Understanding the adaptive evolution of brain function in extreme environments remains a central challenge in evolutionary biology. This study investigates the molecular mechanisms underlying cave ada Show more
Understanding the adaptive evolution of brain function in extreme environments remains a central challenge in evolutionary biology. This study investigates the molecular mechanisms underlying cave adaptation by comparing brain transcriptomes of sympatric cave-dwelling ( Show less
MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that are widely found in organisms and play an important regulatory role in various biological processes, especially immune and infla Show more
MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that are widely found in organisms and play an important regulatory role in various biological processes, especially immune and inflammatory responses. However, the function of miR-320b in the inflammatory responses of bovine mammary epithelial cells (bMECs) remains to be elucidated. In this study, we examined the miR-320b mimic transduction group (miR-320b_mimic) and negative control mimic transduction group (NC_mimic) of lipopolysaccharide-treated bMECs using data-independent acquisition (DIA) proteomics and untargeted metabolomics. Subsequently, we performed a joint analysis of the sequencing data. Proteomic analysis identified 330 differentially abundant proteins (DAPs) primarily related to PPAR, ferroptosis, arachidonic acid metabolism, IL-17, and complement and coagulation cascades. Metabolome analysis identified 128 and 66 differentially accumulated metabolites (DAMs) in the positive and negative ion mode primarily involved in linoleic acid metabolism, cholesterol metabolism, AMPK, MAPK, and chemokine. Integrated metabolomics and proteomics analysis revealed the co-enrichment of DAPs and DAMs in choline metabolism in cancer, endocrine resistance, glycerophospholipid metabolism, primary bile acid biosynthesis, and the ferroptosis signaling pathways. The results of quantitative real-time PCR (RT-qPCR) showed that compared with the NC_mimic group, mRNA expression levels of COX-2, IL-12 A, iNOS, MAPK1, and MAPK14 genes were significantly down-regulated, and the mRNA expression levels of PPARγ, CEBPα, CEBPβ, FABP4, and LPL genes were significantly up-regulated in the miR-320b_mimic group. These results provide crucial insights into the molecular regulatory functions of miR-320b and offer valuable data for further research on molecular breeding aimed at enhancing mastitis resistance in bovine animals. Show less
Kelch-like protein 12 (KLHL12) has been shown to regulate coat complex II (COPII)-mediated endoplasmic reticulum (ER)-to-Golgi trafficking of large cargos carrying procollagen or apolipoprotein B-100 Show more
Kelch-like protein 12 (KLHL12) has been shown to regulate coat complex II (COPII)-mediated endoplasmic reticulum (ER)-to-Golgi trafficking of large cargos carrying procollagen or apolipoprotein B-100 containing very-low-density lipoprotein (VLDL). It is known that lipid absorption and chylomicron metabolism in enterocytes are dependent on apolipoprotein B-48 (ApoB48) and COPII-mediated trafficking. This study aimed to investigate whether KLHL12 in the intestine regulates dietary lipid absorption, chylomicron assembly, and metabolic phenotypes in mice. We generated Show less
The established body of knowledge attests to the pivotal influence of ANGPTL4 on lipid metabolism and vascular biology. Nevertheless, its potential implication in neurodegenerative disease remains to Show more
The established body of knowledge attests to the pivotal influence of ANGPTL4 on lipid metabolism and vascular biology. Nevertheless, its potential implication in neurodegenerative disease remains to be fully characterized. The present investigation delves into the involvement of ANGPTL4 in the pathological progression of PD, both in vitro and in vivo. PD models were induced by intraperitoneal administration of MPTP and LPS in WT and ANGPTL4 The observations unveiled that ANGPTL4 deficiency exacerbated behavioral aberrations, intensified dopaminergic neuron loss, and stimulated microglial activation along with p21-dependent senescence. There was an elevation in the expression of proinflammatory cytokines in the PD model. Furthermore, the administration of rANGPTL4 protein reversed the observed phenotypes in ANGPTL4 Our findings posit a salutary role for ANGPTL4 in counteracting PD, rendering it a prospective therapeutic target for the development of innovative drugs aimed at treating neuroinflammation-associated neurological diseases, including PD. Show less
Endometritis in dairy cows involves complex molecular regulatory mechanisms. Therefore, uncovering the molecular regulatory mechanisms of endometritis in dairy cows is crucial to understand its develo Show more
Endometritis in dairy cows involves complex molecular regulatory mechanisms. Therefore, uncovering the molecular regulatory mechanisms of endometritis in dairy cows is crucial to understand its development, prevention, and treatment. This study aimed to screen and validate key genes associated with endometritis using transcriptome sequencing of blood samples and previously obtained metabolomic sequencing data. Based on gain-of-function and loss-of-function experiments on the gene, multiple techniques, including qRT-PCR, western blotting, detection of reactive oxygen species (ROS), measurement of mitochondrial membrane potential, EdU assay, flow cytometry, and CCK-8 assay were used to explore the function of the key gene in lipopolysaccharide (LPS)-stimulated bovine endometrial epithelial cells (BEECs). The results identified 536 differentially expressed genes (DEGs) between healthy cows and those with endometritis. These DEGs were significantly enriched in apoptosis and HIF-1 signaling pathways. Weighted gene co-expression network analysis of transcriptomic and metabolomic data identified CD83, CTNNAL1, LRRC25, and NR1H3 as potential key genes for endometritis in dairy cows, with CD83 being more significantly expressed in LPS-induced BEECs. Consequently, in vitro functional studies were performed on CD83. In overexpression experiments, downregulation of the expression of inflammatory markers interleukin (IL)-1β, IL-6, and IL-8 and reduced ROS release primarily indicated the role of CD83 in attenuating the inflammatory response of BEECs. Furthermore, overexpression of CD83 regulated the S/G2 phase transition of BEECs by affecting the mRNA and protein expression of proliferation marker genes, thereby promoting proliferation of BEECs. The increased EdU positivity and the cell proliferation rate further provided evidence for the promotion of cell proliferation after overexpression of CD83. Additionally, overexpression of CD83 attenuated LPS-stimulated mitochondrial damage in BEECs, as well as the downregulation of apoptosis marker gene expression. In contrast, knockdown of CD83 expression showed the opposite trend. In summary, CD83 attenuated the inflammatory response of BEECs, promoted their proliferation, and inhibited apoptosis. This study provided basic data for understanding the mechanisms of endometritis regulation at the gene level in dairy cows. Show less
Cardiovascular disease (CVD) is the leading cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), yet traditional risk predictors remain limited in clin Show more
Cardiovascular disease (CVD) is the leading cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), yet traditional risk predictors remain limited in clinical practice. To develop machine learning (ML) models for classifying prevalent atherosclerotic cardiovascular disease (ASCVD) risk in MASLD patients, and to enhance model interpretability using SHapley Additive exPlanations (SHAP). Methods: This retrospective study included 590 MASLD patients diagnosed at the Affiliated Hospital of Qingdao University between December 2019 and December 2024. Patients were randomly divided into a training set (n=413) and a validation set (n=177), and further stratified based on ASCVD status. Least absolute shrinkage and selection operator (LASSO) regression was used for feature selection. Six ML models were developed and evaluated using sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC), and F1 score. SHAP analysis was performed to interpret feature contributions. ASCVD was present in 434 of 590 patients (73.6%). The Gradient Boosting (GB) model achieved the best performance, with AUCs of 0.918 (95% CI: 0.890-0.944) in the training set and 0.817 (95% CI: 0.739-0.883) in the validation set. SHAP analysis identified the top predictors as the Cholesterol-HDL-Glucose (CHG) index, Castelli Risk Index II (CRI-II), lipoprotein(a) [Lp(a)], serum creatinine (Scr), and uric acid (UA). The GB model demonstrated strong high accuracy in identifying existing ASCVD in MASLD patients and may serve as a useful tool for early risk stratification in clinical settings. Show less
At present, there is no consensus on the relationship between selenium (Se) exposure and human serum lipid metabolism. The etiological role of high-Se exposure in lipid markers, dyslipidemia, and nona Show more
At present, there is no consensus on the relationship between selenium (Se) exposure and human serum lipid metabolism. The etiological role of high-Se exposure in lipid markers, dyslipidemia, and nonalcoholic fatty liver (NAFLD) remains unclear. We used serum untargeted metabolomics analysis to evaluate whether high-Se exposure is cross-sectionally associated with lipid metabolism in adults from high-Se exposure area (n = 112) and control area (n = 101) in Hubei Province, China. An untargeted liquid chromatography/mass spectrometry (LC/MS)-based metabolomic analysis identified 144 differential pathways and yielded 204 differentially abundant metabolites, including 32 lipid metabolites associated with lipids profiles. To further explore the correlation between Se exposure and serum lipid metabolism, we measured serum levels of lipid profiles among all the people, including serum cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (APOB). The average serum Se level of the high-Se exposure group was 537.18 μg/L, significantly higher than 72.98 μg/L in the control group (p < 0.0001). The measurement levels of serum TG, LDL-C, HDL-C, and APOB in the high-Se exposure group were 1.03 (0.76, 1.34) mmol/L, 2.25 ± 0.48 mmol/L, 1.12 ± 0.24 mmol/L, and 0.77 ± 0.15 g/L, respectively, while the control group were 1.13 (0.84, 1.80) mmol/L, 2.56 ± 0.61 mmol/L, 1.02 ± 0.22 mmol/L, and 0.83 ± 0.16 g/L, respectively (all p values <0.05). Correlation analysis showed a significant negative correlation between serum Se and CHOL (r = -0.201, p < 0.01), serum Se is also associated with metabolomics markers, the negative correlation includes glyceric acid and ect., the positive correlation includes phosphorylcholine and ect. Our study suggests that high-Se exposure is negatively associated with serum lipid profiles and decreases the risk of high-TC and HDL-C dyslipidemia. 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
Dysregulation of macrophage autophagy plays a critical role in sepsis-induced acute lung injury (ALI); however, its underlying mechanism remains unclear. In this study, we aimed to identify the regula Show more
Dysregulation of macrophage autophagy plays a critical role in sepsis-induced acute lung injury (ALI); however, its underlying mechanism remains unclear. In this study, we aimed to identify the regulatory pathway involving the PIK3C3-MAPK14 signaling axis that drives ALI progression by controlling autophagy and macrophage polarization. Using machine learning transcriptomic analysis, MAPK14 was identified as a core gene associated with ALI, and multi-omics integration confirmed its upregulated expression in ALI tissues. MAPK14 localization to pro-inflammatory macrophages was determined using single-cell sequencing. Furthermore, we observed a significant positive correlation between MAPK14 and autophagy-related genes. Molecular docking and kinetic simulations revealed high-affinity interactions between PIK3C3 and MAPK14 (ΔG-bind = -127.722 ± 33.269 kJ/mol). In vitro experiments followed by Western Blot(WB) and RT-q polymerase chain reaction (PCR) assays demonstrated that lipopolysaccharide stimulation upregulated MAPK14 expression through downregulation of PIK3C3 expression, resulting in impaired autophagic flux (LC3-II/Ⅰ↓, TOM20↑, P62↑, HSP60↑). Flow cytometry and enzyme-linked immunosorbent assay (ELISA) confirmed a shift toward pro-inflammatory (M1) macrophage polarization. RNA pull-down assay directly captured the PIK3C3-MAPK14 complex, and functional validation showed that PIK3C3 overexpression significantly inhibited MAPK14 protein expression, whereas PIK3C3 knockdown enhanced it. In conclusion, targeting the PIK3C3-MAPK14 axis is a promising therapeutic strategy for ALI. Show less
Xiang Lian, Xiaoyan Li, Kexin Wang+3 more · 2025 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · added 2026-04-24
To investigate the gene detection results of 2 patients with familial hypercholesterolemia (FH) caused by complex heterozygous variation, and to clarify the relationship between clinical manifestation Show more
To investigate the gene detection results of 2 patients with familial hypercholesterolemia (FH) caused by complex heterozygous variation, and to clarify the relationship between clinical manifestations and gene variation. Two patients (patient 1 and 2) with FH who visited Beijing Anzhen Hospital Affiliated to Capital Medical University in 2018 were selected as research subjects. A retrospective study method was used to collect clinical and family history data of the two patients. And 2 mL of peripheral venous blood from each of the two patients was collected, and genomic DNA extraction was performed on the blood samples. Sanger sequencing was used to validate the variant sites of the two patients detected by whole-exome sequencing (WES). Pathogenicity of variants was classified based on the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the "ACMG Guidelines"), and the impact of variant was analyzed using multiple bioinformatics tools including SIFT, PolyPhen-2, and SWISS-MODEL. This study has been approved by Beijing Anzhen Hospital Affiliated to Capital Medical University (Ethics No. 2024215X). Patient 1 initially presented with early-onset coronary heart disease, with initial lipid levels of serum total cholesterol (TC) 9.86 mmol/L (normal reference value: 3.10~5.20 mmol/L) and serum low-density lipoprotein cholesterol (LDL-C) 8.37 mmol/L (normal reference value: 1.27~3.12 mmol/L) on admission. Patient 1 initially underwent treatment with rosuvastatin combined with ezetimibe for one month, but the lipid-lowering effect was not significant. The lipid-lowering therapy was then adjusted to atorvastatin combined with ezetimibe and probucol. After one year of treatment, the patient developed paroxysmal chest pain symptoms. A follow-up lipid profile showed a serum TC level of 4.50 mmol/L and a LDL-C level of 3.55 mmol/L. The lipid-lowering regimen was continued, and the serum LDL-C levels were maintained between 2.65 and 3.66 mmol/L. Patient 2 was found to have an abnormally high blood lipid level and carotid artery hardening during physical examination, with an initial blood lipid level of serum TC 11.82 mmol/L and serum LDL-C 9.63 mmol/L. After receiving rosuvastatain therapy, the lipid-lowering effect was significant. WES revealed that patient 1 carried the heterozygous variants c.1871₁₈₇₃del(p.Ile624del) and c.1747C>T (p.His583Tyr) in the LDLR gene (NM₀₀₀₅₂₇.4), while patient 2 carried the heterozygous variants c.1747C>T (p.His583Tyr) in the LDLR gene and c.6936₆₉₃₇inv (p.Ile2313Val) in the APOB gene (NM₀₀₀₃₈₄₎. According to the ACMG Guidelines, the LDLR gene c.1747C>T (p.His583Tyr) was classified as a pathogenic variant (PS3+PM1+PM2_supporting+PM5+PP2+PP3), and c.1871₁₈₇₃del (p.Ile624del) was classified as a pathogenic variant (PS3+PS4+PM2_supporting+PM1+PM4); the APOB gene c.6936₆₉₃₇inv (p.Ile2313Val) was classified as a variant of uncertain clinical significance (PM2_supporting BP4). Patients 1 and 2 in this study were patients with complex heterozygous variant FH, and their genotypic differences may be related to the differences in clinical serum LDL-C levels and the efficacy of hypolipidemic agents. Show less
Dynamic responsive structural colored materials have drawn increased consideration in a wide range of applications, such as colorimetric sensors and high-safety tags. However, the sophisticated intera Show more
Dynamic responsive structural colored materials have drawn increased consideration in a wide range of applications, such as colorimetric sensors and high-safety tags. However, the sophisticated interactions among the individual responsive parts restrict the advanced design of multimodal responsive photonic materials. Inspired by stimuli-responsive color change in chameleon skin, a simple and effective photo-crosslinking strategy is proposed to construct hydroxypropyl cellulose (HPC) based hydrogels with multiple responsive structured colors. By controlling UV exposure time, the structural color of HPC hydrogels can be effectively controlled in a full-color spectrum. At the same time, HPC hydrogels showcase temperature and mechanical dual-responsive structural colors. In particular, the microstructure of HPC hydrogels undergoes a transition from the chiral nematic phase to the nematic phase under the action of external stretching, leading to a significant reflection of circularly polarized light (CPL) to linearly polarized light (LPL). Given the diverse responsiveness exhibited by HPC hydrogels and their unique structural transition properties under external forces, we have explored their potential applications as dynamic anti-counterfeiting labels and optical skins. This work reveals the great possibility of using structural colored cellulose hydrogels in multi-sensing and optical displays, opening up a new path for the exploration of next-generation flexible photonic devices. Show less
Cordyceps has been clinically used to treat atherosclerosis (AS) since the 1980s. However, the active components responsible for its effects and the underlying mechanisms remain poorly understood. In Show more
Cordyceps has been clinically used to treat atherosclerosis (AS) since the 1980s. However, the active components responsible for its effects and the underlying mechanisms remain poorly understood. In this study, we aimed to explore the anti-AS effects and mechanisms of action of wild Cordyceps polysaccharides (WCP). The molecular weight, monosaccharide composition, and structural characteristics of WCP were analyzed. Furthermore, the anti-AS effects of WCP were evaluated using apolipoprotein E knockout ( Show less
Heart failure (HF) is a serious cardiovascular condition resulting from abnormalities in multiple biological processes, affecting over 64 million people worldwide. We sought to expand our understandin Show more
Heart failure (HF) is a serious cardiovascular condition resulting from abnormalities in multiple biological processes, affecting over 64 million people worldwide. We sought to expand our understanding of the genetic basis of HF and more specific NICM subtype in the East Asian populations and evaluate the biological pathways underlying subclinical left ventricular dysfunction. We conducted a meta-analysis of genome-wide association studies (GWAS) for all-cause HF in the East Asian populations (N cases ~ 13,385) and a more precise definition of nonischemic cardiomyopathy (NICM) subtype in multi-ancestry populations (N cases~3,603). We identified a low-frequency East-Asian enriched coding variant near MYBPC3 and a NICM specific locus. Follow up analyses demonstrated male-specific HF association at the MYBPC3 locus, and highlighted SVIL as a candidate causal gene for NICM. Moreover, we demonstrated that SVIL deficiency aggravated cardiomyocyte hypertrophy, apoptosis and impaired cell viability in phenylephrine (PE)-treated H9C2 cells. In addition, the gene expression level of B-type natriuretic peptide (BNP) which was deemed as a hallmark for HF was further elevated by SVIL silencing in PE-stimulated H9C2 cells. RNA-sequencing analysis of H9C2 cells revealed that the function of SVIL might be mediated through pathways relevant to regulation and differentiation of heart muscle. These results enhance our understanding of the genetic architecture of HF in the East Asian populations, and provide important insight into the biological pathways underlying NICM and sex-specific relevance of the MYBPC3 locus that warrants further replication in another datasets. Show less
Lactylation, a recently identified post-translational modification, plays a critical role in tumor progression and immune regulation. However, its cellular heterogeneity and functional impact in lung Show more
Lactylation, a recently identified post-translational modification, plays a critical role in tumor progression and immune regulation. However, its cellular heterogeneity and functional impact in lung adenocarcinoma (LUAD) remain poorly understood. This study was designed as exploratory biological research to characterize lactylation-associated patterns at the single-cell level and to propose a potential lactylation-related prognostic model. Single-cell transcriptomic data from LUAD and normal lung tissues were analyzed to quantify lactylation activity using AUCell based on 332 lactylation-related genes. Cell-cell communication was inferred using CellChat to identify ligand-receptor interactions among subpopulations. Candidate genes were selected by integrating ligand-receptor pair genes, marker genes from highly lactylated subtypes, and previously reported lactylation-related genes. A total of 101 machine learning model combinations were evaluated to construct the prognostic model. Selected genes were further validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the potential relationship between Lactylation activity was higher in tumor epithelial and stromal cells, with particularly elevated levels in specific epithelial subpopulations. A 12-gene signature was identified, comprising nine risk genes (e.g., This study presents a lactylation-based prognostic model for LUAD and uncovers potential immune-related mechanisms by which highly lactylated epithelial cells may contribute to immune evasion and tumor progression. Show less
Yuwen Guo, Huai Bai, Linbo Guan+4 more · 2025 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · added 2026-04-24
To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). A total of 1 514 Show more
To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). A total of 1 514 pregnant women who visited West China Second University Hospital of Sichuan University between January 1, 2013 and December 31, 2021 were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 of the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels of insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by the Medical Ethics Committee of the West China Second University Hospital of Sichuan University (Ethics No.: 2020-036). The main genotype at the rs174575 C/G and rs2845574 C/T loci were CC in both GDM and control groups. No significant difference was found between the GDM and control groups regarding the genotypic or allelic frequencies of rs174575 and rs2845574 sites (P > 0.05). Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype (P < 0.05), and had higher atherogenic indices (AI) compared with the CC and CG genotype (P < 0.05; P < 0.05). Individuals with the TT genotype at the rs2845574 site had higher AI compared with the CT genotype (P < 0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype (P < 0.05). Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in the obese subgroup of control (P < 0.05; P < 0.05; P < 0.05). The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients are associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have a BMI-dependent effect. Show less
The malignant transformation of odontogenic keratocysts (OKC) into cancerous odontogenic keratocysts (COKC) is exceedingly rare, and its mechanisms remain poorly understood. Studies exploring the cell Show more
The malignant transformation of odontogenic keratocysts (OKC) into cancerous odontogenic keratocysts (COKC) is exceedingly rare, and its mechanisms remain poorly understood. Studies exploring the cellular heterogeneity, molecular pathways, and clinical features of COKC are limited. In this study, we performed single-cell RNA sequencing (scRNA-seq) on three COKC samples and integrated the data with a public OKC dataset, identifying 22,509 single cells. Two COKC-specific epithelial subpopulations, Basal-C0-EXT1 and Basal-C3-HIST1H3B, were identified. These subpopulations exhibited enhanced stemness and invasive potential, respectively, suggesting their roles as key drivers of OKC carcinogenesis. Fibroblasts underwent phenotypic transitions, particularly from inflammation-associated fibroblasts (IFBs) to myofibroblasts (MFBs). Similarly, macrophage phenotypic transformation may also play a role in OKC carcinogenesis. Clinical observations of severe lesion-area pain in COKC patients suggest potential neuroinvasiveness, Supported by single-cell transcriptomic data, imaging findings, and histopathological evidence. A review of clinical data revealed that none of the COKC patients exhibited cervical lymph node metastasis. Single-cell transcriptomics suggests that this phenomenon may be associated with an active immune microenvironment in COKC, reduced epithelial-mesenchymal transition (EMT) activity, lower VEGFC expression, and upregulated MAST4 expression as a potential regulator of lymphatic metastasis. In conclusion, COKC exhibits distinct molecular, cellular, and clinical characteristics compared to OKC, featuring potent neuroinvasiveness and low lymph node metastatic potential. These findings provide important insights into the mechanisms underlying COKC development and may guide novel diagnostic and therapeutic strategies. Show less
While fibroblast growth factor receptor 2 (FGFR2) emerges as an appealing cancer therapeutic target, so far there is no selective FGFR2 inhibitor on the market. Here, we report the discovery of a seri Show more
While fibroblast growth factor receptor 2 (FGFR2) emerges as an appealing cancer therapeutic target, so far there is no selective FGFR2 inhibitor on the market. Here, we report the discovery of a series of new selective, irreversible FGFR2 inhibitors with compound BW710 being the representative. Compound BW710 potently inhibited the proliferation of BaF3-FGFR2 cells with an IC Show less
With the aging population in China, research on preventing frailty is crucial. This study aims to investigate the independent and combined associations of the Dietary inflammatory index (DII) and phys Show more
With the aging population in China, research on preventing frailty is crucial. This study aims to investigate the independent and combined associations of the Dietary inflammatory index (DII) and physical activity (PA) with frailty among Chinese older adults. A total of 285 participants aged ≥60 years with 87 males and 186 females were recruited from Hunan Province. Daily moderate physical activity (MPA), vigorous physical activity (VPA) and light physical activity (LPA) were objectively measured using a triaxial accelerometer. A Food Frequency Questionnaire 25 (FFQ25) was used to assess the participants' dietary patterns, and DII was calculated. Six combined exposure groups were formed based on PA and DII: pro-inflammatory diet and insufficient PA group, neutral diet and insufficient PA group, anti-inflammatory diet and insufficient PA group, pro-inflammatory diet and sufficient PA group, neutral diet and sufficient PA group, and anti-inflammatory diet and sufficient PA group. Frailty was assessed using the Frailty Phenotype (FP), logistic regression analyzed the associations between dietary patterns, PA, and frailty. A total of 285 older adults participants were initially recruited, but 12 were excluded due to missing data. Consequently, 273 participants were included in the final analysis. Compared to individuals with insufficient PA, those with sufficient PA were associated with significantly lower odds of frailty (OR = 0.468, 95%CI = 0.242-0.907). Participants following an anti-inflammatory diet had significantly lower odds of frailty compared with those following a pro-inflammatory diet (OR = 0.467, 95%CI = 0.221-0.988). In the combined groups, frailty prevalence was significantly lower the group with anti-inflammatory diet and sufficient PA group (OR = 0.204, 95%CI = 0.072-0.583), compared with pro-inflammatory diet and insufficient PA group. The sensitivity analysis showed that the associations between anti-inflammatory diet and sufficient PA with frailty remained statistically significant, with the direction of the associations unchanged. These findings suggest that the results are robust. Our study indicates that adhering to an anti-inflammatory diet and maintaining sufficient PA may be associated with a lower likelihood of frailty. Achieving an adequate amount of PA and following a healthy dietary pattern may serve as potential preventive measures against frailty. Show less
The embryos of lotus (Nelumbo nucifera Gaertn.) is a famous traditional Chinese medicine used to treat insomnia, memory decline, and dementia for a long time. However, the underlying material basis an Show more
The embryos of lotus (Nelumbo nucifera Gaertn.) is a famous traditional Chinese medicine used to treat insomnia, memory decline, and dementia for a long time. However, the underlying material basis and mechanisms of this medicine are still unclear. Isoliensinine (IL) is a major alkaloid derived from lotus embryos. Our previous research has demonstrated that IL can exert strong anti-inflammatory and neuroprotective effects in vitro. To reveal the underlying therapeutic effect and mechanism of IL on Alzheimer's disease (AD)-like mice induced by AlCl The AD-like mice were modeled by intragastric injection (i.g.) of AlCl IL (1, 3, and 10 mg/kg) treatment effectively ameliorated cognitive impairment in AD-like model mice. IL inhibited the decrease of brain index and body weight in AD-like mice and alleviated neuronal damage in the cortex and hippocampus (DG, CA1, and CA3). IL decreased the levels of Ca IL has a significant therapeutic effect on pathological alterations and cognitive impairment in AlCl Show less
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to u Show more
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to unravel causal associations between 2,940 circulating proteins and 19 CVD. We found 218 proteins that impacted risk of one or more CVDs through forward MR (106 and 182 using cis-pQTLs only and cis- + trans-pQTLs, respectively), among which 107 were previously reported as associated with CVD or CVD-related traits. There were 102 proteins replicated (FDR < 5%, 53 with cis-pQTLs only and 88 with cis- + trans-pQTLs) using the FinnGen Olink data. BTN3A2 was highlighted as a novel candidate gene for ischemic stroke, suggesting a crosstalk between immune modulation and stroke pathogenesis. Single cell integration prioritized PAM for stable angina pectoris and ventricular arrhythmia and LPL for peripheral artery disease, whose transcriptional expressions were enriched in cardiomyocytes. Forward and reverse MR found largely non-overlapping proteins (only 2 overlapped: LGALS4 and MMP12), suggesting distinct proteomic causes and consequences of CVD. Our study provides human genetics-based evidence of novel candidate genes, a foundational step towards full-scale causal human biology-based drug discovery for CVD. Show less
Given the lack of evidence, we cannot definitively determine the relationship between attachment networks and problematic mobile phone use, hindering effective intervention strategies. Therefore, a th Show more
Given the lack of evidence, we cannot definitively determine the relationship between attachment networks and problematic mobile phone use, hindering effective intervention strategies. Therefore, a three-wave longitudinal study was designed to explore the heterogeneity of parent-child attachment networks using latent profile analysis (LPA) and random intercept latent transition analysis (RI-LTA). Participants included 2116 adolescents (ages 14-21; 53.8% girls). Results identified five stable parent-child attachment network profiles, each showing moderate but decreasing stability. Notably, adolescents who were grouped into an attachment network characterized by secure maternal attachment but insecure paternal attachment, similar to those in attachment networks with both insecure maternal and paternal attachment, scored higher levels of problematic mobile phone use than those who were grouped into attachment networks with both secure maternal and paternal attachment. Our findings fill empirical gaps and provide strong evidence supporting attachment-based interventions to reduce problematic mobile phone use. Show less
To date, glucocorticoids remain the mainstay of treatment of nephrotic syndrome (NS). However, serious side effects and development of drug-resistance following long-term use limit the application of Show more
To date, glucocorticoids remain the mainstay of treatment of nephrotic syndrome (NS). However, serious side effects and development of drug-resistance following long-term use limit the application of glucocorticoids. Protopanaxadiol (PPD) possesses activity of dissociating transactivation from transrepression by glucocorticoid receptor (GR), which may serve as a potential selective GR modulator. However, steroid-like effects of PPD in vivo are unclear and not defined. How to translate PPD into clinical practice remains to be explored. The current study explored the renoprotection and potential mechanism of PPD and its combination with steroid hormones using adriamycin-induced NS rats. Adriamycin was given intravenously to rats to induce nephropathy. The determination of proteinuria, biochemical changes and inflammatory cytokines were performed, and pathological changes were examined by histopathological examination. Immunostaining and PCR were used to analyze the expression of interesting proteins and genes. The results showed that PPD, alone and in combination with prednisone, efficiently alleviate the symptoms of NS, attenuate nephropathy, improve adriamycin-induced podocyte injury by reducing desmin and increasing synaptopodin expression. In addition, the combined treatment reduced the expression of NF-κB protein and mRNA, as well as cytokine levels, and yet increased the expression of GR protein and mRNA. PPD modulated the transactivation of GR, manifested as repressing TAT, PEPCK and ANGPTL4 mRNA expressions mediated by GR. Meanwhile, PPD inhibited elevation of blood glucose and immune organ atrophy induced by prednisone. In summary, PPD increases the therapeutic effect of prednisone in NS while effectively prevents or decreases the appearance of side effects of glucocorticoids. Show less
Zhen Guo, Jing Su, Lu Liu+8 more · 2025 · Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · Elsevier · added 2026-04-24
Precise differential diagnosis between lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and marginal zone lymphoma (MZL) remains a challenging issue because of overlapping clinicopath Show more
Precise differential diagnosis between lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and marginal zone lymphoma (MZL) remains a challenging issue because of overlapping clinicopathological and immunophenotypic features. In the present study, the differential diagnostic potential of CD180 was assessed by determining its expression patterns in patients with MZL and LPL/WM through flow cytometry. The results indicated that LPL/WM cases exhibited a complete absence of CD180 expression on malignant B cells, whereas MZL cases showed robust CD180 expression (P < .001). Receiver operating characteristic analysis demonstrated that CD180 expression percentage showed optimal diagnostic accuracy in LPL/WM and MZL cases (area under the curve = 0.998, sensitivity = 100%, and specificity = 98.0%), with a further improvement in differentiation potential by the CD180 mean fluorescence intensity ratio (lymphocytes/monocytes) of ≤ 0.47 (area under the curve = 0.937). Moreover, although the MYD88 Show less
Sperm flagellum defects are tightly associated with male infertility. Centriolar satellites are small multiprotein complexes that recruit satellite proteins to the centrosome and play an essential rol Show more
Sperm flagellum defects are tightly associated with male infertility. Centriolar satellites are small multiprotein complexes that recruit satellite proteins to the centrosome and play an essential role in sperm flagellum biogenesis, but the precise mechanisms underlying this role remain unclear. Show less
Dietary interventions with food-derived natural products have emerged as a promising strategy to alleviate obesity. This study aims to investigate the anti-obesity effect of
The incidence of silent myocardial infarction (SMI) is increasing. Meanwhile, due to the atypical clinical symptoms and signs associated with SMI, the prognosis for patients is often poor. This predic Show more
The incidence of silent myocardial infarction (SMI) is increasing. Meanwhile, due to the atypical clinical symptoms and signs associated with SMI, the prognosis for patients is often poor. This prediction model used the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analyses to screen variables. Predictive accuracy was assessed using the area under the receiver operating characteristic (ROC) curve (AUC). The clinical decision curve analysis (DCA), alongside the calibration curve and clinical impact curve (CIC) analyses, were used to assess model validity. This study included 174 patients, 64 (36.8%) of whom experienced SMI; logistic regression analysis identified six variables: gender, age, high-density lipoprotein cholesterol (HDL-C), apolipoprotein B/apolipoprotein A1 (ApoB/A1), uric acid (UA), and triglyceride glucose-body mass index (TyG-BMI). The results identified the TyG-BMI as a predictor of SMI (odds ratios (OR) = 1.02, 95% CI: 1.01-1.03; The TyG-BMI is an independent predictor of SMI. A prediction model based on the TyG-BMI showed good predictive ability for SMI. Show less
Oxymatrine is an alkaloid with the property of immunomodulation. Recent studies have demonstrated that oxymatrine inhibits experimental autoimmune encephalomyelitis (EAE), an animal model of multiple Show more
Oxymatrine is an alkaloid with the property of immunomodulation. Recent studies have demonstrated that oxymatrine inhibits experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by promoting the production of interferon-β (IFN-β). However, the mechanism through which oxymatrine regulates the production of IFN-β remains unclear. The aim of this study was to investigate the pharmacological effects and related molecular mechanisms of oxymatrine in the treatment of EAE through in vivo and in vitro experiments. Oxymatrine alleviated neurological dysfunction, demyelination, and inflammation in EAE mice. It reduced microglia/macrophage infiltration and polarization, lowered pro-inflammatory cytokine levels (iNOS, TNF-α), and enhanced the expression of IL-10 and IL-27. Additionally, oxymatrine upregulated the STING/TBK1/IRF3 signaling pathway in EAE mice, promoting IFN-β production by microglia. Similarly, in LPS-induced BV2 cells, oxymatrine suppressed inflammatory factors and activated the STING/TBK1/IRF3 pathway to enhance IFN-β production. Notably, treatment with the STING inhibitor, C176, reversed these effects in both EAE mice and LPS-induced BV2 cells, confirming the pathway's critical role in the mechanism of oxymatrine therapy. Oxymatrine promotes IFN-β production in microglia by upregulating the STING/TBK1/IRF3 signaling pathway, thereby alleviating the neurological dysfunction of EAE and reducing pathological and inflammatory events. This study identifies a novel anti-EAE mechanism of oxymatrine: promoting IFN-β production in microglia by activating the STING/TBK1/IRF3 pathway. However, it lacks clinical sample verification. If validated later, oxymatrine may provide a more economical, convenient endogenous IFN-β induction regimen for MS patients. Show less
Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathologic Show more
Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high-dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits. Show less