Changes in trace substances in human metabolites, which are related to disease processes and health status, can serve as chemical markers for disease diagnosis and symptom monitoring. Real-time online detection is an ...Changes in trace substances in human metabolites, which are related to disease processes and health status, can serve as chemical markers for disease diagnosis and symptom monitoring. Real-time online detection is an inevitable trend for the future of health monitoring, and the construction of chips for detection faces major challenges. The response of sensors often fails to meet the requirements for chipbased detection of trace substances due to the low efficiency of interfacial heterogeneous reactions, necessitating a rational design approach for micro-and nano-structures to improve sensor performance with respect to sensitivity and detection limits. This review focuses on the influence of micro-and nanostructures that used in chip on sensing. Firstly, this review categorizes sensors into chemiresistors, electrochemical sensors, fluorescence sensors, and surface enhanced Raman scattering(SERS) sensors based on their sensing principle, which have significant applications in disease diagnosis. Subsequently, commencing from the application requirements in the field of sensing, this review focuses on the different structures of nanoparticle(NP) assemblies, including wire, layered, core-shell, hollow, concave and deformable structures. These structures change in the size, shape, and morphology of conventional structures to achieve characteristics such as ordered alignment, high specific surface area, space limitation,vertical diffusion, and swaying behavior with fluid, thereby addressing issues such as poor signal transmission efficiency, inadequate adsorption and capture capacity, and slow mass transfer speed during sensing. Finally, the design direction of micro-and nano-structures, and possible obstacles and solutions to promote chip-based detection have been discussed. It is hope that this article will inspire the exploration of interface micro-and nano-structures modulated sensing methods.展开更多
According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiol...According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiological agent of COVID-19 has been identified as a novel coronavirus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belonging to Sarbecovirus subgenus(genus Betacoronavirus,family Coronaviridae)and showing 79.6 and 96.2%sequence identity in nucleotide to SARS-CoV and a bat coronavirus(BatCoV RaTG13),respectively.2–4 Like SARS-CoV infection,a substantial fraction of COVID-19 patients exhibits severe respiratory symptoms and has to be hospitalized in intensive care unit.5–8 Although the mortality rate of COVID-19 is significantly lower than that of SARS-CoV infection,SARS-CoV-2 shows much higher human-to-human transmission rate,rapidly leading to a global pandemic declared by WHO on March 11th,2020.展开更多
Epigenetic modifications to histones dictate the differentiation of naïve CD4^(+) T cells into different subsets of effector T helper(TH)cells.The histone methyltransferase enhancer of zeste homolog 2(EZH2)has be...Epigenetic modifications to histones dictate the differentiation of naïve CD4^(+) T cells into different subsets of effector T helper(TH)cells.The histone methyltransferase enhancer of zeste homolog 2(EZH2)has been implicated in the mechanism regulating the differentiation of TH1,TH2 and regulatory T(Treg)cells.However,whether and how EZH2 regulates follicular helper T(TFH)cell differentiation remain unknown.Using a mouse model of acute lymphocytic choriomeningitis virus(LCMV)infection,we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells.Ablation of EZH2 in LCMV-specific CD4^(+) T cells leads to a selective impairment of early TFH cell fate commitment,but not late TFH differentiation or memory TFH maintenance.Mechanistically,EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment,particularly B cell lymphoma 6(Bcl6),and thus directs TFH cell commitment.Therefore,we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.展开更多
Liver X receptors(LXRs)are known as key transcription factors in lipid metabolism and have been reported to play an important role in T-cell proliferation.However,whether LXRs play a role in thymocyte development rema...Liver X receptors(LXRs)are known as key transcription factors in lipid metabolism and have been reported to play an important role in T-cell proliferation.However,whether LXRs play a role in thymocyte development remains largely unknown.Here,we demonstrated that LXRβdeficiency caused a reduction in single-positive(SP)thymocytes,whereas the transitions from the double-negative to SP stage were normal.Meanwhile,LXRβ-null SP thymocytes exhibited increased apoptosis and impairment of the IL-7Rα-Bcl2 axis.In addition,the LXR agonist T0901317 promoted the survival of SP thymocytes with enhanced IL-7Rαexpression in wild-type mice but not in LXRβ-deficient mice.Mechanistically,LXRβpositively regulated the expression of IL-7Rαvia direct binding to the Il7r allele in SP thymocytes,and forced expression of IL-7Rαor Bcl2 restored the survival of LXRβ-defective SP thymocytes.Thus,our results indicate that LXRβfunctions as an important transcription factor upstream of IL-7Rαto promote the survival of SP thymocytes.展开更多
The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and sta...The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and stage-specific during T cell development and differentiation,suggesting their potential roles in T cell programs.However,the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified.Through CD8 T cell subsets profiling of lncRNAs,this study found a key lncRNA-Snhgl with the conserved naivehl-effectorlo-memoryh,expression pattern in CD8 T cells of both mice and human,that can promote memory formation while impeding effector CD8 in acute viral infection.Further,Snhgl was found interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Ra membrane location specifically.With the deep mechanism probing,the results show Snhgl-Vps13D regulated IL-7 signaling with its dual effects in memory CD8 generation,which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival,but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation.Moreover,we performed further study with finding a similar high-low-high expression pattern of human SNHG1A/PS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients.The central role of Snhgl-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potential target for improving the vaccination effects to control the ongoing pandemic.展开更多
基金financially supported by the National Natural Science Foundation of China (No.21925405)。
文摘Changes in trace substances in human metabolites, which are related to disease processes and health status, can serve as chemical markers for disease diagnosis and symptom monitoring. Real-time online detection is an inevitable trend for the future of health monitoring, and the construction of chips for detection faces major challenges. The response of sensors often fails to meet the requirements for chipbased detection of trace substances due to the low efficiency of interfacial heterogeneous reactions, necessitating a rational design approach for micro-and nano-structures to improve sensor performance with respect to sensitivity and detection limits. This review focuses on the influence of micro-and nanostructures that used in chip on sensing. Firstly, this review categorizes sensors into chemiresistors, electrochemical sensors, fluorescence sensors, and surface enhanced Raman scattering(SERS) sensors based on their sensing principle, which have significant applications in disease diagnosis. Subsequently, commencing from the application requirements in the field of sensing, this review focuses on the different structures of nanoparticle(NP) assemblies, including wire, layered, core-shell, hollow, concave and deformable structures. These structures change in the size, shape, and morphology of conventional structures to achieve characteristics such as ordered alignment, high specific surface area, space limitation,vertical diffusion, and swaying behavior with fluid, thereby addressing issues such as poor signal transmission efficiency, inadequate adsorption and capture capacity, and slow mass transfer speed during sensing. Finally, the design direction of micro-and nano-structures, and possible obstacles and solutions to promote chip-based detection have been discussed. It is hope that this article will inspire the exploration of interface micro-and nano-structures modulated sensing methods.
基金supported by grants from the National Natural Science Fund for Distinguished Young Scholars(No.31825011 to L.Y.)the Chongqing Special Research Project for Novel Coronavirus Pneumonia Prevention and Control(No.cstc2020jscx-2 to L.Y.,No.cstc2020jscx-fyzx0074 to Y.C.,cstc2020jscx-fyzx0135 to Y.C.).
文摘According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiological agent of COVID-19 has been identified as a novel coronavirus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belonging to Sarbecovirus subgenus(genus Betacoronavirus,family Coronaviridae)and showing 79.6 and 96.2%sequence identity in nucleotide to SARS-CoV and a bat coronavirus(BatCoV RaTG13),respectively.2–4 Like SARS-CoV infection,a substantial fraction of COVID-19 patients exhibits severe respiratory symptoms and has to be hospitalized in intensive care unit.5–8 Although the mortality rate of COVID-19 is significantly lower than that of SARS-CoV infection,SARS-CoV-2 shows much higher human-to-human transmission rate,rapidly leading to a global pandemic declared by WHO on March 11th,2020.
基金This study was supported by grants from the National Key Research Development Plan(No.2016YFA0502202 to L.Y.)the Open Research Fund of State Key Laboratory of Veterinary Biotechnology(No.SKLVBF2018XX to L.Ye)+3 种基金the National Natural Science Foundation of China(No.31825011 to L.Y.No.31800742 to Q.T.No.31700774 to L.Xu and No.31470870 to X.Z.)Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust(to J.H.).
文摘Epigenetic modifications to histones dictate the differentiation of naïve CD4^(+) T cells into different subsets of effector T helper(TH)cells.The histone methyltransferase enhancer of zeste homolog 2(EZH2)has been implicated in the mechanism regulating the differentiation of TH1,TH2 and regulatory T(Treg)cells.However,whether and how EZH2 regulates follicular helper T(TFH)cell differentiation remain unknown.Using a mouse model of acute lymphocytic choriomeningitis virus(LCMV)infection,we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells.Ablation of EZH2 in LCMV-specific CD4^(+) T cells leads to a selective impairment of early TFH cell fate commitment,but not late TFH differentiation or memory TFH maintenance.Mechanistically,EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment,particularly B cell lymphoma 6(Bcl6),and thus directs TFH cell commitment.Therefore,we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.
基金This work was supported by grants from the National Key Research and Development Program of China(No.2016YFA0502203 to X.Z.and No.2016YFA0502204 to Y.W.)the National Natural Science Foundation of China(No.81571537 to T.Z.,No.31770949 to X.Z.,No.31770972 to Z.X.,and No.81571604 to J.Z.)the Chongqing Basic and Frontier Research Project(No.cstc2015jcyjBX0086 to H.He.).
文摘Liver X receptors(LXRs)are known as key transcription factors in lipid metabolism and have been reported to play an important role in T-cell proliferation.However,whether LXRs play a role in thymocyte development remains largely unknown.Here,we demonstrated that LXRβdeficiency caused a reduction in single-positive(SP)thymocytes,whereas the transitions from the double-negative to SP stage were normal.Meanwhile,LXRβ-null SP thymocytes exhibited increased apoptosis and impairment of the IL-7Rα-Bcl2 axis.In addition,the LXR agonist T0901317 promoted the survival of SP thymocytes with enhanced IL-7Rαexpression in wild-type mice but not in LXRβ-deficient mice.Mechanistically,LXRβpositively regulated the expression of IL-7Rαvia direct binding to the Il7r allele in SP thymocytes,and forced expression of IL-7Rαor Bcl2 restored the survival of LXRβ-defective SP thymocytes.Thus,our results indicate that LXRβfunctions as an important transcription factor upstream of IL-7Rαto promote the survival of SP thymocytes.
基金This study was supported by grants from the National Natural Science Foundation of China(No.31800763 to Y.Z.)Special Grant from Postdoctoral Science Foundation of China(No.2020T130791 to Y.Z.)the National Key Research and Development Plan of China(No.2016YFA0502202 to L.Y).
文摘The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and stage-specific during T cell development and differentiation,suggesting their potential roles in T cell programs.However,the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified.Through CD8 T cell subsets profiling of lncRNAs,this study found a key lncRNA-Snhgl with the conserved naivehl-effectorlo-memoryh,expression pattern in CD8 T cells of both mice and human,that can promote memory formation while impeding effector CD8 in acute viral infection.Further,Snhgl was found interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Ra membrane location specifically.With the deep mechanism probing,the results show Snhgl-Vps13D regulated IL-7 signaling with its dual effects in memory CD8 generation,which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival,but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation.Moreover,we performed further study with finding a similar high-low-high expression pattern of human SNHG1A/PS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients.The central role of Snhgl-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potential target for improving the vaccination effects to control the ongoing pandemic.