Flavor is a crucial parameter for assessing the sensory quality of yak milk. However, there is limited information regarding the factors influencing its taste. In this study, the effects of endogenous Show more
Flavor is a crucial parameter for assessing the sensory quality of yak milk. However, there is limited information regarding the factors influencing its taste. In this study, the effects of endogenous lipoprotein lipase (LPL) on the volatile flavor components of yak milk under storage conditions of 4 °C, 18 °C and 65 °C were analyzed via headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) combined with orthogonal partial least-squares (OPSL) discrimination, and the reasons for the changes in yak milk flavors were investigated. Combined with the difference in the changes in volatile flavor substance before and after the action of LPL, LPL was found to have a significant effect on the flavor of fresh yak milk. Fresh milk was best kept at 4 °C for 24 h and pasteurized for more than 24 h. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to characterize the volatile components in yak milk under various treatment conditions. Twelve substances with significant influence on yak milk flavor were identified by measuring their VIP values. Notably, 2-nonanone, heptanal, and ethyl caprylate exhibited OAV values greater than 1, indicating their significant contribution to the flavor of yak milk. Conversely, 4-octanone and 2-heptanone displayed OAV values between 0.1 and 1, showing their important role in modifying the flavor of yak milk. These findings can serve as monitoring indicators for assessing the freshness of yak milk. Show less
46,XY disorders of sex development (46,XY DSD) are characterized by incomplete masculinization of genitalia with reduced androgenization. Accurate clinical management remains challenging, especially b Show more
46,XY disorders of sex development (46,XY DSD) are characterized by incomplete masculinization of genitalia with reduced androgenization. Accurate clinical management remains challenging, especially based solely on physical examination. Targeted next-generation sequencing (NGS) with known pathogenic genes provides a powerful tool for diagnosis efficiency. This study aims to identify the prevalent genetic variants by targeted NGS technology and investigate the diagnostic rate in a large cohort of 46,XY DSD patients, with most of them presenting atypical phenotypes. Two different DSD panels were developed for sequencing purposes, targeting a cohort of 402 patients diagnosed with 46,XY DSD, who were recruited from the Department of Urology at Children's Hospital, Zhejiang University School of Medicine (Hangzhou, China). The detailed clinical characteristics were evaluated, and peripheral blood was collected for targeted panels to find the patients' variants. The clinical significance of these variants was annotated according to American College of Medical Genetics and Genomics (ACMG) guidelines. A total of 108 variants across 42 genes were found in 107 patients, including 46 pathogenic or likely pathogenic variants, with 45.7%(21/46) being novel. Among these genes, SRD5A2, AR, FGFR1, LHCGR, NR5A1, CHD7 were the most frequently observed. Besides, we also detected some uncommon causative genes like SOS1, and GNAS. Oligogenic variants were also identified in 9 patients, including several combinations PROKR2/FGFR1/CYP11B1, PROKR2/ATRX, PROKR2/AR, FGFR1/LHCGR/POR, FGFR1/NR5A1, GATA4/NR5A1, WNT4/AR, MAP3K1/FOXL2, WNT4/AR, and SOS1/FOXL2. The overall genetic diagnostic rate was 11.2%(45/402), with an additional 15.4% (62/402) having variants of uncertain significance. Additionally, trio/duo patients had a higher genetic diagnostic rate (13.4%) compared to singletons (8.6%), with a higher proportion of singletons (15.1%) presenting variants of uncertain significance. In conclusion, targeted gene panels identified pathogenic variants in a Chinese 46,XY DSD cohort, expanding the genetic understanding and providing evidence for known pathogenic genes' involvement. Show less
Head and neck squamous cell carcinoma (HNSCC) is a significant global health challenge. The identification of reliable prognostic biomarkers and construction of an accurate prognostic model are crucia Show more
Head and neck squamous cell carcinoma (HNSCC) is a significant global health challenge. The identification of reliable prognostic biomarkers and construction of an accurate prognostic model are crucial. In this study, mRNA expression data and clinical data of HNSCC patients from The Cancer Genome Atlas were used. Overlapping candidate genes (OCGs) were identified by intersecting differentially expressed genes and prognosis-related genes. Best prognostic genes were selected using the least absolute shrinkage and selection operator Cox regression based on OCGs, and a risk score was developed using the Cox coefficient of each gene. The prognostic power of the risk score was assessed using Kaplan-Meier survival analysis and time-dependent receiver operating characteristic analysis. Univariate and multivariate Cox regression were performed to identify independent prognostic parameters, which were used to construct a nomogram. The predictive accuracy of the nomogram was evaluated using calibration plots. Functional enrichment analysis of risk score related genes was performed to explore the potential biological functions and pathways. External validation was conducted using data from the Gene Expression Omnibus and ArrayExpress databases. FADS3, TNFRSF12A, TJP3, and FUT6 were screened to be significantly related to prognosis in HNSCC patients. The risk score effectively stratified patients into high-risk group with poor overall survival (OS) and low-risk group with better OS. Risk score, age, clinical M stage and clinical N stage were regarded as independent prognostic parameters by Cox regression analysis and used to construct a nomogram. The nomogram performed well in 1-, 2-, 3-, 5- and 10-year survival predictions. Functional enrichment analysis suggested that tight junction was closely related to the cancer. In addition, the prognostic power of the risk score was validated by external datasets. This study constructed a gene-based model integrating clinical prognostic parameters to accurately predict prognosis in HNSCC patients. 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
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
Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is characterized by insulin resistance and hyperglycemia. It is also known to be a risk factor for Alzheimer's disease (AD). Insulin plays Show more
Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is characterized by insulin resistance and hyperglycemia. It is also known to be a risk factor for Alzheimer's disease (AD). Insulin plays a crucial role in regulating the body's metabolism and is responsible for activating the Phosphoinotide-3-Kinase (PI3K)/Protein Kinase B (Akt) signaling pathway. This pathway is activated when insulin binds to the insulin receptor on nerve cells, and it helps regulate the metabolism of glucose and lipids. Dysfunction in the insulin signaling pathway can lead to a decrease in brain insulin levels and insulin sensitivity, thereby inducing disruptions in insulin signal transduction and leading to disorders in brain energy metabolism. Moreover, these dysfunctions also contribute to the accumulation of β-amyloid (Aβ) deposition and the hyperphosphorylation of Tau protein, both of which are characteristic features of AD. Therefore, this article focuses on insulin resistance to reveal the complex mechanism between brain insulin resistance and AD occurrence in T2DM. On this basis, this article further summarizes the biological effects and mechanisms of antidiabetic drugs on the two diseases, aiming to provide new ideas for the discovery of drugs for the treatment of T2DM combined with AD. Show less
Hematopoietic stem and progenitor cells (HSPCs) possess the potential to produce all types of blood cells throughout their lives. It is well recognized that HSPCs are heterogeneous, which is of great Show more
Hematopoietic stem and progenitor cells (HSPCs) possess the potential to produce all types of blood cells throughout their lives. It is well recognized that HSPCs are heterogeneous, which is of great significance for their clinical applications and the treatment of diseases associated with HSPCs. This study presents a novel technology called Single-Cell transcriptome Analysis and Lentiviral Barcoding (SCALeBa) to investigate the molecular mechanisms underlying the heterogeneity of human HSPCs in vivo. The SCALeBa incorporates a transcribed barcoding library and algorithm to analyze the individual cell fates and their gene expression profiles simultaneously. Our findings using SCALeBa reveal that HSPCs subset with stronger stemness highly expressed MYL6B, ATP2A2, MYO19, MDN1, ING3, and so on. The high expression of COA3, RIF1, RAB14, and GOLGA4 may contribute to the pluripotent-lineage differentiation of HSPCs. Moreover, the roles of the representative genes revealed in this study regarding the stemness of HPSCs were confirmed with biological experiments. HSPCs expressing MRPL23 and RBM4 genes may contribute to differentiation bias into myeloid and lymphoid lineage, respectively. In addition, transcription factor (TF) characteristics of lymphoid and myeloid differentiation bias HSPCs subsets were identified and linked to previously identified genes. Furthermore, the stemness, pluripotency, and differentiation-bias genes identified with SCALeBa were verified in another independent HSPCs dataset. Finally, this study proposes using the SCALeBa-generated tracking trajectory to improve the accuracy of pseudo-time analysis results. In summary, our study provides valuable insights for understanding the heterogeneity of human HSPCs in vivo and introduces a novel technology, SCALeBa, which holds promise for broader applications. KEY POINTS: SCALeBa and its algorithm are developed to study the molecular mechanism underlying human HSPCs identity and function. The human HSPCs expressing MYL6B, MYO19, ATP2A2, MDN1, ING3, and PHF20 may have the capability for high stemness. The human HSPCs expressing COA3, RIF1, RAB14, and GOLGA4 may have the capability for pluripotent-lineage differentiation. The human HSPCs expressing MRPL23 and RBM4 genes may have the capability to differentiate into myeloid and lymphoid lineage respectively in vivo. The legitimacy of the identified genes with SCALeBa was validated using biological experiments and a public human HSPCs dataset. SCALeBa improves the accuracy of differentiation trajectories in monocle2-based pseudo-time analysis. Show less
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
The overexpression of FGFR1 is thought to significantly contribute to the progression of triple-negative breast cancer (TNBC), impacting aspects such as tumorigenesis, growth, metastasis, and drug res Show more
The overexpression of FGFR1 is thought to significantly contribute to the progression of triple-negative breast cancer (TNBC), impacting aspects such as tumorigenesis, growth, metastasis, and drug resistance. Consequently, the pursuit of effective inhibitors for FGFR1 is a key area of research interest. In response to this need, our study developed a hybrid virtual screening method. Utilizing KarmaDock, an innovative algorithm that blends deep learning with molecular docking, alongside Schrödinger's Residue Scanning. This strategy led us to identify compound 6, which demonstrated promising FGFR1 inhibitory activity, evidenced by an IC Show less
Interleukin-27 receptor (IL-27R) is expressed in a variety of immune cells and structural cells, including dendritic cells. The mechanism of IL-27 in asthma has not been fully elucidated. This study a Show more
Interleukin-27 receptor (IL-27R) is expressed in a variety of immune cells and structural cells, including dendritic cells. The mechanism of IL-27 in asthma has not been fully elucidated. This study aimed to examine whether IL-27 regulated the CD39/ATP axis of dendritic cells in asthma. Our results showed that in ovalbumin (OVA)-induced asthma mouse model, IL-27Rα Show less
MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgki Show more
MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value. MNDA expression in a cohort of 1293 cases of B-NHLs and 338 cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated. MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036). MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated. Show less
Many sex-specific biomarkers have been recently revealed in Alzheimer's disease (AD); however, cerebral glial cells were rarely reported. This study analyzed 220,095 single-nuclei transcriptomes from Show more
Many sex-specific biomarkers have been recently revealed in Alzheimer's disease (AD); however, cerebral glial cells were rarely reported. This study analyzed 220,095 single-nuclei transcriptomes from the frontal cortex of thirty-three AD individuals in the GEO database. Sex-specific Differentially Expressed Genes (DEGs) were identified in glial cells, including 243 in astrocytes, 1,154 in microglia, and 572 in oligodendrocytes. Gene Ontology (GO) functional annotation analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed functional concentration in synaptic, neural, and hormone-related pathways. Protein-protein interaction network (PPI) identified MT3, CALM2, DLG2, KCND2, PAKACB, CAMK2D, and NLGN4Y in astrocytes, TREM2, FOS, APOE, APP, and NLGN4Y in microglia, and GRIN2A, ITPR2, GNAS, and NLGN4Y in oligodendrocytes as key genes. NLGN4Y was the only gene shared by the three glia and was identified as the biomarker for the gender specificity of AD. Gene-transcription factor (TF)-miRNA coregulatory network identified key regulators for NLGN4Y and its target TCMs. Ecklonia kurome Okam (Kunbu) and Herba Ephedrae (Mahuang) were identified, and the effects of the active ingredients on AD were displayed. Finally, enrichment analysis of Kunbu and Mahuang suggested that they might act as therapeutic candidates for gender specificity of AD. Show less
Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis is increased in the endothelium of atheroprone areas, accompanied by elevated lactate levels. Histo Show more
Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis is increased in the endothelium of atheroprone areas, accompanied by elevated lactate levels. Histone lactylation, mediated by lactate, can regulate gene expression and participate in disease regulation. However, whether histone lactylation is involved in atherosclerosis remains unknown. Here, we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactate-dependent histone H3 lysine 18 lactylation (H3K18la) Show less
Metal-organic hybrid materials with long persistent luminescence (LPL) properties have attracted a lot of attention due to their enormous potential for applications in information encryption, anticoun Show more
Metal-organic hybrid materials with long persistent luminescence (LPL) properties have attracted a lot of attention due to their enormous potential for applications in information encryption, anticounterfeiting, and other correlation fields. However, achieving multimodal luminescence in a single component remains a significant challenge. Herein, we report two two-dimensional LPL coordination polymers: {[Zn Show less
The excessive accumulation of abdominal fat in chickens has resulted in a reduction in both the feed conversion efficiency and the slaughter yield. To elucidate the regulatory mechanisms and metabolic Show more
The excessive accumulation of abdominal fat in chickens has resulted in a reduction in both the feed conversion efficiency and the slaughter yield. To elucidate the regulatory mechanisms and metabolic pathways affecting abdominal fat deposition in the context of broiler breeding, a cohort of 400 Qingyuan partridge chickens with varying abdominal fat deposition was established. Whole transcriptome sequencing analyses were conducted on the duodenum of 20 representative chickens to ascertain the regulatory networks at this vital digestive and absorptive organ. Consequently, 116 differentially expressed genes were identified, exhibiting a trend of increasing or decreasing expression in correlation with the accumulation of abdominal fat. A total of 36 DEmRNAs, 170 DElncRNAs, 92 DEcircRNAs and 88 DEmiRNAs were identified as differentially expressed between chickens with extremely high and low abdominal fat deposition. The functional enrichment analyses demonstrated that the differentially expressed RNA in the duodenum were involved in the regulation of chicken abdominal fat deposition by mediating a series of metabolic pathways, including the Wnt signaling pathway, the PPAR signaling pathway, the Hippo signaling pathway, the FoxO signaling pathway, the MAPK signaling pathway and other signaling pathways that are involved in fatty acid metabolism and degradation. The construction of putative interaction pairs led to the suggestion of two lncRNA-miRNA-mRNA ceRNA networks comprising two mRNAs, two miRNAs, and 29 lncRNAs, as well as two circRNA-lncRNA-miRNA-mRNA ceRNA networks comprising 26 mRNAs, 12 miRNAs, 17 lncRNAs, and nine circRNAs, as core regulatory networks in the duodenum affecting chicken abdominal fat deposition. The aforementioned genes including TMEM150C, REXO1, PIK3C2G, ppp1cb, PARP12, SERPINE2, LRAT, CYP1A1, INSR and APOA4, were proposed as candidate genes, while the miRNAs, including miR-107-y, miR-22-y, miR-25-y, miR-2404-x and miR-16-x, as well as lncRNAs such as ENSGALT00000100291, TCONS₀₀₀₆₃₅₀₈, TCONS₀₀₀₆₁₂₀₁ and TCONS₀₀₀₇₉₄₀₂ were the candidate regulators associated with chicken abdominal fat deposition. The findings of this study provide a theoretical foundation for the molecular mechanisms of mRNAs and non-coding RNAs in duodenal tissues on abdominal fat deposition in chickens. Show less
Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 Show more
Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) has been shown to promote cancer stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation of esophageal cancer stem cell properties by the interaction of PDIA3P1 with proteins. The GEPIA2 and Gene Expression Omnibus databases were used to analyze gene expression. PDIA3P1 expression in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to determine the effects of PDIA3P1 on ESCC cell proliferation, migration, and invasion. The sphere formation assay, number of side population cells, and CD271 + /CD44 + cells were detected by flow cytometry to identify the cancer stem cell properties. RNA immunoprecipitation (RIP), RNA pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, and cleavage under targets and tagmentation (CUT&Tag) assays were performed to elucidate the underlying molecular mechanisms. PDIA3P1 expression was upregulated in ESCC cell lines and tissues. Functionally, higher PDIA3P1 expression promoted cell proliferation, invasion, and metastasis and inhibited apoptosis in esophageal cancer. Importantly, PDIA3P1 promoted cancer stem cell properties in ESCC. Mechanistically, PDIA3P1 interacted with and stabilized octamer-binding transcription factor 4 (OCT4) by eliminating its ubiquitination by the ubiquitinating enzyme WW domain-containing protein 2 (WWP2). Moreover, as a transcription factor, OCT4 bound to the PDIA3P1 promoter and promoted its transcription. Our research revealed a novel mechanism by which a positive feedback loop exists between PDIA3P1 and OCT4. It also demonstrated that the PDIA3P1-WWP2-OCT4 loop is beneficial for promoting the cancer stem cell properties of ESCC. Owing to this regulatory relationship, the PDIA3P1-WWP2-OCT4-positive feedback loop might be used in the diagnosis and prognosis, as well as in the development of novel therapeutics for esophageal cancer. Show less
Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivota Show more
Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Here, we report that PTEN deficiency induced Krüppel-like factor 5 (KLF5) acetylation and that interruption of KLF5 acetylation orchestrated intricate interactions between cancer cells and CAFs that enhance FGF receptor 1 (FGFR1) signaling and promote tumor growth. Deacetylated KLF5 promoted tumor cells to secrete TNF-α, which stimulated inflammatory CAFs to release FGF9. CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 and sensitized PTEN-deficient prostate cancer to the AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rationale for combined therapies using inhibitors of AKT and CX3CR1. Show less
Spautin-1 is a well-known macroautophagy/autophagy inhibitor via suppressing the deubiquitinases USP10 and USP13 and promoting the degradation of the PIK3C3/VPS34-BECN1 complex, while its effect on se Show more
Spautin-1 is a well-known macroautophagy/autophagy inhibitor via suppressing the deubiquitinases USP10 and USP13 and promoting the degradation of the PIK3C3/VPS34-BECN1 complex, while its effect on selective autophagy remains poorly understood. Mitophagy is a selective form of autophagy for removal of damaged and superfluous mitochondria via the autophagy-lysosome pathway. Here, we report a surprising discovery that, while spautin-1 remains as an effective autophagy inhibitor, it promotes PINK1-PRKN-dependent mitophagy induced by mitochondrial damage agents. Mechanistically, spautin-1 facilitates the stabilization and activation of the full-length PINK1 at the outer mitochondrial membrane (OMM) via binding to components of the TOMM complex (TOMM70 and TOMM20), leading to the disruption of the mitochondrial import of PINK1 and prevention of PARL-mediated PINK1 cleavage. Moreover, spautin-1 induces neuronal mitophagy in Show less
Tunable luminescence-assisted information storage and encryption holds increasing significance in today's society. A promising approach to incorporating the benefits of both organic long persistent lu Show more
Tunable luminescence-assisted information storage and encryption holds increasing significance in today's society. A promising approach to incorporating the benefits of both organic long persistent luminescent (LPL) materials and rare-earth (RE) luminescence lies in utilizing organic host materials to sensitize RE luminescence, as well as employing Förster resonance energy transfer from hydrogen-bonded organic framework (HOF) phosphorescence to RE compound luminescence. This work introduces a one-pot, in situ pyrolytic condensation method, achieved through high-temperature melting calcination, to synthesize lanthanide ion-doped HOF materials. This method circumvents the drawback of molecular triplet energy annihilation, enabling the creation of organic LPL materials with RE characteristics. The HOF material serves as the host, exhibiting blue phosphorescence and cyan LPL. By fine-tuning the doping amount, the composite material U-Tb-100 achieves green LPL with a luminescent quantum yield of 56.4 %, and an LPL duration of approximately 2-3 s, demonstrating tunable persistence. Single-crystal X-ray diffraction, spectral analysis, and theoretical calculation unveil that U-Tb-100 exhibits exceptional quantum yield and long-lived luminescence primarily due to the efficient sensitization of U monomer to RE ions and the PRET process between U and RE complexes. This ingenious strategy not only expands the repertoire of HOF materials but also facilitates the design of multifunctional LPL materials. Show less
The lion-head goose is the only large goose species in China, and it is one of the largest goose species in the world. Lion-head geese have a strong tolerance for massive energy intake and show a prio Show more
The lion-head goose is the only large goose species in China, and it is one of the largest goose species in the world. Lion-head geese have a strong tolerance for massive energy intake and show a priority of fat accumulation in liver tissue through special feeding. Therefore, the aim of this study was to investigate the impact of high feed intake compared to normal feeding conditions on the transcriptome changes associated with fatty liver development in lion-head geese. In this study, 20 healthy adult lion-head geese were randomly assigned to a control group (CONTROL, n = 10) and high-intake-fed group (CASE, n = 10). After 38 d of treatment, all geese were sacrificed, and liver samples were collected. Three geese were randomly selected from the CONTROL and CASE groups, respectively, to perform whole-transcriptome analysis to analyze the key regulatory genes. We identified 716 differentially expressed mRNAs, 145 differentially expressed circRNAs, and 39 differentially expressed lncRNAs, including upregulated and downregulated genes. GO enrichment analysis showed that these genes were significantly enriched in molecular function. The node degree analysis and centrality metrics of the mRNA-lncRNA-circRNA triple regulatory network indicate the presence of crucial functional nodes in the network. We identified differentially expressed genes, including Show less
Sisi Zheng, Sitong Feng, Nan Song+8 more · 2024 · The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · Taylor & Francis · added 2026-04-24
Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor- Show more
Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor-α and interleukin associated with the dissociative symptoms. In this study, we aimed to explore the role of the immune system in the pathology of DPD. We screened the protein expression in serum samples of 30 DPD patients and 32 healthy controls. Using a mass spectrometry-based proteomic approach, we identified differential proteins that were verified in another group of 25 DPD patients and 30 healthy controls using immune assays. Finally, we performed a correlation analysis between the expression of differential proteins and clinical symptoms of patients with DPD. We identified several dysregulated proteins in patients with DPD compared to HCs, including decreased levels of C-reactive protein (CRP), complement C1q subcomponent subunit B, apolipoprotein A-IV, and increased levels of alpha-1-antichymotrypsin (SERPINA3). Moreover, the expression of CRP was positively correlated with visuospatial memory and the ability to inhibit cognitive interference of DPD. The expression of SERPINA3 was positively correlated with the ability to inhibit cognitive interference and negatively correlated with the perceptual alterations of DPD. The dysregulation of the immune system may be the underlying biological mechanism in DPD. And the expressions of CRP and SERPINA3 can be the potential predictors for the cognitive performance of DPD. Show less
Neurexin-3 (Nrxn3) has been genetically associated with obesity, but the underlying neural mechanisms remain poorly understood. This study aimed to investigate the role of Nrxn3 in the paraventricular Show more
Neurexin-3 (Nrxn3) has been genetically associated with obesity, but the underlying neural mechanisms remain poorly understood. This study aimed to investigate the role of Nrxn3 in the paraventricular nucleus of the hypothalamus (PVN) in regulating energy balance and glucose homeostasis. We found that Nrxn3 expression in the PVN was upregulated in response to metabolic stressors, including cold exposure and fasting. Using Cre-loxP technology, we selectively ablated Nrxn3 in CaMKIIα-expressing neurons of the PVN in male mice. This genetic manipulation resulted in marked weight gain attributable to increased adiposity and impaired glucose tolerance, without affecting food intake. Our findings identify PVN CaMKIIα-expressing neurons as a critical locus where Nrxn3 modulates energy balance by regulating adipogenesis and glucose metabolism, independently of appetite. These results reveal a novel neural mechanism potentially linking Nrxn3 dysfunction to obesity pathogenesis, suggesting that targeting PVN Nrxn3-dependent neural pathways may inform new therapeutic approaches for obesity prevention and treatment. Show less
Osteoarthritis (OA) is a degenerative joint disease caused by the deterioration of cartilage. However, the underlying mechanisms of OA pathogenesis remain elusive. Hub genes were screened by bioinform Show more
Osteoarthritis (OA) is a degenerative joint disease caused by the deterioration of cartilage. However, the underlying mechanisms of OA pathogenesis remain elusive. Hub genes were screened by bioinformatics analysis based on the GSE114007 and GSE169077 datasets. The Sprague-Dawley (SD) rat model of OA was constructed by intra-articular injection of a mixture of papain and L-cysteine. Hematoxylin-eosin (HE) staining was used to detect pathological changes in OA rat models. Inflammatory cytokine levels in serum were measured employing the enzyme-linked immunosorbent assay (ELISA). The reverse transcription quantitative PCR (RT-qPCR) was implemented to assess the hub gene expressions in OA rat models. The roles of PDK4 and the mechanism regulating the PPAR pathway were evaluated through western blot, cell counting kit-8 (CCK-8), ELISA, and flow cytometry assays in C28/I2 chondrocytes induced by IL-1β. Six hub genes were identified, of which COL1A1, POSTN, FAP, and CDH11 expressions were elevated, while PDK4 and ANGPTL4 were reduced in OA. Overexpression of PDK4 inhibited apoptosis, inflammatory cytokine levels (TNF-α, IL-8, and IL-6), and extracellular matrix (ECM) degradation protein expressions (MMP-3, MMP-13, and ADAMTS-4) in IL-1β-induced chondrocytes. Further investigation revealed that PDK4 promoted the expression of PPAR signaling pathway-related proteins: PPARA, PPARD, and ACSL1. Additionally, GW9662, an inhibitor of the PPAR pathway, significantly counteracted the inhibitory effect of PDK4 overexpression on IL-1β-induced chondrocytes. PDK4 inhibits OA development by activating the PPAR pathway, which provides new insights into the OA management. Show less
Previous studies show that spinal cord ischemia and hypoxia is an important cause of spinal cord necrosis and neurological loss. Therefore, the study aimed to identify genes related to ischemia and hy Show more
Previous studies show that spinal cord ischemia and hypoxia is an important cause of spinal cord necrosis and neurological loss. Therefore, the study aimed to identify genes related to ischemia and hypoxia after spinal cord injury (SCI) and analyze their functions, regulatory mechanism, and potential in regulating immune infiltration. The expression profiles of GSE5296, GSE47681, and GSE217797 were downloaded from the Gene Expression Omnibus database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to determine the function and pathway enrichment of ischemia- and hypoxia-related differentially expressed genes (IAHRDEGs) in SCI. LASSO model was constructed, and support vector machine analysis was used to identify key genes. The diagnostic values of key genes were evaluated using decision curve analysis and receiver operating characteristic curve analysis. The interaction networks of miRNAs-IAHRDEGs and IAHRDEGs-transcription factors were predicted and constructed with the ENCORI database and Cytoscape software. CIBERSORT algorithm was utilized to analyze the correlation between key gene expression and immune cell infiltration. There were 27 IAHRDEGs identified to be significantly expressed in SCI at first. These genes were mostly significantly enriched in wound healing function and the pathway associated with lipid and atherosclerosis. Next, five key IAHRDEGs (Abca1, Casp1, Lpl, Procr, Tnfrsf1a) were identified and predicted to have diagnostic value. Moreover, the five key genes are closely related to immune cell infiltration. Abca1, Casp1, Lpl, Procr, and Tnfrsf1a may promote the pathogenesis of ischemic or hypoxic SCI by regulating vascular damage, inflammation, and immune infiltration. Show less
Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent form of osteonecrosis in young individuals. More efficacious clinical strategies must be used to prevent and treat this conditi Show more
Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent form of osteonecrosis in young individuals. More efficacious clinical strategies must be used to prevent and treat this condition. One of the mechanisms through which SONFH operates is the disruption of normal differentiation in bone marrow adipocytes and osteoblasts due to prolonged and extensive use of glucocorticoids (GCs). In vitro, it was observed that atorvastatin (ATO) effectively suppressed the impact of dexamethasone (DEX) on bone marrow mesenchymal stem cells (BMSCs), specifically by augmenting their lipogenic differentiation while impeding their osteogenic differentiation. To investigate the underlying mechanisms further, we conducted transcriptome sequencing of BMSCs subjected to different treatments, leading to the identification of Wnt5a as a crucial gene regulated by ATO. The analyses showed that ATO exhibited the ability to enhance the expression of Wnt5a and modulate the MAPK pathway while regulating the Wnt canonical signaling pathway via the WNT5A/LRP5 pathway. Our experimental findings provide further evidence that the combined treatment of ATO and DEX effectively mitigates the effects of DEX, resulting in the upregulation of osteogenic genes (Runx2, Alpl, Tnfrsf11b, Ctnnb1, Col1a) and the downregulation of adipogenic genes (Pparg, Cebpb, Lpl), meanwhile leading to the upregulation of Wnt5a expression. So, this study offers valuable insights into the potential mechanism by which ATO can be utilized in the prevention of SONFH, thereby holding significant implications for the prevention and treatment of SONFH in clinical settings. Show less
Class B1 G protein-coupled receptors (GPCRs) are important regulators of many physiological functions such as glucose homeostasis, which is mainly mediated by three peptide hormones, i.e., glucagon-li Show more
Class B1 G protein-coupled receptors (GPCRs) are important regulators of many physiological functions such as glucose homeostasis, which is mainly mediated by three peptide hormones, i.e., glucagon-like peptide-1 (GLP-1), glucagon (GCG), and glucose-dependent insulinotropic polypeptide (GIP). They trigger a cascade of signaling events leading to the formation of an active agonist-receptor-G protein complex. However, intracellular signal transducers can also activate the receptor independent of extracellular stimuli, suggesting an intrinsic role of G proteins in this process. Here, we report cryo-electron microscopy structures of the human GLP-1 receptor (GLP-1R), GCG receptor (GCGR), and GIP receptor (GIPR) in complex with G Show less
Geese evolved from migratory birds, and when they consume excessive high-energy feed, glucose is converted into triglycerides. A large amount of triglyceride deposition can induce incomplete oxidation Show more
Geese evolved from migratory birds, and when they consume excessive high-energy feed, glucose is converted into triglycerides. A large amount of triglyceride deposition can induce incomplete oxidation of fatty acids, leading to lipid accumulation in the liver and the subsequent formation of fatty liver. In the Chaoshan region of Guangdong, China, Shitou geese develop a unique form of fatty liver through 24 h overfeeding of brown rice. To investigate the mechanisms underlying the formation of fatty liver in Shitou geese, we collected liver samples from normally fed and overfed geese. The results showed that the liver size in the treatment group was significantly larger, weighing 3.5 times more than that in the control group. Extensive infiltration of lipid droplets was observed in the liver upon staining of tissue sections. Biochemical analysis revealed that compared to the control group, the treatment group showed significantly elevated levels of total cholesterol (T-CHO), triglycerides (TG), and glycogen in the liver. However, no significant differences were observed in the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are common indicators of liver damage. Furthermore, we performed a combined transcriptomic and lipidomic analysis of the liver samples and identified 1,510 differentially expressed genes (DEGs) and 1,559 significantly differentially abundant metabolites (SDMs). The enrichment analysis of the DEGs revealed their enrichment in metabolic pathways, cellular process-related signaling pathways, and specific lipid metabolism pathways. We also conducted KEGG enrichment analysis of the SDMs and compared them with the enriched signaling pathways obtained from the DEGs. In this study, we identified 3 key signaling pathways involved in the formation of fatty liver in Shitou geese, namely, the biosynthesis of unsaturated fatty acids, glycerol lipid metabolism, and glycerophospholipid metabolism. In these pathways, genes such as glycerol-3-phosphate acyltransferase, mitochondrial (GPAM), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), diacylglycerol O-acyltransferase 2 (DGAT2), lipase, endothelial (LIPG), lipoprotein lipase (LPL), phospholipase D family member 4 (PLD4), and phospholipase A2 group IVF (PLA2G4F) may regulate the synthesis of metabolites, including triacylglycerol (TG), phosphatidate (PA), 1,2-diglyceride (DG), phosphatidylethanolamine (PE), and phosphatidylcholine (PC). These genes and metabolites may play a predominant role in the development of fatty liver, ultimately promoting the accumulation of TG in the liver and leading to the progression of fatty liver. Show less