To explore the risk factors of post pancreatectomy diabetes mellitus (PPTDM)in pancreatic ductal carcinoma (PDAC) patients and the value of perioperative fasting blood glucose (FBG) level expression o Show more
To explore the risk factors of post pancreatectomy diabetes mellitus (PPTDM)in pancreatic ductal carcinoma (PDAC) patients and the value of perioperative fasting blood glucose (FBG) level expression on the long-term survival after surgery. Between December 2015 and December 2019, a cohort of 509 patients diagnosed with PDAC and undergoing resection at our hospital was analyzed. They were stratified into two groups, Control group (Control) and study group (PPTDM), depending on the onset of postoperative diabetes mellitus. We analyzed the survival rates at 6 months, 12 months and 24 months post-operation in the two groups. We use univariate and logostic multivariate regressions to analyze the risk factors for PPTDM. ROC curve analysis was conducted to assess the diagnostic significance of perioperative FBG levels regarding patients' long-term survival rates. The Kaplan-Meier method was employed to assess the impact of both preoperative and postoperative FBG levels on the survival rates within 24 months for each patient group. The comparison of general clinical data between the two groups shows marginal differences without statistical significance(P > 0.05); Patients in PPTDM group had significantly higher BMI, preoperative jaundice proportion, larger tumor diameter, higher TNM stage and higher proportion of distal pancreatectomy (DP), with P values of 0.023, 0.010, 0.040, 0.012 and 0.005, respectively. The levels of preoperative FBG and postoperative FBG in PPTDM patients exhibited statistically significant elevation compared to the control group (P < 0.05). There were no significant differences in surgery-related indicators between the two groups in operative time, number of dissected positive lymph nodes, total number of dissected lymph nodes, intraoperative blood loss and other related data (P > 0.05). Hospitalization duration of PPTDM patients was longer than control group (P = 0.047). PPTDM group had significantly higher expression concentrations of BUN, Cr, TG, LDL and Apo-B factors (P = 0.023, 0.024, 0.013, 0.045 and 0.017). 17 patients (5.03%) died in the PPTDM group and 4 patients (2.35%) in control group which had significantly difference (P = 0.020). In univariate and logostic multivariate regression analysis indicated tumor size, jaundice, BUN, Cr, TG, LDL, Apo-B concentrations and DP approach were significantly correlated to the risk for PPTDM (P < 0.05). ROC curve analysis results showed combining of preoperative and postoperation FBG showed the highest diagnostic efficacy, followed by postoperation FBG and preoperative FBG. The AUC areas of the three groups were 0.745, 0.623 and 0.588, respectively, and the critical values of the three groups were 9.81/9.95 mmol/L, 10.18 mmol/L and 10.23 mmol/L, respectively, with statistical significance (P < 0.05). Results were considered statistically significant if the p-value was less than 0.05. PPTDM stands as a significant postoperative complication following pancreatic cancer surgery, characterized by a high incidence and severity. Several risk factors have garnered considerable attention among clinical surgeon. PPTDM may be an influential factor in postoperative prognosis of pancreatic cancer. The expression levels of preoperative and postoperative blood glucose hold diagnostic value for the long-term prognosis of pancreatic cancer patients. Early regulation and intervention by surgeons concerning perioperative FBG could potentially mitigate the risk of PPTDM. Show less
Background Myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1(MLN-FGFR1), also referred to as 8p11 myeloproliferative syndrome (EMS), arises from aberrant FGFR1 gene rearrangement Show more
Background Myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1(MLN-FGFR1), also referred to as 8p11 myeloproliferative syndrome (EMS), arises from aberrant FGFR1 gene rearrangement in bone marrow hematopoietic stem cells, resulting in the transformation of myeloid/lymphoid cells into neoplastic growths. The clinical and laboratory features of affected individuals are influenced by the specific partner genes. Purpose This article aims to report a case of MLN-FGFR1 involving a novel CNTRL::FGFR1 splicing variant and to discuss its clinicopathological characteristics and treatment challenges. Methods/Results We report a case of MLN-FGFR1 in a 35-year-old male patient presenting with leukocytosis, lymphadenopathy, hepatosplenomegaly, and a mixed population of B lymphoblasts, T lymphoblasts, and monoblasts in the bone marrow and lymph nodes. Comprehensive molecular profiling, including chromosomal karyotyping, fluorescence in situ hybridization (FISH), targeted transcriptome sequencing, reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing, identified a novel splicing variant of the CNTRL::FGFR1 fusion, resulting from a t(8;9)(p11;q33) translocation. This novel splicing variant involves an in-frame fusion between exon 38 of CNTRL and exon 11 of FGFR1, retaining the kinase domain of FGFR1 and leading to its constitutive activation. Despite multiple treatment regimens, the patient failed to achieve complete remission (CR). Conclusion The findings highlight the urgent need for targeted therapies, such as FGFR inhibitors, to improve outcomes in patients with FGFR1-rearranged malignancies. Show less
Obesity and dysregulated cytokine levels are prevalent in schizophrenia patients undergoing antipsychotic treatment. While cytokines are implicated in obesity, their relationship with psychopathology Show more
Obesity and dysregulated cytokine levels are prevalent in schizophrenia patients undergoing antipsychotic treatment. While cytokines are implicated in obesity, their relationship with psychopathology in schizophrenia remains underexplored. This study investigated associations between body mass index (BMI), cytokine levels, and clinical symptoms in chronic schizophrenia patients. In this cross-sectional study,201chronic schizophrenia patients (Chinese Han population) were stratified into high BMI (BMI≥25kg/m A significant negative correlation was observed between BMI and IL-2( Higher BMI in chronic schizophrenia is associated with reduced IL-2 levels, attenuated negative symptoms, and adverse lipid profiles. TNF-α may modulate psychopathology severity. These findings highlight complex interactions between metabolic dysregulation, immune markers, and clinical manifestations in schizophrenia. Show less
High-abundance serum proteins, mostly modified by N-glycans, are usually depleted from human sera to achieve in-depth analyses of serum proteome and sub-proteomes. In this study, we show that these hi Show more
High-abundance serum proteins, mostly modified by N-glycans, are usually depleted from human sera to achieve in-depth analyses of serum proteome and sub-proteomes. In this study, we show that these high-abundance glycoproteins (HAGPs) can be used as valuable standard glycopeptide resources, as long as the structural features of their glycans have been well defined at the glycosite-specific level. By directly analyzing intact glycopeptides enriched from serum, we identified 1322 unique glycopeptides at 48 N-glycosites from the top 12 HAGPs (19 subclasses). These HAGPs could be further classified into four major groups based on the structural features of their attached N-glycans. Immunoglobins including IGHG1/2/3/4, IGHA1/2 and IGHM were mostly modified by core fucosylated and bisected N-glycans with rarely sialic acids. Alpha-1-acid glycoproteins (ORM1/2) and haptoglobins (HP) were mainly modified by tri-and tetra-antennary (40 %) N-glycans with antenna-fucoses and sialic acids. Complement components C3 and C4A/B were highly modified by oligo-mannose glycans. The other HAGPs including SERPINA1, A2M, TF, FGB/G and APOB mainly contain bi-antennary complex glycans with the common core structure and (sialyl-) LacNAc branch structures. These HAGPs are easily detected by LC-MS analysis and therefore could be used as standard glycopeptides for glycoproteomic methodology studies as well as possible clinical utilities. Show less
One serious consequence of diabetes mellitus is diabetic retinopathy (DR), which impairs eyesight to the point of blindness. While glucocorticoid medications are commonly employed in the management of Show more
One serious consequence of diabetes mellitus is diabetic retinopathy (DR), which impairs eyesight to the point of blindness. While glucocorticoid medications are commonly employed in the management of DR, their therapeutic efficacy requires enhancement. Due to the tight association between glucocorticoid-related genes and the onset and development of DR, a comprehensive examination of its root cause of activity may be able to overcome the drawbacks of existing treatment approaches. R programming tools were used to examine the single-cell RNA sequencing (scRNA-seq) dataset GSE178121, which was obtained from the Gene Expression Omnibus (GEO) database. To evaluate glucocorticoid activity, a gene set related to glucocorticoid phenotypes was sourced from the Molecular Signatures Database (MSigDB), followed by the identification of key cellular populations within DR tissues. Subsequently, these key cells underwent pseudotime analysis, transcription factor (TF) evaluation, cell-cell communication assessment, differential gene screening, and the construction of a regulatory network. Our investigation demonstrated that vascular endothelial cells (VECs) in DR tissue exhibited markedly elevated glucocorticoid activity. KLF4 is among the TFs that are intimately linked to the onset of DR, and hydroxyurea could be a beneficial medication. Cell-cell communication analysis highlighted the PTN and ANGPTL signaling pathways as important signaling pathways in DR. In the meanwhile, we identified 25 Hub genes, including DUSP6, AP1S2, and PTPRB, which were verified to be differentially expressed in DR. In conclusion, our comprehensive study elucidated the complex interactions of glucocorticoids in the pathogenesis of DR, thereby revealing potential signaling pathways and therapeutic targets. Show less
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. Ho Show more
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. However, existing materials mainly cover the 380-1540 nm range, with slight extension to the UV region, impeding their applications in solar-blind imaging, background-free tracking, concealed communication, etc. To address this challenge, here we propose guidelines for far-UVC (200-230 nm) optical design. Accordingly, we achieve multi-stimulated far-UVC luminescence at ~222 nm in Pr Show less
D-2-hydroxyglutarate (D-2HG), an oncometabolite derived from the tricarboxylic acid cycle. Previous studies have reported the diverse effects of D-2HG in pathophysiological processes, yet its role in Show more
D-2-hydroxyglutarate (D-2HG), an oncometabolite derived from the tricarboxylic acid cycle. Previous studies have reported the diverse effects of D-2HG in pathophysiological processes, yet its role in breast cancer remains largely unexplored. We applied an advanced biosensor approach to detect the D-2HG levels in breast cancer samples. We then investigated the biological functions of D-2HG through multiple in vitro and in vivo assays. A joint MeRIP-seq and RNA-seq strategy was used to identify the target genes regulated by D-2HG-mediated N6-methyladenosine (m We found that D-2HG accumulated in triple-negative breast cancer (TNBC), exerting oncogenic effects both in vitro and in vivo by promoting TNBC cell growth and metastasis. Mechanistically, D-2HG enhanced global m Our study unveils a previously unrecognized role for D-2HG-mediated RNA modification in TNBC progression and targeting the D-2HG/FTO/m Show less
Cardiovascular diseases (CVDs), including myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and arrhythmia, are major contributors to global mortality and often share overlappi Show more
Cardiovascular diseases (CVDs), including myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and arrhythmia, are major contributors to global mortality and often share overlapping risk factors and pathophysiological mechanisms. While genome-wide association studies (GWAS) have identified many loci for individual CVDs, the shared genetic architecture across related traits-particularly in East Asian populations-remains underexplored. We integrated large-scale GWAS summary statistics from East Asian populations to perform genome-wide and local genetic correlation analyses across four CVD phenotypes and five cardiometabolic traits (blood pressure and lipid levels). Using stratified LD score regression, we assessed tissue-specific heritability enrichment. Multi-trait analysis of GWAS (MTAG) was then employed to identify pleiotropic loci associated with multiple traits, with functional annotation and expression quantitative trait loci (eQTL) data used to explore biological relevance. We observed extensive genetic correlations among CVDs and between CVDs and cardiometabolic traits, with HF showing the strongest connections to both MI and arrhythmia. Notable genome-wide correlations were found between MI and SBP (rg = 0.35, Our findings provide comprehensive insight into the shared genetic determinants of cardiovascular and metabolic diseases in East Asian populations. The identification of pleiotropic and ancestry-specific loci, along with tissue-specific regulatory patterns, underscores the need for integrative multi-trait and population-informed approaches in cardiovascular genetics and risk prediction. Show less
Infantile hemangioma (IH) is a common benign vascular tumor in infants, often requiring intervention due to potential functional impairment and cosmetic concerns. Propranolol, a nonselective β-adrener Show more
Infantile hemangioma (IH) is a common benign vascular tumor in infants, often requiring intervention due to potential functional impairment and cosmetic concerns. Propranolol, a nonselective β-adrenergic receptor blocker, is the first-line therapy for IH, yet its mechanisms remain incompletely elucidated. This prospective study investigated the systemic angiogenic protein profile changes in response to propranolol in 14 treatment-naïve IH infants compared to 14 healthy controls using antibody array analysis. We identified twenty-six angiogenic proteins significantly downregulated in pretreatment IH patients compared to healthy controls. After 3 months of propranolol treatment, six proteins including HB-EGF, TGFα, ANGPTL4, Follistatin, Tie-1 and PLGF were significantly upregulated. Bioinformatic enrichment analysis revealed that these proteins are involved in key biological processes and signaling pathways, including epithelial cell proliferation, angiogenesis regulation, VEGF signaling, ERBB-EGFR axis, Ras-MAPK, and PI3K-Akt pathways. These results suggest that propranolol treatment is associated with a rebalancing of dysregulated angiogenic proteins in IH, through modulating both pro- and anti-angiogenic factors to rebalance vascular homeostasis. Our study provides novel insights into the systems-level pharmacological actions of propranolol and proposes potential biomarkers for treatment response evaluation. Show less
Prostate cancer is epithelial malignant prostate hyperplasia caused by a tumor. We found prostate cancer GSE141551 and GSE200879 profiles from gene expression omnibus database, followed by differentia Show more
Prostate cancer is epithelial malignant prostate hyperplasia caused by a tumor. We found prostate cancer GSE141551 and GSE200879 profiles from gene expression omnibus database, followed by differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis, protein-protein interaction analysis, gene function enrichment analysis, and comparative toxicology database analysis. Finally, the gene expression heat map was drawn, and miRNA information regulating core DEGs was retrieved. A total of 1151 DEGs were found, most of them focusing on systematic development, cell development, cell differentiation, regulation of multicellular biological processes, anatomical morphogenesis, MAPK signaling pathway, proteoglycans in cancer, fluid shear stress, and atherosclerosis. The core genes (MYL9, TAGLN, SMTN, CNN1, MYH11, MYLK, MYOCD, ACTC1, LMOD1, and TPM2) obtained in end are all lowly expressed in prostate cancer samples and are associated with hypertension, tumor metastasis, prostate tumors, and tumor aggressiveness. LMOD1 and SMTN are lowly expressed in prostate cancer and may be used as markers in prostate cancer nursing. Show less
Existing evidence suggests that elevated 1-hour post-load plasma glucose (1-h PG ≥ 8.6 mmol/L) during an oral glucose tolerance test (OGTT) is associated with atherogenic lipid parameters which are li Show more
Existing evidence suggests that elevated 1-hour post-load plasma glucose (1-h PG ≥ 8.6 mmol/L) during an oral glucose tolerance test (OGTT) is associated with atherogenic lipid parameters which are linked to an increased risk of cardiovascular disease (CVD). However, it remains unclear whether normal glucose tolerance (NGT) individuals with elevated 1-h PG (NGT-1hPG-high) should still be considered low-risk. Therefore, this study aims to demonstrate comprehensive lipid characteristics in individuals with different glycemic status stratified by 1-h PG, with a particular focus on those with NGT-1hPG-high. This cross-sectional study included individuals aged 25-55 years with high-risk of diabetes from the Daqing Diabetes Prevention Study II (Daqing DPS-II). Individuals were categorized into different glycemic status based on the World Health Organization's 1999 criteria and the International Diabetes Federation's 2024 position statement on 1-h PG. Traditional (TC, TG, HDL-C, LDL-C) and non-traditional lipid parameters [ApoA-1, ApoB, sdLDL-C, Lp(a), non-HDL-C, remnant cholesterol (RC), ApoB/ApoA-1, LDL-C/ApoB] were measured. Dyslipidemia was defined according to the 2023 Chinese Guidelines for Lipid Management. The China-PAR equation was used to estimate 10-year CVD risk. Spearman's correlation coefficients were calculated to evaluate the correlation between lipid parameters and 10-year CVD risk. Logistic and multiple linear regression models were performed to assess the association between 1-h PG and dyslipidemia as well as lipid parameters adjusting for covariates. Among 2 469 individuals, 22.7% had NGT with normal 1-h PG (NGT-1hPG-normal), 19.9% had NGT-1hPG-high, 2.6% had prediabetes with normal 1-h PG (PDM-1hPG-normal), 34.2% had prediabetes with elevated 1-h PG (PDM-1hPG-high), and 20.6% had newly diagnosed diabetes. The prevalence of dyslipidemia did not significantly differ between NGT-1hPG-high and PDM-1hPG-high (OR = 1.13, 95%CI: 0.88-1.44, P > 0.05). Higher 1-h PG levels were consistently associated with an atherogenic lipid profile, characterized by increased TC, TG, LDL-C, ApoB, sdLDL-C, non-HDL-C, RC and ApoB/ApoA-1, along with decreased ApoA-1, HDL-C and LDL-C/ApoB (all P < 0.05). Among lipid parameters, TG, sdLDL-C, RC, ApoB/ApoA-1, LDL-C/ApoB and HDL-C showed the strongest correlation with 10-year CVD risk, with Spearman's correlation coefficients of 0.41, 0.38, 0.35, 0.31, - 0.37 and - 0.36, respectively. In the NGT-1hPG-high, TG, sdLDL-C, and ApoB/ApoA-1 levels were significantly higher, while HDL-C and LDL-C/ApoB levels were significantly lower compared to counterparts with NGT-1hPG-normal (all P < 0.05). Moreover, except for TG and RC (both P < 0.01), the majority of lipid parameter levels in NGT-1hPG-high did not significantly differ from those in PDM (all P > 0.05). NGT-1hPG-high exhibited a similar atherogenic lipid profile to that observed in PDM. 1-h PG could serve as a potential indicator for the early identification of at-risk individuals who may otherwise go undetected among NGT population. Show less
Diabetic nephropathy (DN) is the most intractable complication of diabetes. Despite decades of research, accurate diagnostic markers and effective therapeutic drugs are still elusive. Abnormal copper Show more
Diabetic nephropathy (DN) is the most intractable complication of diabetes. Despite decades of research, accurate diagnostic markers and effective therapeutic drugs are still elusive. Abnormal copper metabolism is also implicated in diabetes and its complications. This study aims to identify copper metabolism-related biomarkers and potential drugs for DN. DN datasets and copper metabolism-related genes (CMGs) were obtained from Gene Expression Omnibus (GEO) and GeneCards. Differentially expressed CMGs (DE-CMGs) were identified using the limma package and the Venn algorithm. Functional enrichment analysis and protein-protein interaction (PPI) network were performed to identify candidate hub genes. The single gene with an area under the receiver operating characteristic (ROC) curve > 0.7 was identified as a potential diagnostic biomarker of DN. Finally, these biomarkers were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in high-glucose-treated human proximal tubular (HK-2) cells. These validated hub genes were used to construct a combined prediction model, confirmed by additional GSE30528 and GSE30529 datasets. The correlation analysis between the expression level of the hub genes and the estimated glomerular filtration rate (eGFR) was carried out. Additionally, immune cell infiltration and potential target drugs were investigated for these biomarkers. Five hub genes associated with copper metabolism, namely CD36, CCL2, CASP3, LPL, and APOC3, were identified as biomarkers for the early diagnosis of DN. Utilizing multiple biomarkers enhanced diagnostic accuracy and specificity. CD36, CCL2, and CASP3 correlated negatively with eGFR levels, while LPL and APOC3 correlated positively. Additionally, these hub genes were significantly linked to various immune cell types, including macrophages M1 and M2, T cells, gamma delta resting dendritic cells, neutrophils, and NK cells. Furthermore, 15 agents targeting these biomarkers were retrieved from the DrugBank database. Our study identified key genes possibly related to copper metabolism in the pathological mechanism of DN that could serve as novel targets for the diagnosis and therapy of DN. Show less
Accumulation of various genetics and epigenetics alterations are accepted to result in the initiation and progression of hepatocellular carcinoma (HCC), and its high metastasis is viewed as a critical Show more
Accumulation of various genetics and epigenetics alterations are accepted to result in the initiation and progression of hepatocellular carcinoma (HCC), and its high metastasis is viewed as a critical bottleneck leading to its treatment failure. Amongst them, the microRNAs arising from the lack of the antioxidant transcription factor Nrf2 lead to cancer metastasis. However, much less is known about the regulation of microRNAs by Nrf1, even though it acts as an essential determinon of cell homoeostasis by governing the transcriptional expression of those driver genes contributing to the EMT involved in its metastasis. In this study, distinct EMT phenotypes resulted from specific knockouts of Nrf1 and Nrf2 in HepG2 cells, as accompanied by their differential migratory and invasive capabilities. The Show less
Lactylation, a recently identified post-translational modification, plays a critical role in tumor progression and immune regulation. However, its cellular heterogeneity and functional impact in lung Show more
Lactylation, a recently identified post-translational modification, plays a critical role in tumor progression and immune regulation. However, its cellular heterogeneity and functional impact in lung adenocarcinoma (LUAD) remain poorly understood. This study was designed as exploratory biological research to characterize lactylation-associated patterns at the single-cell level and to propose a potential lactylation-related prognostic model. Single-cell transcriptomic data from LUAD and normal lung tissues were analyzed to quantify lactylation activity using AUCell based on 332 lactylation-related genes. Cell-cell communication was inferred using CellChat to identify ligand-receptor interactions among subpopulations. Candidate genes were selected by integrating ligand-receptor pair genes, marker genes from highly lactylated subtypes, and previously reported lactylation-related genes. A total of 101 machine learning model combinations were evaluated to construct the prognostic model. Selected genes were further validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the potential relationship between Lactylation activity was higher in tumor epithelial and stromal cells, with particularly elevated levels in specific epithelial subpopulations. A 12-gene signature was identified, comprising nine risk genes (e.g., This study presents a lactylation-based prognostic model for LUAD and uncovers potential immune-related mechanisms by which highly lactylated epithelial cells may contribute to immune evasion and tumor progression. Show less
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases Show more
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases such as obesity. Several randomized controlled trials (RCTs) targeting obese or overweight populations have found that individuals with different genotypes exhibit varying responses to the same lifestyle intervention (gene-lifestyle intervention interactions). To date, more than 20 genes, including Show less
Growth traits are among the most important economic phenotypes targeted in the genetic improvement of beef cattle. To understand the genetic basis of growth traits in Huaxi cattle, we performed a geno Show more
Growth traits are among the most important economic phenotypes targeted in the genetic improvement of beef cattle. To understand the genetic basis of growth traits in Huaxi cattle, we performed a genome-wide association study (GWAS) on body weight, eye muscle area, and back fat thickness across five developmental stages in a population of 202 Huaxi cattle. Additionally, publicly available RNA-seq data from the longissimus dorsi muscle of both young and adult cattle were analyzed to identify key genes and genetic markers associated with growth in Huaxi cattle. In total, 7.19 million high-quality variant loci (SNPs and INDELs) were identified across all samples. In the GWAS, the three multilocus models (FarmCPU, MLMM, and BLINK) outperformed the conventional single-locus models (CMLM, GLM, and MLM). Consequently, GWAS analysis was conducted using multilocus models, which identified 99 variant loci significantly associated with growth traits and annotated a total of 83 candidate genes (CDGs). Additionally, 23 of the 83 CDGs overlapped with significantly differentially expressed genes identified from public RNA-seq datasets of longissimus dorsi muscle between young and adult cattle. Furthermore, gene functional enrichment (KEGG and GO) analyses revealed that over 30% of the pathways and GO terms were associated with muscle development and fat deposition, crucial factors for beef production. Specifically, key genes identified included Show less
Iodine is an essential micronutrient for developmental processes in the early stages; however, data on the effect of maternal iodine nutrition on milk lipids are limited. We aimed to explore the effec Show more
Iodine is an essential micronutrient for developmental processes in the early stages; however, data on the effect of maternal iodine nutrition on milk lipids are limited. We aimed to explore the effect of inadequate and excessive iodine intake on milk lipid metabolism and its mechanisms preliminarily. Rats were treated with different concentrations of potassium iodide water to construct animal models of iodine deficiency and excess. Iodine excess reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels during lactation. Iodine deficiency had no significant effect on blood lipid indicators. In early and late lactation, iodine deficiency and excess inhibited triglyceride (TG) levels in milk; in mid-lactation, the inhibitory effect of iodine deficiency was attenuated. Under iodine deficiency and excess, the level of TG and the expression of THRα1, THRβ1, ACC1, FAS, THRSP, BTN1A1, and ADFP proteins in the mammary gland were decreased during lactation; a decrease in LPL protein expression was observed in early and late lactation; and a decline of XOR protein expression was reported in mid and late lactation. Blood lipid metabolism was less sensitive to iodine deficiency during lactation. Iodine excess has a more profound effect on blood lipid metabolism, causing dyslipidemia in lactating rats. Long-term iodine deficiency and excess may have a negative role in the mechanisms regulating milk lipid synthesis and secretion by affecting thyroid hormones to inhibit the milk TG level. Show less
Pathological retinal angiogenesis drives vision loss in diseases like proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO). Erdafitinib, a pan-fibroblast growth factor receptor (F Show more
Pathological retinal angiogenesis drives vision loss in diseases like proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO). Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has shown therapeutic potential in FGFR-mutated urothelial carcinoma. This study aimed to determine whether erdafitinib suppresses pathological retinal angiogenesis beyond its canonical FGFR inhibition, and to dissect its potential mechanisms through multi-model validation. We employed zebrafish developmental angiogenesis and oxygen-induced retinopathy (OIR) mouse models, combined with in vitro endothelial cell assays. In zebrafish, erdafitinib dose-dependently inhibited intersegmental vessel (ISV) formation and disrupted retinal angiogenesis, with confocal microscopy revealing truncated vascular length (by 62% at 4 µM vs. controls). The OIR model demonstrated erdafitinib's efficacy in reducing neovascular density (35% decrease) and pathological tuft formation. Mechanistically, erdafitinib impaired human umbilical vein endothelial cell (HUVEC) tube formation and migration, accompanied by downregulation of VEGFR2 expression (2.1-fold reduction) and inhibition of AKT/ERK phosphorylation. Molecular docking confirmed erdafitinib's binding to VEGFR2 kinase domain (binding energy: -7.8 kcal/mol), albeit with lower affinity than FGFR1 (-10.2 kcal/mol). These findings establish that erdafitinib exerts off-target anti-angiogenic effects by blocking VEGFR2 phosphorylation and downstream signaling, supporting its repurposing potential for anti-VEGF-resistant retinal vascular diseases. Further studies should address its intraocular pharmacokinetics and long-term safety. 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
Symptom burden in primary brain tumor patients varies, emphasizing the need for comprehensive understanding to improve patient care. This study aims to identify distinct symptom clusters among brain t Show more
Symptom burden in primary brain tumor patients varies, emphasizing the need for comprehensive understanding to improve patient care. This study aims to identify distinct symptom clusters among brain tumor patients in Shanghai, China, using Latent Profile Analysis (LPA) to guide personalized diagnosis, treatment, and supportive care. A longitudinal study was conducted among 161 patients with primary brain tumors in Shanghai. Participants completed the MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) at three intervals: the day of admission (T1), three days after surgery (T2), and two weeks after surgery (T3). Latent Profile Analysis (LPA) was used to identify subgroups with unique symptom patterns. Six distinct subgroups were identified (entropy = 0.964), ranging from low-burden to persistently severe patterns. Subgroup membership was partially associated with age, tumor grade, and diagnosis. These subgroups were: transient postoperative burden group, stable symptom with cognitive emergence group, distress-predominant, low burden group, elderly-high grade, persistently severe group, nausea-dominant recovery group, and distress-plus-nausea, younger urban group. Our findings reveal substantial heterogeneity in perioperative symptom experiences among brain tumor patients. Identifying subgroups with high and persistent symptom burden may help clinicians target interventions such as enhanced education, proactive monitoring, rehabilitation, psychological support, and antiemetic management. This subgroup-based approach may improve quality of life, reduce morbidity, and guide precision supportive care in neuro-oncology. Show less
The present investigation set out to examine potential categories regarding depressive symptoms in frail senior individuals in China and to identify the contributing variables associated with each cat Show more
The present investigation set out to examine potential categories regarding depressive symptoms in frail senior individuals in China and to identify the contributing variables associated with each category, with the goal of informing more targeted mental health interventions. Data were drawn from the 2018 China Health and Retirement Longitudinal Survey, commonly called CHARLS, which comprised an overall cohort of 1083 qualifying respondents. A latent profile analysis (LPA) revealed the following four distinct depression profiles: a Low Depression-High Loneliness Group (38.4%), a Moderately Low Depression-High Suicidal Ideation Group (7.5%), a Moderately High Depression-High Negative Emotion Group (33.4%), and a High Depression-High Suicidal Ideation Group (20.7%). Ordered multi-categorical logistic regression and restricted cubic spline analyses revealed that age, gender, body pain, pension insurance, sleep duration, and frailty index were significant predictors of depression classification. These findings suggest that depressive symptoms among frail older individuals in China are markedly heterogeneous, highlighting the need to develop differentiated intervention strategies for distinct depression risk groups to promote their mental health. Show less
William Stewart, Bin Hu, Fengqiao Li+6 more · 2025 · Journal of controlled release : official journal of the Controlled Release Society · Elsevier · added 2026-04-24
Obesity, a widespread global health issue affecting millions, is characterized by excess fat deposition and metabolic dysfunction, significantly elevating the risk of comorbidities like type 2 diabete Show more
Obesity, a widespread global health issue affecting millions, is characterized by excess fat deposition and metabolic dysfunction, significantly elevating the risk of comorbidities like type 2 diabetes, cardiovascular disease, and certain cancers, all of which contribute to rising rates of preventable morbidity and mortality. Current approaches to obesity, including lifestyle modifications, and pharmacotherapy, often face limitations such as poor long-term adherence, side effects, and insufficient targeting of the complex, multifactorial pathways underlying the disease. Herein we report a dual, RNA-mediated combinatorial approach using targeting lipid nanoparticles (LNP) for the treatment of obesity. LNPs were co-encapsulated with mRNA encoding Interleukin-27 (mIL-27) to coactivate PGC-1α, PPARα, and UCP-1, thereby promoting adipocyte differentiation and enhancing adaptive thermogenesis within adipocytes, and siRNA targeting Dipeptidyl peptidase-4 (siDPP-4) to silence the primary inhibitory enzyme of GLP-1, and GIP within the incretin system, effectively restoring glucose homeostasis. Following post translational silencing of DPP-4 and upregulation of IL-27 in a diet-induced obesity (DIO) mice model, increased expression of thermogenic biomarkers PGC-1α, PPARα, and UCP-1 was observed at the molecular, protein, and tissue level, and insulin sensitivity was restored. Importantly, this gene modulation led to a 21.1 % reduction of bodyweight after treatment in the DIO model. These findings demonstrate for the first time a dual RNA-mediated combinatorial approach, leveraging liver targeting LNP delivery with synergistic effects from incretin system regulation and induction of adipocyte differentiation and thermogenesis after codelivery of siDPP-4 and mIL-27. This innovative strategy provides a promising alternate framework for addressing obesity and its associated metabolic dysfunction. Show less
Pharmaceutical and personal care products (PPCPs), as ubiquitous emerging contaminants, present undercharacterized neuropsychiatric hazards through environmental exposure. This investigation employs c Show more
Pharmaceutical and personal care products (PPCPs), as ubiquitous emerging contaminants, present undercharacterized neuropsychiatric hazards through environmental exposure. This investigation employs convergent multi-omics strategies - integrating toxicogenomic discovery, disease-associated genomic mapping, and transcriptomic profiling - to elucidate mechanistic linkages between PPCPs bioactivity and depressive pathogenesis. Through systematic analysis of Nanjing's aquatic chemical burden (prioritizing dimenhydrinate, ibuprofen, padimate-O, caffeine, and roxithromycin), we identified 3073 conserved molecular targets bridging PPCPs toxicity and depression etiology via Comparative Toxicogenomics Database and GeneCards interrogation. Functional ontology revealed dysregulated pathways encompassing lipidomic remodeling, IL-17-mediated neuroinflammation, and synaptic transmission deficits. Ensembled machine learning algorithms (Lasso regression, XGBoost, random forest) converged on seven high-fidelity candidate biomarkers (HSPA8, CBX1, CD59, CHAF1A, CUX1, ID2, RPL3) demonstrating stress-adaptive, chromatin regulatory, and immunomodulatory functions. Molecular docking predicted strong binding affinities between PPCPs and depression-related proteins, notably dimenhydrinate with CHAF1A (- 6.1 kcal/mol) and HSPA8 (- 6.1 kcal/mol), suggesting multi-target modulation. This work proposes a computational framework to map molecular interactions between specific PPCPs and depression-associated pathways. Candidate targets highlight testable hypotheses for future experimental validation. These findings suggest selected PPCPs with neuroactive properties may warrant further investigation as environmental modifiers of depression risk. Show less
Tumorigenesis is typically accompanied by cellular dedifferentiation and the acquisition of stem cell-like attributes. However, few studies have comprehensively evaluated the putative relationships be Show more
Tumorigenesis is typically accompanied by cellular dedifferentiation and the acquisition of stem cell-like attributes. However, few studies have comprehensively evaluated the putative relationships between these characteristics and various cancers. Here, we integrated gene expression and DNA methylation quantitative trait loci (cis-eQTL and cis-mQTL) data from the blood to perform multi-omics Mendelian randomization analysis. Our analyses revealed 967 stem cell-associated genes (P < 0.05) and 11,262 methylation sites (P < 0.01) significantly related to 12 cancers. SMAD7 (cg14321542) in colon cancer, IGF2 (cg13508136) in prostate cancer, and FADS1 (cg07005513) in rectal cancer were prioritized as candidate causal genes and regulatory elements. Notably, using cis-eQTL data from the corresponding tissue sites, we detected 16 stem cell-associated genes dramatically causally associated with six cancers (FDR<0.2). The gene THBS3 was particularly common in both blood and stomach tissues and exhibited prognostic significance. Furthermore, it was markedly associated with one microbial metabolic pathway and four immunophenotypes. Functional validation using the ECC12 gastric cancer cell line revealed that the inhibition of its expression could accelerate oxidative phosphorylation and reactive oxygen species production, reduce clonal proliferation ability, and promote the apoptosis of stomach tumor cells. Additionally, based on spatial transcriptomic data from gastrointestinal cancers, the results demonstrated the clusters enriched with the most stem cell-associated genes exhibited significantly enhanced tumor-promoting potency, and the THBS3-expressing cells displayed suppressed oxidative phosphorylation. Overall, this study enhances our understanding of tumorigenic mechanisms and aids in the identification of therapeutic targets. Show less
PALS1-associated tight junction (PATJ) protein is linked to metabolic disease and stroke in human genetic studies. Despite the recognized role of PATJ in cell polarization, its specific functions in m Show more
PALS1-associated tight junction (PATJ) protein is linked to metabolic disease and stroke in human genetic studies. Despite the recognized role of PATJ in cell polarization, its specific functions in metabolic disease and ischemic stroke recovery remain largely unexplored. We explored the functions of PATJ in an in vitro model and in vivo in C. elegans and mice. Using a mouse model of stroke, we found post-ischemic stroke duration-dependent increase of PATJ abundance in endothelial cells. PATJ knock-out (KO) HEK293 cells generated by CRISPR-Cas9 suggest roles for PATJ in cell proliferation, migration, mitochondrial stress response, and interactions with the Yes-associated protein (YAP)-1 signaling pathway. Notably, PATJ deletion altered YAP1 nuclear translocation. PATJ KO cells demonstrated transcriptional reprogramming based on RNA sequencing analysis, and identified dysregulation in genes central to vascular development, stress response, and metabolism, including RUNX1, HEY1, NUPR1, and HK2. Furthermore, we found that mpz-1, the homolog of PATJ, was significantly upregulated under hypoxic conditions in C. elegans. Knockdown of mpz-1 resulted in abnormal neuronal morphology and increased mortality, both of which were exacerbated by hypoxia exposure, indicating a critical protective role of PATJ/MPZ-1 in maintaining neuronal integrity and survival, particularly during oxygen deprivation stress relevant to ischemic stroke. These insights offer a new understanding of PATJ's regulatory functions within cellular and vascular physiology and help lay the groundwork for therapeutic strategies targeting PATJ-mediated pathways for stroke rehabilitation and neurovascular repair. Show less
To investigate longitudinal changes in pelvic floor support in primiparous women with pelvic organ prolapse (POP) after vaginal delivery, focusing on single- and multiple-compartment involvement. Two Show more
To investigate longitudinal changes in pelvic floor support in primiparous women with pelvic organ prolapse (POP) after vaginal delivery, focusing on single- and multiple-compartment involvement. Two hundred primiparas after vaginal delivery were prospectively enrolled and underwent pelvic floor MRI at six weeks postpartum. POP was diagnosed and classified into subgroups (single or multiple compartments involved) based on MRI findings. Primiparas with POP underwent repeat MRI at four months postpartum. Pelvic floor measurements, including injury score and functional parameters of the levator ani muscle (puborectal hiatus line, H line; muscular pelvic floor relaxation line, M line; levator hiatus area, LHA; iliococcygeus angle, ICA; levator plate angle, LPA), were assessed on MRI. Measurements were compared among POP subgroups and a normal control group (without POP) at six weeks postpartum. Additionally, changes between six weeks and four months postpartum were analyzed within POP subgroups. Based on MRI criteria, approximately 41.5% of primiparas were diagnosed with POP, predominantly cystoceles commonly associated with uterine prolapse. Functional parameters of the levator ani, except for LPA at rest, were significantly increased in POP subgroups compared to controls. At four months postpartum, M line, H line, and LPA significantly decreased, and prolapsed organs were elevated in cases with multiple compartments involved, compared to six weeks postpartum. No significant changes were observed in cases with single-compartment involvement during follow-up. A substantial proportion of primiparas experienced postpartum POP. Impaired levator ani function contributed to POP. Pelvic floor support improved during early postpartum in cases with multiple-compartment involvement. Show less
Jiangliang Chu, Yifan Yang, Keyu Zhang+2 more · 2025 · Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · Elsevier · added 2026-04-24
Polyethylene terephthalate microplastics (PET-MPs) have emerged as significant environmental pollutants with potential health risks. This study investigates the cytotoxic effects of PET-MPs on BEAS-2B Show more
Polyethylene terephthalate microplastics (PET-MPs) have emerged as significant environmental pollutants with potential health risks. This study investigates the cytotoxic effects of PET-MPs on BEAS-2B lung epithelial cells through integrated transcriptomic and metabolomic analyses. The results of the CCK8 assay showed a reduction in the viability of BEAS-2B cells following continuous exposure to PET-MPs. Transcriptomic analysis identified 1412 differentially expressed genes (DEGs) mainly enriched in apoptosis and extracellular matrix organization processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these DEGs are predominantly involved in the PI3K-Akt, TNF, and MAPK signaling pathways. Metabolomic analysis identified 2869 differentially expressed metabolites (DEMs), mainly associated with pyrimidine, arginine, proline, and β-alanine metabolism pathways. Multi-omics analysis indicated that PET-MPs primarily disrupt lipid metabolism, which may lead to an increased risk of apoptosis. We hypothesize that PET-MPs affect lipid metabolism by up-regulating the ANGPTL4 gene, thereby promoting cellular apoptosis. This study reveals the mechanisms of PET-MPs toxicity, emphasizing the potential risks they pose to human health. Show less
Despite the increasing approval and ongoing clinical trials of FGFR-targeted therapies, accurately detecting FGFR fusions remains a challenge due to limited research, low incidence rates, complex fusi Show more
Despite the increasing approval and ongoing clinical trials of FGFR-targeted therapies, accurately detecting FGFR fusions remains a challenge due to limited research, low incidence rates, complex fusion partner distribution, and unique kinase domain distribution. We conducted a multicenter study to comprehensively profile FGFR fusions in the largest Chinese pan-cancer cohort to date, comprising 118 FGFR fusions from 114 individuals. Both DNA- and RNA-based sequencing approaches were utilized to reveal novel and fundamental features of FGFR fusion. Our research reveals an incidence rate of 0.96% for FGFR rearrangements within this Chinese cohort, including a high incidence rate of FGFR fusions (40%) in parotid gland carcinoma. However, this is based on a small sample size of 5 tumors and should be interpreted cautiously pending validation in larger cohorts. We also uncovered distinct breakpoint distribution patterns across various FGFR rearrangements. For example, a primary breakpoint in intron17 of FGFR2 was predominant (21/22), while FGFR1/3 breakpoints displayed substantial diversity. For the first time, we identified "hot" breakpoints in FGFR1 intron17, exon18, and FGFR3's 3' untranslated region. These findings underline the importance of incorporating these regions in targeted sequencing to ensure comprehensive detection of FGFR1/3 fusions. Notably, we observed a predilection for intrachromosomal distribution in common FGFR1/2/3 fusions. In contrast, most novel fusions (12/15) exhibited an interchromosomal distribution pattern, indicating variations in the fusion formation mechanism. Importantly, our study demonstrates the substantial incremental value of RNA-NGS or other orthogonal methods in confirming the functionality of FGFR rearrangements initially identified by DNA sequencing. In our cohort, 46% (6/13) of rare FGFR1/2/3 fusions lacked detectable RNA transcripts; however, this does not definitively indicate non-functionality as factors such as low RNA quality, expression below detection limits, or nonsense-mediated decay may contribute. Therefore, RNA-based validation is critical for accurately identifying potentially targetable FGFR fusions and guiding therapy. Our findings offer critical novel insights into functional FGFR fusions and bear considerable clinical implications for identifying individuals whose tumors are most likely to respond favorably to FGFR-targeted therapies. Show less