Liver fibrosis is a consequence of chronic liver disease,causing morbidity and mortality.Interleukin-33(IL-33)is a critical mediator of inflammation,which may be involved in the development of liver fibrosis.Here,we i...Liver fibrosis is a consequence of chronic liver disease,causing morbidity and mortality.Interleukin-33(IL-33)is a critical mediator of inflammation,which may be involved in the development of liver fibrosis.Here,we investigated the role of IL-33 in human patients and experimental bile-duct ligation(BDL)-induced fibrosis in mice.We report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis.Liver injury,inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor,and the activation of hepatic stellate cells(HSCs)was decreased in ST2-deficient mice.Recombinant IL-33 activated HSCs isolated from C57BL/6 mice,leading to the expression of IL-6,TGF-β,α-SMA and collagen,which was abrogated in the absence of ST2 or by pharmacological inhibition of MAPK signaling.Finally,administration of recombinant IL-33 significantly increased hepatic inflammation in sham-operated BL6 mice but did not enhance BDL-induced hepatic inflammation and fibrosis.In conclusion,BDL-induced liver inflammation and fibrosis are dependent on ST2 signaling in HSCs,and therefore,the IL-33/ST2 pathway may be a potential therapeutic target in human patients with chronic hepatitis and liver fibrosis.展开更多
Negative air ions(NAIs)benefit the mental and physical health of humans,but rapid urbanization can decrease the abundance of NAIs.Quantifying the spatial and seasonal distribution of NAIs and determining the factors t...Negative air ions(NAIs)benefit the mental and physical health of humans,but rapid urbanization can decrease the abundance of NAIs.Quantifying the spatial and seasonal distribution of NAIs and determining the factors that infl uence the concentration during urbanization is thus essential.In the present study of a typical developing urban district in southern China,negative air ion concentrations(NAICs)in 60 forests sites and 30 urban green spaces were quantifi ed on seven consecutive days in each of the four seasons.Large seasonal variations in NAIC were revealed in forests and urban green spaces with trough values in summer.NAIC progressively decreased from forests to urban green spaces and was infl uenced by local land morphology,vegetation characteristics,and climatic factors.The vast,heavily vegetated northeastern region was the richest area for NAIs,whereas the narrow central region(urbanized area)was the poorest,implying dramatic impacts of urbanization on the spatial distribution of NAIs.The relationship between air temperature and NAIC was better fi tted with a quadratic equation than a linear equation.Moreover,the NAIC was more sensitive to local morphology in urban green spaces than in urban forests,indicating the vulnerability of NAIs in urbanized areas.Therefore,the appropriate design of local urban morphology is critical.展开更多
Attenuated Listeria monocytogenes （LM） is a promising candidate vector for the delivery of cancer vaccines. After phagocytosis by antigen-presenting cells, this bacterium stimulates the major histocompatibility comp...Attenuated Listeria monocytogenes （LM） is a promising candidate vector for the delivery of cancer vaccines. After phagocytosis by antigen-presenting cells, this bacterium stimulates the major histocompatibility complex （MHC）-I and MHC-II pathways and induces the proliferation of antigen-specific T lymphocytes. A new strategy involving genetic modification of the replication-deficient LM strain AdalAdat （Lmdd） to express and secrete human CD24 protein has been developed. CD24 is a hepatic cancer stem cell biomarker that is closely associated with apoptosis, metastasis and recurrence of hepatocellular carcinoma （HCC）. After intravenous administration in mice, Lmdd-CD24 was distributed primarily in the spleen and liver and did not cause severe organ injury. Lmdd-CD24 effectively increased the number of interferon （IFN）-7-producing CD8＋ T cells and IFN-7 secretion. Lmdd-CD24 also enhanced the number of IL-4- and IL-lO-producing T helper 2 cells. The efficacy of the Lmdd-CD24 vaccine was further investigated against Hepa1- 6-CD24 tumors, which were inguinally inoculated into mice. Lmdd-CD24 significantly reduced the tumor size in mice and increased their survival. Notably, a reduction of T regulatory cell （Treg） numbers and an enhancement of specific CD8＋ T-cell activity were observed in the tumor-infiltrating lymphocytes （TILs）. These results suggest a potential application of the Lmdd-CD24 vaccine against HCC.展开更多
Dabaoshan Mine,the largest mine in south China,has been developed since the 1970s.Acid mine drainage （AMD） discharged from the mine has caused severe environmental pollution and human health problems.In this article...Dabaoshan Mine,the largest mine in south China,has been developed since the 1970s.Acid mine drainage （AMD） discharged from the mine has caused severe environmental pollution and human health problems.In this article,chemical characteristics,mineralogy of ocher precipitations and heavy metal attenuation in the AMD are discussed based on physicochemical analysis,mineral analysis,sequential extraction experiments and hydrogeochemistry.The AMD chemical characteristics were determined from the initial water composition,water-rock interactions and dissolved sulfide minerals in the mine tailings.The waters,affected and unaffected by AMD,were Ca-SO4 and Ca-HCO3 types,respectively.The affected water had a low pH,high SO42 and high heavy metal content and oxidation as determined by the Fe^2＋ /Fe^3＋ couple.Heavy metal and SO4^2- contents of Hengshi River water decreased,while pH increased,downstream.Schwertmannite was the major mineral at the waste dump,while goethite and quartz were dominant at the tailings dam and streambed.Schwertmannite was transformed into goethite at the tailings dam and streambed.The sulfate ions of the secondary minerals changed from bidentate-to monodentate-complexes downstream.Fe-Mn oxide phases of Zn,Cd and Pb in sediments increased downstream.However,organic matter complexes of Cu in sediments increased further away from the tailings.Fe^3＋ mineral precipitates and transformations controlled the AMD water chemistry.展开更多
Type Ⅱ Epstein-Barr virus （EBV） associated malignancies such as nasopharyngeal carcinoma and non-Hodgkin＇s lymphomas consistently express latent membrane 2A （LMP2A） proteins, which have been suggested to be an i...Type Ⅱ Epstein-Barr virus （EBV） associated malignancies such as nasopharyngeal carcinoma and non-Hodgkin＇s lymphomas consistently express latent membrane 2A （LMP2A） proteins, which have been suggested to be an ideal target for immunotherapy. In previous studies we have demonstrated that using LMP2A protein loaded dendritic cells, the most powerful antigen processing cells in the body can elicit specific and robust anti-tumor cellular immune response in vitro. In this paper, we further investigated the T cell profile of the anti-tumor immune response. We found that LMP2A specific CD4＋ and CD8＋ T cells could be stimulated by LMP2A protein loaded dendritic cells （DCs）. The Thl type immune response is dominant in the immune response mediated by LMP2A specific CD4^＋ T cells. The CD8^＋ cytotoxic T cells can lyse LMP2A bearing cells effectively and specifically. The CD8^＋ cytotoxic T cells can also secrete high level of intracellular IFN-γ, which indicates these cells are EBV-LMP2A specific cytotoxic T cells. Altogether, our studies proved that LMP2A protein loaded DCs can elicit anti-tumor cellular immune responses efficiently. This study provides a rationale for the DC-based immunotherapy against EBV-LMP2A expressing malignancies.展开更多
Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Me...Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(P<0.001).The expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC.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
Aim: To investigate alterations of smooth muscle celis and collagen fibers in corpus cavernosum following cavernous neurectomy and its relation to the expression of transforming growth factor-β1 (TGF-β1). Methods: T...Aim: To investigate alterations of smooth muscle celis and collagen fibers in corpus cavernosum following cavernous neurectomy and its relation to the expression of transforming growth factor-β1 (TGF-β1). Methods: Ten adult male SD rats (neurectomy group) were subject to a bilateral cavernous nerve (CN) resection aseptically under an operating microscope, with 6 sham-operated rats as the control. Fifteen weeks after the operation, the penile speci mens were collected and prepared for quantitative-analyzing of ratio of smooth muscle to collagen fibers in corpus cavernosum with confocal microscopy, and for detecting the expression of TGF-β1 by RT-PCR and western-blot. Resulte: Smooth muscle celis that show red color after fluorescent-labeling with tetramethylrhodamine isothiocyanate phalloidin and collagen fibers that produce green autofluorescence after paraformaldehyde fixation were clearly iden tified under the confocal microscope. Quantification of fluorescent intensity showed that the ratio of smooth muscle to collagen fibers in corpus cavernosum in neurectomy group was 0.265±0.125, which was significantly lower than that in sham-operated group (0.760±0.196, P<0.01). RT-PCR and western-blot analyses revealed a significantly higher expression of TGF-β1 in the penile tissues of the neurectomy animals than that in sham-operated group. Conclusion: Bilateral ablation of CN can lead to fibrosis of corpus cavernosum, which may be related to an increased expression of TGF-β1 induced by hypoxia in cavernous tissue after denervation.展开更多
The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poo...The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poorly clarified.Here,we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation,promoted thymic IL-17A-producingγδT-cell(Tγδ17)lineage commitment,and led to the development of fatal autoimmune hepatitis(AIH)via different mechanisms.Transfer ofγδT cells from TOX-deficient mice reproduced AIH.TOX interacted with and stabilized the TCF1 protein to maintain the balance ofγδT-cell development in thymic progenitors,and overexpression of TCF1 normalizedαβ/γδlineage specification and activation.In addition,TOX expression was downregulated inγδT cells from AIH patients and was inversely correlated with the AIH diagnostic score.Our findings suggest multifaceted roles of TOX in autoimmune control involving mTEC and Tγδ17 development and provide a potential diagnostic marker for AIH.展开更多
Inflammation has been considered as one of the hallmarks of cancer,and chronic hepatitis is a major cause of liver cancer.This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will ...Inflammation has been considered as one of the hallmarks of cancer,and chronic hepatitis is a major cause of liver cancer.This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research,including cellular interaction,cytokines,microRNA and stem cells.All of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma.展开更多
To understand the transfer process of soluble reactive phosphorus （SRP） on the lake sediment-water interface in a mesotrophic shallow lake in South China, the SRP concentrations and the oxidation-reduction potential...To understand the transfer process of soluble reactive phosphorus （SRP） on the lake sediment-water interface in a mesotrophic shallow lake in South China, the SRP concentrations and the oxidation-reduction potential （ORP） across the sediment-water interfaces were continually monitored. Sediment samples were collected from Xinghu Lake in Guangdong Province. The ORP dynamics at different layers of overlying water was similar for six experimental systems, whereas those in porewater were significantly different. The ORP in overlying water was 200-300 mV higher than those in sediments. The oxygen penetration depth ranged from 2 to 10 mm in Xiannu Lake sediments. The variation amplitudes of ORP increased with sediment depth, but the mean ORP values were all about 218 mV. The SRP concentrations in porewater maintained at a low level of about 0.049 mg/L because of high atom ratio of total iron and total manganese to total phosphorus. The SRP concentrations and variation amplitudes in porewater increased with sediment depth. The SRP in overlying water mainly originated from S RP transference of the porewater of middle and bottom sediments （3-15 cm）. The ORP variation and SRP transfer in porewater played important roles in changing SRP concentrations. A distinct SRP concentration gradient appeared in overlying water when intense exchange occurred at the sediment-water interface; therefore, it was necessary to monitor the SRP concentration profiles to accurately estimate the internal loading.展开更多
Intratumoral T cells play a central role in anti-tumor immunity,and the balance between T effector cells(Teff)and regulatory T cells(Treg)affects the prognosis of cancer patients.However,educated by tumor microenviron...Intratumoral T cells play a central role in anti-tumor immunity,and the balance between T effector cells(Teff)and regulatory T cells(Treg)affects the prognosis of cancer patients.However,educated by tumor microenvironment,T cells frequently fail in their responsibility.In this study,we aimed to investigate the role of truncated isoform of protein tyrosine phosphatase receptor-typeO(PTPROt)in T cell-mediated anti-tumor immunity.We recruited 70 hepatocellular carcinoma(HCC)patients and 30 healthy volunteers for clinical investigation,and analyzed cellular tumor immunity by using ptpro^(-/-) C57BL/6 mice and NOD/SCID mice.PTPROt expression was significantly downregulated in human HCC-infiltrating T cells due to the hypoxia microenvironment;PTPROt expression highly correlated with the intratumoral Teff/Treg ratio and clinicopathologic characteristics.Moreover,PTPROt deficiency attenuated T cell-mediated anti-tumor immunity and remarkably promoted mouse HCC growth.Mechanistically,deletion of PTPROt decreased Teff quantity and quality through phosphorylation of lymphocyte-specific tyrosine kinase,but increased Treg differentiation through phosphorylation of signal transducer and activator of transcription 5.In support of the Teff/Treg homeostasis,PTPROt serves as an important tumor suppressor in HCC microenvironment.展开更多
Granulocyte-macrophage colony-stimulating factor （GM-CSF） secreting cellular tumor vaccines contribute to the induction of potent antitumor immune responses in murine models and patients suffering from cancers. Hepa...Granulocyte-macrophage colony-stimulating factor （GM-CSF） secreting cellular tumor vaccines contribute to the induction of potent antitumor immune responses in murine models and patients suffering from cancers. Hepatocellular carcinoma （HCC） is one of the most frequent and malignant cancers in China. We describe, for the first time, a GM-CSF releasing vaccine strategy that represents a step toward combating this type of cancer. In this study, a bystander cell-based GM-CSF secreting vaccine against murine HCC, Hepa 1-6/B78H 1-GM-CSF, was co-administered with a low dose of cyclophosphamide （CY）. After challenging with tumor and vaccination, immunological assays demonstrated that the cellular antitumor immune responses were efficiently activated and that tumor development was significantly retarded, which was dependent on synergy with CY. The promising outcome of the anti-HCC vaccine in the murine model demonstrates the feasibility of a future clinical application for this treatment in HCC patients.展开更多
Dear Editor,The SARS-CoV-2 virus outbreak that started in December 2019 is now a global pandemic with over 42.7 million confirmed cases and 1.15 million deaths as of October 25,2020.It has been predicted that resurgen...Dear Editor,The SARS-CoV-2 virus outbreak that started in December 2019 is now a global pandemic with over 42.7 million confirmed cases and 1.15 million deaths as of October 25,2020.It has been predicted that resurgence in contagion may be possible as late as 2024.1 A persistent anti-SARS-CoV-2 adaptive immune surveillance post infection is critical to lower the risk of resurgence and transmission.T cells are the primary effectors of cellular adaptive immunity that not only clear virus-infected cells during infection but also provide long-term protection post infection as memory cells in some pathogen infections.However,little is known regarding the longitudinal T cell response during and after SARSCoV-2 infection.Single-cell T cell receptor(TCR)sequencing allows rapid identification of expanded T cell clones that are potentially the antigen-specific clonotypes.2 To further characterize the anti-SARS-CoV-2 T cells,we sequenced the circulating T cells of five moderate or severe COVID-19 patients at different stages of infection(two patients at 1,7 and 16 weeks and three patients at 1 and 17 weeks post symptom onset)and of two healthy donors(Supplementary Tables S1,S2 and S7).展开更多
The biological features of intrahepatic CD4^(+)CD25^(+)T regulatory cells in the naturally tolerance of rat liver transplantation were explored.Orthotopic liver transplan-tation was performed in two allogeneic rat str...The biological features of intrahepatic CD4^(+)CD25^(+)T regulatory cells in the naturally tolerance of rat liver transplantation were explored.Orthotopic liver transplan-tation was performed in two allogeneic rat strain combina-tions,one with fatal immunosuppression despite a complete major histocompatibility complex mismatch.The subjects were divided into three groups according to different donors and recipients[Tolerance group:LEW-to-DA;Rejection group:DA-to-LEW;Syngegnic group(control group):DA-to-DA].The proportion of intrahepatic CD4^(+)CD25^(+)T cells from three groups was determined by flow cytometry(FCM)in different time.The intrahepaitc CD4^(+)CD25^(+)T cells were isolated by magnetic activated cell sorting(MACS)method and identified by FCM.The Foxp3 mRNA was detected by reverse transcriptase polymerase chain reaction(RT-PCR).And their suppression on the proliferation of CD4^(+)CD25^(-)T effector cells was analyzed by cell proliferation assay in vitro.Beginning immediately after transplantation,the proportion of Treg cells increased over time in both allogeneic groups but was significantly greater in the Rejection group.The pro-portion of Treg cells declined after day 5,and such reduction was more dramatic in the Rejection group than in the Tole-rance group.Animals in the Tolerance group showed a second increase in the proportion after day 14.Intrahepatic CD4^(+)CD25^(+)T cells isolated from spontaneous tolerance models inhibited the proliferation of mixed lymphocyte reaction.The purity of CD4^(+)CD25^(+)Tcells sorted by MACS was 86%–93%.The CD4^(+)CD25^(+)T cells could specifically express the Foxp3 gene compared with CD4^(+)CD25^(-)T cells.In vitro,the spleen cells from LEW rats can irritate the proliferation of CD4^(+)CD25^(+)T cells more obviously than the syngegnic spleen cells.CD4^(+)CD25^(+)Tr cells could suppress the proliferation of CD4^(+)CD25^(-)T cells,but the inhibition was reversed by exo-genous IL-2(200 U/mL).The CD4^(+)CD25^(+)T regulatory cells specifically express the Foxp3 gene,whic展开更多
The spatial distribution of meteorological elements is important for understanding the regional meteorology and climate changes. However, previous studies rarely focused on the daily changes of the spatial patterns of...The spatial distribution of meteorological elements is important for understanding the regional meteorology and climate changes. However, previous studies rarely focused on the daily changes of the spatial patterns of meteorological elements due to the limitation of remote sensing （RS） techniques and traditional meteorological methods. In this paper, the regional meteorological elements were simulated by the fifth-generation non-hydrostatic Mesoscale Model （MM5）, and the spatial patterns of meteorological elements and their diurnal variations were analyzed in landscape level over the Pearl （Zhujiang） River Delta （PRD）, China. The results showed that there were several centers of urban heat islands, cold islands, dry islands, wet islands, high wind over the PRD at noon. The diurnal changes of Moran I of meteorological elements were obvious and they reached the extremum at noon and 2-3 hours after the sunrise. The landscape indices of meteorological elements, such as area-weighted mean Fractal Dimension Index （FRAC_AM）, Landscape Shape lndex （LSI）, Shannon＇s Diversity Index （SHDI） and Contagion lndex （CONTAG）, were more variable at about the sunrise, noon and sunset. The occurrence of wave crests and vales of landscape indices was affected by the surface net radiation, turbulence and local circumfluence. The spatial patterns of meteorological elements correlated well with the land surface, thermal exchanges and local circumfluence. A new approach combining GIS, RS and numerical simulations technologies and the landscape ecology method was presented to analyze spatial patterns of meteorological elements, which may be useful for studying global and regional climate changes.展开更多
Dear Editor,The SARS-CoV-2 virus outbreak that started in December 2019 is now a global pandemic with over 42.7 million confirmed cases and 1.15 million deaths as of October 25,2020.It has been predicted that resurgen...Dear Editor,The SARS-CoV-2 virus outbreak that started in December 2019 is now a global pandemic with over 42.7 million confirmed cases and 1.15 million deaths as of October 25,2020.It has been predicted that resurgence in contagion may be possible as late as 2024.1 A persistent anti-SARS-CoV-2 adaptive immune surveillance post infection is critical to lower the risk of resurgence and transmission.T cells are the primary effectors of cellular adaptive immunity that not only clear virus-infected cells during infection but also provide long-term protection post infection as memory cells in some pathogen infections.However,little is known regarding the longitudinal T cell response during and after SARSCoV-2 infection.Single-cell T cell receptor(TCR)sequencing allows rapid identification of expanded T cell clones that are potentially the antigen-specific clonotypes.展开更多
In a study published in Cellular&Molecular Immunology,we described a novel mechanism by which IL-33 drives hepatic fibrosis through the MAPK pathway.The study demonstrated that hepatocyte-derived IL-33 is elevated...In a study published in Cellular&Molecular Immunology,we described a novel mechanism by which IL-33 drives hepatic fibrosis through the MAPK pathway.The study demonstrated that hepatocyte-derived IL-33 is elevated upon bile duct ligation(BDL)-induced liver injury and fibrogenesis and activates hepatic stellate cells in a JNK/ERK/p38-dependent manner.展开更多
Fulminant hepatitis is fatal in most cases and timely liver transplantation is the only effective treatment.This study evaluates the survival outcomes of patients who underwent living-donor liver transplantation(LDLT)...Fulminant hepatitis is fatal in most cases and timely liver transplantation is the only effective treatment.This study evaluates the survival outcomes of patients who underwent living-donor liver transplantation(LDLT)using right lobe liver grafts for fulminant liver failure due to hepatitis B infection.Nine cases of adult right lobe LDLT were performed in our department from September 2002 to August 2005 and the clinical and following-up data were reviewed.According to the pre-transplant Child-Pugh-Turcotte classification,the nine patients were classified as grade C.The model for end-stage liver disease(MELD)score of these patients ranged from 16 to 42.The principal complications before transplantation included abnormal renal function,hepatic coma of different degrees and alimentary tract hemorrhage.The main complications after transplantation included pulmonary infection in two cases,acute renal failure in three cases and transplantation-related encephalopathy in one case.No primary failure of vascular or biliary complications occurred.The one-year survival rate was 55.6%.There were no serious complications or deaths in donors.In general,it is extremely difficult to treat fulminant hepatitis by conservative regimen,particularly,in cases with rapid progression.Emergency adult living-donor liver transplantation is an effective treatment for fulminant hepatitis patients and is relatively safe for donors.展开更多
基金This work was supported by grants from the National Natural Science Foundation(81502036 to ZT,81201595 to SS,81201528 to RJ)the Natural Science Foundation of Jiangsu Province(BK20151031 to ZT)+3 种基金the National Key Research and Development Program of China(2016YFC0905900 to BS)the State Key Program of National Natural Science of China(81430062 to BS)the project of the Nanjing Science and Technology Development Plan(201303033 to LL)The work was also supported in part by the Program for Development of Innovative Research Teams in the First Affiliated Hospital of NJMU,the Priority Academic Program of Jiangsu Higher Education Institutions and funds from CNRS and FEDER(BR).
文摘Liver fibrosis is a consequence of chronic liver disease,causing morbidity and mortality.Interleukin-33(IL-33)is a critical mediator of inflammation,which may be involved in the development of liver fibrosis.Here,we investigated the role of IL-33 in human patients and experimental bile-duct ligation(BDL)-induced fibrosis in mice.We report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis.Liver injury,inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor,and the activation of hepatic stellate cells(HSCs)was decreased in ST2-deficient mice.Recombinant IL-33 activated HSCs isolated from C57BL/6 mice,leading to the expression of IL-6,TGF-β,α-SMA and collagen,which was abrogated in the absence of ST2 or by pharmacological inhibition of MAPK signaling.Finally,administration of recombinant IL-33 significantly increased hepatic inflammation in sham-operated BL6 mice but did not enhance BDL-induced hepatic inflammation and fibrosis.In conclusion,BDL-induced liver inflammation and fibrosis are dependent on ST2 signaling in HSCs,and therefore,the IL-33/ST2 pathway may be a potential therapeutic target in human patients with chronic hepatitis and liver fibrosis.
基金The authors acknowledge the volunteers who helped with the fi eld investigations.
文摘Negative air ions(NAIs)benefit the mental and physical health of humans,but rapid urbanization can decrease the abundance of NAIs.Quantifying the spatial and seasonal distribution of NAIs and determining the factors that infl uence the concentration during urbanization is thus essential.In the present study of a typical developing urban district in southern China,negative air ion concentrations(NAICs)in 60 forests sites and 30 urban green spaces were quantifi ed on seven consecutive days in each of the four seasons.Large seasonal variations in NAIC were revealed in forests and urban green spaces with trough values in summer.NAIC progressively decreased from forests to urban green spaces and was infl uenced by local land morphology,vegetation characteristics,and climatic factors.The vast,heavily vegetated northeastern region was the richest area for NAIs,whereas the narrow central region(urbanized area)was the poorest,implying dramatic impacts of urbanization on the spatial distribution of NAIs.The relationship between air temperature and NAIC was better fi tted with a quadratic equation than a linear equation.Moreover,the NAIC was more sensitive to local morphology in urban green spaces than in urban forests,indicating the vulnerability of NAIs in urbanized areas.Therefore,the appropriate design of local urban morphology is critical.
文摘Attenuated Listeria monocytogenes （LM） is a promising candidate vector for the delivery of cancer vaccines. After phagocytosis by antigen-presenting cells, this bacterium stimulates the major histocompatibility complex （MHC）-I and MHC-II pathways and induces the proliferation of antigen-specific T lymphocytes. A new strategy involving genetic modification of the replication-deficient LM strain AdalAdat （Lmdd） to express and secrete human CD24 protein has been developed. CD24 is a hepatic cancer stem cell biomarker that is closely associated with apoptosis, metastasis and recurrence of hepatocellular carcinoma （HCC）. After intravenous administration in mice, Lmdd-CD24 was distributed primarily in the spleen and liver and did not cause severe organ injury. Lmdd-CD24 effectively increased the number of interferon （IFN）-7-producing CD8＋ T cells and IFN-7 secretion. Lmdd-CD24 also enhanced the number of IL-4- and IL-lO-producing T helper 2 cells. The efficacy of the Lmdd-CD24 vaccine was further investigated against Hepa1- 6-CD24 tumors, which were inguinally inoculated into mice. Lmdd-CD24 significantly reduced the tumor size in mice and increased their survival. Notably, a reduction of T regulatory cell （Treg） numbers and an enhancement of specific CD8＋ T-cell activity were observed in the tumor-infiltrating lymphocytes （TILs）. These results suggest a potential application of the Lmdd-CD24 vaccine against HCC.
基金supported by the Guangdong Provincial Natural Science Foundation (No. 06202438)the Research Funds of the Guangxi Key Laboratory of Environmental Engineering,Protection and Assessment (No.GuiKeNeng 0801Z020)
文摘Dabaoshan Mine,the largest mine in south China,has been developed since the 1970s.Acid mine drainage （AMD） discharged from the mine has caused severe environmental pollution and human health problems.In this article,chemical characteristics,mineralogy of ocher precipitations and heavy metal attenuation in the AMD are discussed based on physicochemical analysis,mineral analysis,sequential extraction experiments and hydrogeochemistry.The AMD chemical characteristics were determined from the initial water composition,water-rock interactions and dissolved sulfide minerals in the mine tailings.The waters,affected and unaffected by AMD,were Ca-SO4 and Ca-HCO3 types,respectively.The affected water had a low pH,high SO42 and high heavy metal content and oxidation as determined by the Fe^2＋ /Fe^3＋ couple.Heavy metal and SO4^2- contents of Hengshi River water decreased,while pH increased,downstream.Schwertmannite was the major mineral at the waste dump,while goethite and quartz were dominant at the tailings dam and streambed.Schwertmannite was transformed into goethite at the tailings dam and streambed.The sulfate ions of the secondary minerals changed from bidentate-to monodentate-complexes downstream.Fe-Mn oxide phases of Zn,Cd and Pb in sediments increased downstream.However,organic matter complexes of Cu in sediments increased further away from the tailings.Fe^3＋ mineral precipitates and transformations controlled the AMD water chemistry.
基金Acknowledgements We thank Professor Xueguang Zhang （Soochow University, Suzhou, China） for kindly providing plasmid pGEZ, pHIT456, pHIT60 and 293T cell lines. This work was supported by the National Natural Science Foundation of China （No. 30772003 and No. 30170880）, Jiangsu Province＇s Outstanding Medical Academic Leader programme （RC2007057） and Science Development Foundation of Nanjing Medical University （NMUZ009）.
文摘Type Ⅱ Epstein-Barr virus （EBV） associated malignancies such as nasopharyngeal carcinoma and non-Hodgkin＇s lymphomas consistently express latent membrane 2A （LMP2A） proteins, which have been suggested to be an ideal target for immunotherapy. In previous studies we have demonstrated that using LMP2A protein loaded dendritic cells, the most powerful antigen processing cells in the body can elicit specific and robust anti-tumor cellular immune response in vitro. In this paper, we further investigated the T cell profile of the anti-tumor immune response. We found that LMP2A specific CD4＋ and CD8＋ T cells could be stimulated by LMP2A protein loaded dendritic cells （DCs）. The Thl type immune response is dominant in the immune response mediated by LMP2A specific CD4^＋ T cells. The CD8^＋ cytotoxic T cells can lyse LMP2A bearing cells effectively and specifically. The CD8^＋ cytotoxic T cells can also secrete high level of intracellular IFN-γ, which indicates these cells are EBV-LMP2A specific cytotoxic T cells. Altogether, our studies proved that LMP2A protein loaded DCs can elicit anti-tumor cellular immune responses efficiently. This study provides a rationale for the DC-based immunotherapy against EBV-LMP2A expressing malignancies.
基金the National Key Research and Development Program of China(No.2021YFA1100500)the Major Research Plan of the National Natural Science Foundation of China(No.92159202)+2 种基金the Key Research&Development Plan of Zhejiang Province(No.2019C03050),the Key Research&Development Plan of Zhejiang Province(No.2021C03118)National S&T Major Project(No.2017ZX10203205)the Health Science&Technology Plan of Zhejiang Province(No.2022RC060)。
文摘Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(P<0.001).The expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC.
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.
文摘Aim: To investigate alterations of smooth muscle celis and collagen fibers in corpus cavernosum following cavernous neurectomy and its relation to the expression of transforming growth factor-β1 (TGF-β1). Methods: Ten adult male SD rats (neurectomy group) were subject to a bilateral cavernous nerve (CN) resection aseptically under an operating microscope, with 6 sham-operated rats as the control. Fifteen weeks after the operation, the penile speci mens were collected and prepared for quantitative-analyzing of ratio of smooth muscle to collagen fibers in corpus cavernosum with confocal microscopy, and for detecting the expression of TGF-β1 by RT-PCR and western-blot. Resulte: Smooth muscle celis that show red color after fluorescent-labeling with tetramethylrhodamine isothiocyanate phalloidin and collagen fibers that produce green autofluorescence after paraformaldehyde fixation were clearly iden tified under the confocal microscope. Quantification of fluorescent intensity showed that the ratio of smooth muscle to collagen fibers in corpus cavernosum in neurectomy group was 0.265±0.125, which was significantly lower than that in sham-operated group (0.760±0.196, P<0.01). RT-PCR and western-blot analyses revealed a significantly higher expression of TGF-β1 in the penile tissues of the neurectomy animals than that in sham-operated group. Conclusion: Bilateral ablation of CN can lead to fibrosis of corpus cavernosum, which may be related to an increased expression of TGF-β1 induced by hypoxia in cavernous tissue after denervation.
基金This work was supported by grants from the State Key Program of the National Natural Science Foundation(81930086 and 82120108012 to BS,82073157 and 81600487 to WT)the Science and Technology Project of Jiangsu Province(BE2018603 to BS)the Postgraduate Innovative Research Program of Jiangsu Province(KYCX20_0047 to QH).
文摘The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poorly clarified.Here,we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation,promoted thymic IL-17A-producingγδT-cell(Tγδ17)lineage commitment,and led to the development of fatal autoimmune hepatitis(AIH)via different mechanisms.Transfer ofγδT cells from TOX-deficient mice reproduced AIH.TOX interacted with and stabilized the TCF1 protein to maintain the balance ofγδT-cell development in thymic progenitors,and overexpression of TCF1 normalizedαβ/γδlineage specification and activation.In addition,TOX expression was downregulated inγδT cells from AIH patients and was inversely correlated with the AIH diagnostic score.Our findings suggest multifaceted roles of TOX in autoimmune control involving mTEC and Tγδ17 development and provide a potential diagnostic marker for AIH.
文摘Inflammation has been considered as one of the hallmarks of cancer,and chronic hepatitis is a major cause of liver cancer.This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research,including cellular interaction,cytokines,microRNA and stem cells.All of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma.
基金supported by the Environment and Pollution Control Technology Innovation Program,which is one part of the 985 Project at Sun Yat-sen University
文摘To understand the transfer process of soluble reactive phosphorus （SRP） on the lake sediment-water interface in a mesotrophic shallow lake in South China, the SRP concentrations and the oxidation-reduction potential （ORP） across the sediment-water interfaces were continually monitored. Sediment samples were collected from Xinghu Lake in Guangdong Province. The ORP dynamics at different layers of overlying water was similar for six experimental systems, whereas those in porewater were significantly different. The ORP in overlying water was 200-300 mV higher than those in sediments. The oxygen penetration depth ranged from 2 to 10 mm in Xiannu Lake sediments. The variation amplitudes of ORP increased with sediment depth, but the mean ORP values were all about 218 mV. The SRP concentrations in porewater maintained at a low level of about 0.049 mg/L because of high atom ratio of total iron and total manganese to total phosphorus. The SRP concentrations and variation amplitudes in porewater increased with sediment depth. The SRP in overlying water mainly originated from S RP transference of the porewater of middle and bottom sediments （3-15 cm）. The ORP variation and SRP transfer in porewater played important roles in changing SRP concentrations. A distinct SRP concentration gradient appeared in overlying water when intense exchange occurred at the sediment-water interface; therefore, it was necessary to monitor the SRP concentration profiles to accurately estimate the internal loading.
基金supported by grants from the National Natural Science Foundation for Distinguished Young Scholars(81225017 to B.S.)the State Key Program of National Natural Science of China(81430062 to B.S.)+3 种基金the National Basic Research Program of China(2012CB910800 to B.S.)the National Natural Science Foundation of China(81302106 to J.H.81201528 to R.J.)supported in part by the Priority Academic Program of Jiangsu Higher Education Institutions.
文摘Intratumoral T cells play a central role in anti-tumor immunity,and the balance between T effector cells(Teff)and regulatory T cells(Treg)affects the prognosis of cancer patients.However,educated by tumor microenvironment,T cells frequently fail in their responsibility.In this study,we aimed to investigate the role of truncated isoform of protein tyrosine phosphatase receptor-typeO(PTPROt)in T cell-mediated anti-tumor immunity.We recruited 70 hepatocellular carcinoma(HCC)patients and 30 healthy volunteers for clinical investigation,and analyzed cellular tumor immunity by using ptpro^(-/-) C57BL/6 mice and NOD/SCID mice.PTPROt expression was significantly downregulated in human HCC-infiltrating T cells due to the hypoxia microenvironment;PTPROt expression highly correlated with the intratumoral Teff/Treg ratio and clinicopathologic characteristics.Moreover,PTPROt deficiency attenuated T cell-mediated anti-tumor immunity and remarkably promoted mouse HCC growth.Mechanistically,deletion of PTPROt decreased Teff quantity and quality through phosphorylation of lymphocyte-specific tyrosine kinase,but increased Treg differentiation through phosphorylation of signal transducer and activator of transcription 5.In support of the Teff/Treg homeostasis,PTPROt serves as an important tumor suppressor in HCC microenvironment.
基金This work was supported by grants from National Basic Research Program of China （2012CB910800 to BS）, the National Natural Science Foundation （81072029 to BS and 30901750, 81272322 to YC, 81201528 to RJ）, Major Research Plan of the National Natural Science Foundation （91029721 to BS）, Natural Science Foundation of Jiangsu Province （BK2010532 to YC）, China Postdoctoral Science Foundation-funded project （20090461133 to YC）, Jiangsu Planned Projects for Postdoctoral Research Funds （1001028B to YC）, Jiangsu Province Laboratory of Pathogen Biology （11BYKF02 to QS）, Ministry of Health Research Foundation, China （LW201001 to LD） and the Priority Academic Program Development of Jiangsu Higher Education Institutions. The work was also supported in part by the Program for Development of Innovative Research Teams in the First Affiliated Hospital of NJMU.
文摘Granulocyte-macrophage colony-stimulating factor （GM-CSF） secreting cellular tumor vaccines contribute to the induction of potent antitumor immune responses in murine models and patients suffering from cancers. Hepatocellular carcinoma （HCC） is one of the most frequent and malignant cancers in China. We describe, for the first time, a GM-CSF releasing vaccine strategy that represents a step toward combating this type of cancer. In this study, a bystander cell-based GM-CSF secreting vaccine against murine HCC, Hepa 1-6/B78H 1-GM-CSF, was co-administered with a low dose of cyclophosphamide （CY）. After challenging with tumor and vaccination, immunological assays demonstrated that the cellular antitumor immune responses were efficiently activated and that tumor development was significantly retarded, which was dependent on synergy with CY. The promising outcome of the anti-HCC vaccine in the murine model demonstrates the feasibility of a future clinical application for this treatment in HCC patients.
基金supported by grants from the National Key Research and Development Program of China(2016YFC0905900 to B.S.)State Key Program of the National Natural Science Foundation(81930086 to B.S.)+1 种基金The Key Project by Medical Science and Technology Development Foundation,Nanjing Department of Health(ZKX2020001 to S.J.)Fundamental Research Funds for the Central Universities(0214-14380461 to B.S.).
文摘Dear Editor,The SARS-CoV-2 virus outbreak that started in December 2019 is now a global pandemic with over 42.7 million confirmed cases and 1.15 million deaths as of October 25,2020.It has been predicted that resurgence in contagion may be possible as late as 2024.1 A persistent anti-SARS-CoV-2 adaptive immune surveillance post infection is critical to lower the risk of resurgence and transmission.T cells are the primary effectors of cellular adaptive immunity that not only clear virus-infected cells during infection but also provide long-term protection post infection as memory cells in some pathogen infections.However,little is known regarding the longitudinal T cell response during and after SARSCoV-2 infection.Single-cell T cell receptor(TCR)sequencing allows rapid identification of expanded T cell clones that are potentially the antigen-specific clonotypes.2 To further characterize the anti-SARS-CoV-2 T cells,we sequenced the circulating T cells of five moderate or severe COVID-19 patients at different stages of infection(two patients at 1,7 and 16 weeks and three patients at 1 and 17 weeks post symptom onset)and of two healthy donors(Supplementary Tables S1,S2 and S7).
基金supported by the National Natural Science Foundation of China(Grant No.30271236).
文摘The biological features of intrahepatic CD4^(+)CD25^(+)T regulatory cells in the naturally tolerance of rat liver transplantation were explored.Orthotopic liver transplan-tation was performed in two allogeneic rat strain combina-tions,one with fatal immunosuppression despite a complete major histocompatibility complex mismatch.The subjects were divided into three groups according to different donors and recipients[Tolerance group:LEW-to-DA;Rejection group:DA-to-LEW;Syngegnic group(control group):DA-to-DA].The proportion of intrahepatic CD4^(+)CD25^(+)T cells from three groups was determined by flow cytometry(FCM)in different time.The intrahepaitc CD4^(+)CD25^(+)T cells were isolated by magnetic activated cell sorting(MACS)method and identified by FCM.The Foxp3 mRNA was detected by reverse transcriptase polymerase chain reaction(RT-PCR).And their suppression on the proliferation of CD4^(+)CD25^(-)T effector cells was analyzed by cell proliferation assay in vitro.Beginning immediately after transplantation,the proportion of Treg cells increased over time in both allogeneic groups but was significantly greater in the Rejection group.The pro-portion of Treg cells declined after day 5,and such reduction was more dramatic in the Rejection group than in the Tole-rance group.Animals in the Tolerance group showed a second increase in the proportion after day 14.Intrahepatic CD4^(+)CD25^(+)T cells isolated from spontaneous tolerance models inhibited the proliferation of mixed lymphocyte reaction.The purity of CD4^(+)CD25^(+)Tcells sorted by MACS was 86%–93%.The CD4^(+)CD25^(+)T cells could specifically express the Foxp3 gene compared with CD4^(+)CD25^(-)T cells.In vitro,the spleen cells from LEW rats can irritate the proliferation of CD4^(+)CD25^(+)T cells more obviously than the syngegnic spleen cells.CD4^(+)CD25^(+)Tr cells could suppress the proliferation of CD4^(+)CD25^(-)T cells,but the inhibition was reversed by exo-genous IL-2(200 U/mL).The CD4^(+)CD25^(+)T regulatory cells specifically express the Foxp3 gene,whic
基金Under the auspices of National High-tech Research and Development Program of China (863 Project) (No. 2006AA12Z207)
文摘The spatial distribution of meteorological elements is important for understanding the regional meteorology and climate changes. However, previous studies rarely focused on the daily changes of the spatial patterns of meteorological elements due to the limitation of remote sensing （RS） techniques and traditional meteorological methods. In this paper, the regional meteorological elements were simulated by the fifth-generation non-hydrostatic Mesoscale Model （MM5）, and the spatial patterns of meteorological elements and their diurnal variations were analyzed in landscape level over the Pearl （Zhujiang） River Delta （PRD）, China. The results showed that there were several centers of urban heat islands, cold islands, dry islands, wet islands, high wind over the PRD at noon. The diurnal changes of Moran I of meteorological elements were obvious and they reached the extremum at noon and 2-3 hours after the sunrise. The landscape indices of meteorological elements, such as area-weighted mean Fractal Dimension Index （FRAC_AM）, Landscape Shape lndex （LSI）, Shannon＇s Diversity Index （SHDI） and Contagion lndex （CONTAG）, were more variable at about the sunrise, noon and sunset. The occurrence of wave crests and vales of landscape indices was affected by the surface net radiation, turbulence and local circumfluence. The spatial patterns of meteorological elements correlated well with the land surface, thermal exchanges and local circumfluence. A new approach combining GIS, RS and numerical simulations technologies and the landscape ecology method was presented to analyze spatial patterns of meteorological elements, which may be useful for studying global and regional climate changes.
基金This work was supported by grants from the National Key Research and Development Program of China(2016YFC0905900 to B.S.)State Key Program of the National Natural Science Foundation(81930086 to B.S.)+1 种基金The Key Project by Medical Science and Technology Development Foundation,Nanjing Department of Health(ZKX2020001 to S.J.)Fundamental Research Funds for the Central Universities(0214-14380461 to B.S.)。
文摘Dear Editor,The SARS-CoV-2 virus outbreak that started in December 2019 is now a global pandemic with over 42.7 million confirmed cases and 1.15 million deaths as of October 25,2020.It has been predicted that resurgence in contagion may be possible as late as 2024.1 A persistent anti-SARS-CoV-2 adaptive immune surveillance post infection is critical to lower the risk of resurgence and transmission.T cells are the primary effectors of cellular adaptive immunity that not only clear virus-infected cells during infection but also provide long-term protection post infection as memory cells in some pathogen infections.However,little is known regarding the longitudinal T cell response during and after SARSCoV-2 infection.Single-cell T cell receptor(TCR)sequencing allows rapid identification of expanded T cell clones that are potentially the antigen-specific clonotypes.
基金supported by grants from the National Natural Science Foundation of China(81972675 to Z.T.and 81930086 to B.S.).
文摘In a study published in Cellular&Molecular Immunology,we described a novel mechanism by which IL-33 drives hepatic fibrosis through the MAPK pathway.The study demonstrated that hepatocyte-derived IL-33 is elevated upon bile duct ligation(BDL)-induced liver injury and fibrogenesis and activates hepatic stellate cells in a JNK/ERK/p38-dependent manner.
文摘Fulminant hepatitis is fatal in most cases and timely liver transplantation is the only effective treatment.This study evaluates the survival outcomes of patients who underwent living-donor liver transplantation(LDLT)using right lobe liver grafts for fulminant liver failure due to hepatitis B infection.Nine cases of adult right lobe LDLT were performed in our department from September 2002 to August 2005 and the clinical and following-up data were reviewed.According to the pre-transplant Child-Pugh-Turcotte classification,the nine patients were classified as grade C.The model for end-stage liver disease(MELD)score of these patients ranged from 16 to 42.The principal complications before transplantation included abnormal renal function,hepatic coma of different degrees and alimentary tract hemorrhage.The main complications after transplantation included pulmonary infection in two cases,acute renal failure in three cases and transplantation-related encephalopathy in one case.No primary failure of vascular or biliary complications occurred.The one-year survival rate was 55.6%.There were no serious complications or deaths in donors.In general,it is extremely difficult to treat fulminant hepatitis by conservative regimen,particularly,in cases with rapid progression.Emergency adult living-donor liver transplantation is an effective treatment for fulminant hepatitis patients and is relatively safe for donors.
