Systemic lupus erythematosus(SLE)is a systemic autoimmune disease characterized by abnormal cellular and humoral immune responses and excessive autoantibody production.The precise pathologic mechanism of SLE remains e...Systemic lupus erythematosus(SLE)is a systemic autoimmune disease characterized by abnormal cellular and humoral immune responses and excessive autoantibody production.The precise pathologic mechanism of SLE remains elusive.The advent of single-cell RNA sequencing(scRNA-seq)enables unbiased analysis of the molecular differences of cell populations at the single-cell level.We used scRNA-seq to profile the transcriptomes of peripheral blood mononuclear cells from an SLE patient compared with a healthy control(HC).A total of 16,021 cells were analyzed and partitioned into 12 distinct clusters.The marker genes of each cluster and the four major immune cell types(B cells,CD4+T cells,CD8+T cells,myeloid cells,and NK cells)were determined.Moreover,several genes involved in antigen processing and presentation through MHCII were highly enriched.GO enrichment analyses revealed abnormal gene expression patterns and signaling pathways in SLE.Of note,pseudotime analysis revealed that there was a different lineage hierarchy in the peripheral blood mononuclear cells(PBMCs)of the SLE patient,indicating that the cell states were substantially altered under disease conditions.Our analysis provides a comprehensive map of the cell types and states of the PBMCs of SLE patients at the single-cell level for a better understanding of the pathogenesis,diagnosis,and treatment of SLE.展开更多
Concomitant exotropia is a common chronic eye disease characterized by abnormal movement of the extraocular muscles caused by a functional imbalance of the nerves related to the movement of the extraocular muscles.Thi...Concomitant exotropia is a common chronic eye disease characterized by abnormal movement of the extraocular muscles caused by a functional imbalance of the nerves related to the movement of the extraocular muscles.This study revealed that the expression levels of S-100β and the muscle area decreased in the extraocular muscles of patients with concomitant exotropia,whereas the expression of calcitonin gene-related peptide(CGRP)increased.In CGRP-KO rats,low expression of CGRP was positively correlated with muscle atrophy.Moreover,the expression level of muscle cells,which are fast myosin heavy chain positive and slow myosin positive in CGRP-KO rats,was lower than that in the control group.Drug intervention experiments further confirmed the inhibitory effect of CGRP on muscle atrophy.The level of apoptosis in the extraocular muscles of CGRP-KO rats was significantly greater than that in the control group(P<0.05),and the phosphorylation level of AKT/CREB in the extraocular muscles of patients with concomitant exotropia was greater than that in the control group.The increased expression of CGRP in the extraocular muscles of patients with concomitant exotropia may inhibit the apoptosis of extraocular muscle cells through the AKT/CREB signaling pathway and participate in the protective effect of the extraocular muscles in concomitant exotropia.展开更多
Objectives:Human papillomavirus(HPV)is a globally prevalent infection,with multiple genotypes strongly associated with cancers and other diseases.While epidemiological studies in females are extensive,research on HPV ...Objectives:Human papillomavirus(HPV)is a globally prevalent infection,with multiple genotypes strongly associated with cancers and other diseases.While epidemiological studies in females are extensive,research on HPV genotype distribution in males remains limited.Methods:We conducted a retrospective study by collecting and analyzing clinical and laboratory data from male patients with confirmed HPV infection at Shenzhen People’s Hospital.The distribution of HPV genotypes and their associations with specific disease types were evaluated.Results:A total of 2,037 male participants were included,with an overall HPV infection rate of 45%.Low-risk genotypes predominated,with HPV 6 and HPV 11 accounting for 25%and 12%of cases,respectively.High-risk genotypes such as HPV 16 and HPV 52 showed low prevalence(<3%)but exhibited a slight upward trend in 2022.No significant age distribution differences were observed between HPVpositive and HPV-negative groups.The frequency of multiple HPV genotype infections increased slightly with age.Specific HPV genotypes showed unique associations with acne(HPV 56),allergic dermatitis(HPV 59),and amyloidosis(HPV 58).Conclusions:Low-risk HPV genotypes predominate in males with confirmed exposure.Older males appear more susceptible to multiple infections,and specific genotypes are associated with distinct diseases,supporting the need for male-targeted HPV vaccination and surveillance programs.展开更多
Inflammatory cytokine overproduction is critically involved in immune dysregulation and tissue damage,but the role of interleukin-18(IL-18),a cytokine associated with inflammasome activation,in modulating the T-cell r...Inflammatory cytokine overproduction is critically involved in immune dysregulation and tissue damage,but the role of interleukin-18(IL-18),a cytokine associated with inflammasome activation,in modulating the T-cell response and autoimmune pathogenesis remains largely unclear.In this study,we detected high expression levels of the IL-18 receptorαchain(IL-18Rα)in murine and human Th17 cells.In culture,IL-18 markedly promoted Th17 cell differentiation with increased GM-CSF production,a phenotype of pathogenic Th17(pTh17)cells.Transcriptomic profiling via RNA sequencing revealed that IL-18-induced pTh17 cells presented increased glycolytic flux and proinflammatory signatures.Mechanistically,IL-18 promoted Stat3 phosphorylation,which stabilized Bhlhe40 mRNA to potentiate Bhlhe40-dependent glycolysis and cytokine production.In patients with primary Sjögren’s syndrome(pSS)and systemic lupus erythematosus(SLE),IL-18 levels in plasma and inflamed tissues were significantly increased and positively correlated with disease activity.Moreover,the expression levels of IL-18 were markedly increased in the salivary glands of experimental Sjögren’s syndrome(ESS)model mice and the renal tissues of lupus model mice.Furthermore,adoptive transfer of IL-18-induced pTh17 cells profoundly exacerbated disease severity and tissue damage in recipient IL-17-deficient mice,whereas IL-18 neutralization with a monoclonal antibody effectively suppressed the pTh17 cell response and ameliorated tissue pathology in both ESS and lupus mice.Together,our findings reveal a novel function of IL-18 in driving the pTh17 cell response during autoimmune development,indicating that IL-18 blockade may serve as a promising therapeutic strategy for the treatment of autoimmune diseases.展开更多
Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of ...Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear.In this study,we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A(IL-17)stimulation in SLE patients and lupus mice.Using a humanized lupus mouse model,we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs.Moreover,long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+subsets among IL-17 receptor-expressing plasma cells.Lupus mice deficient in IL-17 or IL-17 receptor C(IL-17RC)exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage,while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice.In reconstituted chimeric mice,IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells.Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization.Together,our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis,which may provide new therapeutic strategies for the treatment of SLE.展开更多
Extensive studies have demonstrated that mesenchymal stem cells(MSCs)are multipotent mesoderm-derived stromal cells that can differentiate into a variety of cell types,including adipocytes,osteoblasts,chondrocytes,myo...Extensive studies have demonstrated that mesenchymal stem cells(MSCs)are multipotent mesoderm-derived stromal cells that can differentiate into a variety of cell types,including adipocytes,osteoblasts,chondrocytes,myocytes and neuronal cells.1 MSCs are found in numerous organs and tissues,including bone marrow,heart,lung,muscle,peripheral blood,adipose tissue,cartilage,synovium,dental pulp,tonsil,umbilical cord,placenta,thymus and olfactory mucosa.1 MSCs have been shown to possess potent immunosuppressive functions and tissue repair capacities,which have facilitated the clinical applications of MSCs in treating a diverse range of disorders involving angiogenesis and fibrosis,including rheumatic diseases and graft-versus-host diseases.2,3 Here,we provide a brief commentary on newly emerging evidence of the immunoregulatory function and potential application of ecto-mesenchymal stem cells.展开更多
In this paper,we consider the problem of Doppler tracking and compensation for a direct sequence spread spectrum(DSSS)signal in underwater acoustic(UWA)communication.Since the dynamic property of the UWA channel and t...In this paper,we consider the problem of Doppler tracking and compensation for a direct sequence spread spectrum(DSSS)signal in underwater acoustic(UWA)communication.Since the dynamic property of the UWA channel and the long duration of DSSS signals result in significant Doppler spread that severely distorts the propagated signal,Doppler tracking and compensation are required.Based on the ultra-wideband property of UWA signal,the Doppler spread not only results in the frequency shift,but also changes the signal duration.Therefore,the accurate estimation of the signal expansion/compression in the time domain can reflect the Doppler spread.Accordingly,we present a Doppler tracking and compensation algorithm for a DSSS signal operating on the correlation output of passband signal at a symbol-by-symbol basis.Note that the carrier frequency of UWA communication is around several kilohertz,and thus the time delay estimation can be performed on the passband to improve the accuracy.Furthermore,the prior information of Doppler limit is used to refine the resolution of delay estimation and achieve sequential estimation.To compensate the correlation magnitude distortion induced by the velocity variation,the local reference signal is selected adaptively based on the filtered Doppler factor.Simulation results demonstrate that the proposed passband Doppler tracking algorithm achieves a superior performance compared with the conventional receiver.展开更多
基金the National Natural Science Foundation of China(Grant No.81671596)the Natural Science Foundation of Guangxi(Grant No.2019GXNSFBA245032,and No.2017GXNSFAA198375)+6 种基金the Guangxi Science and Technology Plan Project(Gui Ke AD20238021)the National Science Foundation for Young Scientists of China(Grant No.31700795)the science and technology plan of Shenzhen(No.JCYJ20170307095606266)Shenzhen science and technology research foundation(JCYJ20160422154407256)Sanming project of medicine in Shenzhen,the group of Rheumatology and Immunology led by Xiaofeng Zeng of Peking Union medical college Hospital and Dongzhou Liu in Shenzhen People’s Hospital(SYJY201704 and SYJY201705)the open funds of the Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation(2019KF004)Guilin science research and technology development project(20190218-5-5).
文摘Systemic lupus erythematosus(SLE)is a systemic autoimmune disease characterized by abnormal cellular and humoral immune responses and excessive autoantibody production.The precise pathologic mechanism of SLE remains elusive.The advent of single-cell RNA sequencing(scRNA-seq)enables unbiased analysis of the molecular differences of cell populations at the single-cell level.We used scRNA-seq to profile the transcriptomes of peripheral blood mononuclear cells from an SLE patient compared with a healthy control(HC).A total of 16,021 cells were analyzed and partitioned into 12 distinct clusters.The marker genes of each cluster and the four major immune cell types(B cells,CD4+T cells,CD8+T cells,myeloid cells,and NK cells)were determined.Moreover,several genes involved in antigen processing and presentation through MHCII were highly enriched.GO enrichment analyses revealed abnormal gene expression patterns and signaling pathways in SLE.Of note,pseudotime analysis revealed that there was a different lineage hierarchy in the peripheral blood mononuclear cells(PBMCs)of the SLE patient,indicating that the cell states were substantially altered under disease conditions.Our analysis provides a comprehensive map of the cell types and states of the PBMCs of SLE patients at the single-cell level for a better understanding of the pathogenesis,diagnosis,and treatment of SLE.
基金supported by the Startup Fund for Scientific Research of Fujian Medical University(no.2021QH1114)the National Natural Science Foundation of China(no.8217-2953)the National Natural Science Foundation of Fujian(2023Y9052).
文摘Concomitant exotropia is a common chronic eye disease characterized by abnormal movement of the extraocular muscles caused by a functional imbalance of the nerves related to the movement of the extraocular muscles.This study revealed that the expression levels of S-100β and the muscle area decreased in the extraocular muscles of patients with concomitant exotropia,whereas the expression of calcitonin gene-related peptide(CGRP)increased.In CGRP-KO rats,low expression of CGRP was positively correlated with muscle atrophy.Moreover,the expression level of muscle cells,which are fast myosin heavy chain positive and slow myosin positive in CGRP-KO rats,was lower than that in the control group.Drug intervention experiments further confirmed the inhibitory effect of CGRP on muscle atrophy.The level of apoptosis in the extraocular muscles of CGRP-KO rats was significantly greater than that in the control group(P<0.05),and the phosphorylation level of AKT/CREB in the extraocular muscles of patients with concomitant exotropia was greater than that in the control group.The increased expression of CGRP in the extraocular muscles of patients with concomitant exotropia may inhibit the apoptosis of extraocular muscle cells through the AKT/CREB signaling pathway and participate in the protective effect of the extraocular muscles in concomitant exotropia.
基金Supported by the National Natural Science Foundation of China(No.81971464)the China National Postdoctoral Program for Innovative Talents(BX20200151)+2 种基金Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(No.SZXK011)the Sanming Project of Medicine in Shenzhen(SZSM201512019)the Research and Development Projects in Key Fields of Guangdong Science and Technology Department(2019B020229001).
文摘Objectives:Human papillomavirus(HPV)is a globally prevalent infection,with multiple genotypes strongly associated with cancers and other diseases.While epidemiological studies in females are extensive,research on HPV genotype distribution in males remains limited.Methods:We conducted a retrospective study by collecting and analyzing clinical and laboratory data from male patients with confirmed HPV infection at Shenzhen People’s Hospital.The distribution of HPV genotypes and their associations with specific disease types were evaluated.Results:A total of 2,037 male participants were included,with an overall HPV infection rate of 45%.Low-risk genotypes predominated,with HPV 6 and HPV 11 accounting for 25%and 12%of cases,respectively.High-risk genotypes such as HPV 16 and HPV 52 showed low prevalence(<3%)but exhibited a slight upward trend in 2022.No significant age distribution differences were observed between HPVpositive and HPV-negative groups.The frequency of multiple HPV genotype infections increased slightly with age.Specific HPV genotypes showed unique associations with acne(HPV 56),allergic dermatitis(HPV 59),and amyloidosis(HPV 58).Conclusions:Low-risk HPV genotypes predominate in males with confirmed exposure.Older males appear more susceptible to multiple infections,and specific genotypes are associated with distinct diseases,supporting the need for male-targeted HPV vaccination and surveillance programs.
基金supported by the Hong Kong Research Grants Council(17116424,17111222,17103821)the National Natural Science Foundation of China(82471821,82171771,82572073 and 82572074)the Sanming Project of Medicine in Shenzhen(No.SZSM202111006)。
文摘Inflammatory cytokine overproduction is critically involved in immune dysregulation and tissue damage,but the role of interleukin-18(IL-18),a cytokine associated with inflammasome activation,in modulating the T-cell response and autoimmune pathogenesis remains largely unclear.In this study,we detected high expression levels of the IL-18 receptorαchain(IL-18Rα)in murine and human Th17 cells.In culture,IL-18 markedly promoted Th17 cell differentiation with increased GM-CSF production,a phenotype of pathogenic Th17(pTh17)cells.Transcriptomic profiling via RNA sequencing revealed that IL-18-induced pTh17 cells presented increased glycolytic flux and proinflammatory signatures.Mechanistically,IL-18 promoted Stat3 phosphorylation,which stabilized Bhlhe40 mRNA to potentiate Bhlhe40-dependent glycolysis and cytokine production.In patients with primary Sjögren’s syndrome(pSS)and systemic lupus erythematosus(SLE),IL-18 levels in plasma and inflamed tissues were significantly increased and positively correlated with disease activity.Moreover,the expression levels of IL-18 were markedly increased in the salivary glands of experimental Sjögren’s syndrome(ESS)model mice and the renal tissues of lupus model mice.Furthermore,adoptive transfer of IL-18-induced pTh17 cells profoundly exacerbated disease severity and tissue damage in recipient IL-17-deficient mice,whereas IL-18 neutralization with a monoclonal antibody effectively suppressed the pTh17 cell response and ameliorated tissue pathology in both ESS and lupus mice.Together,our findings reveal a novel function of IL-18 in driving the pTh17 cell response during autoimmune development,indicating that IL-18 blockade may serve as a promising therapeutic strategy for the treatment of autoimmune diseases.
基金funded by grants from the National Natural Science Foundation of China(Nos.81771761,91842304,and 81901635)Chongqing International Institute for Immunology(2020YJC10)Sanming Project of Medicine in Shenzhen(SZSM201512019)。
文摘Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear.In this study,we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A(IL-17)stimulation in SLE patients and lupus mice.Using a humanized lupus mouse model,we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs.Moreover,long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+subsets among IL-17 receptor-expressing plasma cells.Lupus mice deficient in IL-17 or IL-17 receptor C(IL-17RC)exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage,while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice.In reconstituted chimeric mice,IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells.Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization.Together,our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis,which may provide new therapeutic strategies for the treatment of SLE.
基金This study was supported by grants from the Natural Science Foundation of Jiangsu(BK20170563)National Natural Science Foundation of China(No.81373195)+1 种基金National Basic Research Program of China(2014CB541904)and Natural Science Foundation of Jiangsu(BK20150533).
文摘Extensive studies have demonstrated that mesenchymal stem cells(MSCs)are multipotent mesoderm-derived stromal cells that can differentiate into a variety of cell types,including adipocytes,osteoblasts,chondrocytes,myocytes and neuronal cells.1 MSCs are found in numerous organs and tissues,including bone marrow,heart,lung,muscle,peripheral blood,adipose tissue,cartilage,synovium,dental pulp,tonsil,umbilical cord,placenta,thymus and olfactory mucosa.1 MSCs have been shown to possess potent immunosuppressive functions and tissue repair capacities,which have facilitated the clinical applications of MSCs in treating a diverse range of disorders involving angiogenesis and fibrosis,including rheumatic diseases and graft-versus-host diseases.2,3 Here,we provide a brief commentary on newly emerging evidence of the immunoregulatory function and potential application of ecto-mesenchymal stem cells.
基金This work was supported by National Natural Science Foundation of China(Nos.61701132 and 61601134)National Natural Science Foundation of Heilongjiang(No.YQ2019D003)China Scholarship Council(No.CSC201906680039).
文摘In this paper,we consider the problem of Doppler tracking and compensation for a direct sequence spread spectrum(DSSS)signal in underwater acoustic(UWA)communication.Since the dynamic property of the UWA channel and the long duration of DSSS signals result in significant Doppler spread that severely distorts the propagated signal,Doppler tracking and compensation are required.Based on the ultra-wideband property of UWA signal,the Doppler spread not only results in the frequency shift,but also changes the signal duration.Therefore,the accurate estimation of the signal expansion/compression in the time domain can reflect the Doppler spread.Accordingly,we present a Doppler tracking and compensation algorithm for a DSSS signal operating on the correlation output of passband signal at a symbol-by-symbol basis.Note that the carrier frequency of UWA communication is around several kilohertz,and thus the time delay estimation can be performed on the passband to improve the accuracy.Furthermore,the prior information of Doppler limit is used to refine the resolution of delay estimation and achieve sequential estimation.To compensate the correlation magnitude distortion induced by the velocity variation,the local reference signal is selected adaptively based on the filtered Doppler factor.Simulation results demonstrate that the proposed passband Doppler tracking algorithm achieves a superior performance compared with the conventional receiver.
