COVID-19 is a highly infectious respiratory disease whose progression has been associated with multiple factors. From SARS-CoV-2 infection to death, biomarkers capable of predicting different disease Show more
COVID-19 is a highly infectious respiratory disease whose progression has been associated with multiple factors. From SARS-CoV-2 infection to death, biomarkers capable of predicting different disease processes are needed to help us further understand the molecular progression of COVID-19 disease. The aim is to find differentially expressed proteins that are associated with the progression of COVID-19 disease or can be potential biomarkers, and to provide a reference for further understanding of the molecular mechanisms of COVID-19 occurrence, progression, and treatment. Data-independent Acquisition (DIA) proteomics to obtain sample protein expression data, using R language screening differentially expressed proteins. Gene Ontology and Kyoto Encyclopedia for Genes and Genomes analysis was performed on differential proteins and protein-protein interaction (PPI) network was constructed to screen key proteins. A total of 47 differentially expressed proteins were obtained from COVID-19 incubation patients and healthy population (L/H), mainly enriched in platelet-related functions, and complement and coagulation cascade reaction pathways, such as platelet degranulation and platelet aggregation. A total of 42 differential proteins were obtained in clinical and latent phase patients (C/L), also mainly enriched in platelet-related functions and in complement and coagulation cascade reactions, platelet activation pathways. A total of 10 differential proteins were screened in recovery and clinical phase patients (R/C), mostly immune-related proteins. The differentially expressed proteins in different stages of COVID-19 are mostly closely associated with coagulation, and key differential proteins, such as FGA, FGB, FGG, ACTB, PFN1, VCL, SERPZNCL, APOC3, LTF, and DEFA1, have the potential to be used as early diagnostic markers. Show less
As the drawbacks of antibiotics in treating bacterial infections emerged, physical methods such as near-infrared-activated (NIR-activated) bacterial killing, have attracted great interests for their a Show more
As the drawbacks of antibiotics in treating bacterial infections emerged, physical methods such as near-infrared-activated (NIR-activated) bacterial killing, have attracted great interests for their advantages of no resistance, short action time and few side effects. In this manuscript, NIR-activated bacteria-killing performance of chiral copper sulphide nanoparticles (L-/d-CuS NPs) was investigated using linearly polarized light (LPL) and circularly polarized light (CPL) as illumination sources, respectively. Chiral CuS NPs showed enhanced NIR-activated bacteria-killing effect compared with achiral CuS NPs under the same conditions. Moreover, these chiral CuS NPs showed obvious chirality-related antibacterial effect: the bacterial killing was more efficient under CPL activation, and L- and d-CuS NPs had higher antibacterial efficiency under left circularly polarized light (LCPL) and right circularly polarized light (RCPL), respectively. The possible mechanism of bacteria-killing performance for chiral CuS NPs was discussed in detailed. Photothermal bacteria-killing tests of chiral CuS NPs "sealed" in polydimethylsiloxane (PDMS) demonstrated the individual influence of photothermal effect. These observations in this paper could provide ideas for the potential applications of chiral nanostructures with enhanced photothermal effect in efficient bacterial killing. Show less
Spinal cord injury (SCI) patients have an increased susceptibility to coronary heart disease (CHD) due to dysregulated lipid deposition. We conducted a comprehensive investigation to gain insights int Show more
Spinal cord injury (SCI) patients have an increased susceptibility to coronary heart disease (CHD) due to dysregulated lipid deposition. We conducted a comprehensive investigation to gain insights into the specific roles of Apolipoprotein B-100 (APOB-100) in the development of CHD in patients suffering from SCI. First, we established an SCI rat model through semitransection. APOB-100 expression in plasma exosomes obtained from patients were determined. Subsequently, we found APOB-100 affected macrophage polarization when treating co-cultured neurons/macrophages lacking Sortilin with extracellular vesicles derived from SCI rats, where APOB-100 co-immunoprecipitated with Sortilin. Moreover, APOB-100 upregulation reduced neuronal cell viability and triggered apoptosis by upregulating Sortilin, leading to a decline in the Basso, Beattie, and Bresnahan (BBB) scale, exacerbation of neuron injury, increased macrophage infiltration, and elevated blood lipid-related indicators in SCI rats, which could be reversed by silencing Sortilin. In conclusion, APOB-100 from post-SCI patients' extracellular vesicles upregulates Sortilin, thereby endangering those patients to CHD. Show less
Increasing evidence suggests that metabolic disorders such as obesity are implicated in the development of Alzheimer's disease (AD). The pathological buildup of lipids in microglia is regarded as a ke Show more
Increasing evidence suggests that metabolic disorders such as obesity are implicated in the development of Alzheimer's disease (AD). The pathological buildup of lipids in microglia is regarded as a key indicator in brain aging and the progression of AD, yet the mechanisms behind this process remain uncertain. The adipokine ANGPTL4 is strongly associated with obesity and is thought to play a role in the advancement of neurodegenerative diseases. This study utilized RNA sequencing to identify differential expression in lipid-accumulating BV2 microglia and investigated the potential mechanism through ANGPTL4 overexpression in BV2. Subsequently, animal models and clinical data were employed to further explore alterations in circulating ANGPTL4 levels in AD. RNA sequencing results indicated a correlation between ANGPTL4 and microglial lipid accumulation. The overexpression of ANGPTL4 in microglia resulted in increased secretion of inflammatory factors, elevated oxidative stress levels, and diminished antiviral capacity. Furthermore, when simulating the coexistence of AD and obesity through combined treatment with Amyloid-Beta 1-42 peptide (Aβ) and Free Fatty Acids (FFA) in vitro, we observed a notable upregulation of ANGPTL4 expression, highlighting its potential role in the interplay between AD and obesity. In vivo experiments, we also observed a significant increase in ANGPTL4 expression in the hippocampus and plasma of APP/PS1 mice compared to wild-type controls. This was accompanied by heightened microglial activation and reduced expression of longevity-related genes in the hippocampus. Clinical data from the UK Biobank indicated that plasma ANGPTL4 levels are elevated in patients with AD when compared to healthy controls. Moreover, significantly higher ANGPTL4 levels were observed in obese AD patients relative to their non-obese counterparts. Our findings suggest that ANGPTL4-mediated microglial aging may serve as a crucial link between AD and obesity, proposing ANGPTL4 as a potential biomarker for AD. Show less
This study explored the correlation between peripheral blood lipid levels and clinicopathological parameters in patients with advanced gastric cancer (GC), focusing on changes in lipid levels during d Show more
This study explored the correlation between peripheral blood lipid levels and clinicopathological parameters in patients with advanced gastric cancer (GC), focusing on changes in lipid levels during disease progression. Pathological features and serum lipid profiles of 179 patients with stage III-IV gastric adenocarcinoma were analyzed. Lipid parameters examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein AI (Apo AI), apolipoprotein B (Apo B), lipoprotein(a) (Lp(a)), among others. The total cholesterol-lymphocyte score (TL score) and BMI were also calculated. The association between lipid parameters and clinicopathological characteristics such as age, gender, family history, and metastasis sites was assessed. In GC patients, females had higher TG levels than males. Patients with peritoneal metastasis had significantly lower levels of TC, LDL-C, Apo B, and B/A ratio. Those with lung metastasis exhibited higher LDL-C levels and lower levels of VLDL-C. No significant associations were found between lipid levels and metastasis to distant lymph nodes, liver, or bone. Female patients with ovarian metastasis had significantly lower VLDL-C levels. Multivariate analysis revealed low TC as an independent risk factor for peritoneal metastasis, high LDL-C and low VLDL-C levels for lung metastasis, and younger age and low VLDL-C for ovarian metastasis. Specific blood lipid levels are significantly associated with metastatic sites in advanced gastric cancer. Lipid profiles could serve as potential biomarkers for predicting metastatic sites in GC patients. Show less
Chenchen Yuan, Yao Xu, Guotao Lu+12 more · 2024 · Molecular therapy : the journal of the American Society of Gene Therapy · Elsevier · added 2026-04-24
GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPLs). However, Gpihbp1 knockout mice did not develop hypertriglyceridemia (HTG) during the Show more
GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPLs). However, Gpihbp1 knockout mice did not develop hypertriglyceridemia (HTG) during the suckling period but developed severe HTG after weaning on a chow diet. It has been postulated that LPL expression in the liver of suckling mice may be involved. To determine whether hepatic LPL expression could correct severe HTG in Gpihbp1 deficiency, liver-targeted LPL expression was achieved via intravenous administration of the adeno-associated virus (AAV)-human LPL gene, and the effects of AAV-LPL on HTG and HTG-related acute pancreatitis (HTG-AP) were observed. Suckling Gpihbp1 Show less
The effectiveness of immune checkpoint inhibitor (ICI) therapy for hepatocellular carcinoma (HCC) is limited by treatment resistance. However, the mechanisms underlying immunotherapy resistance remain Show more
The effectiveness of immune checkpoint inhibitor (ICI) therapy for hepatocellular carcinoma (HCC) is limited by treatment resistance. However, the mechanisms underlying immunotherapy resistance remain elusive. We aimed to identify the role of CT10 regulator of kinase-like (CRKL) in resistance to anti-PD-1 therapy in HCC. Gene expression in HCC specimens from 10 patients receiving anti-PD-1 therapy was identified by RNA-sequencing. A total of 404 HCC samples from tissue microarrays were analyzed by immunohistochemistry. Transgenic mice (Alb-Cre/Trp53 CRKL was identified as a candidate anti-PD-1-resistance gene using a pooled genetic screen. CRKL overexpression nullifies anti-PD-1 treatment efficacy by mobilizing tumor-associated neutrophils (TANs), which block the infiltration and function of CD8 Activation of the CRKL/β-catenin/VEGFα and CXCL1 axis is a critical obstacle to successful anti-PD-1 therapy. Therefore, CRKL inhibitors combined with anti-PD-1 could be useful for the treatment of HCC. Here, we found that CRKL was overexpressed in anti-PD-1-resistant hepatocellular carcinoma (HCC) and that CRKL upregulation promotes anti-PD-1 resistance in HCC. We identified that upregulation of the CRKL/β-catenin/VEGFα and CXCL1 axis contributes to anti-PD-1 tolerance by promoting infiltration of tumor-associated neutrophils. These findings support the strategy of bevacizumab-based immune checkpoint inhibitor combination therapy, and CRKL inhibitors combined with anti-PD-1 therapy may be developed for the treatment of HCC. Show less
Developing multitargeted ligands as promising therapeutics for Alzheimer's disease (AD) has been considered important. Herein, a novel class of cinnamamide/ester-triazole hybrids with multifaceted eff Show more
Developing multitargeted ligands as promising therapeutics for Alzheimer's disease (AD) has been considered important. Herein, a novel class of cinnamamide/ester-triazole hybrids with multifaceted effects on AD was developed based on the multitarget-directed ligands strategy. Thirty-seven cinnamamide/ester-triazole hybrids were synthesized, with most exhibiting significant inhibitory activity against Aβ-induced toxicity at a single concentration in vitro. The most optimal hybrid compound 4j inhibited copper-induced Aβ toxicity in AD cells. its action was superior to that of donepezil and memantine. It also moderately inhibited intracellular AChE activity and presented favorable bioavailability and blood-brain barrier penetration with low toxicity in vivo. Of note, it ameliorated cognitive impairment, neuronal degeneration, and Aβ deposition in Aβ Show less
Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Show more
Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA. A drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed. The MR analyses used summary-level data of genome wide association studies (GWAS). Primary MR analysis was conducted using inverse-variance-weighted (IVW) method. Sensitivity analysis was performed using weighted median (WM) and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Genetically proxied low-density lipoprotein cholesterol (LDL-C)-lowering effect of cholesteryl ester transfer protein (CETP) was associated with reduced risk of OSA (odds ratio [OR] =0.75, 95% confidence interval [CI]: 0.60-0.94, false discovery rate [FDR] q value = 0.046). A significant MR association with risk of OSA was observed for CETP expression in subcutaneous adipose tissue (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049), lung (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049) and small intestine (OR = 0.96, 95%CI: 0.93-1.00, FDR q value = 0.049). No significant effects of high-density lipoprotein cholesterol (HDL-C)-raising effect of CETP inhibition, LDL-C-lowering and triglycerides-lowering effect of other drug targets on OSA risk were observed. The present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations. Show less
Alzheimer's disease (AD) is a progressive neurodegenerative disease. Neuronal calcium overload plays an important role in Aβ deposition and neuroinflammation, which are strongly associated with AD. Ho Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disease. Neuronal calcium overload plays an important role in Aβ deposition and neuroinflammation, which are strongly associated with AD. However, the specific mechanisms by which calcium overload contributes to neuroinflammation and AD and the relationship between them have not been elucidated. Phospholipase C (PLC) is involved in regulation of calcium homeostasis, and CN-NFAT1 signaling is dependent on intracellular Ca Show less
Malignant melanoma presents a formidable challenge due to its aggressive metastatic behavior and limited response to current treatments. To address this, our study delves into the impact of anlotinib Show more
Malignant melanoma presents a formidable challenge due to its aggressive metastatic behavior and limited response to current treatments. To address this, our study delves into the impact of anlotinib on angiogenesis and vasculogenic mimicry using malignant melanoma cells and human umbilical vein endothelial cells. Evaluating tubular structure formation, cell proliferation, migration, invasion, and key signaling molecules in angiogenesis, we demonstrated that anlotinib exerts a dose-dependent inhibition on tubular structures and effectively suppresses cell growth and invasion in both cell types. Furthermore, in a mouse xenograft model, anlotinib treatment resulted in reduced tumor growth and vascular density. Notably, the downregulation of VEGFR-2, FGFR-1, PDGFR-β, and PI3K underscored the multitargeted antitumor activity of anlotinib. Our findings emphasize the therapeutic potential of anlotinib in targeting angiogenesis and vasculogenic mimicry, contributing to the development of novel strategies for combating malignant melanoma. Show less
The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this s Show more
The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this study is to explore the regulatory mechanisms for the muscle development differences between genders. Muscovy ducks of both sexes were selected for measurements of body weight, growth traits, hormone levels, and muscle gene expression. The results show that male ducks compared to females had greater weight and growth traits ( Show less
Liang Li, Jianzhong Li, Wendeng Li+2 more · 2024 · Translational research : the journal of laboratory and clinical medicine · Elsevier · added 2026-04-24
Hepatopulmonary syndrome (HPS) is a serious pulmonary complication in the advanced stage of liver disease. The occurrence of pulmonary edema in HPS patients is life-threatening. Increased pulmonary va Show more
Hepatopulmonary syndrome (HPS) is a serious pulmonary complication in the advanced stage of liver disease. The occurrence of pulmonary edema in HPS patients is life-threatening. Increased pulmonary vascular permeability is an important mechanism leading to pulmonary edema, and endothelial glycocalyx (EG) is a barrier that maintains stable vascular permeability. However, in HPS, whether the pulmonary vascular EG changes and its regulatory mechanism are still unclear. Spleen derived monocytes are involved in the pathogenesis of HPS. However, whether they regulate the pulmonary vascular permeability in HPS patients or rats and what is the mechanism is still unclear. Healthy volunteers and HPS patients with splenectomy or not were enrolled in this study. We found that the respiration of HPS patients was significantly improved in response to splenectomy, while the EG degradation and pulmonary edema were aggravated. In addition, HPS patients expressed higher levels of oncostatin M (OSM) and fibroblast growth factor (FGF). Subsequently, the co-culture system of monocytes and human umbilical vein endothelial cells (HUVECs) was constructed. It was found that monocytes secreted OSM and activated the FGF/FGFR1 signaling pathway in HUVECs. Then, an HPS rat model was constructed by common bile duct ligation (CBDL) for in vivo verification. HPS rats were intravenously injected with OSM recombinant protein and/or TNF-α into the rats via tail vein 30 min before CBDL. The results showed that the respiration of HPS rats was improved after splenectomy, while the degradation of EG in pulmonary vessels and vascular permeability were increased, and pulmonary edema was aggravated. Moreover, the expression of OSM and FGF was upregulated in HPS rats, while both were downregulated after splenectomy. Intravenous injection of exogenous OSM eliminated the effect of splenectomy on FGF and improved EG degradation. It can be seen that during HPS, spleen-derived monocytes secrete OSM to promote pulmonary vascular EG remodeling by activating the FGF/FGFR1 pathway, thereby maintaining stable vascular permeability, and diminishing pulmonary edema. This study provides a promising therapeutic target for the treatment of HPS. Show less
In vitro cell culturing witnessed its applications in scientific research and industrial activities. Attempts to shorten the doubling time of cultured cells have never ceased. In plants, auxin is appl Show more
In vitro cell culturing witnessed its applications in scientific research and industrial activities. Attempts to shorten the doubling time of cultured cells have never ceased. In plants, auxin is applied to promote plant growth, the synthetic derivative 1-Naphthaleneacetic acid (NAA) is a good example. Despite the auxin's naturally occurring receptors are not present in mammalian cells, studies suggested they may affect cell culturing. Yet the effects and mechanisms are still unclear. Here, an up to 2-fold increase in the yield of in vitro cultured human cells is observed. Different types of human cell lines and primary cells are tested and found that NAA is effective in all the cells tested. The PI staining followed by FACS suggested that NAA do not affect the cell cycling. Apoptosis-specific dye staining analysis implicated that NAA rescued cell death. Further bulk RNA sequencing is done and it is identified that the lipid metabolism-engaging and anti-apoptosis gene, ANGPTL4, is enhanced in expression upon NAA treatment. Studies on ANGPTL4 knockout cells indicated that ANGPTL4 is required for NAA-mediated response. Thus, the data identified a beneficial role of NAA in human cell culturing and highlighted its potency in in vitro cell culturing. Show less
Staufen-1 (STAU1) is a double-stranded RNA-binding protein (RBP) involved in a variety of pathological conditions. In this study, we investigated the potential role of STAU1 in Alzheimer's disease (AD Show more
Staufen-1 (STAU1) is a double-stranded RNA-binding protein (RBP) involved in a variety of pathological conditions. In this study, we investigated the potential role of STAU1 in Alzheimer's disease (AD), in which two hallmarks are well-established as cerebral β-amyloid protein (Aβ) deposition and Tau-centered neurofibrillary tangles. We found that STAU1 protein level was significantly increased in cells that stably express full-length APP and the brain of APP/PS1 mice, an animal model of AD. STAU1 knockdown, as opposed to overexpression, significantly decreased the protein levels of β-amyloid converting enzyme 1 (BACE1) and Aβ. We further found that STAU1 extended the half-life of the BACE1 mRNA through binding to the 3' untranslated region (3'UTR). Transcriptome analysis revealed that STAU1 enhanced the expression of growth arrest and DNA damage 45 β (GADD45B) upstream of P38 MAPK signaling, which contributed to STAU1-induced regulation of Tau phosphorylation at Ser396 and Thr181. Together, STAU1 promoted amyloidogenesis by inhibiting BACE1 mRNA decay, and augmented Tau phosphorylation through activating GADD45B in relation to P38 MAPK. Targeting STAU1 that acts on both amyloidogenesis and tauopathy may serve as an optimistic approach for AD treatment. Show less
The gut microbiota (GM) has been implicated in neurological disorders, but the relationship with hydrocephalus, especially the underlying mechanistic pathways, is unclear. Using Mendelian randomizatio Show more
The gut microbiota (GM) has been implicated in neurological disorders, but the relationship with hydrocephalus, especially the underlying mechanistic pathways, is unclear. Using Mendelian randomization (MR), we aim to discover the mediating role of inflammatory factors in the relationship between GM and hydrocephalus. After removing confounders, univariable and multivariable MR analyses were performed using summary statistics to assess the causal relationships between GM, inflammatory factors (IL-17A and IL-27), and types of hydrocephalus. Meta-analyses were used to reconcile the differences in MR results between different hydrocephalus sources. Finally, mediator MR analyses were applied to determine the mediating effect of inflammatory factors. Various sensitivity analysis methods were employed to ensure the reliability and stability of the results. After correction for We reveal the connection between GM, inflammatory factors (IL-17A and IL-27), and hydrocephalus, which lays the foundation for unraveling the mechanism between GM and hydrocephalus. Show less
Organic afterglow materials have drawn increasing attention for their great potential in practical applications. Until now, most of them just show the lifetimes in milliseconds or seconds, while the r Show more
Organic afterglow materials have drawn increasing attention for their great potential in practical applications. Until now, most of them just show the lifetimes in milliseconds or seconds, while the realization of long persistent luminescence (LPL) lasting for minutes or even hours is difficult. In 2017, Adachi and Kabe successfully realize the LPL with a duration longer than 1 hour in a purely organic system, which can be even comparable to some excellent inorganic materials. However, partially for the unclear structure-property relationship, organic LPL materials are still rather scarce, especially for the stable ones in air or aqueous solution. In this review, we present the recent progress in organic LPL, mainly focusing on the material design strategy and internal mechanism. It is anticipated that the deep understanding can be beneficial for the further development of organic LPL materials with good stability in air and even aqueous phase. Show less
The hippocampus, with its complex subfields, is linked to numerous neuropsychiatric traits. While most research has focused on its global structure or a few specific subfields, a comprehensive analysi Show more
The hippocampus, with its complex subfields, is linked to numerous neuropsychiatric traits. While most research has focused on its global structure or a few specific subfields, a comprehensive analysis of hippocampal substructures and their genetic correlations across a wide range of neuropsychiatric traits remains underexplored. Given the hippocampus's high heritability, considering hippocampal and subfield volumes (HASV) as endophenotypes for neuropsychiatric conditions is essential. We analyzed MRI-derived volumetric data of hippocampal and subfield structures from 41,525 UK Biobank participants. Genome-wide association studies (GWAS) on 24 HASV traits were conducted, followed by genetic correlation, overlap, and Mendelian randomization (MR) analyses with 10 common neuropsychiatric traits. Polygenic risk scores (PRS) based on HASV traits were also evaluated for predicting these traits. Our analysis identified 352 independent genetic variants surpassing a significance threshold of 2.1 × 10 These findings highlight the extensive distribution of pleiotropic genetic determinants between HASVs and neuropsychiatric traits. Moreover, they suggest a significant potential for effectively managing and intervening in these diseases during their early stages. Show less
Periodontitis is a chronic inflammatory condition triggered by immune system malfunction. Mitochondrial extracellular vesicles (MitoEVs) are a group of highly heterogeneous extracellular vesicles (EVs Show more
Periodontitis is a chronic inflammatory condition triggered by immune system malfunction. Mitochondrial extracellular vesicles (MitoEVs) are a group of highly heterogeneous extracellular vesicles (EVs) enriched in mitochondrial fractions. The objective of this research was to examine the correlation between MitoEVs and the immune microenvironment of periodontitis. Data from MitoCarta 3.0, GeneCards, and GEO databases were utilized to identify differentially expressed MitoEV-related genes (MERGs) and conduct functional enrichment and pathway analyses. The random forest and LASSO algorithms were employed to identify hub MERGs. Infiltration levels of immune cells in periodontitis and healthy groups were estimated using the CIBERSORT algorithm, and phenotypic subgroups of periodontitis based on hub MERG expression levels were explored using a consensus clustering method. A total of 44 differentially expressed MERGs were identified. The random forest and LASSO algorithms identified 9 hub MERGs (BCL2L11, GLDC, CYP24A1, COQ2, MTPAP, NIPSNAP3A, FAM162A, MYO19, and NDUFS1). ROC curve analysis showed that the hub gene and logistic regression model presented excellent diagnostic and discriminating abilities. Immune infiltration and consensus clustering analysis indicated that hub MERGs were highly correlated with various types of immune cells, and there were significant differences in immune cells and hub MERGs among different periodontitis subtypes. The periodontitis classification model based on MERGs shows excellent performance and can offer novel perspectives into the pathogenesis of periodontitis. The high correlation between MERGs and various immune cells and the significant differences between immune cells and MERGs in different periodontitis subtypes can clarify the regulatory roles of MitoEVs in the immune microenvironment of periodontitis. Future research should focus on elucidating the functional mechanisms of hub MERGs and exploring potential therapeutic interventions based on these findings. Show less
Xiaoyi Fei, Min Zhu, Xueling Li · 2024 · Journal of burn care & research : official publication of the American Burn Association · Oxford University Press · added 2026-04-24
Currently, no timeline of cell heterogeneity in thermally injured skin has been reported. In this study, we proposed an approach to deconvoluting cell type abundance and expression from skin bulk tran Show more
Currently, no timeline of cell heterogeneity in thermally injured skin has been reported. In this study, we proposed an approach to deconvoluting cell type abundance and expression from skin bulk transcriptomics with cell type signature matrix constructed by combining independent normal skin and peripheral blood scRNA-seq datasets. Using CIBERSORTx group mode deconvolution, we identified perturbed cell type fractions and cell type-specific gene expression in three stages postthermal injury. We found an increase in cell proportions and cell type-specific gene expression perturbation of neutrophils, macrophages, and endothelial cells and a decrease in CD4+ T cells, keratinocytes, melanocyte, and fibroblast cells, and cell type-specific gene expression perturbation postburn injury. Keratinocyte, fibroblast, and macrophage up regulated genes were dynamically enriched in overlapping and distinct Gene Ontology biological processes including acute phase response, leukocyte migration, metabolic, morphogenesis, and development process. Down-regulated genes were enriched in Wnt signaling, mesenchymal cell differentiation, gland and axon development, epidermal morphogenesis, and fatty acid and glucose metabolic process. We noticed an increase in the expression of CCL7, CCL2, CCL20, CCR1, CCR5, CCXL8, CXCL2, CXCL3, MMP1, MMP8, MMP3, IL24, IL6, IL1B, IL18R1, and TGFBR1 and a decrease in expression of CCL27, CCR10, CCR6, CCR8, CXCL9, IL37, IL17, IL7, IL11R, IL17R, TGFBR3, FGFR1-4, and IGFR1 in keratinocytes and/or fibroblasts. The inferred timeline of wound healing and CC and CXC genes in keratinocyte was validated on independent dataset GSE174661 of purified keratinocytes. The timeline of different cell types postburn may facilitate therapeutic timing. Show less
Colorectal cancer is one of the most common types of cancer worldwide that can lead to serious injury and death. Although polysaccharides are widely recognized as having antitumor activity, there has Show more
Colorectal cancer is one of the most common types of cancer worldwide that can lead to serious injury and death. Although polysaccharides are widely recognized as having antitumor activity, there has been little research on the role of barley polysaccharides (BP) Show less
Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknow Show more
Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial-mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity. Show less
The Ningxiang pig, a distinguished local breed in China, is recognized for its good meat quality traits. This study examines the proteomics of Ningxiang pigs at three developmental stages and delves i Show more
The Ningxiang pig, a distinguished local breed in China, is recognized for its good meat quality traits. This study examines the proteomics of Ningxiang pigs at three developmental stages and delves into the upstream transcriptomics of these proteomics. Such an analysis facilitates a deeper understanding of the molecular interplay between proteins and transcriptomes in the Ningxiang pig muscle, influencing muscle growth and development. In this research, we analyzed the muscles of Ningxiang pigs at three developmental stages: 30 days in weaned piglets, 90 days in nursery pigs, and 210 days in late fattening pigs. There a total of 16 differentially co-expressed miRNAs (ssc-miRNA-1, ssc-miRNA-378, ssc-miRNA-143, ssc-miRNA-30e, etc.), 74 differentially co-expressed mRNA ( Show less
Aberrant activation of fibroblast growth factor receptors (FGFRs) contributes to the development and progression of multiple types of cancer. Although many FGFR inhibitors have been approved by the FD Show more
Aberrant activation of fibroblast growth factor receptors (FGFRs) contributes to the development and progression of multiple types of cancer. Although many FGFR inhibitors have been approved by the FDA, their long-term therapeutic efficacy is hampered by acquired resistance to gatekeeper mutations and low subtype selectivity. FGFR2 has been found to be frequently amplified or mutated in many tumors. In this study, we designed several PROTACs with different E3 ligands based on LY2874455. By screening the length of the linker and the binding site in various degraders, we obtained a novel and highly efficient FGFR2-selective degrader 28e (DC Show less
The clinical application of human bone-marrow derived mesenchymal stem cells (MSCs) for the treatment of refractory diseases has achieved remarkable results. However, there is a need for a systematic Show more
The clinical application of human bone-marrow derived mesenchymal stem cells (MSCs) for the treatment of refractory diseases has achieved remarkable results. However, there is a need for a systematic evaluation of the quality and safety of MSCs sourced from donors. In this study, we sought to assess one potential factor that might impact quality, namely the age of the donor. We downloaded two data sets from each of two Gene Expression Omnibus (GEO), GSE39035 and GSE97311 databases, namely samples form young (< 65 years of age) and old (> 65) donor groups. Through, bioinformatics analysis and experimental validation to these retrieved data, we found that MSCs derived from aged donors can lead to differential expression of gene profiles compared with those from young donors, and potentially affect the function of MSCs, and may even induce malignant tumors. We identified a total of 337 differentially expressed genes (DEGs), including two upregulated and eight downregulated genes from the databases of both GSE39035 and GSE97311. We further identified 13 hub genes. Six of them, TBX15, IGF1, GATA2, PITX2, SNAI1 and VCAN, were highly expressed in many human malignancies in Human Protein Atlas database. In the MSCs in vitro senescent cell model, qPCR analysis validated that all six hub genes were highly expressed in senescent MSCs. Our findings confirm that aged donors of MSCs have a significant effect on gene expression profiles. The MSCs from old donors have the potential to cause a variety of malignancies. These TBX15, IGF1, GATA2, PITX2, SNAI1, VCAN genes could be used as potential biomarkers to diagnosis aging state of donor MSCs, and evaluate whether MSCs derived from an aged donor could be used for therapy in the clinic. Our findings provide a diagnostic basis for the clinical use of MSCs to treat a variety of diseases. Therefore, our findings not only provide guidance for the safe and standardized use of MSCs in the clinic for the treatment of various diseases, but also provide insights into the use of cell regeneration approaches to reverse aging and support rejuvenation. Show less
Hypertrophic cardiomyopathy (HCM) is characterized by thickening of the left ventricular wall, diastolic dysfunction, and fibrosis, and is associated with mutations in genes encoding sarcomere protein Show more
Hypertrophic cardiomyopathy (HCM) is characterized by thickening of the left ventricular wall, diastolic dysfunction, and fibrosis, and is associated with mutations in genes encoding sarcomere proteins. While in vitro studies have used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study HCM, these models have not examined the multicellular interactions involved in fibrosis. Using engineered cardiac microtissues (CMTs) composed of HCM-causing Show less
Few studies are focusing on the mechanism of erastin acts on prostate cancer (PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa therapeutic targets are rarely known. In this s Show more
Few studies are focusing on the mechanism of erastin acts on prostate cancer (PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa therapeutic targets are rarely known. In this study, in vitro assays were performed and RNA-sequencing was used to measure the expression of differentially expressed genes (DEGs) in erastin-induced PCa cells. A series of bioinformatic analyses were applied to analyze the pathways and DEGs. Erastin inhibited the expression of SLC7A11 and cell survivability in LNCaP and PC3 cells. After treatment with erastin, the concentrations of malondialdehyde (MDA) and Fe TMEFF2 might be likely to develop into a potential ferroptosis target in PCa and this study extends our understanding of the molecular mechanism involved in erastin-affected PCa cells. Show less
Incubation temperature is a crucial environmental factor affecting embryonic development and chick quality. Metabolism during the embryonic stage, particularly liver lipid metabolism, is essential for Show more
Incubation temperature is a crucial environmental factor affecting embryonic development and chick quality. Metabolism during the embryonic stage, particularly liver lipid metabolism, is essential for the growth and development of poultry. This study aimed to investigate the effects of embryo thermal manipulation with high (TMH, 39.5 °C, 65% RH, 8 h/d) and low (TML, 20 °C, 65% RH, 1 h/d) temperatures during 8th to 15th embryonic age on hatching performance and liver lipid metabolism in layer chicks. Additionally, the duration of TM effects was evaluated through a short-term feeding trial. The results indicated that TMH accelerated the hatching process without significantly affecting hatchability and growth performance. In contrast, TML delayed hatching time and significantly reduced hatchability and chick quality. After hatching, TML also increased residual yolk weight and reduced the relative liver weight in relation to body weight and yolk-free body mass. Moreover, lipid droplets in the liver were stained with Oil Red O, and the lipid content in the liver and serum was further detected. TMH had no significant impact on triglyceride (TG) and total-cholesterol (TCHO) content in the liver and serum but upregulated the expression of lipogenesis-related genes ACC, Fas, and Fatp1 compared to the TML group. Conversely, TML significantly reduced liver TG content, enhanced lipoprotein lipase (LPL) activity, and promoted the expression of lipid oxidation-related genes CPT-1, PGC-1α, and PPARα. At 7 d of age, liver LPL activity was significantly increased in the TMH group. However, there were no significant changes in the content of TG and TCHO in the liver and the expression of lipid metabolism-related genes in the TML group. Overall, these results indicate that embryonic TM alters hatching performance and liver lipid metabolism in layer chicks. TML reduces TG content by increasing liver lipid oxidation capacity. However, this effect is not long-lasting, as the influence of TM diminishes as the chicks develop. Show less
To explore the prevalence and associated factors of obesity in Tibetan adults in Qinghai, China, and to determine the association between the FTO (rs1121980 and rs17817449) and MC4R gene (rs17782313 a Show more
To explore the prevalence and associated factors of obesity in Tibetan adults in Qinghai, China, and to determine the association between the FTO (rs1121980 and rs17817449) and MC4R gene (rs17782313 and rs12970134) polymorphisms with obesity. A cross-sectional survey was conducted in 2015 in Qinghai to selected Tibetan adults aged 20 to 80 years. Prevalence of obesity (BMI ≥ 28 kg/m A total of 1741 Tibetan adults were enrolled. The age- and sex- standardized prevalence of obesity and overweight was 18.09% and 31.71%, respectively. Male sex, older age, heavy level of leisure-time exercise, current smoke, and heavy level of occupational physical activity were associated with both obesity and overweight. MC4R gene polymorphisms were associated with obesity in Tibetan adults. No significant gene-environment interaction was detected. The prevalence of obesity and overweight in Tibetan adults was high. Both environmental and genetic factors contributed to the obesity prevalent. Show less