Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitu Show more
Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT. Show less
The lion-head goose is the only large goose species in China, and it is one of the largest goose species in the world. Lion-head geese have a strong tolerance for massive energy intake and show a prio Show more
The lion-head goose is the only large goose species in China, and it is one of the largest goose species in the world. Lion-head geese have a strong tolerance for massive energy intake and show a priority of fat accumulation in liver tissue through special feeding. Therefore, the aim of this study was to investigate the impact of high feed intake compared to normal feeding conditions on the transcriptome changes associated with fatty liver development in lion-head geese. In this study, 20 healthy adult lion-head geese were randomly assigned to a control group (CONTROL, n = 10) and high-intake-fed group (CASE, n = 10). After 38 d of treatment, all geese were sacrificed, and liver samples were collected. Three geese were randomly selected from the CONTROL and CASE groups, respectively, to perform whole-transcriptome analysis to analyze the key regulatory genes. We identified 716 differentially expressed mRNAs, 145 differentially expressed circRNAs, and 39 differentially expressed lncRNAs, including upregulated and downregulated genes. GO enrichment analysis showed that these genes were significantly enriched in molecular function. The node degree analysis and centrality metrics of the mRNA-lncRNA-circRNA triple regulatory network indicate the presence of crucial functional nodes in the network. We identified differentially expressed genes, including Show less
Fibroblast growth factor receptor 2 (FGFR2) represents an appealing therapeutic target for multiple cancers, yet no selective FGFR2 inhibitors have been approved for clinical use to date. Here, we rep Show more
Fibroblast growth factor receptor 2 (FGFR2) represents an appealing therapeutic target for multiple cancers, yet no selective FGFR2 inhibitors have been approved for clinical use to date. Here, we report the discovery of a series of new selective, irreversible FGFR2 inhibitors. The representative compound LHQ490 potently inhibited FGFR2 kinase activity with an IC Show less
Large-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like prote Show more
Large-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like protein 4 (ANGPTL4), a protein involved in lipid and glucose metabolism during pregnancy, placental function, growth factors, and the risk of LGA. We conducted a prospective cohort study and recruited women with singleton pregnancies at the National Taiwan University Hospital between 2013 and 2018. First trimester maternal plasma ANGPTL4 concentrations were measured. Among 353 pregnant women recruited, the LGA group had higher first trimester plasma ANGPTL4 concentrations than the appropriate-for-gestational-age group. Plasma ANGPTL4 was associated with hemoglobin A1c, post-load plasma glucose, plasma triglyceride, plasma free fatty acid concentrations, plasma growth hormone variant (GH-V), and birth weight, but was not associated with cord blood growth factors. After adjusting for age, body mass index, hemoglobin A1c, and plasma triglyceride concentrations, plasma ANGPTL4 concentrations were significantly associated with LGA risk, and its predictive performance, as measured by the area under the receiver operating characteristic curve, outperformed traditional risk factors for LGA. Plasma ANGPTL4 is associated with glucose and lipid metabolism during pregnancy, plasma GH-V, and birth weight, and is an early biomarker for predicting the risk of LGA. Show less
Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs), releasing fatty acids (FA) and promoting lipid storage in white adipose tissue (WAT). However, the mechanisms regulating adipose LP Show more
Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs), releasing fatty acids (FA) and promoting lipid storage in white adipose tissue (WAT). However, the mechanisms regulating adipose LPL and its relationship with the development of hypertriglyceridemia are largely unknown. WAT from obese humans exhibited high PAR2 expression, which was inversely correlated with the LPL gene. Decreased LPL expression was also inversely correlated with elevated plasma TG levels, suggesting that adipose PAR2 might regulate hypertriglyceridemia by downregulating LPL. In mice, aging and high palmitic acid diet (PD) increased PAR2 expression in WAT, which was associated with a high level of macrophage migration inhibitory factor (MIF). MIF downregulated LPL expression and activity in adipocytes by binding with CXCR2/4 receptors and inhibiting Akt phosphorylation. In a MIF overexpression model, high-circulating MIF levels suppressed adipose LPL, and this suppression was associated with increased plasma TGs but not FA. Following PD feeding, adipose LPL expression and activity were significantly reduced, and this reduction was reversed in Par2-/- mice. Recombinant MIF infusion restored high plasma MIF levels in Par2-/- mice, and the levels decreased LPL and attenuated adipocyte lipid storage, leading to hypertriglyceridemia. These data collectively suggest that downregulation of adipose LPL by PAR2/MIF may contribute to the development of hypertriglyceridemia. Show less
Lipoprotein lipase (LPL) plays a crucial role in triglyceride hydrolysis. Rare biallelic variants in the LPL gene leading to complete or near-complete loss of function cause autosomal recessive famili Show more
Lipoprotein lipase (LPL) plays a crucial role in triglyceride hydrolysis. Rare biallelic variants in the LPL gene leading to complete or near-complete loss of function cause autosomal recessive familial chylomicronemia syndrome. However, rare biallelic LPL variants resulting in significant but partial loss of function are rarely documented. This study reports a novel occurrence of such rare biallelic LPL variants in a Chinese patient with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) during pregnancy and provides an in-depth functional characterization. The complete coding sequences and adjacent intronic regions of the LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes were analyzed by Sanger sequencing. The aim was to identify rare variants, including nonsense, frameshift, missense, small in-frame deletions or insertions, and canonical splice site mutations. The functional impact of identified LPL missense variants on protein expression, secretion, and activity was assessed in HEK293T cells through single and co-transfection experiments, with and without heparin treatment. Two rare LPL missense variants were identified in the patient: the previously reported c.809G > A (p.Arg270His) and a novel c.331G > C (p.Val111Leu). Genetic testing confirmed these variants were inherited biallelically. Functional analysis showed that the p.Arg270His variant resulted in a near-complete loss of LPL function due to effects on protein synthesis/stability, secretion, and enzymatic activity. In contrast, the p.Val111Leu variant retained approximately 32.3% of wild-type activity, without impacting protein synthesis, stability, or secretion. Co-transfection experiments indicated a combined activity level of 20.7%, suggesting no dominant negative interaction between the variants. The patient's post-heparin plasma LPL activity was about 35% of control levels. This study presents a novel case of partial but significant loss-of-function biallelic LPL variants in a patient with HTG-AP during pregnancy. Our findings enhance the understanding of the nuanced relationship between LPL genotypes and clinical phenotypes, highlighting the importance of residual LPL function in disease manifestation and severity. Additionally, our study underscores the challenges in classifying partial loss-of-function variants in classical Mendelian disease genes according to the American College of Medical Genetics and Genomics (ACMG)'s variant classification guidelines. Show less
Neuroendocrine prostate cancer (PCa) (NEPC), an aggressive subtype that is associated with poor prognosis, may arise after androgen deprivation therapy (ADT). We investigated the molecular mechanisms Show more
Neuroendocrine prostate cancer (PCa) (NEPC), an aggressive subtype that is associated with poor prognosis, may arise after androgen deprivation therapy (ADT). We investigated the molecular mechanisms by which ADT induces neuroendocrine differentiation in advanced PCa. We found that transmembrane protein 1 (MCTP1), which has putative Ca Show less
The cellular mechanism of the formation of abdominal aortic aneurysm (AAA) is very complicated. A series of sophisticated events eventually led to significant pathological changes in the anatomical st Show more
The cellular mechanism of the formation of abdominal aortic aneurysm (AAA) is very complicated. A series of sophisticated events eventually led to significant pathological changes in the anatomical structure and function of the arterial wall and they are still not clear nowadays. We pooled publicly available GEO datasets (GSE57691 and GSE47472) to get a comprehensive comparisons between normal tissues and AAA tissues to try to reveal molecular mechanism underlying the disease. Total 63 AAA samples and 18 normal tissue samples were compared and we fond that there were 784 significantly different gene (DEGs, threshold set as adjusted In the pathway enrichment, we found that FOXP3 related signaling pathways, inflammation-related cytokine signaling pathways, interleukin-8-CXCR1 related signaling pathways and VEGFA and FGFR1 related signal pathway were significantly enrichmented. In Weighted gene co-expression network analysis (WGCNA), we found that the key hub genes were significantly related to lipid catabolic metabolism, which further verified the possibility that AAA might relate to energy metabolism disorders. Based on the comprehensive analysis of previous high-throughput data and the validation of basic experiments, we found that the occurrence of AAA may be related to energy metabolism disorders and local inflammation. Show less
Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic a Show more
Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic architecture between the two. This study aims to explore their common genetic correlations by leveraging genome-wide association studies (GWAS) of smoking behavior-specifically, smoking initiation (SI), never smoking (NS), ever smoking (ES), cigarettes smoked per day (CPD), age of smoking initiation(ASI) and GERD. Firstly, we conducted global cross-trait genetic correlation analysis and heritability estimation from summary statistics (HESS) to explore the genetic correlation between smoking behavior and GERD. Then, a joint cross-trait meta-analysis was performed to identify shared "pleiotropic SNPs" between smoking behavior and GERD, followed by co-localization analysis. Additionally, multi-marker analyses using annotation (MAGMA) were employed to explore the degree of enrichment of single nucleotide polymorphism (SNP) heritability in specific tissues, and summary data-based Mendelian randomization (SMR) was further utilized to investigate potential functional genes. Finally, Mendelian randomization (MR) analysis was conducted to explore the causal relationship between the smoking behavior and GERD. Consistent genetic correlations were observed through global and local genetic correlation analyses, wherein SI, ES, and CPD showed significantly positive genetic correlations with GERD, while NS and ASI showed significantly negative correlations. HESS analysis also identified multiple significantly associated loci between them. Furthermore, three novel "pleiotropic SNPs" (rs4382592, rs200968, rs1510719) were identified through cross-trait meta-analysis and co-localization analysis to exist between SI, NS, ES, ASI, and GERD, mapping the genes MED27, HIST1H2BO, MAML3 as new pleiotropic genes between SI, NS, ES, ASI, and GERD. Moreover, both smoking behavior and GERD were found to be co-enriched in multiple brain tissues, with GMPPB, RNF123, and RBM6 identified as potential functional genes co-enriched in Cerebellar Hemisphere, Cerebellum, Cortex/Nucleus accumbens in SI and GERD, and SUOX identified in Caudate nucleus, Cerebellum, Cortex in NS and GERD. Lastly, consistent causal relationships were found through MR analysis, indicating that SI, ES, and CPD increase the risk of GERD, while NS and higher ASI decrease the risk. We identified genetic loci associated with smoking behavior and GERD, as well as brain tissue sites of shared enrichment, prioritizing three new pleiotropic genes and four new functional genes. Finally, the causal relationship between smoking behavior and GERD was demonstrated, providing insights for early prevention strategies for GERD. Show less
Enteroendocrine cells (EECs) produce over 20 gut hormones which contribute to intestinal physiology, nutrient metabolism and the regulation of food intake. The objective of this study was to generate Show more
Enteroendocrine cells (EECs) produce over 20 gut hormones which contribute to intestinal physiology, nutrient metabolism and the regulation of food intake. The objective of this study was to generate a comprehensive transcriptomic map of mouse EECs from the stomach to the rectum. EECs were purified by flow-cytometry from the stomach, upper small intestine, lower small intestine, caecum and large intestine of NeuroD1-Cre mice, and analysed by single cell RNA sequencing. Regional datasets were analysed bioinformatically and combined into a large cluster map. Findings were validated by L-cell calcium imaging and measurements of CCK secretion in vitro. 20,006 EECs across the full gastrointestinal tract could be subdivided based on their full transcriptome into 10 major clusters, each exhibiting a different pattern of gut hormone expression. EECs from the stomach were largely distinct from those found more distally, even when expressing the same hormone. Cell clustering was also observed when performed only using genes related to GPCR cell signalling, revealing GPCRs predominating in different EEC populations. Mc4r was expressed in 55% of Cck-expressing cells in the upper small intestine, where MC4R agonism was found to stimulate CCK release in primary cultures. Many individual EECs expressed more than one hormone as well as machinery for activation by multiple nutrients, which was supported by the finding that the majority of L-cells exhibited calcium responses to multiple stimuli. This comprehensive transcriptomic map of mouse EECs reveals patterns of GPCR and hormone co-expression that should be helpful in predicting the effects of nutritional and pharmacological stimuli on EECs from different regions of the gut. The finding that MC4R agonism stimulates CCK secretion adds to our understanding of the melanocortin system. Show less
Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). This study aimed to develop and validate a novel genet Show more
Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism. This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram. Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD. Chictr.org.cn , ChiCTR2100049131. Show less
E26 transformation-specific (ETS) factors have emerged as key mediators underlying human tumorigenesis. Here, we sought to characterize the expression pattern, biological roles, and clinical significa Show more
E26 transformation-specific (ETS) factors have emerged as key mediators underlying human tumorigenesis. Here, we sought to characterize the expression pattern, biological roles, and clinical significance of ETS Variant Transcription Factor 5 (ETV5) in head neck squamous cell carcinoma (HNSCC). ETV5 expression pattern in HNSCC was determined by bioinformatics interrogations and immunohistochemical staining in primary samples. The associations between its abundance with clinicopathological parameters, and patient survival were evaluated. Colony formation, CCK-8, flow cytometry, wound healing, and Transwell invasion assays, as well as xenograft models, were utilized to determine the phenotypic changes after ETV5 silencing in vitro and vivo. The potential binding of ETV5 in the Slug promoter was determined by ChIP-qPCR. ETV5 was significantly overexpressed in HNSCC samples. Its overexpression is significantly associated with aggressiveness features and reduced survival. ETV5 knockdown significantly inhibited cell proliferation, migration, invasion, and induced apoptosis in vitro, and impaired tumor growth in vivo. Moreover, ETV5-activated Slug transcription by binding its promoter region in HNSCC cells. Patients with ETV5 Our findings reveal that ETV5 serves as a novel prognostic biomarker and putative oncogene for HNSCC progression likely by activating Slug transcription. Show less
Glucagon-like peptide-1 (GLP-1)-based drugs have been approved by the United States Food and Drug Administration (FDA) and are widely used to treat type 2 diabetes mellitus (T2DM) and obesity. More re Show more
Glucagon-like peptide-1 (GLP-1)-based drugs have been approved by the United States Food and Drug Administration (FDA) and are widely used to treat type 2 diabetes mellitus (T2DM) and obesity. More recent developments of unimolecular peptides targeting multiple incretin-related receptors ("multi-agonists"), including the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and the glucagon (Gcg) receptor (GcgR), have emerged with the aim of enhancing drug benefits. In this study, we utilized human and mouse microglial cell lines, HMC3 and IMG, respectively, together with the human neuroblastoma SH-SY5Y cell line as cellular models of neurodegeneration. Using these cell lines, we studied the neuroprotective and anti-inflammatory capacity of several multi-agonists in comparison with a single GLP-1 receptor (GLP-1R) agonist, exendin-4. Our data demonstrate that the two selected GLP-1R/GIPR dual agonists and a GLP-1R/GIPR/GcgR triple agonist not only have neurotrophic and neuroprotective effects but also have anti-neuroinflammatory properties, as indicated by the decreased microglial cyclooxygenase 2 (COX2) expression, nitrite production, and pro-inflammatory cytokine release. In addition, our results indicate that these multi-agonists have the potential to outperform commercially available single GLP-1R agonists in neurodegenerative disease treatment. Show less
Dong Sun Oh, Eunha Kim, Guangqing Lu+31 more · 2024 · medRxiv : the preprint server for health sciences · Cold Spring Harbor Laboratory · added 2026-04-24
Pregnancy is a risk factor for increased severity of SARS-CoV-2 and other respiratory infections. The mechanisms underlying this risk have not been well-established, partly due to a limited understand Show more
Pregnancy is a risk factor for increased severity of SARS-CoV-2 and other respiratory infections. The mechanisms underlying this risk have not been well-established, partly due to a limited understanding of how pregnancy shapes immune responses. To gain insight into the role of pregnancy in modulating immune responses at steady state and upon perturbation, we collected peripheral blood mononuclear cells (PBMC), plasma, and stool from 226 women, including 152 pregnant individuals (n = 96 with SARS-CoV-2 infection and n = 56 healthy controls) and 74 non-pregnant women (n = 55 with SARS-CoV-2 and n = 19 healthy controls). We found that SARS-CoV-2 infection was associated with altered T cell responses in pregnant compared to non-pregnant women. Differences included a lower percentage of memory T cells, a distinct clonal expansion of CD4-expressing CD8 Show less
Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivota Show more
Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Here, we report that PTEN deficiency induced Krüppel-like factor 5 (KLF5) acetylation and that interruption of KLF5 acetylation orchestrated intricate interactions between cancer cells and CAFs that enhance FGF receptor 1 (FGFR1) signaling and promote tumor growth. Deacetylated KLF5 promoted tumor cells to secrete TNF-α, which stimulated inflammatory CAFs to release FGF9. CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 and sensitized PTEN-deficient prostate cancer to the AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rationale for combined therapies using inhibitors of AKT and CX3CR1. Show less
The aim of this study is to screen key target genes of osteoarthritis associated with aging and to preliminarily explore the associated immune infiltration cells and potential drugs. Differentially ex Show more
The aim of this study is to screen key target genes of osteoarthritis associated with aging and to preliminarily explore the associated immune infiltration cells and potential drugs. Differentially expressed senescence-related genes (DESRGs) selected from Cellular senescence-related genes (SRGs) and differentially expressed genes (DEGs) were analyzed using Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and protein-protein interaction networks. Hub genes in DESRGs were selected based on degree, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. CIBERSORTx and ssGSEA algorithms were then used to assess immune cell infiltration and to analyse the correlation between key DESRGs and immune infiltration. Finally, a miRNA-gene network of diagnostic genes was constructed and targeted drug prediction was performed. Combined with the DEGs and SRGs, we screened 19 DESRGs for further study. Five diagnostic genes were ultimately identified: CDKN1A, VEGFA, MCL1, SNAI1 and MYC. ROC analysis showed that the area under the curve (AUC). Correlation analysis showed that the five hub genes were closely associated with neutrophil, plasmacytoid dendritic cell, activated CD4 T-cell and type 2 T-helper cell infiltration in the development of Osteoarthritis (OA). Finally, we found that drugs such as lithium chloride, acetaminophen, curcumin, celecoxib and resveratrol could be targeted for the treatment of senescence-related OA. The results of this study indicate that CDKN1A, VEGFA, MCL1, SNAI1, and MYC are key biomarkers that can be used to predict and prevent early aging-related OA. Lithium chloride, acetaminophen, curcumin, celecoxib, and resveratrol can be used for personalized treatment of aging-related OA. Show less
The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to Show more
The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to investigate the effect of butyric acid on the proliferation and differentiation of the immortalized chicken preadipocyte 2 (ICP2). ICP2 were treated respectively with 12mM butyric acid for 48h in proliferation trial and 4mM butyric acid plus 200 μM oleic acid for 3 d in differentiation trial. For the proliferation trial, RNA-seq analysis revealed that 2039 genes were significantly up-regulated and 780 genes were significantly down-regulated with 12 mM butyric acid after 48 h treatment. Concurrently, Cell cycle, DNA replication and p53 signaling pathways were down-regulated in Butyric acid group. More importantly, 12 mM butyric acid restrained the expression of cell proliferation genes such as PCNA, CDK1 and CDK2 in Butyric acid group (P < 0.05), and the protein expression levels of PCNA and CDK1 were also significantly decreased (P < 0.05). The Oil red staining revealed a fewer presence of red fat droplets in ICP2 following treatment with 4 mM butyric acid, accompanied by decreased levels of total cholesterol (TC) and triglycerides (TG). RNA-seq analysis shown that the number of up and down-regulated genes were 2095 and 1042 respectively in OAB group (oleic acid+butyric acid) when compared with OA group (oleic acid). Meanwhile the AMPK signaling pathway, FOXO signaling pathway and focal adhesion were significantly enriched in OAB group. Additionally, 4 mM butyric acid inhibited the expression of lipid differentiation genes including FABP4, C/EBPα, PPARγ and LPL in OAB group (P < 0.05), as well as lipogenesis proteins such as FABP4, C/EBP-α and PPARγ (P < 0.05). In conclusion, 12 mM butyric acid effectively inhibited the proliferation of ICP2 by slowing down cell cycle progression, while 4 mM butyric acid alleviated lipid deposition by reducing the production of lipid droplets through inhibiting the expression of lipid differentiation marker genes and proteins. Show less
Adenosine-to-inosine (A-to-I) editing is the most common type of RNA editing in humans and the role of A-to-I RNA editing remains unclear in Parkinson's disease (PD). We aimed to explore the potential Show more
Adenosine-to-inosine (A-to-I) editing is the most common type of RNA editing in humans and the role of A-to-I RNA editing remains unclear in Parkinson's disease (PD). We aimed to explore the potential causal association between A-to-I editing and PD, and to assess whether changes in A-to-I editing were associated with cognitive progression in PD. The RNA-seq data from 380 PD patients and 178 healthy controls in the Parkinson's Progression Marker Initiative cohort was used to quantify A-to-I editing sites. We performed cis-RNA editing quantitative trait loci analysis and a two-sample Mendelian Randomization (MR) study by integrating genome-wide association studies to infer the potential causality between A-to-I editing and PD pathogenesis. The potential causal A-to-I editing sites were further confirmed by Summary-data-based MR analysis. Spearman's correlation analysis was performed to characterize the association between longitudinal A-to-I editing and cognitive progression in patients with PD. We identified 17 potential causal A-to-I editing sites for PD and indicated that genetic risk variants may contribute to the risk of PD through A-to-I editing. These A-to-I editing sites were located in genes NCOR1, KANSL1 and BST1. Moreover, we observed 57 sites whose longitudinal A-to-I editing levels correlated with cognitive progression in PD. We found potential causal A-to-I editing sites for PD onset and longitudinal changes of A-to-I editing were associated with cognitive progression in PD. We anticipate this study will provide new biological insights and drive the discovery of the epitranscriptomic role underlying Parkinson's disease. Show less
The coronavirus disease 2019 (COVID-19) pandemic has caused extensive disruption of public health worldwide. There were reports of COVID-19 patients having multiple complications. This study investiga Show more
The coronavirus disease 2019 (COVID-19) pandemic has caused extensive disruption of public health worldwide. There were reports of COVID-19 patients having multiple complications. This study investigated COVID-19 from a genetic perspective. We conducted RNA sequencing (RNA-Seq) analysis of respiratory tract samples from 24 patients with COVID-19. Eight patients receiving mechanical ventilation or extracorporeal membrane oxygenation were regarded as severe cases; the remaining 16 patients were regarded as non-severe cases. After quality control, statistical analyses were performed by logistic regression and the Kolmogorov-Smirnov test to identify genes associated with disease severity. Six genes were associated with COVID-19 severity in both statistical tests, namely RNA sequencing analysis showed that severe acute respiratory syndrome coronavirus 2 infection is associated with the overexpression of genes involved in nervous system disorders. Show less
Lung adenocarcinoma (LUAD) is a malignant tumor of the respiratory system that has a poor 5-year survival rate. Anoikis, a type of programmed cell death, contributes to tumor development and metastasi Show more
Lung adenocarcinoma (LUAD) is a malignant tumor of the respiratory system that has a poor 5-year survival rate. Anoikis, a type of programmed cell death, contributes to tumor development and metastasis. The aim of this study was to develop an anoikis-based stratified model, and a multivariable-based nomogram for guiding clinical therapy for LUAD. Through differentially expressed analysis, univariate Cox, LASSO Cox regression, and random forest algorithm analysis, we established a 4 anoikis-related genes-based stratified model, and a multivariable-based nomogram, which could accurately predict the prognosis of LUAD patients in the TCGA and GEO databases, respectively. The low and high-risk score LUAD patients stratified by the model showed different tumor mutation burden, tumor microenvironment, gemcitabine sensitivity and immune checkpoint expressions. Through immunohistochemical analysis of clinical LUAD samples, we found that the 4 anoikis-related genes (PLK1, SLC2A1, ANGPTL4, CDKN3) were highly expressed in the tumor samples from clinical LUAD patients, and knockdown of these genes in LUAD cells by transfection with small interfering RNAs significantly inhibited LUAD cell proliferation and migration, and promoted anoikis. In conclusion, we developed an anoikis-based stratified model and a multivariable-based nomogram of LUAD, which could predict the survival of LUAD patients and guide clinical treatment. Show less
This study aimed to evaluate the causal relationship between Interleukin-27 (IL-27) and osteoporosis by bidirectional Mendelian randomization (MR) analysis. Firstly, the genome-wide association study Show more
This study aimed to evaluate the causal relationship between Interleukin-27 (IL-27) and osteoporosis by bidirectional Mendelian randomization (MR) analysis. Firstly, the genome-wide association study summary data of osteoporosis (finn-b-M13_OSTEOPOROSIS) and IL-27 levels (ebi-a-GCST90012017) were picked out from the Integrative Epidemiology Unit (IEU) OpenGWAS database. After filtrating instrumental variables (IVs), the bidirectional MR analysis between IL-27 levels and osteoporosis was performed by MR-Egger, Weighted median, Simple mode, Weighted mode, and Inverse variance weighted (IVW). Subsequently, the sensitivity analysis was adopted to evaluate the reliability of the MR results via the Heterogeneity, Horizontal pleiotropy test and Leave-One-Out (LOO) analysis. Finally, the enrichment analysis of genes corresponding to SNPs related to IL-27 levels derived from eQTLGen database was executed to explore in depth the biological function and regulatory mechanism of these genes on osteoporosis occurrence. The bidirectional MR results based on IVW method revealed that IL-27 level as a risk factor was causally related to osteoporosis (P = 0.004, odds ratio (OR) = 1.123, 95% confidence interval (CI) = 1.037-1.217), whereas osteoporosis was not in significant connection with IL-27 levels (P > 0.05). In regard to the sensitivity analysis for forward MR results, there was no heterogeneity and horizontal pleiotropy, and no SNPs relevant to IL-27 levels existed severe bias, suggesting the reliability of forward MR analysis. Furthermore, a total of 74 genes corresponding to 26 SNPs of IL-27 levels were obtained and were mainly involved in immune and inflammatory pathways including MyD88-dependent toll-like receptor signaling pathway, Toll-like receptor signaling pathway, cytosolic DNA-sensing pathway and so forth. This study supported that IL-27 level as a risk factor was causally connected with osteoporosis and might regulate the disease occurrence and progression by means of immune and inflammatory mechanisms, which could provide important reference and evidence for further exploring the role of IL-27 in the development of osteoporosis. Show less
The apolipoprotein A5 ( In a case study conducted at the First Affiliated Hospital of Xinjiang Medical University between Jan 2019 and Dec 2021, we examined a total of 700 cases of EHT along with 700 Show more
The apolipoprotein A5 ( In a case study conducted at the First Affiliated Hospital of Xinjiang Medical University between Jan 2019 and Dec 2021, we examined a total of 700 cases of EHT along with 700 corresponding controls. The serum concentrations of various lipid parameters were measured by enzymatic method, while the genotyping of the SNP was performed using the improved multiplex ligation detection reaction (iMLDR) method. The independent risk factors of EHT were identified from multivariable logistic regression analysis. The nomogram prediction model that incorporated the Our study revealed a higher prevalence of the G allele of the rs662799 variant in individuals diagnosed with EHT compared to the control group. Logistic regression analysis indicated that with the adjustment of other confounders, the observed difference between the two groups remained statistically significant [odds ratio (OR) =1.519; 95% confidence interval (CI): 1.203-1.917; P<0.001]. Based on 8 independent risk factors including In our study, the rs662799 variant of the Show less
A high-fat diet (HFD) is recognized as an important contributor to inflammatory bowel disease (IBD). However, the precise underlying mechanism of HFD on IBD remains elusive. This study aimed to invest Show more
A high-fat diet (HFD) is recognized as an important contributor to inflammatory bowel disease (IBD). However, the precise underlying mechanism of HFD on IBD remains elusive. This study aimed to investigate the potential mechanism by which HFD affects IBD using 16S rRNA-sequencing and RNA-seq technology. Results indicated that HFD-treated mice exhibited notable alternations in the structure and composition of the gut microbiota, with some of these alternations being associated with the pathogenesis of IBD. Analysis of the colon transcriptome revealed 11 hub genes and 7 hub pathways among control, DSS-induced colitis, and HFD + DSS-treated groups. Further analysis explores the relationship between the hub pathways and genes, as well as the hub genes and gut microbiota. Overall, the findings indicate that the impact of HFD on DSS-induced colitis may be linked to intestinal dysbiosis and specific genes such as Show less
Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infecti Show more
Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD. Show less
To explore the patterns of differentially expressed genes (DEGs) associated with different growth rates in rock carp (Procypris rabaudi), transcriptome sequencing was performed on the muscle, liver, a Show more
To explore the patterns of differentially expressed genes (DEGs) associated with different growth rates in rock carp (Procypris rabaudi), transcriptome sequencing was performed on the muscle, liver, and brain tissues of rock carp. Subsequently, bioinformatics analysis was conducted, and 2129, 1380, and 415 DEGs were identified in the muscle, liver, and brain tissues, respectively. GO enrichment and KEGG pathway analysis revealed that genes related to appetite regulation, protein degradation and digestion, lipid transport and metabolisms, and glycolysis/gluconeogenesis were upregulated in individuals with slower growth rates. Differential expression analysis identified 21 genes associated with feeding and metabolism across three tissues, including mc4r, npy, and npry in brain tissue; fatp, fabp, pparα, and apo in liver tissue; and prss, ctrl, and cela in muscle tissue. All these genes were upregulated in the slow-growing fish. Furthermore, weighted gene co-expression network analyses, including three modules (yellow, turquoise, and brown), significantly associated with growth. A network map that included these three modules enabled the identification of a series of hub genes, including rp13a, ube2o, h6pd, etc. These genes may be key candidate genes regulating the growth of rock carp. This study contributes to a deeper understanding of the growth control mechanism in rock carp and offers a scientific basis for efficient breeding and species improvement. Show less