BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prola...BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prolapse and hemorrhoids,and tissue selecting technique,are employed for treatment,they are often associated with postoperative complications,including unsatisfactory defecation,bleeding,and anal stenosis.In contrast,Xiaozhiling injection,a traditional Chinese medicine-based therapy,has emerged as a minimally invasive and effective alternative for internal hemorrhoids.This treatment offers distinct advantages,such as reduced dietary restrictions,broad applicability,and minimal induction of systemic inflammatory responses.Additionally,Xiaozhiling injection effectively eliminates hemorrhoid nuclei,prevents local tissue necrosis,preserves anal cushion integrity,and mitigates postoperative complications,including bleeding and prolapse.Despite its clinical efficacy,the molecular mechanisms underlying its therapeutic effects remain poorly understood,warranting further investigation.AIM To investigate the molecular mechanism underlying the therapeutic effect of Xiaozhiling injection in the treatment of internal hemorrhoids.METHODS An internal hemorrhoid model was established in rats,and the rats were randomly divided into a modeling group[control group(CK group)]and a treatment group.One week after injection,Stereo-seq and electron microscopy were used to study the changes in gene expression and subcellular structures in fibroblasts.RESULTS Single-cell sequencing revealed differences in the expression and transcript levels of the genes collagen 3 alpha 1,decorin,and actin alpha 2 in fibroblasts between the CK group and the treatment group.Spatial transcriptome analysis revealed that genes of the sphingosine kinase 1(Sphk1)/sphingosine-1-phosphate(S1P)pathway spatially overlapped with key genes of the transforming growth factor beta 1 pathway,namely,Sphk1,S1P receptor,and transforming growth factor beta 1,in the treatment group.The proportion of fibroblasts was lower in the treatment group than in the CK group,and Xiaozhiling treatment had a significant effect on the proportion of fibroblasts in hemorrhoidal tissue.Immunohistochemistry revealed a significant increase in the expression of a fibroblast marker.Electron microscopy showed that the endoplasmic reticulum of fibroblasts contained a large amount of glycogen,indicating cell activation.Fibroblast activation and the expression of key genes of the Sphk1-S1P pathway could be observed at the injection site,suggesting that after Xiaozhiling intervention,the Sphk1-S1P pathway could be activated to promote fibrosis.CONCLUSION Xiaozhiling injection exerts its therapeutic effects on internal hemorrhoids by promoting collagen synthesis and secretion in fibroblasts.After Xiaozhiling intervention,the Sphk1-S1P pathway can be activated to promote fibrosis.展开更多
The Daming Temple,built during 457–464 C.E.,is one of the developing ancient temple heritage spaces located in Yangzhou city,P.R.China.Over the past 60 years,variation in visitors’spatial perception along the tour r...The Daming Temple,built during 457–464 C.E.,is one of the developing ancient temple heritage spaces located in Yangzhou city,P.R.China.Over the past 60 years,variation in visitors’spatial perception along the tour routes in the temple has occurred.This research attempts to reveal the changes in visitors’visual perception along the spatial sequences at 3 different times(i.e.,1962,1973 and 2022).A quantitative GIS-based method,which includes analysing the distribution of visitors’spatial preferences and spatial configuration,is proposed.Digital landscape tools and quantitative estimation methods are used,including mapping within Rhinoceros software,the kernel density estimation(KDE)method within ArcGIS software and spatial syntax analysis within DepthMap software.Extracted geodata from 500 photographs of the heritage space taken by volunteer visitors are analysed within the GIS environment.Values of the mean depth(MD)at both levels of visibility and accessibility are calculated within the visibility graph analysis(VGA)model.Comparisons between the visual preferences of the visitors and the spatial configuration along the spatial sequence are conducted.The results indicate that the spatial sequence has a significant impact on visitors’visual preferences and tour routes.The phenomenon of spatial sequence among dynamic temporal variations and the effects of narrative spaces along the spatial sequence are highlighted and explained,which reveal the relationship between visitors’geospatial preference and the spatial configuration of the temple.Some suggestions are put forwards for further studies on the revitalisation and management of East Asian ancient temple heritage spaces.展开更多
Based on 294 earthquake sequences with magnitude greater than or equal to 5.0 occurred in Chinese mainland since 1970, the spatial distribution features of sequence types have been studied. In southwestern China, it t...Based on 294 earthquake sequences with magnitude greater than or equal to 5.0 occurred in Chinese mainland since 1970, the spatial distribution features of sequence types have been studied. In southwestern China, it takes mainshock-aftershock sequence type （MAT） as the major in Chuan-Dian rhombic block and concerned Xianshuihe-Anninghe-Xiaojiang seismic belt, as well as in Jinshajiang-Honghe seismic belt. Multiple mainshock type （MMT） mainly distributes in western Yunnan, and Longlin and Lancang areas in Tengchong-Baoshan block in west of Nujiang-Lancangjiang fault zone. A few isolated earthquake type （IET） mainly occurred in northwestern Sichuan and there is no IET occurred in Yunnan region. In northwestern China, it takes mainshock-aftershock sequence type （MAT） as the major in west segment of South Tianshan in Xinjiang region. Some MMT also occurred in this area in the intersection of Kalpin block and the Puchang fault zone. It takes IET as the major in middle Tianshan in Xinjiang. Along the Qilianshan seismic belt, most of sequences are MAT. In Qinghai region, it takes MAT as the major, but the regional feature of the spatial distribution of sequence types is not very clear. In North China, it takes MAT as the major in Yinshan-Yanshan-Bohai seismic belt, north edge of North China, and in Hebei plain seismic belt, as well as in sub-plate of lower river area of Yangtze River. In intersection of north segment of Shanxi seismic belt and the NW-trending Yinshan-Yanshan-Bohai seismic belt, there are several moderate or strong MMT with magnitude from 5.0 to 6.0 occurred. In south of North China around the latitude line of 35°N, it takes IET as the major. The spatial distribution of sequence types is relevant to the patterns of tectonic movements. MAT is mostly produced by the ruptures of locked units or asperities or the neonatal separating segments inside the fault zones. MMT is generally relevant to the conjugate structures or intersection of many tectonic settings. Further extension of simple fault often produces IET. Spatial distribution of sequence types is also correlative to the regional and deep environment of crustal medium to some extent. MAT mainly distributes in high velocity area in upper crust or in the transition zone between high velocity area and low velocity area, MMT mostly occurred in the low velocity area in upper crust.展开更多
Autism Spectrum Disorders(ASDs)are reported as a group of neurodevelopmental disorders.The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with ...Autism Spectrum Disorders(ASDs)are reported as a group of neurodevelopmental disorders.The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes,but the underlying mechanisms are not fully understood.Here,we report that deletion of Trio,a high-susceptibility gene of ASDs,causes a postnatal dentate gyrus(DG)hypoplasia with a zigzagged suprapyramidal blade,and the Trio-defcient mice display autism-like behaviors.The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells(GCs),which further results in a migration defcit of neural progenitors.Furthermore,we reveal that Trio plays diferent roles in various excitatory neural cells by spatial transcriptomic sequencing,especially the role of regulating the migration of postmitotic GCs.In summary,our fndings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.展开更多
Background:Tumor heterogeneity is contributed by tumor cells and the microenvironment.Dynamics of tumor heterogeneity during colorectal cancer(CRC)progression have not been elucidated.Methods:Eight single-cell RNA seq...Background:Tumor heterogeneity is contributed by tumor cells and the microenvironment.Dynamics of tumor heterogeneity during colorectal cancer(CRC)progression have not been elucidated.Methods:Eight single-cell RNA sequencing(scRNA-seq)data sets of CRC were included.Milo was utilized to reveal the differential abundance of cell clusters during progression.The differentiation trajectory was imputed by using the Palantir algorithm and metabolic states were assessed by using scMetabolism.Three spatial transcription sequencing(ST-seq)data sets of CRC were used to validate cell-type abundances and colocalization.Cancer-associated regulatory hubs were defined as communication networks affecting tumor biological behaviors.Finally,quantitative reverse transcription polymerase chain reaction and immunohistochemistry staining were performed for validation.Results:TM4SF1t,SOX4t,and MKI67t tumor cells;CXCL12t cancer-associated fibroblasts;CD4t resident memory T cells;Treg;IgAt plasma cells;and several myeloid subsets were enriched in stage IV CRC,most of which were associated with overall survival of patients.Trajectory analysis indicated that tumor cells from patients with advanced-stage CRC were less differentiated,when metabolic heterogeneity showed a highest metabolic signature in terminal states of stromal cells,T cells,and myeloid cells.Moreover,ST-seq validated cell-type abundance in a spatial context and also revealed the correlation of immune infiltration between tertiary lymphoid structures and tumors followed by validation in our cohort.Importantly,analysis of cancer-associated regulatory hubs revealed a cascade of activated pathways including leukocyte apoptotic process,MAPK pathway,myeloid leukocyte differentiation,and angiogenesis during CRC progression.Conclusions:Tumor heterogeneity was dynamic during progression,with the enrichment of immunosuppressive Treg,myeloid cells,and fibrotic cells.The differential state of tumor cells was associated with cancer staging.Assessment of cancer-associated regulatory hubs suggested impaired antitumor immunity and increased metastatic ability during CRC progression.展开更多
Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world,which seriously threatens the life and health of middle-aged and elderly men.The progression of prostate ...Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world,which seriously threatens the life and health of middle-aged and elderly men.The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment.Understanding the mechanisms of pros-tate cancer pathogenesis and disease progression is important to guide diagnosis and therapy.The emergence of single-cell RNA sequencing(scRNA-seq)and spatial transcriptome sequencing(ST-seq)technologies has brought breakthroughs in the study of prostate cancer.It makes up for the defects of traditional techniques such as fluo-rescence-activated cell sorting that are difficult to elucidate cell-specific gene expression.This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq,aims to provide a reference for the optimal diagnosis and treatment of prostate cancer.展开更多
Spatial transcriptomics,which combine gene expression data with spatial information,has quickly expanded in recent years.With application of this method in liver research,our knowledge about liver development,regenera...Spatial transcriptomics,which combine gene expression data with spatial information,has quickly expanded in recent years.With application of this method in liver research,our knowledge about liver development,regeneration,and diseases have been greatly improved.While this field is moving forward,a variety of problems still need to be addressed,including sensitivity,limited capacity to obtain exact single-cell information,data processing methods,as well as others.Methods like single-cell RNA sequencing(scRNA-seq)are usually used together with spatial transcriptome sequencing(ST-seq)to clarify cell-specific gene expression.In this review,we explore how advances of scRNA-seq and ST-seq,especially ST-seq,will pave the way to new opportunities to investigate fundamental questions in liver research.Finally,we will discuss the strengths,limitations,and future perspectives of ST-seq in liver research.展开更多
基金Supported by the National Natural Science Foundation of China,No.81774118the Foreign Cooperation Project of Science and Technology Department of Fujian Province,No.2023I0021the Medical Innovation Project of Fujian Province,No.2024CXB013.
文摘BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prolapse and hemorrhoids,and tissue selecting technique,are employed for treatment,they are often associated with postoperative complications,including unsatisfactory defecation,bleeding,and anal stenosis.In contrast,Xiaozhiling injection,a traditional Chinese medicine-based therapy,has emerged as a minimally invasive and effective alternative for internal hemorrhoids.This treatment offers distinct advantages,such as reduced dietary restrictions,broad applicability,and minimal induction of systemic inflammatory responses.Additionally,Xiaozhiling injection effectively eliminates hemorrhoid nuclei,prevents local tissue necrosis,preserves anal cushion integrity,and mitigates postoperative complications,including bleeding and prolapse.Despite its clinical efficacy,the molecular mechanisms underlying its therapeutic effects remain poorly understood,warranting further investigation.AIM To investigate the molecular mechanism underlying the therapeutic effect of Xiaozhiling injection in the treatment of internal hemorrhoids.METHODS An internal hemorrhoid model was established in rats,and the rats were randomly divided into a modeling group[control group(CK group)]and a treatment group.One week after injection,Stereo-seq and electron microscopy were used to study the changes in gene expression and subcellular structures in fibroblasts.RESULTS Single-cell sequencing revealed differences in the expression and transcript levels of the genes collagen 3 alpha 1,decorin,and actin alpha 2 in fibroblasts between the CK group and the treatment group.Spatial transcriptome analysis revealed that genes of the sphingosine kinase 1(Sphk1)/sphingosine-1-phosphate(S1P)pathway spatially overlapped with key genes of the transforming growth factor beta 1 pathway,namely,Sphk1,S1P receptor,and transforming growth factor beta 1,in the treatment group.The proportion of fibroblasts was lower in the treatment group than in the CK group,and Xiaozhiling treatment had a significant effect on the proportion of fibroblasts in hemorrhoidal tissue.Immunohistochemistry revealed a significant increase in the expression of a fibroblast marker.Electron microscopy showed that the endoplasmic reticulum of fibroblasts contained a large amount of glycogen,indicating cell activation.Fibroblast activation and the expression of key genes of the Sphk1-S1P pathway could be observed at the injection site,suggesting that after Xiaozhiling intervention,the Sphk1-S1P pathway could be activated to promote fibrosis.CONCLUSION Xiaozhiling injection exerts its therapeutic effects on internal hemorrhoids by promoting collagen synthesis and secretion in fibroblasts.After Xiaozhiling intervention,the Sphk1-S1P pathway can be activated to promote fibrosis.
基金supported by the National Natural Science Foundation of China(project#52278083)the Ministry of Education Humanities and Social Sciences Research Planning Fund(project#18YJAZH103).
文摘The Daming Temple,built during 457–464 C.E.,is one of the developing ancient temple heritage spaces located in Yangzhou city,P.R.China.Over the past 60 years,variation in visitors’spatial perception along the tour routes in the temple has occurred.This research attempts to reveal the changes in visitors’visual perception along the spatial sequences at 3 different times(i.e.,1962,1973 and 2022).A quantitative GIS-based method,which includes analysing the distribution of visitors’spatial preferences and spatial configuration,is proposed.Digital landscape tools and quantitative estimation methods are used,including mapping within Rhinoceros software,the kernel density estimation(KDE)method within ArcGIS software and spatial syntax analysis within DepthMap software.Extracted geodata from 500 photographs of the heritage space taken by volunteer visitors are analysed within the GIS environment.Values of the mean depth(MD)at both levels of visibility and accessibility are calculated within the visibility graph analysis(VGA)model.Comparisons between the visual preferences of the visitors and the spatial configuration along the spatial sequence are conducted.The results indicate that the spatial sequence has a significant impact on visitors’visual preferences and tour routes.The phenomenon of spatial sequence among dynamic temporal variations and the effects of narrative spaces along the spatial sequence are highlighted and explained,which reveal the relationship between visitors’geospatial preference and the spatial configuration of the temple.Some suggestions are put forwards for further studies on the revitalisation and management of East Asian ancient temple heritage spaces.
基金Joint Seismological Science Foundation of China (105076) and continued subject ″Statistic Features of Aftershock Sequences and Forecast of the Large Aftershocks″ (2004BA601B01-04-02), Ministry of Science and Technology of China in the 10th Five-Year Plan.
文摘Based on 294 earthquake sequences with magnitude greater than or equal to 5.0 occurred in Chinese mainland since 1970, the spatial distribution features of sequence types have been studied. In southwestern China, it takes mainshock-aftershock sequence type （MAT） as the major in Chuan-Dian rhombic block and concerned Xianshuihe-Anninghe-Xiaojiang seismic belt, as well as in Jinshajiang-Honghe seismic belt. Multiple mainshock type （MMT） mainly distributes in western Yunnan, and Longlin and Lancang areas in Tengchong-Baoshan block in west of Nujiang-Lancangjiang fault zone. A few isolated earthquake type （IET） mainly occurred in northwestern Sichuan and there is no IET occurred in Yunnan region. In northwestern China, it takes mainshock-aftershock sequence type （MAT） as the major in west segment of South Tianshan in Xinjiang region. Some MMT also occurred in this area in the intersection of Kalpin block and the Puchang fault zone. It takes IET as the major in middle Tianshan in Xinjiang. Along the Qilianshan seismic belt, most of sequences are MAT. In Qinghai region, it takes MAT as the major, but the regional feature of the spatial distribution of sequence types is not very clear. In North China, it takes MAT as the major in Yinshan-Yanshan-Bohai seismic belt, north edge of North China, and in Hebei plain seismic belt, as well as in sub-plate of lower river area of Yangtze River. In intersection of north segment of Shanxi seismic belt and the NW-trending Yinshan-Yanshan-Bohai seismic belt, there are several moderate or strong MMT with magnitude from 5.0 to 6.0 occurred. In south of North China around the latitude line of 35°N, it takes IET as the major. The spatial distribution of sequence types is relevant to the patterns of tectonic movements. MAT is mostly produced by the ruptures of locked units or asperities or the neonatal separating segments inside the fault zones. MMT is generally relevant to the conjugate structures or intersection of many tectonic settings. Further extension of simple fault often produces IET. Spatial distribution of sequence types is also correlative to the regional and deep environment of crustal medium to some extent. MAT mainly distributes in high velocity area in upper crust or in the transition zone between high velocity area and low velocity area, MMT mostly occurred in the low velocity area in upper crust.
基金supported by grants from the Key Realm R&D Program of Guangdong Province(2019B030335001)the National Natural Science Foundation of China(82071541,81971283,82271576,and 82101570)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT320-08).
文摘Autism Spectrum Disorders(ASDs)are reported as a group of neurodevelopmental disorders.The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes,but the underlying mechanisms are not fully understood.Here,we report that deletion of Trio,a high-susceptibility gene of ASDs,causes a postnatal dentate gyrus(DG)hypoplasia with a zigzagged suprapyramidal blade,and the Trio-defcient mice display autism-like behaviors.The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells(GCs),which further results in a migration defcit of neural progenitors.Furthermore,we reveal that Trio plays diferent roles in various excitatory neural cells by spatial transcriptomic sequencing,especially the role of regulating the migration of postmitotic GCs.In summary,our fndings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
基金supported by the National Key Research and Development Program of China[grant number 2022YFA1304000]the National Natural Science Foundation of China Key Joint Project[grant number U21A20344]+5 种基金the National Natural Science Foundation of China[grant number 81970452]the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases[grant number 2020B1111170004]the Science and Technology Program of Shenzhen,China[grant number JCYJ20190807161807867]the Starting Funding of Faculty from Sun Yat-sen University[grant number 2021276]the Regional Joint Project for Basic and Applied Basic Research Fund of Guangdong Province[grant number 2022A1515111043]the Science and Technology Planning Project of Guangzhou City[grant number 2023A04J01601],and National Key Clinical Discipline.
文摘Background:Tumor heterogeneity is contributed by tumor cells and the microenvironment.Dynamics of tumor heterogeneity during colorectal cancer(CRC)progression have not been elucidated.Methods:Eight single-cell RNA sequencing(scRNA-seq)data sets of CRC were included.Milo was utilized to reveal the differential abundance of cell clusters during progression.The differentiation trajectory was imputed by using the Palantir algorithm and metabolic states were assessed by using scMetabolism.Three spatial transcription sequencing(ST-seq)data sets of CRC were used to validate cell-type abundances and colocalization.Cancer-associated regulatory hubs were defined as communication networks affecting tumor biological behaviors.Finally,quantitative reverse transcription polymerase chain reaction and immunohistochemistry staining were performed for validation.Results:TM4SF1t,SOX4t,and MKI67t tumor cells;CXCL12t cancer-associated fibroblasts;CD4t resident memory T cells;Treg;IgAt plasma cells;and several myeloid subsets were enriched in stage IV CRC,most of which were associated with overall survival of patients.Trajectory analysis indicated that tumor cells from patients with advanced-stage CRC were less differentiated,when metabolic heterogeneity showed a highest metabolic signature in terminal states of stromal cells,T cells,and myeloid cells.Moreover,ST-seq validated cell-type abundance in a spatial context and also revealed the correlation of immune infiltration between tertiary lymphoid structures and tumors followed by validation in our cohort.Importantly,analysis of cancer-associated regulatory hubs revealed a cascade of activated pathways including leukocyte apoptotic process,MAPK pathway,myeloid leukocyte differentiation,and angiogenesis during CRC progression.Conclusions:Tumor heterogeneity was dynamic during progression,with the enrichment of immunosuppressive Treg,myeloid cells,and fibrotic cells.The differential state of tumor cells was associated with cancer staging.Assessment of cancer-associated regulatory hubs suggested impaired antitumor immunity and increased metastatic ability during CRC progression.
基金J.Z.received The National Natural Science Foundation of China(82160551)B.Y.received Guizhou Provincial Science and Technology Program Project(Qiankehejichu-ZK[2023]No.210).
文摘Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world,which seriously threatens the life and health of middle-aged and elderly men.The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment.Understanding the mechanisms of pros-tate cancer pathogenesis and disease progression is important to guide diagnosis and therapy.The emergence of single-cell RNA sequencing(scRNA-seq)and spatial transcriptome sequencing(ST-seq)technologies has brought breakthroughs in the study of prostate cancer.It makes up for the defects of traditional techniques such as fluo-rescence-activated cell sorting that are difficult to elucidate cell-specific gene expression.This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq,aims to provide a reference for the optimal diagnosis and treatment of prostate cancer.
基金funding from NSFC(32071129)Yunnan fundamental research program(202101AT070022,202001AW070006)Double First-Class University Plan(C1762201000142).
文摘Spatial transcriptomics,which combine gene expression data with spatial information,has quickly expanded in recent years.With application of this method in liver research,our knowledge about liver development,regeneration,and diseases have been greatly improved.While this field is moving forward,a variety of problems still need to be addressed,including sensitivity,limited capacity to obtain exact single-cell information,data processing methods,as well as others.Methods like single-cell RNA sequencing(scRNA-seq)are usually used together with spatial transcriptome sequencing(ST-seq)to clarify cell-specific gene expression.In this review,we explore how advances of scRNA-seq and ST-seq,especially ST-seq,will pave the way to new opportunities to investigate fundamental questions in liver research.Finally,we will discuss the strengths,limitations,and future perspectives of ST-seq in liver research.
