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| 1 | Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression显示文摘Recently,increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease(AD)progression,yet the role of gut microbiota in AD pathogenesis remains obscure.Herein,we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression.Using AD mouse models,we discovered that,during AD progression,the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine,which stimulates the differentiation and proliferation of pro-inflammatory T helper 1(Thl)cells.The brain-infiltrated peripheral Th1 immune cells are associated with the Ml microglia aaivation,contributing to AD-associated neuroinflammation.Importantly,the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment(MCI)due to AD.Furthermore,GV-971,a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China,suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation,harnesses neuroinflammation and reverses the cognition impairment.Together,our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota. | Xinyi Wang Guangqiang Sun Teng Feng Jing Zhang Xun Huang Tao Wang Zuoquan Xie Xingkun Chu Jun Yang Huan Wang Shuaishuai Chang Yanxue Gong Lingfei Ruan Guanqun Zhang Siyuan Yan Wen Lian Chen Du Dabing Yang Qingli Zhang Feifei Lin Jia Liu Haiyan Zhang Changrong Ge Shifu Xiao Jian Ding Meiyu Geng | 2019 | Cell Research2019，29，10： | 192 |
| 2 | Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis显示文摘精子发生在双 spermatogonial 干细胞(SSC ) 哪个生产 haploid 精子期间是一个区别过程。这个高度专业化的过程精确在 transcriptional, posttranscriptional,和翻译层次被控制。这里,我们报导那 N 6-methyladenosine (m 6 一) ,调整基因表示的一个 epitranscriptomic 标记,在精子发生期间起必要作用。我们现在的全面 m 6 从五个发展阶段的老鼠 spermatogenic 房间的 mRNA methylomes:无差别的 spermatogonia,类型 A 1 spermatogonia, preleptotene spermatocytes, pachytene/diplotene spermatocytes,和圆 spermatids。m 6 有 Vasa-Cre 的 RNA methyltransferase Mettl3 或 Mettl14 引起 m 6 SSC 的 A 和弄空。m 6 为 SSC 增长 / 区别被要求的抄本的一个弄空 dysregulates 翻译。在有 Stra8-GFPCre 的先进细菌房间的 Mettl3 和 Mettl14 的联合删除破坏精子形式,而有在先进细菌房间的 Mettl3 或 Mettl14 的单个删除的老鼠显示出正常精子发生。从双异种老鼠展览的 spermatids 损害了为精子形式是必要的 haploid 特定的基因的翻译。这研究加亮 mRNA m 6 在 germline 开发的修正,潜在地保证在精子发生的不同阶段协调了翻译。 | Zhen Lin Phillip J Hsu Xudong Xing Jianhuo Fang Zhike Lu Qin Zou Ke-Jia Zhang Xiao Zhang Yuchuan Zhou Teng Zhang Youcheng Zhang Wanlu Song Guifang Jia Xuerui Yang Chuan He Ming-Han Tong | 2017 | Cell Research2017，27，10： | 61 |
| 3 | Hepatoprotective role of ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice显示文摘AIM: To examine the effect of ganoderma lucidumpolysaccharide (GLP) on the immune liver injuryinduced by BCG infection, and investigate therelationship between degrees of hepatic damage andNO production in mice.METHODS: Immune hepatic injury was markedlyinduced by BCG-pretreatment (125 mg.kg-1, 2-week, iv)or by BCG-pretreatment plus lipopolysaccharide (LPS,125 μg.kg-1, 12-hour, iv) in mice in vivo.Hepatocellulardamage induced by BCG-pretreated plus inflammatorycytokines mixture (CM), which was included TNF-α, IL1β, IFN-γ and LPS in culture medium in vitro.Administration of GLP was performed by oral orincubating with culture medium at immune stimulisimultaneity. Liver damage was determined by activityof alanine aminotransferase (ALT) in serum and inhepatocytes cultured supernatant, by liver weightchanges and histopathological examination. NOproduction in the cultured supematant was determinedby the Griess reaction. Moreover, inducible nitric oxidesynthase (iNOS) protein expression was alsoexaminated by immunohistochemi1cal method.RESULTS: Immune hepatic injury was markedly inducedby BCG or BCG plus inflammatory cytokines in BALB/cmice in vivoand in vitro. Under BCG-stimulated condition,augment of the liver weight and increase of the serum/supernatant ALT level were observed, as well asgranuloma forming and inflammatory cells soakage wereobserved by microscopic analysis within liver tissues.Moreover, NO production was also increased by BCG or/and CH stimuli in the culture supernatant, and a lot ofiNOS positive staining was observed in BCG-prestimulated hepatic sections. Application of GLPsignificantly mitigated hepatic tumefaction, decreasedALT enzyme release and NO production in serum/supernatant, improved the pathological changes ofchronic and acute inflammation induced by BCG-stimuliin mice. Moreover, the immunohistochemical resultshowed that GLP inhibited iNOS protein expression inBCG-immune hepatic damage model.CONCLUSION: The present study indicates that NOparticipates in immune liver injury induced byMycobacterium bovis BCG infection. The mechanismsof protective roles by GLP for BCG-induced immune liverinjury may be due to influence NO production in mice. | Guo-Liang Zhang Ye-Hong Wang Wei Ni Hui-Ling Teng Zhi-Bin Lin Department of Pharmacology,School of Basic Medical Sciences,Beijing University,Beijing 100083,China | 2002 | World Journal of Gastroenterology2002，8，4： | 47 |
| 4 | Effects of stem structure andcell wall components on bending strength in wheat显示文摘Morphological traits, anatomical features, chemical components and bending stress in the stems of three genotypes of wheat (Triticum aestivum L.), namely Xiaoyan54, 8602 and Xiaoyan81, were ex- amined by means of light microscopy coupled with Fourier transform infrared spectroscopy (FTIR). No- ticeable changes in morphological and anatomical traits were observed, including outer radius of stem, the ratio of stem outer radius to stem wall thickness, various tissue proportions and variations among dif- ferent types of vascular bundles. The results of chemical analysis revealed that Xiaoyan81 had the highest cellulose content in comparison with Xiao- yan54 and 8602, whereas lignin level in Xiaoyan81 was lower than that in 8602 but higher that that in Xiaoyan54. Bending stress analysis demonstrated that Xiaoyan81 may be the main target for identifica- tion, for it had the highest bending stress among the stems of three genotypes. Associated with bending stress, all the results presented here suggested that the ratio of stem wall thickness to its outer radius, schlerenchyma tissue proportion, the average num- ber of big VB per unit and the cellulose content are four important factors affecting the mechanical strength of Xiaoyan81 wheat stems, which can be considered as the key parameters for selecting varie- ties with bending stress. Therefore, it was suggested that in the selection of lodging resistant cultivars one should consider those characterized with large ratio of outer radius of stem to stem wall thickness, great-erschlerenchyma tissue proportion, high average number of big VB per unit with high cellulose content in their stems. | WANG Jian ZHU Jinmao LIN Qinqin LI Xiaojuan TENG Nianjun LI Zhensheng LI Bin ZHANG Aimin LIN Jinxing | 2006 | Chinese Science Bulletin2006，51，7： | 30 |
| 5 | Engineering a New Chloroplastic Photorespiratory Bypass to In crease Photosynthetic Efficiency and Productivity in Rice显示文摘Over the past few years, three photorespiratory bypasses have been introduced into plants, two of which led to observable in creases in photos yn thesis and biomass yield. However, most of the experiments were carried out using Arabidopsis under controlled environmental conditions, and the increases were only observed under low-light and short-day conditions. In this study, we designed a new photorespiratory bypass (called GOC bypass), characterized by no reducing equivalents being produced during a complete oxidation of glycolate into CO2 catalyzed by three rice-self-originating enzymes, i.e., glycolate oxidase, oxalate oxidase, and catalase. We successfully established this bypass in rice chloroplasts using a multi-gene assembly and transformation system. Transgenic rice plants carrying GOC bypass (GOC plants) showed significant increases in photosynthesis efficiency, biomass yield, and nitrogen content, as well as several other CO2-enriched phe no types under both greenhouse and field conditions .Grain yield of GOC plants varied depending on seeding season and was increased significantly in the spring. We further demonstrated that GOC plants had significant advantages under high-light conditions and that the improvements in GOC plants resulted primarily from a photosynthetic CO2-concentrating effect rather than from improved energy balance. Taken together, our results reveal that engineering a newly designed chloroplastic photorespiratory bypass could increase photosynthetic efficiency and yield of rice plants grown in field conditions, particularly under high light. | Bo-Ran Shen Li-Min Wang Xiu-Ling Lin Zhen Yao Hua-Wei Xu Cheng-Hua Zhu Hai-Yan Teng Li-Li Cui E.-E. Liu Jian-Jun Zhang Zheng-Hui He Xin-Xiang Peng | 2019 | Molecular Plant2019，12，2： | 30 |
| 6 | Biological effects of low-dose-rate irradiation of pancreatic carcinoma cells in vitro using ^(125)I seeds显示文摘AIM:To determine the mechanism of the radiationinduced biological effects of 125I seeds on pancreatic carcinoma cells in vitro.METHODS:SW1990 and PANC-1 pancreatic cancer cell lines were cultured in DMEM in a suitable environment.Gray’s model of iodine-125(125I)seed irradiation was used.In vitro,exponential phase SW1990,and PANC-1cells were exposed to 0,2,4,6,and 8 Gy using 125I radioactive seeds,with an initial dose rate of 12.13c Gy/h.A clonogenic survival experiment was performed to observe the ability of the cells to maintain their clonogenic capacity and to form colonies.Cell-cycle and apoptosis analyses were conducted to detect the apoptosis percentage in the SW1990 and PANC-1 cells.DNA synthesis was measured via a tritiated thymidine(3H-Td R)incorporation experiment.After continuous low-dose-rate irradiation with 125I radioactive seeds,the survival fractions at 2 Gy(SF2),percentage apoptosis,and cell cycle phases of the SW1990 and PANC-1 pancreatic cancer cell lines were calculated and compared.RESULTS:The survival fractions of the PANC-1 andSW1990 cells irradiated with 125I seeds decreased exponentially as the dose increased.No significant difference in SF2 was observed between SW1990 and PANC-1 cells(0.766±0.063 vs 0.729±0.045,P<0.05).The 125I seeds induced a higher percentage of apoptosis than that observed in the control in both the SW1990and PANC-1 cells.The rate of apoptosis increased with increasing radiation dosage.The percentage of apoptosis was slightly higher in the SW1990 cells than in the PANC-1 cells.Dose-dependent G2/M cellcycle arrest was observed after 125I seed irradiation,with a peak value at 6 Gy.As the dose increased,the percentage of G2/M cell cycle arrest increased in both cell lines,whereas the rate of DNA incorporation decreased.In the 3H-Td R incorporation experiment,the dosimetry results of both the SW1990 and PANC-1cells decreased as the radiation dose increased,with a minimum at 6 Gy.There were no significant differences in the dosimetry results of the two cell lines when they were exposed to the same dose of radiation.CONCLUSION:The pancreatic cancer cell-killing effects induced by 125I radioactive seeds mainly occurred via apoptosis and G2/M cell cycle arrest. | Zhong-Min Wang Jian Lu Li-Yun Zhang Xiao-Zhu Lin Ke-Min Chen Zhi-Jin Chen Fen-Ju Liu Fu-Hua Yan Gao-Jun Teng Ai-Wu Mao | 2015 | World Journal of Gastroenterology2015，21，8： | 27 |
| 7 | Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes显示文摘AIM To study the effects of aminoguanidine(AG) and two L-arginine analogues Nω-nitro-L-arginine methyl ester (L-NAME) and Nω-nitro-L-arginine (L-NNA) on nitric oxide (NO) productioninduced by cytokines (TNF-α, IL-11β, and IFN-γ)and bacterial lipopolysaccharide (LPS) mixture(CM) in the cultured rat hepatocytes, andexamine their mechanisms action.METHODS Rat hepatocytes were incubatedwith AG, L-NAME, L-NNA, Actinomycin D (ActD)and dexamethasene in a medium containing CM(LPS plus TNF-α, IL-1β, and IFN-γ) for 24 h. NOproduction in the cultured supernatant wasmeasured with the Griese reaction. IntracellularcGMP level was detected with radioimmunoasey.RESULTS NO production was markedlyblocked by AG and L-NAME in a dose-dependentmanner under inflammatory stimuli conditiontriggered by CM in vitro. The rate of themaximum inhibitory effects of L-NAME (38.9%)was less potent than that obtained with AG(53.7%, P<0.05). There was no significantdifference between the inhibitory effects of AGand two L-arginine analogues on intracellularcGMP accumulation in rat cultured hepatocytes.Non-specific NOS expression inhibitordexamethasone ( DEX ) and iNOS mRNAtranscriptional inhibitor ActD also significantlyinhibited CM-induced NO production. AG(0.1mmol.L-1) and ActD (0.2ng@Lt) wereequipotent in decreasing NO production inducedby inflammatory stimuli in vitro, and botheffects were more potent than that induced bynon-selectivity NOS activity inhibitor L-NAME(0. 1 mmol@ L- 1) under similar stimuli conditions(P | Guo Liang Zhang Ye Hong Wang Hui Ling Teng Zhi Bin Lin Department of Pharmacology,School of Basic Medical Sciences,Beijing University,Beijiog 100083,ChinaDr.Guo Liang Zhang graduated from Xinxiang Medical College in 1982,got Ph.D.at Nagoya City University Medical School,Japan in 1994,finished postdoctoral research at Beijing Medical Univcrsity in 1996,now an associate professor of pharmacology,specialized in hepatic pharmacology,having 15 papers published. | 2001 | World Journal of Gastroenterology2001，7，3： | 20 |
| 8 | The rice OsV4 encoding a novel pentatricopeptide repeat protein is required for chloroplast development during the early leaf stage under cold stress显示文摘Pentatricopeptide repeat(PPR)proteins,characterized by tandem arrays of a 35 amino acid motif,have been suggested to play central and broad roles in modulating the expression of organelle genes in plants.However,the molecular mechanisms of most rice PPR genes remains unclear.In this paper,we isolated and characterized a temperature-conditional virescent mutant,OsV4,in rice(Oryza sativa cultivar Jiahua1(WT,japonica rice variety)).The mutant displays albino phenotype and abnormal chloroplasts at the three leaf stage,which gradually turns green after the four leaf stage at a low temperature(20°C).But the mutant always develops green leaves and well-developed chloroplasts at a high temperature(32°C).Genetic and molecular analyses uncovered that OsV4 encodes a novel chloroplast-targeted PPR protein including four PPR motifs.Further investigations show that the mutant phenotype is associated with changes in chlorophyll content and chloroplast development.The OsV4transcripts only accumulate to high levels in young leaves,indicating that its expression is tissue-specific.In addition,transcript levels of some ribosomal components and plastid-encoded polymerase-dependent genes are dramatically reduced in the albino mutants grown at 20°C.These findings suggest that OsV4 plays an important role during early chloroplast development under cold stress in rice. | Xiaodi Gong Qianqian Su Dongzhi Lin Quan Jiang Jianlong Xu Jianhui Zhang Sheng Teng Yanjun Dong | 2014 | Journal of Integrative Plant Biology2014，56，4： | 19 |
| 9 | Ubiquitination of Rheb governs growth factor-induced mTORC1 activation显示文摘Mechanistic target of rapamycin mTOR complex 1 (mTORC1)plays a key role in the integration of various environmental signals to regulate cell growth and metabolism,mTORC1 is recruited to the lysosome where it is activated by its interaction with GTP-bound Rheb GTPase.However,the regulatory mechanism of Rheb activity remains largely unknown.Here,we show that ubiquitination governs the nucleotide-bound status of Rheb.Lysosome-anchored E3 ligase RNF152 catalyzes Rheb ubiquitination and promotes its binding to the TSC complex.EGF enhances the deubiquitination of Rheb through AKT-dependent USP4 phosphorylation,leading to the release of Rheb from the TSC complex.Functionally,ubiquitination of Rheb is linked to mTORC1-mediated signaling and consequently regulates tumor growth.Thus,we propose a mechanistic model whereby Rheb-mediated mTORC1 activation is dictated by a dynamic opposing act between Rheb ubiquitination and deubiquitination that are catalyzed by RNF152 and USP4 respectively. | Lu Deng Lei Chen Linlin Zhao Yan Xu Xiaoping Peng Xinbo Wang Lin Ding Jiali Jin Hongqi Teng Yanming Wang Weijuan Pan Fei Yu Lujian Liao Li Li Xin Ge Ping Wang | 2019 | Cell Research2019，29，2： | 16 |
| 10 | Serial stimulated thyroglobulin measurements are more specific for detecting distant metastatic differentiated thyroid cancer before radioiodine therapy显示文摘Objective: Preablative stimulated thyroglobulin(ps-Tg) has the potential to be used in identifying distant metastatic differentiated thyroid carcinoma(DM-DTC), but its single level can be affected by remnant thyroid tissue and thyrotropin(TSH). The objective of this retrospective study was to evaluate the value of serial ps-Tg measurements in identifying DM-DTC specifically.Methods: A total of 317 DTC patients with serial measurements of ps-Tg, TSH and anti-Tg antibody were divided into M1(n=72) and M0(n=245) according to the presence of distant metastasis(DM) or not. The initial psTg measurement, with a corresponding TSH exceeding 30 μIU/m L, was marked as Tg1, and ps-Tg measured right before radioactive iodine(RAI) therapy was defined as Tg2, with a median interval of 8 days. ΔTg denotes Tg2–Tg1, and ΔTSH denotes TSH2–TSH1. Tg1, Tg2, ΔTg, and ΔTg/ΔTSH were tested for efficacy in identifying DM-DTC using receiver operating characteristic(ROC) curve analysis, and further compared with chest computed tomography(CT) and posttreatment whole-body RAI scan(Rx WBS).Results: Compared with single ps-Tg measurement(Tg1 or Tg2), both ΔTg and ΔTg/ΔTSH were more narrowly distributed around zero in the M0 group, which made their distribution in the M1 group more distinguished in a relatively dispersed way. ΔTg/ΔTSH manifested a higher accuracy(88.64%) and specificity(90.20%) in identifying DM-DTC than Tg1 or Tg2 measurements, with a much higher specificity than chest CT(90.20% vs. 66.00%) and a much higher sensitivity than Rx WBS(83.33% vs. 61.11%).Conclusions: Serial ps-Tg measurements even over as short an interval as 8 days hold incremental value in identifying DM-DTC. ΔTg/ΔTSH is a specific early biochemical marker for DM-DTC. | Teng Zhao Jun Liang Tianjun Li Wen Gao Yansong Lin | 2017 | Chinese Journal of Cancer Research2017，29，3： | 15 |
| 11 | A GPCR/secretase complex regulates β- and γ-secretase specificity for Aβ production and contributes to AD pathogenesis显示文摘尾 - 地点的 Dysregulation 劈开应用软件的酶(BACE ) 或纬 - secretase 导致异常生产淀粉 -- 尾肽(尾) 并且贡献 Alzheimer 的疾病(广告) 的病原学。自从这些 secretases,调停众多的蛋白质的解朊的处理,因为不可避免的不希望得到的副作用,小成功都没被获得由 secretase 禁止者对待广告。因此,解开具有重要性这些 secretases 的规章的机制。这里,我们证明那未 - opioid 受体(欧洲粪金龟子) 支持由 BACE1 和纬 - 处理尾先锋蛋白质(应用软件) secretase,然而并非槽口, N-cadherin 或 APLP 的。进一步的调查表明那只欧洲粪金龟子与 BACE1 和纬 - secretase 形成建筑群,并且欧洲粪金龟子的激活调停为应用软件 endoproteolysis secretases/receptor 建筑群排序的 co-endocytic。受体的机能障碍延迟 BACE1 和纬 - secretase 并且这样的 endocytosis 尾的生产。一致地,击倒或欧洲粪金龟子的 antagonization 减少 secretase 活动并且改善一个尾病理和 A 尾 - 依赖者行为的赤字,但是不影响在广告模型老鼠处理槽口, N-cadherin 或 APLP。我们的学习不仅揭开为为尾生产调整 secretase 的特性而且建议形成的那干预或 GPCR/secretase 建筑群的 trafficking 的 DOR/secretase 建筑群的形成的分子的机制能对广告导致新策略,潜在地与更少副作用。 | Lin Teng Jian Zhao Feifei Wang Lan Ma Gang Pei | 2010 | Cell Research2010，20，2： | 14 |
| 12 | Inhibition of Autophagy by Estradiol Promotes Locomotor Recovery after Spinal Cord Injury in Rats显示文摘17β-estradiol(E2) has been shown to have neuroprotective effects in different central nervous system diseases. The mechanisms underlying estrogen neuroprotection in spinal cord injury(SCI) remain unclear. Previous studies have shown that autophagy plays a crucial role in the course of nerve injury. In this study, we showed that E2 treatment improved the restoration of locomotor function and decreased the loss of motor neurons in SCI rats. Realtime PCR and western blot analysis revealed that the protective function of E2 was related to the suppression of LC3 II and beclin-1 expression. Immunohistochemical study further confirmed that the immunoreactivity of LC3 in the motor neurons was down-regulated when treated with E2. In vitro studies demonstrated similar results that E2 pretreatment decreased the autophagic activity induced by rapamycin(autophagy sensitizer) and increased viability in a PC12 cell model. These results indicated that the neuroprotective effects of E2 in SCI are partly related to the suppression of excessive autophagy. | Chao-Wei Lin Bi Chen Ke-Lun Huang Yu-Sen Dai Hong-Lin Teng | 2016 | Neuroscience Bulletin2016，32，2： | 14 |
| 13 | Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer显示文摘Metastasis,the development of secondary malignant growths at a distance from a primary tumor,is the cause of death for 90%of cancer patients,but little is known about how metastatic cancer cells adapt to and colonize new tissue environments.Here,using clinical samples,patient-derived xenograft(PDX)samples,PDX cells,and primary/metastatic cell lines,we discovered that liver metastatic colorectal cancer(CRC)cells lose their colon-specific gene transcription program yet gain a liver-specific gene transcription program.We showed that this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical enhancers and super-enhancers.Further,we identified that the liver-specific transcription factors FOXA2 and HNF1A can bind to the gained enhancers and activate the liver-specific gene transcription,thereby driving CRC liver metastasis.Importantly,similar transcription reprogramming can be observed in multiple cancer types.Our data suggest that reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically. | Shuaishuai Teng Yang Eric Li Ming Yang Rui Qi Yiming Huang Qianyu Wang Yanmei Zhang Shanwen Chen Shasha Li Kequan Lin Yang Cao Qunsheng Ji Qingyang Gu Yujing Cheng Zai Chang Wei Guo Pengyuan Wang Ivan Garcia-Bassets Zhi John Lu Dong Wang | 2020 | Cell Research2020，30，1： | 11 |
| 14 | NUMERICAL SIMULATION OF TURBULENT FREE SURFACE FLOW OVER OBSTRUCTION显示文摘A two-dimensional hybrid numerical model, FEM-LES-VOF, for free surface flows is proposed in this study, which is a combination of three-step Taylor-Galerkin finite element method, large eddy simulation with the Smagorinsky sub-grid model and Computational Lagrangian-Eulerian Advection Remap Volume of Fluid (CLEAR-VOF) method. The present FEM-LES-VOF model allows the fluid flows involving violent free surface and turbulence subject to complex boundary configuration to be simulated in a straightforward manner with unstructured grids in the context of finite element method. Numerical simulation of a benchmark problem of dam breaking is conducted to verify the present model. Comparisons with experimental data show that the proposed model works well and is capable of producing reliable predictions for free surface flows. Using the FEM-LES-VOF model, the free surface flow over a semi-circular obstruction is investigated. The simulation results are compared with available experimental and numerical results. Good performance of the FEM-LES-VOF model is demonstrated again. Moreover, the numerical studies show that the turbulence plays an important role in the evolution of free surface when the reflected wave propagates upstream during the fluid flow passing the submerged obstacle. | LU Lin LI Yu-cheng TENG Bin CHEN Bing | 2008 | Journal of Hydrodynamics2008，20，4： | 10 |
| 15 | Three-dimensional-printed individualized porous implants:A new“implant-bone”interface fusion concept for large bone defect treatment显示文摘Bone defect repairs are based on bone graft fusion or replacement.Current large bone defect treatments are inadequate and lack of reliable technology.Therefore,we aimed to investigate a simple technique using three-dimensional(3D)-printed individualized porous implants without any bone grafts,osteoinductive agents,or surface biofunctionalization to treat large bone defects,and systematically study its long-term therapeutic effects and osseointegration characteristics.Twenty-six patients with large bone defects caused by tumor,infection,or trauma received treatment with individualized porous implants;among them,three typical cases underwent a detailed study.Additionally,a large segmental femur defect sheep model was used to study the osseointegration characteristics.Immediate and long-term biomechanical stability was achieved,and the animal study revealed that the bone grew into the pores with gradual remodeling,resulting in a long-term mechanically stable implant-bone complex.Advantages of 3D-printed microporous implants for the repair of bone defects included 1)that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility,and 2)that osseointegration between the host bone and implants was achieved without bone grafting.Our osseointegration method,in which the“implant-bone”interface fusion concept was used instead of“bone-bone”fusion,subverts the traditional idea of osseointegration. | Teng Zhang Qingguang Wei Hua Zhou Zehao Jing Xiaoguang Liu Yufeng Zheng Hong Cai Feng Wei Liang Jiang Miao Yu Yan Cheng Daoyang Fan Wenhao Zhou Xinhong Lin Huijie Leng Jian Li Xinyu Li Caimei Wang Yun Tian Zhongjun Liu | 2021 | Bioactive Materials2021，6，11： | 9 |
| 16 | Sonographic evaluation of proximal gastric accommodation in patients with functional dyspepsia显示文摘AIM: To assess the value of ultrasonography (US) in evaluation of proximal gastric accommodation disorder in patients with functional dyspepsia (FD). METHODS: Between April 2011 and March 2012, 45 patients with FD and 27 healthy volunteers were enrolled in this study. Two-dimensional ultrasound (2DUS) and 3-dimensional ultrasound (3DUS) were performed sequentially to measure proximal gastric area (PGA), maximal proximal gastric diameter (MPGD), and proximal gastric volume (PGV). These values were measured separately in the two groups every other 5 min for a duration of 25 min after the beginning of ingestion of a test meal. Air pocket grading was done separately for images of 2DUS and blocks of 3DUS obtained at five scanning time points. RESULTS: Both PGA and PGV of patients were significantly smaller than healthy controls (P = 0.000 and 0.002, respectively). Comparing the two parameters between the groups at each time point, the differences were also statistically significant (P = 0.000-0.013), except at 10 min for the PGV (P = 0.077). However, no overall difference was found between the groups in the MPGD measurements (P = 0.114), though it was statistically significant at a 20-minute examination point (P = 0.026). A total of 360 sets or blocks of images were obtained for both 2DUS and 3DUS. For the images analyzed by 2DUS, none were excluded because of gastric gas, and 50 (13.9%) and 310 (86.1%) sets were determined as air pockets grades 1 and 2, respectively. For the images analyzed by 3DUS, 23 (6.4%) blocks were excluded from the measurement due to presence of a large fundus air pocket (grade 3); fifty (13.9%) and 287 (79.7%) blocks were also graded as 1 and 2, respectively. CONCLUSION: Measurement of both PGA and PGV by 2DUS and 3DUS could be useful for assessment of the proximal gastric accommodation. | Xiu-Ping Fan Lin Wang Qiang Zhu Teng Ma Chun-Xia Xia Ya-Jing Zhou | 2013 | World Journal of Gastroenterology2013，19，29： | 9 |
| 17 | Sustained Akt signaling in articular chondrocytes causes osteoarthritis via oxidative stress-induced senescence in mice显示文摘Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus.Genetic mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^(ERT2) developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient mice.Mechanistically, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore,inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA. | Jing Xie Jingting Lin Min Wei Yan Teng Qi He Guan Yang Xiao Yang | 2019 | Bone Research2019，7，3： | 8 |
| 18 | Preparation of Tolterodine Metabolite Loaded Biodegradable PLGA Microspheres显示文摘Biodegradable polymer poly(lactic-co-glycolic acid)(PLGA) was used to encapsulate the pharmacological activity metabolite of tolterodine by means of O/W emulsion solvent evaporation method via homogenization in the emulsification process. The influences of preparation parameters were investigated. The results indicate that increasing PLGA concentration from 15% to 40% made the encapsulation efficiency of 5-hydroxymethyl derivative of tolterodine(5-HMT) increased from 55.39% to 76.32%, and the particle size increased from 34.33 μm to 70.78 μm. In addition, when homogenization speed increased from 850 r/min to 2300 r/min, both particle size and encapsulation efficiency of microspheres decreased. An increase in the volume of aqueous phase led to higher encapsulation efficiency and bigger particle size. Increasing temperature made encapsulation efficiency and particle size change significantly. While reaction temperature increased from 20 °C to 50 °C, the encapsulation efficiency decreased from 70.44% to 24.07%, and particle size increased from 38.66 μm to 69.38 μm. High reaction temperature(over 40 °C) may lead to porous surface of microspheres. Porous surface, encapsulation efficiency and particle size influenced on the in vitro release of 5-HMT together. | TENG Le-sheng JIANG Chao-jun LIN Xiang-you DONG Yuan-chen LI Chun-mei MENG Qing-fan LI You-xin | 2010 | Chemical Research in Chinese Universities2010，26，1： | 8 |
| 19 | BubR1 phosphorylates CENP-E as a switch enabling the transition from lateral association to end-on capture of spindle microtubules显示文摘Error-free mitosis depends on accurate chromosome attachment to spindle microtubules, powered congression of those chromosomes, their segregation in anaphase, and assembly of a spindle midzone at mitotic exit. The centromere-associated kinesin motor CENP-E, whose binding partner is BubR1, has been implicated in congression of misaligned chromosomes and the transition from lateral kinetochore-microtubule association to end-on capture. Although previously proposed to be a pseudokinase, here we report the structure of the kinase domain of Drosophila melanogaster BubR1, revealing its folding into a conformation predicted to be catalytically active. BubR1 is shown to be a bona fide kinase whose phosphorylation of CENP-E switches it from a laterally attached microtubule motor to a plus-end microtubule tip tracker. Computational modeling is used to identify bubristatin as a selective BubR1 kinase antagonist that targets the αN1 helix of N-terminal extension and αC helix of the BubR1 kinase domain. Inhibition of CENP-E phosphorylation is shown to prevent proper microtubule capture at kinetochores and, surprisingly, proper assembly of the central spindle at mitotic exit. Thus, BubR1-mediated CENP-E phosphorylation produces a temporal switch that enables transition from lateral to end-on microtubule capture and organization of microtubules into stable midzone arrays. | Yuejia Huang Lin Lin Xing Liu Sheng Ye Phil Y. Yao Wenwen Wang Fengrui Yang Xinjiao Gao Junying Li Yin Zhang Jiancun Zhang Zhihong Yang Xu Liu Zhenye Yang Jianye Zang Maikun Teng Zhiyong Wang Ke Ruan Xia Ding Lin Li Don W. Cleveland Rongguang Zhang Xuebiao Yao | 2019 | Cell Research2019，29，7： | 8 |
| 20 | Odontoblast β-catenin signaling regulates fenestration of mouse Hertwig's epithelial root sheath显示文摘The interaction between Hertwig's epithelial root sheath(HERS) and the adjacent mesenchyme is vitally important in mouse tooth root development. We previously generated odontoblast-specific Ctnnb1(encoding β-catenin) deletion mice, and demonstrated that odontoblast β-catenin signaling regulates odontoblast proliferation and differentiation. However, the role of odontoblast β-catenin signaling in regulation of HERS behavior has not been fully investigated. Here, using the same odontoblast-specific Ctnnb1 deletion mice, we found that ablation of β-catenin signaling in odontoblasts led to aberrant HERS formation. Mechanistically, odontoblast-specific Ctnnb1 deletion resulted in elevated bone morphogenetic protein 7(Bmp7) expression and reduced expression of noggin and follistatin, both of which encode extracellular inhibitors of BMPs. Furthermore, the levels of phosphorylated Smad1/5/8 were increased in HERS cells. In vitro tissue culture confirmed that BMP7 treatment disrupted the HERS structure. Taken together, we demonstrated that odontoblast β-catenin signaling may act through regulation of BMP signaling to maintain the integrity of HERS cells. | ZHANG Ran TENG Yan ZHU Liang LIN JingTing YANG Xiao YANG Guan LI TieJun | 2015 | Science China(Life Sciences)2015，58，9： | 8 |
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