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
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
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
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
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
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
Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer's disease (AD). However, it is known that other pathways independent of APOE also play a role in AD. Disentangling APOE-de Show more
Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer's disease (AD). However, it is known that other pathways independent of APOE also play a role in AD. Disentangling APOE-dependent and independent effects is instrumental for understanding the biology of AD. We conducted an APOE-stratified multi-omic analysis in multiple large datasets to identify AD-associated plasma proteins and metabolites. More than 64% of the identified proteins were not found in non-APOE stratified studies, and 17% of the proteins showed APOE-specific trends. Mitochondrial dysfunction was associated in AD independently of APOE and was accompanied by disruptions in glucose and lipid metabolism and cell death and increased in inflammatory signaling activation. Lipid upregulation was found in AD cases when compared with controls with the same APOE genotype, indicating that additional factors beyond APOE affect lipid regulation and AD risk. These findings may be informative in guiding the development of effective medications for AD. 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
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
While the epithelial-mesenchymal transition (EMT) is known to promote cancer stemness and metastasis, a hybrid partial EMT (p-EMT) state has recently been identified. This study examined the influence Show more
While the epithelial-mesenchymal transition (EMT) is known to promote cancer stemness and metastasis, a hybrid partial EMT (p-EMT) state has recently been identified. This study examined the influence of HCT 116 cells were infected with Show less
Extensive research has documented a high comorbidity prevalence between depression and Internet gaming disorder (IGD). However, the distinct comorbidity patterns in adolescents have not been thoroughl Show more
Extensive research has documented a high comorbidity prevalence between depression and Internet gaming disorder (IGD). However, the distinct comorbidity patterns in adolescents have not been thoroughly investigated. Additionally, the longitudinal dynamics of these comorbidity patterns over time and the specific factors that may drive these transitions remain poorly understood. A total of 3,296 adolescents (1,501 boys; age baseline: 15.17 [1.44] years) were included in the current study. Latent profile analysis (LPA) was used to identify optimal comorbidity patterns of depression and IGD, while random intercept latent transition analysis (RI-LTA) was conducted to assess transitions in the comorbidity patterns over one and a half years and to identify factors influencing these transitions. Three patterns of comorbidity between depression and IGD symptoms were identified: no symptoms, low depression-high IGD symptoms, and high depression-low IGD symptoms. Results indicate that 72 % of individuals exhibited a stable symptom pattern trajectory. From Time 1 to Time 2, the probabilities of remaining in the three patterns were 78.3 %, 31.5 %, and 51.5 %, respectively. Findings also showed that sex, grade levels, boarding status, father's occupation as well as educational attainment, intra-week and weekend screen time, parent-child relationship, and perceived social support influenced the probabilities of transitions between comorbidity patterns in adolescents over time. Adopting targeted interventions for different comorbidity patterns and transitions, while considering specific influencing factors, provides insights into adolescent mental health dynamics and inform more effective prevention and support strategies. 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
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
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
Decline in pulmonary function (PF) and respiratory muscle strength (RMS) is influenced by environmental and genetic factors and is inconsistently linked to cognitive outcomes. This study explores the Show more
Decline in pulmonary function (PF) and respiratory muscle strength (RMS) is influenced by environmental and genetic factors and is inconsistently linked to cognitive outcomes. This study explores the associations between PF, RMS, and cognitive function among community-dwelling older adults in China, analyzing interactions with APOE Ɛ4 and the mediating effect of serum total bilirubin. About 1,081 Hubei Memory and Aging Cohort (HMACS) participants underwent PF (PEF, FEV1 and FVC), RMS (MIP and MEP) assessment, cognitive tests, APOE genotyping, and bilirubin measurement. Multivariate logistic regression and general linear regression were used to analyze associations. Among 1,081 participants (mean age 70.52 ± 5.55 years), 26.1% had cognitive impairment. Lower PF and RMS scores were associated with cognitive impairment. Higher comprehensive PF (c-PF) and RMS indices protected against cognitive impairment (eg, c-PF: OR = 0.482-0.609, PF (especially PEF) and RMS (especially MEP) indices are significantly associated with cognitive function and impairment in older adults, independent of APOE Ɛ4 status. These findings provide biomarkers for assessing cognitive health risk and a basis for interventions targeting PF and RMS to preserve cognitive function. 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
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
Brain metastasis significantly worsens prognosis in late-stage cancer., with Its treatment hindered by the blood-brain barrier (BBB) and an immunosuppressive tumor microenvironment. Within this enviro Show more
Brain metastasis significantly worsens prognosis in late-stage cancer., with Its treatment hindered by the blood-brain barrier (BBB) and an immunosuppressive tumor microenvironment. Within this environment, tumor-associated macrophages (TAMs) represent the predominant immune population. Through their roles in immune modulation, angiogenesis, and tumor invasion, TAMs are critical drivers of disease progression. TAMs are highly heterogeneous. While traditionally categorized into M1 (anti-tumor) or M2 (pro-tumor) phenotypes, this dichotomy is an oversimplification. Recent single-cell studies have revealed a spectrum of functional subpopulations, such as lipid-associated, interferon-responsive, and pro-angiogenic TAMs, with M2-like states typically prevailing to mediate immunosuppression. This review explores the diversity and functions of TAMs in brain metastasis. We first detail their biological characteristics, including origins, heterogeneous subtype classifications (e.g., lipid-associated macrophages that extend beyond the simple M1/M2 dichotomy), and polarization states. We further discuss how polarization is regulated by signaling pathways (e.g., STAT, NF-κB) and microenvironmental factors (e.g., hypoxia, metabolic reprogramming). We examine TAM roles from pre-metastatic niche formation to tumor colonization, using breast and lung cancer brain metastases to illustrate how TAMs disrupt the BBB and facilitate immune evasion through molecules like ANGPTL4 (angiopoietin-like 4) and MMP9. Key pathways of TAM-tumor cell interactions, including neuro-cancer interactions, immune-metabolic regulation, and exosome-mediated communication, are also discussed. Targeting TAMs offers promising therapeutic avenues. These strategies include reprogramming TAMs (e.g., using CSF1R inhibitors), combining TAM-targeted therapy with immune checkpoint inhibitors, and developing novel approaches such as nanotechnology and CAR-macrophages. However, several challenges remain, including TAM heterogeneity, lack of targeting specificity, and the obstacle of BBB delivery. Future research should leverage technologies like single-cell sequencing and spatial transcriptomics to decode TAM heterogeneity, and develop personalized treatments based on biomarkers such as GPNMB and TRAIL, aiming to improve patient outcomes in brain metastasis. 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
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
To explore the therapeutic mechanism of The active components and disease targets of JZQBR were screened using TCMSP and GeneCards databases, followed by protein-protein interaction analysis and GO an Show more
To explore the therapeutic mechanism of The active components and disease targets of JZQBR were screened using TCMSP and GeneCards databases, followed by protein-protein interaction analysis and GO and KEGG enrichment analyses. In the animal experiments, Network pharmacology identified 65 potential targets, with quercetin, kaempferol, and luteolin as the core components and IL-6, IL-1β, and TNF‑α as the key targets. The targets were enriched mainly in the pathways involving inflammatory responses and diabetic complications. In the JZQBR improves T2DM complicated with hyperlipidemia possibly by multi-target regulation of the inflammation-metabolism network. 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
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