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| 1 | Reappraisement and refinement of zircon U-Pb isotope and trace element analyses by LA-ICP-MS显示文摘A protocol was established for simultaneous measurements of zircon U-Pb ages and trace elements by LA-ICP-MS at spot sizes of 16 32 μm.This was accomplished by introducing N 2 into ICP to increase the sensitivity.The obtained U-Pb ages for zircon standards GJ-1,TEMORA and SK10-2 are consistent with the preferred values within about 1% uncertainty (2σ) by simple external calibration against zircon standard 91500.Different data reduction softwares could yield different uncertainties for calculation of U-Pb ages.The commercially available program GLITTER4.4 could apply an improper uncertainty calculation strategy,but it may yield artificial high precisions for single analyses.Our trace element analyses indicate that Si is not an ideal internal standard for zircon when calibrated against the NIST glasses.Calibration against the NIST glasses using Si as an internal standard,a systematic deviation of 10% 30% was found for most trace elements including Zr.However,the trace element compositions of zircon can be accurately measured by calibration against multiple reference materials with natural compositions (e.g.,BCR-2G,BHVO-2G and BIR-1G),or calibration against NIST SRM 610 and using Zr as an internal standard.Analyses of two pieces of GJ-1 demonstrate that it is relatively homogenous for most trace elements (except for Ti). | LIU YongSheng HU ZhaoChu ZONG KeQing GAO ChangGui GAO Shan XU Juan CHEN HaiHong | 2010 | Chinese Science Bulletin2010，55，15： | 1011 |
| 2 | Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman's syndrome显示文摘Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS. | Guangfeng Zhao Yun Cao Xianghong Zhu Xiaoqiu Tang Lijun Ding Haixiang Sun Juan Li Xinan Li Chenyan Dai Tong Ru Hui Zhu Jingjie Lu Caimei Lin Jingmei Wang Guijun Yan Huiyan Wang Lei Wang Yimin Dai Bin Wang Ruotian Li Jianwu Dai Yan Zhou Yali Hu | 2017 | Science China(Life Sciences)2017，60，4： | 39 |
| 3 | Constraining the timing of the India-Asia continental collision by the sedimentary record显示文摘Placing precise constraints on the timing of the India-Asia continental collision is essential to understand the successive geological and geomorphological evolution of the orogenic belt as well as the uplift mechanism of the Tibetan Plateau and their effects on climate,environment and life.Based on the extensive study of the sedimentary record on both sides of the Yarlung-Zangbo suture zone in Tibet,we review here the present state of knowledge on the timing of collision onset,discuss its possible diachroneity along strike,and reconstruct the early structural and topographic evolution of the Himalayan collided range.We define continent-continent collision as the moment when the oceanic crust is completely consumed at one point where the two continental margins come into contact.We use two methods to constrain the timing of collision onset:(1) dating the provenance change from Indian to Asian recorded by deep-water turbidites near the suture zone,and(2) dating the age of unconformities on both sides of the suture zone.The first method allowed us to constrain precisely collision onset as middle Palaeocene(59±l Ma).Marine sedimentation persisted in the collisional zone for another 20-25 Ma locally in southern Tibet,and molassic-type deposition in the Indian foreland basin did not begin until another 10-15 Ma later.Available sedimentary evidence failed to firmly document any significant diachroneity of collision onset from the central Himalaya to the western Himalaya and Pakistan so far.Based on the Cenozoic stratigraphic record of the Tibetan Himalaya,four distinct stages can be identified in the early evolution of the Himalayan orogen:(1) middle Palaeocene-early Eocene earliest Eohimalayan stage(from 59 to 52 Ma):collision onset and filling of the deep-water trough along the suture zone while carbonate platform sedimentation persisted on the inner Indian margin;(2) early-middle Eocene early Eohimalayan stage(from 52 to 41 or 35 Ma):filling of intervening seaways and cessation of marine sedimentation;(3) late Eocene-Oligocene late Eohimalayan stage(from 41 to 25 Ma):huge gap in the sedimentary record both in the collision zone and in the Indian foreland;and(4) late Oligocene-early Miocene early Neohimalayan stage(from 26 to 17 Ma):rapid Himalayan growth and onset of molasse-type sedimentation in the Indian foreland basin. | HU XiuMian WANG JianGang AN Wei Eduardo GARZANTI LI Juan | 2017 | Science China Earth Sciences2017，60，4： | 32 |
| 4 | Clinical Characteristics of Patients with Diabetic Nephropathy on Maintenance Hemodialysis: A Multicenter Cross-sectional Survey in Anhui Province, Eastern China显示文摘 | Hu Chen De-Guang Wang Liang Yuan Gui-Ling Liu Heng-Jie He Juan Wang Sen Zhang Li Hao | 2016 | Chinese Medical Journal2016，，11： | 24 |
| 5 | Dynamic Prediction Method of Production Logistics Bottleneck Based on Bottleneck Index显示文摘In modern manufacturing pattern,there are many uncertain factors in the modern manufacturing process,such as changes of product attribute,changes of manufacturing resources' state,and so on,which cause production logistics bottleneck frequently shift,and make decisions of production planning and control based on formed bottleneck deviated from practical production process.Considering these factors,present researches mainly apply afterwards control to optimize production process to passively adapt to bottleneck changes.If the direction of bottleneck shifting can be accurately forecasted,the transition from afterwards control of chasing bottleneck to beforehand control can be realized.Therefore,aiming at the phenomenon of production logistics bottleneck shifting under uncertain manufacturing circumstances,this paper starts off with dynamic property of capability and requirement and then builds the concepts of bottleneck degree and bottleneck index to describe dynamic bottleneck characteristic of production unit;taken production capability,production load and quality assurance capability into consideration,mathematical model of bottleneck index is established to measure bottleneck degree accurately,consequently,quantitative research on mechanism of production logistics shifting is achieved.Based on bottleneck index,the prediction model of production logistics bottleneck is founded to predict dynamic change of bottleneck accurately.Finally,an example of forecasting and monitoring the production logistics bottleneck in one manufacturing shop is given to testify the validation and practicability of the prediction method. | LIU Mingzhou TANG Juan GE Maogen JIANG Zengqiang HU Jing LING Lin | 2009 | Chinese Journal of Mechanical Engineering2009，22，5： | 22 |
| 6 | Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China显示文摘Asthma,rhinitis and eczema(allergic or non-allergic)have increased throughout the world during the last decades,especially among children.Changes in the indoor environment are suspected to be important causes.China has experienced a dramatic change in indoor environmental exposures during the past two decades.However,such changes and their associations with children’s asthma and other health aspects have not been thoroughly studied.China,Children,Homes,Health(CCHH),Phase I,was a cross-sectional questionnaire survey of 48219 children 1–8 years old in 10 Chinese cities during 2010–2012.The questionnaire includes the International Study of Asthma and Allergies in Childhood(ISAAC)core health questions and additional questions regarding housing,life habits and outdoor environment.In health analyses,children aged 3–6 years old were included.The prevalences of doctor diagnosed asthma varied from 1.7%to 9.8%(mean 6.8%),a large increase from 0.91%in 1999 and 1.50%in2000.The prevalence of wheeze,rhinitis and atopic eczema(last 12 months)varied from 13.9%to 23.7%,24.0%to 50.8%and4.8%to 15.8%,respectively.Taiyuan had the lowest prevalences of all illnesses and Shanghai the highest,except for wheezewhere the highest value was for Urumqi.We found(1)no obvious association between disease prevalences and ambient PM10concentrations and(2)higher prevalences of disease in humid climates with hot summers and cold winters,but with no centrally heated buildings.Associations between the diseases and economic status as indexed by Gross Domestic Product(GDP)requires further study. | ZHANG YinPing LI BaiZhan HUANG Chen YANG Xu QIAN Hua DENG QiHong ZHAO ZhuoHui LI AnGui ZHAO JiaNing ZHANG Xin QU Fang HU Yu YANG Qin WANG Juan ZHANG Ming WANG Fang ZHENG XiaoHong LU Chan LIU ZhiJian SUN YueXia MO JinHan ZHAO YiLi LIU Wei WANG TingTing NORBCK Dan BORNEHAG Carl-Gustaf SUNDELL Jan | 2013 | Chinese Science Bulletin2013，58，34： | 22 |
| 7 | Neuroprotective effects of salidroside on focal cerebral ischemia/reperfusion injury involve the nuclear erythroid 2-related factor 2 pathway显示文摘Salidroside,the main active ingredient extracted from Rhodiola crenulata,has been shown to be neuroprotective in ischemic cerebral injury,but the underlying mechanism for this neuroprotection is poorly understood.In the current study,the neuroprotective effect of salidroside on cerebral ischemia-induced oxidative stress and the role of the nuclear factor erythroid 2-related factor 2(Nrf2)pathway was investigated in a rat model of middle cerebral artery occlusion.Salidroside(30 mg/kg)reduced infarct size,improved neurological function and histological changes,increased activity of superoxide dismutase and glutathione-S-transferase,and reduced malon-dialdehyde levels after cerebral ischemia and reperfusion.Furthermore,salidroside apparently increased Nrf2 and heme oxygenase-1 expression.These results suggest that salidroside exerts its neuroprotective effect against cerebral ischemia through anti-oxidant mechanisms and that activation of the Nrf2 pathway is involved.The Nrf2/antioxidant response element pathway may become a new therapeutic target for the treatment of ischemic stroke. | Jing Han Qing Xiao Yan-hua Lin Zhen-zhu Zheng Zhao-dong He Juan Hu Li-dian Chen | 2015 | Neural Regeneration Research2015，10，12： | 23 |
| 8 | Preliminary molecular epidemiology of the Staphylococcus aureus in lower respiratory tract infections: a multicenter study in China显示文摘 | LI De-zhi CHEN Yu-sheng YANG Jing-ping ZHANG Wei HU Cheng-ping LI Jia-shu MU Lan HU Ying-hui GENG Rong HU Ke CAI Shao-xi WAN Huan-ying WANG Qiu-yue WEI Li-ping DU Juan YU Qin ZHONG Xiao-ning WANG Rui-qin MA Jian-jun TIAN Gui-zhen WANG Si-qin GAO Zhan-cheng | 2011 | Chinese Medical Journal2011，，5： | 21 |
| 9 | Human ESC-derived expandable hepatic organoids enable therapeutic liver repopulation and pathophysiological modeling of alcoholic liver injury显示文摘We report the generation of human ESC-derived,expandable hepatic organoids(hEHOs)using our newly established method with wholly defined(serum-free,feeder free)media.The hEHOs stably maintain phenotypic features of bipotential liver stem/progenitor cells that can differentiate into functional hepatocytes or cholangiocytes.The hEHOs can expand for 20 passages enabling large scale expansion to cell numbers requisite for industry or clinical programs.The cells from hEHOs display remarkable repopulation capacity in injured livers of FRG mice following transplantation,and they differentiate in vivo into mature hepatocytes.If implanted into the epididymal fat pads of immune-deficient mice,they do not generate non-hepatic lineages and have no tendency to form teratomas.We further develop a derivative model by incorporating human fetal liver mesenchymal cells(hFLMCs)into the hEHOs,referred to as hFLMC/hEHO,which can model alcoholic liver disease-associated pathophysiologic changes,including oxidative stress generation,steatosis,inflammatory mediators release and fibrosis,under ethanol treatment.Our work demonstrates that the hEHOs have considerable potential to be a novel,ex vivo pathophysiological model for studying alcoholic liver disease as well as a promising cellular source for treating human liver diseases. | Shuyong Wang Xuan Wang Zuolong Tan Yuxin Su Juan Liu Mingyang Chang Fang Yan Jie Chen Tao Chen Chuanjiang Li Jie Hu Yunfang Wang | 2019 | Cell Research2019，29，12： | 20 |
| 10 | Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs.3 doses in young women显示文摘A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women.A randomized,immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China.Girls aged 9–14 years were randomized to receive 2 doses at months 0 and 6(n=301)or 3 doses at months 0,1 and 6(n=304).Girls aged 15–17 years(n=149)and women aged 18–26 years(n=225)received 3 doses.The objectives included noninferiority analysis of the IgG geometric mean concentration(GMC)ratio(95%CI,lower bound>0.5)to HPV-16 and HPV-18 at month 7 in girls compared with women.In the per-protocol set,the GMC ratio of IgG was noninferior for girls aged 9–17 years receiving 3 doses compared with women(1.76(95%CI,1.56,1.99)for HPV-16 and 1.93(95%CI,1.69,2.21)for HPV-18)and noninferior for girls aged 9–14 years receiving 2 doses compared with women(1.45(95%CI,1.25,1.62)for HPV-16 and 1.17(95%CI,1.02,1.33)for HPV-18).Noninferiority was also demonstrated for neutralizing antibodies.The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women. | Yue-Mei Hu Meng Guo Chang-Gui Li Kai Chu Wen-Gang He Jing Zhang Jian-Xiang Gu Juan Li Hui Zhao Xiang-Hong Wu Bi-Zhen Lin Zhi-Jie Lin Xing-Mei Yao Ya-Fei Li Fei-Xue Wei Yue Huang Ying-Ying Su Feng-Cai Zhu Shou-Jie Huang Hui-Rong Pan Ting Wu Jun Zhang Ning-Shao Xia | 2020 | Science China(Life Sciences)2020，63，4： | 19 |
| 11 | Infection 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 | 2020 | Cell Research2020，30，8： | 19 |
| 12 | Endothelial Nitric Oxide Synthase Gene Intron 4, 27 bp Repeat Polymorphism and Essential Hypertension in the Kazakh Chinese Population显示文摘为了调查在 27 bp 之间的关系,在内含子 4in 重复多型性 endothelial 在 KazakhChinese 人口的氮的氧化物合酶( eNOS4 )基因和必要高血压,有必要高血压和 138 个健康的人的 151 个病人在 Xinjiang uygur 从 Shawan 区域的 Boertonggu 农村被选择中国 in2006 的自治区域。在二个组的 eNOS 的多型性与聚合酶链反应试金被检测,在每个组的遗传型频率是计算的跟随 Hardy-Weinberg 法律。Fourand 27 bp 重复的五辆双人脚踏车是被指明一 and “ b' 分别地。b/b, b/a 和 eNOS4 基因的 a/a 遗传型的频率在控制组是 84.06% , 15.22% 和 0.72% ,这被发现,并且 81.46% , 15.89% 和 2.65% 分别地在高血压组织。基因的频率一 and “ b' 在控制组是 91.67% 和 8.33% , 89.40% 和 10.60% 分别地在高血压组织。血浆 eNOS 活动没与 eNOS 基因的遗传型和等位基因被联系,这被发现。在高血压组的血浆 eNOS 活动显著地与控制组(P<0.01 ) 相比被减少。结果建议 eNOS4 基因多型性是不大可能的是为在 Xinjiang 哈萨克人口的必要高血压的主要基因危险性因素。然而,在血浆 eNOS 活动之间的一个积极协会和必要高血压被揭示了。 | Fengmei DENG Qinghua HU Bin TANG Fang HE Shuxia GUO Jiang CHEN Feng LI Xuehua WU Jun ZHANG Huimin ZHANG Juan ZHAO Hua ZHONG Ling HE Jun LI Le ZHANG Shuren WANG | 2007 | Acta Biochimica et Biophysica Sinica2007，39，5： | 18 |
| 13 | Palmitic acid induces autophagy in hepatocytes via JNK2 activation显示文摘 | Qian-qian TU Rui-ying ZHENG Juan LI Liang HU Yan-xin CHANG Liang LI Min-hong LI Ruo-yu WANG Dan-dan HUANG Meng-chao WU He-ping HU Lei CHEN Hong-yang WANG | 2014 | Acta Pharmacologica Sinica2014，35，4： | 18 |
| 14 | Gain-of-function mutant p53 in cancer progression and therapy显示文摘p53 is a key tumor suppressor,and loss of p53 function is frequently a prerequisite for cancer development.The p53 gene is the most frequently mutated gene in human cancers;p53 mutations occur in>50%of all human cancers and in almost every type of human cancers.Most of p53 mutations in cancers are missense mutations,which produce the full-length mutant p53(mutp53)protein with only one amino acid difference from wild-type p53 protein.In addition to loss of the tumor-suppressive function of wild-type p53,many mutp53 proteins acquire new oncogenic activities independently of wild-type p53 to promote cancer progression,termed gain-of-function(GOF).Mutp53 protein often accumulates to very high levels in cancer cells,which is critical for its GOF.Given the high mutation frequency of the p53 gene and the GOF activities of mutp53 in cancer,therapies targeting mutp53 have attracted great interest.Further understanding the mechanisms underlying mutp53 protein accumulation and GOF will help develop effective therapies treating human cancers containing mutp53.In this review,we summarize the recent advances in the studies on mutp53 regulation and GOF as well as therapies targeting mutp53 in human cancers. | Cen Zhang Juan Liu Dandan Xu Tianliang Zhang Wenwei Hu Zhaohui Feng | 2020 | Journal of Molecular Cell Biology2020，12，9： | 18 |
| 15 | Recurrent gain-of-function USP8 mutations in Cushing's disease显示文摘库欣的疾病,引起过量皮质醇生产的也已知的同样促肾上腺皮质的荷尔蒙(ACTH )-secreting 垂体腺瘤(舞步) ,占多达 85%corticotrophin 依赖的库欣的症候群盒子。然而,在这疾病的基因改变是不清楚的。这里,我们执行了从 12 秘密 ACTH 舞步导出并且匹配血样品的 DNA 定序的 whole-exome,它在候选人基因揭示了体的变化的三种类型, USP8 (编码 ubiquitin 特定的朊酶 8 ) ,专门在 exon 14 在 12 秘密 ACTH 舞步中的 8 个。我们进一步评估了体的 USP8 变化在另外由定序的 Sanger 的 258 舞步。进一步定序指向在 108 秘密 ACTH 舞步(62.04%) 中的 67 个识别了 USP8 变体的 17 种类型的一个总数。然而,任何一个都没在舞步的另外的类型这些变化被检测(n = 150 ) 。这些变化在 USP8 的 14-3-3 绑定主题以内聚集并且破坏在 USP8 和 14-3-3 蛋白质之间的相互作用,导致保护 EGFR 免受 lysosomal 降级的伤害的一个提高的能力。因此,有 EGFR 表示,提高的 EGFR 蛋白质丰富和 mRNA 表示的更高的发生 POMC 铺平的变异的 USP8 显示的舞步,它编码 ACTH 的先锋。有变异的 USP8 的舞步在尺寸是显著地更小的并且比野类型的舞步有更高的 ACTH 生产。在里面通过手术 resected 主要变异 USP8 的肿瘤房间, USP8 击倒或堵住的 EGFR 有效地稀释 ACTH 分泌物。一起拿,体的 gain-of-function USP8 变化是普通的并且在库欣的疾病贡献 ACTH 生产过剩。USP8 或 EGFR 的抑制为对待变异 USP8 的 corticotrophin 腺瘤是有希望的。我们的学习在库欣的疾病加亮潜在地功能的变异的基因并且提供卓见进这疾病的治疗学。 | Zeng-Yi Ma Zhi-Jian Song Jian-Hua Chen Yong-Fei Wang Shi-Qi Li Liang-Fu Zhou Ying Mao Yi-Ming Li Rong-Gui Hu Zhao-Yun Zhang Hong-Ying Ye Ming Shen Xue-Fei Shou Zhi-Qiang Li Hong Peng Qing-Zhong Wang Dai-Zhan Zhou Xiao-Lan Qin Jue Ji Jie Zheng Hong Chen Yin Wang Dao-Ying Geng Wei-Jun Tang Chao-Wei Fu Zhi-Feng Shi Yi-Chao Zhang Zhao Ye Wen-Qiang He Qi-Lin Zhang Qi-Sheng Tang Rong Xie Jia-Wei Shen Zu-Jia Wen Juan Zhou Tao Wang Shan Huang Hui-Jia Qiu Ni-Dan Qiao Yi Zhang Li Pan Wei-Min Bao Ying-Chao Liu Chuan-Xin Huang Yong-Yong Shi Yao Zhao | 2015 | Cell Research2015，25，3： | 16 |
| 16 | Prostate cancer identification: quantitative analysis of T2-weighted MR images based on a back propagation artificial neural network model显示文摘Computer-aided diagnosis(CAD) systems have been proposed to assist radiologists in making diagnostic decisions by providing helpful information. As one of the most important sequences in prostate magnetic resonance imaging(MRI), image features from T2-weighted images(T2WI) were extracted and evaluated for the diagnostic performances by using CAD. We extracted 12 quantitative image features from prostate T2-weighted MR images. The importance of each feature in cancer identification was compared in the peripheral zone(PZ) and central gland(CG), respectively. The performance of the computer-aided diagnosis system supported by an artificial neural network was tested. With computer-aided analysis of T2-weighted images, many characteristic features with different diagnostic capabilities can be extracted. We discovered most of the features(10/12) had significant difference(P<0.01) between PCa and non-PCa in the PZ, while only five features(sum average, minimum value, standard deviation, 10 th percentile, and entropy) had significant difference in CG. CAD prediction by features from T2 w images can reach high accuracy and specificity while maintaining acceptable sensitivity. The outcome is convictive and helpful in medical diagnosis. | ZHAO Kai WANG ChengYan HU Juan YANG XueDong WANG He LI FeiYu ZHANG XiaoDong ZHANG Jue WANG XiaoYing | 2015 | Science China(Life Sciences)2015，58，7： | 16 |
| 17 | Omentin-1 prevents inflammation-induced osteoporosis by downregulating the pro-inflammatory cytokines显示文摘Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout(omentin-1^(-/-)) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α(TNF-α), we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines. | Shan-Shan Rao Yin Hu Ping-Li Xie Jia Cao Zhen-Xing Wang Jiang-Hua Liu Hao Yin Jie Huang Yi-Juan Tan Juan Luo Ming-Jie Luo Si-Yuan Tang Tuan-Hui Chen Ling-Qing Yuan Er-Yuan Liao Ran Xu Zheng-Zhao Liu Chun-Yuan Chen Hui Xie | 2018 | Bone Research2018，6，2： | 16 |
| 18 | Generation of B Cell-Deficient Pigs by Highly Efficient CRISPR/Cas9-Mediated Gene Targeting显示文摘Generating B cell-deficient mutant is the first step to produce human antibody repertoires in large animal models. In this study, we applied the clustered regularly interspaced short palindromic repeat(CRISPR)/CRISPR-associated(Cas) system to target the JHregion of the pig Ig M heavy chain gene which is crucial for B cell development and differentiation. Transfection of Ig M-targeting Cas9 plasmid in primary porcine fetal fibroblasts(PFFs) enabled inducing gene knock out(KO) in up to 53.3% of colonies analyzed, a quarter of which harbored biallelic modification, which was much higher than that of the traditional homologous recombination(HR). With the aid of somatic cell nuclear transfer(SCNT) technology, three piglets with the biallelic Ig M heavy chain gene mutation were produced. The piglets showed no antibody-producing B cells which indicated that the biallelic mutation of the Ig M heavy chain gene effectively knocked out the function of the Ig M and resulted in a B cell-deficient phenotype. Our study suggests that the CRISPR/Cas9 system combined with SCNT technology is an efficient genome-editing approach in pigs. | Fengjiao Chen Ying Wang Yilin Yuan Wei Zhang Zijian Ren Yong Jin Xiaorui Liu Qiang Xiong Qin Chen Manling Zhang Xiaokang Li Lihua Zhao Ze Li Zhaoqiang Wu Yanfei Zhang Feifei Hu Juan Huang Rongfeng Li Yifan Dai | 2015 | Journal of Genetics and Genomics2015，42，8： | 15 |
| 19 | Gualou Guizhi decoction promotes neurological functional recovery and neurogenesis following focal cerebral ischemia/reperfusion显示文摘Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction(GLGZD) is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurological function was assessed immediately after reperfusion using Longa's 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2′-deoxyuridine(BrdU) as well as expression of the neural precursor marker doublecortin(DCX), the astrocyte marker glial fibrillary acidic protein(GFAP) and the axon regeneration marker growth associated protein-43(GAP-43). GLGZD substantially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and increasing the numbers of neuronal precursors and astrocytes in the peri-infarct area. | Jing Han Ji-Zhou Zhang Zhi-Feng Zhong Zuan-Fang Li Wen-Sheng Pang Juan Hu Li-Dian Chen | 2018 | Neural Regeneration Research2018，13，8： | 14 |
| 20 | Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats显示文摘Hyperlipidemia(HPL)characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases.Proprotein convertase subtilsin/kexin type 9(PCSK9)is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor(LDLR)in the lysosome of hepatocytes.Aloe-emodin(AE)is one of potentially bioactive components of Chinese traditionalmedicine Daming capsule.In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models.High-fat diet-induced rats were treated with AE(100 mg/kg per day,ig)for 6 weeks.We found that AE administration significantly decreased the levels of total cholesterol(TC)and LDL in the serum and liver tissues.Moreover,AE administration ameliorated HPL-induced hepaticlipid aggregation.But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats.A cellular model of HPL was established in human hepatoma(HepG2)cells treated with cholesterol(20 μg/mL)and 25-hydroxycholesterol(2 μg/mL),which exhibited markedly elevated cholesterol levels.The increased cholesterol levels could be reversed by subsequent treatment with AE(30 μM).In both the in vivo and in vitro HPL models,we revealed that AE selectively suppressed the stero-regulatory element-binding protein-2(SREBP-2)and hepatocyte nuclear factor(HNF)1α-mediated PCSK9 signaling,which in turn upregulated LDL receptor(LDLR)and promoted LDL uptake.This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway. | Zhen-li Su Peng-zhou Hang Juan Hu Yu-yang Zheng Han-qi Sun Jing Guo Ke-yu Liu Zhi-min Du | 2020 | Acta Pharmacologica Sinica2020，41，8： | 14 |
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