Yu-Xuan Peng, Hong-Zheng Li, Wen-Wen Yang+4 more · 2025 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
This study aims to investigate the anti-atherosclerotic mechanism of Maiguan Fukang Tablets(MGFK) by integrating ultra-high-performance liquid chromatography-quadrupole orbitrap mass spectrometry(UHPL Show more
This study aims to investigate the anti-atherosclerotic mechanism of Maiguan Fukang Tablets(MGFK) by integrating ultra-high-performance liquid chromatography-quadrupole orbitrap mass spectrometry(UHPLC-QE-MS), network pharmacology, and animal experiments. UHPLC-QE-MS identified 131 compounds in MGFK. Network pharmacology databases were utilized to retrieve drug targets and disease-related targets, and a "component-target-disease" network was constructed, yielding 418 overlapping potential therapeutic targets. These targets were further analyzed via protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, which revealed significant associations primarily with inflammatory response, negative regulation of apoptotic process, and the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT) signaling pathway. Molecular docking demonstrated strong binding affinities between protein kinase B1(AKT1) and core active compounds including luteolin, liquiritigenin, apigenin, and kaempferol. An atherosclerosis(AS) model was established in ApoE~(-/-) mice by feeding a high-fat diet for 14 weeks, and mice were randomly divided into a model group, MGFK high-dose group, MGFK low-dose group, and atorvastatin group. Experimental results confirmed that MGFK significantly reduced aortic plaque area, decreased lipid and foam cell proportion within plaques, lowered serum total cholesterol(TC), and reduced the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and IL-6. Furthermore, MGFK decreased the apoptosis rate within plaques, upregulated B-cell lymphoma-2(BCL-2) expression, downregulated BCL-2-associated X protein(BAX) and cleaved caspase-3, and promoted the phosphorylation of PI3K and AKT. These findings suggest that MGFK exerts anti-atherosclerotic effects potentially by regulating the PI3K/AKT signaling pathway, thereby reducing apoptosis within plaques, lowering levels of inflammatory cytokines and blood lipids, and attenuating plaque size, lipid content, and foam cell formation. Show less
Cancer persists as one of the most formidable global public health crises and socioeconomic burdens of our era, compelling the scientific community to develop innovative and diversified therapeutic mo Show more
Cancer persists as one of the most formidable global public health crises and socioeconomic burdens of our era, compelling the scientific community to develop innovative and diversified therapeutic modalities to revolutionize clinical management and enhance patient outcomes. The recent seminal discovery by Swamynathan et al. has unveiled menadione, a vitamin K precursor, as a potent inducer of triaptosis-a novel regulated cell death pathway mediated through the oxidative modulation of phosphatidylinositol 3-kinase PIK3C3/VPS34. This mechanistically distinct cell death paradigm, characterized by its intimate association with endosomal dysfunction and oxidative stress-induced cellular catastrophe, has demonstrated remarkable therapeutic efficacy in preclinical prostate cancer models, outperforming conventional therapeutic regimens and emerging as a potential paradigm-shifting strategy in oncology. This comprehensive review provides a critical synthesis of the triaptosis discovery landscape, elucidating its molecular intricacies and pathophysiological implications. We systematically examine the multifaceted roles of endosomal biology in oncogenesis and tumor progression, while offering a nuanced perspective on redox homeostasis in malignant cells and the therapeutic potential of oxidative stress modulation. Furthermore, we address the inherent dichotomy of oxidative stress induction in cancer therapy, balancing its therapeutic promise against potential adverse effects. Looking toward the horizon of cancer research, we explore transformative therapeutic strategies leveraging triaptosis induction and its potential applications beyond oncology, aiming to catalyze a new era of precision medicine that ultimately enhances patient survival and quality of life. Show less
Metabolic dysfunction-associated fatty liver disease (MAFLD), driven by dyslipidemia and hepatic lipid deposition, has become a major public health concern. Angiopoietin-like protein 3 (ANGPTL3), a li Show more
Metabolic dysfunction-associated fatty liver disease (MAFLD), driven by dyslipidemia and hepatic lipid deposition, has become a major public health concern. Angiopoietin-like protein 3 (ANGPTL3), a lipoprotein lipase (LPL) activity inhibitor, can inhibit triglycerides (TGs) decomposition, and fibroblast growth factor 21 (FGF21) enhances fatty acids' β-oxidation in liver. We constructed a novel fusion protein combining the anti-ANGPTL3 nanobody FD03 and FGF21 (FD03-FGF21), which exerted appropriate binding affinities to ANGPTL3 and β-Klotho respectively. Our results showed FD03-FGF21 restored bioactivity of LPL which inhibited by ANGPTL3 and activated downstream pathway of FGF21 in iLite FGF21 assay-ready cells. Next, FD03-FGF21 showed a significant therapeutic effect in MAFLD mice, including attenuation of metabolic dyslipidemia, hepatic lipid accumulation, and impaired glucose tolerance. Compared to other treatments, FD03-FGF21 achieved the most significant therapeutic effect with a 79.78 % attenuation of low-density lipoprotein cholesterol (LDL-C) and a 95.8 % reduction of hepatic lipid accumulation. Mechanistically, transcriptomic analysis revealed that differential expression genes (DEGs) were principally clustered into lipid metabolism and oxidative stress pathways after the fusion protein treatment, especially the key lipid metabolism genes of LDLR and CD36 were significantly upregulated and downregulated respectively, as confirmed by WB. Furthermore, lipidomic and metabolomic analysis indicated the fusion protein ameliorated disorders in lipid and protein metabolism mainly through the downregulation of DG and upregulation of PC. Hepatic oxidative stress and inflammation were significantly reduced after administration of the fusion protein in MAFLD mice. Collectively, FD03-FGF21 represents an effective therapeutic strategy for MAFLD therapy through ameliorating lipid metabolism and oxidative stress. Show less
To construct a nomogram for predicting metabolic syndrome (MetS) in women with polycystic ovary syndrome. In this retrospective study, we analyzed clinical and biochemical data from 859 Chinese women Show more
To construct a nomogram for predicting metabolic syndrome (MetS) in women with polycystic ovary syndrome. In this retrospective study, we analyzed clinical and biochemical data from 859 Chinese women diagnosed with PCOS. Univariable logistic regression and forward stepwise logistic regression were employed to identify independent predictors of MetS. A predictive nomogram was developed that integrates age, acne status, body mass index (BMI), fasting insulin levels (FINS), and the ApoB/ApoA ratio. The model's discriminative performance, calibration accuracy, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration curves accompanied by Brier scores, Hosmer - Lemeshow tests, decision curve analysis (DCA), and clinical impact curves (CIC). Internal validation was conducted through bootstrap resampling over 1,000 iterations. The nomogram exhibited strong discriminative capability with an AUC of 0.874 (95% CI: 0.850-0.899), surpassing BMI alone which had an AUC of 0.824 ( The proposed nomogram accurately predicts MetS risk in PCOS patients, supporting early identification and individualized management. Show less
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatment Show more
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatments (H1: 18:6, H2: 24:6, and H3: 30:6) were tested using agricultural unmanned aerial vehicles (AUAVs) for pollination assistance. The results showed that row-ratio had little effect on sterile line flowering dynamics. The index of flowers meeting (IFM) was 0.71-0.72 at Qionglai and 0.81-0.86 at Mianzhu, with 11 to 12 days of flowering duration. As the row-ratio increased, total pollen quantity in the panicle layer and grain filling rate (GFR) decreased, while grain infection rate (GIR) increased. The responses of grain blighted rate (GBR), grain empty rate (GER), and fertilization success rate (FSR) to row-ratio varied between sites. Pollen density and GFR followed the pattern of near region (NR) > central region (CR) > far region (FR). Within the panicle, pollen density was generally highest in the upper panicle layer (UPL), followed by the middle (MPL) and lower (LPL) layers, with partial exceptions observed in the H2 and H3 treatments at Mianzhu. The vertical distribution of GFR varied by site: at Qionglai, it was apical parts of panicle (APP) > median parts (MPP) > basal parts (BPP), whereas at Mianzhu the order was MPP > APP > BPP. With wider row-ratios, yield per unit area (YUA) and GFR declined (H1 > H2 > H3), while 1,000-grain weight increased or decreased and then increased. Under H1, yields reached 2,107.50 kg ha Show less
Sepsis is associated with high morbidity and high mortality and has strongly motivated intense studies into its mechanisms. Antibiotics, aimed to eradicate bacteria, have some impact on the immune sys Show more
Sepsis is associated with high morbidity and high mortality and has strongly motivated intense studies into its mechanisms. Antibiotics, aimed to eradicate bacteria, have some impact on the immune system due to anti-inflammatory properties. Tigecycline, an antibiotic of the glycylcycline class, is commonly used for severe infections. This study aimed to investigate tigecycline's mechanism on the inflammatory response of sepsis to find new targets for sepsis treatment. The objective included (i) to observe the changes in inflammatory factors in LPS (lipopolysaccharide) induced septic mice after tigecycline administration, (ii) to detect the effect of tigecycline on macrophages NF-κB (nuclear factor kappa B) signalling. For LPS-induced sepsis in mice and intervention with tigecycline, mice were first injected with tigecycline (6.5 mg/kg) via tail vein followed by LPS (15 mg/kg). Luminex analysis was performed on 16 mediators. NF-κB signalling pathway antibody chip detected the expression of target sites in macrophages of the LPS group and tigecycline + LPS group. Tigecycline has inhibitory effects on LPS-induced inflammatory response in septic mice, decreasing the concentrations of IL (interleukin)-6, IL-27, TNF-α (tumour necrosis factor-α), TNF RII, IFN-γ (interferon-gamma), CCL5/RANTES (CC Motif Chemokine Ligand) while increasing IL-6Rα, IL-10, and TWEAK (TNF-related weak inducer of apoptosis). Tigecycline downregulated phosphorylation levels of key sites JNK (c-Jun N-terminal kinase)1/2/3, p-p65 (s468) and p-p105/p50 (s907) in NF-κB signalling. Tigecycline may inhibit the excessive immune response induced by LPS in sepsis, which may cause a potential protective effect on the host through immune regulation. Show less
Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. The Show more
Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. There is a high unmet need for an effective therapeutic for this disorder, especially in early neonatal patients where mortality is excessive. However, development of an adeno-associated virus (AAV)-based approach is hampered by large cDNA size and high protein requirement. We developed an oversized AAV vector as a gene therapy to treat Show less
This study aimed to elucidate the molecular mechanisms by which celastrol (Cel) alleviates atherosclerosis (AS) through the regulation of macrophage autophagy. An AS model was established using ApoE C Show more
This study aimed to elucidate the molecular mechanisms by which celastrol (Cel) alleviates atherosclerosis (AS) through the regulation of macrophage autophagy. An AS model was established using ApoE Cel markedly reduced aortic plaque formation, ameliorated dyslipidemia, attenuated inflammatory responses, and enhanced plaque stability in ApoE Cel exerts anti-atherosclerotic effects by activating macrophage autophagy via the AMPK/ULK1 pathway, thereby improving lipid metabolism, reducing inflammation, and stabilizing plaques. These findings highlight the therapeutic potential of Cel and provide new insights into autophagy-targeted strategies against AS. Show less
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from Show more
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from colorectal cancer (CRLM) remain poorly understood. Here we show that patients with CRLM whose liver metastases (LM) exhibited tumor fibrosis (Fibrosis+ LM) had significantly worse progression-free survival (P = 0.025) and overall survival (P = 0.008). Single-cell RNA sequencing revealed that the tumor microenvironment of the Fibrosis+ LM was characterized by T cells with an exhausted phenotype, macrophages displaying a profibrotic and suppressive phenotype and fibrosis-promoting fibroblasts. Further investigation highlighted the pivotal role of VCAN_eCAF in remodeling the tumor fibrosis in the tumor microenvironment of Fibrosis+ LM, emphasizing potential targetable interactions such as FGF23 or FGF3-FGFR1. Validation through multiplex immunohistochemistry/immunofluorescence and spatial transcriptomics supported these findings. Here we present a comprehensive single-cell atlas of tumor fibrosis in LM, revealing the intricate multicellular environment and molecular features associated with it. These insights deepen our understanding of tumor fibrosis mechanisms and inform improved clinical diagnosis and treatment strategies. Show less
The differential diagnosis between Tuberculosis (TB) and Non-tuberculous Mycobacteria (NTM) has historically been constrained by the inadequate sensitivity and specificity of current diagnostic method Show more
The differential diagnosis between Tuberculosis (TB) and Non-tuberculous Mycobacteria (NTM) has historically been constrained by the inadequate sensitivity and specificity of current diagnostic methods. Furthermore, distinguishing between Active Tuberculosis (ATB) and Latent Tuberculosis Infection (LTBI) poses significant challenges. This study aims to develop a molecular differentiation system for ATB, LTBI, and NTM by integrating plasma proteomics with multi-dimensional analytical techniques, while also exploring key biomarkers associated with disease progression and treatment response. Using label-free quantitative technology, we conducted a plasma proteomics analysis across five groups: ATB, LTBI, NTM, Cured Patients (CPs), and Healthy Donors (HD). Differentially Expressed Proteins (DEPs) were identified through screening (FC > 1.5 or <0.67, P < 0.05), followed by Gene Ontology/KEGG pathway enrichment, STRING interaction network, and Mfuzz dynamic clustering analysis to systematically elucidate molecular characteristics. Experimental data were validated through a multidimensional quality control system (Pearson correlation coefficient, peptide distribution, molecular weight distribution, etc.). Enzyme-linked immunosorbent assay (ELISA) was employed to detect the plasma expression levels of target proteins across the groups and to facilitate comparisons. This study identified 1,338 non-redundant proteins across five cohorts. Comparative analysis revealed 142 DEPs across the three comparative groups (ATB, LTBI, and NTM), which were primarily localized in the extracellular domain. Key findings include: 27 DEPs in the ATB-LTBI group, primarily enriched in inflammatory responses (such as A2M, IL-1R2) and epithelial barrier functions (TGM3, KRT3); 69 DEPs in the ATB-NTM group, characterized by significant changes in immunoglobulin light chains (IGLV2-11) and innate immune effector molecules (S100A8); 46 DEPs in the NTM-LTBI group, closely related to lipid metabolism (APOC3) and extracellular matrix remodeling (FN1). KEGG pathway analysis revealed that DEPs in the ATB-LTBI group were enriched in nitrogen metabolism pathways, those in the ATB-NTM group were associated with thyroid hormone synthesis, and the NTM-LTBI group was involved in phagosome function. Dynamic clustering results showed six treatment response modules: Cluster 1/2 (riboflavin metabolism, complement coagulation pathway) were activated post-treatment, Cluster 3/4 (proteasome, cardiac signaling pathway) exhibited partial reversal in expression, and Cluster 5/6 (platelet activation, cytoskeleton) showed delayed regression. Research confirmed 10 differential proteins between the ATB-CPs and ATB-HD groups, including S100A8, LTA4H, and DEFA1B, which constitute a molecular fingerprint specific to ATB. ELISA validation confirmed significantly elevated S100A8 and GPX3 in ATB group, while NTM group showed higher FGB and lower ATRN levels. This study systematically reveals the plasma proteomic characteristics under infection statuses caused by different mycobacteria. A discrimination framework for ATB/LTBI/NTM was constructed based on disease-specific differential proteins, overcoming the limitations of traditional diagnostic techniques in distinguishing infection states. Through dynamic analysis of six temporal therapeutic modules, the reprogramming patterns of the host protein network during tuberculosis treatment were elucidated. This research lays a multidimensional molecular foundation for the precise typing, personalized treatment, and prognostic evaluation of mycobacterial infections. Show less
A meta-analysis was conducted to assess the effects of citric acid (CA) on silage fermentation, and then used whole-plant cassava silage as a model to explore the underlying microbiological mechanisms Show more
A meta-analysis was conducted to assess the effects of citric acid (CA) on silage fermentation, and then used whole-plant cassava silage as a model to explore the underlying microbiological mechanisms with metagenomic and metabolomic data. The meta-analysis revealed that CA supplementation increased the dry matter, crude protein, water-soluble carbohydrate, and lactic acid contents in silage, but decreased the pH, dry matter loss, and the contents of fiber, NH Show less
Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent type of heart failure, but effective treatments are lacking. Cardiac lymphatics play a crucial role in maintaining Show more
Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent type of heart failure, but effective treatments are lacking. Cardiac lymphatics play a crucial role in maintaining heart health by draining fluids and immune cells. However, their involvement in HFpEF remains largely unexplored. We examined cardiac lymphatic alterations in mice with HFpEF with comorbid obesity and hypertension, and in heart tissues from patients with HFpEF. Using genetically engineered mouse models and various cellular and molecular techniques, we investigated the role of cardiac lymphatics in HFpEF and the underlying mechanisms. In mice with HFpEF, cardiac lymphatics displayed substantial structural and functional anomalies, including decreased lymphatic endothelial cell (LEC) density, vessel fragmentation, reduced branch connections, and impaired capacity to drain fluids and immune cells. LEC numbers and marker expression levels were also decreased in heart tissues from patients with HFpEF. Stimulating lymphangiogenesis with an adeno-associated virus expressing an engineered variant of vascular endothelial growth factor C (VEGFC Our study provides evidence that cardiac lymphatic disruption, driven by impaired BCAA catabolism in LECs, is a key factor contributing to HFpEF. These findings unravel the crucial role of BCAA catabolism in modulating lymphatic biology, and suggest that preserving cardiac lymphatic integrity may present a novel therapeutic strategy for HFpEF. Show less
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
Metastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of canc Show more
Metastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of cancer research. Fibroblast growth factor-inducible 14 (Fn14) has been shown to regulate wound repair, inflammation, angiogenesis, and chemoresistance, but its functional role in metastasis in EOC is still unknown. Here it is reported that Fn14 is identified as a cancer metastasis suppressor that inhibits the migratory and invasive potential of EOC cells by down-regulating epithelial-mesenchymal transition (EMT). Mechanistically, it is identified that Fn14 promotes acetylation-dependent protein degradation of Slug, a key transcriptional factor associated with EMT. The deacetylase Sirtuin 2 (SIRT2) has been reported to be involved in the deacetylation of Slug protein to stabilize it and then prevent its degradation in the nucleus. The results showed that Fn14 alters the subcellular localization of (SIRT2) by interacting with SIRT2, leading to reduced SIRT2 shuttling into the nucleus and subsequently promoting the acetylated degradation of Slug. Collectively, the work has demonstrated for the first time that Fn14 inhibits EOC metastasis by regulating SIRT2-mediated Slug deacetylation, providing a new perspective and method for the development of future novel therapeutic strategies for the treatment of EOC metastasis. Show less
Although the human cerebellum is known to be neuropathologically impaired in Alzheimer's disease (AD) and AD-related dementias (ADRD), the cell type-specific transcriptional and epigenomic changes tha Show more
Although the human cerebellum is known to be neuropathologically impaired in Alzheimer's disease (AD) and AD-related dementias (ADRD), the cell type-specific transcriptional and epigenomic changes that contribute to this pathology are not well understood. Here, we report single-nucleus multiome (snRNA-seq and snATAC-seq) analysis of 103,861 nuclei isolated from both cerebellum and frontal cortex of AD/ADRD patients and normal controls. Using peak-to-gene linkage analysis, we identified 431,834 significant linkages between gene expression and cell subtype-specific chromatin accessibility regions enriched for candidate cis-regulatory elements (cCREs). These cCREs were associated with AD/ADRD-specific transcriptomic changes and disease-related gene regulatory networks, especially for RAR Related Orphan Receptor A (RORA) and E74 Like ETS Transcription Factor 1 (ELF1) in cerebellar Purkinje cells and granule cells, respectively. Trajectory analysis of granule cell populations further identified disease-relevant transcription factors, such as RORA, and their regulatory targets. Finally, we pinpointed two likely causal genes, Seizure Related 6 Homolog Like 2 (SEZ6L2) in Purkinje cells and KAT8 Regulatory NSL Complex Subunit 1 (KANSL1) in granule cells, through integrative analysis of cCREs derived from snATAC-seq, genome-wide AD/ADRD loci, and three-dimensional (3D) genome data. Via CRISPRi experiments, we found that perturbation of rs4788201 and rs62056801 significantly inhibited the expression of their target genes, SEZ6L2 and KANSL1, in human iPSC-derived neurons. This cell subtype-specific regulatory landscape in the human cerebellum identified here offers novel genomic and epigenomic insights into the neuropathology and pathobiology of AD/ADRD and other neurological disorders if broadly applied. Show less
Neurodevelopmental disorders such as attention deficit and disruptive behaviour disorders (ADHD), autism spectrum disorder (ASD), and schizophrenia have been increasingly prevalent recently. Previous Show more
Neurodevelopmental disorders such as attention deficit and disruptive behaviour disorders (ADHD), autism spectrum disorder (ASD), and schizophrenia have been increasingly prevalent recently. Previous research has demonstrated that inflammatory activity from autoimmune diseases is involved in neurological diseases. However, some studies question the association between inflammatory activities and neurodevelopmental disorders. Herein, we attempt to clarify this relationship using Mendelian randomization (MR) analysis. We used systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 1 diabetes mellitus (T1D) to represent autoimmune diseases. First, we conducted MR analysis to examine associated SNPs between autoimmune and neurodevelopmental disorders. Second, we performed bidirectional MR analysis to identify 429 types of signalling peptides and proteins or relevant receptors with causality reported diseases. Finally, we compared the genes with the gene loci identified in the available TWAS-hub site. The MR results of autoimmune diseases on neurodevelopmental disorders did not present any significant association in all models. However, we identified 20-45 factors in ADHD, ASD, and schizophrenia, including semaphorin 3, IL-27 receptor subunit alpha, and fibroblast growth factor 16, which were considered clinically significant pro-inflammatory mediators. GO and KEGG enrichment analyses revealed unequal integrities among the three neurodevelopmental diseases, and we failed to identify a shared pathway linking autoimmune diseases and neurodevelopmental disorders. TWAS analysis indicated that CHRNA5 potentially mediates inflammatory activities in schizophrenia. According to our data, we failed to identify an association between autoimmune diseases and neurodevelopmental disorders. However, we demonstrated that some pro-inflammatory factors are involved in neurodevelopmental disorders. Show less
The primary aim of this study is to explore distinct patterns of post-traumatic growth (PTG) and fear of cancer progression (FOP) among breast cancer patients through latent profile analysis (LPA). Ad Show more
The primary aim of this study is to explore distinct patterns of post-traumatic growth (PTG) and fear of cancer progression (FOP) among breast cancer patients through latent profile analysis (LPA). Additionally, we assessed the differences in demographic and disease-related factors among breast cancer patients with varying patterns. Finally, we examined the influence of socio-demographic, disease-related, social support, anxiety, depression, and post-traumatic stress disorder (PTSD) factors on the varying patterns, aiming to assist healthcare providers in developing more effective psychological care strategies for breast cancer patients. A questionnaire survey was conducted on 752 breast cancer patients. Latent profile analysis was employed to explore the patterns of post-traumatic growth and fear of cancer progression in these patients, and multiple logistic regression analysis was used to identify the predictive factors for the different patterns. Based on the fit indices of latent class analysis, a three-class model was identified as the optimal solution, which included the Resisting group, Struggling group, and Growth group. In the Resisting group (24.33%), patients reported low levels of post-traumatic growth and high levels of fear of cancer progression; in the Struggling group (46.14%), patients exhibited moderate levels of post-traumatic growth and low levels of fear of cancer progression; in the Growth group (29.52%), patients demonstrated high levels of post-traumatic growth and moderate levels of fear of cancer progression. Additionally, the multiple logistic regression analysis reveals that marital status, place of residence, education level, disease stage, social support, anxiety, and post-traumatic stress disorder levels in breast cancer patients serve as significant factors influencing the distinct patterns of post-traumatic growth and fear of progression. This study suggests that there is heterogeneity in the PTG and FOP patterns in breast cancer patients. It provides a research basis for promoting the psychological recovery of breast cancer patients and highlights the importance of focusing on the positive effects of PTG while mitigating the negative impact of FOP. Healthcare providers can implement targeted nursing interventions based on the different patterns observed in breast cancer patients. Show less
The highly organized structures of the immunological synapse (IS) are crucial for T cell activation. PDZ domains might be involved in the formation of the IS by serving as docking sites for protein in Show more
The highly organized structures of the immunological synapse (IS) are crucial for T cell activation. PDZ domains might be involved in the formation of the IS by serving as docking sites for protein interactions. In this study, we investigate the role of the PALS1-associated tight junction protein (PATJ), which contains 10 PDZ domains, in the formation of IS and its subsequent impact on T cell activation. To elucidate the function of PATJ, we generated murine models with conditional T cell-specific knockout of We observed a rapid increase in PATJ expression during T cell activation. Conditional knockout of Our study reveals an important role of PATJ in the formation of IS and provides an approach to improve the efficacy of CAR-T therapy. Show less
SLC35B4, a nucleotide sugar transporter that mediates the transport of UDP-GlcNAc and UDP-xylose, was found to be required for the replication of influenza A virus (IAV) of the H5N1 subtype in our gen Show more
SLC35B4, a nucleotide sugar transporter that mediates the transport of UDP-GlcNAc and UDP-xylose, was found to be required for the replication of influenza A virus (IAV) of the H5N1 subtype in our genome-wide siRNA library screen. We found that defective IAV replication in SLC35B4-deficient A549 cells was independent of virus strain specificity, and the virulence of IAV in Slc35b4 knockdown mice was also decreased. By examining the individual stages of the IAV replication cycle, we discovered that the amount of internalized IAV was significantly reduced in SLC35B4-knockout A549 cells. Mechanistically, SLC35B4 facilitated IAV replication by transporting UDP-xylose, which attaches to the serine residue of heparan sulfate proteoglycans (HSPGs) in the heparan sulfate (HS) biosynthesis pathway. Knockdown of associated host factors (i.e., XYLT2, B4GALT7, EXT1, and EXT2) in the HS biosynthesis pathway also impaired IAV replication. Furthermore, we revealed that AGRN, a unique HSPG family member, was important for the endocytosis of IAV in A549 cells. Moreover, we found that the homeostasis of the AGRN protein was regulated by HS modification mediated by the initial UDP-xylose transporter SLC35B4, thereby affecting the expression level of endocytic adapter AP2B1 to influence IAV internalization. Collectively, these findings establish that SLC35B4 is an important regulator of IAV replication and uncover the underlying mechanisms by which SLC35B4 employs UDP-xylose transport activity to promote IAV internalization.IMPORTANCEThe entry process of IAV represents a favorable target for drug development. In this study, we identified SLC35B4 as an important host factor for the efficient replication of different subtypes of IAV Show less
The etiology of spontaneous abortion (SA) is complex, and the underlying mechanisms remain largely elusive. Environmental toxins have been implicated in the increased occurrence of SA. However, the as Show more
The etiology of spontaneous abortion (SA) is complex, and the underlying mechanisms remain largely elusive. Environmental toxins have been implicated in the increased occurrence of SA. However, the association between aminomethylphosphonic acid (AMPA) exposure and SA has not yet been established. We found that AMPA, along with the lactate were significantly elevated in villous tissues from SA patients compared to normal controls, with a robust positive correlation between AMPA and lactate concentrations. More importantly, AMPA exposure induced SA in C57BL/6 mice probably through the dysfunctions of human trophoblast cell. Further studies indicated that the L-lactate production which can be induced by AMPA via PPARγ/ANGPTL4 pathway caused similar defects of human trophoblast cells. A global elevation of protein lactylation has been detected in the villous tissues from SA patients as well as AMPA or lactate treated human trophoblast cells. Pan-Kla antibody coimmunoprecipitation coupled with mass spectrometry of AMPA or lactate treated human trophoblast cells revealed JunB, which was reduced in the placenta villus from SA patients and AMPA/lactate treated human trophoblast cells, could be lactylated at lysine (K) 36. JunB K36R mutation abolished JunB lactylation and ameliorated AMPA induced JunB loss via ubiquitination in human trophoblast cells. In comparison to wild type JunB, JunB K36R mutation had better protective roles in AMPA induced trophoblast dysfunctions. In conclusion, our results demonstrate that AMPA exposure promotes lactate production via the PPARγ/ANGPTL4 pathway, which subsequently inhibits the proliferation, migration and invasion of trophoblasts through JunB K38 lactylation, ultimately leading to SA. Show less
Deep brain stimulation (DBS) has emerged as a prospective treatment for psychiatric disorders; for example, DBS targeting the nucleus accumbens (NAc) abolishes addictive behaviors. However, neither th Show more
Deep brain stimulation (DBS) has emerged as a prospective treatment for psychiatric disorders; for example, DBS targeting the nucleus accumbens (NAc) abolishes addictive behaviors. However, neither the core pathway nor the cellular mechanisms underlying these therapeutic effects are known. Here, morphine-induced conditioned place preference (CPP) in mice as an addiction model and NAc-DBS combined with adeno-associated virus gene delivery for activity-dependent tagging, transgenic and chemogenetic manipulation of recruited neuronal networks are used. It is reported that a cortical-accumbal pathway and local fibroblast growth factor 1 (FGF1) signaling in the medial prefrontal cortex (mPFC) are critical for NAc-DBS to be effective in altering morphine CPP. It is shown that NAc-DBS retrogradely activates mPFC neurons projecting to the NAc, and chemogenetic activation/inhibition of these DBS-activated neuron ensembles in the mPFC reproduces the NAc-DBS effects on CPP. Sustained therapeutic effects accompany reductions in local FGF1 binding to fibroblast growth factor receptor 1 (FGFR1) in these neurons. Additionally, overexpressing FGF1 in the mPFC-NAc pathway abolishes the therapeutic effects of NAc-DBS. These results demonstrate that the mPFC-NAc pathway forms a top-down motif to regulate the therapeutic effects of subcortical DBS on addiction. These results support the potential for addiction treatments involving FGF1 signaling and highlight the mPFC as a target for noninvasive brain stimulation. Show less
Phenotypic switching of vascular smooth muscle cells (VSMCs) from a contractile toward a synthetic phenotype plays a critical role in atherosclerosis. Although the redox-sensitive sentrin/Small Ubiqui Show more
Phenotypic switching of vascular smooth muscle cells (VSMCs) from a contractile toward a synthetic phenotype plays a critical role in atherosclerosis. Although the redox-sensitive sentrin/Small Ubiquitin-like Modifier (SUMO)-specific protease 3 (SENP3), which preferentially deconjugates SUMO2/3, has been linked to oxidative stress, its role in atherosclerosis remains poorly defined. In this study, we demonstrate that SENP3 is significantly upregulated in human and mouse atherosclerotic lesions and in VSMCs exposed to pro-atherogenic stimuli. Using smooth muscle-specific Senp3 knockout mice (ApoE Show less
Nolan Priedigkeit, Beth Harrison, Robert Shue+27 more · 2025 · Clinical cancer research : an official journal of the American Association for Cancer Research · added 2026-04-24
Inflammatory breast cancer (IBC) is a rare and clinically distinct form of breast cancer associated with poor outcomes. The biological mechanisms driving IBC remain poorly understood, partly due to li Show more
Inflammatory breast cancer (IBC) is a rare and clinically distinct form of breast cancer associated with poor outcomes. The biological mechanisms driving IBC remain poorly understood, partly due to limited large-scale genomic studies that directly compare IBC with non-IBC cases. We conducted a retrospective analysis of 140 patients with IBC (68 primary tumors and 72 metastatic tumors) and 2,317 patients with non-IBC (700 primary tumors, 65 local recurrences, and 1,552 metastases). We compared clinicopathologic features, single-nucleotide variants, copy-number variants, tumor mutational burden, and exploratory survival outcomes between IBC and non-IBC tumors. The most frequent somatic alterations in IBC were detected in TP53 (72%), ERBB2 (32%), PIK3CA (24%), CCND1 (12%), MYC (9%), FGFR1 (8%), and GATA3 (8%). Multivariate logistic regression revealed a significant enrichment of TP53 single-nucleotide variants in IBC, particularly in HER2+ and hormone receptor-positive disease. Tumor mutational burden did not differ between IBC and non-IBC cases. In HER2+ disease, a pathway analysis revealed an enrichment of NOTCH pathway alterations. TP53, CCND1, and RB1 alterations were associated with poor outcomes in IBC. This study provides a comprehensive resource of somatic alterations in a large cohort of patients with metastatic IBC and non-IBC, highlighting genomic features associated with worse outcomes. Our findings reveal a significant enrichment of TP53 mutations, reinforcing its critical role in IBC pathogenesis. Few other distinct differences in IBC were observed, suggesting further investigations-beyond bulk sequencing of the somatic genome-are required to better understand the biology driving this aggressive disease. Show less
Metal-organic frameworks (MOFs) have been considered as ideal platforms to achieve long persistent luminescence (LPL), to utilize as optical recording devices, security systems and sensors. Despite th Show more
Metal-organic frameworks (MOFs) have been considered as ideal platforms to achieve long persistent luminescence (LPL), to utilize as optical recording devices, security systems and sensors. Despite the rapid emergence, it is still a challenge to develop single-component red LPL MOFs. In this work, two hetero-ligand MOFs are synthesized using a D-π-A-type ligand (source of red phosphorescence) and a monocyclic carboxylic ligand (appropriate void constructer), which show efficient red LPL after removal of wide excitations at ambient conditions. Experiment and calculation suggest that the effective red LPL originates from the D-π-A-type ligand, while the auxiliary carboxylic ligand mediates the orientation/arrangement of the D-π-A linker in MOFs affecting phosphorescence. The MOFs are further used in the field of multiple message encryption, initiating a new perspective for designing new red LPL MOFs. Show less
Yan Huang, Bo-Wen Yue, Yue-Qin Hu+5 more · 2025 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mec Show more
Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mechanisms of saponins from Panax japonicus(SPJ) on anxiety disorder in mice fed a high-fat diet(HFD). Fifty C57BL/6J mice were randomly divided into normal control diet(NCD) group, HFD group, and low-and high-dose SPJ groups. At week 12, six mice from the HFD group were further divided into a control group(treated with DMSO) and an exogenous fibroblast growth factor 21(FGF21) group(administered rFGF21). The anxiety-like behavior of the mice was assessed using the open field test and elevated plus maze test. Hematoxylin-eosin(HE) staining and oil red O staining were performed to observe pathological changes in the liver and adipose tissue. Glucose metabolism was evaluated through the glucose tolerance test(GTT) and insulin tolerance test(ITT). Western blot analysis was performed to detect the expression of FGF21 and its downstream-related proteins in the liver and cortex, along with the expression of brain-derived neurotrophic factor(BDNF), disks large homolog 4(DLG4), and synaptophysin(SYP) in the cortex. Real-time quantitative fluorescent PCR(qPCR) was used to detect the expression of FGF21 and its receptor genes in the liver and cortex. Immunofluorescence staining was employed to examine the expression of neuronal activator c-Fos, FGF21, and the FGF21 co-receptor β-klotho in the cerebral cortex. The results showed that SPJ significantly improved the frequency of activity in the open arms of the elevated plus maze and the central area of the open field in HFD mice, up-regulated the expression of BDNF, DLG4, and SYP, and effectively alleviated anxiety-like behaviors in HFD mice. Compared with the NCD group, HFD mice exhibited up-regulated expression of FGF21 in the liver and cerebral cortex, while the expression of fibroblast growth factor receptor 1(FGFR1) and β-klotho was significantly down-regulated, suggesting that HFD mice exhibited FGF21 resistance. SPJ markedly up-regulated the β-klotho levels in HFD mice, reversing FGF21 resistance. Further comparison with exogenously administered FGF21 revealed that SPJ activates brain cortical regions in a consistent manner, and additionally, SPJ promotes the number and colocalization of c-Fos and β-klotho positive cells in the brain cortex. In summary, SPJ effectively alleviates anxiety-like behaviors in HFD mice. Its mechanism is associated with up-regulation of β-klotho expression in the brain, reversal of FGF21 resistance, and subsequent activation of neurons in the cerebral cortex and amygdala. Show less