As an indispensable tool for transcriptome-wide analysis of differential gene expression, RNA seq... more As an indispensable tool for transcriptome-wide analysis of differential gene expression, RNA sequencing (RNAseq) has demonstrated great potential in clinical applications. However, the lack of multi-group RNA reference materials of biological relevance and the corresponding reference datasets for assessing the reliability of RNAseq hampers its wide clinical applications wherein the underlying biological differences among study groups are often small. As part of the Quartet Project for quality control and data integration of multiomic profiling, we established four RNA reference materials derived from immortalized B-lymphoblastoid cell lines from four members of a monozygotic twin family. Additionally, we constructed ratio-based transcriptome-wide reference datasets using multi-batch RNAseq datasets, providing “ground truth” for benchmarking. Moreover, Quartet-sample-based quality metrics were developed for assessing reliability of RNAseq technology in terms of intra-batch proficien...
In the field of computer vision development, the core problem is how to obtain high-level semanti... more In the field of computer vision development, the core problem is how to obtain high-level semantic information from the lowest level of original video data, and make a correct understanding. At present, the research topics proposed at home and abroad are mainly focused on the visual analysis of moving objects. Especially for image research in automobile field, visual analysis of moving objects is one of the most common topics. Its focus is to use computer vision technology to detect moving objects, and describe and understand them after tracking and recognizing relevant user portraits and behaviors. In this paper, taking vehicle driving posture preference as an example, linear dimension parameters were used instead of human joint Angle parameters to simply present the driving posture of vehicle users, and corresponding dimension parameters were obtained to present the driving posture characteristics of vehicle users. By inviting 50 drivers to participate in the test of driving attit...
Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer charac... more Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer characterized by high invasiveness, heterogeneity, and mainly occurs in the ultraviolet (UV)-exposed regions of the skin, but its pathogenesis is still unclear. Here, we generated single-cell transcriptome profiles for 350 cells from six primary UV-induced cSCCs, together with matched adjacent skin samples, and three healthy control skin tissues by single-cell RNA-sequencing technology based on Smart-seq2 strategy. A series of bioinformatics analyses and in vitro experiments were used to decipher and validate the critical molecular pattern of cSCC. Results showed that cSCC cells and normal keratinocytes were significantly distinct in gene expression and chromosomal copy number variation. Furthermore, cSCC cells exhibited 18 hallmark pathways of cancer by gene set enrichment analysis. Differential expression analysis demonstrated that many members belonging to S100 gene family, SPRR gene family...
Low-grade gliomas (LGG) are the slowest growing type of brain cancer that often affects young adu... more Low-grade gliomas (LGG) are the slowest growing type of brain cancer that often affects young adults. Of all LGG cases, older patients were associated with the poor prognosis compared to younger patients. However, the molecular mechanism underlying this association remains unclear. Here, we compared genes expression profiles between younger (age[≤]50) and older (age > 50) patients from The Cancer Genome Atlas (TCGA) and demonstrate the age-related gene expressions. Pathway and gene set enrichment analysis reveal that differentially expressed genes (DEGs) between tumors of older and younger patients have been involved in cancer-related biological procedures, such as, transcriptional misregulation in cancer, nucleotide synthesis, mTOR, and DNA damage repair signaling. We also demonstrated that older patients have higher expression of Mitosis Kinase Score (MKS) and Tumor Inflammation Signature (TIS) which reflects high cell proliferation and high immune cell activity; respectively. ...
Additional file 1. Study case, sample preparation, data generation, bioinformatics analyses, cell... more Additional file 1. Study case, sample preparation, data generation, bioinformatics analyses, cell culture assays, development of mouse models with specific mutations, and in vivo irradiation assays with mutant mice were performed as described.
Additional file 1 : Supplementary figure 1. The top features of the predictive model for post-ope... more Additional file 1 : Supplementary figure 1. The top features of the predictive model for post-operative admission to ICU.
The goal of the present study was to investigate the protective effect of calcitriol on high-salt... more The goal of the present study was to investigate the protective effect of calcitriol on high-salt diet-induced hypertension. The hypertension rat model was established by a long-term high-salt diet (8% NaCl). Rats were treated with calcitriol, losartan, or their combination. Histological staining was used to confirm renal pathology. Global transcriptome analysis of renal tissues was performed, and the mechanism of the therapeutic effect of calcitriol was analysed by functional annotation and pathway analysis of the differentially expressed genes (DEGs) as well as by Western blotting analysis. The core genes for potential therapeutic regulation were identified through the coexpression gene network. For in vitro HK-2 cell experiments, small interfering RNA (siRNA) was used to knockdown key a transcription factor (TF) Glis2 to validate the therapeutic target of calcitriol. MAPK1 and CXCL12 expression was downregulated and the apoptosis pathway was significantly enriched by calcitriol treatment. The western blotting results showed that calcitriol treatment increased AMPK phosphorylation and decreased downstream mTOR phosphorylation, which was accompanied by a decrease in autophagy protein p62 expression and an increase in LC3-II/I expression. GLIS2 was identified as a specific therapeutic target for calcitriol. GLIS2 expression was upregulated by calcitriol and confirmed by HK-2 cells in vitro. Our omics data show that calcitriol can alleviate oxidative stress and fibrosis. Moreover, calcitriol can regulate the CXCL12/ERK1/2 cascade to inhibit the inflammatory response and renal cell apoptosis and induce renal autophagy through the AMPK/mTOR pathway. Our study partially elucidate the pathogenesis and treatment mechanism underlying hypertension, and provide new insights into the treatment of hypertension.
Kaposi sarcoma‐associated herpesvirus (KSHV) is endemic in Xinjiang, China. Determinants of KSHV ... more Kaposi sarcoma‐associated herpesvirus (KSHV) is endemic in Xinjiang, China. Determinants of KSHV seropositivity among high‐risk groups are not well understood. We seek to identify genetic and environmental predisposing factors for KSHV infection among Uygurs in this endemic region. A cross‐sectional study was performed among the Uygur population in Xinjiang, China. KSHV‐antibodies were detected using immunofluorescence assay (IFA) and human leukocyte antigen (HLA) alleles were genotyped. Univariate and multivariate logistic regression analyses were applied to explore the environmental and genetic risk factors of KSHV seropositivity. Finally, a total of 721 participants were included. The seroprevalence of KSHV was 24.1% among this population. Sweet‐food preference (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.03–3.34), and coronary heart disease (OR 1.91, 95%CI 1.24–2.94) were statistically correlated with KSHV infection. HLA‐DQB1*06:09 were found to significantly increase the risk of KSHV infection under all 3 models (ORAllelic = 4.06; ORDominant = 3.27; and ORRecessive = 8.06). Six SNPs (SNP0260, SNP0361, SNP0797, SNP0852, SNP1159, and SNP1375) in the DQB1 and DRB1 region and haploid type GTCTAACTAATC in block 17 were statistically associated with KSHV infection. We demonstrated that genetic variations in HLA‐DQB1/DRB1 and environmental risk factors were strongly associated with KSHV infection among this population.
Several studies have established a link between high-salt diet, inflammation, and hypertension. V... more Several studies have established a link between high-salt diet, inflammation, and hypertension. Vitamin D supplementation has shown anti-inflammatory effects in many diseases; gut microbiota is also associated with a wide variety of cardiovascular diseases, but potential role of vitamin D and gut microbiota in high-salt diet-induced hypertension remains unclear. Therefore, we used rats with hypertension induced by a high-salt diet as the research object and analyzed the transcriptome of their tissues (kidney and colon) and gut microbiome to conduct an overall analysis of the gut–kidney axis. We aimed to confirm the effects of high salt and calcitriol on the gut–kidney immune system and the composition of the intestinal flora. We demonstrate that consumption of a high-salt diet results in hypertension and inflammation in the colon and kidney and alteration of gut microbiota composition and function. High-salt diet-induced hypertension was found to be associated with seven microbial t...
Hepatocellular carcinoma (HCC) is a globally prevailing cancer with a low 5-year survival rate. L... more Hepatocellular carcinoma (HCC) is a globally prevailing cancer with a low 5-year survival rate. Little is known about its intricate gene expression profile. Single-cell RNA sequencing is an indispensable tool to explore the genetic characteristics of HCC at a more detailed level. In this study, we profiled the gene expression of single cells from human HCC tumor and para-tumor tissues using the Smart-seq 2 sequencing method. Based on differentially expressed genes, we identified heterogeneous subclones in HCC tissues, including five HCC and two hepatocyte subclones. We then carried out hub-gene co-network and functional annotations analysis followed pseudo-time analysis with regulated transcriptional factor co-networks to determine HCC cellular trajectory. We found that MLX interacting protein like (MLXIPL) was commonly upregulated in the single cells and tissues and associated with a poor survival rate in HCC. Mechanistically, MLXIPL activation is crucial for promoting cell prolife...
Gastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with meta... more Gastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with metastasis. The mechanism of gastric carcinoma lymph node metastasis remains unknown due to traditional bulk-leveled approaches masking the roles of subpopulations. To answer questions concerning metastasis from the gastric carcinoma intratumoural perspective, we performed single-cell level analysis on three gastric cancer patients with primary cancer and paired metastatic lymph node cancer tissues using single-cell RNA-seq (scRNA-seq). The results showed distinct carcinoma profiles from each patient, and diverse microenvironmental subsets were shared across different patients. Clustering data showed significant intratumoural heterogeneity. The results also revealed a subgroup of cells bridging the metastatic group and primary group, implying the transition state of cancer during the metastatic process. In the present study, we obtained a more comprehensive picture of gastric cancer lymph no...
Abnormal lipid metabolism is regarded as a crucial cause of psoriasis. The specific mechanism of ... more Abnormal lipid metabolism is regarded as a crucial cause of psoriasis. The specific mechanism of how phospholipase PLA2G4B mediates local immune dysfunction and skin lesions remains unclear. The aim of this study was to explore the mechanisms of anti-psoriasis and immune suppression effect by inhibiting PLA2G4B in psoriasis progression. We successfully transfected si-PLA2G4B in a murine keratinocyte cell-line PAM212 to verify the effect of progression by PLA2G4B. The Imiquimod psoriasis mouse model was then successfully constructed, followed by emulsion wrapped PLA2G4B-siRNA applied to the skin lesions. The phenotype, pathology, immunofluorescence staining of PLA2G4B, IL17, CD3, and CD1b, and bulk transcriptome analysis were performed to decipher the effect and mechanism of si-PLA2G4B. Interfering with PLA2G4B significantly inhibited the proliferation and migration of PAM212. The interference of PLA2G4B in vivo showed a therapeutic effect on psoriasis, comparable to that of betameth...
China has the largest number of patients with dementia in the world. However, dementia in the Chi... more China has the largest number of patients with dementia in the world. However, dementia in the Chinese population is still poorly understood and under‐researched. Given the differences in genetic, demographic, sociocultural, lifestyle, and health profiles among Chinese and other ethnic/racial groups, it is crucial to build appropriate infrastructure for long‐term longitudinal studies to advance Chinese cognitive aging and dementia research. We initiated a community‐based prospective cohort—the Taizhou Imaging Study (TIS)—to accelerate the understanding of dementia and cerebrovascular diseases in Chinese. This article presents the rationale, aims, study design, and organization of TIS. In addition, we described some examples of the types of studies such a resource might support. The TIS provides a new framework for facilitating Chinese dementia research, encompassing invaluable resources including detailed epidemiological, sociocultural, neuroimaging, and omics data.
We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogen... more We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. We demonstrated in cell and mouse models that, compared to the wild-type, (1) c.403G>A mutant cell lines were more sensitive to irradiation, a DNA damage agent, and a PARP inhibitor; (2) c.403G>A mutation inhibited interaction between BARD1 and RAD51 (but not BRCA1); and (3) c.403G>A mutant mice were hypersensitive to ionizing radiation. Our study shed lights on the clinical interpretation of rare germline mutations of BARD1.
Background Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood l... more Background Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood lipid metabolism is an important risk factor. Transforming growth factor-ß (TGF-ß) and its receptor (TGF-ßR) can inhibit the release of inflammatory factors through the SMAD pathway-mediated immune response, thereby suppressing the progression of CAD. Endoglin (TGF-ßRIII), a TGF-ßR family homologous receptor protein, is directly involved in the immunoregulatory process, but the exact mechanism is unclear. This study aimed to clarify the pathophysiological effects of endoglin on the development of atherosclerosis and to explore the mechanism of the signalling pathway. Methods We downloaded the GEO dataset to perform a functional analysis of SMAD family activity and TGF-ß receptor protein expression in the monocyte expression profiles of patients with familial hyperlipidaemia (FH). The effect of endoglin on endothelial cell proliferation, migration, and apoptosis was examined by disrupting ...
AIMS Nearly one third of patients receiving cardiac resynchronization therapy (CRT) suffer non-re... more AIMS Nearly one third of patients receiving cardiac resynchronization therapy (CRT) suffer non-response. We intend to develop predictive models using machine learning (ML) approaches and easily attainable features before CRT implantation. METHODS AND RESULTS The baseline characteristics of 752 CRT recipients from two hospitals were retrospectively collected. Nine ML predictive models were established, including logistic regression (LR), elastic network (EN), lasso regression (Lasso), ridge regression (Ridge), neural network (NN), support vector machine (SVM), random forest (RF), XGBoost and k-nearest neighbour (k-NN). Sensitivity, specificity, precision, accuracy, F1, log-loss, area under the receiver operating characteristic (AU-ROC), and average precision (AP) of each model were evaluated. AU-ROC was compared between models and the latest guidelines. Six models had an AU-ROC value above 0.75. The LR, EN and Ridge models showed the highest overall predictive power compared with other models with AU-ROC at 0.77. The XGBoost model reached the highest sensitivity at 0.72, while the highest specificity was achieved by Ridge model at 0.92. All ML models achieved higher AU-ROCs that those derived from the latest guidelines (all P < 0.05). The effect size analysis identified left bundle branch block, left ventricular end-systolic diameter, and history of percutaneous coronary intervention as the most crucial predictors of CRT response. An online tool to facilitate the prediction of CRT response is freely available at http://www.crt-response.com/. CONCLUSIONS ML algorithms produced efficient predictive models for evaluation of CRT response with features before implantation. Tools developed accordingly could improve the selection of CRT candidates and reduce the incidence of non-response.
As an indispensable tool for transcriptome-wide analysis of differential gene expression, RNA seq... more As an indispensable tool for transcriptome-wide analysis of differential gene expression, RNA sequencing (RNAseq) has demonstrated great potential in clinical applications. However, the lack of multi-group RNA reference materials of biological relevance and the corresponding reference datasets for assessing the reliability of RNAseq hampers its wide clinical applications wherein the underlying biological differences among study groups are often small. As part of the Quartet Project for quality control and data integration of multiomic profiling, we established four RNA reference materials derived from immortalized B-lymphoblastoid cell lines from four members of a monozygotic twin family. Additionally, we constructed ratio-based transcriptome-wide reference datasets using multi-batch RNAseq datasets, providing “ground truth” for benchmarking. Moreover, Quartet-sample-based quality metrics were developed for assessing reliability of RNAseq technology in terms of intra-batch proficien...
In the field of computer vision development, the core problem is how to obtain high-level semanti... more In the field of computer vision development, the core problem is how to obtain high-level semantic information from the lowest level of original video data, and make a correct understanding. At present, the research topics proposed at home and abroad are mainly focused on the visual analysis of moving objects. Especially for image research in automobile field, visual analysis of moving objects is one of the most common topics. Its focus is to use computer vision technology to detect moving objects, and describe and understand them after tracking and recognizing relevant user portraits and behaviors. In this paper, taking vehicle driving posture preference as an example, linear dimension parameters were used instead of human joint Angle parameters to simply present the driving posture of vehicle users, and corresponding dimension parameters were obtained to present the driving posture characteristics of vehicle users. By inviting 50 drivers to participate in the test of driving attit...
Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer charac... more Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer characterized by high invasiveness, heterogeneity, and mainly occurs in the ultraviolet (UV)-exposed regions of the skin, but its pathogenesis is still unclear. Here, we generated single-cell transcriptome profiles for 350 cells from six primary UV-induced cSCCs, together with matched adjacent skin samples, and three healthy control skin tissues by single-cell RNA-sequencing technology based on Smart-seq2 strategy. A series of bioinformatics analyses and in vitro experiments were used to decipher and validate the critical molecular pattern of cSCC. Results showed that cSCC cells and normal keratinocytes were significantly distinct in gene expression and chromosomal copy number variation. Furthermore, cSCC cells exhibited 18 hallmark pathways of cancer by gene set enrichment analysis. Differential expression analysis demonstrated that many members belonging to S100 gene family, SPRR gene family...
Low-grade gliomas (LGG) are the slowest growing type of brain cancer that often affects young adu... more Low-grade gliomas (LGG) are the slowest growing type of brain cancer that often affects young adults. Of all LGG cases, older patients were associated with the poor prognosis compared to younger patients. However, the molecular mechanism underlying this association remains unclear. Here, we compared genes expression profiles between younger (age[≤]50) and older (age > 50) patients from The Cancer Genome Atlas (TCGA) and demonstrate the age-related gene expressions. Pathway and gene set enrichment analysis reveal that differentially expressed genes (DEGs) between tumors of older and younger patients have been involved in cancer-related biological procedures, such as, transcriptional misregulation in cancer, nucleotide synthesis, mTOR, and DNA damage repair signaling. We also demonstrated that older patients have higher expression of Mitosis Kinase Score (MKS) and Tumor Inflammation Signature (TIS) which reflects high cell proliferation and high immune cell activity; respectively. ...
Additional file 1. Study case, sample preparation, data generation, bioinformatics analyses, cell... more Additional file 1. Study case, sample preparation, data generation, bioinformatics analyses, cell culture assays, development of mouse models with specific mutations, and in vivo irradiation assays with mutant mice were performed as described.
Additional file 1 : Supplementary figure 1. The top features of the predictive model for post-ope... more Additional file 1 : Supplementary figure 1. The top features of the predictive model for post-operative admission to ICU.
The goal of the present study was to investigate the protective effect of calcitriol on high-salt... more The goal of the present study was to investigate the protective effect of calcitriol on high-salt diet-induced hypertension. The hypertension rat model was established by a long-term high-salt diet (8% NaCl). Rats were treated with calcitriol, losartan, or their combination. Histological staining was used to confirm renal pathology. Global transcriptome analysis of renal tissues was performed, and the mechanism of the therapeutic effect of calcitriol was analysed by functional annotation and pathway analysis of the differentially expressed genes (DEGs) as well as by Western blotting analysis. The core genes for potential therapeutic regulation were identified through the coexpression gene network. For in vitro HK-2 cell experiments, small interfering RNA (siRNA) was used to knockdown key a transcription factor (TF) Glis2 to validate the therapeutic target of calcitriol. MAPK1 and CXCL12 expression was downregulated and the apoptosis pathway was significantly enriched by calcitriol treatment. The western blotting results showed that calcitriol treatment increased AMPK phosphorylation and decreased downstream mTOR phosphorylation, which was accompanied by a decrease in autophagy protein p62 expression and an increase in LC3-II/I expression. GLIS2 was identified as a specific therapeutic target for calcitriol. GLIS2 expression was upregulated by calcitriol and confirmed by HK-2 cells in vitro. Our omics data show that calcitriol can alleviate oxidative stress and fibrosis. Moreover, calcitriol can regulate the CXCL12/ERK1/2 cascade to inhibit the inflammatory response and renal cell apoptosis and induce renal autophagy through the AMPK/mTOR pathway. Our study partially elucidate the pathogenesis and treatment mechanism underlying hypertension, and provide new insights into the treatment of hypertension.
Kaposi sarcoma‐associated herpesvirus (KSHV) is endemic in Xinjiang, China. Determinants of KSHV ... more Kaposi sarcoma‐associated herpesvirus (KSHV) is endemic in Xinjiang, China. Determinants of KSHV seropositivity among high‐risk groups are not well understood. We seek to identify genetic and environmental predisposing factors for KSHV infection among Uygurs in this endemic region. A cross‐sectional study was performed among the Uygur population in Xinjiang, China. KSHV‐antibodies were detected using immunofluorescence assay (IFA) and human leukocyte antigen (HLA) alleles were genotyped. Univariate and multivariate logistic regression analyses were applied to explore the environmental and genetic risk factors of KSHV seropositivity. Finally, a total of 721 participants were included. The seroprevalence of KSHV was 24.1% among this population. Sweet‐food preference (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.03–3.34), and coronary heart disease (OR 1.91, 95%CI 1.24–2.94) were statistically correlated with KSHV infection. HLA‐DQB1*06:09 were found to significantly increase the risk of KSHV infection under all 3 models (ORAllelic = 4.06; ORDominant = 3.27; and ORRecessive = 8.06). Six SNPs (SNP0260, SNP0361, SNP0797, SNP0852, SNP1159, and SNP1375) in the DQB1 and DRB1 region and haploid type GTCTAACTAATC in block 17 were statistically associated with KSHV infection. We demonstrated that genetic variations in HLA‐DQB1/DRB1 and environmental risk factors were strongly associated with KSHV infection among this population.
Several studies have established a link between high-salt diet, inflammation, and hypertension. V... more Several studies have established a link between high-salt diet, inflammation, and hypertension. Vitamin D supplementation has shown anti-inflammatory effects in many diseases; gut microbiota is also associated with a wide variety of cardiovascular diseases, but potential role of vitamin D and gut microbiota in high-salt diet-induced hypertension remains unclear. Therefore, we used rats with hypertension induced by a high-salt diet as the research object and analyzed the transcriptome of their tissues (kidney and colon) and gut microbiome to conduct an overall analysis of the gut–kidney axis. We aimed to confirm the effects of high salt and calcitriol on the gut–kidney immune system and the composition of the intestinal flora. We demonstrate that consumption of a high-salt diet results in hypertension and inflammation in the colon and kidney and alteration of gut microbiota composition and function. High-salt diet-induced hypertension was found to be associated with seven microbial t...
Hepatocellular carcinoma (HCC) is a globally prevailing cancer with a low 5-year survival rate. L... more Hepatocellular carcinoma (HCC) is a globally prevailing cancer with a low 5-year survival rate. Little is known about its intricate gene expression profile. Single-cell RNA sequencing is an indispensable tool to explore the genetic characteristics of HCC at a more detailed level. In this study, we profiled the gene expression of single cells from human HCC tumor and para-tumor tissues using the Smart-seq 2 sequencing method. Based on differentially expressed genes, we identified heterogeneous subclones in HCC tissues, including five HCC and two hepatocyte subclones. We then carried out hub-gene co-network and functional annotations analysis followed pseudo-time analysis with regulated transcriptional factor co-networks to determine HCC cellular trajectory. We found that MLX interacting protein like (MLXIPL) was commonly upregulated in the single cells and tissues and associated with a poor survival rate in HCC. Mechanistically, MLXIPL activation is crucial for promoting cell prolife...
Gastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with meta... more Gastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with metastasis. The mechanism of gastric carcinoma lymph node metastasis remains unknown due to traditional bulk-leveled approaches masking the roles of subpopulations. To answer questions concerning metastasis from the gastric carcinoma intratumoural perspective, we performed single-cell level analysis on three gastric cancer patients with primary cancer and paired metastatic lymph node cancer tissues using single-cell RNA-seq (scRNA-seq). The results showed distinct carcinoma profiles from each patient, and diverse microenvironmental subsets were shared across different patients. Clustering data showed significant intratumoural heterogeneity. The results also revealed a subgroup of cells bridging the metastatic group and primary group, implying the transition state of cancer during the metastatic process. In the present study, we obtained a more comprehensive picture of gastric cancer lymph no...
Abnormal lipid metabolism is regarded as a crucial cause of psoriasis. The specific mechanism of ... more Abnormal lipid metabolism is regarded as a crucial cause of psoriasis. The specific mechanism of how phospholipase PLA2G4B mediates local immune dysfunction and skin lesions remains unclear. The aim of this study was to explore the mechanisms of anti-psoriasis and immune suppression effect by inhibiting PLA2G4B in psoriasis progression. We successfully transfected si-PLA2G4B in a murine keratinocyte cell-line PAM212 to verify the effect of progression by PLA2G4B. The Imiquimod psoriasis mouse model was then successfully constructed, followed by emulsion wrapped PLA2G4B-siRNA applied to the skin lesions. The phenotype, pathology, immunofluorescence staining of PLA2G4B, IL17, CD3, and CD1b, and bulk transcriptome analysis were performed to decipher the effect and mechanism of si-PLA2G4B. Interfering with PLA2G4B significantly inhibited the proliferation and migration of PAM212. The interference of PLA2G4B in vivo showed a therapeutic effect on psoriasis, comparable to that of betameth...
China has the largest number of patients with dementia in the world. However, dementia in the Chi... more China has the largest number of patients with dementia in the world. However, dementia in the Chinese population is still poorly understood and under‐researched. Given the differences in genetic, demographic, sociocultural, lifestyle, and health profiles among Chinese and other ethnic/racial groups, it is crucial to build appropriate infrastructure for long‐term longitudinal studies to advance Chinese cognitive aging and dementia research. We initiated a community‐based prospective cohort—the Taizhou Imaging Study (TIS)—to accelerate the understanding of dementia and cerebrovascular diseases in Chinese. This article presents the rationale, aims, study design, and organization of TIS. In addition, we described some examples of the types of studies such a resource might support. The TIS provides a new framework for facilitating Chinese dementia research, encompassing invaluable resources including detailed epidemiological, sociocultural, neuroimaging, and omics data.
We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogen... more We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. We demonstrated in cell and mouse models that, compared to the wild-type, (1) c.403G>A mutant cell lines were more sensitive to irradiation, a DNA damage agent, and a PARP inhibitor; (2) c.403G>A mutation inhibited interaction between BARD1 and RAD51 (but not BRCA1); and (3) c.403G>A mutant mice were hypersensitive to ionizing radiation. Our study shed lights on the clinical interpretation of rare germline mutations of BARD1.
Background Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood l... more Background Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood lipid metabolism is an important risk factor. Transforming growth factor-ß (TGF-ß) and its receptor (TGF-ßR) can inhibit the release of inflammatory factors through the SMAD pathway-mediated immune response, thereby suppressing the progression of CAD. Endoglin (TGF-ßRIII), a TGF-ßR family homologous receptor protein, is directly involved in the immunoregulatory process, but the exact mechanism is unclear. This study aimed to clarify the pathophysiological effects of endoglin on the development of atherosclerosis and to explore the mechanism of the signalling pathway. Methods We downloaded the GEO dataset to perform a functional analysis of SMAD family activity and TGF-ß receptor protein expression in the monocyte expression profiles of patients with familial hyperlipidaemia (FH). The effect of endoglin on endothelial cell proliferation, migration, and apoptosis was examined by disrupting ...
AIMS Nearly one third of patients receiving cardiac resynchronization therapy (CRT) suffer non-re... more AIMS Nearly one third of patients receiving cardiac resynchronization therapy (CRT) suffer non-response. We intend to develop predictive models using machine learning (ML) approaches and easily attainable features before CRT implantation. METHODS AND RESULTS The baseline characteristics of 752 CRT recipients from two hospitals were retrospectively collected. Nine ML predictive models were established, including logistic regression (LR), elastic network (EN), lasso regression (Lasso), ridge regression (Ridge), neural network (NN), support vector machine (SVM), random forest (RF), XGBoost and k-nearest neighbour (k-NN). Sensitivity, specificity, precision, accuracy, F1, log-loss, area under the receiver operating characteristic (AU-ROC), and average precision (AP) of each model were evaluated. AU-ROC was compared between models and the latest guidelines. Six models had an AU-ROC value above 0.75. The LR, EN and Ridge models showed the highest overall predictive power compared with other models with AU-ROC at 0.77. The XGBoost model reached the highest sensitivity at 0.72, while the highest specificity was achieved by Ridge model at 0.92. All ML models achieved higher AU-ROCs that those derived from the latest guidelines (all P < 0.05). The effect size analysis identified left bundle branch block, left ventricular end-systolic diameter, and history of percutaneous coronary intervention as the most crucial predictors of CRT response. An online tool to facilitate the prediction of CRT response is freely available at http://www.crt-response.com/. CONCLUSIONS ML algorithms produced efficient predictive models for evaluation of CRT response with features before implantation. Tools developed accordingly could improve the selection of CRT candidates and reduce the incidence of non-response.
Uploads
Papers by sibo zhu