Derazantinib (DZB), a pan-fibroblast growth factor receptor (FGFR) inhibitor, exhibits potent activity against FGFR1-3 kinases and has been clinically approved for antitumor therapy. However, its anti Show more
Derazantinib (DZB), a pan-fibroblast growth factor receptor (FGFR) inhibitor, exhibits potent activity against FGFR1-3 kinases and has been clinically approved for antitumor therapy. However, its antibacterial properties remain unknown. Here, we demonstrated that DZB displays broad-spectrum activity against Show less
Colorectal cancer (CRC) is a malignant tumor. Slug has been found to display a key role in diversified cancers, but its relevant regulatory mechanisms in CRC development are not fully explored. Hence, Show more
Colorectal cancer (CRC) is a malignant tumor. Slug has been found to display a key role in diversified cancers, but its relevant regulatory mechanisms in CRC development are not fully explored. Hence, exploring the function and regulatory mechanisms of Slug is critical for the treatment of CRC. Protein expressions of Slug, N-cadherin, E-cadherin, Snail, HIF-1α, SUMO- 1, Drp1, Opa1, Mfn1/2, PGC-1α, NRF1, and TFAM were measured through western blot. To evaluate the protein expression of Slug and SUMO-1, an immunofluorescence assay was used. Cell migration ability was tested through transwell assay. The SUMOylation of Slug was examined through CO-IP assay. Slug displayed higher expression and facilitated tumor metastasis in CRC. In addition, hypoxia treatment was discovered to upregulate HIF-1α, Slug, and SUMO-1 levels, as well as induce Slug SUMOylation. Slug SUMOylation markedly affected mitochondrial biosynthesis, fusion, and mitogen-related protein expression levels to trigger mitochondrial stress. Additionally, the induced mitochondrial stress by hypoxia could be rescued by Slug inhibition and TAK-981 treatment. Our study expounded that hypoxia affects mitochondrial stress and facilitates tumor metastasis of CRC through Slug SUMOylation. Show less
Metabolism alteration is a common complication of rheumatic arthritis (RA). This work investigated the reason behind RA-caused triglyceride (TG) changes. Fresh RA patients' whole blood was transfused Show more
Metabolism alteration is a common complication of rheumatic arthritis (RA). This work investigated the reason behind RA-caused triglyceride (TG) changes. Fresh RA patients' whole blood was transfused into NOD-SCID mice. Metabolism-regulatory tissues were examined after sacrifice. To verify the findings, tissues of the rats with long-lasting adjuvant-induced arthritis (AIA) were analyzed. Some rats were injected with human plasma and GPIHBP1, and their blood TG was monitored. Various cells were stimulated by cytokines or rheumatic subjects' serum. Some pre-adipocytes were cultured by human serum or in the presence of HUVEC cells and GPIHBP1. TG decrease occurred in blood and white adipose tissues (WAT) of the RA blood-transfused NOD-SCID mice and chronic AIA rats. Fatty acids (FA) oxidation in muscles was accelerated a bit, while TG catabolism status in their livers was varied. TNF-α, IL-1β, IL-6 and RA/AIA serum promoted expression of TG utilization-related enzymes and FA uptake transporters in pre-adipocytes, but barely affected LPL. Mild IL-6 stimulus promoted GPIHBP1 release of HUVEC cells. GPIHBP1 was increased in RA serum. This change can decrease blood TG in rats, which was overshadowed by an injection of excessive GPIHBP1. RA serum slightly inhibited LPL secretion in pre-adipocytes. Both HUVEC cells co-culture and GPIHBP1 supplement reduced LPL distribution on pre-adipocytes, and eliminated LPL activity difference between normal and RA serum-treated cells. No TG uptake difference was observed in these circumstances. RA-associated inflammation induces GPIHBP1 secretion of endothelial cells, which facilitates blood TG hydrolysis and uptake to compensate the loss in WAT. Show less
As global population aging intensifies, mental health issues in older adults are increasingly prominent, with depression being particularly prevalent and detrimental. The study investigated how substi Show more
As global population aging intensifies, mental health issues in older adults are increasingly prominent, with depression being particularly prevalent and detrimental. The study investigated how substituting sedentary behavior (SB) and sleep (SLP) with physical activity (PA) affects depression risk in this population. Meta-analysis was conducted by searching four databases: PubMed, Scopus, SPORTdiscus, and PsycINFO (via EBSCOhost platform) for relevant studies published until January 2025. Regression coefficients (β) with 95% confidence intervals (CIs) for depressive symptoms were estimated. Publication bias was assessed using funnel plots and Egger's tests, and heterogeneity was evaluated using Q tests and the I Among 18,912 participants (53.45% female, ≥60 years) across nine studies, replacing SB with MVPA significantly reduced depression (β = -0.12, 95% CI: -0.20, -0.04), subgroup analyses indicated that reallocating 10, 30 and 60 min/day of SB to MVPA ( Substituting SB and SLP with MVPA is significantly associated with a reduction in depression, whereas no significant association is observed when replaced by LPA. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=546666, identifier CRD42024546666. Show less
Hair follicle stem cells (HFSCs) are resident stem cells within hair follicles (HFs) that possess self-renewal and differentiation capacities, serving as a critical model for regenerative medicine res Show more
Hair follicle stem cells (HFSCs) are resident stem cells within hair follicles (HFs) that possess self-renewal and differentiation capacities, serving as a critical model for regenerative medicine research. Their dynamic interaction with dermal papilla cells (DPCs) plays a decisive role in HF development and cycling. Show less
Chronic intakes of functional foods (probiotics, apples and oats) have been reported to have beneficial effects on hepatic lipid regulation and glycaemic control, but mechanistic human studies humans Show more
Chronic intakes of functional foods (probiotics, apples and oats) have been reported to have beneficial effects on hepatic lipid regulation and glycaemic control, but mechanistic human studies humans are limited. An ex-vivo study was performed to determine the chronic effects of probiotics, oats, and apples on the expression of genes related to markers of cardiometabolic health in peripheral blood monocular cells (PBMC). In this CABALA sub-study (n = 59/61, age: 52 ± 12y), blood PBMC were also isolated before and 8 weeks after the daily consumption of either a probiotic with bile salt hydrolase activity (Lactobacillus reuteri), porridge oats, Renetta Canada apples or a control. Relative PBMC mRNA gene expression was determined and correlations performed between the fold change in response to the functional interventions and change in cardiometabolic disease risk markers. Relative to baseline, there was an upregulation in the PBMC TLR4 mRNA expression in the control compared with the probiotics and apples groups (p[Formula: see text]0.024). Moderate inverse correlations were found between the fold change in GPBAR1 mRNA expression and change in plasma total and secondary BAs, HMGCR and SREBF1 mRNA gene expressions and high-density lipoprotein-cholesterol, and SREBF1 and GIPR mRNA gene expressions and glucose. TLR4 and TNFSF14 mRNA gene expressions were associated with pro-inflammatory cytokines (p=0.05). Probiotic and apples interventions attenuated the upregulation in PBMC TLR4 mRNA expression observed with the control. Correlations between fold change in mRNA gene expression and changes in cardiometabolic disease risk markers in response to the functional interventions were in agreement with previous studies. The study was registered at clinical trials.gov (ref. NCT03369548). Show less
By integrating single-cell and bulk RNA-sequencing data for esophageal cancer (ESCA), we developed and validated a seven-macrophage-gene prognostic signature (FCN1, SCARB2, ATF5, PHLDA2, GLIPR1, CHORD Show more
By integrating single-cell and bulk RNA-sequencing data for esophageal cancer (ESCA), we developed and validated a seven-macrophage-gene prognostic signature (FCN1, SCARB2, ATF5, PHLDA2, GLIPR1, CHORDC1, and BCKDK). This signature effectively stratified patients into high- and low-risk groups with significantly different overall survival, achieving area under the curve (AUC) values greater than 0.7 for 1-, 2-, and 3-year survival prediction. A high-risk status correlated with an immunosuppressive tumor microenvironment, characterized by lower infiltration of B cells and CD8 + T cells, and was associated with reduced sensitivity to multiple chemotherapeutic agents, including Cisplatin and 5-Fluorouracil. Conversely, a low-risk status was linked to greater immune cell infiltration and higher predicted chemosensitivity. At the single-cell level, pseudotime analysis revealed that macrophage maturation significantly correlated with a decreasing risk score, suggesting that mature macrophages may contribute to a favorable prognosis. Furthermore, cell communication analysis identified high-risk macrophages as dominant drivers of a pro-tumorigenic microenvironment via signaling pathways, such as SPP1 and complement. In conclusion, this seven-gene signature is a robust prognostic biomarker that offers a new strategy for personalized risk assessment and treatment selection in ESCA. The online version contains supplementary material available at 10.1007/s13205-025-04452-w. Show less
ObjectivesThis study aimed to compare the effects of different exercise interventions on brain-derived neurotrophic factor (BDNF) levels in patients with neurodegenerative diseases and to explore regu Show more
ObjectivesThis study aimed to compare the effects of different exercise interventions on brain-derived neurotrophic factor (BDNF) levels in patients with neurodegenerative diseases and to explore regulatory factors.MethodsSearched PubMed, Scopus, Web of Science Core Collection, CNKI and Cochrane Library databases up to March 15, 2025. Bayesian network meta-analysis was conducted using R software, and meta-regression analyzed the moderating effects of training period and frequency.Results42 randomized controlled trials covering 1482 patients were included. The Surface Under the Cumulative Ranking (SUCRA) indicated that stretching training (SUCRA = 78.92) and high-intensity interval training (SUCRA = 69.73) were ranked higher than other exercise modalities and exhibited more favorable effect on BDNF enhancement, although neither demonstrated statistically significant superiority over the blank control. In contrast, combined training (SUCRA = 35.58), aerobic training (SUCRA = 35.17), and resistance training (SUCRA = 12.98) showed relatively lower potential for BDNF enhancement (blank control SUCRA = 67.62). Meta-regression analysis showed that the effect of combined training was significantly and positively correlated with intervention period ( Show less
Osteoarthritis (OA) is a common progressive joint disorder marked by synovial inflammation, cartilage degeneration, the formation of osteophytes, though its underlying molecular mechanisms remain uncl Show more
Osteoarthritis (OA) is a common progressive joint disorder marked by synovial inflammation, cartilage degeneration, the formation of osteophytes, though its underlying molecular mechanisms remain unclear. This study integrated bioinformatics and experimental validation to identify key genes in OA synovium and their association with immune infiltration. Analysis of the GSE82107 dataset (10 OA, 7 controls) revealed 909 differentially expressed genes (525 upregulated, 384 downregulated). WGCNA identified the "midnightblue" module, and its intersection with DEGs yielded 122 genes enriched in cytokine-cytokine receptor interaction, JAK-STAT signaling, and autophagy pathways. Protein-protein interaction analysis highlighted FLT3LG, MC4R, CXCL10, CARTPT, and LHX2 as core genes (AUC 0.743-0.871). Immune infiltration analysis showed elevated M0 macrophages in OA, with CXCL10 showing a strong positive correlation with M1 macrophage infiltration (r = 0.74), and MC4R correlating with the presence of follicular helper T cells (r = 0.85). In vitro, OA-derived fibroblast-like synoviocytes exhibited CXCL10 upregulation, MC4R downregulation, and increased IL-6, IL-8, and TNF-α secretion, which were markedly reduced by CXCL10 knockdown or MC4R overexpression. Synovial tissue assays confirmed these expression patterns. CXCL10 and MC4R may represent promising diagnostic markers and therapeutic targets, offering new insights into OA immunopathogenesis and precision intervention. Show less
To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD). A bidirectional and multivariable Mendelia Show more
To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD). A bidirectional and multivariable Mendelian randomization study. The summary statistics for anti-VEGF nAMD treatment response included a total of 128 responders, 51 nonresponders, and 6 908 005 genetic variants available for analysis. The sample size of lipid biomarkers is 441 016 and 12 321 875 genetic variants available for analysis. Two-sample Mendelian randomization (MR) method was conducted to exhaustively appraise the causalities among 13 lipid biomarkers and the risk of different anti-VEGF treatment responses (including visual acuity [VA] and central retinal thickness [CRT]) for nAMD subtypes. Thirteen lipid biomarkers, VA, and CRT. A positive causal relationship was identified between triglycerides (TGs), apolipoproteins (Apos) E2, ApoE3, total cholesterol (TC), and VA response to anti-VEGF therapy in patients with nAMD, as confirmed by MR-Egger, weighted median, and weighted mode models. The MR-Egger model yielded statistically significant results for TC, ApoA-I, ApoB, and ApoA-V in relation to the CRT response to anti-VEGF treatment in patients with nAMD. In the reverse MR, the MR-Egger model identified significant causal relationships between ApoA-I, low-density lipoprotein cholesterol (LDL-c), ApoE3, and ApoF and the VA response. However, this was not the case in the weighted median and weighted mode models. In the MR-Egger model, ApoB, LDL-c, ApoE3, and ApoM were identified as significantly influencing the CRT response. In the multisample MR analysis, TC, high-density lipoprotein cholesterol, LDL-c, and TG were found to be causally related to VA response, and TC was also identified as being causally related to the CRT response to anti-VEGF therapy in patients with nAMD. This MR study suggests unidirectional causality between TG and ApoE3 and the response to anti-VEGF treatment in patients with nAMD. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Show less
Alzheimer's disease (AD) is a chronic neurodegenerative disorder predominantly affecting the elderly population. The pathogenesis of AD involves the production of highly neurotoxic amyloid-β peptide 1 Show more
Alzheimer's disease (AD) is a chronic neurodegenerative disorder predominantly affecting the elderly population. The pathogenesis of AD involves the production of highly neurotoxic amyloid-β peptide 1-42 (Aβ Show less
Dysregulation of hepatic lipid homeostasis constitutes a core pathogenic mechanism in metabolic dysfunction-associated fatty liver disease (MAFLD); however, the regulatory role of circular RNAs (circR Show more
Dysregulation of hepatic lipid homeostasis constitutes a core pathogenic mechanism in metabolic dysfunction-associated fatty liver disease (MAFLD); however, the regulatory role of circular RNAs (circRNAs) in this process remains unclear. In this study, hepatic circRNAs transcriptomic profiling of MAFLD patients identified circSETD2-generated from exons 16-18 of the SETD2 gene-as a stably expressed and significantly upregulated novel circRNA with a closed circular structure localized in the cytoplasm of MAFLD patient liver tissues. Silencing circSETD2 attenuated free fatty acid - induced lipid accumulation in vitro by reducing lipogenesis and enhancing fatty acid β-oxidation. In high fat diet - fed mice, hepatic circSETD2 silencing mitigated steatosis, improved liver function, and reversed dyslipidemia. Mechanistically, RNA pull-down coupled with LC-MS/MS identified carbamoyl phosphate synthetase 1 (CPS1) as a circSETD2-interacting protein, which was subsequently validated by RNA immunoprecipitation and fluorescence in situ hybridization. Pharmacological modulation of CPS1 enzymatic activity in circSETD2-silenced cells established its mediator role. Specifically, circSETD2 directly bound to CPS1, reducing its enzymatic activity and thereby exacerbating lipid metabolic disturbances and disease progression in MAFLD. In summary, circSETD2 drives MAFLD pathogenesis by impairing CPS1-mediated regulation of lipid homeostasis, positioning it as a promising prognostic biomarker and therapeutic target. Show less
Sparstolonin B (SSNB) and Curcumin (Cur), from a pair of compatible herbs, were previously identified as anti-inflammation and T helper 17 (Th17) modulation reagents. However, their compatible roles i Show more
Sparstolonin B (SSNB) and Curcumin (Cur), from a pair of compatible herbs, were previously identified as anti-inflammation and T helper 17 (Th17) modulation reagents. However, their compatible roles in atherosclerosis (AS) and underlying mechanisms remain uninvestigated. In vivo, the apoE The gene-disease interaction and hub gene network reveals Th17-associated genes in the pathogenesis of atherosclerosis. In vitro, SSNB and Cur reduced oxLDL-induced BMDC activation by downregulating CD36. SSNB showed stronger inhibition to inflammatory activation of DC, while Cur more intensively suppressed co-stimulatory molecules. For the Th17/Treg bias in co-culture of BMDC and CD4 Our findings reveal, for the first time, that SSNB and Cur alleviate AS by modulating Th17-stromal cell interactions, with the IL-17RA-TAK1-NF-κB pathway as a related mediator. Notably, SSNB and Cur exhibit distinct anti-atherogenic roles. SSNB primarily targets TLR4/CD36 to inhibit DC activation, Th17 differentiation, VSMC inflammation and mainly inhibited TAK1 phosphorylation, while Cur more significant inhibited macrophage inflammation, and more directly inhibited NF-κB P65 phosphorylation. This study will be valuable for developing novel and precise adjuvant therapies for AS. Show less
Aging-related lipid metabolic disorder is related to oxidative stress. Selenium (Se)-enriched Cardamine violifolia (SEC) is known for its excellent antioxidant function. The objective of this study wa Show more
Aging-related lipid metabolic disorder is related to oxidative stress. Selenium (Se)-enriched Cardamine violifolia (SEC) is known for its excellent antioxidant function. The objective of this study was to evaluate the effects of SEC on antioxidant capacity and lipid metabolism in the liver of aged laying hens. A total of 450 sixty-five-wk-old Roman laying hens were randomly divided into 5 treatments: a basal diet (without Se supplementation, CON) and basal diets supplemented with 0.3 mg/kg Se from sodium selenite (SS), 0.3 mg/kg Se from Se-enriched yeast (SEY), 0.3 mg/kg Se from SEC (SEC), or 0.3 mg/kg Se from SEC and 0.3 mg/kg Se from SEY (SEC + SEY). The experiment lasted for 8 wk. The results showed that dietary SEC + SEY supplementation decreased (P < 0.05) triglyceride (in the plasma and liver) and total cholesterol levels (in the plasma), and increased (P < 0.05) HDL-C concentration in plasma compared to CON diet. Compared with CON diet, SEC and/or SEY supplementation decreased (P < 0.05) the mRNA expression of hepatic ACC, FAS and HMGCR, and increased (P < 0.05) PPARα, VTG-II, Apo-VLDL II and ApoB expression. Dietary SEC + SEY and SEY supplementation increased (P < 0.05) Se content in egg yolk and breast muscle compared to CON diet. Dietary SEC, SEY or SEC + SEY supplementation increased (P < 0.05) the activity of antioxidant enzymes (GSH-PX, T-AOC and T-SOD) in the plasma and liver and decreased (P < 0.05) MDA content in the plasma compared to CON diet. Dietary Se supplementation promoted (P < 0.05) mRNA expression of Nrf2 in the liver. In contrast, dietary SEY and SEC supplementation resulted in a decrease (P < 0.05) of hepatic Keap1 mRNA expression compared to CON diet. Dietary SEC + SEY and/or SEC supplementation increased (P < 0.05) mRNA expression of Selenof, GPX1 and GPX4 in the liver compared with CON diet. In conclusion, dietary SEC (0.3 mg/kg Se) or SEC (0.3 mg/kg Se) + SEY (0.3 mg/kg Se) improved the antioxidant capacity and the lipid metabolism in the liver of aged laying hens, which might be associated with regulating Nrf2/Keap1 signaling pathway. Show less
Acetylcholinesterase (AChE) inhibitors are crucial for the symptomatic management of Alzheimer's disease (AD), with natural products-particularly botanical sources like Yellow Gastrodia elata (YGE)-se Show more
Acetylcholinesterase (AChE) inhibitors are crucial for the symptomatic management of Alzheimer's disease (AD), with natural products-particularly botanical sources like Yellow Gastrodia elata (YGE)-serving as promising reservoirs of such inhibitors. Nevertheless, comprehensive screening and mechanistic characterization of their inhibitory potential remain limited. This study sought to identify potent AChE inhibitors from YGE, investigate their mechanisms of action, and assess their therapeutic prospects for AD. Methodologically, an integrated approach was employed, combining ultrafiltration-liquid chromatography (UF-LC) for rapid inhibitor screening, molecular docking and dynamics simulations for mechanistic insight, two-stage high-speed countercurrent chromatography for compound isolation, enzyme kinetics to delineate inhibition modalities, and network pharmacology to uncover relevant AD-related targets. The findings identified seven active constituents with notable AChE inhibition, among which parishins A and G were obtained at high purity (98.26% and 97.26%, respectively) and exhibited mixed-type inhibition with low IC Show less
Patients with schizophrenia (SCZ) face multiple health challenges due to the complication of chronic diseases and psychiatric disorders. Among these, cardiovascular comorbidities are the leading cause Show more
Patients with schizophrenia (SCZ) face multiple health challenges due to the complication of chronic diseases and psychiatric disorders. Among these, cardiovascular comorbidities are the leading cause of their life expectancy being 15-20 years shorter than that of the general population. Identifying comorbidity patterns and uncovering differences in immune and metabolic function are crucial steps toward improving prevention and management strategies. A retrospective cross-sectional study was conducted using electronic medical records of inpatients discharged between 2015 and 2024 from a municipal psychiatric hospital in China. The study included patients diagnosed with Schizophrenia, Schizotypal, and Delusional Disorders (SSDs) (ICD-10: F20-F29). Comorbidity patterns were identified through latent class analysis (LCA) based on the 20 most common comorbid conditions among SSD patients. To investigate differences in peripheral blood metabolic and immune function, linear regression or generalized linear models were applied to 44 laboratory test indicators collected during the acute episode. The Benjamini-Hochberg method was used for p-value correction, and the false discovery rate (FDR) was calculated, with statistical significance set at FDR < 0.05. Among 3,697 inpatients with SSDs, four distinct comorbidity clusters were identified: SSDs only (Class 1), High-Risk Metabolic Multisystem Disorders (Class 2, n = 39), Low-Risk Metabolic Multisystem Disorders (Class 3, n = 573), and Sleep Disorders (Class 4, n = 205). Compared to Class 1, Class 2 exhibited significantly elevated levels of apolipoprotein A (ApoA; β = 90.62), apolipoprotein B (ApoB; β = 0.181), mean platelet volume (MPV; β = 0.994), red cell distribution width-coefficient of variation (RDW-CV; β = 1.182), antistreptolysin O (ASO; β = 276.80), and absolute lymphocyte count (ALC; β = 0.306), along with reduced apolipoprotein AI (ApoAI; β = -0.173) and hematocrit (HCT; β = -35.13). Class 3 showed moderate increases in low-density lipoprotein cholesterol (LDL-C; β = 0.113), MPV (β = 0.267), white blood cell count (WBC; β = 0.476), and absolute neutrophil count (ANC; β = 0.272), with decreased HCT (β = -9.81). Class 4 was characterized by elevated aggregate index of systemic inflammation (AISI; β = 81.07), neutrophil-to-lymphocyte ratio (NLR; β = 0.465), and systemic inflammation response index (SIRI; β = 0.346), indicating a heightened inflammatory state. The comorbidity patterns of patients with SCZ can be distinctly classified. During the acute episode, those with comorbid metabolic disorders exhibit a higher risk of cardiovascular diseases and immune system abnormalities, while patients with comorbid sleep disorders present a pronounced systemic inflammatory state and immune dysfunction. This study provides a basis for the chronic disease management and anti-inflammatory treatment, while also offering objective biomarker insights for transdiagnostic research. Show less
Heart failure (HF) is a serious cardiovascular condition resulting from abnormalities in multiple biological processes, affecting over 64 million people worldwide. We sought to expand our understandin Show more
Heart failure (HF) is a serious cardiovascular condition resulting from abnormalities in multiple biological processes, affecting over 64 million people worldwide. We sought to expand our understanding of the genetic basis of HF and more specific NICM subtype in the East Asian populations and evaluate the biological pathways underlying subclinical left ventricular dysfunction. We conducted a meta-analysis of genome-wide association studies (GWAS) for all-cause HF in the East Asian populations (N cases ~ 13,385) and a more precise definition of nonischemic cardiomyopathy (NICM) subtype in multi-ancestry populations (N cases~3,603). We identified a low-frequency East-Asian enriched coding variant near MYBPC3 and a NICM specific locus. Follow up analyses demonstrated male-specific HF association at the MYBPC3 locus, and highlighted SVIL as a candidate causal gene for NICM. Moreover, we demonstrated that SVIL deficiency aggravated cardiomyocyte hypertrophy, apoptosis and impaired cell viability in phenylephrine (PE)-treated H9C2 cells. In addition, the gene expression level of B-type natriuretic peptide (BNP) which was deemed as a hallmark for HF was further elevated by SVIL silencing in PE-stimulated H9C2 cells. RNA-sequencing analysis of H9C2 cells revealed that the function of SVIL might be mediated through pathways relevant to regulation and differentiation of heart muscle. These results enhance our understanding of the genetic architecture of HF in the East Asian populations, and provide important insight into the biological pathways underlying NICM and sex-specific relevance of the MYBPC3 locus that warrants further replication in another datasets. Show less
Post-hemorrhagic hydrocephalus (PHH) is a neurological disease that primarily affects premature infants and involves infiltration of blood into the brain's ventricles followed by excessive accumulatio Show more
Post-hemorrhagic hydrocephalus (PHH) is a neurological disease that primarily affects premature infants and involves infiltration of blood into the brain's ventricles followed by excessive accumulation of cerebrospinal fluid (CSF), leading to ventricular enlargement and increased intracranial pressure. The precise mechanisms driving PHH development and persistence are incompletely understood and lack disease-modifying treatments. Using a mouse model of PHH, we have identified transcriptomic, proteomic, and cellular features of PHH involving neuroimmune and neurovascular alterations recapitulating those reported in human disease. Improvement upon a lysophosphatidic acid (LPA)-induced PHH mouse model was combined with unbiased proteomic and single-nucleus transcriptomics that identified microglial molecular pathways propagating PHH. Pharmacological depletion of microglia in vivo significantly reduced PHH-associated ventriculomegaly. These data identify microglial and neurovascular elements in the development of PHH, implicating them as other potentially tractable therapeutic targets beyond LPA receptors, towards developing medical treatments for PHH. Show less
Tianhe Ye, Cong Liu · 2025 · Frontiers in pediatrics · Frontiers · added 2026-04-24
Pulmonary artery sling (PAS) is a rare congenital vascular anomaly in which the left pulmonary artery (LPA) originates from the right pulmonary artery (RPA), forming a ring around the tracheobronchial Show more
Pulmonary artery sling (PAS) is a rare congenital vascular anomaly in which the left pulmonary artery (LPA) originates from the right pulmonary artery (RPA), forming a ring around the tracheobronchial tree. Due to non-specific respiratory symptoms, it is frequently misdiagnosed, leading to significant delays in diagnosis. This report emphasizes the crucial role of quantitative multimodal imaging in establishing a definitive diagnosis, stratifying risk, and guiding optimal surgical planning. A 4-year-and-7-month-old boy presented with a 4-year history of recurrent cough and wheezing that was refractory to standard medical therapy. Echocardiography revealed a dilated main pulmonary artery (MPA) measuring 1.9 cm ( This case of isolated PAS underscores the indispensable role of a multimodal imaging strategy. While echocardiography can provide initial clues, quantitative CTA is paramount for definitive anatomical classification, precise stenosis quantification, and comprehensive preoperative planning. Early consideration of PAS in children presenting with refractory respiratory symptoms, coupled with advanced imaging, can prevent misdiagnosis and optimize outcomes. Show less
The selective inhibition of fibroblast growth factor receptors (FGFR) presents a significant challenge due to the high degree of sequence and the close structural similarity of the subtypes. Herein, w Show more
The selective inhibition of fibroblast growth factor receptors (FGFR) presents a significant challenge due to the high degree of sequence and the close structural similarity of the subtypes. Herein, we designed selective dual FGFR2/3 inhibitors based on the in-depth understanding of protein-ligand interaction contributions. We efficiently identified ISM7594 ( Show less
Paraneoplastic syndromes arise when tumor-derived cytokines reprogram distant organs. Although mediators such as Interleukin-6 have been implicated, how these signals impair host organ function remain Show more
Paraneoplastic syndromes arise when tumor-derived cytokines reprogram distant organs. Although mediators such as Interleukin-6 have been implicated, how these signals impair host organ function remains incompletely defined. Here, we identify a cytokine-lipid axis that drives hepatic autophagy dysfunction. Specifically, in Show less
Cognitive impairments in major depressive disorder (MDD) affect patients' social functioning, with underlying mechanisms involving gut microbiota and inflammatory factors remaining unclear. The study Show more
Cognitive impairments in major depressive disorder (MDD) affect patients' social functioning, with underlying mechanisms involving gut microbiota and inflammatory factors remaining unclear. The study analyzed cognitive function, gut microbiota changes, and inflammatory factor levels in 39 unmedicated MDD patients and 41 healthy controls, employing correlation and moderation effect analysis. MDD patients scored lower than controls in cognitive functions like information processing speed, attention/vigilance, verbal learning, visual learning and social cognition. They showed reduced gut microbiota diversity and increased levels of inflammatory markers (TNF-α, IL-1, IL-6, IL-17, IL-27, IL-33). Sellimonas abundance correlated negatively with attention/vigilance, moderated by TNF-α, IL-27, and IL-33. This relationship was stronger at lower inflammation levels. MDD patients exhibit multi-domain cognitive dysfunction alongside pro-inflammatory states and disrupted gut microbiota. The abundance of Sellimonas significantly predicts attention/vigilance deficits. Inflammatory factors modulate the impact of gut microbiota on cognitive function, suggesting chronic low-grade inflammation as a key risk factor for cognitive impairment in MDD. Show less
D-2-hydroxyglutarate (D-2HG), an oncometabolite derived from the tricarboxylic acid cycle. Previous studies have reported the diverse effects of D-2HG in pathophysiological processes, yet its role in Show more
D-2-hydroxyglutarate (D-2HG), an oncometabolite derived from the tricarboxylic acid cycle. Previous studies have reported the diverse effects of D-2HG in pathophysiological processes, yet its role in breast cancer remains largely unexplored. We applied an advanced biosensor approach to detect the D-2HG levels in breast cancer samples. We then investigated the biological functions of D-2HG through multiple in vitro and in vivo assays. A joint MeRIP-seq and RNA-seq strategy was used to identify the target genes regulated by D-2HG-mediated N6-methyladenosine (m We found that D-2HG accumulated in triple-negative breast cancer (TNBC), exerting oncogenic effects both in vitro and in vivo by promoting TNBC cell growth and metastasis. Mechanistically, D-2HG enhanced global m Our study unveils a previously unrecognized role for D-2HG-mediated RNA modification in TNBC progression and targeting the D-2HG/FTO/m Show less
Selenium (Se) foliar fertilizers enhance crop nutrition and address human selenium deficiency, while improper application may lead to excessive intake and residue accumulation. Our study comprehensive Show more
Selenium (Se) foliar fertilizers enhance crop nutrition and address human selenium deficiency, while improper application may lead to excessive intake and residue accumulation. Our study comprehensively assessed the toxicity and function of novel selenium nanoparticles and traditional sodium selenite fertilizers across cell, zebrafish, and murine models. Both fertilizers enhanced antioxidant pathways at low doses, but selenium nanoparticles exhibited stronger antioxidant and ferroptosis-modulating effects with lower toxicity at a high dose. Sodium selenite increased total and lipid ROS production, leading to decreased viability of cells and increased distortion and mortality of zebrafish. In mice, sodium selenite induced hepatic toxicity and decreased GPX4. Transcriptome analysis revealed that sodium selenite downregulated c-JUN and APOA4, weakening the antioxidant defense, whereas selenium nanoparticles promoted ferroptosis resistance through FGF21. These findings suggest selenium nanoparticles as a safer alternative for Se biofortification, mitigating health risks while supporting food security and environmental sustainability. Show less
This study aims to identify and characterize daily activity accumulation patterns (bouts of physical activity and sedentary behavior) among adolescents and then to explore the associations between the Show more
This study aims to identify and characterize daily activity accumulation patterns (bouts of physical activity and sedentary behavior) among adolescents and then to explore the associations between these groups and depressive symptoms. A total of 521 adolescents aged 13-18 years from Wuhan and Changsha, China, were included. Bouts of physical activity (PA) and sedentary behavior (SED) were measured using accelerometers. The Center for Epidemiologic Studies Depression Scale was used to assess participants' depressive symptoms. Latent profile analysis was employed to identify distinct groups based on their activity patterns. Three distinct groups were identified: "Prolonged sitters" ( The synergistic effect of strategies to reduce total SED duration by limiting SED bouts to 30 min or less and increasing light physical activity (LPA) may also be effective in alleviating depressive symptoms in adolescents. Show less
The Interaction of Person-Affect-Cognition-Execution (I-PACE) model offers a framework for understanding the interplay between cognitive, affective, and behavioral factors in internet addiction (IA). Show more
The Interaction of Person-Affect-Cognition-Execution (I-PACE) model offers a framework for understanding the interplay between cognitive, affective, and behavioral factors in internet addiction (IA). Our study aims to explore the heterogeneity of IA, identify bridge connectors, and compare the efficacy of cognitive behavioral therapy combined with mindfulness-based intervention (CBT+MBI) versus CBT alone in reducing IA levels among Chinese college students. In study 1, 1,030 Chinese college students completed assessments of IA, automatic thoughts, self-control, and anxiety. Latent profile analysis (LPA) was employed to identify distinct symptom profiles of IA across individuals. Network analysis (NA) identified bridge connectors for targeted intervention. In study 2, 36 participants randomly selected from the high IA and low IA groups of study 1 were randomly assigned to CBT+MBI, CBT alone, or a control group. The CBT+MBI group received an 8-week dual-modality intervention and the CBT alone received an 8-week CBT intervention, both designed to target the bridge connectors identified via NA in Study 1, while the control group only completed basic questionnaires. In study 1, LPA identified four subgroups: regular, at-risk, low IA, and high IA groups. NA pinpointed automatic thoughts and anxiety as bridge connectors. In study 2, targeted interventions significantly reduced college students' levels of IA. CBT+MBI resulted in greater and more sustained improvements compared to CBT alone, with effects maintained for six-month post-intervention. Our study not only reinforces the I-PACE model but also provides actionable strategies for designing evidence-based, multidimensional interventions to reduce addictive behaviors among college students. Show less
The Kirgiz, a Turkic-speaking ethnic group with a rich nomadic heritage, represent a pivotal population for understanding human migration and adaptation in Central Asia. However, their genetic origins Show more
The Kirgiz, a Turkic-speaking ethnic group with a rich nomadic heritage, represent a pivotal population for understanding human migration and adaptation in Central Asia. However, their genetic origins and admixture history remain largely unexplored. Here, we present the first comprehensive genomic study of Kirgiz populations from Xinjiang, China (XJ.KGZ, n = 36) and their counterparts in Kyrgyzstan (KRG), integrating genome-wide data of 2,406 global individuals. Our analyses reveal four primary ancestry components in XJ.KGZ: East Asian (41.7%), Siberian (25.6%), West Eurasian (25.2%), and South Asian (7.6%). Despite close genetic affinity (FST = 0.13%), XJ.KGZ and KRG diverged ∼447 years ago, with limited gene flow post-split. A two-wave admixture model elucidates their demographic history: an initial East-West Eurasian mixture ∼2,225 years ago, likely reflecting west-east contacts during the period of the Warring States and the Qin Dynasty, followed by secondary admixture events (∼875 to 425 years ago) linked to historical migrations under Mongol and post-Mongol rule. Local adaptation signatures implicate genes critical for cellular tight junction (e.g. PATJ), pathogen invasion (e.g. OR14I1), and cardiac functions (e.g. RYR2) with allele frequency deviations suggesting ancestry-specific selection. While no classical high-altitude adaptation genes (e.g. EPAS1) showed selection signals, RYR2 and C10orf67-implicated in hypoxia response in Tibetan fauna-displayed Western ancestry bias, hinting at convergent adaptation mechanisms. This study advances our understanding of the genetic makeup and admixture history of the Kirgiz people and provides novel insights into human dispersal in Central Asia. Show less
This study aimed to assess the prognostic significance of serum lipoprotein(a) [Lp(a)] levels regarding overall survival (OS) and progression-free survival (PFS) among patients diagnosed with pancreat Show more
This study aimed to assess the prognostic significance of serum lipoprotein(a) [Lp(a)] levels regarding overall survival (OS) and progression-free survival (PFS) among patients diagnosed with pancreatic cancer (PC). A retrospective cohort of 364 pathologically confirmed PC patients treated at the Affiliated Hospital of Qingdao University between January 2019 and December 2022 was analyzed. The optimal cutoff for Lp(a) was identified using X-tile software, allowing categorization into high and low Lp(a) groups. To minimize selection bias, propensity score matching (PSM) was utilized. Survival outcomes were compared using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models were applied to identify independent prognostic variables affecting OS and PFS. Patients with high Lp(a) had significantly shorter OS and PFS both before and after PSM (post-PSM OS: 12.28 vs. 27.67 months, P = 0.003; PFS: 7.00 vs. 11.30 months, P = 0.002). Multivariate Cox analysis confirmed high Lp(a) as an independent predictor of poor OS [HR = 2.11 (1.17-3.81), P = 0.013] and PFS [HR = 2.14 (1.20-3.83), P = 0.010]. In the surgical subgroup (n = 215), high Lp(a) was also associated with worse OS (16.43 vs. 35.47 months, P = 0.02) and PFS (8.40 vs. 11.77 months, P = 0.036). Multivariate analysis in this subgroup showed that high Lp(a) remained an independent risk factor for OS [HR = 2.82 (1.36-5.87), P = 0.006] and PFS [HR = 2.01 (1.06-3.86), P = 0.034]. Elevated serum Lp(a) is an independent predictor of reduced OS and PFS in patients with pancreatic cancer. In contrast to conventional lipid profiles, the genetic stability of Lp(a) makes it a reliable baseline prognostic marker. Show less