Long interspersed element 1 (LINE-1; L1) are a family of transposons that occupy ~17% of the human genome. Though a small number of L1 copies remain capable of autonomous transposition, the overwhelmi Show more
Long interspersed element 1 (LINE-1; L1) are a family of transposons that occupy ~17% of the human genome. Though a small number of L1 copies remain capable of autonomous transposition, the overwhelming majority of copies are degenerate and immobile. Nevertheless, both mobile and immobile L1s can exert pleiotropic effects (promoting genome instability, inflammation, or cellular senescence) on their hosts, and L1's contributions to aging and aging diseases is an area of active research. However, because of the cell type-specific nature of transposon control, the catalogue of L1 regulators remains incomplete. Here, we employ an eQTL approach leveraging transcriptomic and genomic data from the GEUVADIS and 1000Genomes projects to computationally identify new candidate regulators of L1 RNA levels in lymphoblastoid cell lines. To cement the role of candidate genes in L1 regulation, we experimentally modulate the levels of top candidates in vitro, including IL16, STARD5, HSD17B12, and RNF5, and assess changes in TE family expression by Gene Set Enrichment Analysis (GSEA). Remarkably, we observe subtle but widespread upregulation of TE family expression following IL16 and STARD5 overexpression. Moreover, a short-term 24-hour exposure to recombinant human IL16 was sufficient to transiently induce subtle, but widespread, upregulation of L1 subfamilies. Finally, we find that many L1 expression-associated genetic variants are co-associated with aging traits across genome-wide association study databases. Our results expand the catalogue of genes implicated in L1 RNA control and further suggest that L1-derived RNA contributes to aging processes. Given the ever-increasing availability of paired genomic and transcriptomic data, we anticipate this new approach to be a starting point for more comprehensive computational scans for regulators of transposon RNA levels. Show less
Understanding the liver stem cells (LSCs) holds great promise for new insights into liver diseases and liver regeneration. However, the heterogenicity and plasticity of liver cells have made it contro Show more
Understanding the liver stem cells (LSCs) holds great promise for new insights into liver diseases and liver regeneration. However, the heterogenicity and plasticity of liver cells have made it controversial. Here, by employing single-cell RNA-sequencing technology, transcriptome features of Krt19 Show less
Bullous pemphigoid (BP) and prurigo nodularis (PN) are chronic pruritic skin diseases that severely impact patients' quality of life. Despite the widespread attention these two diseases have garnered Show more
Bullous pemphigoid (BP) and prurigo nodularis (PN) are chronic pruritic skin diseases that severely impact patients' quality of life. Despite the widespread attention these two diseases have garnered within the dermatological field, the specific pathogenesis, particularly the molecular mechanisms underlying the pruritus, remains largely unclear. Limited clinical sequencing studies focusing on BP and PN have hindered the identification of pathological mechanisms and the exploration of effective treatment strategies. To address this gap, we collected a total of 23 peripheral blood mononuclear cell samples from BP and PN patients, as well as healthy controls, and performed RNA sequencing analysis. By integrating bioinformatics and machine learning techniques, we aimed to uncover the shared immune regulatory networks and pruritus-related mechanisms between BP and PN. Our study identified 161 differentially expressed genes shared between BP and PN, which were primarily enriched in immune activation and neural pathways, providing crucial molecular insights into the pruritus-related mechanisms of both diseases. Furthermore, using the machine learning algorithms of support vector machines and random forest, we pinpoint 7 crucial genes shared between the BP and PN databases. Among these, IL-27 emerged as a potential pivotal gene, as its mRNA expression levels strongly correlated with clinical parameters including pruritus scores, immunoglobulin E levels, and eosinophil counts. Validation experiments conducted on clinical samples from an additional 22 participants confirmed the upregulation of IL-27 expression in both BP and PN lesions. This study is the first to unveil the shared inflammatory and immune pathways common to BP and PN, highlighting the critical role of IL-27 in the pathogenesis of these conditions. Our findings not only enhance the understanding of the intricate relationship between BP and PN, but also provide a foundation for the development of novel therapeutic strategies targeting these two dermatological conditions. Show less
The gold standard of milk is human milk, not cow milk. The present study expects to explored the comprehensive nutritional value of different kinds of milk and the differences between them through mul Show more
The gold standard of milk is human milk, not cow milk. The present study expects to explored the comprehensive nutritional value of different kinds of milk and the differences between them through multi-omics analysis and found functional components that are more similar to human milk. This study employed untargeted LC-MS/MS metabolomics, untargeted LC-MS/MS lipidomics, and 4D label-free proteomics analysis techniques. The findings revealed substantial disparities in metabolites, lipids, and proteins among the five types of milk. Notably, pig milk exhibited a remarkable abundance of N-acetylneuraminic acid (Neu5Ac) and specific polar lipids. Yak milk stood out with significantly elevated levels of creatine and lipoprotein lipase (LPL) compared to other species. Buffalo milk boasted the highest concentrations of L-isoleucine, echinocystic acid, and alkaline phosphatase, tissue-nonspecific isozyme (ALPL). The concentrations of iminostilbene and osteopontin (OPN) were higher in cow milk. 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
To evaluate the potential of zinc finger protein 1 (ZPR1) as a diagnostic biomarker and explore the underlying role for esophageal squamous cell carcinoma (ESCC). A human proteome microarray was custo Show more
To evaluate the potential of zinc finger protein 1 (ZPR1) as a diagnostic biomarker and explore the underlying role for esophageal squamous cell carcinoma (ESCC). A human proteome microarray was customized to identify anti-ZPR1 autoantibody, and enzyme-linked immunosorbent assay (ELISA) was adopted to assess the diagnostic performance of anti-ZPR1 autoantibody in 294 patients with ESCC and 294 normal controls. The expression of ZPR1 protein was measured by immunohistochemistry. The effect of ZPR1 on the proliferation, migration, and invasion of ESCC cells was investigated through CCK-8, wound healing, and Transwell assays. The expression level of anti-ZPR1 autoantibody (fold change = 2.77) in ESCC patients was higher than that in normal controls. The receiver operating characteristic (ROC) analysis manifested anti-ZPR1 autoantibody achieved area under the ROC curve (AUC) of 0.726 and 0.734 to distinguish ESCC from normal controls with sensitivity of 50.0% and 42.3%, and specificity of 91.0% and 92.0% in the test group and validation group, respectively. The positive rate of ZPR1 protein was significantly higher in ESCC tissues (75.5%, 80/106) than paracancerous tissues (9.4%, 5/53). Compared with the human normal esophageal cell line, the expression level of ZPR1 mRNA and protein in ESCC lines (KYSE150, Eca109, and TE1) had an increased trend. The knockdown or overexpression of ZPR1 reduced and enhanced the proliferation, migration, and invasion of ESCC cell, respectively. ZPR1 was a potential immunodiagnostic biomarker for noninvasive detection and could be a promotional factor in tumor progression of ESCC. Show less
Recurrent spontaneous abortion (RSA) is a complex pathological process involving diverse factors, in which the dysregulated functions of trophoblasts cannot be ignored. Long noncoding RNA (lncRNA) has Show more
Recurrent spontaneous abortion (RSA) is a complex pathological process involving diverse factors, in which the dysregulated functions of trophoblasts cannot be ignored. Long noncoding RNA (lncRNA) has been reported to play a significant role in regulating the functions of trophoblasts in RSA. However, the impact and potential mechanism of lncRNA small nucleolar RNA host gene 12 (lncSNHG12) remain unclear. The role of lncSNHG12 in RSA was investigated through in vivo experiments and clinical samples. Co-IP and RNA pull down were conducted to explore the molecular mechanisms in trophoblasts. Our results showed that lncSNHG12 promoted the migration and invasion of trophoblasts by interacting with Iodothyronine deiodinase 2 (Dio2), which regulating the EMT process of trophoblasts by interacting with Snail. Moreover, in vivo experiments confirmed that lncSNHG12 could improve the fetal absorption rate of the abortion mice. The clinical samples revealed that lncSNHG12, Dio2 and Snail were down-regulated in the villous tissues of RSA patients, and positive correlations were confirmed between lncSNHG12 and Dio2, as well as Dio2 and Snail. In summary, the lncSNHG12/Dio2/Snail axis might be involved in the development of RSA by regulating the invasion and migration of trophoblasts. Abbreviations: RSA, recurrent spontaneous abortion; EVTs, extravillous trophoblasts; EMT, epithelial-to-mesenchymal transition; lncRNA, long non-coding RNA; Dio2, iodothyronine deiodinase 2; SNHGs, small nuclear RNA host genes; snoRNAs, small nuclear cell RNAs; LPS, lipopolysaccharide; De, derived decidua; Jz, junctional zone; Lz, labyrinth zones; RIP, RNA Binding Protein Immunoprecipitation; Co-IP, Co-Immunoprecipitation; RPISeq, RNA-Protein Interaction Prediction. Show less
Diabetes mellitus is generally accompanied by dyslipidaemia, but inconsistent relationships between lipid profiles and diabetes are noted. Moreover, genetic variations in insertion/deletion (I/D) poly Show more
Diabetes mellitus is generally accompanied by dyslipidaemia, but inconsistent relationships between lipid profiles and diabetes are noted. Moreover, genetic variations in insertion/deletion (I/D) polymorphisms at angiotensin-converting enzyme gene (ACE) and T/C polymorphisms in the angiotensin type 1 receptor gene (AGTR1) are related to diabetes and lipid levels, but the associations are controversial. Thus, the current research aimed to explore the effects of ACE I/D, AGTR1 rs5182 and diabetes mellitus on serum lipid profiles in 385 Chinese participants with an average age of 75.01 years. The ACE I/D variant was identified using the polymerase chain reaction (PCR) method, whereas the AGTR1 rs5182 polymorphism was identified using the PCR-based restriction fragment length polymorphism (PCR-RFLP) method and verified with DNA sequencing. Total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured using routine methods, and the lipid ratios were calculated. ACE I/D, but not AGTR1 rs5182, was a predictor of TG/HDL-C for the whole study population. Both ACE I/D and AGTR1 rs5182 were predictors of HDL-C and LDL-C levels in females but not in males. Moreover, in females, diabetes mellitus and ACE I/D were identified as predictors of TG and TG/HDL-C, whereas AGTR1 rs5182 and diabetes mellitus were predictors of TG/HDL-C. Moreover, diabetes mellitus and the combination of ACE I/D and AGTR1 rs5182 variations were predictors of TG and TG/HDL-C exclusively in females. The results demonstrated the potential for gender-dependent interactions of ACE I/D, AGTR1 rs5182, and diabetes on lipid profiles. These findings may serve as an additional explanation for the inconsistent changes of blood lipids in individuals with diabetes mellitus, thereby offering a novel perspective for the clinical management of blood lipid levels in diabetic patients. Show less
RNA structure constitutes a new layer of gene regulatory mechanisms. RNA binding proteins can modulate RNA secondary structures, thus participating in post-transcriptional regulation. The DEAH-box hel Show more
RNA structure constitutes a new layer of gene regulatory mechanisms. RNA binding proteins can modulate RNA secondary structures, thus participating in post-transcriptional regulation. The DEAH-box helicase 36 (DHX36) is known to bind and unwind RNA G-quadruplex (rG4) structure but the transcriptome-wide RNA structure remodeling induced by DHX36 binding and the impact on RNA fate remain poorly understood. Here, we investigate the RNA structurome alteration induced by DHX36 depletion. Our findings reveal that DHX36 binding induces structural remodeling not only at the localized binding sites but also on the entire mRNA transcript most pronounced in 3'UTR regions. DHX36 binding increases structural accessibility at 3'UTRs which is correlated with decreased post-transcriptional mRNA abundance. Further analyses and experiments uncover that DHX36 binding sites are enriched for N6-methyladenosine (m Show less
Organic afterglow with long-persistent luminescence (LPL) after photoexcitation is highly attractive, but the realization of narrowband afterglow with small full-width at half-maximum (FWHM) is a huge Show more
Organic afterglow with long-persistent luminescence (LPL) after photoexcitation is highly attractive, but the realization of narrowband afterglow with small full-width at half-maximum (FWHM) is a huge challenge since it is intrinsically contradictory to the triplet- and solid-state emission nature of organic afterglow. Here, narrow-band, long-lived, and full-color organic LPL is realized by isolating multi-resonant thermally activated delayed fluorescent (MR-TADF) fluorophores in a glassy steroid-type host through a facile melt-cooling treatment. Such prepared host becomes capable of exciton dissociation and recombination (EDR) upon photoirradiation for both long-lived fluorescence and phosphorescence; and, the efficient Förster resonance energy transfer (FRET) from the host to various MR-TADF emitters leads to high-performance LPL, exhibiting small FWHM of 33 nm, long persistent time over 10 s, and facile color-tuning in a wide range from deep-blue to orange (414-600 nm). Moreover, with the extraordinary narrowband LPL and easy processability of the material, centimeter-scale flexible optical waveguide fibers and integrated FWHM/color/lifetime-resolved multilevel encryption/decryption devices have been designed and fabricated. This novel EDR and singlet/triplet-to-singlet FRET strategy to achieve excellent LPL performances illustrates a promising way for constructing flexible organic afterglow with easy preparation methods, shedding valuable scientific insights into the design of narrow-band emission in organic afterglow. Show less
Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms. These conditions share overlapping clinical presentati Show more
Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms. These conditions share overlapping clinical presentations; however, their prognoses differ significantly. Current morphological diagnostic methods lack reliability in subtype differentiation, underlining the need for improved diagnostics. The aim of this study was to investigate the multi-omics alterations in bone marrow biopsies of patients with ET and pre-PMF to improve our understanding of the nuanced diagnostic characteristics of both diseases. We performed proteomic analysis with 4D direct data-independent acquisition and microbiome analysis with 2bRAD-M sequencing technology to identify differential protein and microbe levels between untreated patients with ET and pre-PMF. Laboratory and multi-omics differences were observed between ET and pre-PMF, encompassing diverse pathways, such as lipid metabolism and immune response. The pre-PMF group showed an increased neutrophil-to-lymphocyte ratio and decreased high-density lipoprotein and cholesterol levels. Protein analysis revealed significantly higher CXCR2, CXCR4, and MX1 levels in pre-PMF, while APOC3, APOA4, FABP4, C5, and CFB levels were elevated in ET, with diagnostic accuracy indicated by AUC values ranging from 0.786 to 0.881. Microbiome assessment identified increased levels of Mycobacterium, Xanthobacter, and L1I39 in pre-PMF, whereas Sphingomonas, Brevibacillus, and Pseudomonas_E were significantly decreased, with AUCs for these genera ranging from 0.833 to 0.929. Our study provides preliminary insights into the proteomic and microbiome variations in the bone marrow of patients with ET and pre-PMF, identifying specific proteins and bacterial genera that warrant further investigation as potential diagnostic indicators. These observations contribute to our evolving understanding of the multi-omics variations and possible mechanisms underlying ET and pre-PMF. Show less
Accumulating evidences indicate that abnormalities in tubular lipid metabolism play a crucial role in the development of diabetic kidney disease (DKD). We aim to identify novel lipid metabolism-relate Show more
Accumulating evidences indicate that abnormalities in tubular lipid metabolism play a crucial role in the development of diabetic kidney disease (DKD). We aim to identify novel lipid metabolism-related genes associated with tubular injury in DKD by utilizing bioinformatics approaches. Differentially expressed genes (DEGs) between control and DKD tubular tissue samples were screened from the Gene Expression Omnibus (GEO) database, and then were intersected with lipid metabolism-related genes. Hub genes were further determined by combined weighted gene correlation network analysis (WGCNA) and protein-protein interaction (PPI) network. We performed enrichment analysis, immune analysis, clustering analysis, and constructed networks between hub genes and miRNAs, transcription factors and small molecule drugs. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic efficacy of hub genes. We validated the relationships between hub genes and DKD with external datasets and our own clinical samples. There were 5 of 37 lipid metabolism-related DEGs identified as hub genes. Enrichment analysis demonstrated that lipid metabolism-related DEGs were enriched in pathways such as peroxisome proliferator-activated receptors (PPAR) signaling and pyruvate metabolism. Hub genes had potential regulatory relationships with a variety of miRNAs, transcription factors and small molecule drugs, and had high diagnostic efficacy. Immune infiltration analysis revealed that 13 immune cells were altered in DKD, and hub genes exhibited significant correlations with a variety of immune cells. Through clustering analysis, DKD patients could be classified into 3 immune subtypes and 2 lipid metabolism subtypes, respectively. The tubular expression of hub genes in DKD was further verified by other external datasets, and immunohistochemistry (IHC) staining showed that except ACACB, the other 4 hub genes (LPL, AHR, ME1 and ALOX5) exhibited the same results as the bioinformatics analysis. Our study identified several key lipid metabolism-related genes (LPL, AHR, ME1 and ALOX5) that might be involved in tubular injury in DKD, which provide new insights and perspectives for exploring the pathogenesis and potential therapeutic targets of DKD. Show less
Major depressive disorder (MDD) is a highly prevalent condition and one of the most common psychiatric disorders worldwide. Circular RNA (circRNA) has been increasingly implicated in MDD. However, a c Show more
Major depressive disorder (MDD) is a highly prevalent condition and one of the most common psychiatric disorders worldwide. Circular RNA (circRNA) has been increasingly implicated in MDD. However, a comprehensive understanding of circRNA and microglial apoptosis in depression is incomplete. Here, we show that circDYM inhibits microglial apoptosis induced by LPS via CEBPB/ZC3H4 axis. CircDYM prevents the translocation of CEBPB from cytoplasm to the nucleus by binding with CEBPB. Moreover, LPS-induced CEBPB nuclear entry downregulates the expression of ZC3H4, in which promotes autophagy and apoptosis in microglia. Taken together, our findings provide new insights into the relationship between circDYM and microglial apoptosis and shed new light on the function of this novel mechanism in depression-associated complex changes in the brain. Show less
Mixed hyperlipidemia represents a substantial public health issue and a considerable burden on healthcare systems. Although the introduction of statins and LDL-cholesterol lowering agents have signifi Show more
Mixed hyperlipidemia represents a substantial public health issue and a considerable burden on healthcare systems. Although the introduction of statins and LDL-cholesterol lowering agents have significantly reduced the incidence of atherosclerotic cardiovascular diseases (ASCVD), a significant portion of the population continues to exhibit ASCVD progression due to elevated triglyceride-rich lipoprotein (TRL) levels. This persistent risk has catalyzed the development of novel pharmacological interventions targeting these lipoproteins. Our special report commenced with a targeted PubMed search using keywords such as 'plozasiran,' 'zodasiran,' and terms related to APOC3 and ANGPTL3. As the review progressed, emergent research questions guided further searches, allowing for the inclusion of additional relevant articles to comprehensively illustrate the linkage between TRLs and cardiovascular disease, discuss the roles of APOC3, ANGPTL3, and the pharmaceutical agents that target these proteins, and provide a comparison on the ARCHES-2 and MUIR trials. The ARCHES-2 and MUIR trials demonstrated effective triglyceride reduction by these therapies, yet it is uncertain if this correlates with significant clinical benefits. Advances in antisense oligonucleotide technology, especially the GalNAc delivery platform, show promise for personalized lipid management, though challenges such as cost and safety concerns remain. Show less
Multiply adverse effects including declines in production performance and excessive fat deposition were noticed with the extension of the laying cycle in hens, which are pertinent to animal welfare an Show more
Multiply adverse effects including declines in production performance and excessive fat deposition were noticed with the extension of the laying cycle in hens, which are pertinent to animal welfare and human food safety. This study aimed to investigate the effect of dietary supplementation of bile acids (BAs) on production performance and lipid metabolism in late-phase laying hens. A total of 144 70-week-old hens were distributed into three treatments with eight replicates per treatment, including the basal diet with 0 (Ctrl), 95.01 (Low-BA), and 189.99 mg/kg (High-BA) of porcine BAs, respectively. The test period was from 70 to 75 weeks. The supplementation of BAs did not significantly alter laying performance during the trial, whereas it increased ( Show less
The utilization of denosumab in treating osteoporosis highlights promising prospects for osteoporosis intervention guided by gene targets. While omics-based research into osteoporosis pathogenesis yie Show more
The utilization of denosumab in treating osteoporosis highlights promising prospects for osteoporosis intervention guided by gene targets. While omics-based research into osteoporosis pathogenesis yields a plethora of potential gene targets for clinical transformation, identifying effective gene targets has posed challenges. We first queried the omics data of osteoporosis clinical samples on PubMed, used International Mouse Phenotyping Consortium (IMPC) to screen differentially expressed genes, and conducted preliminary functional verification of candidate genes in human Saos2 cells through osteogenic differentiation and mineralization experiments. We then selected the candidate genes with the most significant effects on osteogenic differentiation and further verified the osteogenic differentiation and mineralization functions in mouse 3T3-E1 and bone marrow mesenchymal stem cells (BMSC). Finally, we used RNA-seq to explore the regulation of osteogenesis by the target gene. We identified Our study provides several novel molecular mechanisms involved in the pathogenesis of osteoporosis. Show less
Numerous observational studies have reported associations between circulating cytokines and atopic dermatitis (AD); however, the causal relationships between them remain unclear. To explore the causal Show more
Numerous observational studies have reported associations between circulating cytokines and atopic dermatitis (AD); however, the causal relationships between them remain unclear. To explore the causal correlations and direction of causal effects between AD and levels of 91 circulating cytokines. Two-sample Mendelian randomization (MR) analyses were conducted to examine the causal relationships between 91 circulating cytokines and AD using summary statistics from genome-wide association studies (GWAS). Reverse MR analyses were performed to investigate reverse causation. Pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings. Additional transcriptome database and clinical peripheral blood mononuclear cells (PBMCs) samples were utilized to validate the results of MR analyses. Levels of interleukin (IL)-13, IL-18 Receptor 1, Tumor necrosis factor ligand superfamily member 14 (TNFSF14), TNF-related activation-induced cytokine (TRANCE), C-X-C motif chemokine (CXCL)11, IL-33, TNF-beta and CD5 were suggestively associated with the risk of AD (odds ratio, OR: 1.202, 95% CI: 1.018 The study indicates that several cytokines, including IL-13, IL-18R1, TNFSF14, TRANCE, CXCL11, IL-33, TNF-beta, and CD5, are upstream of AD development, whereas a few circulating cytokines are potentially downstream in the development of AD. Show less
The human extravillous trophoblast (EVT) cell invasion is an important process during placentation. Although the placenta is normal tissue, the EVT cells exhibit some features common to cancer cells, Show more
The human extravillous trophoblast (EVT) cell invasion is an important process during placentation. Although the placenta is normal tissue, the EVT cells exhibit some features common to cancer cells, including high migratory and invasive properties. Snail and Slug are transcription factors that mediate the epithelial-mesenchymal transition (EMT), a crucial event for cancer cell migration and invasion. It has been shown that GDF-11-induced matrix metalloproteinase 2 (MMP2) expression is required for EVT cell invasion. Whether GDF-11 can regulate Snail and Slug expression in human EVT cells remains unknown. If it does, the involvement of Snail and Slug in GDF-11-induced MMP2 expression and EVT cell invasion must also be defined. In the present study, using the immortalized human EVT cell line, HTR-8/SVneo, and primary cultures of human EVT cells as experimental models, our results show that GDF-11 upregulates Snail and Slug expression. ALK4 and ALK5 mediate the stimulatory effects of GDF-11 on Snail and Slug expression. In addition, we demonstrate that SMAD2 and SMAD3 are required for the GDF-11-upregulated Snail expression, while only SMAD3 is involved in GDF-11-induced Slug expression. Moreover, our results reveal that Snail mediates GDF-11-induced MMP2 expression and cell invasion but not Slug. This study increases our understanding of the biological function of GDF-11 in human EVT cells and provides a novel mechanism for regulating MMP2 and EVT cell invasion. Show less
The current clinical pulse lavage technique for flushing fresh osteochondral allografts (OCAs) to remove immunogenic elements from the subchondral bone is ineffective. This study aimed to identify the Show more
The current clinical pulse lavage technique for flushing fresh osteochondral allografts (OCAs) to remove immunogenic elements from the subchondral bone is ineffective. This study aimed to identify the optimal method for removing immunogenic elements from OCAs. We examined five methods for the physical removal of immunogenic elements from OCAs from the femoral condyle of porcine knees. We distributed the OCAs randomly into the following seven groups: (1) control, (2) saline, (3) ultrasound, (4) vortex vibration (VV), (5) low-pulse lavage (LPL), (6) high-pulse lavage (HPL), and (7) high-speed centrifugation (HSC). OCAs were evaluated using weight measurement, micro-computed tomography (micro-CT), macroscopic and histological evaluation, DNA quantification, and chondrocyte activity testing. Additionally, the subchondral bone was zoned to assess the bone marrow and nucleated cell contents. One-way ANOVA and paired two-tailed Student's t-test are used for statistical analysis. Histological evaluation and DNA quantification showed no significant reduction in marrow elements compared to the control group after the OCAs were treated with saline, ultrasound, or VV treatments; however, there was a significant reduction in marrow elements after LPL, HPL, and HSC treatments. Furthermore, HSC more effectively reduced the marrow elements of OCAs in the middle and deep zones compared with LPL (p < 0.0001) and HPL (p < 0.0001). Macroscopic evaluation revealed a significant reduction in blood, lipid, and marrow elements in the subchondral bone after HSC. Micro-CT, histological analyses, and chondrocyte viability results showed that HSC did not damage the subchondral bone and cartilage; however, LPL and HPL may damage the subchondral bone. HSC may play an important role in decreasing immunogenicity and therefore potentially increasing the success of OCA transplantation. Show less
The use of phytosterols and phytostanols (PS) as food supplements to control plasma cholesterol concentrations has recently received attention as its efficacy has been endorsed by scientific authoriti Show more
The use of phytosterols and phytostanols (PS) as food supplements to control plasma cholesterol concentrations has recently received attention as its efficacy has been endorsed by scientific authorities and leading guidelines. However, the effects of phytosterols on lipid profiles and atherosclerosis remain incomplete and controversial. This study aims to investigate the effects of PS supplementation on lipid profiles and apolipoproteins in adults based on a systematic review of the literature and a meta-analysis of randomized controlled trials (RCTs). A comprehensive search was conducted for RCTs published in PubMed, Embase, Cochrane Library, and Web of Science as of May 2024. Random effects model was utilized to determine the mean differences and 95% confidence interval for changes in circulating lipid profiles and apolipoproteins. Twenty-eight RCTs with a total of 1777 participants (895 cases and 882 controls) are included in the qualitative synthesis. PS supplementation significantly reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and apolipoprotein B (Apo-B) levels, as well as Apo-B/apolipoprotein A1 ratios, but increased high-density lipoprotein cholesterol levels. PS supplementation dose is associated with TC, LDL-c, and Apo-B levels in a dose-response manner. Our findings suggest that dietary phytosterols can effectively promote the reduction of TC, LDL-c, and Apo-B, along with increased high-density lipoprotein cholesterol in adults. Show less
Egg performance significantly impacts the development of the local goose industry. The hypothalamus plays an essential role in the egg production of birds. However, few potential candidate genes and b Show more
Egg performance significantly impacts the development of the local goose industry. The hypothalamus plays an essential role in the egg production of birds. However, few potential candidate genes and biological functions related to egg production in geese have been identified in hypothalamus tissue. In this study, 115 geese were raised and observed for 5 months during the laying period. To understand the regulation mechanism of egg production, the hypothalamus transcriptome profiles of these geese were sequenced using RNA-seq. The hypothalamus samples of four high egg production (HEP) and four low egg production (LEP) geese were selected and collected, respectively. A total of 14,679 genes were identified in the samples. After multiple bioinformatics analyses, Gene Ontology (GO) annotations indicated that genes related to egg production were mainly enriched in biological processes of "response to light stimulus," "sensory system development," and "visual perception." Six potential candidate genes ( Show less
Extracranial arteriovenous malformations (eAVMs) are complex vascular lesions characterized by anomalous arteriovenous connections, vascular instability, and disruptions in endothelial cell (EC)-to-mu Show more
Extracranial arteriovenous malformations (eAVMs) are complex vascular lesions characterized by anomalous arteriovenous connections, vascular instability, and disruptions in endothelial cell (EC)-to-mural cell (MC) interactions. This study sought to determine whether eAVM-MCs could induce endothelial-to-mesenchymal transition (EndMT), a process known to disrupt vascular integrity, in the eAVM microenvironment. eAVM and paired control tissues were analyzed using RT-PCR for EC ( Show less
Pancreatic adenocarcinoma (PAAD) is one of the most malignancy diseases. Lysine β-hydroxybutyrylation (Kbhb) has been reported to involve various metabolism and cancer progression. Data from online da Show more
Pancreatic adenocarcinoma (PAAD) is one of the most malignancy diseases. Lysine β-hydroxybutyrylation (Kbhb) has been reported to involve various metabolism and cancer progression. Data from online databases (TCGA and GEO) were retrieved for the selection of differential expressed Kbhb site genes (DTRGs). Univariate cox and LASSO analysis were performed to identify the prognostic DTRGs. Based on the optimal DTRGs, a prognostic risk score model was established. Kaplan-Meier and Receiver operator characteristic analysis were conducted to evaluate the predicting ability of the prognosis model. Generated with clinical data, independent analysis and nomogram model were performed. Finally, the differences of survival, immune cell levels, immunotherapy response, drug sensitivity between high- and low-risk groups were explored. A total of 63 DTRGs were identified in PAAD, and these genes were related to cell division and apoptosis biological functions. Through univariate cox regression and LASSO analysis, 30 DTRGs were selected to be related to prognosis and five ( A five-gene prognosis risk model which exhibit promising predictive ability in survival is constructed for patients with PAAD. Show less
Carcass traits are crucial indicators of meat production efficiency. However, the molecular regulatory mechanisms associated with these traits remain unclear. In this study, we conducted comprehensive Show more
Carcass traits are crucial indicators of meat production efficiency. However, the molecular regulatory mechanisms associated with these traits remain unclear. In this study, we conducted comprehensive transcriptomic and genomic analyses on 399 Tiannong partridge chickens to identify key genes and variants associated with carcass traits and to elucidate the underlying regulatory mechanisms. Based on association analyses with the elastic net (EN) model, we identified 12 candidate genes (AMY1A, AP3B2, CEBPG, EEF2, EIF4EBP1, FGFR1, FOXD3, GOLM1, LOC107052698, PABPC1, SERPINB6 and TBC1D16) for 4 carcass-related traits, namely live weight, dressed weight, eviscerated weight, and breast muscle weight. SERPINB6 was identified as the only overlapping gene by 3 analyses, EN model analysis, weighted gene co-expression network analysis and differential expression analysis. Cell-level experiments confirmed that SERPINB6 promotes the proliferation of chicken DF1 cells and primary myoblasts. Further expression genome-wide association study and association analysis indicated that rs317934171 is the critical site that enhances SERPINB6 expression. Furthermore, a dual-luciferase reporter assay proved that gga-miR-1615 targets the 3'UTR of SERPINB6. Collectively, our findings reveal that SERPINB6 serves as a novel gene for chicken carcass traits by promoting fibroblast and myoblast proliferation. Additionally, the downstream variant rs317934171 regulates SERPINB6 expression. These results identify a new target gene and molecular marker for the molecular mechanisms of chicken carcass traits. Show less
Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. Renal ischemia-reperfusion injury (RIRI) is one of the main causes of AKI with the underlying mecha Show more
Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. Renal ischemia-reperfusion injury (RIRI) is one of the main causes of AKI with the underlying mechanism incompletely clarified. The liver X receptors (LXRs), including LXRα and LXRβ, are members of the nuclear receptor superfamily. It has been shown that LXRs play an important role in regulating glucose and lipid metabolism, cholesterol efflux, and inflammation. The purpose of this study was to explore the role and mechanism of LXRs in RIRI. We determined the effects of LXR activation on renal function and histological changes in a mouse RIRI model and a cellular model of hypoxia/reoxygenation (H/R). Show less
Three-dimensional (3D) chromatin architecture frequently altered in cancer. However, its changes during the pathogenesis of hepatocellular carcinoma (HCC) remained elusive. Hi-C and RNA-seq were appli Show more
Three-dimensional (3D) chromatin architecture frequently altered in cancer. However, its changes during the pathogenesis of hepatocellular carcinoma (HCC) remained elusive. Hi-C and RNA-seq were applied to study the 3D chromatin landscapes and gene expression of HCC and ANHT. Hi-C Pro was used to generate genome-wide raw interaction matrices, which were normalized via iterative correction (ICE). Moreover, the chromosomes were divided into different compartments according to the first principal component (E1). Furthermore, topologically associated domains (TADs) were visualized via WashU Epigenome Browser. Furthermore, differential expression analysis of ANHT and HCC was performed using the DESeq2 R package. Additionally, dysregulated genes associated with 3D genome architecture altered were confirmed using TCGA, qRT-PCR, immunohistochemistry (IHC), etc. RESULTS: First, the intrachromosomal interactions of chr1, chr2, chr5, and chr11 were significantly different, and the interchromosomal interactions of chr4-chr10, chr13-chr21, chr15-chr22, and chr16-chr19 are remarkably different between ANHT and HCC, which resulted in the up-regulation of TP53I3 and ZNF738 and the down-regulation of APOC3 and APOA5 in HCC. Second, 49 compartment regions on 18 chromosomes have significantly switched (A-B or B-A) during HCC tumorigenesis, contributing to up-regulation of RAP2A. Finally, a tumor-specific TAD boundary located on chr5: 6271000-6478000 and enhancer hijacking were identified in HCC tissues, potentially associated with the elevated expression of MED10, whose expression were associated with poor prognosis of HCC patients. This study demonstrates the crucial role of chromosomal structure variation in HCC oncogenesis and potential novel biomarkers of HCC, laying a foundation for cancer precision medicine development. Show less
During a sepsis infection, the lung is extremely susceptible to damage. A condition known as acute respiratory distress syndrome (ARDS) may develop in extreme circumstances. The primary objective of t Show more
During a sepsis infection, the lung is extremely susceptible to damage. A condition known as acute respiratory distress syndrome (ARDS) may develop in extreme circumstances. The primary objective of this research is to identify important genes that are related with both sepsis and lung injury. These genes have the potential to act as novel biomarkers in the investigation of sepsis-induced lung injury prevention strategies. It was possible to download from GEO data both the sepsis-related dataset (GSE64457) and the lung injury-related dataset (GSE40839). In the GSE64457 dataset, using the "limma" package in R revealed 429 differentially expressed genes (DEGs) with logFC values more than or equal to -1 and p values <0.05. There were 266 genes that were up-regulated and 163 genes that were down-regulated. Through the use of Gene Ontology (GO), it was discovered that the majority of the DEGs were associated with the inflammatory response (BP terms), a particular granule lumen (CC terms), and protein binding (MF terms). By doing a pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG), researchers were able to identify DEGs that were mostly associated with the NOD-like receptor signalling pathway, the TNF signalling pathway, and Epstein-Barr virus infection. Within the GSE40839 dataset, Weighted Gene Co-Expression Network Analysis (WGCNA) yielded a total of 7 modules, from which it was possible to screen out 2 critical modules and 693 key genes. The important genes and DEGs were both subjected to a Venn analysis. Finally, 14 genes that overlapped (ARL4A, LAIR1, MTHFD2, TSPAN13, DUSP6, PECR, CBS, TES, ASNS, SYNE1, FGF13, LCN2, KLF10, BCAT1) were closely associated to the incidence and development of sepsis-induced lung injury. This indicates that these genes are the essential genes to avoid the occurrence of sepsis-induced lung injury. This study provides novel strategies for preventing lung harm brought on by sepsis. Show less
CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, biallelic CDH1 alterations may be found in nonlobular breast carcino Show more
CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, biallelic CDH1 alterations may be found in nonlobular breast carcinomas (NL-BCs). We sought to determine the clinicopathologic characteristics and repertoire of genetic alterations of NL-BCs harboring CDH1 biallelic genetic alterations. Analysis of 5842 breast cancers (BCs) subjected to clinical tumor-normal sequencing with an FDA-cleared multigene panel was conducted to identify BCs with biallelic CDH1 pathogenic/likely pathogenic somatic mutations lacking lobular features. The genomic profiles of NL-BCs with CDH1 biallelic genetic alterations were compared with those of ILCs and invasive ductal carcinomas (IDCs), matched by clinicopathologic characteristics. Of the 896 CDH1-altered BCs, 889 samples were excluded based on the diagnosis of invasive mixed ductal/lobular carcinoma or ILC or the detection of monoallelic CDH1 alterations. Only 7 of the 5842 (0.11%) BCs harbored biallelic CDH1 alterations and lacked lobular features. Of these, 4/7 (57%) cases were ER-positive/HER2-negative, 1/7 (14%) was ER-positive/HER2-positive, and 2/7 (29%) were ER-negative/HER2-negative. In total, 5/7 (71%) were of Nottingham grade 2, and 2/7 (29%) were of grade 3. The NL-BCs with CDH1 biallelic genetic alterations included a mucinous carcinoma (n = 1), IDCs with focal nested growth (n = 2), IDC with solid papillary (n = 1) or apocrine (n = 2) features, and an IDC of no special type (NST; n = 1). E-cadherin expression, as detected by immunohistochemistry, was absent (3/5) or aberrant (discontinuous membranous/cytoplasmic/granular; 2/5). However, NL-BCs with CDH1 biallelic genetic alterations displayed recurrent genetic alterations, including TP53, PIK3CA (57%, 4/7; each), FGFR1, and NCOR1 (28%, 2/7, each) alterations. Compared with CDH1 wild-type IDC-NSTs, NL-BCs less frequently harbored GATA3 mutations (0% vs 47%, P = .03), but no significant differences were detected when compared with matched ILCs. Therefore, NL-BCs with CDH1 biallelic genetic alterations are vanishingly rare, predominantly comprise IDCs with special histologic features, and have genomic features akin to luminal B ER-positive BCs. Show less