Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer's disease. These biomarkers better reflect disease pathogenesis compared to clinical d Show more
Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer's disease. These biomarkers better reflect disease pathogenesis compared to clinical diagnosis. Here, we perform a genome wide association study meta-analysis including 18,948 individuals of European ancestry and identify 12 genome-wide significant loci across all three biomarkers, eight of them novel. We replicate the association of biomarkers with APOE, CR1, GMNC/CCDC50 and C16orf95/MAP1LC3B. Novel loci include BIN1 for amyloid beta and GNA12, MS4A6A, SLCO1A2 with both total tau and phosphorylated tau 181, as well as additional loci on chr. 8, near ANGPT1 and chr. 9 near SMARCA2. We also demonstrate that these variants have significant association with Alzheimer's disease risk, disease progression and/or brain amyloidosis. The associated genes are implicated in lipid metabolism independent of APOE, coupled with autophagy and brain volume regulation driven by total tau and phosphorylated tau 181 dysregulation. 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
The Lipoprotein(a) (LPA) rs3798220 and rs10455872 polymorphisms have been indicated to be involved with the coronary heart disease (CHD) susceptibility. However, there are still differences between th Show more
The Lipoprotein(a) (LPA) rs3798220 and rs10455872 polymorphisms have been indicated to be involved with the coronary heart disease (CHD) susceptibility. However, there are still differences between the individual studies. To explore the correlation of LPA gene rs3798220 and rs10455872 polymorphisms and CHD, the current meta-analysis was performed. The random or fixed effect genetic models were used to calculate the pooled odds ratios (ORs) and their corresponding 95 % confidence intervals (CI). A significant association was found between LPA rs3798220 polymorphism and CHD under allelic (OR: 1.488), recessive (OR: 1.543), dominant (OR: 1.534), homozygous (OR: 1.544), heterozygous (OR: 1.498) and additive genetic models (OR: 1.531). There was also a significant association between LPA rs10455872 polymorphism and CHD under allelic (OR: 1.607), dominant (OR: 1.751), heterozygous (OR: 1.723) and additive genetic models (OR: 1.686). LPA rs3798220 and rs10455872 polymorphisms were significantly associated with increased CAD risk. The persons carrying C allele of LPA rs3798220 and G allele of LPA rs10455872 polymorphisms might have higher CHD risk than the T allele of rs3798220 or A allele of rs10455872 carriers. Show less
The paraventricular hypothalamus (PVH) controls behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular marker Show more
The paraventricular hypothalamus (PVH) controls behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for centrally projecting PVH neuron populations remain largely undefined, and a complete census of PVH cell types has not been established. Therefore, we performed extensive single-cell/nucleus RNA sequencing to catalog PVH neuron subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to map them spatially. Our spatial transcriptomic atlas resolves 26 Sim1 Show less
Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase of the TRIM superfamily, modulates critical cellular processes including ubiquitination, autophagy, and oxidative stress respons Show more
Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase of the TRIM superfamily, modulates critical cellular processes including ubiquitination, autophagy, and oxidative stress response. Accumulating evidence highlights its context-dependent regulatory roles in hepatocellular carcinoma (HCC)-the most prevalent primary liver malignancy with high mortality and limited therapeutic efficacy. This review systematically summarizes the core mechanisms by which TRIM21 orchestrates HCC progression: ① Autophagy regulation: TRIM21 modulates HCC autophagy via multiple axes, including CCR4-NOT complex (TNKS1BP1/CNOT4)-mediated substrate ubiquitination, ATG14-dependent autophagosome initiation, and RETREG1-driven reticulophagy, with context-dependent effects on tumor proliferation. ② Drug resistance: TRIM21 enhances oxaliplatin sensitivity by ubiquitinating and degrading G6PD (the rate-limiting enzyme of the pentose phosphate pathway), while its role in sorafenib resistance involves dual pathways-the MST1/YAP axis and the ApoE/cholesterol/PI3K-AKT cascade. ③ Metastasis suppression: TRIM21 restricts HCC invasion and metastasis by ubiquitinating key oncoproteins, preserving epithelial integrity and inhibiting mesenchymal transition. ④ Reactive oxygen species (ROS) balance: TRIM21 regulates oxidative stress in HCC via the SQSTM1/p62-Keap1-NRF2 axis, coordinating with HIF1α to modulate antioxidant responses and tumor cell survival. Additionally, we discuss the regulatory significance of TRIM21 in HCC associated with hepatitis B virus (HBV) infection (via HBx/DNA polymerase ubiquitination) and nonalcoholic steatohepatitis (NASH) (via suppressing lipogenic enzymes to reduce steatosis-driven carcinogenesis). This review provides a theoretical basis for TRIM21 as a potential diagnostic marker and therapeutic target for HCC. Show less
Dandan Wang, Peng Li · 2026 · Ecotoxicology and environmental safety · Elsevier · added 2026-04-24
Depression is a prevalent mental disorder in modern society, with a complex and incompletely understood etiology. Accumulating evidence indicates that pesticide exposure is a potential risk factor for Show more
Depression is a prevalent mental disorder in modern society, with a complex and incompletely understood etiology. Accumulating evidence indicates that pesticide exposure is a potential risk factor for mental health disorders. Atrazine (ATR), a widely used herbicide with the highest global application rates and frequently detected in environmental media, has been confirmed to possess neurotoxicity. However, there are currently no reports examining its effects on depression. Therefore, this study aimed to investigate the effects of subchronic ATR exposure on depression-like phenotypes in mice through behavioral tests, pathological examinations, and molecular analyses. The results demonstrated that ATR exposure induced significant depressive-like behaviors and led to neuronal reductions in key brain regions associated with depression, such as the hippocampus and prefrontal cortex. These effects were mechanistically linked to oxidative damage and decreased expression levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF). Collectively, this study not only reveals the potential role and mechanism of ATR as an environmental risk factor for depression, but also provides a theoretical basis for the prevention and treatment of its new neurotoxicological effects and future related research. 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
Ying Yang, Xiang Li, Dan-Li Tang+4 more · 2026 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
This study established a hyperlipidemia model by feeding Sprague-Dawley rats a high-fat diet for 8 weeks. The rats were randomly assigned to the following groups: model group, atorvastatin calcium gro Show more
This study established a hyperlipidemia model by feeding Sprague-Dawley rats a high-fat diet for 8 weeks. The rats were randomly assigned to the following groups: model group, atorvastatin calcium group(4.8 mg·kg~(-1)), low-, medium-, and high-dose Tanyu Tongzhi Optimization Decoction(TYTZD) groups(3.6, 7.2, and 14.4 g·kg~(-1)), and a normal diet control group. After 4 weeks of continuous administration, hematoxylin-eosin(HE) and oil red O staining were used to observe liver pathological changes and lipid infiltration. Automatic biochemical analyzer were performed to assess blood lipid profiles, coagulation function, and liver function. Transcriptomic and proteomic analyses were employed to identify differentially expressed genes(DEGs) and proteins(DEPs), followed by enrichment analysis. The MCODE algorithm was applied to classify DEGs and DEPs into modules, and network separation index(S₍AB)) was calculated to assess module separation, enabling construction of a gene-protein co-expression network for core target screening. The diagnostic accuracy of core targets was evaluated by area under the receiver operating characteristic(ROC) curve(AUC), and ELISA was used to measure core target expression. Western blot detected the expression of core pathway-related proteins in liver tissue. RESULTS:: demonstrated that TYTZD significantly improved dyslipidemia, coagulation dysfunction, liver injury, hepatic pathology, and lipid infiltration in hyperlipidemic rats. Transcriptomic analysis identified 571 DEGs significantly reversed by TYTZD, mainly enriched in inflammatory signaling pathways such as Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB). Proteomic analysis identified 102 reversed DEPs, mainly involved in cholesterol metabolism pathways. Integrated analysis identified core targets including TLR4, tumor necrosis factor-α(TNF-α), integrin subunit alpha M(ITGAM), Toll-like receptor 2(TLR2), matrix metalloproteinase 9(MMP9), interleukin-1β(IL-1β), apolipoprotein E(APOE), and apolipoprotein C2(APOC2), all with AUC values greater than 0.70. ELISA showed that TYTZD intervention significantly downregulated MMP9, TNF-α, IL-1β, TLR2, ITGAM, and TLR4, and upregulated APOC2 and APOE. Western blot indicated that TYTZD reduced TLR4, p-NF-κB, and IL-1β protein expression in liver tissue. In conclusion, TYTZD may exert anti-hyperlipidemic effects through regulation of core targets such as ITGAM, TLR4, and APOC2, and by modulating the TLR4/NF-κB signaling pathway to intervene in inflammatory responses and cholesterol metabolism, thereby achieving multi-target, multi-pathway therapeutic effects against hyperlipidemia. Show less
Gene fusions are common primary drivers of pediatric leukemias and are the result of underlying structural variants (SVs). Current clinical workflows to detect such alterations rely on a multimodal ap Show more
Gene fusions are common primary drivers of pediatric leukemias and are the result of underlying structural variants (SVs). Current clinical workflows to detect such alterations rely on a multimodal approach, which often increases analysis time and overall cost of testing. In this study, we used long-read sequencing (lrSeq) as a proof-of-concept to determine whether clinically relevant (cr) SVs could be detected within a small (n = 17) pediatric leukemia cohort. We show that this methodology successfully determined all known crSVs (n = 5/5) detected through routine clinical testing. This approach also identified crSVs that resulted in the classification of a leukemia genetic subtype for four additional patients (n = 4/12), such as an ins(11;10)(q23.3;p12p12) forming a KMT2A::MLLT10 fusion, that were missed by routine clinical approaches. This study demonstrates the diagnostic potential of lrSeq as an assay for SV detection in pediatric leukemia and supports lrSeq as a valuable tool for the accurate detection of crSVs. Show less
Alzheimer's disease (AD) is increasingly recognized as a multisystem disorder shaped not only by central neurodegeneration but also by peripheral metabolic and immune dysregulation. Growing evidence h Show more
Alzheimer's disease (AD) is increasingly recognized as a multisystem disorder shaped not only by central neurodegeneration but also by peripheral metabolic and immune dysregulation. Growing evidence highlights the gut microbiota and its metabolites as key modulators of amyloid accumulation, tau phosphorylation, neuroinflammation, and microglial dysfunction. This review aims to synthesize current advances on how plant-derived bioactive compounds modulate AD pathophysiology through microbiota-dependent metabolic and neuroimmune mechanisms, and to establish a systems-level framework linking botanical interventions to gut microbiota remodeling and metabolite signaling. A comprehensive literature survey was conducted using PubMed, Web of Science, ScienceDirect, and Google Scholar, covering publications from 2010 to 2026. Studies investigating gut microbiota, microbial metabolites, and plant-derived bioactive compounds in AD-related metabolic, immune, and neurodegenerative pathways were systematically reviewed and integrated. Plant-derived bioactive compounds, including phytochemicals, polysaccharides, and multi-herb formulations, interact extensively with the gut microbiota, undergoing microbial biotransformation to yield more active metabolites while simultaneously reshaping microbial community structure and metabolite profiles. These bidirectional interactions position the microbiota as a central mediator of plant-derived therapeutic activity. We summarize current evidence on how plant-derived compounds influence AD pathophysiology through microbiota-dependent metabolic and neuroimmune pathways. Major microbial metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), bile acids (BAs), and indole derivatives, are discussed, together with their regulatory roles in signaling networks such as nuclear factor κB (NF-κB), phosphatidylinositol 3-kinase/Akt (PI3K/Akt), cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF), and triggering receptor expressed on myeloid cells 2 (TREM2)-associated microglial states. We further summarize evidence for synergistic strategies combining plant bioactives with probiotics and highlight advances in microbial biotransformation, precision metabolite modulation, and engineered microbial systems. Finally, future directions integrating multi-omics, personalized microbiota-guided interventions, and synthetic biology are outlined to support the development of targeted, mechanism-based therapies. By framing AD through a gut microbiota-centered perspective, this review provides a unified mechanistic foundation for the development of next-generation interventions based on plant-derived compounds and microbiota regulation. Show less
Disruption of circadian rhythms is increasingly recognized as a contributor to cognitive dysfunction, but its role in gestation-associated cognitive changes remains unexplored. Here we combine human c Show more
Disruption of circadian rhythms is increasingly recognized as a contributor to cognitive dysfunction, but its role in gestation-associated cognitive changes remains unexplored. Here we combine human cognitive screening with a comprehensive longitudinal mouse model to investigate whether gestational cognitive impairment and postpartum recovery are coupled with disruption and restoration of hippocampal circadian rhythms. Cognitive function was assessed in pregnant and postpartum women using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). In mice, four reproductive stages were compared: control, gestation, 1 month postpartum, and 3 months postpartum. Serum gonadotropins and sex hormones levels were quantified using ELISA. Home-cage locomotor activity was recorded over 48 h under a 12 h:12 h light-dark cycle. Hippocampal-dependent memory was evaluated using the novel object recognition test and Barnes maze at Zeitgeber times ZT6 (day) and ZT18 (night). Hippocampal amyloid β (Aβ) deposition was visualized via immunofluorescence; protein expression of amyloid precursor protein (APP), β-site amyloid precursor protein cleaving enzyme-1 (BACE1), and phosphorylated tau was measured by Western blots. Hippocampal clock gene expression was quantified by RT-qPCR at six time points; circadian parameters (mesor, amplitude, acrophase) were derived by cosinor analysis and compared between groups. Human cognitive screening confirmed modest gestational decline with postpartum recovery. In mice, gestation disrupted daily locomotor activity rhythms and reduced nocturnal preference; both partially recovered by 1 month and fully by 3 months postpartum. Behaviourally, pregnancy impaired the normal day-night difference and performance in novel object exploration and Barnes maze, which recovered progressively. At the molecular level, gestation increased hippocampal APP and BACE1 expression, elevated Aβ42 deposition, and induced tau hyperphosphorylation at multiple sites-hallmarks of Alzheimer's disease-related pathology. These alterations partially reversed by 1 month postpartum and normalized by 3 months. Hippocampal clock genes maintained 24 h rhythmicity, but gestation induced gene-specific phase shifts, amplitude reductions, and mesor alterations. These parameters showed gradual, gene-dependent normalization postpartum. Gestational cognitive impairment and postpartum recovery are associated with reversible disruption and restoration of both hippocampal circadian rhythms and Alzheimer's disease-related molecular pathology. These findings are correlational in nature and provide a foundation for future causal investigations. Show less
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with limited treatment options and frequent drug resistance. Novel therapeutic targets are urgently needed. We performed a druggabl Show more
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with limited treatment options and frequent drug resistance. Novel therapeutic targets are urgently needed. We performed a druggable genome-wide Mendelian randomization (MR) analysis using blood cis-expression quantitative trait locus (eQTL) and HS genome-wide association study (GWAS) data. Colocalization, transcriptomic validation, single-cell RNA sequencing, and cell-cell communication analyses were integrated to explore gene function and cell-type specificity. We identified eight genes that showed significant associations with HS through MR analysis. Colocalization analysis further prioritized PSMA4 and MAST3 as the most promising druggable targets for HS. Specifically, PSMA4 (single nucleotide polymorphisms [SNPs] = 10; inverse-variance weighted [IVW] OR = 1.912, 95% CI: 1.492-2.450, 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
Sepsis is a syndrome caused by the host's inflammatory response to an infection with an unknown mechanism. This study aimed to identify differentially expressed genes (DEGs) potentially involved in th Show more
Sepsis is a syndrome caused by the host's inflammatory response to an infection with an unknown mechanism. This study aimed to identify differentially expressed genes (DEGs) potentially involved in the development and recovery of tracheal injury from septic shock. Nine New Zealand white rabbits were randomized to control (CON), septic shock model (SS), and septic shock norepinephrine treatment (SSNE) groups (each group n = 3). The SS and SSNE groups were injected with lipopolysaccharide to induce septic shock. The SSNE group was administered Ringer lactate with norepinephrine to maintain normal blood pressure. All animals underwent cuffed endotracheal intubation for 2 h. The injured tracheal segment was harvested. RNA sequencing was performed to identify the DEGs, followed by bioinformatics analysis, and pathological staining (both HE and Masson) was performed for pathological evaluation. Bioinformatics analysis included principal component analysis (PCA), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) network construction. Key findings were validated by qRT-PCR and immunohistochemistry. We obtained 124 upregulated and 28 downregulated DEGs in SS vs. CON groups, along with 60 upregulated and 178 downregulated DEGs in SSNE vs. SS groups. The pathological score showed that trachea tissue in the SS group had the highest score. The protein-protein interaction (PPI) prediction identified APOB and CD36 as the hub genes. The molecular experiments further confirmed that at mRNA and protein levels, APOB was significantly upregulated, while CD36 was significantly downregulated. Subsequent qRT-PCR and immunohistochemical analyses confirmed that APOB expression was significantly upregulated while CD36 was downregulated in the septic shock group, a trend partially reversed by norepinephrine treatment. Our study results suggest that APOB and CD36 may be involved in the pathogenesis of tracheal injury recovery in septic shock patients treated with NE. Not applicable. Show less
Diabetes mellitus (DM) is hypothesized to increase the risk of Alzheimer's disease (AD). However, existing studies have yielded conflicting results, with some demonstrating a significant association b Show more
Diabetes mellitus (DM) is hypothesized to increase the risk of Alzheimer's disease (AD). However, existing studies have yielded conflicting results, with some demonstrating a significant association between DM and AD risk while others have not. Therefore, this meta-analysis aimed to systematically evaluate the association between DM and AD risk. Comprehensive searches were conducted in PubMed, Web of Science, and Embase databases to identify cohort or case-control studies investigating the association between DM and AD risk. All eligible studies published before October 2025 were included. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias. Hazard ratio (HR) and 95% confidence interval (CI) were pooled as the effect size for meta-analysis. Heterogeneity among studies was evaluated using Cochran's A total of 11 studies involving 3,393,545 participants were included. A meta-analysis revealed that DM was significantly associated with an increased risk of AD (HR = 1.36, 95% CI (1.19, 1.55), This meta-analysis provides compelling evidence that DM is an independent risk factor for AD, offering important implications for clinical practice and future research. However, due to the methodological limitations of this study, the results should be interpreted with caution. Large-scale, high-quality prospective cohort studies are needed to fully investigate the relationship between DM and AD risk. https://www.crd.york.ac.uk/prospero/, identifier CRD420251159844. Show less
Major depressive disorder (MDD) in adolescents is a critical public health concern, yet objective diagnostic biomarkers remain lacking. We conducted an integrative lipidomics study across human cohort Show more
Major depressive disorder (MDD) in adolescents is a critical public health concern, yet objective diagnostic biomarkers remain lacking. We conducted an integrative lipidomics study across human cohorts and a chronic unpredictable mild stress (CUMS) rat model. Targeted UPLC-MS/MS profiling was applied to a training cohort (95 MDD, 40 controls), and untargeted UPLC-HRMS profiling to an independent cohort (56 MDD, 37 controls). Candidate biomarkers were identified using univariate tests, partial least squares discriminant analysis, and three feature-selection methods (Boruta, LASSO, RFE), with predictive performance evaluated by cross-validation and external replication. Translational relevance was examined in CUMS rats through behavioral assays and lipidomic profiling of serum and brain tissues. Pathway enrichment and regression models explored metabolic context and clinical associations. In the training cohort, we found that 244 lipids were significantly altered, highlighting altered glycerophospholipid, glycerolipid, and sphingolipid metabolism. A 29-lipid panel achieved 90.4% cross-validation accuracy, while a reduced 7-lipid subset reached 94.8%. In the validation cohort, an 8-lipid panel achieved 71.2% accuracy, and a minimal 2-lipid set-LPA(18:2) and SPH(d16:1)-reached 72.1%. Cross-species analysis confirmed consistent downregulation of SPH(d16:1) in serum of both humans and rats, and of LPC(0:0/16:0) specifically in the rat prefrontal cortex. Regression analyses linked sex, age, and anxiety severity to lipid alterations. This cross-platform, cross-species study identifies reproducible lipid signatures of adolescent MDD, highlights SPH(d16:1) and LPC(0:0/16:0) as translational biomarkers, and implicates glycerophospholipid metabolism in MDD pathophysiology, providing a foundation for biomarker-guided diagnostics and therapeutics. Show less
Depression is a debilitating psychiatric disorder with high prevalence and suicide risk, imposing significant burdens on global health. Against this global health burden, the active ingredients of Gek Show more
Depression is a debilitating psychiatric disorder with high prevalence and suicide risk, imposing significant burdens on global health. Against this global health burden, the active ingredients of Gekko gecko Linnaeus (AIGG), a traditional Chinese medicine (TCM), have shown empirical antidepressant effects. However, their specific pharmacological mechanisms remain unclear. This study systematically elucidated the antidepressant mechanisms of AIGG by integrating GC-MS-based component analysis, network pharmacology, molecular docking, and a corticosterone (CORT)-induced depressive mouse model. GC-MS identified 10 bioactive compounds (including fatty acids) in AIGG. Network pharmacology screening of 51 potential targets revealed significant enrichment in synaptic transmission and cAMP pathways. Molecular docking confirmed strong binding affinities between AIGG-derived compounds and key targets. In vivo experiments demonstrated that AIGG significantly reversed depression-like behaviors in both forced swim and tail suspension tests, suppressed Interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and elevated β-nerve growth factor (β-NGF) levels, attenuated neuroinflammatory infiltration and neuronal apoptosis in brain tissue, and upregulated protein expression of protein kinase cAMP-activated catalytic subunit alpha (PRKACA), brain-derived neurotrophic factor (BDNF), and postsynaptic density protein 95 (PSD95). The study confirmed that AIGG alleviates depression by activating the cAMP-PRKACA-BDNF axis to restore synaptic plasticity, providing a novel natural product-based strategy for treatment of the resistant depression. Show less
To ascertain the level of psychological resilience, examine the latent profiles of individuals within infertile couples who experience recurrent implantation failure (RIF), identify the relevant influ Show more
To ascertain the level of psychological resilience, examine the latent profiles of individuals within infertile couples who experience recurrent implantation failure (RIF), identify the relevant influencing factors, and lay a foundation for developing customized intervention strategies. Convenience sampling was adopted in this study. Participants were selected from individuals in infertile couples with RIF who attended the Second West China Hospital of Sichuan University between November 2024 and July 2025. Data were collected via a general information questionnaire and validated scales assessing psychological resilience, social support, sleep quality, family adaptability and cohesion, anxiety, and depression. Latent profile analysis (LPA) was performed to explore the psychological resilience profiles of individuals with RIF, while univariate analysis and multivariate Logistic regression analyses were employed to identify the influencing factors associated with different profile categories. A total of 303 valid questionnaires were collected, including 194 from females and 109 from males. The overall psychological resilience score was (26.66 ± 6.319). Latent profile analysis categorized psychological resilience into three subgroups: the low tenacity-low strength subgroup (31.4%), the moderate tenacity-moderate strength subgroup (53.1%), and the high tenacity-high strength subgroup (15.5%); Multivariate Logistic regression analysis indicated that gender, family adaptability and depression severity (all Marked interindividual heterogeneity exists in the psychological resilience of individuals with RIF. Gender, family adaptability and depression severity serve as the core influencing factors. In clinical practice, stratified and targeted interventions should be delivered according to distinct psychological resilience subgroups. It yields clinical implications for an association between improved psychological resilience among individuals from couples with RIF and enhanced treatment adherence. 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
Diabetic kidney disease (DKD) is a major diabetic complication that often progresses to end-stage renal disease and causes high mortality. Early diagnosis is essential for effective prevention and tre Show more
Diabetic kidney disease (DKD) is a major diabetic complication that often progresses to end-stage renal disease and causes high mortality. Early diagnosis is essential for effective prevention and treatment. To explore the underlying mechanisms of DKD and identify plasma biomarkers for early diagnosis. In this study, healthy adults and individuals with diabetes mellitus (classified into normal albuminuria (NA), microalbuminuria (MI), and macroalbuminuria (MA) groups) were recruited. Plasma samples were collected from all participants, and 12 subjects per group were then randomly selected as a discovery cohort for proteomic analysis. Proteomics identified 95 differentially expressed proteins (DEPs) among the groups. These DEPs associated pathways evolved in a stage-specific manner in which inflammation dominated the early NA/Ctrl stage, complement and coagulation cascades became the main drivers during MI/NA, and MA/MI exhibited newly emerged disturbances in oxidative detoxification, lysosomal function, and nitrogen metabolism alongside sustained complement and coagulation changes. Among them, the complement and coagulation cascades were closely related to DKD progression. Through hub protein analysis, five proteins (FGG, ITIH4, A2M, C3, and APOE) that showed consistent trends across disease stages were identified as potential diagnostic biomarkers for DKD. Our research provides new insights into the mechanisms and early diagnosis of DKD. Show less
Liver metastasis is the predominant cause of mortality among individuals diagnosed with colorectal cancer (CRC). However, the mechanisms underlying the tumor-microenvironment interactions that promote Show more
Liver metastasis is the predominant cause of mortality among individuals diagnosed with colorectal cancer (CRC). However, the mechanisms underlying the tumor-microenvironment interactions that promote this process remain poorly defined. Here, we developed an integrative multiomics framework to dissect the cellular and molecular determinants of colorectal cancer liver metastasis (CRLM). By analyzing 1,156 metastasis-associated genes, we identified three molecular subtypes with distinct prognostic and immunometabolic features: C1 with mixed phenotypes and favorable survival, C2 with metabolic activation and immune suppression, and C3 with immune activation and signaling dysregulation, which had the poorest outcomes. Mechanistically, we discovered that SPP1⁺ macrophages secrete PDGFB, which activates PDGFRB signaling in FADS1⁺ tumor cells to trigger epithelial-mesenchymal transition (EMT) and promote liver metastasis. This macrophage-tumor crosstalk was validated by single-cell transcriptomics, genetic perturbation, and coculture experiments. Collectively, our findings define a macrophage-derived PDGFB-PDGFRB axis that drives CRC liver metastasis and highlight a potential therapeutic target for overcoming metastatic progression and immune resistance. Show less
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the ef Show more
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the effects of Orientin on oxidized low-density lipoprotein and high glucose (ox-LDL/HG)-triggered endothelial cell injury and diabetes-accelerated atherosclerosis remain unclear. ApoE Show less
Gliomas comprise a heterogeneous group of central nervous system tumors in which gene fusions (GFs) are significant oncogenic drivers and emerging diagnostic and therapeutic biomarkers. In cancer diag Show more
Gliomas comprise a heterogeneous group of central nervous system tumors in which gene fusions (GFs) are significant oncogenic drivers and emerging diagnostic and therapeutic biomarkers. In cancer diagnosis, GF detection largely relies on targeted short-read sequencing fusion panels, such as the Children's Hospital of Philadelphia (CHOP) Fusion Panel (FUSIP). While these panels are effective for detecting recurrent, well-characterized GFs, they are limited to predefined gene sets and cannot identify full-length transcripts. Here, we analyzed 49 high- and low-grade gliomas previously classified as fusion-negative by FUSIP using an untargeted whole-transcriptome RNA sequencing approach with Oxford Nanopore Technologies (ONT) long-read sequencing. This enabled transcriptome-wide fusion discovery of additional known and potentially novel oncogenic GFs beyond panel constraints. Long-read sequencing further allowed direct resolution of full-length fusion transcripts and their associated isoform structures. By integrating GF detection with isoform-level transcript analysis, we identified fusion-associated transcript isoforms with alternative splicing patterns that aligned near reported GF breakpoints, including Show less
AllergoOncology has emerged as an interdisciplinary field exploring the interaction between allergic diseases and cancer; however, the lack of stable in vivo models has limited mechanistic investigati Show more
AllergoOncology has emerged as an interdisciplinary field exploring the interaction between allergic diseases and cancer; however, the lack of stable in vivo models has limited mechanistic investigations. This study aimed to establish an experimental animal model to explore the impact of systemic allergic responses on tumor progression and to provide preliminary insights into the regulatory role of allergy in cancer development. An ovalbumin (OVA)-induced systemic allergy tumor-bearing mouse model (OVA-TM) was established by OVA sensitization followed by subcutaneous implantation of CT26 colon cancer cells. Tumor growth, immune responses, and behavioral changes were systematically evaluated. Tumor immune microenvironment alterations were assessed using immunological and histological analyses. Transcriptomic profiling and mass spectrometry imaging (MSI) were integrated to investigate immune-related metabolic alterations. Human tumor survival datasets were used to validate the prognostic relevance of differentially expressed genes (DEGs), and enrichment analyses of allergy- and cancer-associated genes were performed using humanized databases. OVA-induced systemic allergy significantly suppressed tumor growth and promoted immune cell infiltration, particularly CD3 This study establishes a practical in vivo model for AllergoOncology and demonstrates that systemic allergic responses can modulate tumor progression through immune activation, apoptosis, and inflammation-metabolism axis reprogramming, providing a foundation for future mechanistic and therapeutic studies. Show less
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Show more
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Alzheimer's disease patients (mild cognitive impairment to moderate dementia) received biweekly lecanemab (10 mg/kg). A matched Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort served as comparator. Cognitive tests, plasma biomarkers, and optional amyloid/tau positron emission tomography (PET) were assessed over 6 months. Lecanemab significantly attenuated cognitive decline versus ADNI. Plasma Aβ42, Aβ40, phosphorylated tau 217 (p‑tau217), glial fibrillary acidic protein (GFAP), and ratios showed robust changes; a p‑tau217 reduction correlated with amyloid PET clearance (mean -22.1 Centiloid; 29.2% turned amyloid-negative). Apolipoprotein E (APOE) ε4 non-carriers showed greater improvements. Infusion reactions occurred in 11.1% and amyloid-related imaging abnormalities in 9.2% (1.6% symptomatic), with no stage-related safety differences. Lecanemab was effective and well tolerated in real-world Chinese patients. Plasma p‑tau217 may serve as a sensitive, minimally invasive treatment-response biomarker. Show less
To characterize ultra-processed food (UPF) circulating metabolic signatures associated with Crohn's disease (CD) and to localize key metabolic mediators linking UPF intake to CD risk. Prospective coho Show more
To characterize ultra-processed food (UPF) circulating metabolic signatures associated with Crohn's disease (CD) and to localize key metabolic mediators linking UPF intake to CD risk. Prospective cohort study. Two large multi-center cohorts (UK Biobank [UKB] and Whitehall II [WHII] study) across the UK and an Eastern multi-center cohort ONE-IBD Study from China. UK Biobank discovery cohort (n=10,229) for signature derivation, internal validation cohort (n=91,306), external validation cohort Whitehall-II (n=7,893), and three additional cohorts (two Western and ONE-IBD) for validation of key metabolic drivers. Primary outcomes were UPF-related circulating metabolic signatures and their associations with CD risk; secondary outcomes included evidence supporting causal roles of candidate metabolites and genetic pathways assessed by Mendelian randomization, colocalization, and gene-environment analysis. A UPF metabolic signature of 73 metabolites was constructed and validated across cohorts (Spearman ρ: 0.20-0.25). More pronounced UPF metabolic signature was associated with increased CD risk (HR The adverse effects of UPF on CD risk may be driven by a relative deficiency of protective metabolites such as DHA, apart from additive harm to metabolic depletion. This reframes UPF-related risk and highlighting potential targets for precision nutrition in CD prevention. Show less
Although immune-mediated diseases (IMDs) and major depressive disorder (MDD) commonly co-occur, the bidirectional relationship between them remains to be fully elucidated. Using data from the prospect Show more
Although immune-mediated diseases (IMDs) and major depressive disorder (MDD) commonly co-occur, the bidirectional relationship between them remains to be fully elucidated. Using data from the prospective UK Biobank cohort, we evaluated the bidirectional associations by time-varying Cox proportional hazards regression models and assessed shared genetic architecture using genome-wide association study summary statistics. Additionally, we employed collagen-induced arthritis (CIA) and chronic social defeat stress (CSDS) mouse models to investigate the relationship between rheumatoid arthritis (RA) and depression. Over 5,226,841 person-years of follow-up, 23,534 incident MDD cases were identified. The presence of any IMD was associated with higher MDD risk (hazard ratio [HR]: 1.95; 95% CI: 1.89-2.01). Conversely, 59,742 incident cases of IMD were documented. MDD was associated with increased IMD risk (HR: 1.47; 95% CI: 1.40-1.54). We observed significant global genetic correlations between IMDs and MDD (r Show less
The brain is vulnerable to DNA damage and cardiometabolic risk. Yet, whether genetic variation in DNA repair interacts with cardiometabolic factors to explain cognitive variability remains unclear. Pa Show more
The brain is vulnerable to DNA damage and cardiometabolic risk. Yet, whether genetic variation in DNA repair interacts with cardiometabolic factors to explain cognitive variability remains unclear. Participants (n = 376,533) of white-British ancestry from the UK biobank with cognitive, neuroimaging, and whole-exome sequencing data were included. Six cognitive outcomes were assessed: fluid intelligence (FIQ), symbol-digit matching task (SDMT), visual matching (MATCH), trail making (TRAIL1 and TRAIL2), and prospective memory (PMEM). Seven brain regions of interest were assessed: total brain (TBV), grey matter (GMV), left and right white matter (LWM/RWM), left and right hippocampi (LHC/RHC), and white matter hyperintensities (WMH) volumes. A total of 3487 genetic variants across 39 DNA repair genes were tested. SNP and gene/gene-set level associations were tested using regression models adjusted for age, sex, APOE ε4, ancestry, and outcome-specific covariates. Genetic interactions with a multidimensional cardiometabolic risk index (CMRI), encompassing established risk factors, were assessed. We detected 107 genetic variants (mostly extremely rare) across 36 DNA repair genes associated at Bonferroni-significance (p ≤ 1.4 × 10 Show less
Frailty is associated with increased risks of falls, disability, hospitalization, and mortality. The 24-h movement behaviors (24HMB) framework conceptualizes sleep, sedentary behavior (SB), light-inte Show more
Frailty is associated with increased risks of falls, disability, hospitalization, and mortality. The 24-h movement behaviors (24HMB) framework conceptualizes sleep, sedentary behavior (SB), light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) as mutually constrained components of daily time use and may inform frailty prevention and management. This scoping review maps evidence on associations between 24HMB and frailty and identifies methodological gaps to inform future research and nursing practice. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and follows Joanna Briggs Institute (JBI) guidance. We searched PubMed, Embase, CINAHL, and Web of Science. We included observational studies of adults aged ≥18 years. Exposures were objectively measured or validated self-reported sleep, SB, LPA, and MVPA, including step counts, breaks in SB, isotemporal substitution models (ISM), and compositional data analysis (CoDA). Outcomes were frailty or prefrailty assessed using validated instruments. Quality was appraised with JBI tools. Thirty-three studies showed good methodological quality. Longer SB, particularly prolonged, uninterrupted bouts, was associated with higher frailty. Greater MVPA was consistently associated with lower frailty. Light-intensity physical activity was generally beneficial but often attenuated when MVPA or total activity volume was modeled. Sleep fragmentation and poor sleep quality were associated with frailty. Isotemporal substitution models and compositional data analysis indicated that reallocating sedentary time to MVPA would yield the largest theoretical benefit, followed by reallocating to LPA. Higher daily step counts and more frequent or higher-intensity breaks in SB were associated with lower frailty. Evidence supports a 24-h integrated movement-behavior approach centered on MVPA, combined with reducing prolonged SB and improving sleep quality, for the prevention and nursing management of frailty. The study design and analytical protocol were prospectively registered on the Open Science Framework (OSF). The unique identifier is S39Y4, and the publicly accessible URL is https://doi.org/10.17605/OSF.IO/S39Y4. Show less
Zhongxiao Lin, Jianyu Xiong, Fuyuan Zhang+15 more · 2026 · Molecular therapy : the journal of the American Society of Gene Therapy · Elsevier · added 2026-04-24
Vascular senescence is a fundamental driver of age-related cardiovascular diseases, yet the epigenetic mechanisms controlling this process remain poorly understood. This study investigated the role an Show more
Vascular senescence is a fundamental driver of age-related cardiovascular diseases, yet the epigenetic mechanisms controlling this process remain poorly understood. This study investigated the role and underlying mechanisms of lysine acetyltransferase 8 (KAT8), a key histone acetyltransferase, in maintaining endothelial cell homeostasis and preventing vascular senescence. We found that KAT8 expression is consistently downregulated in human aged vessels, senescent rats and mice, and cellular models of aging. Using CRISPR-Cas9-based loss-of-function and gain-of-function approaches in endothelial cells, C57BL/6J mice, and ApoE Show less