BACKGROUND Ulcerative colitis(UC)is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response.Single-cell ...BACKGROUND Ulcerative colitis(UC)is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response.Single-cell RNA sequencing(scRNA-seq)can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine,analyze the characteristics of cells with the same phenotype,and provide new insights into the growth and development of intestinal organs,the clonal evolution of cells,and immune cell changes.These findings can provide new ideas for the diagnosis and treatment of intestinal diseases.To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC.METHODS Using the Gene Expression Omnibus(GEO)database,we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing(RNA-seq)to reveal the core genes of UC.We then combined weighted gene correlation network analysis(WGCNA)and least absolute shrinkage and selection operator(LASSO)analysis to reveal diagnostic markers of UC.RESULTS After processing the scRNA-seq data,we obtained data from approximately 24340 cells and identified 17 cell types.Through intercellular communication analysis,we selected monocyte marker genes as the candidate gene set for the prediction model.Construction of a WGCNA coexpression network identified RhoB,cathepsin D(CTSD)and zyxin(ZYX)as core genes.Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells.Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses,which are associated with many challenges in the diagnosis and treatment of UC.CONCLUSION Through scRNA-seq analysis,LASSO diagnostic model building and WGCNA,we identified RhoB,CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.展开更多
Background:Systemic lupus erythematosus(SLE)is a complex chronic autoimmune disease with no known cure.However,the regulatory mechanism of immunity-related genes is not fully understood in SLE.In order to explore new ...Background:Systemic lupus erythematosus(SLE)is a complex chronic autoimmune disease with no known cure.However,the regulatory mechanism of immunity-related genes is not fully understood in SLE.In order to explore new therapeutic targets,we used bioinformatical methods to analyze a series of data.Methods:After downloading and processing the data from Gene Expression Omnibus database,the differentially expressed genes of SLE were analyzed.CIBERSORT algorithm was used to analyze the immune infiltration of SLE.Based on single-cell RNA-sequencing data,the role of immune-related genes in SLE and its target organ(kidney)were analyzed.Key transcription factors affecting immune-related genes were identified.Cell-cell communication networks in SLE were analyzed.Results:In total,15 hub genes and 4 transcription factors were found in the bulk data.Monocytes and macrophages in GSE81622(SLE)showed more infiltration.There were four cell types were annotated in scRNA sequencing dataset(GSE135779),as follows T cells,monocyte,NK cells and B cells.Immunity-related genes were overexpressed in monocytes.Conclusion:The present study shows that immune-related genes affect SLE through monocytes and play an important role in target organ renal injury.展开更多
As a disorder of lipid metabolism,hyperlipidemia(HLP)is characterized by elevated levels of lipids in the blood circulation.It is consistently related to the development of cardiovascular events and diseases associate...As a disorder of lipid metabolism,hyperlipidemia(HLP)is characterized by elevated levels of lipids in the blood circulation.It is consistently related to the development of cardiovascular events and diseases associated with metabolic syndrome.Alismatis Rhizoma decoction(ARD),a well-known traditional Chinese medicine prescription,has long been used for treating vertigo,which is a symptom experienced by HLP patients.In this study,we aimed to investigate the hyperlipidemic activity and the potential molecular mechanisms of ARD in HLP rats at the transcriptional level.RNA sequencing and transcriptome analysis were performed collaboratively,including analysis of differentially expressed genes(DEGs),GO functions,and KEGG pathway analysis.The results showed that 1981 DEGs(1370 upregulated and 611 downregulated)were identified in the HFD group compared with the CON group.Moreover,474 DEGs(350 upregulated and 124 downregulated)were detected in the ARD group compared with the HFD group.Furthermore,GO analysis revealed that DEGs were mainly involved in the following functions:developmental process,response to an external stimulus,ion transport,alcohol binding,and plasma membrane part.Pathway analysis suggested that these DEGs were significantly enriched in bile secretion,malaria,cell adhesion molecules,retinol metabolism,the sphingolipid signaling pathway,chemical carcinogenesis,and the T cell receptor signaling pathway.In conclusion,our study demonstrated that ARD alleviated the lipid metabolism disorder caused by HLP through multiple mechanisms,which provided vital scientific evidence for further pharmacological studies of ARD.展开更多
Barley(Hordeum vulgare L.)is one of the earliest domesticated crop species and ranked as the fourth largest cereal production worldwide.Forward genetic studies in barley have greatly advanced plant genetics during the...Barley(Hordeum vulgare L.)is one of the earliest domesticated crop species and ranked as the fourth largest cereal production worldwide.Forward genetic studies in barley have greatly advanced plant genetics during the last century;however,most genes are identified by the conventional mapping method.Array genotyping and exome-capture sequencing have also been successfully used to target the causal mutation in barley populations,but these techniques are not widely adopted because of associated costs and partly due to the huge genome size of barley.This review summarizes three mapping cases of barley cuticle mutants in our laboratory with the help of RNA-sequencing.The causal mutations have been successfully identified for two of them and the target genes are located in the pericentromeric regions.Detailed information on the mapping-by-sequencing,mapping-and-sequencing,and RNA-sequencing assisted linkage mapping are presented and some limitations and challenges on the mapping assisted by RNA sequencing are also discussed.The alternative and elegant methods presented in this review may greatly accelerate forward genetics of barley mapping,especially for laboratories without large funding.展开更多
Human cytomegalovirus(HCMV)is a common herpesvirus that persistently infects a large portion of the world's population.Despite the robust host immune response,HCMV is able to replicate,evade host defenses,and esta...Human cytomegalovirus(HCMV)is a common herpesvirus that persistently infects a large portion of the world's population.Despite the robust host immune response,HCMV is able to replicate,evade host defenses,and establish latency throughout the lifespan by developing multiple immunomodulatory strategies,making the studies on the interaction between HCMV infection and host response particularly important.HCMV has a strict host specificity that specifically infects humans.Therefore,most of the in vivo researches of HCMV rely on clinical samples.Fortunately,the establishment of humanized mouse models allows for convenient in-lab animal experiments involving HCMV infection.Single-cell RNA sequencing enables the study of the relationship between viral and host gene expressions at the single-cell level within host cells.In this study,we assessed the gene expression alterations of PBMCs at the single-cell level within HCMV-infected humanized mice,which sheds light onto the virus-host interactions in the context of HCMV infection of humanized mice and provides a valuable dataset for the related researches.展开更多
The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have bee...The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have been made in the treatment of neovascular AMD,effective intervention for atrophic AMD is largely absent.The adequate knowledge of RPE pathology is hindered by a lack of the patients'RPE datasets,especially at the single-cell resolution.In the current study,we delved into a large-scale single-cell resource of AMD donors,in which RPE cells were occupied in a substantial proportion.Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD.Both in vivo and in vitro models revealed that carboxypeptidase X,M14 family member 2(CPXM2),was specifically expressed in the RPE cells of atrophic AMD,which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells.Additionally,silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model.Thus,our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.展开更多
The organic compound composition ofwastewater,serves as a crucial indicator for the operational performance of activated sludge processes and has a major influence on the development of filamentous bulking in activate...The organic compound composition ofwastewater,serves as a crucial indicator for the operational performance of activated sludge processes and has a major influence on the development of filamentous bulking in activated sludge.This study focused on the impact of typical soluble and slowly-biodegradable organic compounds,investigating the pathways through which these substrates affect the occurrence of filamentous bulking in systems operated under both high-and low-oxygen conditions.Results showed that slowly-biodegradable organic compounds lead to a concentrated distribution of microorganisms within flocs,with inward growth of filamentous bacteria.Both Tween-80 and granular starch treated systems exhibited a significant increase in protein content.The glucose system,utilizing soluble substrates,exhibited a markedly higher total polysaccharide content.Microbial communities in the Tween-80 and granular starch treated systems were characterized by a higher abundance of bacteria known to enhance sludge flocculation and settling,such as Competibacter,Xanthomonadaceae and Zoogloea.These findings are of high significance for controlling the operational performance and stability of activated sludge systems,deepening our understanding and providing a novel perspective for the improvement of wastewater treatment processes.展开更多
A bulk superconductor hosting intrinsic surface superconductivity provides a unique platform for exploring Majorana bound states.Trigonal γ-PtBi_(2),a superconductor,is a promising candidate,as both surface supercond...A bulk superconductor hosting intrinsic surface superconductivity provides a unique platform for exploring Majorana bound states.Trigonal γ-PtBi_(2),a superconductor,is a promising candidate,as both surface superconducting gaps and topological surface states have been observed.However,the simultaneous presence of bulk and surface superconductivity has remained unresolved.In this study,we directly visualize coexisting bulk and surface superconducting gaps in trigonal PtBi2 using ultra-low-temperature scanning tunneling microscopy/spectroscopy.The bulk gap,Δ,is∼0.053 meV,with a critical temperature(T_(c))of∼0.5K and a critical field below 0.01 T,accompanied by a vortex lattice and vortex bound states and yielding a coherence length of∼200 nm.Remarkably,certain surface regions exhibit a much larger gap(Δ)of∼0.42 meV,persisting up to a T_(c)value of∼3K and surviving magnetic fields of up to 2 T,yet lacking a static vortex lattice.This coexistence of robust surface and bulk superconductivity establishes γ-PtBi_(2)as a unique platform for exploring the interplay between bulk and surface Cooper pairings in topological superconductors.展开更多
目的基于网络拓扑学、Bulk转录组学和空间转录组学探究绿茶多酚抗胰腺癌(pancreatic adenocarcinoma,PAAD)的分子机制。方法利用网络拓扑学分析绿茶多酚抗PAAD的潜在作用靶点,基于BEST平台和GSCA数据库评估靶基因的富集通路和肿瘤免疫...目的基于网络拓扑学、Bulk转录组学和空间转录组学探究绿茶多酚抗胰腺癌(pancreatic adenocarcinoma,PAAD)的分子机制。方法利用网络拓扑学分析绿茶多酚抗PAAD的潜在作用靶点,基于BEST平台和GSCA数据库评估靶基因的富集通路和肿瘤免疫微环境,通过SpatialTME数据库探究靶基因的空间作用机制。结果绿茶多酚能够通过多条通路和多靶点干预PAAD的发生发展。靶基因表达水平与受体酪氨酸激酶(receptor tyrosine kinase,RTK)信号通路呈显著正相关关系。此外,靶基因表达与中性粒细胞(neutrophil)、辅助性T细胞2型(T helper 2 cell,Th2)和初始CD4阳性T淋巴细胞(naive CD4-positive T lymphocyte,CD4_naive)浸润丰度呈显著负相关关系(P<0.05),而与黏膜相关恒定T细胞(mucosal-associated invariant T cells,MAIT)、CD4阳性T淋巴细胞(CD4-positive T lymphocyte,CD4_T)和1型调节性T细胞(type 1 regulatory T cell,Tr1)等丰度呈显著正相关关系(P<0.05)。靶基因在免疫治疗抗程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)和抗PD-1/程序性死亡配体1(PD-1/programmed death-ligand 1,PD-1/PD-L1)队列中能够显著区分有反应者和无反应者。结论本研究揭示了绿茶多酚干预PAAD的组织定位机制,提示靶基因有望作为PAAD的肿瘤标志物,对其临床诊断和治疗具有重要意义。展开更多
Bulk modulus is a constant that measures the incompressibility of materials, which can be obtained in high pressure experiment by fitting the equations of state(EOS), like third-order Birch–Murnaghan EOS(BM EOS) and ...Bulk modulus is a constant that measures the incompressibility of materials, which can be obtained in high pressure experiment by fitting the equations of state(EOS), like third-order Birch–Murnaghan EOS(BM EOS) and Vinet EOS. Bulk modulus reflects the intermolecular interaction inside molecular crystals, making it useful for researchers to design novel high pressure materials. This review systematically examines bulk moduli of various molecular crystals, including rare-gas solids, di-atom and triplet-atom molecules, saturated organic molecules, and aromatic organic crystals. Comparisons with ionic crystals are presented, along with an analysis of connections between bulk modulus and crystal structures.展开更多
To advance materials with superior performance,the construction of gradient structures has emerged as a promising strategy.In this study,a gradient nanocrystalline-amorphous structure was induced in Zr46Cu46Al8 bulk m...To advance materials with superior performance,the construction of gradient structures has emerged as a promising strategy.In this study,a gradient nanocrystalline-amorphous structure was induced in Zr46Cu46Al8 bulk metallic glass(BMG)through ultrasonic vibration(UV)treatment.Applying a 20 kHz ultrasonic cyclic loading in the elastic regime,controllable gradient structures with varying crystallized volume fractions can be achieved in less than 2 s by adjusting the input UV energy.In contrast to tradi-tional methods of inducing structural gradients in BMGs,this novel approach offers distinct advantages:it is exceptionally rapid,requires minimal stress,and allows for easy tuning of the extent of structural gradients through precise adjustment of processing parameters.Nanoindentation tests reveal higher hard-ness near the struck surface,attributed to a greater degree of nanocrystal formation,which gradually di-minishes with depth.As a result of the gradient dispersion of nanocrystals,an increased plasticity was found after UV treatment,characterized by the formation of multiple shear bands.Microstructural in-vestigations suggest that UV-induced nanocrystallization originates from local atomic rearrangements in phase-separated Cu-rich regions with high diffusional mobility.Our study underscores the tunability of structural gradients and corresponding performance improvements in BMGs through ultrasonic energy modulation,offering valuable insights for designing advanced metallic materials with tailored mechanical properties.展开更多
The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components....The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.展开更多
To understand the differences in the composition and sources of PM_(2.5) and PM_(10) caused by coarse particles,integrated PM_(2.5) and PM_(10) samples were synchronously collected in Nanjing,East China,in summer 2020...To understand the differences in the composition and sources of PM_(2.5) and PM_(10) caused by coarse particles,integrated PM_(2.5) and PM_(10) samples were synchronously collected in Nanjing,East China,in summer 2020 and winter 2020/2021.Bulk and molecular speciation and light absorption measurements of aerosol extractswere performed,followed by positivematrix factorization(PMF)based on the PM_(2.5) and PM_(10) data sets,respectively.The difference in average concentrations of total bulk species between PM_(2.5) and PM_(10) was mainly caused by the distribution of considerable NO_(3)^(–),SO42–,Ca^(2+),and organic carbon(OC)in coarse particles.Coarse PMinfluenced by abrasion products from tirewear and leaves contributed about half of the low-volatility n-alkanes in summer.The contribution of coarse PM to biomass burning tracers and water-soluble OC increased in winter when biomass combustion was excessively active.More than 70%of sugar polyols were attributable to coarse PM in summer,and biomass burning could be an important source in winter.The light-absorbing organic chromophores were almost entirely associated with PM_(2.5),but water-soluble organic carbon(WSOC)exhibited stronger light absorption in PM_(10) extracts than in PM_(2.5) extracts possibly due to the influence of coarse PMon pH.PMF analysis indicated that biomass burning,aqueous-phase reactions,and processed dust were the main contributors of organic matter and its light absorption in winter.Biogenic primary and secondary sources made discernable contributions only in summer.The differences between PM_(2.5) and PM_(10) were likely attributed to mixing of crustal dust,combustion particles,and surface reactions.展开更多
Water depth significantly affects ship resistance,which,in turn,influences fuel consumption.Furthermore,the urgent need to reduce carbon emissions for environmental sustainability highlights the importance of applying...Water depth significantly affects ship resistance,which,in turn,influences fuel consumption.Furthermore,the urgent need to reduce carbon emissions for environmental sustainability highlights the importance of applying drag reduction methods to shallow-water vehicles.To effectively employ these methods,the initial step entails an in-depth investigation of how shallow water impacts the resistance and flow dynamics of a mini-bulk carrier.This study extensively analyzes the hydrodynamic characteristics of mini-bulk carriers,focusing on the impact of shallow water on resistance and flow dynamics utilizing a combination of experimental tests and numerical analyses.This study emphasizes the interaction between the hull and the shallow seabed.This study also highlights increased frictional drag and significant residual resistance by analyzing the total resistance at various speeds in shallow waters.The results of five key factors influencing resistance in shallow waters,namely,boundary layer thickness,shear stress,velocity and pressure,turbulence,and waves,are discussed.A decrease in water depth accelerates the flow under the hull,increasing shear stress and resistance.The accelerated flow reduces the gap between the hull and the shallow seabed,elevating water pressure and increasing sinkage and resistance.Heightened turbulence in shallow water intensifies Reynolds stress,augmenting friction and viscous resistance.展开更多
Avoiding crystallization while maintaining the original microstructure and mechanical properties of the material are long-term goals of laser welding of Zr-based bulk metallic glass(BMG).In this paper,the effect of pu...Avoiding crystallization while maintaining the original microstructure and mechanical properties of the material are long-term goals of laser welding of Zr-based bulk metallic glass(BMG).In this paper,the effect of pulsed laser welding parameters on the microstructure,crystallization degree,and mechanical properties of Zr57Nb5Cu15.4Ni12.6Al10 BMG is investigated.Non-crystallized welding forming of a zirconium-based amorphous alloy is achieved by optimizing the process parameters of pulsed laser welding.The crystallization degree of Zr-based BMG is mainly determined by the welding speed and power.The welding depth and crystallization area fraction increase with an increase in the effective peak power density.The optimized welding process can effectively reduce the heat accumulation of the weld,thus avoiding crystallization.The flexural strength of the weld can be maintained at 96.5%of the matrix.展开更多
Ti-based bulk metallic glasses(BMGs)have attracted increasing attention due to their high specific strength.However,a fundamental conflict exists between the specific strength and glass-forming ability(GFA)of Ti-based...Ti-based bulk metallic glasses(BMGs)have attracted increasing attention due to their high specific strength.However,a fundamental conflict exists between the specific strength and glass-forming ability(GFA)of Ti-based BMGs,restricting their commercial applications significantly.In this study,this challenge was addressed by introducing a two-step alloying strategy to mitigate the remarkable density increment effect associated with heavy alloying elements required for enhancing the GFA.Consequently,through two-step alloying with Al and Fe in sequence,simultaneous enhancements in specific strength and GFA were achieved based on a Ti-Zr-Be ternary metallic glass,resulting in the development of a series of centimeter-sized metallic glasses exhibiting ultrahigh-specific strength.Notably,the newly developed(Ti_(45)Zr_(20)Be_(31)A_(l4))_(94)Fe_(6)alloy established a new record for the specific strength of Ti-based BMGs.Along with a critical diameter(D_(c))of 10 mm,it offers the optimal scheme for balancing the specific strength and GFA of Ti-based BMGs.The present results further brighten the application prospects of Ti-based BMGs as lightweight materials.展开更多
Large-grain REBa_(2)Cu_(3)O_(7-δ)(REBCO,RE=rare earth)bulk superconductors offer promising magnetic field trapping capabilities due to their high critical current density,making them ideal for many important applicat...Large-grain REBa_(2)Cu_(3)O_(7-δ)(REBCO,RE=rare earth)bulk superconductors offer promising magnetic field trapping capabilities due to their high critical current density,making them ideal for many important applications such as trapped field magnets.However,for such large-grain superconductor bulks,there are lots of voids and cracks forming during the process of melting preparation,and some of them can be up to hundreds of microns or even millimeters in size.Consequently,these larger size voids/cracks pose a great threat to the strength of the bulks due to the inherent brittleness of superconductor REBCO materials.In order to ensure the operational safety of related superconducting devices with bulk superconductors,it is firstly important to accurately detect these voids/cracks in them.In this paper,we proposed a method for quantitatively evaluating multiple voids/cracks in bulk superconductors through the magnetic field and displacement response signals at superconductor bulk surface.The proposed method utilizes a damage index constructed from the magnetic field signals and displacement responses to identify the number and preliminary location of multiple defects.By dividing the detection area into subdomains and combining the magnetic field signals with displacement responses within each subdomain,a particle swarm algorithm was employed to evaluate the location and size parameters of the defects.In contrast to other evaluation methods using only magnetic field or displacement response signals,the combined evaluation method using both signals can identify the number of cracks effectively.Numerical studies demonstrate that the morphology of voids and cracks reconstructed using the proposed algorithm ideally matches real defects and is applicable to cases where voids and cracks coexist.This study provides a theoretical basis for the quantitative detection of voids/cracks in bulk superconductors.展开更多
基金Supported by the National Natural Science Foundation of China,No.81873253 and 81704009the Shanghai Natural Science Foundation,No.22ZR1458800+1 种基金the Hongkou District Health Committee,No.HKZK2020A01the Xinglin Scholar Program of Shanghai University of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine 2020 Document No.23.
文摘BACKGROUND Ulcerative colitis(UC)is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response.Single-cell RNA sequencing(scRNA-seq)can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine,analyze the characteristics of cells with the same phenotype,and provide new insights into the growth and development of intestinal organs,the clonal evolution of cells,and immune cell changes.These findings can provide new ideas for the diagnosis and treatment of intestinal diseases.To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC.METHODS Using the Gene Expression Omnibus(GEO)database,we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing(RNA-seq)to reveal the core genes of UC.We then combined weighted gene correlation network analysis(WGCNA)and least absolute shrinkage and selection operator(LASSO)analysis to reveal diagnostic markers of UC.RESULTS After processing the scRNA-seq data,we obtained data from approximately 24340 cells and identified 17 cell types.Through intercellular communication analysis,we selected monocyte marker genes as the candidate gene set for the prediction model.Construction of a WGCNA coexpression network identified RhoB,cathepsin D(CTSD)and zyxin(ZYX)as core genes.Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells.Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses,which are associated with many challenges in the diagnosis and treatment of UC.CONCLUSION Through scRNA-seq analysis,LASSO diagnostic model building and WGCNA,we identified RhoB,CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.
文摘Background:Systemic lupus erythematosus(SLE)is a complex chronic autoimmune disease with no known cure.However,the regulatory mechanism of immunity-related genes is not fully understood in SLE.In order to explore new therapeutic targets,we used bioinformatical methods to analyze a series of data.Methods:After downloading and processing the data from Gene Expression Omnibus database,the differentially expressed genes of SLE were analyzed.CIBERSORT algorithm was used to analyze the immune infiltration of SLE.Based on single-cell RNA-sequencing data,the role of immune-related genes in SLE and its target organ(kidney)were analyzed.Key transcription factors affecting immune-related genes were identified.Cell-cell communication networks in SLE were analyzed.Results:In total,15 hub genes and 4 transcription factors were found in the bulk data.Monocytes and macrophages in GSE81622(SLE)showed more infiltration.There were four cell types were annotated in scRNA sequencing dataset(GSE135779),as follows T cells,monocyte,NK cells and B cells.Immunity-related genes were overexpressed in monocytes.Conclusion:The present study shows that immune-related genes affect SLE through monocytes and play an important role in target organ renal injury.
基金The Basic Research Project of Fujian Provincial Public Welfare Research Institute(Grant No.2018R1031-3)Medical Innovation Project of Fujian Provincial Health Commission(Grant No.2018-CX-15)+1 种基金Basic Research Project of Fujian Provincial Public Welfare Research Institute,China(Grant No.2019R1011-5)High-Level Hospital grants(Grant No.2017GL-001)from Fujian Provincial Hospita,Fujian Province,China。
文摘As a disorder of lipid metabolism,hyperlipidemia(HLP)is characterized by elevated levels of lipids in the blood circulation.It is consistently related to the development of cardiovascular events and diseases associated with metabolic syndrome.Alismatis Rhizoma decoction(ARD),a well-known traditional Chinese medicine prescription,has long been used for treating vertigo,which is a symptom experienced by HLP patients.In this study,we aimed to investigate the hyperlipidemic activity and the potential molecular mechanisms of ARD in HLP rats at the transcriptional level.RNA sequencing and transcriptome analysis were performed collaboratively,including analysis of differentially expressed genes(DEGs),GO functions,and KEGG pathway analysis.The results showed that 1981 DEGs(1370 upregulated and 611 downregulated)were identified in the HFD group compared with the CON group.Moreover,474 DEGs(350 upregulated and 124 downregulated)were detected in the ARD group compared with the HFD group.Furthermore,GO analysis revealed that DEGs were mainly involved in the following functions:developmental process,response to an external stimulus,ion transport,alcohol binding,and plasma membrane part.Pathway analysis suggested that these DEGs were significantly enriched in bile secretion,malaria,cell adhesion molecules,retinol metabolism,the sphingolipid signaling pathway,chemical carcinogenesis,and the T cell receptor signaling pathway.In conclusion,our study demonstrated that ARD alleviated the lipid metabolism disorder caused by HLP through multiple mechanisms,which provided vital scientific evidence for further pharmacological studies of ARD.
基金grants from the National Natural Science Foundation of China(No.41621001,No.31870381,and No.31970352)by the Youth Innovation Promotion Association,CAS(2018463).
文摘Barley(Hordeum vulgare L.)is one of the earliest domesticated crop species and ranked as the fourth largest cereal production worldwide.Forward genetic studies in barley have greatly advanced plant genetics during the last century;however,most genes are identified by the conventional mapping method.Array genotyping and exome-capture sequencing have also been successfully used to target the causal mutation in barley populations,but these techniques are not widely adopted because of associated costs and partly due to the huge genome size of barley.This review summarizes three mapping cases of barley cuticle mutants in our laboratory with the help of RNA-sequencing.The causal mutations have been successfully identified for two of them and the target genes are located in the pericentromeric regions.Detailed information on the mapping-by-sequencing,mapping-and-sequencing,and RNA-sequencing assisted linkage mapping are presented and some limitations and challenges on the mapping assisted by RNA sequencing are also discussed.The alternative and elegant methods presented in this review may greatly accelerate forward genetics of barley mapping,especially for laboratories without large funding.
基金supported by the National Key R&D Program of China(2023YFC23066000 to Y.R.)the National Natural Science Foundation of China(32100106 to Y.R.,and U21A20423 and 32225004 to X.Z.)+2 种基金the CAS Youth Innovation Promotion Association(2023351 to Y.R.)Hubei Province Natural Science Funds(2023AFB582 to Y.R.and 2023AFA008 to X.Z)the Fund of the Science and Technology Bureau of Wuhan(2023020201010086 to Y.R.).
文摘Human cytomegalovirus(HCMV)is a common herpesvirus that persistently infects a large portion of the world's population.Despite the robust host immune response,HCMV is able to replicate,evade host defenses,and establish latency throughout the lifespan by developing multiple immunomodulatory strategies,making the studies on the interaction between HCMV infection and host response particularly important.HCMV has a strict host specificity that specifically infects humans.Therefore,most of the in vivo researches of HCMV rely on clinical samples.Fortunately,the establishment of humanized mouse models allows for convenient in-lab animal experiments involving HCMV infection.Single-cell RNA sequencing enables the study of the relationship between viral and host gene expressions at the single-cell level within host cells.In this study,we assessed the gene expression alterations of PBMCs at the single-cell level within HCMV-infected humanized mice,which sheds light onto the virus-host interactions in the context of HCMV infection of humanized mice and provides a valuable dataset for the related researches.
基金the National Natural Science Foundation of China(Grant Nos.81970821 and 82271100 to Q.L.).
文摘The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have been made in the treatment of neovascular AMD,effective intervention for atrophic AMD is largely absent.The adequate knowledge of RPE pathology is hindered by a lack of the patients'RPE datasets,especially at the single-cell resolution.In the current study,we delved into a large-scale single-cell resource of AMD donors,in which RPE cells were occupied in a substantial proportion.Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD.Both in vivo and in vitro models revealed that carboxypeptidase X,M14 family member 2(CPXM2),was specifically expressed in the RPE cells of atrophic AMD,which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells.Additionally,silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model.Thus,our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.
基金supported by the Opening Project of National Engineering Laboratory for Advanced Municipal Wastewater Treatment and Reuse Technology,and the National Natural Science Foundation of China(No.52270017).
文摘The organic compound composition ofwastewater,serves as a crucial indicator for the operational performance of activated sludge processes and has a major influence on the development of filamentous bulking in activated sludge.This study focused on the impact of typical soluble and slowly-biodegradable organic compounds,investigating the pathways through which these substrates affect the occurrence of filamentous bulking in systems operated under both high-and low-oxygen conditions.Results showed that slowly-biodegradable organic compounds lead to a concentrated distribution of microorganisms within flocs,with inward growth of filamentous bacteria.Both Tween-80 and granular starch treated systems exhibited a significant increase in protein content.The glucose system,utilizing soluble substrates,exhibited a markedly higher total polysaccharide content.Microbial communities in the Tween-80 and granular starch treated systems were characterized by a higher abundance of bacteria known to enhance sludge flocculation and settling,such as Competibacter,Xanthomonadaceae and Zoogloea.These findings are of high significance for controlling the operational performance and stability of activated sludge systems,deepening our understanding and providing a novel perspective for the improvement of wastewater treatment processes.
基金supported by the National Natural Science Foundation of China(Grant No.62488201)the National Key Research and Development Projects of China(Grant Nos.2022YFA1204100 and 2023YFA1607400)+1 种基金the CAS Project for Young Scientists in Basic Research(Grant No.YSBR-003)the Innovation Program of Quantum Science and Technology(Grant No.2021ZD0302700)。
文摘A bulk superconductor hosting intrinsic surface superconductivity provides a unique platform for exploring Majorana bound states.Trigonal γ-PtBi_(2),a superconductor,is a promising candidate,as both surface superconducting gaps and topological surface states have been observed.However,the simultaneous presence of bulk and surface superconductivity has remained unresolved.In this study,we directly visualize coexisting bulk and surface superconducting gaps in trigonal PtBi2 using ultra-low-temperature scanning tunneling microscopy/spectroscopy.The bulk gap,Δ,is∼0.053 meV,with a critical temperature(T_(c))of∼0.5K and a critical field below 0.01 T,accompanied by a vortex lattice and vortex bound states and yielding a coherence length of∼200 nm.Remarkably,certain surface regions exhibit a much larger gap(Δ)of∼0.42 meV,persisting up to a T_(c)value of∼3K and surviving magnetic fields of up to 2 T,yet lacking a static vortex lattice.This coexistence of robust surface and bulk superconductivity establishes γ-PtBi_(2)as a unique platform for exploring the interplay between bulk and surface Cooper pairings in topological superconductors.
文摘目的基于网络拓扑学、Bulk转录组学和空间转录组学探究绿茶多酚抗胰腺癌(pancreatic adenocarcinoma,PAAD)的分子机制。方法利用网络拓扑学分析绿茶多酚抗PAAD的潜在作用靶点,基于BEST平台和GSCA数据库评估靶基因的富集通路和肿瘤免疫微环境,通过SpatialTME数据库探究靶基因的空间作用机制。结果绿茶多酚能够通过多条通路和多靶点干预PAAD的发生发展。靶基因表达水平与受体酪氨酸激酶(receptor tyrosine kinase,RTK)信号通路呈显著正相关关系。此外,靶基因表达与中性粒细胞(neutrophil)、辅助性T细胞2型(T helper 2 cell,Th2)和初始CD4阳性T淋巴细胞(naive CD4-positive T lymphocyte,CD4_naive)浸润丰度呈显著负相关关系(P<0.05),而与黏膜相关恒定T细胞(mucosal-associated invariant T cells,MAIT)、CD4阳性T淋巴细胞(CD4-positive T lymphocyte,CD4_T)和1型调节性T细胞(type 1 regulatory T cell,Tr1)等丰度呈显著正相关关系(P<0.05)。靶基因在免疫治疗抗程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)和抗PD-1/程序性死亡配体1(PD-1/programmed death-ligand 1,PD-1/PD-L1)队列中能够显著区分有反应者和无反应者。结论本研究揭示了绿茶多酚干预PAAD的组织定位机制,提示靶基因有望作为PAAD的肿瘤标志物,对其临床诊断和治疗具有重要意义。
基金Project supported by the National Key Research and Development Program of China (Grant Nos. 2019YFA0708502 and 2023YFA1406200)the National Natural Science Foundation of China (Grant No. 22022101)。
文摘Bulk modulus is a constant that measures the incompressibility of materials, which can be obtained in high pressure experiment by fitting the equations of state(EOS), like third-order Birch–Murnaghan EOS(BM EOS) and Vinet EOS. Bulk modulus reflects the intermolecular interaction inside molecular crystals, making it useful for researchers to design novel high pressure materials. This review systematically examines bulk moduli of various molecular crystals, including rare-gas solids, di-atom and triplet-atom molecules, saturated organic molecules, and aromatic organic crystals. Comparisons with ionic crystals are presented, along with an analysis of connections between bulk modulus and crystal structures.
基金supported by the Key Basic and Applied Research Program of Guangdong Province,China(Grant No.2019B030302010)the NSF of China(Grant Nos.52122105,52271150,52201185,52201186,52371160)+1 种基金the Science and Technology Innovation Commission Shenzhen(Grants Nos.RCJC20221008092730037,20220804091920001)the Research Team Cultivation Program of Shenzhen University,Grant No.2023QNT001.
文摘To advance materials with superior performance,the construction of gradient structures has emerged as a promising strategy.In this study,a gradient nanocrystalline-amorphous structure was induced in Zr46Cu46Al8 bulk metallic glass(BMG)through ultrasonic vibration(UV)treatment.Applying a 20 kHz ultrasonic cyclic loading in the elastic regime,controllable gradient structures with varying crystallized volume fractions can be achieved in less than 2 s by adjusting the input UV energy.In contrast to tradi-tional methods of inducing structural gradients in BMGs,this novel approach offers distinct advantages:it is exceptionally rapid,requires minimal stress,and allows for easy tuning of the extent of structural gradients through precise adjustment of processing parameters.Nanoindentation tests reveal higher hard-ness near the struck surface,attributed to a greater degree of nanocrystal formation,which gradually di-minishes with depth.As a result of the gradient dispersion of nanocrystals,an increased plasticity was found after UV treatment,characterized by the formation of multiple shear bands.Microstructural in-vestigations suggest that UV-induced nanocrystallization originates from local atomic rearrangements in phase-separated Cu-rich regions with high diffusional mobility.Our study underscores the tunability of structural gradients and corresponding performance improvements in BMGs through ultrasonic energy modulation,offering valuable insights for designing advanced metallic materials with tailored mechanical properties.
基金supported by the National Institutes of Health-Office of Research Infrastructure Programs(P40 OD010440)supported in part by grants from the National Cancer Center of Korea(NCC-2110160,NCC-2110263,and NCC-2310750)supported by the Basic Science Research Program of the National Research Foundation of Korea,funded by the Ministry of Science,ICT,and Future Planning(NRF-2015R1C1A1A01053611).
文摘The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.
基金supported by the National Natural Science Foundation of China(Nos.42007325 and 42177211).
文摘To understand the differences in the composition and sources of PM_(2.5) and PM_(10) caused by coarse particles,integrated PM_(2.5) and PM_(10) samples were synchronously collected in Nanjing,East China,in summer 2020 and winter 2020/2021.Bulk and molecular speciation and light absorption measurements of aerosol extractswere performed,followed by positivematrix factorization(PMF)based on the PM_(2.5) and PM_(10) data sets,respectively.The difference in average concentrations of total bulk species between PM_(2.5) and PM_(10) was mainly caused by the distribution of considerable NO_(3)^(–),SO42–,Ca^(2+),and organic carbon(OC)in coarse particles.Coarse PMinfluenced by abrasion products from tirewear and leaves contributed about half of the low-volatility n-alkanes in summer.The contribution of coarse PM to biomass burning tracers and water-soluble OC increased in winter when biomass combustion was excessively active.More than 70%of sugar polyols were attributable to coarse PM in summer,and biomass burning could be an important source in winter.The light-absorbing organic chromophores were almost entirely associated with PM_(2.5),but water-soluble organic carbon(WSOC)exhibited stronger light absorption in PM_(10) extracts than in PM_(2.5) extracts possibly due to the influence of coarse PMon pH.PMF analysis indicated that biomass burning,aqueous-phase reactions,and processed dust were the main contributors of organic matter and its light absorption in winter.Biogenic primary and secondary sources made discernable contributions only in summer.The differences between PM_(2.5) and PM_(10) were likely attributed to mixing of crustal dust,combustion particles,and surface reactions.
基金Supported by the Ministry of Shipping,India(Grant No.OEC/18-19/157/MOSH/RVIJ).
文摘Water depth significantly affects ship resistance,which,in turn,influences fuel consumption.Furthermore,the urgent need to reduce carbon emissions for environmental sustainability highlights the importance of applying drag reduction methods to shallow-water vehicles.To effectively employ these methods,the initial step entails an in-depth investigation of how shallow water impacts the resistance and flow dynamics of a mini-bulk carrier.This study extensively analyzes the hydrodynamic characteristics of mini-bulk carriers,focusing on the impact of shallow water on resistance and flow dynamics utilizing a combination of experimental tests and numerical analyses.This study emphasizes the interaction between the hull and the shallow seabed.This study also highlights increased frictional drag and significant residual resistance by analyzing the total resistance at various speeds in shallow waters.The results of five key factors influencing resistance in shallow waters,namely,boundary layer thickness,shear stress,velocity and pressure,turbulence,and waves,are discussed.A decrease in water depth accelerates the flow under the hull,increasing shear stress and resistance.The accelerated flow reduces the gap between the hull and the shallow seabed,elevating water pressure and increasing sinkage and resistance.Heightened turbulence in shallow water intensifies Reynolds stress,augmenting friction and viscous resistance.
基金Supported by Guangdong Major Project of Basic and Applied Research,China(Grant No.2019B030302010)National Natural Science Foundation of China (Grant Nos.51735003,52205456)
文摘Avoiding crystallization while maintaining the original microstructure and mechanical properties of the material are long-term goals of laser welding of Zr-based bulk metallic glass(BMG).In this paper,the effect of pulsed laser welding parameters on the microstructure,crystallization degree,and mechanical properties of Zr57Nb5Cu15.4Ni12.6Al10 BMG is investigated.Non-crystallized welding forming of a zirconium-based amorphous alloy is achieved by optimizing the process parameters of pulsed laser welding.The crystallization degree of Zr-based BMG is mainly determined by the welding speed and power.The welding depth and crystallization area fraction increase with an increase in the effective peak power density.The optimized welding process can effectively reduce the heat accumulation of the weld,thus avoiding crystallization.The flexural strength of the weld can be maintained at 96.5%of the matrix.
基金supported by the National Natural Science Foundation of China(Nos.52271148 and 51871129).
文摘Ti-based bulk metallic glasses(BMGs)have attracted increasing attention due to their high specific strength.However,a fundamental conflict exists between the specific strength and glass-forming ability(GFA)of Ti-based BMGs,restricting their commercial applications significantly.In this study,this challenge was addressed by introducing a two-step alloying strategy to mitigate the remarkable density increment effect associated with heavy alloying elements required for enhancing the GFA.Consequently,through two-step alloying with Al and Fe in sequence,simultaneous enhancements in specific strength and GFA were achieved based on a Ti-Zr-Be ternary metallic glass,resulting in the development of a series of centimeter-sized metallic glasses exhibiting ultrahigh-specific strength.Notably,the newly developed(Ti_(45)Zr_(20)Be_(31)A_(l4))_(94)Fe_(6)alloy established a new record for the specific strength of Ti-based BMGs.Along with a critical diameter(D_(c))of 10 mm,it offers the optimal scheme for balancing the specific strength and GFA of Ti-based BMGs.The present results further brighten the application prospects of Ti-based BMGs as lightweight materials.
基金supported by the National Natural Science Foundation of China(Grant Nos.12232005 and 12072101).
文摘Large-grain REBa_(2)Cu_(3)O_(7-δ)(REBCO,RE=rare earth)bulk superconductors offer promising magnetic field trapping capabilities due to their high critical current density,making them ideal for many important applications such as trapped field magnets.However,for such large-grain superconductor bulks,there are lots of voids and cracks forming during the process of melting preparation,and some of them can be up to hundreds of microns or even millimeters in size.Consequently,these larger size voids/cracks pose a great threat to the strength of the bulks due to the inherent brittleness of superconductor REBCO materials.In order to ensure the operational safety of related superconducting devices with bulk superconductors,it is firstly important to accurately detect these voids/cracks in them.In this paper,we proposed a method for quantitatively evaluating multiple voids/cracks in bulk superconductors through the magnetic field and displacement response signals at superconductor bulk surface.The proposed method utilizes a damage index constructed from the magnetic field signals and displacement responses to identify the number and preliminary location of multiple defects.By dividing the detection area into subdomains and combining the magnetic field signals with displacement responses within each subdomain,a particle swarm algorithm was employed to evaluate the location and size parameters of the defects.In contrast to other evaluation methods using only magnetic field or displacement response signals,the combined evaluation method using both signals can identify the number of cracks effectively.Numerical studies demonstrate that the morphology of voids and cracks reconstructed using the proposed algorithm ideally matches real defects and is applicable to cases where voids and cracks coexist.This study provides a theoretical basis for the quantitative detection of voids/cracks in bulk superconductors.
