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1MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2显示文摘新兴的证据与肿瘤开发和前进显示出异常地表示的 microRNAs (miRNAs ) 的协会。然而,很少在胃的 carcinogenesis 对 miRNAs 的潜在的角色被知道。这里,我们执行了 miRNA microarray 屏蔽在配对的胃的癌症和他们的邻近的 nontumor 纸巾表示并且发现 miR-375 是的 miRNAs 差别极大地在胃的癌症纸巾的 downregulated。量的即时 PCR 分析证实那 miR-375 表情显著地从经历胃的切除术的病人与他们的 nontumor 对应物相比在超过 90% 主要胃的癌症被减少。miR-375 的 Overexpression 显著地在 vitro 并且在 vivo 禁止了胃的癌症房间增长。在胃的癌症房间的 miR-375 的强迫的表示显著地减少了 Janus kinase 的蛋白质水平 2 ( JAK2 )并且镇压带 JAK2 的 3 鈥? untranslated 区域的一个酶记者的活动,被预言的 miR-375-binding 地点的变化废除,显示那 JAK2 可以是 miR-375 目标基因。由由 RNAi 的 JAK2 的 AG490 或 silencing 的 JAK2 活动的任何一个抑制压制了类似于 miR-375 overexpression 的胃的癌症房间增长。而且, JAK2 的宫外的表示能部分颠倒 miR-375 引起的房间增长的抑制。最后,我们在胃的癌症发现了在 miR-375 表示和 JAK2 蛋白质水平之间的重要反的关联。因此,这些数据建议 miR-375 可以作为肿瘤 suppressor 工作由指向 JAK2 oncogene 潜在地调整胃的癌症房间增长,含有在胃的癌症的致病的 miR-375 的一个角色。Ling Ding Yanjun Xu Wei Zhang Yujie Deng Misi Si Ying Du Haomi Yao Xuyan Liu Yuehai Ke Jianmin Si Tianhua Zhou 2010Cell Research2010,20,7:59
2Infection with novel coronavirus(SARS-CoV-2)causes pneumonia in Rhesus macaques显示文摘The 2019 novel coronavirus(SARS-CoV-2)outbreak is a major challenge for public health.SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases,with a mortality rate of^6.4%worldwide(based on World Health Organization daily situation report).However,the dynamics of viral infection,replication and shedding are poorly understood.Here,we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2.After intratracheal inoculation,the first peak of viral RNA was observed in oropharyngeal swabs one day post infection(1 d.p.i.),mainly from the input of the inoculation,while the second peak occurred at 5 d.p.i.,which reflected on-site replication in the respiratory tract.Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals,characterized by hyperemia and edema,and infiltration of monocytes and lymphocytes in alveoli.We also identified SARS-CoV-2 RNA in respiratory tract tissues,including trachea,bronchus and lung;and viruses were also re-isolated from oropharyngeal swabs,bronchus and lung,respectively.Furthermore,we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2.The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.Chao Shan Yan-Feng Yao Xing-Lou Yang Yi-Wu Zhou Ge Gao Yun Peng Lian Yang Xue Hu Jin Xiong Ren-Di Jiang Hua-Jun Zhang Xiao-Xiao Gao Cheng Peng Juan Min Ying Chen Hao-Rui Si Jia Wu Peng Zhou Yan-Yi Wang Hong-Ping Wei Wei Pang Zheng-Fei Hu Long-Bao Lv Yong-Tang Zheng Zheng-Li Shi Zhi-Ming Yuan 2020Cell Research2020,30,8:19
3Prognosis-related classifi cation and dynamic monitoring of immune status in patients with sepsis:A prospective observational study显示文摘BACKGROUND:The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis.In this study,we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value.METHODS:A prospective observational study was carried out in Zhongshan Hospital,Fudan University,enrolling septic patients admitted between July 2016 and December 2018.Blood samples were collected at days 1 and 3.Serum cytokine levels(e.g.,tumor necrosis factor-α[TNF-α],interleukin-10[IL-10])and CD14+monocyte human leukocyte antigen-D-related(HLA-DR)expression were measured to serve as immune markers.Classifi cation of each immune status,namely systemic inflammatory response syndrome(SIRS),compensatory anti-inflammatory response syndrome(CARS),and mixed antagonistic response syndrome(MARS),was defined based on levels of immune markers.Changes of immune status were classifi ed into four groups which were stabilization(SB),deterioration(DT),remission(RM),and non-remission(NR).RESULTS:A total of 174 septic patients were enrolled including 50 non-survivors.Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors.Patients with MARS had the highest mortality rate.Immune status of 46.1%patients changed from day 1 to day 3.Among four groups of immune status changes,DT had the highest mortality rate,followed by NR,RM,and SB with mortality rates of 64.7%,42.9%,and 11.2%,respectively.CONCLUSIONS:Severe immune disorder defi ned as MARS or deterioration of immune status defi ned as DT lead to the worst outcomes.The preliminary model of the classifi cation and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.Jun Yin Yao Chen Jun-ling Huang Lei Yan Zhong-shu Kuang Ming-ming Xue Si Sun Hao Xiang Yan-yan Hu Zhi-min Dong Chao-yang Tong Chun-xue Bai Zhen-ju Song 2021World Journal of Emergency Medicine2021,12,3:16
4Highly Stretchable,Elastic,and Sensitive MXene-Based Hydrogel for Flexible Strain and Pressure Sensors显示文摘Electronic skin is driving the next generation of cutting-edge wearable electronic products due to its good wearability and high accuracy of information acquisition.However,it remains a challenge to fulfill the requirements on detecting full-range human activities with existing flexible strain sensors.Herein,highly stretchable,sensitive,and multifunctional flexible strain sensors based on MXene-(Ti_(3)C_(2)T_(x)-)composited poly(vinyl alcohol)/polyvinyl pyrrolidone double-network hydrogels were prepared.The uniformly distributed hydrophilic MXene nanosheets formed a three-dimensional conductive network throughout the hydrogel,endowing the flexible sensor with high sensitivity.The strong interaction between the double-network hydrogel matrix and MXene greatly improved the mechanical properties of the hydrogels.The resulting nanocomposited hydrogels featured great tensile performance(2400%),toughness,and resilience.Particularly,the as-prepared flexible pressure sensor revealed ultrahigh sensitivity(10.75 kPa^(-1))with a wide response range(0-61.5 kPa),fast response(33.5 ms),and low limit of detection(0.87 Pa).Moreover,the hydrogel-based flexible sensors,with high sensitivity and durability,could be employed to monitor fullrange human motions and assembled into some aligned devices for subtle pressure detection,providing enormous potential in facial expression and phonation recognition,handwriting verification,healthy diagnosis,and wearable electronics.Yao Lu Xinyu Qu Wen Zhao Yanfang Ren Weili Si Wenjun Wang Qian Wang Wei Huang Xiaochen Dong 2020Research2020,,1:14
5Eleven 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 2021China CDC weekly2021,3,41:13
6Carbon pools and fluxes in the China Seas and adjacent oceans显示文摘The China Seas include the South China Sea, East China Sea, Yellow Sea, and Bohai Sea. Located off the Northwestern Pacific margin, covering 4700000 km^2 from tropical to northern temperate zones, and including a variety of continental margins/basins and depths, the China Seas provide typical cases for carbon budget studies. The South China Sea being a deep basin and part of the Western Pacific Warm Pool is characterized by oceanic features; the East China Sea with a wide continental shelf, enormous terrestrial discharges and open margins to the West Pacific, is featured by strong cross-shelf materials transport; the Yellow Sea is featured by the confluence of cold and warm waters; and the Bohai Sea is a shallow semiclosed gulf with strong impacts of human activities. Three large rivers, the Yangtze River, Yellow River, and Pearl River, flow into the East China Sea, the Bohai Sea, and the South China Sea, respectively. The Kuroshio Current at the outer margin of the Chinese continental shelf is one of the two major western boundary currents of the world oceans and its strength and position directly affect the regional climate of China. These characteristics make the China Seas a typical case of marginal seas to study carbon storage and fluxes. This paper systematically analyzes the literature data on the carbon pools and fluxes of the Bohai Sea,Yellow Sea, East China Sea, and South China Sea, including different interfaces(land-sea, sea-air, sediment-water, and marginal sea-open ocean) and different ecosystems(mangroves, wetland, seagrass beds, macroalgae mariculture, coral reefs, euphotic zones, and water column). Among the four seas, the Bohai Sea and South China Sea are acting as CO_2 sources, releasing about0.22 and 13.86–33.60 Tg C yr^(-1) into the atmosphere, respectively, whereas the Yellow Sea and East China Sea are acting as carbon sinks, absorbing about 1.15 and 6.92–23.30 Tg C yr^(-1) of atmospheric CO_2, respectively. Overall, if only the CO_2 exchange at the sea-air interface is considered, the Chinese marginal seas appear to be a source of atmospheric CO_2, with a net release of 6.01–9.33 Tg C yr^(-1), mainly from the inputs of rivers and adjacent oceans. The riverine dissolved inorganic carbon (DIC) input into the Bohai Sea and Yellow Sea, East China Sea, and South China Sea are 5.04, 14.60, and 40.14 Tg C yr^(-1),respectively. The DIC input from adjacent oceans is as high as 144.81 Tg C yr^(-1), significantly exceeding the carbon released from the seas to the atmosphere. In terms of output, the depositional fluxes of organic carbon in the Bohai Sea, Yellow Sea, East China Sea, and South China Sea are 2.00, 3.60, 7.40, and 5.92 Tg C yr^(-1), respectively. The fluxes of organic carbon from the East China Sea and South China Sea to the adjacent oceans are 15.25–36.70 and 43.93 Tg C yr^(-1), respectively. The annual carbon storage of mangroves, wetlands, and seagrass in Chinese coastal waters is 0.36–1.75 Tg C yr^(-1), with a dissolved organic carbon(DOC) output from seagrass beds of up to 0.59 Tg C yr^(-1). Removable organic carbon flux by Chinese macroalgae mariculture account for 0.68 Tg C yr^(-1) and the associated POC depositional and DOC releasing fluxes are 0.14 and 0.82 Tg C yr^(-1), respectively. Thus, in total, the annual output of organic carbon, which is mainly DOC, in the China Seas is 81.72–104.56 Tg C yr^(-1). The DOC efflux from the East China Sea to the adjacent oceans is 15.00–35.00 Tg C yr^(-1). The DOC efflux from the South China Sea is 31.39 Tg C yr^(-1). Although the marginal China Seas seem to be a source of atmospheric CO_2 based on the CO_2 flux at the sea-air interface, the combined effects of the riverine input in the area, oceanic input, depositional export,and microbial carbon pump(DOC conversion and output) indicate that the China Seas represent an important carbon storage area.Nianzhi JIAO Yantao LIANG Yongyu ZHANG Jihua LIU Yao ZHANG Rui ZHANG Meixun ZHAO Minhan DAI Weidong ZHAI Kunshan GAO Jinming SONG Dongliang YUAN Chao LI Guanghui LIN Xiaoping HUANG Hongqiang YAN Limin HU Zenghu ZHANG Long WANG Chunjie CAO Yawei LUO Tingwei LUO Nannan WANG Hongyue DANG Dongxiao WANG Si ZHANG 2018Science China Earth Sciences2018,61,11:12
7Drag reduction in ultrahydrophobic channels with micro-nano structured surfaces显示文摘A series of experiments have been performed to demonstrate the significant drag reduction of the laminar flow in the ultrahydrophobic channels with dual-scale micro-nano structured surfaces.However,in previous experiments,the ultrahydrophobic surfaces were fabricated with micro-structures or nano-structures and the channels were on the microscale.For the drag reduction in macro-scale channels few reports are available.Here a new method was developed to fabricate ultrahydrophobic surfaces with micro-nano hierarchical structures made from carbon nanotubes.The drag reductions up to 36.3% were observed in the macro-channels with ultrahydrophobic surfaces.The micro-PIV was used to measure the flow velocity in channels.Compared with the traditional no-slip theory at walls,a significant slip velocity was observed on the ultrahydrophobic surfaces.LU Si,YAO ZhaoHui *,HAO PengFei & FU ChengSong School of Aerospace,Tsinghua University,Beijing 100084,China 2010Science China(Physics,Mechanics & Astronomy)2010,53,7:11
8Spatial and temporal dynamics of phytoplankton and bacterioplankton biomass in Sanya Bay, northern South China Sea显示文摘The composition of phytoplankton and the dynamics of phytoplankton and bacterioplankton biomass (PB and BB, respectively) of Sanya Bay, South China Sea, were determined. A total of 168 species (67 genera) phytoplankton were identified, including Bacillariophyta (diatom, 128 species), Pyrrophyta (35 species), Cyanophyta (3 species), and Chrysophyta (2 species). Annual average abundance of phytoplankton was 1.2 × 107 cells/m3, with the highest abundance in autumn, and the lowest in summer. Annual average diversity index (H ) and evenness (J) values were 3.96 and 0.70, respectively. Average chlorophyll-a was 2.5 mg/m3, and the average PB was 124 mg C/m3, with the highest value in autumn. Surface PB was higher than the bottom, except for summer. Annual mean bacterioplankton abundance and BB were 6.9 × 1011 cells/m3 and 13.8 mg C/m3, respectively. The highest BB was found in summer, followed by winter, spring, and autumn. Surface BB was higher than bottom all year round. The spatial distribution patterns of PB and BB were very similar with the highest biomass in the estuary, and decreased seaward, primarily due to the terrestrial input from the Sanya River and influx of oceanic water. The main factor influencing PB and BB was dissolved inorganic nitrogen (DIN). Other factors such as temperature, which is above 22°C throughout the year, had a negligible impact. The correlation between BB and PB was significant (P < 0.01). The annual average ratio of BB/PB was 0.12 (0.06-0.15). Phytoplankton primary production was one of the most important factors in controlling the distribution of bacterioplankton.ZHOU Weihua 2009Journal of Environmental Sciences2009,21,5:11
9Enhanced Poly(ethylene terephthalate)Hydrolase Activity by Protein Engineering显示文摘Poly(ethylene terephthalate)hydrolase(PETase)from Ideonella sakaiensis exhibits a strong ability to degrade poly(ethylene terephthalate)(PET)at room temperature,and is thus regarded as a potential tool to solve the issue of polyester plastic pollution.Therefore,we explored the interaction between PETase and the substrate(a dimer of the PET monomer ethylene terephthalate,2PET),using a model of PETase and its substrate.In this study,we focused on six key residues around the substrate-binding groove in order to create novel high-efficiency PETase mutants through protein engineering.These PETase mutants were designed and tested.The enzymatic activities of the R61A,L88F,and I179F mutants,which were obtained with a rapid cell-free screening system,exhibited 1.4 fold,2.1 fold,and 2.5 fold increases,respectively,in comparison with wild-type PETase.The I179F mutant showed the highest activity,with the degradation rate of a PET film reaching 22.5 mg perμmol·L^-1 PETase per day.Thus,this study has created enhanced artificial PETase enzymes through the rational protein engineering of key hydrophobic sites,and has further illustrated the potential of biodegradable plastics.Yuan Ma Mingdong Yao Bingzhi Li Mingzhu Ding Bo He Si Chen Xiao Zhou Yingjin Yuan 2018Engineering2018,4,6:10
10SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer显示文摘SIRT7,a sirtuin family member implicated in aging and disease,is a regulator of metabolism and stress responses.It remains elusive how human somatic stem cell populations might be impacted by SIRT7.Here,we found that SIRT7 expression declines during human mesenchymal stem cell(hMSC)aging and that SIRT7 deficiency accelerates senescence.Mechanistically,SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins,thus maintaining the repressive state of heterochromatin at nuclear periphery.Accordingly,deficiency of SIRT7 results in loss of heterochromatin,derepression of the LINE1 retrotransposon(LINE1),and activation of innate immune signaling via the cGAS-STING pathway.These agingassociated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor.Together,these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.Shijia Bi Zunpeng Liu Zeming Wu Zehua Wang Xiaoqian Liu Si Wang Jie Ren Yan Yao Weiqi Zhang Moshi Song Guang-Hui Liu Jing Qu 2020Protein & Cell2020,11,7:10
11WATER TUNNEL EXPERIMENTAL INVESTIGATION ON THE DRAG REDUCTION CHARACTERISTICS OF THE TRAVELING WAVY WALL显示文摘Drag reduction experiment of the traveling wavy wall at high Reynolds number is conducted.A suit of traveling wavy wall device is developed.The drag forces of the traveling wavy wall with various wave speeds(c)are measured under different water speeds(U)in the K15 cavitation water tunnel and are compared with that of the flat plate.The results show that the mean drag force of the traveling wavy wall have decreased and then increased with oscillation frequency increasing at the same flow speed.Under different flow speeds,when traveling wave wall reached to the minimum of drag force,the corresponding the ratio of the wall motion phase speed c to flow speed U,c /U is slightly different.Within the parameters of the experiment,whenc /U reaches a certain value,the drag force of the traveling wavy wall can be less than that of the flat plate.The drag reduction can be up to 42%.Furthermore,as the value ofc /U increases,the traveling wavy wall can restrain the separation and improve the quality of flow field.YAO Yan LU Chuan-jing SI Ting ZHU Kun 2011Journal of Hydrodynamics2011,23,1:10
12Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein-Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma显示文摘Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.Ji‑Jin Yao Guan‑Qun Zhou Ya‑Qin Wang Si‑Yang Wang Wang‑Jian Zhang Ya‑Nan Jin Fan Zhang Li Li Li‑Zhi Liu Zhi‑Bin Cheng Jun Ma Zhen‑Yu Qi 2017Chinese Journal of Cancer2017,36,12:9
13Targeting neuroinflammation in Alzheimer's disease:from mechanisms to clinical applications显示文摘Alzheimer’s disease is characterized by sustained neuroinflammation leading to memory loss and cognitive decline.The past decade has witnessed tremendous efforts in Alzheimer’s disease research;however,no effective treatment is available to prevent disease progression.An increasing body of evidence suggests that neuroinflammation plays an important role in Alzheimer’s disease pathogenesis,alongside the classical pathological hallmarks such as misfolded and aggregated proteins(e.g.,amyloid-beta and tau).Firstly,this review summarized the clinical and pathological characteristics of Alzheimer’s disease.Secondly,we outlined key aspects of glial cell-associated inflammation in Alzheimer’s disease pathogenesis and provided the latest evidence on the roles of microglia and astrocytes in Alzheimer’s disease pathology.Then,we revealed the double-edged nature of inflammatory cytokines and inflammasomes in Alzheimer’s disease.In addition,the potential therapeutic roles of innate immunity and neuroinflammation for Alzheimer’s disease were also discussed through these mechanisms.In the final section,the remaining key problems according to the current research status were discussed.Zi-Zhen Si Chen-Jun Zou Xi Mei Xiao-Fang Li Hu Luo Yao Shen Jun Hu Xing-Xing Li Lun Wu Yu Liu 2023Neural Regeneration Research2023,18,4:7
14Promoting hepatic growth factor in the treatment of heavy type hepatitis and severe chronic hepatitis: a multicenter clinical study显示文摘BACKGROUND: The mortality rate of heavy type hepatitisis high. No special treatment is available except generaltreatment. This multicenter clinical study was designed toobserve the safety and efficacy of promoting hepatic growthfactor (PHGF) in the treatment of heavy type hepatitis andsevere chronic hepatitis.METHODS: 347 patients with heavy type hepatitis and 324with severe chronic hepatitis were subjected to administra-tion of 120 μg of PHGF per day for 4 weeks on the basis ofgeneral treatment. Those who were being effectively treat-ed would last additional 2 to 4 weeks. Blood routine, urineroutine, blood urea nitrogen (BUN), blood creatinine(Cr), blood ammonia, alpha fetoprotein (AFP), electro-lyte, alanine transaminase (ALT), aspartate transaminase(AST), serum total bilirubin (TBIL), serum direct biliru-bin (DBIL), prothrombin time activity (PTA), total pro-tein (TP) and albumin (ALB) were detected in the pa-tients before treatment, 2 weeks after treatment, and at theend of the treatment. Any side-effect would be recorded.RESULTS: In the patients with severe chronic hepatitis, thetotal effective rate of the treatment was 88. 9% The levelsof ALT, AST and TBIL decreased significantly (P<0.001),whereas those of PTA and ALB increased significantly (P <0.001), and the level of AFP increased slightly. In patientswith heavy type hepatitis, the total effective rate of thistreatment was 78.4%, and patients at different stage showeddifferent results. The total effective rates of patients withearly, medium and terminal stage heavy type hepatitis were89.9%, 84.8% and 27.5%, respectively. No severe side-effect was shown.CONCLUSION: PHGF is effective and safe in the treat-ment of patients with heavy type hepatitis and severe chro-nic hepatitis. But it should be administered early in patientswith heavy type hepatitis so as to get better curative effects.Jing-Hang Xu, Yan-Yan Yu, Chong-Wen Si, Zheng Zeng, Qin-Huan Wang, Duan-De Luo,Yong-Xing Zhou, Min-De Zeng, Guang-Yan Qiao, Ji-Lu Yao and Wei-Lun Lu Department of Infectious Diseases, First Hospital ofBeijing University, Beijing 100034, China Department of Gastroenterology, Wuhan UnionHospital, Wuhan 430022, China Department of Gastroentero-logy , Affiliated Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China Department of Gastroenterology, RenjiHospital, Shanghai 200001 , China Department of InfectiousDiseases, Second Affiliated Hospital, China Medical University, Shenyang110004, China Department of Gastroenterology, Third Affilia-ted Hospital, China Medical University, Shenyang 110004 , China 2004Hepatobiliary & Pancreatic Diseases International2004,3,3:7
15Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction显示文摘Cockayne syndrome(CS)is a rare autosomal recessive inherited disorder characterized by a variety of clinical features,including increased sensitivity to sunlight,progressive neurological abnormalities,and the appearance of premature aging.However,the pathogenesis of CS remains unclear due to the limitations of current disease models.Here,we generate integration-free induced pluripotent stem cells(iPSCs)from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs(GC-iPSCs)using the CRISPR/Cas9 system.CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells(MSCs)and neural stem cells(NSCs),both of which display increased susceptibility to DNA damage stress.Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6.We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives(MSCs and NSCs)in the absence or presence of ultraviolet(UV)and replicative stresses,revealing that defects in DNA repair account for CS pathologies.Moreover,we generate autologous GC-MSCs free of pathogenic mutation under a cGMP(Current Good Manufacturing Practice)-compliant condition,which hold potential for use as improved biomaterials for future stem cell replacement therapy for CS.Collectively,our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS.Si Wang Zheying Min Qianzhao Ji Lingling Geng Yao Su Zunpeng Liu Huifang Hu Lixia Wang Weiqi Zhang Keiichiro Suzuiki Yu Huang Puyao Zhang Tie-Shan Tang Jing Qu Yang Yu Guang-Hui Liu Jie Qiao 2020Protein & Cell2020,11,1:7
16Agglutinin isolated from Arisema heterophyllum Blume induces apoptosis and autophagy in A549 cells through inhibiting PI3K/Akt pathway and inducing ER stress显示文摘Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis(RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear. The present study was designed to determine the cytotoxicity of agglutinin isolated from Arisema heterophyllum Blume(AHA) and explore the possible mechanisms in human non-small-cell lung cancer A549 cells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction chromatography. AHA dose-dependently inhibited the proliferation of A549 cells and induced G_1 phase cell cycle arrest. AHA induced apoptosis by up-regulating pro-apoptotic Bax, decreasing anti-apoptotic Bcl-2, and activating caspase-9 and caspase-3. In A549 cells treated with AHA, the PI3K/Akt pathway was inhibited. Furthermore, AHA induced increase in the levels of ER stress markers such as phosphorylated eukaryotic initiation factor 2α(p-eIF2α), C/EBP-homologous protein(CHOP), inositol-requiring enzyme 1α(IRE1α), and phosphorylated c-Jun NH_2-terminal kinase(p-JNK). AHA also induced autophagy in A549 cells. Staining of acidic vesicular organelles(AVOs) and increase in the levels of LC3II and ATG7 were observed in AHA-treated cells. These findings suggested that AHA might be one of the active components with anti-cancer effects in Arisaema heterophyllum Blume. In conclusion, cytotoxicity of AHA on cancer cells might be related to its effects on apoptosis and autophagy through inhibition of PI3K/Akt pathway and induction of ER stress.FENG Li-Xing SUN Peng MI Tian LIU Miao LIU Wang YAO Si CAO Yi-Min YU Xiao-Lu WU Wan-Ying JIANG Bao-Hong YANG Min GUO De-An LIU Xuan 2016Chinese Journal of Natural Medicines2016,14,11:6
17S100A8 promotes epithelial-mesenchymal transition and metastasis under TGF-β/USF2 axis in colorectal cancer显示文摘Background:The transforming growth factor-β(TGF-β)pathway plays a pivotal role in inducing epithelial-mesenchymal transition(EMT),which is a key step in cancer invasion and metastasis.However,the regulatory mechanism of TGF-βin inducing EMT in colorectal cancer(CRC)has not been fully elucidated.In previous studies,it was found that S100A8 may regulate EMT.This study aimed to clarify the role of S100A8 in TGF-β-induced EMT and explore the underlying mechanism in CRC.Methods:S100A8 and upstream transcription factor 2(USF2)expression was detected by immunohistochemistry in 412 CRC tissues.Kaplan-Meier survival analysis was performed.In vitro,Western blot,and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF-β-induced EMT.Mouse metastasis models were used to determine in vivo metastasis ability.Luciferase reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 transcription.Results:During TGF-β-induced EMT in CRC cells,S100A8 and the transcription factor USF2 were upregulated.S100A8 promoted cell migration and invasion and EMT.USF2 transcriptionally regulated S100A8 expression by directly binding to its promoter region.Furthermore,TGF-βenhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells.S100A8 expression in tumor cells was associated with poor overall survival in CRC.USF2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8-positive stromal cells.Conclusions:TGF-βwas found to promote EMT and metastasis through the USF2/S100A8 axis in CRC while extracellular S100A8 suppressed the USF2/S100A8 axis.USF2 was identified as an important switch on the intracellular and extracellular S100A8 feedback loop.Si Li Jun Zhang Senmi Qian Xuesong Wu Liang Sun Tianyi Ling Yao Jin Wenxiao Li Lichao Sun Maode Lai Fangying Xu 2021Cancer Communications2021,41,2:5
18Contralateral S1 function is involved in electroacupuncture treatment-mediated recovery after focal unilateral M1 infarction显示文摘Acupuncture at acupoints Baihui(GV20)and Dazhui(GV14)has been shown to promote functional recovery after stroke.However,the contribution of the contralateral primary sensory cortex(S1)to recovery remains unclear.In this study,unilateral local ischemic infarction of the primary motor cortex(M1)was induced by photothrombosis in a mouse model.Electroacupuncture(EA)was subsequently performed at acupoints GV20 and GV14 and neuronal activity and functional connectivity of contralateral S1 and M1 were detected using in vivo and in vitro electrophysiological recording techniques.Our results showed that blood perfusion and neuronal interaction between contralateral M1 and S1 is impaired after unilateral M1 infarction.Intrinsic neuronal excitability and activity were also disturbed,which was rescued by EA.Furthermore,the effectiveness of EA treatment was inhibited after virus-mediated neuronal ablation of the contralateral S1.We conclude that neuronal activity of the contralateral S1 is important for EA-mediated recovery after focal M1 infarction.Our study provides insight into how the S1-M1 circuit might be involved in the mechanism of EA treatment of unilateral cerebral infarction.The animal experiments were approved by the Committee for Care and Use of Research Animals of Guangzhou University of Chinese Medicine(approval No.20200407009)April 7,2020.Lu-Lu Yao Si Yuan Zhen-Nan Wu Jian-Yu Luo Xiao-Rong Tang Chun-Zhi Tang Shuai Cui Neng-Gui Xu 2022Neural Regeneration Research2022,17,6:5
19Sex-specific and Dose-response Relationship between the Incidence of Gallstones and Components of the Metabolic Syndrome in Jinchang Cohort:A Prospective Study显示文摘Gallstones is a very common gastrointestinal disease,involving the formation of masses in the gall bladder or biliary tract,due to abnormally high concentrations of cholesterol or bilirubin in the bile[1].There is a 10%–20%prevalence of gallstones worldwide,and>20%of patients with gallstones show clinical symptoms,implying a substantial disease burden[1].YANG Jing Li HUANG Jun Jun CHENG Ning ZHANG De Sheng LIU Si Min HUANG Wen Ya LI Na HUANG Pei Yao DING Jiao LIU Nian BAO Kai Fang DING Jie CHEN Xiao Liang ZHENG Tong Zhang BAI Ya Na 2020Biomedical and Environmental Sciences2020,33,8:4
20Expanding base editing scope to near-PAMless with engineered CRISPR/Cas9 variants in plants显示文摘Dear Editor,Base editors(BEs),including cytosine base editor(CBE)and adenine base editor(ABE),have been widely used to generate irreversible nucleotide substitution in plants and animals.However,their wide applications are largely hindered by the strict NG protospacer adjacent motif(PAM)sequences recognized by Streptococcus pyogenes Cas9(SpCas9)and its engineered variants,such as SpCas9-NG and xCas9(Hua et al.,2019;Ren et al.,2019;Wu et al.,2019;Zhong et al.,2019;Zhang et al.,2020).Most recently,it was reported that three new SpCas9 variants,SpCas9-NRRH,SpCas9-NRTH,and SpCas9-NRCH,could recognize non-G PAMs(NRNH,where R is A or G and H is A,C,or T)in human cells(Miller et al.,2020).Meanwhile,SPRY,another new SpCas9 variant,was developed to greatly expand the editing scope of BEs to nearly PAMless(Walton et al.,2020).In this study,we generated a series of efficient BE toolkits and almost achieved C-to-T mutation without PAM restriction except for NTG PAM,and largely expanded A-to-G mutation scope in stable transformed rice,providing a reference for application in other plants.Chengwei Zhang Yao Wang Feipeng Wang Si Zhao Jinling Song Feng Feng Jiuran Zhao Jinxiao Yang 2021Molecular Plant2021,14,2:4
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