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| 1 | Washed microbiota transplantation vs.manual fecal microbiota transplantation:clinical findings,animal studies and in vitro screening显示文摘Fecal microbiota transplantation(FMT)by manual preparation has been applied to treat diseases for thousands of years.However,this method still endures safety risks and challenges the psychological endurance and acceptance of doctors,patients and donors.Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events.This washing preparation makes delivering a precise dose of the enriched microbiota feasible,instead of using the weight of stool.Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration.The toxic reactions that include death,the change in the level of peripheral white blood cells,and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted.The metagenomic next-generation sequencing(NGS)indicated the increasing types and amount of viruses could be washed out during the washing process.Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4,corticosterone,and prostaglandin G2 could be removed by repeated washing.Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washingprocess.In conclusion,this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation(WMT)is safer,more precise and more quality-controllable than the crude FMT by manual. | Ting Zhang Gaochen Lu Zhe Zhao Yafei Liu Quan Shen Pan Li Yaoyao Chen Haoran Yin Huiquan Wang Cicilia Marcella Bota Cui Lei Cheng Guozhong Ji Faming Zhang | 2020 | Protein & Cell2020，11，4： | 44 |
| 2 | Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study显示文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy. | Zhi Peng Tianshu Liu Jia Wei Airong Wang Yifu He Liuzhong Yang Xizhi Zhang Nanfeng Fan Suxia Luo Zhen Li Kangsheng Gu Jianwei Lu Jianming Xu Qingxia Fan Ruihua Xu Liangming Zhang Enxiao Li Yuping Sun Guohua Yu Chunmei Bai Yong Liu Jiangzheng Zeng Jieer Ying Xinjun Liang Nong Xu Chao Gao Yongqian Shu Dong Ma Guanghai Dai Shengmian Li Ting Deng Yuehong Cui Jianmin Fang Yi Ba Lin Shen | 2021 | Cancer Communications2021，41，11： | 29 |
| 3 | Prevalence of Thyroid Nodules and Its Relationship with Iodine Status in Shanghai:a Population-based Study显示文摘Objective This study was designed to evaluate the prevalence of thyroid nodules(TNs) and its relationship with urine iodine concentrations(UICs) after the regional rapid economic growth and lifestyle changes. Methods A cross-sectional survey was conducted in the general population aged 15-69 years. A questionnaire regarding general and personal characteristics and relevant information was administered. Ultrasonography of the thyroid was performed, and serum triiodothyronine(T3), tetraiodothyronine(T4), serum thyroid stimulating hormone(TSH), free triiodothyronine(FT3), free tetraiodothyronine(FT4), thyroglobulin antibody(Tg Ab), thyroid peroxidase antibody(TPOAb), and TSH receptor antibody(TRAb) levels were measured for each individual subject. Results The prevalence rates of TNs in the whole population, females and males were 27.76%, 34.04%, and 21.60%, respectively. The prevalence of multiple nodules increased with age, whereas the prevalence peaks differed between males and females. The median UICs in the whole population and females with non-TNs were higher than those of subjects with TNs(P=0.0035, P=0.0068). The median UICs in subjects with a single TN were higher than those in subjects with multiple TNs(P=0.0164, P=0.0127). The result showed a U-shaped curve relationship between UIC and prevalence of TNs. The prevalence of TNs was the lowest when the UIC was 140-400 μg/L. Conclusion The prevalence of TNs was nearly 30% and increased with age. The relationship between UIC and prevalence of TNs is U-shaped, with an increase in risk when the UIC was <140 μg/L and >400 μg/L. Very low or high UIC levels need attention and correction. | SONG Jun ZOU Shu Rong GUO Chang Yi ZANG Jia Jie ZHU Zhen Ni MI Ming HUANG Cui Hua YU Hui Ting LU Xi RUAN Ye WU Fan | 2016 | Biomedical and Environmental Sciences2016，29，6： | 25 |
| 4 | Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma显示文摘Esophageal squamous cell carcinoma(ESCC)is a poor-prognosis cancer type with limited understanding of its molecular etiology.Using 508 ESCC genomes,we identified five novel significantly mutated genes and uncovered mutational signature clusters associated with metastasis and patients’outcomes.Several functional assays implicated that NFE2L2 may act as a tumor suppressor in ESCC and that mutations in NFE2L2 probably impaired its tumor-suppressive function,or even conferred oncogenic activities.Additionally,we found that the NFE2L2 mutations were significantly associated with worse prognosis of ESCC.We also identified potential noncoding driver mutations including hotspot mutations in the promoter region of SLC35E2 that were correlated with worse survival.Approximately 5.9%and 15.2%of patients had high tumor mutation burden or actionable mutations,respectively,and may benefit from immunotherapy or targeted therapies.We found clinically relevant coding and noncoding genomic alterations and revealed three major subtypes that robustly predicted patients’outcomes.Collectively,we report the largest dataset of genomic profiling of ESCC useful for developing ESCC-specific biomarkers for diagnosis and treatment. | Yongping Cui Hongyan Chen Ruibin Xi Heyang Cui Yahui Zhao Enwei Xu Ting Yan Xiaomei Lu Furong Huang Pengzhou Kong Yang Li Xiaolin Zhu Jiawei Wang Wenjie Zhu Jie Wang Yanchun Ma Yong Zhou Shiping Guo Ling Zhang Yiqian Liu Bin Wang Yanfeng Xi Ruifang Sun Xiao Yu Yuanfang Zhai Fang Wang Jian Yang Bin Yang Caixia Cheng Jing Liu Bin Song Hongyi Li Yi Wang Yingchun Zhang Xiaolong Cheng Qimin Zhan Yanhong Li Zhihua Liu-Show | 2020 | Cell Research2020，30，10： | 19 |
| 5 | An HBV-encoded miRNA activates innate immunity to restrict HBV replication显示文摘We previously identified that hepatitis B virus(HBV)encodes a microRNA(HBV-miR-3)that restrains HBV replication by targeting the HBV transcript.However,whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains unclear.Here,we examined the vital functions of HBV-miR-3 in the innate immune response after HBV infection.We found that HBV-miR-3 expression gradually increased in a dose-and time-dependent manner in HBV-infected HepG2-NTCP cells.HBV-miR-3 activated the JAK/STAT signaling pathway by downregulating SOCS5 in hepatocytes,thereby enhancing the IFN-induced anti-HBV effect.In addition,HBVmiR-3 in exosomes facilitated the Ml polarization of macrophages.Furthermore,exosomes containing HBV-miR-3 enhanced the secretion of IL-6 via inhibiting the SOCS5-mediated ubiquitination of EGFR.In short,these results demonstrate that HBV-miR-3 activates the innate immune response to restrain HBV replication by multiple pathways,which may suppress HBV-induced acute liver cell injury and affect the progression of persistent HBV infection. | Xiaoqing Zhao Lu Sun Ting Mu Jianying Yi Chaoqun Ma Hong Xie Min Liu Hua Tang | 2020 | Journal of Molecular Cell Biology2020，12，4： | 17 |
| 6 | Uric formaldehyde levels are negatively correlated with cognitive abilities in healthy older adults显示文摘Recent studies have shown that the abnormal accumulation of endogenous formaldehyde could be a critical factor in age-related cognitive decline. The aim of this study was to estimate the correlation between uric formaldehyde and general cognitive abilities in a community-based elderly population, and to measure the extent and direction in which the correlation varied with demographic characteristics. Using a double-blind design, formaldehyde in human urine was analyzed by high-performance liquid chromatography(n = 604), and general cognitive abilities were measured using the Montreal Cognitive Assessment(MoCA). Demographic characteristics, in terms of age, gender, residential region, and education were taken into consideration. We found that uric formaldehyde levels were inversely correlated with the MoCA score, and the concentration varied with demographic features: higher odds of a high formaldehyde level occurred among the less educated and those living in old urban or rural areas. In cytological experiments, the level of cellular formaldehyde released into the medium increased as SH-SY5Y and BV2 cells were incubated for three days. Formaldehyde in excess impairedthe processes of N2a cells and neurites of primary cultured rat hippocampal cells. However, removal of formaldehyde markedly rescued and regenerated the processes of N2a cells. These results demonstrated a negative correlation between the endogenous formaldehyde and general cognitive abilities. High formaldehyde levels could be a risk factor for cognitive impairment in older adults, and could be developed as a non-invasive marker for detection and monitoring of age-related cognitive impairment. | Jing Yu Tao Su Ting Zhou Yingge He Jing Lu Juan Li Rongqiao He | 2014 | Neuroscience Bulletin2014，30，2： | 14 |
| 7 | Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells显示文摘瞄准: Platycodin D,从中国植物 Platycodonis 根值孤立的主要 saponin,对各种各样的癌症房间线的展览 anticancer 活动。这里,我们在 vitro 并且在 vivo 把它的 anticancer 行动与人的 hepatocellular 癌房间作比较,并且阐明在 platycodin 之间的关系导致 D 的 apoptosis 和 autophagy.Methods : 人的 hepatocellular 癌 BEL-7402 房间的生存能力与 MTT 试金被评估,并且 apoptosis 用染色试金的 Annexin V/PI 和 Hoechst 33342 被检验。染色的 Monodansylcadaverine (MDC ) 被用来标记 autophagic 为液泡。蛋白质用西方的污点分析被检测。为在 vivo 学习它的 anticancer 行动, platycodin D (5 和 10 mg· kg −1·d−1) intraperitoneally 为 21 days.Results 被注射到 BEL-7402-bearing 鼠标: Platycodin D ( 5-40 μ ; mol/L )与 37.70 ± 的 IC50 值在 vitro 禁止了房间增长; 3.99 , 24.30 ± ; 2.30 和 19.70 ± ; 2.36 μ ;在 24 , 48 和 72 h 的 mol/L ,分别地。Platycodin D (5-20 μ mol/L ) dose-dependently 增加了 BEL-7402 房间 apoptosis,增加了 Bax/Bcl-2 比率和劈开的 PARP 的层次并且劈开 caspase-3,并且减少 Bcl-2 的水平。而且, platycodin D (5-20 μ mol/L ) 在 BEL-7402 房间导致了 autophagy,由细胞质的液泡的形成证实了 LC3-II 的增加的数量,和 MDC 积极的房间的增加的数字。有 autophagy 禁止者 chloroquine 的预告的处理(5 μ mol/L ) 或 BAF (50 nmol/L ) 显著地提高了 platycodin 导致 D 的增长抑制和 apoptosis。而且, platycodin D (20 μ mol/L ) 激活 ERK,在 BEL-7402 房间的 JNK 小径,和二条小径的同时的阻塞有效地压制了 platycodin 导致 D 的 autophagy 和提高的 platycodin 导致 D 的 apoptosis。在 BEL-7402-bearing 鼠标, platycodin D (10 mg· kg −1•d−1) 显著地与减少的身体 weight.Conclusion 减少了相对肿瘤体积: Platycodin D 不仅禁止 BEL-7402 房间的增长而且压制 BEL-7402 异种皮移植肿瘤生长。Platycodin 导致 D 的房间增长抑制和 apoptosis 被合作处理与 autophagy | Ting LI Xiao-huang XU Zheng-hai TANG Ya-fang WANG Chung-hang LEUNG Dik-lung MA Xiu-ping CHEN Yi-tao WANG Yi CHEN Jin-jian LU | 2015 | Acta Pharmacologica Sinica2015，0，12： | 13 |
| 8 | Management of granulomatous lobular mastitis: an international multidisciplinary consensus(2021 edition)显示文摘Granulomatous lobular mastitis(GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence.Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions,etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology.The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidencebased consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM. | Qian-Qian Yuan Shu-Yuan Xiao Omar Farouk Yu-Tang Du Fereshte Sheybani Qing Ting Tan Sami Akbulut Kenan Cetin Afsaneh Alikhassi Rami Jalal Yaghan Irmak Durur-Subasi Fatih Altintoprak Tae Ik Eom Fatih Alper Mustafa Hasbahceci David Martínez-Ramos Pelin Seher Oztekin Ava Kwong Cedric W.Pluguez-Turul Kirstyn EBrownson Shirish Chandanwale Mehran Habib Liu-Yi Lan Rui Zhou Xian-Tao Zeng Jiao Bai Jun-Wen Bai Qiong-Rong Chen Xing Chen Xiao-Ming Zha Wen-Jie Dai Zhi-Jun Dai Qin-Yu Feng Qing-Jun Gao Run-Fang Gao Bao-San Han Jin-Xuan Hou Wei Hou Hai-Ying Liao Hong Luo Zheng-Ren Liu Jing-Hua Lu Bin Luo Xiao-Peng Ma Jun Qian Jian-Yong Qin Wei Wei Gang Wei Li-Ying Xu Hui-Chao Xue Hua-Wei Yang Wei-Ge Yang Chao-Jie Zhang Fan Zhang Guan-Xin Zhang Shao-Kun Zhang Shu-Qun Zhang Ye-Qiang Zhang Yue-Peng Zhang Sheng-Chu Zhang Dai-Wei Zhao Xiang-Min Zheng Le-Wei Zheng Gao-Ran Xu Wen-Bo Zhou Gao-Song Wu | 2022 | Military Medical Research2022，9，4： | 13 |
| 9 | Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development显示文摘Brain size and cognitive skills are the most dramatically changed traits in humans during evolution and yet the genetic mechanisms underlying these human-specific changes remain elusive.Here,we successfully generated 11 transgenic rhesus monkeys(8 first-generation and 3 second-generation)carrying human copies of MCPH1,an important gene for brain development and brain evolution.Brain-image and tissue-section analyses indicated an altered pattern of neural-cell differentiation,resulting in a delayed neuronal maturation and neural-fiber myelination of the transgenic monkeys,similar to the known evolutionary change of developmental delay(neoteny)in humans.Further brain-transcriptome and tissue-section analyses of major developmental stages showed a marked human-like expression delay of neuron differentiation and synaptic-signaling genes,providing a molecular explanation for the observed brain-developmental delay of the transgenic monkeys.More importantly,the transgenic monkeys exhibited better short-term memory and shorter reaction time compared with the wild-type controls in the delayed-matching-to-sample task.The presented data represent the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model and it values the use of non-human primates in understanding unique human traits. | Lei Shi Xin Luo Jin Jiang Yongchang chen Cirong Liu Ting Hu Min Li Qiang Lin Yanjiao Li Jun Huang Hong Wang Yuyu Niu Yundi Shi Martin Styner Jianhong Wang Yi Lu Xuejin Sun Hualin Yu Weizhi Ji Bing Su | 2019 | National Science Review2019，6，3： | 12 |
| 10 | Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells显示文摘Objective: To evaluate the effects of Celastrus Orbiculatus extracts(COE) on metastasis in hypoxiainduced hepatocellular carcinoma cells(Hep G2) and to explore the underlying molecular mechanisms. Methods:The effect of COE(160, 200 and 240 μg/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide(MTT), scratch-wound and transwell assays, respectively. Co Cl2 was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immuno?uorescence analysis,respectively. Results: COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner(P<0.01). Furthermore, the expression of epithelial-mesenchymal transition(EMT) related markers were also remarkably suppressed in a dose-dependent manner(P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1α(Hif-1α) and Twist1 were suppressed by COE. Additionally, the Hif-1α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole(YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced Hep G2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect(P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced Hep G2 cells. Conclusions: COE signi?cantly inhibited the tumor metastasis and EMT by suppressing Hif-1α/Twist1 signaling pathway in hypoxia-induced Hep G2 cell. Thus, COE might have potential effect to inhibit the progression of Hep G2 in the context of tumor hypoxia. | QIAN Ya-yun SHI You-yang LU Song-hua YANG Ting ZHAO Xue-yu YAN Yan LI Wen-yuan LIU Yan-qing | 2019 | Chinese Journal of Integrative Medicine2019，25，5： | 12 |
| 11 | Jianpijiedu Fang improves survival of hepatocarcinoma mice by affecting phosphatase and tensin homolog, phosphoinositide 3-kinase, and focal adhesion kinase显示文摘OBJECTIVE: To investigate the effect of Jianpijiedu Fang (JPJDF) on phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and focal adhesion kinase (FAK), and on the survival of hepatocellular carcinoma (HCC) nude mice. METHODS: Forty male nude mice were randomly divided into 4 groups. Human HCC tissue was implanted in the livers of three groups. After 24 h, the three groups were treated respectively with JPJDF (37.5 g/kg), saline (20 mL/kg) and Tegafur (FT-207, 160 mg/kg) once a day for 10 weeks. The control group without implanting the tissue was concurrently treated with saline (20 mL/kg). The survival data and body weight of all mice were recorded, and expression levels of PTEN, PI3K and FAK in normal tissue and cancer tissue of the livers were eval-uated with immunohistochemical method. RESULTS: The cumulative survival rate of the mice in the JPJDF group was higher than those of the other groups. The rate of weight loss was the lowest in JPJDF group. The survivability and weight loss rate in FT-207 group were the poorest in all groups. The expression intensity of PTEN was higher in normal tissues than in cancer tissues, and lower in the normal tissues of HCC models than in that of mice without HCC. The PTEN expression intensity in normal tissue and cancer tissue from mice treated with FT-207 were lower than that from the mice treated with JPJDF or saline.The expression intensity of PI3K was higher in cancer tissue than in normal tissue. The PI3K expression intensity was the lowest in normal tissue and cancer tissue from mice treated with JPJDF, and the intensity from mice treated with FT-207 was the highest. In mice treated with JPJDF, the expression intensity of FAK was higher in the normal tissue and lower in the cancer tissue than those of the other treatment groups. CONCLUSION: The mechanism accounting for the prolonged survival of HCC-bearing mice treated with JPJDF might be related to the reduction in weight loss and the benign regulation of PTEN, PI3K, and FAK. | Baoguo Sun Jun Meng Ting Xiang Zexiong Chen Yulong Li Lisha Lu Shijun Zhang Xiaolin Chen | 2013 | Journal of Traditional Chinese Medicine2013，33，4： | 12 |
| 12 | MiR-122-5p suppresses the proliferation, migration, and invasion of gastric cancer cells by targeting LYN显示文摘Gastric cancer(GC)is one of malignant tumors with high mortality and morbidity in the world.MicroRNA-122(miR-122)acts as a tumor suppressor in a variety of cancers and has been found to be dominant in gastric adenocarcinoma.However,the specific biological function of miR-122-5p in GC is not completely clear.In this study,we found that miR-122-5p was low-expressed in GC tissues and cell lines by using qRT-PCR.Overexpression of miR-122-5p inhibited the proliferation,migration,and invasion of GC cells by using CCK-8 and transwell assays.On the contrary,downregulation of miR-122-5p promoted the proliferation,migration,and invasion of GC cells.In addition,we found that the expression of LYN,an Src family tyrosine kinase,was inversely correlated with miR-122-5p expression in GC tissues by using western blot analysis,immunohistochemistry,and qRT-PCR assays.Meanwhile,luciferase assay results indicated that LYN is a direct target of miR-122-5p in GC cells.Moreover,silencing LYN expression by its siRNA inhibited the proliferation,migration,and invasion of GC cells.Importantly,overexpression of LYN restored miR-122-5p-mediated inhibition of the proliferation,migration,and invasion of GC cells.Taken together,our results indicated miR-122-5p inhibited the proliferation,migration,and invasion by targeting LYN in GC. | Lei Meng Zhangming Chen Zhe Jiang Ting Huang Jie Hu Panquan Luo Hongli Zhang Mengqi Huang Lei Huang Yu Chen Ming Lu A-man Xu Songcheng Ying | 2020 | Acta Biochimica et Biophysica Sinica2020，52，1： | 12 |
| 13 | Potentiating CD8^(+) T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling显示文摘Metabolic regulation has been proven to play a critical role in T cell antitumor immunity.However,cholesterol metabolism as a key component of this regulation remains largely unexplored.Herein,we found that the low-density lipoprotein receptor(LDLR),which has been previously identified as a transporter for cholesterol,plays a pivotal role in regulating CD8+T cell antitumor activity.Besides the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion,we also found a non-canonical function of LDLR in CD8+T cells:LDLR interacts with the T-cell receptor(TCR)complex and regulates TCR recycling and signaling,thus facilitating the effector function of cytotoxic T-lymphocytes(CTLs).Furthermore,we found that the tumor microenvironment(TME)downregulates CD8+T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9(PCSK9)which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of CTLs.Moreover,genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+T cells by alleviating the suppressive effect on CD8+T cells and consequently inhibit tumor progression.While previously established as a hypercholesterolemia target,this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well. | Juanjuan Yuan Ting Cai Xiaojun Zheng Yangzi Ren Jingwen Qi Xiaofei Lu Huihui Chen Huizhen Lin Zijie Chen Mengnan Liu Shangwen He Qijun Chen Siyang Feng Yingjun Wu Zhenhai Zhang Yanqing Ding Wei Yang | 2021 | Protein & Cell2021，12，4： | 12 |
| 14 | Preparation of high-affinity rabbit monoclonal antibodies for ciprofloxacin and development of an indirect competitive ELISA for residues in milk显示文摘A convenient competitive enzyme-linked immunosorbent assay(ELISA) for ciprofloxacin(CPFX) was developed by using rabbit monoclonal antibodies(RabMAbs) against a hapten-protein conjugate of CPFX-bovine serum albumin(BSA).The indirect competitive ELISA of CPFX had a concentration at 50% inhibition(IC50) of 1.47 ng/ml and a limit of detection(LOD) of 0.095 ng/ml.The mAb exhibited some cross-reactivity,however,not so high with enrofloxacin(28.8%),ofloxacin(13.1%),norfloxacin(11.0%),fleroxacin(22.6%),and pefloxacin(20.4%).And it showed almost no cross-reactivity with other antibiotics or sulfonamides evaluated in this study.The competitive ELISA kit developed here could be used as a screening tool to detect and control illegal addition of CPFX in food products.This kit had been applied to milk detection and the recovery rates from samples spiked by CPFX were in a range of 63.02%-84.60%,with coefficients of variation of less than 12.2%. | Bin HUANG Yun YIN Lei LU Hai DING Lin WANG Ting YU Jia-jin ZHU Xiao-dong ZHENG Yan-zhen ZHANG | 2010 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2010，11，10： | 11 |
| 15 | Visualizing the microtubule-associated protein tau in the nucleus显示文摘Although tau is mainly known as an axonal microtubule-associated protein,many studies indicate that it is not restricted to this subcellular compartment.Assessing tau’s subcellular distribution,however,is not trivial as is evident from transgenic mouse studies.When human tau is over-expressed,it can be immunohistochemically localized to axons and the somatodendritic domain,modeling what is found in neurodegenerative diseases such as Alzheimer’s disease.Yet,in wild-type mice,despite its abundance,tau is difficult to visualize even in the axon.It is even more challenging to detect this protein in the nucleus,where tau has been proposed to protect DNA from damage.To establish a framework for future studies into tau’s nuclear functions,we compared several methods to visualize endogenous nuclear tau in cell lines and mouse brain.While depending on the fixation and permeabilization protocol,we were able to detect nuclear tau in SH-SY5Y human neuroblastoma cells,we failed to do so in N2a murine neuroblastoma cells.As a second method we used subcellular fractionation of mouse tissue and found that in the nucleus tau is mainly present in a hypophosphorylated form.When either full-length or truncated human tau was expressed,both accumulated in the cytoplasm,but were also found in the nuclear fraction.Because subcellular fractionation methods have their limitations,we finally isolated nuclei to probe for nuclear tau and found that the nuclei were free of cytoplasmic contamination.Together our analysis identifies several protocols for detecting tau in the nucleus where it is found in a less phosphorylated form. | LU Jing LI Ting HE RongQiao BARTLETT Perry F GTZ Jürgen | 2014 | Science China(Life Sciences)2014，57，4： | 11 |
| 16 | Low-loss metasurface optics down to the deep ultraviolet region显示文摘Shrinking conventional optical systems to chip-scale dimensions will benefit custom applications in imaging,displaying,sensing,spectroscopy,and metrology.Towards this goal,metasurfaces-planar arrays of subwavelength electromagnetic structures that collectively mimic the functionality of thicker conventional optical elements-have been exploited at frequencies ranging from the microwave range up to the visible range.Here,we demonstrate highperformance metasurface optical components that operate at ultraviolet wavelengths,including wavelengths down to the record-short deep ultraviolet range,and perform representative wavefront shaping functions,namely,highnumerical-aperture lensing,accelerating beam generation,and hologram projection.The constituent nanostructured elements of the metasurfaces are formed of hafnium oxide-a loss-less,high-refractive-index dielectric material deposited using low-temperature atomic layer deposition and patterned using high-aspect-ratio Damascene lithography.This study opens the way towards low-form factor,multifunctional ultraviolet nanophotonic platforms based on flat optical components,enabling diverse applications including lithography,imaging,spectroscopy,and quantum information processing. | Cheng Zhang Shawn Divitt Qingbin Fan Wenqi Zhu Amit Agrawal Yanqing Lu Ting Xu Henri J.Lezec | 2020 | Light(Science & Applications)2020，9，1： | 11 |
| 17 | Very high baseline HIV viremia impairs efficacy of non-nucleoside reverse transcriptase inhibitor-based ART:a longterm observation in treatment-naïve patients显示文摘Background:It is not completely clear whether a very high pre-therapy viral load(≥500000 copies/ml)can impair the virological response.The aim of this study was to examine the influence of very high baseline HIV-RNA levels on long-term virological responses under one type of regimen.Methods:A retrospective study was performed based on data from two multicenter cohorts in China from January to November 2009,and from May 2013 to December 2015.Untreated HIV infected adults between 18 and 65 years old were recruited before receiving non-nucleoside reverse transcriptase inhibitor-based regimen.All patients had baseline HIV-RNA levels over 500 copies/ml,good adherence,and were followed for at least 24 weeks.Virological suppression was defined as the first HIV-RNA<50 copies/ml.Virological failure was defined as any of incomplete viral suppression(HIV-RNA≥200 copies/ml without virological suppression within 24 weeks of treatment)and viral rebound(confirmed HIV-RNA level≥50 copies/ml after virological suppression).Chi-square test,Kaplan–Meier analysis,Cox proportional hazards model and Logistic regression were used to compare virological response between each pretreated viral load stratum.Results:A total of 758 treatment-naïve HIV patients in China were enlisted.Median follow-up time(IQR)was 144(108–276)weeks.By week 48,rates of virological suppression in three groups(<100000,100000–500000 and≥500000 copies/ml)were 94.1,85.0,and 63.8%,respectively(P<0.001).Very high baseline HIV viremia over 500000 copies/ml were found to be associated with delayed virological suppression(≥500000 vs<100000,adjusted relative hazard=0.455,95%CI:0.32–0.65;P<0.001)as well as incomplete viral suppression(≥500000 vs<100000,adjusted odds ratio[aOR]=6.084,95%CI:2.761–13.407;P<0.001)and viral rebound(≥50000 vs<100000,aOR=3.671,95%CI:1.009–13.355,P=0.048).Conclusions:Very high levels of pre-treatment HIV-RNA were related with delayed efficacy of NNRTI-based ART and increased risk of treatment failure.More potent initial regimens should be considered for those with this clinical character. | Shuai Chen Yang Han Xiao-Jing Song Yan-ling Li Ting Zhu Hong-Zhou Lu Xiao-Ping Tang Tong Zhang Min Zhao Yun He Sheng-Hua He Min Wang Yong-Zhen Li Shao-Biao Huang Yong Li Jing Liu Wei Cao Tai-Sheng Li | 2020 | Infectious Diseases of Poverty2020，9，3： | 10 |
| 18 | Proteomic analysis of hepatocellular carcinoma HepG2 cells treated with platycodin D显示文摘Platycodin D(PD), a triterpenoid saponin isolated from Platycodonis Radix, is a famous Chinese herbal medicine that has been shown to have anti-proliferative effects in several cancer cell lines. The aim of this study was to determine the changes in cellular proteins after the treatment of hepatocellular carcinoma HepG2 cells with PD using proteomics approaches. The cell viability was determined using the MTT assay. The proteome was analyzed by two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Western blot analysis was used to confirm the expression of changed proteins. Our results showed that PD inhibited the proliferation of HepG2 cells in concentration- and time-dependent manners. Sixteen proteins were identified to be up-regulated in PD-treated HepG2 cells, including ATP5 H, OXCT1, KRT9, CCDC40, ERP29, RCN1, ZNF175, HNRNPH1, HSP27, PA2G4, PHB, BANF1, TPM3, ECH1, LGALS1, and MYL6. Three proteins(i.e., RPS12, EMG1, and KRT1) decreased in HepG2 cells after treatment with PD. The changes in HSP27 and PHB were further confirmed by Western blotting. In conclusion, our results shed new lights on the mechanisms of action for the anti-cancer activity of PD. | LU Jin-Jian LU De-Zhao CHEN Yu-Fei DONG Ya-Ting ZHANG Jun-Ren LI Ting TANG Zheng-Hai YANG Zhen | 2015 | Chinese Journal of Natural Medicines2015，13，9： | 10 |
| 19 | Research on the reconstruction method of porous media using multiple-point geostatistics显示文摘The pore structural characteristics have been the key to the studies on the mechanisms of fluids flow in porous media. With the development of experimental technology, the modern high-resolution equipments are capable of capturing pore structure images with a resolution of microns. But so far only 3D volume data of millimeter-scale rock samples can be obtained losslessly. It is necessary to explore the way of virtually reconstructing larger volume digital samples of porous media with the representative structural characteristics of the pore space. This paper proposes a reconstruction method of porous media using the structural characteristics captured by the data templates of multiple-point geostatistics. In this method, the probability of each structural characteristic of a pore space is acquired first, and then these characteristics are reproduced according to the probabilities to present the real structural characteristics in the reconstructed images. Our experimental results have shown that: (i) the deviation of LBM computed permeability respectively on the virtually reconstructed sandstone and the original sample is less than 1.2%; (ii) the reconstructed sandstone and the original sample have similar structural characteristics demonstrated by the variogram curves. | ZHANG Ting 1,2,3, LI DaoLun 1,2 , LU DeTang 1,2 & YANG JiaQing 1,2 1 Department of Modern Mechanics, University of Science and Technology of China, Hefei 230027, China 2 Research Center of Oil and Natural Gas, University of Science and Technology of China, Hefei 230027, China 3 The 28th Research Institute, China Electronics Technology Group Corporation, Nanjing, 210007, China | 2010 | Science China(Physics,Mechanics & Astronomy)2010，53，1： | 10 |
| 20 | WATER 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 | 2011 | Journal of Hydrodynamics2011，23，1： | 10 |
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