Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (P Show more
Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (PZI) and trioxytriphenylamine (TOT) ligands, was synthesized. PZI-Au-TOT displays decent thermally activated delayed fluorescence (TADF) with a quantum yield of 93 % in doped film. The crystals of PZI-Au-TOT show simultaneous TADF, polymorphism, and linearly polarized luminescence (LPL). The polymorph-dependent emission properties with widely varied peaks from 560 to 655 nm are attributed to different packing modes in terms of isolated monomers, discrete π-π stacked dimers or dimer PLUS. Two well-defined microcrystals of PZI-Au-TOT exhibit linearly polarized thermally activated delayed fluorescence with a degree of polarization up to 0.64. This work demonstrates that the molecular rotational flexibility of D-M-A type complexes endows an integration of multiple functions into one complex through manipulation of supramolecular aggregation. This type of complexes is expected to serve as a versatile platform for the fabrication of crystal materials for advanced photonic applications. Show less
Twenty types of GABAergic interneurons form intricate networks to fine-tune neural circuits in the brain. Parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons, which are the two la Show more
Twenty types of GABAergic interneurons form intricate networks to fine-tune neural circuits in the brain. Parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons, which are the two largest populations of neocortical interneurons, innervate the soma and/or proximal dendrites, and distal dendrites of pyramidal neurons, respectively. Using PV- and SST-specific knockout mouse models, we show that PV+ interneurons require FGFR2, which responds to FGF7, to drive PV+ inhibitory presynaptic maturation on perisomatic regions of Layer V pyramidal neurons. In contrast, SST+ interneurons rely on both FGFR1 and FGFR2, which respond to FGF10 or FGF22, to promote SST+ inhibitory presynaptic maturation on distal dendrites of pyramidal neurons in cortical Layer I. Mechanistically, FGF-FGFR signaling sustains VGAT protein levels in interneurons through PP2A and Akt pathways. Together, these findings demonstrate that distinct FGF ligand-receptor combinations regulate inhibitory presynaptic differentiation by PV+ and SST+ interneurons, contributing to the formation of compartment-specific synaptic patterns. Show less
Cholesterol stress profoundly modulates cellular processes, but its underlying mechanisms remain incompletely understood. To investigate cholesterol-responsive networks, we performed integrated transc Show more
Cholesterol stress profoundly modulates cellular processes, but its underlying mechanisms remain incompletely understood. To investigate cholesterol-responsive networks, we performed integrated transcriptome (RNA-seq) and metabolome (LC-MS) analyses on HeLa cells treated with cholesterol for 6 and 24 h. Through transcriptomic analysis of cholesterol-stressed HeLa cells, we identified stage-specific responses characterized by early-phase stress responses and late-phase immune-metabolic coordination. This revealed 1340 upregulated and 976 downregulated genes after a 6 h cholesterol treatment, including induction and suppression of genes involved in cholesterol efflux and sterol biosynthesis, respectively, transitioning to Nuclear Factor kappa-B (NF-κB) activation and Peroxisome Proliferator-Activated Receptor (PPAR) pathway modulation by 24 h. Co-expression network analysis prioritized functional modules intersecting with differentially expressed genes. We also performed untargeted metabolomics using cells treated with cholesterol for 6 h, which demonstrated extensive remodeling of lipid species. Interestingly, integrated transcriptomic and metabolic analysis uncovered GFPT1-driven Uridine Diphosphate-N-Acetylglucosamine (UDP-GlcNAc) accumulation and increased taurine levels. Validation experiments confirmed Show less
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data fr Show more
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10 Show less
To investigate the risk factors associated with coronary heart disease (CHD) in patients with metabolic-associated fatty liver disease (MAFLD) and develop a nomogram prediction model. This study inclu Show more
To investigate the risk factors associated with coronary heart disease (CHD) in patients with metabolic-associated fatty liver disease (MAFLD) and develop a nomogram prediction model. This study included 394 patients with MAFLD who underwent coronary angiography at The Affiliated Hospital of Qingdao University between December 2019 and December 2024. The study cohort was divided in a 7:3 ratio into training and validation sets comprising 277 and 117 cases, respectively. The training group was further divided into the MAFLD-only ( Of the 394 MAFLD cases, 313 had CHD-related complications. Of the 277 patients in the training set, 220 had CHD, and of the 117 patients in the validation set, 93 had CHD. LASSO regression analysis revealed that the following variables were associated with the risk of CHD: sex, lipoprotein(a) (Lp[a]), low-density lipoprotein cholesterol, white blood cell count (WBC), glycated triglyceride-glucose index (TyG), and atherosclerosis index (AIP). Multivariate logistic regression analysis revealed that sex, Lp(a), WBC, TyG, and AIP were independent risk factors for CHD in MAFLD cases. A nomogram was constructed and an ROC curve was plotted, based on which the optimal cutoff value was determined as 0.698. The area under the curve of the nomogram in the training and validation cohorts was 0.860 (95% CI = 0.807-0.913) and 0.843 (95% CI = 0.757-0.929), respectively. Calibration curves for CHD risk probability showed good agreement between the nomogram's predicted probabilities and the observed event rates. DCA demonstrated the net clinical benefit of the constructed nomogram. Sex, Lp(a), WBC, TyG, and AIP emerged as independent risk factors for CHD in patients with MAFLD and the nomogram prediction model constructed using these factors could effectively predict CHD occurrence. Show less
Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate Show more
Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in Show less
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel enteric coronavirus that causes severe clinical diarrhea and intestinal pathological injury in pigs. Selective autophagy is an important Show more
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel enteric coronavirus that causes severe clinical diarrhea and intestinal pathological injury in pigs. Selective autophagy is an important mechanism of host defense against virus invasion. However, the mechanism through which SADS-CoV-mediated selective autophagy mediates the innate immune response remains unknown. Here, we report that the host protein PABPC4 can inhibit SADS-CoV replication through targeting and degrading its N protein. Furthermore, we demonstrate that PABPC4 recruits MARCHF8 (an E3 ubiquitin ligase), which ubiquitinates the N protein and is degraded via NDP52/CALCOCO2 (a selective autophagy cargo receptor). Taken together, these findings reveal a new mechanism by which PABPC4 inhibits virus replication, and reveal a new target for antiviral drug development. Show less
Peritoneal metastasis (PM) in gastric cancer (GC) remains a formidable clinical challenge. Although exosomes are critical mediators of tumor-microenvironment communication, their mechanistic role in l Show more
Peritoneal metastasis (PM) in gastric cancer (GC) remains a formidable clinical challenge. Although exosomes are critical mediators of tumor-microenvironment communication, their mechanistic role in linking mesothelial-mesenchymal transition (MMT) to peritoneal dissemination remains poorly understood. This study elucidates a GC-derived exosomal microRNA (miRNA)-driven pathway that orchestrates peritoneal metastasis. Integrated exosomal miRNA sequencing and The Cancer Genome Atlas (TCGA) analysis identified miR-196a-5p as highly enriched in GC-derived exosomes. Functional assays, including in vitro co-culture experiments, and in vivo PM models, demonstrated that GC-derived exosomal miR-196a-5p directly induces MMT in peritoneal mesothelial cells (HMrSV5) and contributed to the formation of metastatic tumors. Mechanistically, miR-196a-5p binds the 3'-untranslated region (UTR) of F-box protein 45 (FBXO45), an E3 ubiquitin ligase, suppressing its expression and thereby stabilizing snail family transcriptional repressor 1 (Snai1)-a key transcription factor in epithelial-mesenchymal transition (EMT). RNA immunoprecipitation sequencing (RIP seq), dual-luciferase reporter assays, co-immunoprecipitation (CO-IP), and rescue experiments validated the miR-196a-5p/FBXO45/Snai1 axis. Notably, miR-196a-5p disrupts FBXO45-mediated Snai1 ubiquitination and degradation, promoting MMT-driven peritoneal niche remodeling and metastatic progression. These findings reveal a novel exosome-mediated mechanism underlying GC dissemination and highlight miR-196a-5p and FBXO45 as promising therapeutic targets for PM. Show less
This study aims to identify oxidative stress-related genes (OSGs) in papillary thyroid carcinoma (PTC) and their common targets with resveratrol. Oxidative stress-related differentially expressed gene Show more
This study aims to identify oxidative stress-related genes (OSGs) in papillary thyroid carcinoma (PTC) and their common targets with resveratrol. Oxidative stress-related differentially expressed genes (OS-DEGs) were identified by intersecting datasets. The screened core genes were utilized to construct a prognostic model, and their prognostic value, along with their associations with clinical pathological characteristics and immune infiltration, was assessed. Subsequently, the core targets at the intersection of resveratrol and oxidative stress (OS) in PTC were screened, and their binding properties with resveratrol were analyzed. By conducting cross-database analysis, 38 OS-DEGs were identified, and 3 core genes APOE、CDKN2A、APOD were determined. The prognostic model based on core genes exhibited robust prognostic capabilities. The core genes displayed significant correlations with various clinical pathological parameters and a range of immune cells. Additionally, 13 targets of resveratrol for antioxidative stress were screened from databases. 6 high-performing targets, JUN, TGFB1, BCL2, CDKN1A, FOS, ICAM1, were revealed by topological analysis, all exhibiting binding energies lower than - 5.0 kcal/mol. Our study is the pioneering research to provide new insights into the diagnosis, prognosis, and treatment of PTC through the analysis of OSGs, presenting potential clinical implications. Furthermore, this research reveals the molecular functions associated with resveratrol and its pharmacological targets regulating OS in PTC for the first time. Show less
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of Show more
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of chlorogenic acid (CHA), a multifunctional natural active compound, in AD therapy by developing a trifunctional nanocarrier (MC-H/R/si). CHA was effectively conjugated with iron-based metal-organic frameworks (MIL/Fe-100) through chelation interaction. The resulting nanocomplex (MC) not only enhances the bioavailability of CHA but also facilitates a synergistic antioxidant effect between CHA and MIL/Fe-100. Importantly, CHA can chelate Zn Show less
Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition. Traditional genetic testing is typically conducted on the proband only, with family members undergoing Sanger sequencing, which Show more
Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition. Traditional genetic testing is typically conducted on the proband only, with family members undergoing Sanger sequencing, which may overlook other pathogenic variants. This study explores the gene sequencing strategy in a three-generation family based on genetic carrier status and examines the relationship between phenotypic characteristics and genotype. High-throughput second-generation sequencing was performed on the proband to analyze HCM-related pathogenic genes. Subsequently, the identified pathogenic variants were validated by Sanger sequencing in the proband and family members. Clinical, electrocardiographic, and echocardiographic assessments were conducted for family members. Second-generation sequencing of the proband (III7) revealed a pathogenic variant MYBPC3-P453Lfs. Initially, no HCM-related pathogenic variants were detected in another patient (III11), prompting additional sequencing of III11, which identified the MYH7-G823E pathogenic variant. Both patients had severe left ventricular outflow tract obstruction. Sanger sequencing showed that five family members carried both mutations. Among them, three died suddenly before age 40, one required an implantable cardioverter defibrillator for arrhythmias, and one developed HCM before adulthood. Cardiac magnetic resonance imaging (MRI) of patients carrying both mutations showed myocardial fibrosis of 32.75%, significantly higher than the 6.98% observed in patients carrying only one mutation. In families with varying HCM phenotypes, second-generation sequencing should be considered for all members. In this family, carrying one variant led to outflow tract obstruction, while carrying both variants resulted in severe disease, including sudden death and early onset. Cardiac MRI is crucial for assessing the severity of the disease within the family. Show less
To investigate longitudinal changes in pelvic floor support in primiparous women with pelvic organ prolapse (POP) after vaginal delivery, focusing on single- and multiple-compartment involvement. Two Show more
To investigate longitudinal changes in pelvic floor support in primiparous women with pelvic organ prolapse (POP) after vaginal delivery, focusing on single- and multiple-compartment involvement. Two hundred primiparas after vaginal delivery were prospectively enrolled and underwent pelvic floor MRI at six weeks postpartum. POP was diagnosed and classified into subgroups (single or multiple compartments involved) based on MRI findings. Primiparas with POP underwent repeat MRI at four months postpartum. Pelvic floor measurements, including injury score and functional parameters of the levator ani muscle (puborectal hiatus line, H line; muscular pelvic floor relaxation line, M line; levator hiatus area, LHA; iliococcygeus angle, ICA; levator plate angle, LPA), were assessed on MRI. Measurements were compared among POP subgroups and a normal control group (without POP) at six weeks postpartum. Additionally, changes between six weeks and four months postpartum were analyzed within POP subgroups. Based on MRI criteria, approximately 41.5% of primiparas were diagnosed with POP, predominantly cystoceles commonly associated with uterine prolapse. Functional parameters of the levator ani, except for LPA at rest, were significantly increased in POP subgroups compared to controls. At four months postpartum, M line, H line, and LPA significantly decreased, and prolapsed organs were elevated in cases with multiple compartments involved, compared to six weeks postpartum. No significant changes were observed in cases with single-compartment involvement during follow-up. A substantial proportion of primiparas experienced postpartum POP. Impaired levator ani function contributed to POP. Pelvic floor support improved during early postpartum in cases with multiple-compartment involvement. Show less
The remodeling of the extracellular matrix (ECM) plays a pivotal role in tumor progression and drug resistance. However, the compositional patterns of ECM in breast cancer and their underlying biologi Show more
The remodeling of the extracellular matrix (ECM) plays a pivotal role in tumor progression and drug resistance. However, the compositional patterns of ECM in breast cancer and their underlying biological functions remain elusive. Transcriptome and genome data of breast cancer patients from TCGA database was downloaded. Patients were classified into different clusters by using non-negative matrix factorization (NMF) based on signatures of ECM components and regulators. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify core genes related to ECM clusters. Additional 10 independent public cohorts including Metabric, SCAN_B, GSE12276, GSE16446, GSE19615, GSE20685, GSE21653, GSE58644, GSE58812, and GSE88770 were collected to construct Training or Testing cohort, following machine learning calculating ECM correlated index (ECI) for survival analysis. Pathway enrichment and correlation analysis were used to explore the relationship among ECM clusters, ECI and TME. Single-cell transcriptome data from GSE161529 was processed for uncovering the differences among ECM clusters. Using NMF, we identified three ECM clusters in the TCGA database: C1 (Neuron), C2 (ECM), and C3 (Immune). Subsequently, WGCNA was employed to pinpoint cluster-specific genes and develop a prognostic model. This model demonstrated robust predictive power for breast cancer patient survival in both the Training cohort (n = 5,392, AUC = 0.861) and the Testing cohort (n = 1,344, AUC = 0.711). Upon analyzing the tumor microenvironment (TME), we discovered that fibroblasts and B cell lineage were the core cell types associated with the ECM cluster phenotypes. Single-cell RNA sequencing data further revealed that angiopoietin like 4 (ANGPTL4) We identified distinct ECM clusters in breast cancer patients, irrespective of molecular subtypes. Additionally, we constructed an effective prognostic model based on these ECM clusters and recognized ANGPTL4 Show less
Light-responsive porous liquids (LPLs) attract significant attention for their controllable gas uptake under light irradiation, while their preparation has remained a great challenge. Here we report t Show more
Light-responsive porous liquids (LPLs) attract significant attention for their controllable gas uptake under light irradiation, while their preparation has remained a great challenge. Here we report the fabrication of type II LPLs with enhanced light-responsive efficiency by tailoring the host's functionality for the first time. The functionality of light-responsive metal-organic cage (MOC-RL, constructed from dicopper and responsive ligands) is modified by introducing the second long-chain alkyl ligand, producing MOC-RL-AL as a new host. A spatially hindered solvent based on polyethylene glycol, IL-NTf Show less
Idiopathic frozen shoulder (FS) can lead to difficulties in daily activities and significantly impact the quality of life. Early diagnosis and treatment can help alleviate symptoms and restore shoulde Show more
Idiopathic frozen shoulder (FS) can lead to difficulties in daily activities and significantly impact the quality of life. Early diagnosis and treatment can help alleviate symptoms and restore shoulder function. Therefore, we aimed to explore the diagnostic biomarkers and potential mechanisms of FS from a transcriptomics perspective. Total RNA was extracted from tissue samples of 15 FS and 11 controls. At the outset, we conducted differential expression analysis, weighted gene co-expression network analysis (WGCNA), and utilized the cytoHubba plugin, complemented by two machine learning algorithms, receiver operating characteristic (ROC) analysis, and expression level evaluation to identify biomarkers for FS. Subsequently, a nomogram was constructed based on the biomarkers. Additionally, we conducted enrichment and immune infiltration analyses to explore the mechanisms associated with these biomarkers. Finally, we confirmed the expression patterns of the biomarkers at the clinical level through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). This study established a link between FS biomarkers that have strong diagnostic potential and specific immune responses, highlighting possible targets for diagnosing and treating FS. Show less
Asthma severity assessment is essential for asthma management. Transcriptomics contributes substantially to asthma pathogenesis. Then, this study aimed to explore asthma severity-associated transcript Show more
Asthma severity assessment is essential for asthma management. Transcriptomics contributes substantially to asthma pathogenesis. Then, this study aimed to explore asthma severity-associated transcriptomics profile and promising biomarkers for asthma severity prediction. In discovery cohort, induced sputum cells from 3 non-severe and 3 severe asthma patients were collected and analyzed using RNA-seq. Multivariate analysis was performed to explore asthma severity-associated transcriptomics profile and differential expressed genes (DEGs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used for pathway enrichment analysis. Subsequently, based on the previous study and clinical experience, the mRNA expressions of 6 overlapped asthma severity-associated DEGs and Distinct asthma severity-associated transcriptomics profile was identified in induced sputum cells in discovery cohort. Then, 345 DEGs were found, of which 38 terms and 32 pathways were enriched using GO and KEGG, respectively. In validation cohort, the mRNA expressions of Collectively, this study provides the first identification of the association between induced sputum cells transcriptomics profile and asthma severity, indicating the potential value of transcriptomics for asthma management. The study also reveals the promising value of serum C3 for predicting asthma severity in clinical practice. Show less
Bo Lin, Mengsen Li · 2025 · Frontiers in immunology · Frontiers · added 2026-04-24
Abnormalities in the Wnt/β-catenin pathway promote the development of hepatocellular carcinoma (HCC). Mutations in CTNNB1, which encodes β-catenin, are frequently found in clinical HCC samples, as are Show more
Abnormalities in the Wnt/β-catenin pathway promote the development of hepatocellular carcinoma (HCC). Mutations in CTNNB1, which encodes β-catenin, are frequently found in clinical HCC samples, as are loss-of-function mutations in signaling pathway regulators such as axis inhibition protein 1 (Axin1) and adenomatous polyposis coli (APC). The activation of the Wnt/β-catenin pathway synergizes with other oncogenic signal molecules such as c-Met or glypican-3, contributing to HCC development. Furthermore, Wnt/β-catenin pathway activation in the tumour microenvironment (TME) leads to cold tumour and resistance to immunotherapy. In this review, we discuss two models of Wnt/β-catenin signaling activation, role of Wnt/β-catenin signaling pathway in the development of HCC, the association between Wnt/β-catenin pathway and tumour angiogenesis, metastasis, and immune escape in the TME, and the targeting of this signaling pathway for HCC treatment. Show less
With the sharp increase in the incidence of papillary thyroid carcinoma (PTC), the disease-specific survival rate has not improved significantly. Cholesterol metabolism plays a crucial role in tumor p Show more
With the sharp increase in the incidence of papillary thyroid carcinoma (PTC), the disease-specific survival rate has not improved significantly. Cholesterol metabolism plays a crucial role in tumor proliferation, regulation of tumor immune escape, and tumor drug resistance. However, there are few studies on the role of cholesterol metabolism in the occurrence and development of thyroid cancer (THCA). This study aimed to investigate the predictive value of cholesterol metabolism-related genes (CMRGs) in THCA and the relationship between immune invasion and drug sensitivity. Cholesterol metabolism-related genes we identified from the molecular signatures database, and univariate Cox regression and least absolute shrinkage and selection operator(LASSO) were used to construct a predictive model of cholesterol metabolism-related genes based on the TCGA-THCA dataset. The TCGA dataset was randomly divided into a training group and a validation group to verify the model's predictive value and independent prognostic effect. We then constructed a nomogram and performed enrichment analysis, immune cell infiltration, and drug sensitivity analysis. Finally, TCGA-THCA and GSE33630 datasets were used to detect the expression of signature genes, which was further verified by the HPA database. Six CMRGs (FADS1, NPC2, HSD17B7, ACSL4, APOE, HMGCS2) we identified by univariate Cox and LASSO regression to construct a prognostic model for 155 genes related to cholesterol metabolism. Their prognostic value was confirmed in the validation set, and a highly accurate nomogram was constructed combined with clinical features. We found that the mortality rate of high-risk patients increased by 11.41 times, and the infiltration of immune cells in the high-risk group was significantly reduced. Moreover, through drug sensitivity analysis, we obtained sensitive drugs for different risk groups. The GSE33630 dataset verified the expression of six CMRGs, and the HPA database verified the protein expression of the NPC2 gene. Cholesterol metabolism-related features are a promising biomarker for predicting THCA prognosis and can potentially guide personalized immunization and targeted therapy. Show less
Little is known about the importance of blood lipids for risk of myocardial infarction (MI) in Chinese vs. European populations. We compared the associations with MI of apolioprotein B (ApoB) vs. low- Show more
Little is known about the importance of blood lipids for risk of myocardial infarction (MI) in Chinese vs. European populations. We compared the associations with MI of apolioprotein B (ApoB) vs. low-density lipoprotein cholesterol (LDL-C) and remnant-cholesterol (remnant-C) vs. triglycerides in the China Kadoorie Biobank (CKB) and UK Biobank (UKB). Plasma levels of LDL-C, high-density lipoprotein-cholesterol (HDL-C), apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), non-HDL-C, remnant-C, LDL-C/ApoB, and HDL-C/ApoA1 ratios were measured in a nested case-control study of MI (948 cases, 6101 controls) in CKB and a prospective study (5344 cases in 279 989 participants) in UKB. Associations of lipids with MI were assessed using logistic regression in CKB and Cox regression in UKB after adjustment for confounders and correction for regression dilution. The mean levels of LDL-C were about 30% lower in CKB than in UKB [2.3 (0.6) vs. 3.7 (0.8) mmol/L], but mean levels of HDL-C were comparable [1.3 (0.3) vs. 1.5 (0.4) mmol/L], as were those for triglycerides [1.8 (1.1) vs. 1.7 (1.1) mmol/L]. While the rate ratios (RRs) of MI for 1 SD higher usual levels of LDL-C in Chinese were about half those in Europeans (1.27; 1.13-1.44 vs. 1.55; 1.49-1.61), the corresponding RRs for ApoB or non-HDL with MI were comparable between Chinese and Europeans. The findings reinforce current guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in China that advocate initiation of statin treatment in individuals at high-risk of ASCVD rather than high levels of LDL-C. Show less
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. W Show more
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1 Show less
Head and neck squamous cell carcinoma (HNSCC) poses a global health challenge. The management of HNSCC is complicated by the difficulty in detecting occult lymph node metastases, leading to dilemmas i Show more
Head and neck squamous cell carcinoma (HNSCC) poses a global health challenge. The management of HNSCC is complicated by the difficulty in detecting occult lymph node metastases, leading to dilemmas in elective neck dissection decisions, which will impair patients' quality of life without improving survival for nodal negative patients. We conducted a comparative analysis of the clinical features, genomic alterations, gene expression and methylation, tumor microenvironment and cellular states between the clinically N0 and pathologically N0 (cN0-pN0) patients and occult lymph node metastatic patients. Patients with occult lymph node metastases typically present with more poorly differentiated primary tumors and higher rates of angiolymphatic and perineural invasion. We identified a distinctive genomic mutation spectrum in the primary tumors of patients with occult metastases, notably in genes such as NSD1, ARHGAP15 and SMARCA4. A whole-genome DNA hypomethylation and altered gene expression profiles are identified in occult lymph node metastatic patients. Analysis of the tumor microenvironment revealed an enrichment of CARNS1 + NK cells and CBX1 + tumor cells in occult metastatic patients. In conclusion, patients with occult lymph node metastases exhibit distinct molecular and clinical features compared with cN0-pN0 patients. Show less
The association between low-density lipoprotein (LDL) cholesterol and increased mortality risk has been well-documented, yet apolipoprotein B (apoB) is regarded as a more precise risk indicator. Howev Show more
The association between low-density lipoprotein (LDL) cholesterol and increased mortality risk has been well-documented, yet apolipoprotein B (apoB) is regarded as a more precise risk indicator. However, a comprehensive analysis integrating both markers in relation to mortality risk remains unreported. This study aimed to investigate the relationship between LDL cholesterol levels and mortality across varying apoB concentrations within the general population. Data from 15,380 participants in the 2005-2016 National Health and Nutrition Examination Survey (NHANES) were utilized to construct Cox regression models and apply restricted cubic splines, assessing the association between LDL cholesterol and mortality across distinct apoB stratifications. The study cohort had a median (IQR) age of 46.0 (32.0, 60.0) years, with 7949 (51.8%) males. During a median follow-up of 101.0 months (IQR: 67-137), 1771 (8.8%) all-cause mortality events were observed; 443 (2.1%) deaths were attributed to cardiovascular diseases, while 109 (0.5%) resulted from cerebrovascular diseases. Low apoB and LDL-cholesterol levels were independently linked to an elevated risk of all-cause and cardiovascular mortality. Compared with participants having apoB <90 mg/dL and LDL-cholesterol levels between 100-129 mg/dL, those with LDL-cholesterol <70 mg/dL (HR, 1.81; 95%CI: 1.39-2.36) and 70-99 mg/dL (HR, 1.28; 95%CI: 1.01-1.62) demonstrated a higher risk of all-cause mortality. Additionally, reduced apoB levels contributed to an increased risk of cardiovascular mortality among individuals with low LDL-cholesterol levels. Low apoB and LDL-cholesterol levels were associated with heightened all-cause and cardiovascular mortality risk in the general population. Conversely, high apoB and low LDL-cholesterol levels did not correlate with increased mortality risk. Show less
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined r Show more
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined receptor signals, and assessed their regulatory capacities and specificities through in silico analysis of ligand-receptor interactions. Consequently, we identified a B cell subset that expressed cytokine interleukin-27 (IL-27) and chemokine CXCL10. Through the IL-27-IL-27 receptor interaction, these IL-27/CXCL10-producing B cells targeted CD40-activated B cells in vitro and, upon induction by immunization and viral infection, optimized antibody responses and antiviral immunity in vivo. Also present in breast cancer tumors and retained there through CXCL10-CXCR3 interaction-mediated self-targeting, these cells promoted B cell PD-L1 expression and immune evasion. Mechanistically, Show less
Atherosclerosis, a progressive inflammatory disease and the leading cause of cardiovascular disease (CVD), remains a global health burden due to the lack of effective early therapeutic interventions. Show more
Atherosclerosis, a progressive inflammatory disease and the leading cause of cardiovascular disease (CVD), remains a global health burden due to the lack of effective early therapeutic interventions. Although growing evidence highlights the involvement of plasma proteins in atherogenesis, their causal contributions to disease pathogenesis are poorly understood. To address this gap, we conducted a proteome-wide Mendelian randomization (MR) analysis using cis-pQTLs (cis-protein quantitative trait loci) from the deCODE and UKB-PPP cohorts (~90,000 individuals) as instrumental variables. We integrated colocalization analysis, summary-data-based MR (SMR), and HEIDI tests to systematically prioritize causal plasma proteins. Key findings were replicated in the CARDIOGRAMplusC4D (coronary artery disease, CAD) and FinnGen (CVD) cohorts. Functional validation was performed through phenome-wide association studies (PheWAS), single-cell transcriptomics, histological staining, and ELISA assays to characterize protein expression patterns in specific cell types and tissues. Among 2,711 plasma proteins analyzed, 28 showed strong genetic associations with atherosclerosis. Of these, five proteins (ADK, ANGPTL4, CD4, MGAT1, SYT11) met strict validation criteria through colocalization (posterior probability of colocalization, PP.H4 > 0.8) and SMR. Subsequent replication using MR and PheWAS further confirmed the causal roles of ADK, CALB2, and COMT in CAD and other CVD outcomes. Notably, CALB2 was specifically enriched in mast cells within atherosclerotic plaques and adipose tissue, and plasma levels were significantly elevated in patients with severe carotid artery stenosis (CAS). This study identifies 28 novel therapeutic targets for atherosclerosis using a rigorous multi-omics approach. Our findings establish CALB2 as a promising biomarker and therapeutic target, particularly in severe CAS, by linking genetic evidence to cell-type-specific expression and clinical phenotypes. These insights pave the way for precision medicine approaches in the prevention and treatment of CVD. The online version contains supplementary material available at 10.1186/s12967-025-07269-6. Show less
CKN is a self-developed LXRα agonist capable of up-regulating the expression of ABCA1, diminishing intracellular lipid deposition, and attenuating the inflammatory response. Nevertheless, the protecti Show more
CKN is a self-developed LXRα agonist capable of up-regulating the expression of ABCA1, diminishing intracellular lipid deposition, and attenuating the inflammatory response. Nevertheless, the protective effect and mechanism of ischemic stroke remain indistinct. The aim of this study is to investigate the therapeutic effects and the underlying mechanisms of CKN in ischemic stroke. In this study, the tMCAO model was utilized to induce cerebral artery occlusion in mice, and cholesterol-induced BV2 and primary microglia models were adopted. Neuronal damage and the effect of CKN on ABCA1 expression, lipid deposition, and TLR4 signaling in penumbra microglia were assessed. The results demonstrated that: (1) CKN treatment markedly ameliorated the neurological deficit score of the tMCAO model, contracted the infarct size, and mitigated the damage of the cerebral cortex. (2) CKN has the capacity to up-regulate the expression of ABCA1 in microglia within the ischemic penumbra by activating the LXRα/ABCA1 signaling pathway, and minimize lipid deposition and inflammatory responses. (3) The activation of the LXRα/ABCA1 signaling pathway is profoundly implicated in the inflammatory response triggered by CKN inhibition of the TLR4 signaling pathway in microglia. The present study demonstrated for the first time that the activation of the LXRα/ABCA1 signaling possessed the ability to attenuate reperfusion injury in ischemic stroke by means of reducing lipid droplet formation and TLR4-mediated inflammatory signaling within microglia in the ischemic penumbra. Show less
Low-density lipoprotein cholesterol (LDL-C) has now been the primary target for lipid-lowering therapy in the European and US guidelines for the management of dyslipidemia, with increasing interest in Show more
Low-density lipoprotein cholesterol (LDL-C) has now been the primary target for lipid-lowering therapy in the European and US guidelines for the management of dyslipidemia, with increasing interest in apolipoprotein B (ApoB) as a secondary target. The relationship between ApoB and the severity of acute myocardial infarction as well as residual risk still needs to be further determined. Coronary atherosclerosis occurs as a result of a complex set of factors, and there is a strong relationship between insulin resistance and cardiovascular disease. In contrast, there are limited studies on the relationship between TyG index (triglyceride glucose index), an indicator of insulin resistance, and cardiovascular disease. The purpose of this study was to investigate the value of ApoB and TyG index in assessing the severity of myocardial infarction and predicting prognosis. This study included 712 participants with acute myocardial infarction for a 5-year follow-up. Spearman correlation analysis and generalized linear model analysis were used to assess the correlation between ApoB and the severity of coronary atherosclerosis. Risk regression analysis was used to assess the correlation between ApoB and residual risk in patients with acute myocardial infarction, and the C-statistic, net reclassification index (NRI), and integrated discriminant improvement index (IDI) were further calculated to assess the predictive value of ApoB for residual risk after myocardial infarction. Categorizing apoB, LDL-C, and TyG indices according to tertiles, higher levels of ApoB were significantly associated with the severity of coronary artery stenosis in patients with acute myocardial infarction ( ApoB is an independent risk factor for major adverse cardiovascular events (MACE) following myocardial infarction. Elevated ApoB levels are more advantageous than elevated LDL-C levels in assessing the severity of coronary artery stenosis in myocardial infarction patients and predicting residual risk after myocardial infarction. Therefore, in patients with acute myocardial infarction, ApoB can be considered to guide further intensive treatment. However, the TyG index did not demonstrate a significant advantage in predicting cardiovascular residual risk in this study. Show less
Intensive aquaculture frequently utilizes high-fat diets (HF) as a cost-effective strategy, yet this practice often induces hepatic steatosis, oxidative stress, and chronic inflammation in carnivorous Show more
Intensive aquaculture frequently utilizes high-fat diets (HF) as a cost-effective strategy, yet this practice often induces hepatic steatosis, oxidative stress, and chronic inflammation in carnivorous fish. Betaine, a natural methyl donor, has shown potential as a functional feed additive, but its comprehensive protective mechanisms under HF stress remain to be fully elucidated. Juvenile largemouth bass (Micropterus salmoides) were fed one of four isonitrogenous diets for 8 weeks: a normal-fat control (Control), a high-fat diet (HF), and two high-fat diets supplemented with 0.5% (HFB0.5) or 1.0% (HFB1) betaine. Growth performance, digestive enzyme activities, serum biochemical parameters, hepatic antioxidant capacity, and the expression of genes related to antioxidant defense, lipid metabolism, and inflammation were analyzed. The HF group exhibited significantly impaired growth, digestive function, and antioxidant capacity, along with elevated lipid peroxidation, dyslipidemia, and pro-inflammatory cytokine expression. Betaine supplementation restored growth performance and feed efficiency to control levels, ameliorated digestive enzyme activities (particularly enhancing lipase), and activated the hepatic Nrf2-Keap1 pathway, upregulating antioxidant genes (nrf2, sod1, cat, gpx, ho-1, gr) and enhancing enzyme activities. Betaine also improved serum lipid profiles, upregulated genes related to fatty acid oxidation (pparα, cpt-1) and lipolysis (lpl, hsl), suppressed lipogenic genes (srebp-1, fas), and rebalanced inflammatory cytokines by reducing tnf-α and il-1β while increasing tgf-β1 and il-10. Dietary betaine effectively counteracts HF-induced metabolic stress in M. salmoides through coordinated multi-pathway regulation. It enhances antioxidant defense, reprograms hepatic lipid metabolism toward catabolism, and restores inflammatory homeostasis. These findings underscore betaine's role as a multi-functional feed additive capable of mitigating HF-related metabolic disorders and promoting overall health in carnivorous fish aquaculture. Show less
This study aims to comprehensively analyze the genetic characteristics and prognostic value of stemness- and epithelial-mesenchymal transformation (EMT)-related gene signatures in lung adenocarcinoma Show more
This study aims to comprehensively analyze the genetic characteristics and prognostic value of stemness- and epithelial-mesenchymal transformation (EMT)-related gene signatures in lung adenocarcinoma (LUAD). The RNA-sequencing transcriptome profiling data and corresponding clinical information of LUAD were procured from TCGA-LUAD and GEO datasets. After screening, we first obtained 1488 stemness- and EMT-related genes. Then 304 hub genes were obtained via WGCNA, of which 52 genes were established to be prognosis-related hub genes. Thereafter, a prognostic model containing 11 genes (ANGPTL4, CCL20, ENO1, FGF2, LGR4, PIM2, S100P, SATB2, SHOX2, ZNF322, and CFTR) was constructed. We demonstrated that a higher risk score was an independent negative prognostic factor in LUAD patients. A nomogram was further constructed to better predict the survival of LUAD patients. More importantly, we found that the low-risk group has a more favorable anti-tumor immune microenvironment and may benefit more from immunotherapy. We finally noticed that the high-risk group was more sensitive to most drugs including drugs commonly used to treat LUAD patients. In conclusion, this study has summarized the alterations and prognostic role of stemness- and EMT-related gene signatures in LUAD and constructed a prognostic model to accurately and stably predict survival and guide individualized treatment decisions. Show less