Neovascular age-related macular degeneration (nAMD) is an advanced stage of AMD and is associated with an increased risk of visual impairment. Disturbances in lipid metabolism have been proposed as a Show more
Neovascular age-related macular degeneration (nAMD) is an advanced stage of AMD and is associated with an increased risk of visual impairment. Disturbances in lipid metabolism have been proposed as a major contributing factor to the pathogenesis of AMD. This study aims to investigate whether lipid profiles in the serum and components of dyslipidemia can be used as indicators for predicting progression to nAMD. A retrospective analysis was conducted involving 125 participants with nAMD. 125 non-AMD controls, matched by age, sex, and BMI, were incorporated into the study. The comparative analysis between the groups involved six lipid biomarkers in the serum: HDL-C, LDL-C TG, TC, ApoA1, and ApoB. Moreover, the existence of dyslipidemia and its constituents was assessed through t-tests, as well as univariate and multivariable logistic regression models. Individuals with nAMD exhibited significantly higher serum HDL-C (P = 0.02) compared to the controls without AMD. Furthermore, the concentrations of ApoB were significantly less in the nAMD cohort (P < 0.01) when compared to the control group. During the investigation of the correlation between levels of serum HDL-C (P < 0.01) and serum ApoB (P < 0.01) with nAMD through logistic regression analysis, notable findings indicated a significant association between both variables and nAMD. However, by multivariate logistic regression analysis, neither serum HDL-C nor serum ApoB was an independent risk factor for nAMD. While individuals with nAMD demonstrated elevated serum HDL-C and reduced serum ApoB levels, these lipid markers may not be suitable as biomarkers for monitoring or preventing nAMD. Show less
This study investigates the heterogeneity in kindergarten teachers' perceptions of organizational climate and its impact on job burnout. Guided by the AGIL model from social systems theory and the Job Show more
This study investigates the heterogeneity in kindergarten teachers' perceptions of organizational climate and its impact on job burnout. Guided by the AGIL model from social systems theory and the Job Demands-Resources (JD-R) model, it addresses the need to move beyond variable-centered approaches to understand how distinct climate profiles are associated with teacher well-being. A person-centered latent profile analysis (LPA) was employed. A sample of 1,008 kindergarten teachers from China completed measures assessing organizational climate and burnout. The analysis aimed to identify distinct climate profiles and examine their relationships with demographic variables (kindergarten type, assessment level, teaching experience) and the three dimensions of burnout (emotional exhaustion, depersonalization, reduced personal accomplishment). The LPA revealed five distinct organizational climate profiles: Controlled, Moderate, Indifferent, Positive, and Authoritative. Profile membership was significantly predicted by kindergarten assessment level and teachers' years of experience, but not by kindergarten type. Crucially, the profiles differed significantly across all burnout dimensions. Teachers in Positive climates reported the lowest burnout levels, whereas those in Controlled and Indifferent climates experienced the highest. The findings underscore the structural diversity of organizational climates in early childhood settings and their profound psychological consequences. This study validates the application of social systems theory and the JD-R model in this context, revealing how different configurations of job demands and resources shape teacher well-being. The results provide a theoretical lens for understanding educational organizations and offer practical implications for developing tailored, climate-specific intervention strategies to mitigate burnout and support sustainable professional development. Show less
To explore the molecular mechanisms underlying clozapine-induced metabolic syndrome (MetS) in schizophrenia patients, providing scientific evidence for clinicians to prevent and manage metabolic syndr Show more
To explore the molecular mechanisms underlying clozapine-induced metabolic syndrome (MetS) in schizophrenia patients, providing scientific evidence for clinicians to prevent and manage metabolic syndrome during the treatment of psychiatric disorders. Ten schizophrenia patients with MetS and ten matched controls were recruited from Shanghai Mental Health Center according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for schizophrenia and the 2016 Chinese Adult Dyslipidemia Prevention and Treatment Guidelines for MetS. Peripheral blood RNA sequencing was performed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were used to pinpoint hub genes. Mendelian randomization (MR) was conducted to validate causal relationship between serum brain-derived neurotrophic factor (BDNF) levels and MetS components. A total of 1019 DEGs were identified, grouped into eight mRNA modules through WGCNA. Key hub genes included Significant differences in gene expression are observed between schizophrenia patients with and without MetS. Individual variability in clozapine-induced MetS may be linked to DEGs. Show less
Colorectal cancer (CRC) is a leading cause of cancer mortality while diabetes is a recognized risk factor for CRC. Here we report that tirzepatide (TZP), a novel polypeptide/glucagon-like peptide 1 re Show more
Colorectal cancer (CRC) is a leading cause of cancer mortality while diabetes is a recognized risk factor for CRC. Here we report that tirzepatide (TZP), a novel polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist for the treatment of diabetes, has a role in attenuating CRC growth. TZP significantly inhibited colon cancer cell proliferation promoted apoptosis in vitro and induced durable tumor regression in vivo under hyperglycemic and nonhyperglycemic conditions across multiple murine cancer models. As glucose metabolism is known to critically regulate colon cancer progression, spatial metabolomics results revealed that glucose metabolites are robustly reduced in the colon cancer regions of the TZP-treated mice. TZP inhibited glucose uptake and destabilized hypoxia-inducible factor-1 alpha (HIF-1α) with reduced expression and activity of the rate-limiting enzymes 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) and phosphofructokinase 1 (PFK-1). These effects contributed to the downregulation of glycolysis and the tricarboxylic acid (TCA) cycle. TZP also delayed tumor development in a patient-derived xenograft (PDX) mouse model accompanied by HIF-1α mediated PFKFB3-PFK-1 inhibition. Therefore, the study provides strong evidence that glycolysis-blocking TZP, besides its application in treating type 2 diabetes, has the potential for preclinical studies as a therapy for colorectal cancer used either as monotherapy or in combination with other anticancer therapies. Show less
G-patch domain-containing protein 2 (GPATCH2), a member of the G-patch domain-containing family, has been implicated in tumor cell growth, but the link between GPATCH2 and hepatocellular carcinoma (HC Show more
G-patch domain-containing protein 2 (GPATCH2), a member of the G-patch domain-containing family, has been implicated in tumor cell growth, but the link between GPATCH2 and hepatocellular carcinoma (HCC) remains uncertain. In the current study, comprehensive bioinformatics analysis revealed that GPATCH2 was markedly upregulated in HCC and positively correlated with aggressive clinicopathological features, including histologic grade, AFP, albumin level, and adjacent hepatic tissue inflammation, as well as miserable outcomes in HCC. GPATCH2 also has certain diagnostic value for HCC, histologic grade, and 1-, 3-, and 5-year survival outcomes. Functionally, loss-of-function experiments disclosed that silencing GPATCH2 suppressed HCC cell proliferation, migration, invasion, and xenograft tumor growth in the subcutaneous mouse model. Silencing GPATCH2 also resulted in an increase in the expression level of CDH1, while causing a decrease in the expression levels of FN1, TWIST1, SNAI1, and SNAI2. Rescue experiments further confirmed SNAI2 as a critical downstream effector mediating GPATCH2-driven oncogenic activity in HCC. Mechanistically, GPATCH2 was uncovered to be transcriptionally activated by the transcription factor Yin Yang 1 (YY1), and can mediate the role of YY1 in promoting HCC progression and elevating SNAI2 expression. Taken together, GPATCH2 is a YY1-regulated oncogenic driver that promotes HCC advancement through SNAI2, highlighting its potential as a diagnostic, prognostic, and therapeutic target for HCC. Show less
Fatty liver hemorrhage syndrome (FLHS) is the most common metabolic diseases in laying hens during the late-laying period, and it causes a significant economic burden on the poultry industry. The comp Show more
Fatty liver hemorrhage syndrome (FLHS) is the most common metabolic diseases in laying hens during the late-laying period, and it causes a significant economic burden on the poultry industry. The competing endogenous RNA plays crucial roles in the occurrence and development of fatty liver. Based on the previously constructed lncRNA-miRNA-mRNA networks, we selected the axis of ENSGALT00000079786-LPL-miR-143-5p for further study to elucidate its mechanistic role in development of fatty liver. In this study, we identified a novel highly conserved lncRNA (ENSGALT00000079786) in poultry, which we designated as lncRNA A2ml2 based on its chromosomal location. Fluorescent in situ hybridization (FISH) revealed that lncRNA A2ml2 was localized in both the nucleus and cytoplasm. Dual-luciferase reporter assay validated the targeted relationship between lncRNA A2ml2, miR-143-5p, and the LPL gene. To further analyze the lncRNA A2ml2 and miR-143-5p function, lncRNA A2ml2 overexpression vector was successfully constructed and transfected into Leghorn male hepatocellular (LMH) cells, which could remarkably inhibit cellular lipid deposition was detected by oil red staining (P < 0.01), the opposite occurred for miR-143-5p (P < 0.01). qPCR demonstrated an inverse correlation between miR-143-5p expression and lncRNA A2ml2 expression, and confirmed that miR-143-5p directly target lncRNA A2ml2. Similarly, we found an inverse correlation between expression of LPL and the expression of miR-143-5p. To further investigate the interactions among these three factors and their effects on cellular lipid metabolism, we assessed the expression levels of LPL by co-transfecting lncRNA A2ml2 with miR-143-5p mimic and miR-143-5p mimic binding site mutants. Co-transfection experiments showed that miR-143-5p diminished the promoting effect of lncRNA A2ml2 on LPL. Meanwhile, miR-143-5p has the capacity to mitigate the suppressive impact of lncRNA A2ml2 overexpression on lipid accumulation in LMH cells. The results revealed that lncRNA A2ml2 attenuated hepatic lipid accumulation through negatively regulating miR-143-5p and enhancing LPL expression in LMH cells. Our findings offer novel insights into ceRNA-mediated in FLHS and identify a novel lncRNA as a potential molecular biomarker. 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
Yifei Dou, Ying Li, Meng Zhang · 2025 · Wei sheng yan jiu = Journal of hygiene research · added 2026-04-24
To explore the latent classes and their associated factors of sleep quality among police officers, and to analyze the potential heterogeneity in sleep quality within this population. A total of 1162 p Show more
To explore the latent classes and their associated factors of sleep quality among police officers, and to analyze the potential heterogeneity in sleep quality within this population. A total of 1162 police officers were selected using cluster random sampling in the Inner Mongolia Autonomous Region between September and December 2021. Participants completed a basic information questionnaire and the Pittsburgh sleep quality index(PSQI). Latent profile analysis(LPA) was employed to examine heterogeneity in sleep quality, and multinomial Logistic regression was used to identify associated factors of the latent profiles. The mean age of participants was(43.08±8.98) years. The sample comprised 920 males(79.2%) and 242 females(20.8%), 987(84.9%) were married and 175(15.1%) were single, 644(55.4%) had a high school education or below, and 518(44.6%) had college education or above. By department, 607(52.2%) worked in grassroots police stations, 200(17.2%) were criminal police, and 355(30.6%) served in other units. Significant heterogeneity in sleep quality was identified, revealing four distinct latent classes: good sleep group(n=821, 70.6%), moderate sleep group(n=46, 4.0%), sleep-disordered group(n=249, 21.4%), and medication-assisted sleep group(n=46, 4.0%). Using the good sleepers as the reference group, multinomial Logistic regression indicated that older age was a significant risk factor for belonging to the medication-assisted sleep group(OR=1.348, 95%CI 1.078-1.822). Higher education level was a protective factor against membership in the moderate sleep group(OR=4.101, 95%CI 1.304-12.893). Serving as a grassroots police station officer or criminal police officer was a significant risk factor for membership in both the moderate sleep group(OR = 3.329, 95%CI 1.338-8.284; OR=4.188, 95%CI 1.415-12.396) and sleep-disordered group(OR=1.701, 95%CI 1.196-2.420; OR=1.587, 95%CI 1.073-2.533). Sleep quality among police officers demonstrates significant heterogeneity. Age, police department assignment, and educational level are key associated factors of distinct latent classes of sleep quality. Show less
no PDFDOI: 10.19813/j.cnki.weishengyanjiu.2025.05.015
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
Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) is a neuronal system-specific transmembrane protein that is highly expressed in the brains o Show more
Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) is a neuronal system-specific transmembrane protein that is highly expressed in the brains of patients with Alzheimer's disease (AD), and our previous findings showed that LINGO-1 antagonism can improve cognitive function and protect hippocampal GABAergic interneurons in AD model mice. However, the specific mechanism underlying these effects is not clear. In this study, an adeno-associated virus (AAV) was used to directly interfere with hippocampal LINGO-1 in vivo, and LINGO-1 antagonists, cannabinoid type 1 receptor (CB1R) agonists, and CB1R antagonists were used to treat mouse hippocampal neurons (HT22 neurons) in vitro. We found that overexpressing hippocampal LINGO-1 in normal young mice impaired spatial learning and memory and reduced hippocampal CB1R protein levels, whereas silencing hippocampal LINGO-1 in AD model mice had the opposite effect. Additionally, antagonizing LINGO-1 increased CB1R/tyrosine kinase receptor B (TrkB) signalling and rescued CB1R- rich cholecystokinin-GABAergic (CCK-GABAergic) interneurons in HT22 neurons transduced with an APP/PS1-expressing virus. Competitive inhibition of LINGO-1 and CB1R was observed, and antagonizing LINGO-1 reversed the changes in HT22 neurons caused by the inhibition of CB1R, such as the decreases in the protein levels of doublecortin (DCX), TrkB, and phosphorylated TrkB (p-TrkB). These findings provide an important scientific basis for further exploration of the mechanism by which LINGO-1 regulates cognitive function and hippocampal GABAergic interneurons in AD model mice. Show less
Posttranslational modification (PTM) of the amyloid precursor protein (APP) plays a critical role in Alzheimer's disease (AD). Recent evidence reveals that lactylation modification, as a novel PTM, is Show more
Posttranslational modification (PTM) of the amyloid precursor protein (APP) plays a critical role in Alzheimer's disease (AD). Recent evidence reveals that lactylation modification, as a novel PTM, is implicated in the occurrence and development of AD. However, whether and how APP lactylation contributes to both the pathogenesis and cognitive function in AD remains unknown. Here, we observed a reduction in APP lactylation in AD patients and AD model mice and cells. Proteomic mass spectrometry analysis further identified lysine 612 (APP-K612la) as a crucial site for APP lactylation, influencing APP amyloidogenic processing. A lactyl-mimicking mutant (APPK612T) reduced amyloid-β peptide (Aβ) generation and slowed down cognitive deficits in vivo. Mechanistically, APPK612T appeared to facilitate APP trafficking and metabolism. However, lactylated APP entering the endosome inhibited its binding to BACE1, suppressing subsequent cleavage. Instead, it promoted protein interaction between APP and CD2-associated protein (CD2AP), thereby accelerating the endosomal-lysosomal degradation pathway of APP. In the APP23/PS45 double-transgenic mouse model of AD, APP-Kla was susceptible to L-lactate regulation, which reduced Aβ pathology and repaired spatial learning and memory deficits. Thus, these findings suggest that targeting APP lactylation may be a promising therapeutic strategy for AD in humans. Show less
Homologous recombination repair (HRR) is crucial for maintaining genomic stability by repairing DNA damage. Despite its importance, HRR's role in cancer progression is not fully elucidated. Here, this Show more
Homologous recombination repair (HRR) is crucial for maintaining genomic stability by repairing DNA damage. Despite its importance, HRR's role in cancer progression is not fully elucidated. Here, this work shows that nuclear-localized branched-chain α-ketoacid dehydrogenase kinase (BCKDK) acts as a modulator of HRR, promoting cell resistance against DNA damage-inducing therapy in breast cancer. Mechanistically, this work demonstrates that BCKDK is localized in the nucleus and phosphorylates RNF8 at Ser157, preventing the ubiquitin-mediated degradation of RAD51, thereby facilitating HRR-mediated DNA repair under replication stress. Notably, aberrant expression of the BCKDK/p-RNF8/RAD51 axis correlates with breast cancer progression and poor patient survival. Furthermore, this work identifies a small molecule inhibitor of BCKDK, GSK180736A, that disrupts its HRR function and exhibits strong tumor suppression when combined with DNA damage-inducing drugs. Collectively, this study reveals a new role of BCKDK in regulating HRR, independent of its metabolic function, presenting it as a potential therapeutic target and predictive biomarker in breast cancer. Show less
At present, studies on tadpole nutrition and metabolism are scarce. This study aimed at comparing the influence of two protein sources, fishmeal (FM) and dried whole egg powder (DWEP), on tadpoles fro Show more
At present, studies on tadpole nutrition and metabolism are scarce. This study aimed at comparing the influence of two protein sources, fishmeal (FM) and dried whole egg powder (DWEP), on tadpoles from the perspective of growth, the metamorphosis rate, lipid metabolism, antioxidant properties and the intestinal flora. In this experiment, the control diet was set to contain no FM or DWEP. Based on the control diet, 5% and 10% FM or DWEP were included, respectively. The results of the experiment indicated that FM or DWEP inclusion significantly enhanced the growth performance and metamorphosis rate ( Show less
R-loop is a common chromatin feature consisting of a displaced single-stranded DNA and an RNA-DNA hybrid, and dysregulation of R-loop surveillance results in genomic and transcriptomic instability. Al Show more
R-loop is a common chromatin feature consisting of a displaced single-stranded DNA and an RNA-DNA hybrid, and dysregulation of R-loop surveillance results in genomic and transcriptomic instability. Although the RNA moiety of most R-loops originates from linear transcripts, circular RNAs (circRNAs), outputs from back-splicing, can also hybridize with the complementary strand of a DNA duplex. However, how circRNA-associated R-loops (ciR-loops) are monitored remains elusive. Here, we identify the DEAD-box RNA helicase Brr2 as an evolutionarily-conserved ciR-loop repressor with dual roles in inhibiting circRNA generation and resolving harmful ciR-loops. Accumulation of ciR-loops caused by loss-of-function of this dual-action factor induces antisense transcription and premature transcription termination for many genes and generates significant DNA damage, which further leads to a series of defects in DNA replication, cell division and cell proliferation. We propose that functional integration of multilayered regulation by a single protein can be an efficient double protection against genome instability. 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
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
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, with current therapies offering only limited symptomatic relief and lacking disease-modifying ef Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, with current therapies offering only limited symptomatic relief and lacking disease-modifying efficacy. Addressing this critical therapeutic gap, natural multi-target compounds like mulberroside A (MsA)-a bioactive glycoside from Show less
Excessive inflammation is a capital cause of scar formation and inflammation microenvironment that result in challenge of axonal regeneration after spinal cord injury (SCI). Macrophages and astrocytes Show more
Excessive inflammation is a capital cause of scar formation and inflammation microenvironment that result in challenge of axonal regeneration after spinal cord injury (SCI). Macrophages and astrocytes play important roles in the inflammatory response. Tip cells, a critical endothelial sub-population, play pivotal roles in post-injury vascular regeneration. Nevertheless, their characteristics in SCI remain poorly documented. This study based on single cell RNA sequencing (scRNA-seq) and in vitro experiment, investigates the effects of tip cells on astrocytes and macrophages. For astrocytes, tip cells can recruit astrocytes to migrant, contribute to the formation of fence-like structure of astrocytes, finally inhibit the diffusion of inflammation via the Angptl4-Sdc4 ligand-receptor pathway. For macrophages, similarly through the Angptl4-Sdc4 ligand-receptor pathway, tip cells can promote macrophages to polarize more toward the M2 phenotype and inhibit their polarization toward M1 phenotype, thus alleviate the inflammatory response. Tip cells after SCI exhibit conserved ribosomal protein expression, implicating ribosome-dependent signaling in their function. These finding highlight the critical role of tip cells in microenvironment after SCI, offering a potential treatment target for SCI. Show less
Acute rejection (AR) is a significant complication in liver transplantation, impacting graft function and patient survival. Kupffer cells (KCs), liver-specific macrophages, can polarize into pro-infla Show more
Acute rejection (AR) is a significant complication in liver transplantation, impacting graft function and patient survival. Kupffer cells (KCs), liver-specific macrophages, can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes, both of which critically influence AR outcomes. Angiopoietin-like 4 (ANGPTL4), a secretory protein, is recognized for its function in regulating inflammation and macrophage polarization. This study investigates the effects of ANGPTL4 on KC polarization through cellular interactions between hepatocytes (HCs) and KCs. Using a rat orthotopic liver transplantation model, we observed reduced ANGPTL4 expression during AR, whereas increased ANGPTL4 levels were linked to immune tolerance. Administration of ANGPTL4 recombinant protein improved liver function, suppressed inflammation, and promoted M2 polarization of KCs. Co-culture experiments demonstrated that hepatocyte-derived ANGPTL4 significantly modulates KC polarization and inflammatory responses, mainly by inhibiting the NF-κB signaling pathway. The results emphasize the promise of ANGPTL4 as a therapeutic target to reduce AR and improve liver transplant outcomes by influencing hepatocyte-KC interactions. Show less
Zinc finger protein 750 (ZNF750) has been identified as a potential tumor suppressor across multiple malignancies. Nevertheless, the specific involvement of ZNF750 in the regulation of mesenchymal cel Show more
Zinc finger protein 750 (ZNF750) has been identified as a potential tumor suppressor across multiple malignancies. Nevertheless, the specific involvement of ZNF750 in the regulation of mesenchymal cell differentiation and bone homeostasis has yet to be elucidated. In the current study, we observed a substantial presence of ZNF750 in bone tissue and noted alterations in its expression during osteogenic differentiation of mesenchymal progenitor cells. Functional experiments indicated that ZNF750 promoted osteogenic differentiation while impeding adipogenic differentiation from mesenchymal stem/progenitor cells. Further mechanistic investigations revealed that ZNF750 transcriptionally suppressed the expression of Snail family transcriptional repressor 1 (SNAI1) by binding to the proximal promoter region of Snai1 gene, thereby activating Wnt/β-catenin signaling. SNAI1 exerted opposing effects on cell differentiation towards osteoblasts and adipocytes in comparison to ZNF750. The overexpression of SNAI1 counteracted the dysregulated osteogenic and adipogenic differentiation induced by ZNF750. Furthermore, the transplantation of Znf750-silenced bone marrow stromal cells into the marrow of wild-type mice resulted in a reduction in cancellous and cortical bone mass, alongside a decrease in osteoblasts and an increase in marrow adipocytes, while the number of osteoclasts remained unchanged. This study presents the first demonstration that ZNF750 regulates the differentiation of osteoblasts and adipocytes from mesenchymal stem/progenitor cells by transcriptionally deactivating SNAI1 signaling, thereby contributing to the maintenance of bone homeostasis. It suggests that ZNF750 may represent a promising therapeutic target for metabolic bone disorders such as osteoporosis. 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
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contr Show more
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contributing to stroke remains poorly understood. This study aims to investigate the association between the apoB/apoA1 ratio and intracranial or extracranial atherosclerosis. We enrolled 408 patients with acute ischemic stroke who had never been treated with statins or fibrates. Based on the images from computed tomography angiography (CTA), the patients were categorized into four groups: intracranial atherosclerosis stenosis (ICAS, n = 136), extracranial carotid atherosclerosis stenosis (ECAS, n = 45), combined intracranial and extracranial atherosclerosis stenosis (COAS, n = 73), and non-cerebral atherosclerosis stenosis (NCAS, n = 154). Demographic characteristics, clinical factors, and serum lipid levels were collected and then compared across groups. The apoB/apoA1 ratio was significantly higher in patients with ICAS, ECAS and COAS compared to those in the NCAS group. Multivariable logistic regression analysis demonstrated that the ApoB/ApoA1 ratio was independently associated with ICAS, but not with ECAS. ROC curve analysis showed that the ApoB/ApoA1 ratio had a good diagnostic ability for ICAS, with an area under the curve (AUC) of 0.764, an optimal cut-off value of 0.8122, a sensitivity of 81.3%, and a specificity of 59.8%. An higher apoB/apoA1 ratio is associated with ICAS in ischemic stroke patients. Show less
Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccha Show more
Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccharides (EPS) could modulate the gut microbiota structure and function to prevent and treat MAFLD. Herein, a novel EPS designated BVP1 was isolated from Bacillus velezensis CGMCC 24752. Structural analysis revealed that BVP1 is a neutral α-mannan consisting of a backbone of 1,2,6-linked α-D-Manp, with branches composed of T-linked α-D-Manp, 1,2-linked α-D-Manp, and 1,3-linked α-D-Manp. Animal experiments showed that BVP1 significantly alleviated hepatic steatosis, liver injury and inflammation, and enhanced antioxidant activity in MAFLD mice. Single-nucleus RNA sequencing analysis revealed that BVP1 could restore HFD-induced imbalances in liver sinusoidal endothelial cells, hepatic stellate cells, macrophages and Kupffer cells by upregulating the expression of the lipid degradation gene Cps1 and downregulating the expression of the lipid synthesis gene Acsl1 in these cell subpopulations. Interestingly, BVP1 reshaped the gut microbiota and fecal metabolite profile by enriching beneficial bacteria and associated metabolites including salicylic acid, spermidine, and 4-hydroxyphenyl acetate. Fecal microbiota transplantation experiments verified that the anti-MAFLD effects are mediated by the BVP1-modified gut microbiota. Our findings highlight the potential of BVP1 as a promising therapeutic agent for MAFLD treatment. 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
Neuromyelitis optica spectrum disorder (NMOSD) is a group of immune-mediated disorders that often lead to severe disability. The diagnosis and monitoring of NMOSD can be challenging, particularly in s Show more
Neuromyelitis optica spectrum disorder (NMOSD) is a group of immune-mediated disorders that often lead to severe disability. The diagnosis and monitoring of NMOSD can be challenging, particularly in seronegative cases, highlighting the need for reliable biomarkers to enhance clinical management. This study aimed to identify serum lipid biomarkers for the diagnosis and monitoring of NMOSD and to assess their potential to improve clinical decision-making. We conducted a comprehensive serum proteomic analysis in a discovery cohort of NMOSD patients and controls to identify lipid-related proteins associated with NMOSD. Subsequently, we validated the candidate biomarkers in the retrospective cohort and developed diagnostic models using a random forest algorithm. The association between these lipid biomarkers and disease activity was further evaluated in longitudinal analysis. Our analysis identified a panel of serum lipid-related biomarkers that demonstrated significant differences between NMOSD patients and controls. The diagnostic models achieved the impressive accuracy of 72% for the full NMOSD spectrum, 72% for AQP4-IgG+ NMOSD, and 68% for double seronegative NMOSD. Importantly, these biomarkers showed a correlation with disease activity, with levels changing from relapse to remission. Additionally, a combination of these lipid biomarkers was found to predict relapse with the AUC of 0.861. A user-friendly smartphone application was developed to facilitate the straightforward "input-index, output-answer" screening process, enhancing both clinical decision-making and patient care. The diagnostic model based on the serum lipid-related indexes (TC, TG, LDL, HDL, ApoA1, and ApoB) may be the useful tool for NMOSD in diagnosis and monitoring of disease stage, thereby improving the treatment outcome for patients. Future studies should focus on integrating these biomarkers into routine clinical practice to realize their full potential in enhancing NMOSD management. Show less
Hongqin Li, Rong Xu, Liquan Xie+3 more · 2025 · Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · SAGE Publications · added 2026-04-24
Bushen Huoxue Acupuncture shows potential in treating neurodegenerative diseases, but its mechanisms remain incompletely understood. Using the senescence-accelerated mouse-prone 8 (SAMP8) mouse model, Show more
Bushen Huoxue Acupuncture shows potential in treating neurodegenerative diseases, but its mechanisms remain incompletely understood. Using the senescence-accelerated mouse-prone 8 (SAMP8) mouse model, we assessed cognitive function via the Morris water maze test, hippocampal neuronal apoptosis with terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and microglial activation through immunohistochemistry. Serum levels of inflammatory cytokines [tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6] were quantified by enzyme-linked immunosorbent assay. The expression of SIRT2 pathway-related proteins, along with Aβ deposition, was analyzed using Western blotting, immunohistochemistry, and immunofluorescence. The results demonstrated that Bushen Huoxue Acupuncture improved cognitive function in SAMP8 mice, reducing hippocampal neuronal apoptosis and decreasing serum levels of pro-inflammatory cytokines. Additionally, it reduced the levels of Aβ42, a more aggregation-prone and toxic Aβ subtype, in both hippocampal tissues and serum, as well as the number of CD68-positive cells in hippocampal tissues, suggesting the inhibition of amyloid pathology and neuroinflammatory. The treatment also downregulated SIRT2, BACE1, and APP-CTF while increasing RTN4B expression. Notably, Bushen Huoxue Acupuncture outperformed non-acupoint acupuncture in enhancing cognitive function and reducing inflammation. Our findings indicate that Bushen Huoxue Acupuncture alleviates cognitive deficits and neuroinflammation by suppressing the SIRT2-mediated RTN4B/BACE1 pathway, highlighting acupuncture as a promising therapy for neurodegenerative diseases. Show less
To investigate the causal relationship between various lipid-modifying drugs and new-onset diabetes, as well as the mediators contributing to this relationship. Mediation Mendelian randomization was p Show more
To investigate the causal relationship between various lipid-modifying drugs and new-onset diabetes, as well as the mediators contributing to this relationship. Mediation Mendelian randomization was performed to investigate the causal effect of lipid-modifying drug targets on type 2 diabetes (T2D) outcomes and the proportion of this association that is mediated through ectopic fat accumulation traits. Specific sets of variants in or near genes that encode 11 lipid-modifying drug targets (LDLR, HMGCR, NPC1L1, PCSK9, APOB, ABCG5/ABCG8, LPL, PPARA, ANGPTL3, APOC3, and CETP; for expansion of gene symbols, use search tool at www.genenames.org) were extracted. Random effects inverse variance weighted were performed to evaluate the causal effects among outcomes. Mediation analyses were performed to identify the mediators of the association between lipid-modifying drugs and T2D. The study was conducted from November 10, 2023, to April 2, 2024 RESULTS: The genetic mimicry of HMGCR and APOB inhibition was associated with an increased T2D risk, whereas the genetic mimicry of LPL enhancement was linked to a lower T2D risk. Gluteofemoral adipose tissue volume was a mediator for explaining 9.52% (P=.002), 16.90% (P=.03), and 10.50% (P=.003) of the total effect of HMGCR, APOB, and LPL on T2D susceptibility, respectively. Liver fat was a mediator for explaining 21.12% (P=.005), 12.28% (P=.03), and 9.84% (P=.005) of the total effect of HMGCR, APOB, and LPL on T2D susceptibility, respectively. Our findings support the hypothesis that liver fat and gluteofemoral adipose tissue play a mediating role in the prodiabetic effects of HMGCR and APOB inhibition, as well as in the antidiabetic effects of LPL enhancement. Show less
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregn Show more
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregnancy women and 317 healthy non-pregnant women. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and hypersensitive C-reactive protein (hs-CRP) were measured in both groups. The mean and standard deviation of each index were calculated to establish the reference range of normal serum lipid levels in pregnant women in mid-to-late pregnancy. The associations between serum lipid levels and perinatal outcomes were assessed statistically. There were no significant differences in age, pregnancy, or parity between the adverse outcome and normal delivery groups, but the caesarean section rate was significantly higher in the adverse outcome group. The levels of hs-CRP, TG, TC, HDL-C, LDL-C, and ApoA1 were significantly higher in the adverse outcome group. Elevated hs-CRP, TG, and HDL-C levels were risk factors for adverse pregnancy outcomes. According to the receiver operating characteristic curve, the optimal threshold of the combined diagnosis of these three indicators to predict adverse pregnancy outcomes was 0.534, and the area under the curve was 0.822. The establishment of lipid reference intervals in the second and third trimesters of pregnancy can effectively evaluate lipid metabolism in pregnant women, and the measurement of lipid metabolism in pregnant women is helpful in predicting adverse pregnancy outcomes. Show less