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| 1 | Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis显示文摘Necroptosis 和 pyroptosis 是有血浆膜破裂的一个普通特征的规划房间死亡的二种形式。这里,我们与 necroptosis 比较学习了 pyroptosis 的形态学和机制。与 necroptosis 不同, pyroptosis 经历膜 blebbing 并且生产 apoptotic 在血浆膜以前的像身体的房间伸出(称为的 pyroptotic 身体) 破裂。在 necroptosis 的破裂是像爆炸的,而在 pyroptosis 它导致房间变平。necroptosis 的实行被混合的系 kinase 调停,这被知道像域(MLKL ) 在血浆膜的 oligomers,而 gasdermin-D (GSDMD ) 调停在它由 caspase-1 或 caspase-11 的劈开以后的 pyroptosis。我们显示出那 N 终端碎片 caspase 劈开产生的 GSDMD (GSDMD-N ) 也形成 oligomer 并且移居到血浆膜杀死房间。MLKL 和 GSDMD-N 是脂性的,两蛋白质的 N 终端序列为他们的 oligomerization 和血浆膜 translocation 是重要的。不同于在血浆膜上形成隧道的 MLKL,那导致渗透地胀大的选择离子的流入冲破的房间, GSDMD-N 形成非选择的毛孔并且不依靠增加的 osmolarity 破坏房间。我们的学习表明 GSDMD 的形成毛孔的活动和 MLKL 的形成隧道的活动在 pyroptosis 和 necroptosis 决定血浆膜破裂的不同方法。 | Xin Chen Wan-ting He Lichen Hu Jingxian Li Yuan Fang Xin Wang Xiaozheng Xu Zhuo Wang Kai Huang Jiahuai Han | 2016 | Cell Research2016，26，9： | 110 |
| 2 | Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage显示文摘Ischemic stroke and ischemia/reperfusion(I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species(ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier(BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine(TCM)has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases.In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica,and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage. | Kai Sun Jingyu Fan Jingyan Han | 2015 | Acta Pharmaceutica Sinica B2015，5，1： | 85 |
| 3 | Prognostic factors of refractory NSCLC patients receiving anlotinib hydrochloride as the third-or further-line treatment显示文摘Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified. | Jing Wang Yizhuo Zhao Qiming Wang Li Zhang Jianhua Shi Zhehai Wang Ying Cheng Jianxing He Yuankai Shi Hao Yu Yang Zhao Weiqiang Chen Yi Luo Xiuwen Wang Kejun Nan Faguang Jin Jian Dong Baolan Li Zhujun Liu Baohui Han Kai Li | 2018 | Cancer Biology & Medicine2018，15，4： | 46 |
| 4 | Maize-soybean strip intercropping: Achieved a balance between high productivity and sustainability显示文摘Intercropping is one of the most vital practice to improve land utilization rate in China that has limited arable land resource. However, the traditional intercropping systems have many disadvantages including illogical field lay-out of crops, low economic value, and labor deficiency, which cannot balance the crop production and agricultural sustainability. In view of this, we developed a novel soybean strip intercropping model using maize as the partner, the regular maize-soybean strip intercropping mainly popularized in northern China and maize-soybean relay-strip intercropping principally extended in southwestern China. Compared to the traditional maize-soybean intercropping systems, the main innovation of field lay-out style in our present intercropping systems is that the distance of two adjacent maize rows are shrunk as a narrow strip, and a strip called wide strip between two adjacent narrow strips is expanded reserving for the growth of two or three rows of soybean plants. The distance between outer rows of maize and soybean strips are expanded enough for light use efficiency improvement and tractors working in the soybean strips. Importantly, optimal cultivar screening and increase of plant density achieved a high yield of both the two crops in the intercropping systems and increased land equivalent ratio as high as 2.2. Annually alternative rotation of the adjacent maize-and soybean-strips increased the grain yield of next seasonal maize, improved the absorption of nitrogen, phosphorus, and potasium of maize, while prevented the continuous cropping obstacles. Extra soybean production was obtained without affecting maize yield in our strip intercropping systems, which balanced the high crop production and agricultural sustainability. | DU Jun-bo HAN Tian-fu GAI Jun-yi YONG Tai-wen SUN Xin WANG Xiao-chun YANG Feng LIU Jiang SHU Kai LIU Wei-guo YANG Wen-yu | 2018 | Journal of Integrative Agriculture2018，17，4： | 34 |
| 5 | Feeding of Riptortus pedestris on soybean plants, the primary cause of soybean staygreen syndrome in the Huang-Huai-Hai river basin显示文摘Staygreen syndrome or Zhengqing in soybean has recently become a major issue for Chinese growers in the Huang-Huai-Hai river basin.Although previous studies revealed that staygreen can be induced when pods/seeds are damaged, it is unknown whether virus infection or insect infestation causes staygreen.To determine whether viral infection causes staygreen, a survey of soybean staygreen incidence in the Huang-Huai-Hai river basin was conducted in 2016 and 2017.Diseased samples were collected and analyzed using DAS-ELISA for Soybean mosaic virus, Watermelon mosaic virus, Bean pod mottle virus, Cucumber mosaic virus, and Bean common mosaic virus.The survey showed that the severity of soybean staygreen syndrome was most prevalent in Beijing, Henan, Shaanxi, and some parts of Shandong provinces, with yield losses from 0 to nearly 100%, but only a small fraction of samples were positive for the tested viruses.A field cage experiment and an insecticide treatment field trial were conducted to determine the contribution of the bean bug, Riptortus pedestris, to staygreen incidence.The field cage experiment showed that R.pedestris treatment resulted in shorter plants, more empty pods, increased numbers of abnormal seeds, and decreased yields.The field experiment showed that there were fewer R.pedestris and less soybean staygreen incidence in fields treated with insecticide than in untreated control fields.Together, these results suggest that R.pedestris infestation rather than virus infection induces staygreen syndrome and that growers in this region can mitigate staygreen syndrome via bean bug control. | Kai Li Xinxin Zhang Jianqiu Guo Hannah Penn Tingting Wu Lin Li Hong Jiang Lidan Chang Cunxiang Wu Tianfu Han | 2019 | The Crop Journal2019，7，3： | 30 |
| 6 | Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery显示文摘AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation,such as diameters of arterioles and venules,velocity of RBCs in venules,leukocyte rolling,adhesion and emigration,free radicals released from post-capillary venules,FITC- albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile,the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils,and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation,including a significant increase in the positive region of venulestained with Monastral blue B,rolling and adhesion of leukocytes,production of oxygen radical in venular wall,albumin efflux and enhanced mast cell degranulation in vivo,all of which,except for the leukocyte rolling,were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils,and the expression of ICAM-1 in HUVECs were increased by exposure to LPS,and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance. | Jing-Yan Han Yoshinori Horie Soichiro Miura, Yasutada Akiba Jun Guo Dan Li Jing-Yu Fan Yu-Ying Liu Bai-He Hu Li-Hua An Xin Chang Man Xu De-An Guo Kai Sun Ji-Ying Yang Shu-Ping Fang Ming-Ji Xian Masahiro Kizaki Hiroshi Nagata Toshifumi Hibi | 2007 | World Journal of Gastroenterology2007，13，26： | 26 |
| 7 | An in vivo study with an MRI tracer method reveals the biophysical properties of interstitial fluid in the rat brain显示文摘The nature of brain interstitial fluid (ISF) has long been a subject of controversy. Most of the previous studies on brain ISF were carried out in vitro. In the present study, a novel method was developed to characterize ISF in the living rat brain by magnetic resonance (MR) imaging using gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) as a tracer. Sprague Dawley rats (n=8) were subjected to MR scanning before and after the introduction of Gd-DTPA into the caudate nucleus. A one-way drainage of brain ISF was demonstrated on the dynamic MR images. According to the traditional diffusion model, the diffusion and clearance rate constants of the tracer within brain extracellular space (ECS) were derived as (3.38±1.07)×10-4 mm 2 s-1 and (7.60±4.18)×10-5 s-1 . Both diffusion and bulk flow contributed to the drainage of ISF from the caudate nucleus, which demonstrated an ISF-cerebrospinal fluid confluence in the subarachnoid space at the lateral and ventral surface of the brain cortex at 3 h after the injection. By using this newly developed method, the brain ECS and ISF can be quantitatively measured simultaneously in the living brain, which will enhance the understanding of ISF and improve the efficiency of drug therapy via the brain interstitium. | HAN HongBin LI Kai YAN JunHao ZHU Kai FU Yu | 2012 | Science China(Life Sciences)2012，55，9： | 25 |
| 8 | Genome Engineering in Rice Using Cas9 Variants that Recognize NG PAM Sequences显示文摘CRISPR/Cas9 genome editing relies on sgRNA-target DNA base pairing and a short downstream PAM sequence to recognize target DNA. The strict protospacer adjacent motif (PAM) requirement hinders applications of the CRISPR/Cas9 system since it restricts the targetable sites in the genomes. xCas9 and SpCas9-NG are two recently engineered SpCas9 variants that can recognize more relaxed NG PAMs, implying a great potential in addressing the issue of PAM constraint. Here we use stable transgenic lines to evaluate the efficacies of xCas9 and SpCas9-NG in performing gene editing and base editing in rice. We found that xCas9 can efficiently induce mutations at target sites with NG and GAT PAM sequences in rice. However, base editors containing xCas9 failed to edit most of the tested target sites. SpCas9-NG exhibited a robust editing activity at sites with various NG PAMs without showing any preference for the third nucleotide after NG. Moreover, we showed that xCas9 and SpCas9-NG have higher specificity than SpCas9 at the CGG PAM site. We further demonstrated that different forms of cytosine or adenine base editors containing SpCas9-NG worked efficiently in rice with broadened PAM compatibility. Taken together, our work has yielded versatile genome-engineering tools that will significantly expand the target scope in rice and other crops. | Kai Hua Xiaoping Tao Peijin Han Rui Wang Jian-Kang Zhu | 2019 | Molecular Plant2019，12，7： | 22 |
| 9 | Left posterior fascicular block: a new endpoint of ablation for verapamil-sensitive idiopathic ventricular tachycardia显示文摘Background Verapamil-sensitive, idiopathic left ventricular tachycardia (ILVT) with right bundle branch block configuration and left-axis deviation is known to be due to re-entry mechanism but the exact nature of reentrant circuit in ILVT is not fully elucidated. Radiofrequency (RF) ablation was applied during ventricular tachycardia (VT) and termination of the VT or abolishing the inducibility of the tachycardia was used as an endpoint for successful RF. In this study, the left posterior fascicular block in surface electrocardiogram (ECG) was used as a new endpoint of ablation to cure ILVT. Methods Electrophysiological studies and radiofrequency ablation were performed in 39 consecutive patients [30 men, 9 women; age ranging from 10 to 64 years, mean (29±16) years] with verapamil-sensitive ILVT and structurally normal hearts. VT could be terminated by the intravenous administration of verapamil in all patients. The target site was the midseptum of LV where the earliest Purkinje potentials were recorded during VT. RF current was applied to the target site with or without late diastolic potential (LDP) during sinus rhythm in 37 patients and during VT in 2 patients to meet the ablation endpoint: the left posterior fascicular block in the surface ECG. Results Thirty-seven patients with ILVT had been treated by RF ablation during sinus rhythm and two had been treated during VT. All of them met the endpoint of the left posterior fascicular block. Thirty-eight cases were symptom-free without medications during the follow-up period (range from 3 to 95 months, median 17 months). One patient developed a clinical recurrence and the left posterior fascicular block in surface ECG disappeared. The patient received another treatment. The endpoint was met and the procedure was successful. Conclusions The left posterior fascicular block in surface ECG used as an endpoint of RF ablation to treat ILVT is effective. It is important especially in those patients whose VT can not be induced or the inducible condition is unstable. The effective endpoint implied that the left posterior fascicle might be a critical part of the re-entrant circuit. | MA Fu-sheng MA Jian TANG Kai HAN Hao JIAYu-he FANG Pi-hua CHU Jian-min PU Jie-lin ZHANG Shu | 2006 | Chinese Medical Journal2006，，5： | 21 |
| 10 | Identification of coastal wetlands of international importance for waterbirds:a review of China Coastal Waterbird Surveys 2005–2013显示文摘Background:China's coastal wetlands belong to some of the most threatened ecosystems worldwide.The loss and degradation of these wetlands seriously threaten waterbirds that depend on wetlands.Methods:The China Coastal Waterbird Census was organized by volunteer birdwatchers in China's coastal region.Waterbirds were surveyed synchronously once every month at 14 sites,as well as irregularly at a further 18 sites,between September 2005 and December 2013.Results:A total of 75 species of waterbirds met the 1 % population level Ramsar listing criterion at least once at one site.The number of birds of the following species accounted for over 20 % of the total flyway populations at a single site:Mute Swan(Cygnus olor),Siberia Crane(Grus leucogeranus),Far Eastern Oystercatcher(Haematopus osculans),Bar-tailed Godwit(Limosa lapponica),Spotted Greenshank(Tringa guttifer),Great Knot(Calidris tenuirostris),Spoon-billed Sandpiper(Calidris pygmeus),Saunders' s Gull(Larus saundersi),Relict Gull(Larus relictus),Great Cormorant(Phalacrocorax carbo),Eurasian Spoonbill(Platalea leucorodia),Black-faced Spoonbill(Platalea minor) and Dalmatian Pelican(Pelecanus crispus).A total of 26 sites supported at least one species of which their number met the1 % criterion.Forty-two species met the 1 % criterion in the Yellow River Delta,Shandong;29 at the Cangzhou coast,Hebei and 26 species at the Lianyungang coast,Jiangsu.Conclusions:The results highlight the international importance of China's coastal wetlands for waterbirds.This study also demonstrates that participation of local birdwatchers in waterbird surveys results in data that are invaluable not only for understanding the current status of waterbirds in China's coastal regions but also for waterbird conservation and management. | Qingquan Bai Jianzhong Chen Zhihong Chen Guotai Dong Jiangtian Dong Wenxiao Dong Vivian Wing Kan Fu Yongxiang Han Gang Lu Jing Li Yang Liu Zhi Lin Derong Meng Jonathan Martinez Guanghui Ni Kai Shan Renjie Sun Suixing Tian Fengqin Wang Zhiwei Xu Yat-tung Yu Jin Yang Zhidong Yang Lin Zhang Ming Zhang Xiangwu Zeng | 2015 | Chinese Birds2015，，3： | 20 |
| 11 | Hydrogen Peroxide-Mediated Growth of the Root System Occurs via Auxin Signaling Modification and Variations in the Expression of Cell-Cycle Genes in Rice Seedlings Exposed to Cadmium Stress显示文摘The link between root growth,H2O2,auxin signaling,and the cell cycle in cadmium (Cd)-stressed rice (Oryza sativa L.cv.Zhonghua No.11) was analyzed in this study.Exposure to Cd induced a significant accumulation of Cd,but caused a decrease in zinc (Zn) content which resulted from the decreased expression of OsHMA9 and OsZIP.Analysis using a Cd-specific probe showed that Cd was mainly localized in the meristematic zone and vascular tissues.Formation and elongation of the root system were significantly promoted by 3-amino-1,2,4-triazole (AT),but were markedly inhibited by N,N'dimethylthiourea (DMTU) under Cd stress.The effect of H2O2 on Cd-stressed root growth was further confirmed by examining a gain-of-function rice mutant (carrying catalase1 and glutathione-S-transferase) in the presence or absence of diphenylene iodonium.DR5-GUS staining revealed close associations between H2O2 and the concentration and distribution of auxin.H2O2 affected the expression of key genes,including OsYUCCA,OsPIN,OsARF,and OsIAA,in the auxin signaling pathway in Cd-treated plants.These results suggest that H2O2 functions upstream of the auxin signaling pathway.Furthermore,H2O2 modified the expression of cell-cycle genes in Cd-treated roots.The effects of H2O2 on root system growth are therefore linked to auxin signal modification and to variations in the expression of cell-cycle genes in Cd-stressed rice.A working model for the effects of H2O2 on Cd-stressed root system growth is thus proposed and discussed in this paper. | Feng-Yun Zhao Ming-Ming Han Shi-Yong Zhang Kai Wang Cheng-Ren Zhang Tao Liu Wen Liu | 2012 | Journal of Integrative Plant Biology2012，54，12： | 18 |
| 12 | Suppression of m6A reader Ythdf2 promotes hematopoietic stem cell expansion显示文摘 | Zhenrui Li Pengxu Qian Wanqing Shao Hailing Shi Xi C. He Madelaine Gogol Zulin Yu Yongfu Wang Meijie Qi Yunfei Zhu John M. Perry Kai Zhang Fang Tao Kun Zhou Deqing Hu Yingli Han Chongbei Zhao Richard Alexander Hanzhang Xu Shiyuan Chen Allison Peak Kathyrn Hall Michael Peterson Anoja Perera Jeffrey S. Haug Tari Parmely Hua Li Bin Shen Julia Zeitlinger Chuan He Linheng Li | 2018 | Cell Research2018，28，9： | 18 |
| 13 | Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion显示文摘AIM: To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion (I/R) in mice.METHODS: The superior mesenteric artery (SMA) of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-min reperfusion. In another set of experiments, R1 was continuously infused (10 mg/kg per hour) from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell (RBC) velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate transaminase (AST) in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in plasma were evaluated by flow cytometry. E-selectin and intercellular adhesion molecule-1 (ICAM-1) in hepatic tissue were examined by immunofluorescence. RESULTS: After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1.CONCLUSION: R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury. The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils. | Wei-Xing Chen Fang Wang, Yu-Ying Liu, Qing-Jiang Zeng, Kai Sun, Xin Xue, Xiang Li, Ji-Ying Yang, Li-Hua An,Bai-He Hu, Jin-Hui Yang, Chuan-She Wang, Zhi-Xin Li, Lian-Yi Liu, Yan Li, Jun Zheng, Fu-Long Liao, Dong Han,Jing-Yu Fan, Jing-Yan Han Fang Wang Yu-Ying Liu Qing-Jiang Zeng Kai Sun Xin Xue Xiang Li Ji-Ying Yang Li-Hua An Bai-He Hu Jin-Hui Yang Chuan-She Wang Zhi-Xin Li Lian-Yi Liu Yan Li Jun Zheng Fu-Long Liao Dong Han Jing-Yu Fan Jing-Yan Han | 2008 | World Journal of Gastroenterology2008，14，1： | 17 |
| 14 | A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Study of the Effects of Tongxinluo Capsules in Acute Coronary Syndrome Patients with High On-Treatment Platelet Reactivity显示文摘 | Lei Zhang Yi Li Bai-Song Yang Lu Li Xiao-Zeng Wang Mei-Ling Ge Quan-Min Jing Ying-Yan Ma Geng Wang Hai-Wei Liu Xin Zhao Bin Wang Kai Xu Ya-Ling Han | 2018 | Chinese Medical Journal2018，，5： | 16 |
| 15 | BH3-only proteins target BCL-xL/MCL-1,not BAX/BAK,to initiate apoptosis显示文摘It has been widely accepted that mitochondria-dependent apoptosis initiates when select BH3-only proteins(BID,BIM,etc.)directly engage and allosterically activate effector proteins BAX/BAK.Here,through reconstitution of cells lacking all eight pro-apoptotic BH3-only proteins,we demonstrate that all BH3-only proteins primarily target the anti-apoptotic BCL-2 proteins BCL-xL/MCL-1,whose simultaneous suppression enables membrane-mediated spontaneous activation of BAX/BAK.BH3-only proteins*apoptotic activities correlate with affinities for BCL-xL/MCL1 instead of abilities to directly activate BAX/BAK.Further,BID and BIM do not distinguish BAX from BAK or accelerate BAX/BAK activation following inactivation of BCL-xL/MCL-1.Remarkably,death ligandinduced apoptosis in cells lacking BH3-only proteins and MCL-1 is fully restored by BID mutants capable of neutralizing BCL-xL,but not direct activation of BAX/BAK.Taken together,our findings provide a'Membrane-mediated Permissive'model,in which the BH3-only proteins only indirectly activate BAX/BAK by neutralizing the anti-apoptotic BCL-2 proteins,and thus allowing BAX/BAK to undergo unimpeded,spontaneous activation in the mitochondrial outer membrane milieu,leading to apoptosis initiation. | Kai Huang Katelyn L.O'Neill Jian Li Wei Zhou Na Han Xiaming Pang Wei Wu Lucas Struble Gloria Borgstahl Zhaorui Liu Liqiana Zhang Xu Luo | 2019 | Cell Research2019，29，11： | 16 |
| 16 | Ethnopharmacology, Phytochemistry, Pharmacology, Toxicology and Clinical Applications of Radix Astragali显示文摘Radix Astragali(RA),a traditional Chinese medicine from the dried root of Astragalus species,is widely distributed throughout the temperate regions of the world.The major bioactive constituents of RA are triterpene glycosides,flavonoids,saponins,and alkaloids,and these compounds mostly exert pharmacological activities on the cardiovascular,immune,respiratory,and hepatic systems.This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources,ethnopharmacology,phytochemistry,pharmacology,toxicology,clinical application,and patent release of RA.We hope this review can provide a guidance for further development of therapeutic agents from RA. | ZHANG Chun-hong YANG Xiao WEI Jing-ran CHEN Na-mu-han XU Jian-ping BI Ya-qiong YANG Min GONG Xue LI Zi-yan REN Kai HAN Qi-heng ZHANG Lei LI Xue JI Ming-yue WANG Cong-cong LI Min-hui | 2021 | Chinese Journal of Integrative Medicine2021，27，3： | 16 |
| 17 | Total salvianolic acid improves ischemia-reperfusion-induced microcirculatory disturbance in rat mesentery显示文摘AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 each):Sham group and I/R group(infused with saline),TSA group,TSA + I/R group and I/R + TSA group(infused with TSA,5 mg/kg per hour).Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein(10 min) and subsequent release of the occlusion.TSA was continuously infused either starting from 10 min before the ischemia or 10 min after reperfusion.Changes in mesenteric microcirculatory variables,including diameter of venule,velocity of red blood cells in venule,leukocyte adhesion,free radicals released from venule,albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope.Meanwhile,the expression of adhesion molecules CD11b/CD18 on neutrophils was evaluated by flow cytometry.Ultrastructural evidence of mesenteric venules damage was assessed after microcirculation observation.RESULTS:I/R led to multiple responses in mesenteric post-capillary venules,including a significant increase in the adhesion of leukocytes,production of oxygen radicals in the venular wall,albumin efflux and enhanced mast cell degranulation in vivo.All the I/R-induced manifestations were significantly reduced by pre-or post-treatment with TSA,with the exception that the I/R-induced increase in mast cell degranulation was inhibited only by pre-treatment with TSA.Moreover,preor post-treatment with TSA significantly attenuated the expression of CD11b/CD18 on neutrophils,reducing the increase in the number of caveolae in the endothelial cells of mesentery post-capillary venules induced by I/R.CONCLUSION:The results demonstrated that TSA protects from and ameliorates the microcirculation disturbance induced by I/R,which was associated with TSA inhibiting the production of oxygen-free radicals in the venular wall and the expression of CD11b/CD18 on neutrophils. | Ming-Xia Wang Yu-Ying Liu Bai-He Hu Xiao-Hong Wei Xin Chang Kai Sun Jing-Yu Fan Fu-Long Liao ChuanShe Wang Jun Zheng Jing-Yan Han Ming-Xia Wang | 2010 | World Journal of Gastroenterology2010，16，42： | 15 |
| 18 | Establishment and preliminery use of hepatitis Bvirus preS1/2 antigen assay显示文摘 | CHEN Kun, HAN Bao Guang, MA Xian Kai, ZHANG He Qiu, MENG Li, WANG Guo Hua, XIA Fang, SONG Xiao Guo and LING Shi Gan | 1999 | World Journal of Gastroenterology1999，5，6： | 14 |
| 19 | Eleven COVID-19 Outbreaks with Local Transmissions Caused by the Imported SARS-CoV-2 Delta VOC-China,July-August,2021显示文摘Starting from December 2019,Wuhan,China,encountered the first outbreak of coronavirus disease 2019(COVID-19)(1-2).The epidemic was successfully suppressed by strict containment so that the number of infected people was reduced to 0 on April 8,2020(3–4).After that,China experienced roughly 3 dozen outbreaks with local transmission caused by imported severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). | Lei Zhou Kai Nie Hongting Zhao Xiang Zhao Bixiong Ye Ji Wang Cao Chen Hong Wang Jiangli Di Jinsong Li Chao Li Zhixiao Chen Ruiqi Ren Peihua Niu Hui Chen Tao Chen Yali Wang Lili Li Bingxue Han Ruhan A Si Chen Dan Li Dan Li Chunxia Jin Xin Zhang Jiangmei Liu Chunyu Xu Yecheng Yao Yenan Feng Zhili Li Bike Zhang Yang Song Peter Hao Yanping Zhang Hao Li Qun Li George F.Gao Guoqing Shi Wenbo Xu | 2021 | China CDC weekly2021，3，41： | 13 |
| 20 | Piglets cloned from induced pluripotent stem cells显示文摘 | Nana Fan Jijun Chen Zhouchun Shang Hongwei Dou Guangzhen Ji Qingjian Zou Lu Wu Lixiazi He Fang Wang Kai Liu Na Liu Jianyong Han Qi Zhou Dengke Pan Dongshan Yang Bentian Zhao Zhen Ouyang Zhaoming Liu Yu Zhao Lin Lin Chongming Zhong Quanlei Wang Shouqi Wang Ying Xu Jing Luan Yu Liang Zhenzhen Yang Jing Li Chunxia Lu Gabor Vajta Ziyi Li Hongsheng Ouyang Huayan Wang Yong Wang Yang Yang Zhonghua Liu Hong Wei Zhidong Luan Miguel A Esteban Hongkui Deng Huanming Yang Duanqing Pei Ning Li Gang Pei Lin Liu Yutao Du Lei Xiao Liangxue Lai | 2013 | Cell Research2013，23，1： | 12 |
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