neuroinflammation, through the reduction of IGF1R Sumoylation. KPT-330, as a potential alternative to physical exercise, enhances the neuroprotective role of IGF1R by inhibiting SUMOylation through targeting XPO1, presenting a promising therapeutic strategy for AD. Show less
Yuanpeng Zhu, Di Liu, Xiangjie Yin+3 more · 2025 · The spine journal : official journal of the North American Spine Society · Elsevier · added 2026-04-24
Current clinical guidelines lack clear, quantitative recommendations on intensity-specific physical activity (PA) levels for preventing back pain. Moreover, accelerometer-based evidence regarding dose Show more
Current clinical guidelines lack clear, quantitative recommendations on intensity-specific physical activity (PA) levels for preventing back pain. Moreover, accelerometer-based evidence regarding dose-response relationships and interactions between PA and genetic susceptibility remains limited. To determine the relationships between accelerometer-measured total and intensity-specific PA and incident back pain, and to assess potential effect modification by polygenic risk scores (PRS). Prospective, large-scale, population-based study using UK Biobank data. UK Biobank participants who wore wrist accelerometers for 7 days (N=71,601). Incident back pain, defined as the first recorded ICD-10 dorsalgia code (M54). Total PA, light PA (LPA), and moderate-to-vigorous PA (MVPA) were derived using validated machine-learning algorithms from raw accelerometer data. Dose-response relationships were modeled using restricted cubic splines within Cox proportional hazards models, with adjustment for and stratification by a polygenic risk score (PRS). Point estimates for the population attributable fraction (PAF) were then calculated. Body mass index (BMI) mediation was assessed. Over a median follow-up of 7.0 years, total PA and MVPA exhibited nonlinear inverse associations with incident back pain, independent of genetic risk, with thresholds at approximately 35 milli-g (total PA) and 60 min/day (MVPA). The adjusted PAF was 15.9% for low MVPA and 9.9% for low total PA. Associations were strongest for MVPA, followed by total PA; no significant association was observed for LPA. Within both PRS strata, risk declined monotonically across PA quartiles, with similar effect sizes and no PA × PRS interaction. Notably, participants with high PRS and high PA had lower risk than those with low PRS and low PA. BMI mediated 26.2% of the total PA association and 15.5% of the MVPA association. Accelerometer-measured MVPA robustly reduces back-pain risk, independent of genetic predisposition. Future guidelines should provide clear, intensity-specific recommendations and account for the observed nonlinear dose-response to optimize prevention. Show less