Kidney Yang Deficiency (KYD) is a metabolic disorder associated with kidney damage. Its slow progression means that causative factors and effective therapeutic agents remain unclear. Extensive evidenc Show more
Kidney Yang Deficiency (KYD) is a metabolic disorder associated with kidney damage. Its slow progression means that causative factors and effective therapeutic agents remain unclear. Extensive evidence links KYD to gut microbiome metabolic diseases and the Hypothalamic-Pituitary-Thyroid (HPT) axis. CDG was extracted from both raw and processed CD and analyzed via HPLC. Propylthiouracil-induced KYD rats were used to assess pharmacological effects, including serum levels of T Fecal non-targeted metabolomics identified 98 metabolites associated with KYD, while 16S rRNA sequencing revealed 13 key intestinal microbiotas linked to KYD. CDG therapy effectively alleviated KYD symptoms by modulating the gut microbiota, improving metabolic and microbial imbalances in KYD. RG/WG significantly improves KYD rats mainly through the relationship between the intestinal microbiota and arachidonic acid metabolism. The key bacterial genera This integrative approach of gut microbiome and fecal metabolomics not only provides a scientific basis for CDG's preventive effects on KYD via the HPT axis but also elucidates the potential mechanisms underlying CDG's action against KYD. Show less
This study aimed to investigate the association between objectively and subjectively measured 24-hour movement behaviors and physical fitness, and explore how the reallocation of time between 24-hour Show more
This study aimed to investigate the association between objectively and subjectively measured 24-hour movement behaviors and physical fitness, and explore how the reallocation of time between 24-hour movement behaviors is associated with changes in physical fitness in adolescents. A total of 690 adolescents aged 14-17 years (55% girls) were included in this cross-sectional study conducted in Foshan, China. Moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior, and sleep were assessed using accelerometers in combination with a questionnaire. Physical fitness was tested through body mass index, forced vital capacity, 50-m sprint, standing long jump, sit-and-reach, gender-specific 800/1000-m run, and pull-ups/sit-ups. MVPA was significantly associated with better performance in the 50-m sprint ( Show less
Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition. Traditional genetic testing is typically conducted on the proband only, with family members undergoing Sanger sequencing, which Show more
Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition. Traditional genetic testing is typically conducted on the proband only, with family members undergoing Sanger sequencing, which may overlook other pathogenic variants. This study explores the gene sequencing strategy in a three-generation family based on genetic carrier status and examines the relationship between phenotypic characteristics and genotype. High-throughput second-generation sequencing was performed on the proband to analyze HCM-related pathogenic genes. Subsequently, the identified pathogenic variants were validated by Sanger sequencing in the proband and family members. Clinical, electrocardiographic, and echocardiographic assessments were conducted for family members. Second-generation sequencing of the proband (III7) revealed a pathogenic variant MYBPC3-P453Lfs. Initially, no HCM-related pathogenic variants were detected in another patient (III11), prompting additional sequencing of III11, which identified the MYH7-G823E pathogenic variant. Both patients had severe left ventricular outflow tract obstruction. Sanger sequencing showed that five family members carried both mutations. Among them, three died suddenly before age 40, one required an implantable cardioverter defibrillator for arrhythmias, and one developed HCM before adulthood. Cardiac magnetic resonance imaging (MRI) of patients carrying both mutations showed myocardial fibrosis of 32.75%, significantly higher than the 6.98% observed in patients carrying only one mutation. In families with varying HCM phenotypes, second-generation sequencing should be considered for all members. In this family, carrying one variant led to outflow tract obstruction, while carrying both variants resulted in severe disease, including sudden death and early onset. Cardiac MRI is crucial for assessing the severity of the disease within the family. Show less
Our aim was to explore the IL-27 effect in sepsis (SP)-related acute hepatic injury (AHI) as well as its possible mechanism. Herein, we utilized both wild-type (WT) and IL-27 receptor (WSX-1)-deficien Show more
Our aim was to explore the IL-27 effect in sepsis (SP)-related acute hepatic injury (AHI) as well as its possible mechanism. Herein, we utilized both wild-type (WT) and IL-27 receptor (WSX-1)-deficient (IL-27R The results revealed that IL-27 exacerbated systemic inflammation and liver damage in AHI mice by promoting M1 macrophage polarization, thereby increasing pro-inflammatory phenotype macrophages (M1). This further exacerbated the inflammatory response and pyroptosis in vivo and in vitro. Additionally, IL-27 down-regulated p-AMPK and SIRT1 protein expression while overexpressing macrophage inflammatory mediators including IL-1β/6 and TNFα. Furthermore, IL-27 promoted increased RAGE and caspase-11 protein expression, aggravating macrophage pyroptosis. Employing CC to block the AMPK pathway further aggravated M1 macrophage polarization and pyroptosis in vitro and in vivo, ultimately worsening liver injury. Here, IL-27 aggravates AHI by promoting macrophage M1 polarization to induce caspase-11-mediated pyroptosis in vitro and in vivo, which may be linked to the AMPK/SIRT1 signaling pathway. Show less
Peritoneal metastasis (PM) in gastric cancer (GC) remains a formidable clinical challenge. Although exosomes are critical mediators of tumor-microenvironment communication, their mechanistic role in l Show more
Peritoneal metastasis (PM) in gastric cancer (GC) remains a formidable clinical challenge. Although exosomes are critical mediators of tumor-microenvironment communication, their mechanistic role in linking mesothelial-mesenchymal transition (MMT) to peritoneal dissemination remains poorly understood. This study elucidates a GC-derived exosomal microRNA (miRNA)-driven pathway that orchestrates peritoneal metastasis. Integrated exosomal miRNA sequencing and The Cancer Genome Atlas (TCGA) analysis identified miR-196a-5p as highly enriched in GC-derived exosomes. Functional assays, including in vitro co-culture experiments, and in vivo PM models, demonstrated that GC-derived exosomal miR-196a-5p directly induces MMT in peritoneal mesothelial cells (HMrSV5) and contributed to the formation of metastatic tumors. Mechanistically, miR-196a-5p binds the 3'-untranslated region (UTR) of F-box protein 45 (FBXO45), an E3 ubiquitin ligase, suppressing its expression and thereby stabilizing snail family transcriptional repressor 1 (Snai1)-a key transcription factor in epithelial-mesenchymal transition (EMT). RNA immunoprecipitation sequencing (RIP seq), dual-luciferase reporter assays, co-immunoprecipitation (CO-IP), and rescue experiments validated the miR-196a-5p/FBXO45/Snai1 axis. Notably, miR-196a-5p disrupts FBXO45-mediated Snai1 ubiquitination and degradation, promoting MMT-driven peritoneal niche remodeling and metastatic progression. These findings reveal a novel exosome-mediated mechanism underlying GC dissemination and highlight miR-196a-5p and FBXO45 as promising therapeutic targets for PM. Show less
The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive v Show more
The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive virtual screening protocol that combines energy-based screening and machine learning techniques, leading to the identification of a novel compound, Show less
Remote ischemic preconditioning (rIPC) has been reported to protect against kidney ischemia-reperfusion injury (IRI) through the delivery of extracellular vesicles (EVs). Among these, apoptosis-induce Show more
Remote ischemic preconditioning (rIPC) has been reported to protect against kidney ischemia-reperfusion injury (IRI) through the delivery of extracellular vesicles (EVs). Among these, apoptosis-induced compensatory proliferation signaling-related vesicles (ACPSVs) can transmit proliferation signals to surrounding cells. However, the underlying mechanisms remain unclear. This study aimed to investigate the role of ACPSVs in renal IRI following rIPC and to elucidate the associated mechanisms. We demonstrated that rIPC plasma or ACPSVs alleviated renal damage and inflammation, with the protective effects abolished upon the removal of ACPSVs from the plasma. EVs isolated via differential centrifugation exhibited defining characteristics of ACPSVs. Co-culture experiments revealed that ACPSVs reduced apoptosis and enhanced the viability of HK-2 cells under hypoxia/reoxygenation (H/R) conditions. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted the critical role of macrophage migration inhibitory factor (MIF) protein in ACPSVs. Using CRISPR/Cas9 technology, we generated MIF-knockout HeLa cells to induce the production of MIF-deficient ACPSVs. The protective effects of ACPSVs were significantly attenuated when MIF was knocked out. Transcriptome sequencing and chromatin immunoprecipitation (ChIP) assays revealed that MIF suppresses dual-specificity phosphatase 6 (DUSP6) expression by promoting H3K9 trimethylation (H3K9me3) in the DUSP6 promoter region, thereby activating the JNK signaling pathway. In rescue experiments, treatment with the DUSP6 inhibitor BCI effectively restored the protective function of MIF-deficient ACPSVs. This study underscores the protective role of ACPSVs derived from rIPC-treated rats and serum-starved cells against renal IRI through the MIF/DUSP6/JNK signaling axis, offering a potential clinical therapeutic strategy for acute kidney injury induced by IRI. [Image: see text] The online version contains supplementary material available at 10.1186/s12951-025-03505-9. Show less
Pulmonary embolism is a potentially fatal cardiovascular condition that demands prompt and accurate diagnostic imaging. Traditional single-energy computed tomography pulmonary angiography (CTPA), whil Show more
Pulmonary embolism is a potentially fatal cardiovascular condition that demands prompt and accurate diagnostic imaging. Traditional single-energy computed tomography pulmonary angiography (CTPA), while widely used, is associated with high radiation doses and substantial volumes of contrast agents, which may increase the risks of radiation-induced tissue damage and contrast-induced nephropathy (CIN), respectively. Dual-energy CTPA (DE-CTPA) presents a promising alternative, though challenges, including elevated image noise at low kilo-electron volt (keV) levels (e.g., 40 keV), persist. The primary aim of this study is to evaluate and compare the image quality of 40 keV virtual monoenergetic images (VMI) reconstructed using deep learning image reconstruction (DLIR) and Adaptive Statistical Iterative Reconstruction-V (ASIR-V) algorithms within the context of low-dose DE-CTPA protocols. This prospective study enrolled patients who underwent DE-CTPA between January and April 2025. Using a Revolution CT scanner, 40 keV VMI were reconstructed with four distinct algorithms: ASIR-V 50%, ASIR-V 70%, Deep learning image reconstruction with medium setting (DLIR-M), and deep learning image reconstruction with high setting (DLIR-H). Iodixanol (350 mgI/mL) was administered at a dose of 0.4 mL/kg. The image quality was assessed through both objective measures [image noise, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR)] and subjective evaluation via a Likert scale. Statistical analysis was conducted using SPSS 27.0, employing analysis of variance (ANOVA) for normally distributed data and the Kruskal-Wallis test for non-normally distributed data. A total of 75 patients with clinical suspicion of pulmonary embolism were included in the study. The mean effective dose (ED) was 3.76±1.02 mSv, with a mean CT volume dose index (CTDIvol) of 6.13±1.69 mGy and a mean dose-length product (DLP) of 221.12±59.85 mGy·cm. The mean contrast agent volume was 26.0±5.0 mL. Statistical analysis of image quality revealed significant differences between the four groups in terms of image noise, CNR, and SNR, measured at the levels of the main pulmonary artery, left pulmonary artery, and right pulmonary artery (P<0.001). Post-hoc analysis demonstrated that the DLIR-H algorithm provided the highest image quality, significantly reducing noise while enhancing CNR and SNR relative to both ASIR-V and DLIR-M (P<0.001). Compared with ASIR-V 50%, DLIR-H reduced image noise by 45% at the PA [24.25±16.18 The DLIR-H algorithm significantly enhances the image quality of 40 keV VMI images under low-dose DE-CTPA scanning protocols. It outperforms DLIR-M, ASIR-V 50%, and ASIR-V 70%, making it a promising tool for improving image quality in CTPA, particularly in clinical settings where minimizing radiation dose and contrast agent volume is essential. Show less
Meng Xiong, Renjie Luo, Zhijiao Zhang+4 more · 2025 · Inflammation research : official journal of the European Histamine Research Society ... [et al.] · Springer · added 2026-04-24
Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulate Show more
Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulated by macrophages. This study aimed to elucidate the effect of Recombinant Mouse IL-27 Protein on macrophage ferroptosis and polarization, as well as its impact on sepsis-induced ARDS. A cecal ligation and puncture (CLP)-induced sepsis model was established using wild-type (WT) or IL27R In vitro, IL-27 alone did not alter the expression of proteins linked to the ferroptosis pathway or macrophage polarization. Contrastingly, the combination of IL-27 with LPS further amplified LPS-induced alterations in the ferroptosis pathway, thereby promoting macrophage M1 polarization and inhibiting M2 polarization. Additionally, IL-27 + LPS increased ROS levels in macrophages. A sepsis-induced ARDS mouse model was then established via CLP. In vivo, IL-27 exacerbated CLP-induced lung injury in WT mice. Additionally, it decreased the expression levels of ferroptosis-related proteins (Nrf2, HO-1, GPX4) and increased those of Ptgs2 in the lung tissue of septic mice. Besides, GSH and SOD levels in lung tissue were also reduced. Moreover, IL-27 also promoted M1 polarization and inhibited M2 polarization in macrophages. In IL27R Oltipraz may alleviate ARDS-related lung injury by up-regulating Nrf2 expression and concurrently inhibiting macrophage ferroptosis. Show less
The embryos of lotus (Nelumbo nucifera Gaertn.) is a famous traditional Chinese medicine used to treat insomnia, memory decline, and dementia for a long time. However, the underlying material basis an Show more
The embryos of lotus (Nelumbo nucifera Gaertn.) is a famous traditional Chinese medicine used to treat insomnia, memory decline, and dementia for a long time. However, the underlying material basis and mechanisms of this medicine are still unclear. Isoliensinine (IL) is a major alkaloid derived from lotus embryos. Our previous research has demonstrated that IL can exert strong anti-inflammatory and neuroprotective effects in vitro. To reveal the underlying therapeutic effect and mechanism of IL on Alzheimer's disease (AD)-like mice induced by AlCl The AD-like mice were modeled by intragastric injection (i.g.) of AlCl IL (1, 3, and 10 mg/kg) treatment effectively ameliorated cognitive impairment in AD-like model mice. IL inhibited the decrease of brain index and body weight in AD-like mice and alleviated neuronal damage in the cortex and hippocampus (DG, CA1, and CA3). IL decreased the levels of Ca IL has a significant therapeutic effect on pathological alterations and cognitive impairment in AlCl Show less
Dysregulation of the fibroblast growth factor receptor 1 (FGFR1) signaling has prompted efforts to develop therapeutic agents, which is a carcinogenic driver of many cancers, including breast, prostat Show more
Dysregulation of the fibroblast growth factor receptor 1 (FGFR1) signaling has prompted efforts to develop therapeutic agents, which is a carcinogenic driver of many cancers, including breast, prostate, bladder, and chronic myeloid leukemia. Despite significant progress in the development of potent and selective FGFR inhibitors, the long-term efficacy of these drugs in cancer therapy has been hampered by the rapid onset of acquired resistance. Therefore, more drug discovery strategies are needed to promote the development of FGFR-targeted drugs. Here, we discovered compound S2h, a compound that selectively and effectively degrades FGFR1 at nanomolar concentrations in KG1a cells (IC Show less
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data fr Show more
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10 Show less
Depression is a pervasive mental illness that has a significant impact on public health globally. This study aimed to identify risk factors for depression and elucidate their causal relationships. Usi Show more
Depression is a pervasive mental illness that has a significant impact on public health globally. This study aimed to identify risk factors for depression and elucidate their causal relationships. Using data from the National Health and Nutrition Examination Survey (NHANES) and Genome-Wide Association Studies (GWAS). Serum ApoB was log-transformed and further divided into 4 groups. Multifactorial logistic regression analysis was used to assess the relationship between serum ApoB and depression. Subgroup analyses and interaction tests were used to observe the stability of the association between them. Smooth curve fitting was used to investigate nonlinear correlations. The causal effect of serum ApoB on depression was assessed using Mendelian randomization (MR) analysis. A total of 6531 participated in the study. After adjusting for all covariates, serum ApoB levels were positively associated with depression after adjustment for all covariates (OR = 1.40, 95 % CI = 1.06-1.84; P = 0.0176). Unfortunately, there was no significant causal relationship between serum ApoB and depression (OR = 0.9985,95 % CI = 0.9962-1.0008; P = 0.1923). Sensitivity analysis verified the reliability of the results. Serum ApoB was positively associated with an increased risk of depression, but MR analysis did not show a genetic causal relationship between ApoB and depression. Based on the results of the current study, no indication maintaining high levels of ApoB contributes to the management of depression. The main limitation of this study is the inconsistency of the cross-sectional study and the MR population. Show less
Oxidative deterioration of fish oil in aquafeeds poses a significant challenge to fish health and aquaculture sustainability, making it crucial to mitigate this issue through healthy and green nutriti Show more
Oxidative deterioration of fish oil in aquafeeds poses a significant challenge to fish health and aquaculture sustainability, making it crucial to mitigate this issue through healthy and green nutritional strategies. This study examined the potential of stevia chlorogenic acid (SCGA), a bioactive byproduct of stevia processing, to alleviate intestinal injury, gut microbiota dysbiosis, and lipid metabolism disorders induced by oxidized fish oil in turbot. Four diets with equal nitrogen and lipid contents were formulated: a control diet (PC) containing 5 % fresh fish oil, an oxidized fish oil diet (OFO) comprising 5 % oxidized fish oil, and two additional OFO diets supplemented with 200 mg/kg (OFO200) or 400 mg/kg (OFO400) of SCGA. Each dietary treatment was randomly assigned to three replicates, each containing 40 fish weighing approximately 16.99 ± 0.01 g, and administered over a 10-week period. Fish fed the OFO diet exhibited significantly compromised growth performance, as indicated by decreased WGR and SGR, along with reduced serum immune indices (IgM, C3, and C4) and lipid parameters (TC, HDL, LDL), and elevated serum D-LA levels (P < 0.05). Moreover, dietary OFO markedly suppressed antioxidant enzyme activities (serum SOD; intestinal SOD, GSH-Px, and CAT) and elevated MDA concentrations (P < 0.05). Additionally, OFO reduced intestinal expression of tight junction-associated genes (Claudin-4, Claudin-7, Occludin) while increasing expression levels of MLCK, Keap1, inflammatory mediators (IL-6, IL-1β, TNF-α2, NF-κB, IFN-γ), and Caspase7 (P < 0.05). Notably, the TLR signaling pathway-related genes were upregulated, accompanied by pronounced shifts in gut microbiota composition (P < 0.05). In hepatic tissue, lipogenesis-associated genes (FAS, ACC) were significantly increased, while key genes involved in lipid transport and β-oxidation (CD36, LPL, ACOX1, PPARγ) exhibited reduced expression (P < 0.05). Dietary supplementation with 200 and 400 mg/kg SCGA effectively mitigated these detrimental impacts. SCGA restored growth performance, serum immune parameters, and antioxidant enzyme activities to levels comparable to the PC group. It also normalized gene expression related to intestinal barrier function, inflammation, apoptosis, and hepatic lipid metabolism. Furthermore, SCGA supplementation modulated gut microbiota structure by increasing beneficial genera and decreasing potential pathogens. In conclusion, SCGA effectively improves growth performance, alleviates OFO-induced intestinal injury and microbial dysbiosis, and regulates lipid metabolism in turbot. These findings provide theoretical insights and technical support for the application of SCGA in aquaculture. Show less
As one of the most common malignant tumors in men, prostate cancer (PCa) still lacks convenient, non-invasive and highly specific diagnostic markers. The advantages of Extracellular vesicle (EV) DNA i Show more
As one of the most common malignant tumors in men, prostate cancer (PCa) still lacks convenient, non-invasive and highly specific diagnostic markers. The advantages of Extracellular vesicle (EV) DNA in tumor diagnosis have gradually attracted the attention of researchers. However, methylation detection, which is more advantageous than mutation detection in tumor diagnosis, has not been widely practiced in EV DNA, and its value in PCa diagnosis also remains underexplored. This study aims to establish and optimize an EV DNA methylation detection system and evaluate its diagnostic and classification potential for PCa. We characterized EV DNA biological properties, optimized pretreatment strategies, validated its correlation with genomic DNA methylation, and explored urine EV DNA methylation targets in 86 benign prostatic hyperplasia (BPH) and 109 PCa patients across three cohorts (screening: 30 BPH/33 PCa; training: 27 BPH/30 PCa; validation: 29 BPH/46 PCa). Heterogeneous biological characteristics were observed among DNA from different subtypes of EV, but methylation profiles remained consistent across subtypes and post-DNase I treatment. EV DNA accurately reflected the methylation state of source cell genomic DNA. By combining our screening results with data from the TCGA database and previously reported, we developed a panel consisting of 667 PCa-specific methylation targets for detection. Among these, six methylation sites (MACF1、LINC01359-1、LINC01359-2、ADCY4、GAPLINC、C19orf25) demonstrated high diagnostic value for PCa, enabling construction of PCa and aggressive PCa differential diagnosis model with AUCs up to 0.74 and 0.91 respectively. The diagnostic value of these six markers was further confirmed using methylight PCR in the validation cohort which also displayed promising performance as a tool for diagnosing PCa. This study highlights the potential of urine EV DNA methylation as a novel diagnostic marker for PCa and lays a foundation for future EV DNA research. Show less
Ankylosing spondylitis (AS) is a chronic and progressive inflammatory arthritis involving disorders of both the immune and skeletal systems. Multiple osteochondromas (MO) is a rare skeletal disorder w Show more
Ankylosing spondylitis (AS) is a chronic and progressive inflammatory arthritis involving disorders of both the immune and skeletal systems. Multiple osteochondromas (MO) is a rare skeletal disorder with a variety of clinical manifestations characterized by multiple benign exostoses. Here, we investigate a Chinese family with HLA-B27-negative AS complicated with MO. Whole-exome sequencing (WES) and Sanger sequencing were used to screen and identify the pathogenic gene. In vitro functional analysis was performed, and a pathogenesis-associated interleukin (IL)-17 receptor C (IL17RC) mutation was analyzed to investigate its effect on phenotypes. WES was used to identify a known missense mutation, NM₀₀₀₁₂₇.3:c.1019 G > A(p.Arg340His), in the pathogenic gene EXT1 that is causal for MO. Moreover, a missense mutation, NM₁₅₃₄₆₁.3:c.1067 C > T(p.Thr356Met), in the IL17RC gene was identified as potentially responsible for AS or spondyloarthritis symptoms in this family. In vitro over-expression of mutant IL17RC decreased its expression and increased the expression of IL17RA, consistent with the expression of these two genes in patients. Mechanistically, mutant IL17RC enhanced the activation of the NF-κB pathway. This study increases our understanding of the pathogenesis and progression of these diseases. Our findings broaden the risk factors in non-HLA-B genes associated with the NF-κB pathway in AS. Show less
Lung adenocarcinoma (LUAD) is one of the leading causes of death worldwide, and thus, more biomarker and therapeutic targets need to be explored. Herein, we aimed to explore new biomarkers of LUAD by Show more
Lung adenocarcinoma (LUAD) is one of the leading causes of death worldwide, and thus, more biomarker and therapeutic targets need to be explored. Herein, we aimed to explore new biomarkers of LUAD by integrating bioinformatics analysis with cell experiments. We firstly identified 266 druggable genes that were significantly differentially expressed between LUAD tissues and adjacent normal lung tissues. Among these genes, SMR analysis with Show less
Breast cancer (BRCA) is a prevalent malignant tumor among women, and the use of anesthetic drugs during surgical resection may influence tumor biology and patient prognosis. This study aimed to identi Show more
Breast cancer (BRCA) is a prevalent malignant tumor among women, and the use of anesthetic drugs during surgical resection may influence tumor biology and patient prognosis. This study aimed to identify prognostic biomarkers associated with dexmedetomidine and dezocine (DD) in BRCA patients. Through Mendelian Randomization analysis, we screened four DD targets that had a causal relationship with BRCA. Subsequently, utilizing TCGA-BRCA data, univariate and Lasso Cox analyses revealed two significant prognostic biomarkers (NR1H3 and ADRB1) associated with BRCA patient prognosis, leading to the successful construction and validation of a prognostic risk model. Kaplan-Meier survival curves indicated that patients with higher NR1H3 and ADRB1 expression had longer overall survival (OS). Immunoinfiltration analysis showed that high-risk group patients exhibited increased infiltration levels of CD56 bright natural killer cells, CD56 dim natural killer cells, eosinophils, and plasmacytoid dendritic cells. Conversely, activated B cells and immature B cells demonstrated greater infiltration in the low-risk group. Correlation analysis revealed significant associations between prognostic biomarkers and various immune cells, including CD56 bright natural killer cells, CD56 dim natural killer cells, and activated CD8 T cells. NR1H3 was highly positively correlated with immune checkpoints such as TIGIT, PDCD1, CD274, CTLA4, LAG3, and HAVCR2 (|cor|≥0.3, The online version contains supplementary material available at 10.1007/s12672-025-03694-7. Show less
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to u Show more
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to unravel causal associations between 2,940 circulating proteins and 19 CVD. We found 218 proteins that impacted risk of one or more CVDs through forward MR (106 and 182 using cis-pQTLs only and cis- + trans-pQTLs, respectively), among which 107 were previously reported as associated with CVD or CVD-related traits. There were 102 proteins replicated (FDR < 5%, 53 with cis-pQTLs only and 88 with cis- + trans-pQTLs) using the FinnGen Olink data. BTN3A2 was highlighted as a novel candidate gene for ischemic stroke, suggesting a crosstalk between immune modulation and stroke pathogenesis. Single cell integration prioritized PAM for stable angina pectoris and ventricular arrhythmia and LPL for peripheral artery disease, whose transcriptional expressions were enriched in cardiomyocytes. Forward and reverse MR found largely non-overlapping proteins (only 2 overlapped: LGALS4 and MMP12), suggesting distinct proteomic causes and consequences of CVD. Our study provides human genetics-based evidence of novel candidate genes, a foundational step towards full-scale causal human biology-based drug discovery for CVD. Show less
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
Lung squamous cell carcinoma (LUSC) is a highly aggressive malignancy with limited targeted therapies and poor clinical outcomes. Ferroptosis, an iron-dependent form of regulated cell death, plays a c Show more
Lung squamous cell carcinoma (LUSC) is a highly aggressive malignancy with limited targeted therapies and poor clinical outcomes. Ferroptosis, an iron-dependent form of regulated cell death, plays a crucial role in tumor progression, metabolic reprogramming, and immune modulation. Increasing evidence suggests that dysregulation of ferroptosis contributes to therapeutic resistance and immune escape in various cancers. MYO19, a mitochondrial trafficking protein, has recently been implicated in oxidative stress and metabolic control, but its role in ferroptosis and tumor immunity remains unclear. Meanwhile, microRNAs (miRNAs) are recognized as key post-transcriptional regulators in cancer biology. Among them, hsa-miR-520a-3p has been reported to exhibit tumor-suppressive functions in several malignancies. However, the interplay between hsa-miR-520a-3p and MYO19, and their potential involvement in ferroptosis regulation and immune modulation in LUSC, has not been systematically investigated. Data were collected from TCGA, UCSC XENA, ENCORI, HPA, and UALCAN public database. Differential expression, prognostic, correlation analyses and miRNA analyses were performed using bioinformatics tools including TIMER, TISIDB, Kaplan-Meier Plotter, and ENCORI. Ferroptosis-related analysis utilized Ze-Xian Liu's dataset. Functional assays, including CCK-8 viability, Transwell migration, and MDA/GSH measurements, were performed in NCI-H226 and NCI-H2170 cells after transfection with miR-520a-3p mimics/inhibitors or MYO19 knockdown/overexpression constructs. Ferroptosis sensitivity was further tested under RSL3 treatment, and ferroptosis protein markers as well as rescue experiments were analyzed by Western blotting. The result revealed that MYO19 was significantly upregulated in multiple tumor types and correlated with unfavorable prognosis. Especially in LUSC, elevated MYO19 expression was associated with advanced stage, reduced immune infiltration, and enrichment of ferroptosis-resistant transcriptional programs, whereas hsa-miR-520a-3p showed opposite patterns. Overexpression of hsa-miR-520a-3p in NCI-H226 and NCI-H2170 cells increased lipid peroxidation (MDA increased), reduced intracellular GSH, and enhanced RSL3-induced cytotoxicity, indicative of ferroptosis activation. Conversely, MYO19 knockdown elevated ACSL4 and reduced SLC7A11, changes that were partially reversed by MYO19 re-expression. These findings suggest that the hsa-miR-520a-3p/MYO19 axis is associated with ferroptosis susceptibility and may influence the immunosuppressive tumor microenvironment. Show less
To optimize livestock production of integrated farms, dietary crude fat levels are often increased, making efficient fat utilization crucial. Bile acids are known to improve fat utilization, but their Show more
To optimize livestock production of integrated farms, dietary crude fat levels are often increased, making efficient fat utilization crucial. Bile acids are known to improve fat utilization, but their impact on growth performance and breast muscle development in Zhijiang ducks remains unclear. In this study, a total of 360 twenty-day-old Zhijiang ducks with similar body weights were divided into three groups: the control group (CN) received a basal diet; the high-fat group (FA) received the basal diet plus 1.25 % rapeseed oil; and the high-fat plus bile acids compound (BA) group (FB) received the FA diet supplemented with 250 mg/kg BA for 30 days. Results indicated that the addition of rapeseed oil and BA significantly increased (P < 0.05) average daily gain (ADG) and reduced (P < 0.05) feed conversion ratio (FCR). Slaughter data showed that BA significantly enhanced (P < 0.05) breast muscle weight and percentage while decreasing (P < 0.05) abdominal fat weight. Additionally, BA increased (P < 0.05) the cross-sectional area of breast muscle fibers, total bile acid content, and levels of insulin-like growth factors 1/2 (IGF1/2). Transcriptomic analysis further revealed that BA significantly upregulated (P < 0.05) the levels of PPARα, CPT1α, NR1H4, and CETP in breast muscle. 16S rRNA analysis showed a significant increase (P < 0.05) in the relative abundances of genera Enorma, [Eubacterium nodatum group], Rikenellaceae RC9 gut group, and SP3-e08. Additionally, the Spearman correlation suggested a positive correlation between the genera Olsenella, SP3-e08, Enorma, Rikenellaceae_RC9_gut_group, and [Eubacterium_nodatum_group] with PPARα, CETP, NR1H4, and CPT1α. In contrast, the genera Christensenellaceae_R₇_group and Sutterella exhibited negative correlations with PPARα. These findings provide new insights into the role of BA in promoting growth performance and skeletal muscle development in Zhijiang ducks fed a high-fat diet, with this effect potentially linked to changes in the gut microbiota. Show less
The microtubule actin crosslinking factor 1 ( Trios-based whole-exome sequencing was performed on a cohort with generalised epilepsy from the China Epilepsy Gene 1.0 project. The spatial-temporal expr Show more
The microtubule actin crosslinking factor 1 ( Trios-based whole-exome sequencing was performed on a cohort with generalised epilepsy from the China Epilepsy Gene 1.0 project. The spatial-temporal expression, single-cell sequencing and genotype-phenotype correlation were analysed to explore the role of Two de novo heterozygous and eight biallelic Show less
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined r Show more
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined receptor signals, and assessed their regulatory capacities and specificities through in silico analysis of ligand-receptor interactions. Consequently, we identified a B cell subset that expressed cytokine interleukin-27 (IL-27) and chemokine CXCL10. Through the IL-27-IL-27 receptor interaction, these IL-27/CXCL10-producing B cells targeted CD40-activated B cells in vitro and, upon induction by immunization and viral infection, optimized antibody responses and antiviral immunity in vivo. Also present in breast cancer tumors and retained there through CXCL10-CXCR3 interaction-mediated self-targeting, these cells promoted B cell PD-L1 expression and immune evasion. Mechanistically, Show less
Does preconception mental health status in either partner affect fertility and infertility, and is this association modified by socioeconomic status (SES)? Preconception mental health problems in both Show more
Does preconception mental health status in either partner affect fertility and infertility, and is this association modified by socioeconomic status (SES)? Preconception mental health problems in both partners are associated with lower couple fertility, with the synergistic impact being most pronounced among couples with low SES status. Mental health problems are rising among young adults, and fertility rates are declining. Women's preconception mental health has been linked to lower fertility, but few studies have examined the combined impact of both partners' mental health. The modifying role of SES in these associations is also poorly understood. This couple-based prospective cohort study included 966 preconception couples who sought preconception care and were followed for 12 months in the Shanghai Birth Cohort between 2013 and 2015. The couples' mental health status was evaluated at enrolment using the Center for Epidemiological Studies-Depression Scale, Zung Self-Rating Anxiety Scale, and Perceived Stress Scale. The outcomes included couple fecundability (measured by the TTP) and infertility (i.e. TTP >12 menstrual cycles). In the partner-specific model, Cox proportional hazards models and logistic regression were used to evaluate the associations between each partner's depression, anxiety, and stress levels and couples' fertility. In the couple-based model, cross-classification and quantile g-computation were first applied to identify couples' joint exposure to specific psychological conditions in relation to fertility. Latent profile analysis (LPA) was then conducted to characterize distinct latent profiles of couples' overall mental health statuses, followed by Cox proportional hazards models and logistic regression to examine the corresponding associations. Key symptoms in the couples' depression, anxiety, and stress scales were determined by elastic net regression and least absolute shrinkage and selection operator. To assess the potential effect modification of SES on the association between couples' mental health and fertility, we conducted stratified analyses by male and female partner education levels and household income. In the female partner-specific model, a 1 SD increase in depression score was associated with 10% lower fecundability (FOR = 0.90, 95% CI: 0.82, 0.99). Likewise, a 1 SD increase in the stress score was associated with 13% lower fecundability (FOR = 0.87, 95% CI: 0.79, 0.96). Male anxiety was associated with a higher risk of infertility (OR = 1.19, 95% CI: 1.01, 1.42). Stratified analyses showed that depression, anxiety, and stress were significantly associated with lower fecundability among males with an education level Show less
Despite the critical role of e-Health literacy (eHL) in modern healthcare, current research predominantly concentrates on conditions such as cancer and diabetes, as well as outpatient care settings. H Show more
Despite the critical role of e-Health literacy (eHL) in modern healthcare, current research predominantly concentrates on conditions such as cancer and diabetes, as well as outpatient care settings. However, there remains a significant gap in studies specifically addressing the eHL needs of patients with maintenance hemodialysis (MHD). This study aims to explore the latent categories of eHL among MHD patients and its impact on health-promoting lifestyle (HPL). A survey was conducted using a convenience sampling method involving 500 MHD patients from three tertiary hospitals in Baoding. Data were analyzed using latent profile analysis (LPA) and a mixed regression model. This study showed that MHD patients could be classified into low (23.17%), middle (49.78%), and high (27.05%) eHL groups, with the three-class model showing optimal fit (AIC = 2321.213, BIC = 2271.168, entropy = 0.967). MHD Patients in the high literacy group scored significantly higher in all dimensions of e-HL and overall HPL (119.58 ± 13.86) compared to those in the low literacy group (91.82 ± 11.73) (all The findings suggest a heterogeneous stratification of eHL among MHD patients, closely linked to HPL. Stratified intervention strategies should be developed for different patient groups to potentially improve their health behaviors. The study provides evidence-based support for personalized health management. Show less