Non-obstructive azoospermia (NOA) is a major contributor of male infertility. Herein, we used existing datasets to identify novel biomarkers for the diagnosis and prognosis of NOA, which could have gr Show more
Non-obstructive azoospermia (NOA) is a major contributor of male infertility. Herein, we used existing datasets to identify novel biomarkers for the diagnosis and prognosis of NOA, which could have great significance in the field of male infertility. NOA datasets were obtained from the Gene Expression Omnibus (GEO) database. CIBERSORT was utilized to analyze the distributions of 22 immune cell populations. Hub genes were identified by applying weighted gene co-expression network analysis (WGCNA), machine learning methods, and protein-protein interaction (PPI) network analysis. The expression of hub genes was verified in external datasets and was assessed by receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was applied to explore the important functions and pathways of hub genes. The mRNA-microRNA (miRNA)-transcription factors (TFs) regulatory network and potential drugs were predicted based on hub genes. Single-cell RNA sequencing data from the testes of patients with NOA were applied for analyzing the distribution of hub genes in single-cell clusters. Furthermore, testis tissue samples were obtained from patients with NOA and obstructive azoospermia (OA) who underwent testicular biopsy. RT-PCR and Western blot were used to validate hub gene expression. Two immune-related oxidative stress hub genes ( It appears that Show less
Pulmonary neutrophils may play a crucial role in the development of bronchiolitis obliterans (BO) following measles virus infection. IL-27 could potentially have a negative regulatory effect on the re Show more
Pulmonary neutrophils may play a crucial role in the development of bronchiolitis obliterans (BO) following measles virus infection. IL-27 could potentially have a negative regulatory effect on the release of reactive oxygen species and cytotoxic granules in neutrophils. To investigate the levels of IL-27 in the bronchoalveolar lavage fluid (BALF) of children with post-infectious bronchiolitis obliterans (PIBO) and analyze the relationship between IL-27 levels and neutrophil proportions. A total of 24 children with PIBO were recruited for the experimental group, while 23 children with bronchial foreign bodies were included in the control group. Bronchoscopic alveolar lavage was performed in both groups. The levels of IL-27 in BALF were measured using enzyme-linked immunosorbent assay (ELISA). The proportions of neutrophils in BALF were determined by smear staining. The relationship between the levels of IL-27 in BALF and the neutrophil proportions was analyzed by the Pearson test. The levels of IL-27 in BALF were significantly lower in children with PIBO compared to children with bronchial foreign bodies (p<0.05). Additionally, the proportions of neutrophils in BALF were significantly higher in children with PIBO compared to children with bronchial foreign bodies (p<0.05). The levels of IL-27 were negatively correlated with the neutrophil proportions in BALF in children with PIBO (p<0.05), but not in children with bronchial foreign bodies (p>0.05). The present study suggests that a decrease in IL-27 may be associated with an increase in neutrophils in BALF and may contribute to the pathogenesis of PIBO. Show less
The role of circulating metabolome in cognitive impairment is inconclusive, and whether the associations are in the severity-dependent manner remains unclear. We aimed to identify plasma metabolites a Show more
The role of circulating metabolome in cognitive impairment is inconclusive, and whether the associations are in the severity-dependent manner remains unclear. We aimed to identify plasma metabolites associated with cognitive impairment and evaluate the added predictive capacity of metabolite biomarkers on incident cognitive impairment beyond traditional risk factors. In the Rugao Longevity and Ageing Study (RuLAS), plasma metabolome was profiled by nuclear magnetic resonance spectroscopy. Participants were classified into the cognitively normal, moderately impaired, and severely impaired groups according to their performance in two objective cognitive tests. A two-step strategy of cross-sectional discovery followed by prospective validation was applied. In the discovery stage, we included 1643 participants (age: 78.9 ± 4.5 years) and conducted multinomial logistic regression. In the validation stage, we matched 68 incident cases of cognitive impairment (moderately-to-severely impaired) during the 2-year follow-up with 204 cognitively normal controls by age and sex at a 1:3 ratio, and conducted conditional logistic regression. We identified 28 out of 78 metabolites cross-sectionally related to severely impaired cognition, among which IDL particle number, ApoB in IDL, leucine, and valine were prospectively associated with 28%, 28%, 29%, and 33% lower risk of developing cognitive impairment, respectively. Incorporating 13 metabolite biomarkers selected through Lasso regression into the traditional risk factors-based prediction model substantially improved the ability to predict incident cognitive impairment (AUROC: 0.839 vs. 0.703, P < 0.001; AUPRC: 0.705 vs. 0.405, P < 0.001). This study identified specific plasma metabolites related to cognitive impairment. Incorporation of specific metabolites substantially improved the prediction performance for cognitive impairment. Show less
Organophosphate esters (OPEs) exposure could affect offspring health. However, the underlying mechanisms are not well documented. Based on a birth cohort study, we aimed to investigate the association Show more
Organophosphate esters (OPEs) exposure could affect offspring health. However, the underlying mechanisms are not well documented. Based on a birth cohort study, we aimed to investigate the associations among gestational OPEs exposure, placental DNA methylation levels of peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes, and fetal growth. We measured the concentrations of eight OPE metabolites in maternal urine samples and neonatal anthropometric measurements in 733 mother-child pairs. In 327 placental samples, we assessed the DNA methylation levels of 14 genes which were involved in the PPARs signaling pathway and expressed in placenta. Multiple linear regression models were used to examine the associations of OPEs exposure with placental DNA methylation, and of OPEs and placental DNA methylation with neonatal anthropometric measurements. Causal mediation analyses were conducted to examine the potential mediating role of placental DNA methylation in the pathway between OPEs exposure and fetal growth. We observed a general pattern of OPEs exposure being associated with hypermethylation of candidate genes, with statistically significant associations identified for several OPEs with RXRA, ACAA1, ACADL, ACADM, PLTP, and NR1H3 methylation. Further, gestational exposure to BCIPP, DPP, BBOEP, ∑NCl-OPEs, and ∑OPEs tended to be associated with lower anthropometric measurements, with more significant associations observed on arm circumference, and abdominal and back skinfold thickness. Notably, RXRA, ACAA1, ACOX1, CPT2, ACADM, and NR1H3 methylation tended to be associated with lower neonatal anthropometric measurements, especially for abdominal and back skinfold thickness. Moreover, mediation analyses showed that 19.42 % of the total effect of DPP on the back skinfold thickness was mediated by changes in RXRA methylation, and there was a significant indirect effect of RXRA methylation. Gestational OPEs exposure could disrupt the placental DNA methylation levels of PPAR signaling pathway-related genes, which might contribute to the effect of OPEs on fetal growth. Show less
Spurs, which mainly appear in roosters, are protrusions near the tarsometatarsus on both sides of the calves of chickens, and are connected to the tarsometatarsus by a bony core. As a male-biased morp Show more
Spurs, which mainly appear in roosters, are protrusions near the tarsometatarsus on both sides of the calves of chickens, and are connected to the tarsometatarsus by a bony core. As a male-biased morphological characteristic, the diameter and length of spurs vary significantly between different individuals, mainly related to genetics and age. As a specific behavior of hens, egg-laying also varies greatly between individuals in terms of traits such as age at first egg ( Show less
To explore the relationship between vitamin D (VitD) deficiency and the apolipoprotein B/apolipoprotein A1 (apo B/A1) in type 2 diabetes mellitus (T2DM) patients. This was a retrospective study that l Show more
To explore the relationship between vitamin D (VitD) deficiency and the apolipoprotein B/apolipoprotein A1 (apo B/A1) in type 2 diabetes mellitus (T2DM) patients. This was a retrospective study that lasted 2 years and 6 months, collecting information and laboratory data from 784 patients with T2DM. Patients were divided into VitD deficiency group (n = 433) and non-VitD deficiency group (n = 351) based on VitD levels. Calculated apo B/A1 ratio, and patients were further divided into high-apo B/A1 group (n = 392) and low-apo B/A1 group (n = 392) based on the median of the apo B/A1. All data were analyzed using Prism 8.0.1 and R version 4.3.1 software. Apo B/A1 levels of T2DM patients combined with VitD deficiency was significantly higher than that of non-VitD deficiency patients, and the VitD levels of patients with high apo B/A1 was significantly lower than that patients with low apo B/A1 (all P<0.001). Spearman correlation analysis showed that VitD levels were negatively correlated with apo B/A1 (r=-0.238, P<0.001). Multiple linear regression analysis revealed after adjusting other factors, VitD levels were significantly negatively associated with apo B/A1 (β=-0.123, P=0.001). Binary logistic regression analysis showed apoB/A1 was an independent risk factor for VitD deficiency in T2DM patients. Restrictive cubic spline indicated a significant linear relationship between apoB/A1 and VitD deficiency (P general trend <0.0001, P nonlinear = 0.0896), after stratification of gender, the results showed that apo B/A1 was more susceptible to VitD deficiency in female patients. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve, sensitivity and specificity of the apo B/A1 for VitD deficiency were 0.654, 66.3% and 59.8%, respectively. The apo B/A1 was significantly negatively associated with VitD levels and an independent risk factor for VitD deficiency in patients with T2DM. Show less
Migraine is a common primary headache that has a significant impact on patients' quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poo Show more
Migraine is a common primary headache that has a significant impact on patients' quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background. The aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort. In this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom's MALDI-TOF iPLEX platform. In univariate analysis, The study indicates that there is an association between Show less
This study aimed to investigate the possible mechanisms by which ANGPTL4 is involved in the pathogenesis of choroidal neovascularization (CNV) and subretinal fibrosis. Differentially expressed genes i Show more
This study aimed to investigate the possible mechanisms by which ANGPTL4 is involved in the pathogenesis of choroidal neovascularization (CNV) and subretinal fibrosis. Differentially expressed genes in retinal pigmented epithelium (RPE)-choroid-sclera complex tissues from nAMD patients and control individuals were identified via the GEO database, followed by GO and KEGG analyses. A Venn diagram was used to identify EndMT-related DEGs. A logistic regression model was constructed to screen for prognostic genes. Laser-induced CNV mouse models were established and validated with FFA and OCTA. The expression of ANGPTL4 and EndMT-related markers in the RPE-choroid-sclera complex was measured via RT‒qPCR and Western blotting. TGF-β2-induced HUVECs were used as EndMT cell models, and specific siRNAs targeting ANGPTL4 (si-ANGPTL4) were designed and screened. The effects of ANGPTL4 knockdown on the migration and invasion of HUVECs were also examined. Laser-induced CNV mouse models were constructed, and an intravitreal injection of cholesterol-modified si-ANGPTL4 was used to knock down ANGPTL4. FFA, OCTA and immunofluorescence staining were used to observe CNV formation and subretinal fibrosis, and the expression of ANGPTL4 and EndMT-related markers was determined. ANGPTL4 expression was significantly increased in mice with CNV and colocalized with IB4. In TGF-β2-induced EndMT, ANGPTL4 was also upregulated, and its knockdown led to the inhibition of EndMT and cell migration and invasion, while its overexpression promoted the EndMT process. ANGPTL4 knockdown reduced the formation of CNV and subretinal fibrosis in mice with CNV by suppressing EndMT. ANGPTL4 may promote CNV and subretinal fibrosis through EndMT, suggesting that ANGPTL4 may be a novel potential target for nAMD therapy. Show less
Heike Schönherr, Pelin Ayaz, Alexander M Taylor+26 more · 2024 · Proceedings of the National Academy of Sciences of the United States of America · National Academy of Sciences · added 2026-04-24
Fibroblast growth factor receptor (FGFR) kinase inhibitors have been shown to be effective in the treatment of intrahepatic cholangiocarcinoma and other advanced solid tumors harboring
Hepatocellular carcinoma (HCC) is among the most prevalent digestive system malignancies and is associated with a poor prognosis. Necroptosis, a form of regulated death mediated by death receptors, ex Show more
Hepatocellular carcinoma (HCC) is among the most prevalent digestive system malignancies and is associated with a poor prognosis. Necroptosis, a form of regulated death mediated by death receptors, exhibits characteristics of both necrosis and apoptosis. Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in tumor necroptosis. This study aims to identify the necroptosis-related lncRNAs (np-lncRNA) in HCC and investigate their relationships with prognosis. The RNA-sequencing data, along with clinicopathological and survival information of HCC patients were sourced from The Cancer Genome Atlas (TCGA) database. The np-lncRNAs were analyzed to assess their potential in predicting HCC prognosis. Prognostic signatures related to necroptosis were constructed using stepwise multivariate Cox regression analysis. The prognosis of patients was compared using Kaplan-Meier (KM) analysis. The accuracy of the prognostic signature was evaluated using Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Quantitative real-time polymerase chain reaction(qPCR) was employed to validate the lncRNAs expression levels of lncRNAs among samples from an independent cohort. The np-lncRNAs ZFPM2-AS1, AC099850.3, BACE1-AS, KDM4A-AS1 and MKLN1-AS were identified as potential prognostic biomarkers. The prognostic signature constructed from these np-lncRNAs achieved an Area Under the Curve (AUC) of 0.773. Based on the risk score derived from the signature, patients were divided into two groups, with the high-risk group exhibiting poorer overall survival. Gene Set Enrichment Analysis (GSEA) revealed significantly different between the low risk and high risk groups in tumor-related pathways (such as mTOR, MAPK and p53 signaling pathways) and immune-related functions (like T cell receptor signaling pathway and natural killer cell mediated cytotoxicity). The increased expression of np-lncRNAs was confirmed in another independent HCC cohort. This signature offers a dependable method for forecasting the prognosis of HCC patients. Our findings indicate a subset of np-lncRNA biomarkers that could be utilized for prognosis prediction and personalized treatment strategies of HCC patients. Show less
D. Yan, D. Chen, H.-J. Im · 2024 · Journal of cellular biochemistry · Wiley · added 2026-04-24
D. Yan, D. Chen, and H.-J. Im, "Fibroblast Growth Factor-2 Promotes Catabolism via FGFR1-Ras-Raf-MEK1/2-ERK1/2 Axis That Coordinates With the PKCδ Pathway in Human Articular Chondrocytes," Journal of Show more
D. Yan, D. Chen, and H.-J. Im, "Fibroblast Growth Factor-2 Promotes Catabolism via FGFR1-Ras-Raf-MEK1/2-ERK1/2 Axis That Coordinates With the PKCδ Pathway in Human Articular Chondrocytes," Journal of Cellular Biochemistry 113, no. 9 (2012): 2856-2865, https://doi.org/10.1002/jcb.24160. The above article, published online on 5 April 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has occurred due to concerns related to the data presented in the article raised by the Office of Research Compliance at Rush University Medical Center following an investigation jointly conducted by Rush University and the Jesse Brown Veterans Affairs Medical Center (JBVAMC). Specifically, image elements of the experimental data in Figures 2, 4 A and 5 C were found to have been used by the same author(s) for publication elsewhere in a different scientific context. The corresponding author, Dr. Hee-Jeong Im Sampen, has been informed of the decision to retract but did not agree with it, as she is confident that any errors in the publication do not impact the reliability of the paper's findings. She also advised the editors that she stands ready to cooperate fully to make any necessary corrections. However, the article is retracted as the editors lost trust in the accuracy of the data and consider the conclusions invalid. Show less
Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer's disease (AD Show more
Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer's disease (AD). This study delves into the intricate role of miR-671/CDR1as regulation in the etiology of AD-like lesions triggered by chronic Pb exposure in adult mice. To emulate the chronic effects of Pb, we established a rodent model spanning 10 months of controlled Pb administration, dividing 52 C57BL/6J mice into groups receiving varying concentrations of Pb (1, 2, or 4 g/L) alongside an unexposed control. Blood Pb levels were monitored using serum samples to ensure accurate dosing and to correlate with observed toxicological outcomes. Utilizing the Morris water maze, a robust behavioral assay for assessing cognitive functions, we documented a dose-dependent decline in learning and memory capabilities among the Pb-exposed mice. Histopathological examination of the hippocampal tissue revealed tell-tale signs of AD-like neurodegeneration, characterized by the accumulation of amyloid plaques and neurofibrillary tangles. At the molecular level, a significant upregulation of AD-associated genes, namely amyloid precursor protein (APP), β-secretase 1 (BACE1), and tau, was observed in the hippocampal tissue of Pb-exposed mice. This was accompanied by a corresponding surge in the protein levels of APP, BACE1, amyloid-β (Aβ), and phosphorylated tau (p-tau), further implicating Pb in the dysregulation of these key AD markers. The expression of CDR1as, a long non-coding RNA implicated in AD pathogenesis, was found to be suppressed in Pb-exposed mice. This observation suggests a potential mechanistic link between Pb-induced neurotoxicity and the dysregulation of the CDR1as/miR-671 axis, which warrants further investigation. Moreover, our study identified a dose-dependent alteration in the intracellular and extracellular levels of the transcription factor nuclear factor-kappa B (NF-κB). This finding implicates Pb in the modulation of NF-κB signaling, a pathway that plays a pivotal role in neuroinflammation and neurodegeneration. In conclusion, our findings underscored the deleterious effects of Pb exposure on the CNS, leading to the development of AD-like pathology. The observed modulation of NF-κB signaling and miR-671/CDR1as regulation provides a plausible mechanistic framework for understanding the neurotoxic effects of Pb and its potential contribution to AD pathogenesis. Show less
An in-situ nanozyme signal tag combined with a DNA-mediated universal antibody-oriented strategy was proposed to establish a high-performance immunosensing platform for Alzheimer's disease (AD)-relate Show more
An in-situ nanozyme signal tag combined with a DNA-mediated universal antibody-oriented strategy was proposed to establish a high-performance immunosensing platform for Alzheimer's disease (AD)-related biomarker detection. Briefly, a Zr-based metal-organic framework (MOF) with peroxidase (POD)-like activity was synthesized to encapsulating the electroactive molecule methylene blue (MB), and subsequently modified with a layer of gold nanoparticles on its surface. This led to the creation of double POD-like activity nanozymes surrounding the MB molecule to form a nanozyme signal tag. A large number of hydroxyl radicals were generated by the nanozyme signal tag with the help of H Show less
To investigate the role of high-mobility group AT-hook 2 (HMGA2) in osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) and the effect of Bioinformatics studies using the GEO Show more
To investigate the role of high-mobility group AT-hook 2 (HMGA2) in osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) and the effect of Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs. The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2. Primary mouse ADSCs (mADSCs) were transfected with GEO database analysis showed that HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs, and Show less
Cardiovascular disease (CVD) represents the leading cause of death worldwide. For individuals at elevated risk for cardiovascular disease, early detection and monitoring of lipid status is imperative. Show more
Cardiovascular disease (CVD) represents the leading cause of death worldwide. For individuals at elevated risk for cardiovascular disease, early detection and monitoring of lipid status is imperative. The majority of lipid measurements conducted in hospital settings employ optical detection, which necessitates the use of relatively large-sized detection machines. It is, therefore, necessary to develop point-of-care testing (POCT) for lipoprotein in order to monitor CVD. To enhance the management and surveillance of CVD, this study sought to develop a POCT approach for apolipoprotein B (ApoB) utilizing a shear horizontal surface acoustic wave (SH-SAW) platform to assess the risk of heart disease. The platform employs a reflective SH-SAW sensor to reduce the sensor size and enhance the phase-shifted signals. In this study, the platform was utilized to monitor the impact of a weekly almond and oat milk or statins intervention on alterations in CVD risk. The SH-SAW ApoB test exhibited a linear range of 0 to 212 mg/dL, and a coefficient correlation (R) of 0.9912. Following a four-week intervention period, both the almond and oat milk intervention (-23.3%, Show less
Drug-induced liver injury (DILI) is a significant global health issue that poses high mortality and morbidity risks. One commonly observed cause of DILI is acetaminophen (APAP) overdose. GSDME is an e Show more
Drug-induced liver injury (DILI) is a significant global health issue that poses high mortality and morbidity risks. One commonly observed cause of DILI is acetaminophen (APAP) overdose. GSDME is an effector protein that induces non-canonical pyroptosis. In this study, the activation of GSDME, but not GSDMD, in the liver tissue of mice and patients with APAP-DILI is reported. Knockout of GSDME, rather than GSDMD, in mice protected them from APAP-DILI. Mice with hepatocyte-specific rescue of GSDME reproduced APAP-induced liver injury. Furthermore, alterations in the immune cell pools observed in APAP-induced DILI, such as the replacement of TIM4 Show less
Schizophrenia significantly impacts cognitive and behavioral functions and is primarily treated with second-generation antipsychotics (SGAs) such as olanzapine. Despite their efficacy, these drugs are Show more
Schizophrenia significantly impacts cognitive and behavioral functions and is primarily treated with second-generation antipsychotics (SGAs) such as olanzapine. Despite their efficacy, these drugs are linked to serious metabolic side effects which can diminish patient compliance, worsen psychiatric symptoms and increase cardiovascular disease risk. This study explores the hypothesis that SGAs affect the molecular determinants of synaptic plasticity and brain activity, particularly focusing on the lateral septum (LS) and its interactions within hypothalamic circuits that regulate feeding and energy expenditure. Utilizing functional ultrasound imaging, RNA sequencing, and weighted gene co-expression network analysis, we identified significant alterations in the functional connection between the hypothalamus and LS, along with changes in gene expression in the LS of mice following prolonged olanzapine exposure. Our analysis revealed a module closely linked to increases in body weight and adiposity, featuring genes primarily involved in lipid metabolism pathways, notably Show less
Autophagy is a ubiquitous pathological/physiological antioxidant cellular reaction in eukaryotic cells. Vacuolar protein sorting 34 (Vps34 or PIK3C3), which plays a crucial role in autophagy, has rece Show more
Autophagy is a ubiquitous pathological/physiological antioxidant cellular reaction in eukaryotic cells. Vacuolar protein sorting 34 (Vps34 or PIK3C3), which plays a crucial role in autophagy, has received much attention. As the only Class III phosphatidylinositol-3 kinase in mammals, Vps34 participates in vesicular transport, nutrient signaling and autophagy. Dysfunctionality of Vps34 induces carcinogenesis, and abnormal autophagy mediated by dysfunction of Vps34 is closely related to the pathological progression of various human diseases, which makes Vps34 a novel target for tumor immunotherapy. In this review, we summarize the molecular mechanisms underlying macroautophagy, and further discuss the structure-activity relationship of Vps34 inhibitors that have been reported in the past decade as well as their potential roles in anticancer immunotherapy to better understand the antitumor mechanism underlying the effects of these inhibitors. Show less
Reducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance fe Show more
Reducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed. The results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P < 0.05), and the half-even-chamber rate was significantly increased (P < 0.05); (2) The mRNA expression levels of Cd36, Dgat2, Apob, Fatp4, Fabp2, and Mttp in the small intestine were significantly increased (P < 0.05). (3) Furthermore, liver TG content significantly decreased (P < 0.05), and the mRNA expression level of Fasn in liver was significantly decreased (P < 0.05), while the expression of Apob, Lpl, Cpt-1, and Pparα significantly increased (P < 0.05). (4) The mRNA expression levels of Lpl and Fatp4 in adipose tissue were significantly increased (P < 0.05), while the expression of Atgl was significantly decreased (P < 0.05). (5) Compared with the reduced oil diet group, the half-evading rate and abdominal fat rate of broilers in the reduced oil diet + 500 mg/kg emulsifier group were significantly increased (P < 0.05), and the serum level of LDL-C increased significantly (P < 0.05)0.6) The mRNA expression levels of Cd36, Fatp4, Dgat2, Apob, and Mttp in the small intestine were significantly increased (P < 0.05). 7) The mRNA expression levels of Fasn and Acc were significantly decreased in the liver (P < 0.05), while the mRNA expression levels of Lpin1, Dgat2, Apob, Lpl, Cpt-1, and Pparα were significantly increased (P < 0.05). These results suggest that dietary emulsifier can enhance the fat utilization efficiency of broilers by increasing the small intestinal fatty acid uptake capacity, inhibiting hepatic fatty acid synthesis and promoting hepatic TG synthesis and transport capacity. This study provides valuable insights for the potential use of emulsifier supplementation to improve the performance of broiler chickens. 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
The relationship between insulin resistance-related indices and the outcomes of acute ischemic stroke (AIS) is still unclear. This study aimed to explore the association between the Apo B/Apo A-1 rati Show more
The relationship between insulin resistance-related indices and the outcomes of acute ischemic stroke (AIS) is still unclear. This study aimed to explore the association between the Apo B/Apo A-1 ratio and the Prognostic Nutritional Index (PNI) with the 90-day outcomes of AIS. A total of 2011 AIS patients with a 3-month follow-up were enrolled in the present study from January 2017 to July 2021. Multivariate logistic regression modeling was performed to analyze the relationship between Apo B/Apo A-1 ratio, PNI, and AIS poor outcomes. The mediating effect between the three was analyzed using the Bootstrap method with PNI as the mediating variable. Among the 2011 included AIS patients, 20.3% had a poor outcome. Patients were categorized according to quartiles of Apo B/Apo A-1 ratio and PNI. Multivariate logistic regression revealed that the fourth Apo B/Apo A-1 ratio quartile had poorer outcomes than the first quartile (OR 1.75,95%CL 1.21-2.53, P=0.003), and the fourth PNI quartile exhibited a lower risk of poor outcomes than the first quartile (OR 0.40, 95%CL 0.27-0.61, P<0.001). PNI displayed a significant partially mediating effect (21.4%) between the Apo B/Apo A-1 ratio and poor AIS outcomes. The Apo B/Apo A-1 ratio is a risk factor for poor AIS outcomes, whereas PNI acts as a protective factor. The association between the ApoB/ApoA-1 ratio and poor AIS outcomes was partially mediated by PNI. Show less
Recently, FGFR4 has become a hot target for the treatment of cancer owing to its important role in cellular physiological processes. FGFR4 has been validated to be closely related to the occurrence of Show more
Recently, FGFR4 has become a hot target for the treatment of cancer owing to its important role in cellular physiological processes. FGFR4 has been validated to be closely related to the occurrence of cancers, such as hepatocellular carcinoma, rhabdomyosarcoma, breast cancer and colorectal cancer. Hence, the development of FGFR4 small-molecule inhibitors is essential to further understanding the functions of FGFR4 in cancer and the treatment of FGFR4-dependent diseases. Given the particular structures of FGFR1-4, the development of FGFR4 selective inhibitors presents significant challenges. The non-conserved Cys552 in the hinge region of the FGFR4 complex becomes the key to the selectivity of FGFR4 and FGFR1/2/3 inhibitors. In this review, we systematically introduce the close relationship between FGFR4 and cancer, and conduct an in-depth analysis of the developing methodology, binding mechanism, kinase selectivity, pharmacokinetic characteristics of FGFR4 selectivity inhibitors, and their application in clinical research. Show less
Congenital myasthenic syndrome is a heterogeneous group of inherited neuromuscular transmission disorders. Variants in RAPSN are a common cause of CMS, accounting for approximately 14%-27% of all CMS Show more
Congenital myasthenic syndrome is a heterogeneous group of inherited neuromuscular transmission disorders. Variants in RAPSN are a common cause of CMS, accounting for approximately 14%-27% of all CMS cases. Whether preimplantation genetic testing for monogenic disease (PGT-M) could be used to prevent the potential birth of CMS-affected children is unclear. Application of WES (whole-exome sequencing) for carrier testing and guidance for the PGT-M in the absence of a genetically characterized index patient as well as assisted reproductive technology were employed to prevent the occurrence of birth defects in subsequent pregnancy. The clinical phenotypes of stillborn fetuses were also assessed. The family carried two likely pathogenic variants in RAPSN(NM₀₀₅₀₅₅.5): c.133G>A (p.V45M) and c.280G>A (p.E94K). And the potential birth of CMS-affected child was successfully prevented, allowing the family to have offspring devoid of disease-associated variants and exhibiting a normal phenotype. This report constitutes the first documented case of achieving a CMS-free offspring through PGT-M in a CMS-affected family. By broadening the known variant spectrum of RAPSN in the Chinese population, our findings underscore the feasibility and effectiveness of PGT-M for preventing CMS, offering valuable insights for similarly affected families. Show less
The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. Show more
The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. This study was divided into four phases: discovery, verification, validation, and modeling. A total of four candidate tumor-associated autoantibodies (TAAb; anti-ZIC2, anti-PCNA, anti-CDC37L1, and anti-DUSP6) were identified by human proteome microarray (52 samples) and bioinformatics analysis. Subsequently, these candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts (120 samples for verification and 663 samples for validation). The AUC for these four TAAbs to identify patients with HBV-HCC from chronic hepatitis B (CHB) patients ranged from 0.693 to 0.739. Finally, a diagnostic panel with three TAAbs (anti-ZIC2, anti-CDC37L1, and anti-DUSP6) was developed. This panel showed superior diagnostic efficiency in identifying early HBV-HCC compared with alpha-fetoprotein (AFP), with an AUC of 0.834 [95% confidence interval (CI), 0.772-0.897] for this panel and 0.727 (95% CI, 0.642-0.812) for AFP (P = 0.0359). In addition, the AUC for this panel to identify AFP-negative patients with HBV-HCC was 0.796 (95% CI, 0.734-0.858), with a sensitivity of 52.4% and a specificity of 89.0%. Importantly, the panel in combination with AFP significantly increased the positive rate for early HBV-HCC to 84.1% (P = 0.005) and for late HBV-HCC to 96.3% (P < 0.001). Our findings suggest that AFP and the autoantibody panel may be independent but complementary serologic biomarkers for HBV-HCC detection. We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection. Show less
FGFR1 is a key member of the fibroblast growth factor receptor family, mediating critical signaling pathways such as RAS-MAPK and PI3K-AKT. which are integral to regulating essential cellular processe Show more
FGFR1 is a key member of the fibroblast growth factor receptor family, mediating critical signaling pathways such as RAS-MAPK and PI3K-AKT. which are integral to regulating essential cellular processes, including proliferation, differentiation, and survival. Alterations in FGFR1 can lead to constitutive activation of signaling pathways that drive oncogenesis by promoting uncontrolled cell division, inhibiting apoptosis, and enhancing the metastatic potential of cancer cells. This article reviews the activation mechanisms and signaling pathways of FGFR1 and provides a detailed exposition of the types of FGFR1 aberration. Furthermore, we have compiled a comprehensive overview of current therapies targeting FGFR1 aberration in cancer, aiming to offer new perspectives for future cancer treatments by focusing on drugs that address specific FGFR1 alterations. Show less
Ran Zhao, Fanxiang Yin, Mangaladoss Fredimoses+12 more · 2024 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
Colorectal cancer (CRC) continues to be a major global health challenge, ranking as a top cause of cancer-related mortality. Alarmingly, the five-year survival rate for CRC patients hovers around a me Show more
Colorectal cancer (CRC) continues to be a major global health challenge, ranking as a top cause of cancer-related mortality. Alarmingly, the five-year survival rate for CRC patients hovers around a mere 10-30 %. The disruption of fibroblast growth factor receptor (FGFRs) signaling pathways is significantly implicated in the onset and advancement of CRC, presenting a promising target for therapeutic intervention in CRC management. Further investigation is essential to comprehensively elucidate FGFR1's function in CRC and to create potent therapies that specifically target FGFR1. This study aims to demonstrate the oncogenic role of FGFR1 in colorectal cancer and to explore the potential of β,β-dimethylacrylalkannin (β,β-DMAA) as a therapeutic option to inhibit FGFR1. In this research, we employed a comprehensive suite of techniques including tissue array, kinase profiling, computational docking, knockdown assay to predict and explore the inhibitor of FGFR1. Furthermore, we utilized kinase assay, pull-down, cell proliferation tests, and Patient derived xenograft (PDX) mouse models to further investigate a novel FGFR1 inhibitor and its impact on the growth of CRC. In our research, we discovered that FGFR1 protein is markedly upregulated in colorectal cancer tissues, suggesting a significant role in regulating cellular proliferation, particularly in patients with colorectal cancer. Furthermore, we conducted a computational docking, kinase profiling analysis, simulation and identified that β,β-DMAA could directly bind with FGFR1 within ATP binding pocket domain. Cell-based assays confirmed that β,β-DMAA effectively inhibited the proliferation of colon cancer cells and also triggered cell cycle arrest, apoptosis, and altered FGFR1-mediated signaling pathways. Moreover, β,β-DMAA effectively attenuated the development of PDX tumors in mice that were FGFR1-positive, with no notable toxicity observed. In summary, our study highlights the pivotal role of FGFR1 in colorectal cancer, suggesting that inhibiting FGFR1 activity could be a promising strategy for therapeutic intervention. We present strong evidence that targeting FGFR1 with β,β-DMAA is a viable approach for the management of colorectal cancer. Given its low toxicity and high efficacy, β,β-DMAA, as an FGFR1 inhibitor, warrants further investigation in clinical settings for the treatment of FGFR1-positive tumors. Show less
Chen Chen, Qingxiang Liu, Jianfei Wang+7 more · 2024 · Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · Elsevier · added 2026-04-24
Early evaluation and intervention for post-stroke cognitive impairment are crucial for improving the prognosis of acute ischemic stroke. The search for specific diagnostic markers and feasible therape Show more
Early evaluation and intervention for post-stroke cognitive impairment are crucial for improving the prognosis of acute ischemic stroke. The search for specific diagnostic markers and feasible therapeutic targets is extremely urgent.The characteristics of circular RNAs make them promising candidates. To screen circular RNAs as novel biomarkers and therapeutic targets for post-stroke cognitive impairment in large-artery atherosclerosis anterior circulation cerebral infarction patients. In this prospective observational study, patients with first-ever large-artery atherosclerosis anterior circulation cerebral infarction were recruited. The Montreal Cognitive Assessment was used to assess the cognitive statuses of patients. Venous blood samples were collected on the seventh day after stroke onset. A circRNA microarray was used to identify differentially expressed circular RNAs in the discovery cohort (four patients with post-stroke cognitive impairment and four patients with post-stroke cognitive normal characteristics), and validation was performed in the validation cohorts (45 patients with post-stroke cognitive impairment and 30 patients with post-stroke cognitive normal characteristics) using quantitative real-time polymerase chain reaction. Receiver operating characteristic curves of the validated circular RNAs and the NIHSS score were constructed, and the area under the curve, sensitivity, and specificity were calculated. Correlation analysis was performed to explore the relationship between the copy number of circular RNAs and the cognitive status. The functions of the differentially expressed circular RNAs were predicted using bioinformatics analysis. CircRNA microarray analysis revealed 189 human circular RNAs (152 upregulated and 37 downregulated) that were differentially expressed in the plasma samples of patients with post-stroke cognitive impairment and PSCN characteristics. The expression of hsa_circ₀₀₈₉₇₆₃, hsa_circ₀₀₆₄₆₄₄, and hsa_circ₀₀₈₉₇₆₂ was validated using quantitative real-time polymerase chain reaction. The area under the curve, sensitivity, and specificity of hsa_circ₀₀₈₉₇₆₂ in post-stroke cognitive impairment diagnosis were 0.993, 97.8%, and 96.7%, respectively, and the correlation coefficient between hsa_circ₀₀₈₉₇₆₂ expression and the Montreal Cognitive Assessment score was -0.693 (p < 0.001), which made it an ideal biomarker. Bioinformatic analysis revealed that the targeted mRNAs of the three circular RNAs were enriched in pathologically related signaling pathways of post-stroke cognitive impairment, such as the MAPK and PI3K-Akt signaling pathways. Based on the circRNA-miRNA-mRNA network, the three circular RNAs play a crucial role in numerous pathological processes of acute ischemic stroke and post-stroke cognitive impairment by sponging miRNAs such as MiR-335, MiR-424, and MiR-670. By building the protein-protein interaction network, we identified cluster 1 according to the MCODE score; cluster 1 was composed of ERBB4, FGFR1, CACNA2D1, NRG1, PPP2R5E, CACNB4, CACNB2, CCND1, NTRK2, and PTCH. Hsa_circ₀₀₈₉₇₆₂, hsa_circ₀₀₆₄₆₄₄, and hsa_circ₀₀₈₉₇₆₃ are potential novel biomarkers and focal points for exploring intervention targets in post-stroke cognitive impairment of large-artery atherosclerosis anterior circulation cerebral infarction patients. ChiCTR2000035074. Show less
no PDFDOI: 10.1016/j.jstrokecerebrovasdis.2024.107945
This experiment aims to evaluate the effect of bile acids (BAs) in alleviating fatty liver disease induced by a high-fat diet (HFD) in broilers, and the modulation of the gut microbiota involved in th Show more
This experiment aims to evaluate the effect of bile acids (BAs) in alleviating fatty liver disease induced by a high-fat diet (HFD) in broilers, and the modulation of the gut microbiota involved in this process. A total of 192 one-day-old Arbor Acres (AA) commercial male broilers were randomly divided into 4 groups and treated with the following diet: a basal-fat diet (BFD), a basal-fat diet plus bile acids (BFD + BAs), an HFD, and a high-fat diet plus bile acids (HFD + BAs). Bile acids were supplemented at the early growth stage (3-7 d), middle stage (17-21 d), and late stage (31-35 d). Results showed that BAs treatment had a significant effect on body weight on 14 d and 35 d, and increased the breast muscle weight and its index, but decreased the liver weight and abdominal fat weight on 35 d (P < 0.05). The supplementation of BAs significantly improved the serum lipid profile and decreased the level of triglycerides (TG), total cholesterol (TCHO), and nonesterified fatty acids (NEFA) on 35 d (P < 0.05). Dietary BAs supplementation significantly alleviated the hepatic TG deposition induced by HFD (P < 0.05), which was accompanied by upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) gene expression (P < 0.05). Moreover, the expression levels of hepatic gene adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor α (PPARα), and apolipoprotein B (APOB) were greatly increased by BAs treatment. The analysis of 16S rRNA sequencing showed that the microbial diversity of the cecal digesta was increased by BAs in broilers with elevated abundances of Firmicutes, Lactobacillus, Anaerostipes, Sellimonas, and CHKCI002 and decreased abundances of Barnesiella and Akkermansia genus (P < 0.05). Hepatic TG content was positively correlated with the abundance of Oscillospiraceae, but it was negatively correlated with the abundance of Lactobacillus in cecal digesta (P < 0.05). These results indicate that dietary BAs can improve growth performance and alleviate fatty liver disease induced by an HFD via modulating gut microbiota in broilers. Show less
This study replicated a mouse model of sperm DNA damage induced by benzo(a)pyrene (BaP), and the transcriptomic and proteomic features of the model were examined to clarify the pathways related to BaP Show more
This study replicated a mouse model of sperm DNA damage induced by benzo(a)pyrene (BaP), and the transcriptomic and proteomic features of the model were examined to clarify the pathways related to BaP-induced damage to sperm DNA. Male mice in the BaP group were subjected to BaP at a dosage of 100 mg/kg/d or an equivalent quantity of saline solution in the control group for 60 days. Subsequently, the DNA fragmentation index (DFI) in sperm was assessed using a sperm chromatin structure assay (SCSA). RNA-seq and data-independent acquisition (DIA) were used to identify the mRNA and protein expression patterns in the testis. The sperm DFI significantly increased in the BaP group. Compared to the control group, the BaP group exhibited differential expression of 240 genes (referred to as DEGs) and 616 proteins (referred to as DEPs). These molecules included Aldh1a1, Cyb5r3, Fads1, Oxsm, Rcn3, and Prss45. Pathways in cancer, the PI3K-Akt signaling pathway, metabolic pathways, and the MAPK signaling pathway were the primary areas where these genes showed enrichment. BaP can damage the DNA of sperm and affect metabolism, the PI3K-Akt pathway, and pathways associated with cancer signaling. Show less