Regulatory T(T_(reg))cells play an essential role in maintaining immune balance across various physiological and pathological conditions.However,the mechanisms underlying T_(reg)homeostasis remain incompletely underst...Regulatory T(T_(reg))cells play an essential role in maintaining immune balance across various physiological and pathological conditions.However,the mechanisms underlying T_(reg)homeostasis remain incompletely understood.Here,we report that RIPK1 is crucial for T_(reg) cell survival and homeostasis.We generated mice with T_(reg) cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell death.Unlike conventional T cells,Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis.However,simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death pathways.Thus,our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis,thereby providing novel insights into the mechanisms of Treg cell homeostasis.展开更多
Approaches for controlling inflammatory responses and reducing the mortality rate of septic patients remain clinically ineffective; new drugs need to be identified that can induce anti-inflammatory responses. Ephedrin...Approaches for controlling inflammatory responses and reducing the mortality rate of septic patients remain clinically ineffective; new drugs need to be identified that can induce anti-inflammatory responses. Ephedrine hydrochloride （EH） is a compound that is widely used in cardiovascular diseases, especially to treat hypotension caused by either anesthesia or overdose of antihypertensive drugs. In this study, we reported that EH also plays an important role in the control of the inflammatory response. EH increased IL-IO and decreased proinflammatory cytokine （IL-6, tumor-necrosis factor （TNF）-a, IL-12 and IL-11~） expression in primary peritoneal macrophages and Raw264.7 cells treated with peptidoglycan （PGN）, a Gram-positive cell wall component. The anti-inflammatory role of EH was also demonstrated in an experimental mouse model of peritonitis induced by intraperitoneal PGN injection. The phosphatidylinositol 3-kinase （PI3K）/Akt pathway was found to be responsible for the EH-mediated increase in IL-IO production and decrease in IL-6 expression. Therefore, our results illustrated that EH can help maintain immune equilibrium and diminish host damage by balancing the production of pro- and anti-inflammatory cytokines after PGN challenge. EH may be a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection.展开更多
Recently,the global existence of weak solutions to the compressible Navier-Stokes equations with vacuum has attracted much attention.In this paper,we study the one-dimension isentropic Navier-Stokes equations with gra...Recently,the global existence of weak solutions to the compressible Navier-Stokes equations with vacuum has attracted much attention.In this paper,we study the one-dimension isentropic Navier-Stokes equations with gravitational force and fixed boundary condition when the density connects with vacuum discontinuously.We prove the global existence and the uniqueness of weak solution,requiring less regularity of the initial data.展开更多
Objective Tumor sprouting can reflect independent risk factors for tumor malignancy and a poor clinical progno-sis.However,there are significant differences and difficulties associated with manually identifying tumor ...Objective Tumor sprouting can reflect independent risk factors for tumor malignancy and a poor clinical progno-sis.However,there are significant differences and difficulties associated with manually identifying tumor sprout-ing.This study used the Faster region convolutional neural network(RCNN)model to build a colorectal cancer tumor sprouting artificial intelligence recognition framework based on pathological sections to automatically identify the budding area to assist in the clinical diagnosis and treatment of colorectal cancer.Methods We retrospectively collected 100 surgical pathological sections of colorectal cancer from January 2019 to October 2019.The pathologists used LabelImg software to identify tumor buds and to count their numbers.Finally,1,000 images were screened,and the total number of tumor buds was approximately 3,226;the images were randomly divided into a training set and a test set at a ratio of 6:4.After the images in the training set were manually identified,the identified buds in the 600 images were used to train the Faster RCNN identification model.After the establishment of the artificial intelligence identification detection platform,400 images in the test set were used to test the identification detection system to identify and predict the area and number of tumor buds.Finally,by comparing the results of the Faster RCNN system and the identification information of pathologists,the performance of the artificial intelligence automatic detection platform was evaluated to determine the area and number of tumor sprouting in the pathological sections of the colorectal cancers to achieve an auxiliary diagnosis and to suggest appropriate treatment.The selected performance indicators include accuracy,precision,specificity,etc.ROC(receiver operator characteristic)and AUC(area under the curve)were used to quantify the performance of the system to automatically identify tumor budding areas and numbers.Results The AUC of the receiver operating characteristic curve of the artificial intelligence de展开更多
基金supported by the following grants:National Key Research and Development Program of China(2021YFA1301402)Shanghai Municipal Science and Technology Major Project(ZD2021CY001)+4 种基金National Key Research and Development Program of China(2021YFE0200900,2022YFA0807300)National Natural Science Foundation of China(82101833,82073901)Three-year Action Plan for Shanghai TCM Development and Inheritance Program[ZY(2021-2023)-0103]Top-level Clinical Discipline Project of Shanghai Pudong District(grant/award number:PWYgf 2021-01)Training Plan for Discipline Leaders of Shanghai Pudong New Area Health Commission(grant/award number:PWRd2020-09).
文摘Regulatory T(T_(reg))cells play an essential role in maintaining immune balance across various physiological and pathological conditions.However,the mechanisms underlying T_(reg)homeostasis remain incompletely understood.Here,we report that RIPK1 is crucial for T_(reg) cell survival and homeostasis.We generated mice with T_(reg) cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell death.Unlike conventional T cells,Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis.However,simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death pathways.Thus,our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis,thereby providing novel insights into the mechanisms of Treg cell homeostasis.
基金This work was supported by grants from the National Key Basic Research Program of China （2010CB529901 and 2010CB530600）, the National Natural Science Foundation of China （31100619 and 30972705）, the China Postdoctoral Science Foundation （20110490186）, the Chen-guang Plan Project of Shanghai Educational Municipal Education Commission （11CG48 and szyl0004）, the Specialized Research Fund for the Doctoral Program of Higher Education （20113107120014） and the Leading Academic Discipline Project of Shanghai Municipal Education Commission （J50301） （Yuejuan Zheng, Shanghai University of T.C.M）.
文摘Approaches for controlling inflammatory responses and reducing the mortality rate of septic patients remain clinically ineffective; new drugs need to be identified that can induce anti-inflammatory responses. Ephedrine hydrochloride （EH） is a compound that is widely used in cardiovascular diseases, especially to treat hypotension caused by either anesthesia or overdose of antihypertensive drugs. In this study, we reported that EH also plays an important role in the control of the inflammatory response. EH increased IL-IO and decreased proinflammatory cytokine （IL-6, tumor-necrosis factor （TNF）-a, IL-12 and IL-11~） expression in primary peritoneal macrophages and Raw264.7 cells treated with peptidoglycan （PGN）, a Gram-positive cell wall component. The anti-inflammatory role of EH was also demonstrated in an experimental mouse model of peritonitis induced by intraperitoneal PGN injection. The phosphatidylinositol 3-kinase （PI3K）/Akt pathway was found to be responsible for the EH-mediated increase in IL-IO production and decrease in IL-6 expression. Therefore, our results illustrated that EH can help maintain immune equilibrium and diminish host damage by balancing the production of pro- and anti-inflammatory cytokines after PGN challenge. EH may be a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection.
文摘Recently,the global existence of weak solutions to the compressible Navier-Stokes equations with vacuum has attracted much attention.In this paper,we study the one-dimension isentropic Navier-Stokes equations with gravitational force and fixed boundary condition when the density connects with vacuum discontinuously.We prove the global existence and the uniqueness of weak solution,requiring less regularity of the initial data.
基金National Natural Science Foun-dation of China Youth Project(Grant No.81802473)Shandong Nat-ural Science Foundation of China(Grant No.ZR201910310332).
文摘Objective Tumor sprouting can reflect independent risk factors for tumor malignancy and a poor clinical progno-sis.However,there are significant differences and difficulties associated with manually identifying tumor sprout-ing.This study used the Faster region convolutional neural network(RCNN)model to build a colorectal cancer tumor sprouting artificial intelligence recognition framework based on pathological sections to automatically identify the budding area to assist in the clinical diagnosis and treatment of colorectal cancer.Methods We retrospectively collected 100 surgical pathological sections of colorectal cancer from January 2019 to October 2019.The pathologists used LabelImg software to identify tumor buds and to count their numbers.Finally,1,000 images were screened,and the total number of tumor buds was approximately 3,226;the images were randomly divided into a training set and a test set at a ratio of 6:4.After the images in the training set were manually identified,the identified buds in the 600 images were used to train the Faster RCNN identification model.After the establishment of the artificial intelligence identification detection platform,400 images in the test set were used to test the identification detection system to identify and predict the area and number of tumor buds.Finally,by comparing the results of the Faster RCNN system and the identification information of pathologists,the performance of the artificial intelligence automatic detection platform was evaluated to determine the area and number of tumor sprouting in the pathological sections of the colorectal cancers to achieve an auxiliary diagnosis and to suggest appropriate treatment.The selected performance indicators include accuracy,precision,specificity,etc.ROC(receiver operator characteristic)and AUC(area under the curve)were used to quantify the performance of the system to automatically identify tumor budding areas and numbers.Results The AUC of the receiver operating characteristic curve of the artificial intelligence de
