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| 1 | MicroRNA changes of bone marrow-derived mesenchymal stem cells differentiated into neuronal-like cells by Schwann cell-conditioned medium显示文摘Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potentially associated with neural differentiation of bone marrow-derived mesenchymal stem cells. This study, which carried out successful microRNA analysis of neuronal-like cells differentiated from bone marrow-derived mesenchymal stem cells by Schwann cell induction, revealed key microRNAs and pathways involved in neural differentiation of bone marrow-derived mesenchymal stem cells. All protocols were approved by the Animal Ethics Committee of Institute of Radiation Medicine, Chinese Academy of Medical Sciences on March 12, 2017 (approval number: DWLI-20170311). | Zhi-Jian Wei Bao-You Fan Yang Liu Han Ding Hao-Shuai Tang Da-Yu Pan Jia-Xiao Shi Peng-Yuan Zheng Hong-Yu Shi Heng Wu Ang Li Shi-Qing Feng | 2019 | Neural Regeneration Research2019，14，8： | 13 |
| 2 | Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45显示文摘Objective:Side population(SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer.Many kinds of cell lines and tissues have demonstrated the presence of SP cells,including several gastric cancer cell lines.This study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line MKN-45.Methods:We used fluorescence activated cell sorting(FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45(cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP cells.Results:This study found that the SP cells had higher clone formation efficiency than major population(MP) cells.Five stemness-related gene expression profiles,including OCT-4,SOX-2,NANOG,CD44,and adenosine triphosphate(ATP)-binding cassette transporters gene ABCG2,were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction(RT-PCR).Western blot was used to show the difference of protein expression between SP and MP cells.Both results show that there was significantly higher protein expression in SP cells than in MP cells.When inoculated into non-obese diabetic/severe combined immunodeficiency(NOD/SCID) mice,SP cells show higher tumorigenesis tendency than MP cells.Conclusions:These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells. | Hai-hong ZHANG Ai-zhen CA Xue-ming WEI Li DING Feng-zhi LI Ai-ming ZHENG Da-jiang DAI Rong-rong HUANG Hou-jun CAO Hai-yang ZHOU Jian-mei WANG Xue-jing WANG Wei SHI Heng ZHU Xiao-ying YUAN Lin CHEN | 2013 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2013，14，3： | 9 |
| 3 | The localization of type 2 diabetes susceptibility gene loci in northern Chinese Han families显示文摘We conducted a genome-wide scan, in which 358 well distributed fluorescent dye-labeled microsatellite marker sets were applied in 32 Chinese Han type 2 diabetes families from Northern China to search for the susceptibility gene loci. The data collected from screening all the chromosomes of genome were genotyped by using genescan and genotyping software, then, parametric and non-parametric multipoint test, and affected sib-pair analysis as well, were used to analyze the data. We identified some susceptibility gene loci residing in chromosomes 1,12,18,20, respectively, or precisely, located around D1S214, D1S207, D1S218, D1S235, D12S336, D18S61 and D20S118. The comparison of this result with those from other regions and races reflected the complexity and heterogeneity of type 2 diabetes. | ZHAO Jinying WANG Heng XIONG Momiao HUANG Wei ZUO Jin CHEN Zhu QIANG Boqin SUN Qi LI Yuxiu LIU Qiuying DU Weinan CHEN Jialun DING Wei YUAN Wentao ZHAO Yang XU Hongyan JIN Li FANG Fude | 2000 | Chinese Science Bulletin2000，45，19： | 8 |
| 4 | A cohort autopsy study defines COVID-19 systemic pathogenesis显示文摘Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs.However,the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown.We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan,China,and determined the systemic distribution of SARS-CoV-2. | Xiao-Hong Yao Tao Luo Yu Shi Zhi-Cheng He Rui Tang Pei-Pei Zhang Jun Cai Xiang-Dong Zhou Dong-Po Jiang Xiao-Chun Fei Xue-Quan Huang Lei Zhao Heng Zhang Hai-Bo Wu Yong Ren Zhen-Hua Liu Hua-Rong Zhang Cong Chen Wen-Juan Fu Heng Li Xin-Yi Xia Rong Chen Yan Wang Xin-Dong Liu Chang-Lin Yin Ze-Xuan Yan Juan Wang Rui Jing Tai-Sheng Li Wei-Qin Li Chao-Fu Wang Yan-Qing Ding Qing Mao Ding-Yu Zhang Shu-Yang Zhang Yi-Fang Ping Xiu-Wu Bian | 2021 | Cell Research2021，31，8： | 7 |
| 5 | Structural analysis of asparaginyl endopeptidase reveals the activation mechanism and a reversible intermediate maturation stage显示文摘Asparaginyl endopeptidase (AEP ) 是有为在 P1 地点的天门冬素残余的偏爱的 endo/lysosomal 半胱氨酸 endopeptidase 并且在像使用费的受体 3/7/9 的成熟起一个重要作用。AEP 被知道为催化激活在酸的 pH 经历 autoproteolytic 成熟。这里,我们描述 AEP 酶原的水晶结构和 AEP 的成熟形式。在 AEP 和 caspases 之间的结构的比较在关键残余的作文并且在催化机制揭示了类似。Mutagenesis 研究作为为肽底层的劈开是必要的残余识别了 N44, R46, H150, E189, C191, S217/S218 和 D233。在成熟期间, AEP 的帽子领域的 autoproteolytic 劈开在核心领域上开创存取到活跃地点。出人意料地,一个中间的 autoproteolytic 成熟阶段被发现在近似 pH 4.5 在哪个部分激活的 AEP 能被颠倒回到它的酶原形式。这个唯一的特征被 AEP pH4.5 (AEP 在 pH 被成熟 4.5 并且在 pH 结晶 8.5 ) ,在哪个破肽契约被重新绑扎,结构被转变回到它的酶原形式。另外, AEP 禁止者 cystatin C 能被充分激活的 AEP 消化,但是不能被激活的组织蛋白酶消化。因此,我们第一次证明 cystatins 可以为活跃地点通过底层竞争调整 AEP 的活动。 | Lixia Zhao Tian Hua Christopher Crowley Heng Ru Xiangmin Ni Neil Shaw Lianying Jiao Wei Ding Lu Qu Li-Wei Hung Wei Huang Lei Liu Keqiang Ye Songying Ouyang Genhong Cheng Zhi-Jie Liu | 2014 | Cell Research2014，24，3： | 6 |
| 6 | Resveratrol inhibits collagen Ⅰ synthesis by suppressing IGF-1R activation in intestinal fibroblasts显示文摘AIM:To investigate whether resveratrol(3,4,5-trihydroxy-trans-stilbene)inhibits collagenⅠsynthesis induced by insulin growth factor-1(IGF-1)in intestinal fibroblasts,and to explore the possible molecular mechanisms.METHODS:Male Sprague-Dawley rats were randomly divided into two groups:a control group and a2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced colitis group.After 21 d of TNBS administration,the degree of inflammation and fibrosis in colon was measured by HE staining and Masson’s trichrome staining.Western blotting was used to examine collagenⅠ,IGF-1 and silent information regulator 1(SIRT1)protein expression in colitis tissues.Western blotting and quantitative realtime polymerase chain reaction were used to characterize collagenⅠprotein and col1a2 mRNA expression in mouse intestinal fibroblasts and CCD-18Co cells treated with IGF-1.A MEK inhibitor(U0126)was used to determine whether IGF-1-induced collagenⅠexpression was mediated by extracellular signal-regulated kinase 1/2(ERK1/2)-dependent mechanism.Effects of resveratrol on collagenⅠprotein level,insulin growth factor-1receptor(IGF-1R)and ERK1/2 phosphorylation levels were also examined after IGF-1 treatment in fibroblasts.To evaluate whether SIRT1 was necessary for the anti-fibrosis effect of resveratrol,cells were transfected with SIRT1-specific small interfering RNAs,wildtype SIRT1,and deacetylase-inactive mutant SIRT1.RESULTS:CollagenⅠand IGF-1 expression was increased,and SIRT1 expression was decreased(0.67±0.04 vs 1.05±0.07,P<0.001)in TNBS-induced colitis compared with the control group.In vitro,IGF-1 could induce collagenⅠexpression,mainly through the ERK1/2 signal pathway.Resveratrol reduced basal and IGF-1-induced collagenⅠ?gene and protein expression in intestinal fibroblasts.Overexpression of wild-type SIRT1,not deacetylase-inactive mutant SIRT1,decreased expression of collagenⅠinduced by IGF-1.Moreover,silencing SIRT1 restored collagen?Ⅰ?expression in fibroblasts challenged with resveratrol.However,disruption of SIRT1 did not influence the anti-fibrotic effects of resveratrol and IGF-1-induced collagenⅠexpression.Further analysis revealed that resveratrol significantly decreased phosphorylation of IGF-1R and its downstream signaling molecules by inhibiting IGF-1 binding to its receptor.CONCLUSION:Our data suggest that resveratrol effectively inhibits collagenⅠsynthesis in IGF-1-stimulated fibroblasts,partly by inhibiting IGF-1R activation,and SIRT1 is also responsible for the process. | Ping Li Mei-Lan Liang Ying Zhu Yao-Yao Gong Yun Wang Ding Heng Lin Lin | 2014 | World Journal of Gastroenterology2014，20，16： | 6 |
| 7 | PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus显示文摘地岬在许多细胞的活动起一个枢轴的作用,并且它的 subcellular 区分提供空间、时间的选择。这里,我们报导由二高度相应的蛋白质 PAQR10 和孕激素和 AdipoQ 受体家庭的 PAQR11 在 Golgi 仪器发信号的地岬的空间规定的一个模式。PAQR10 和 PAQR11 在 Golgi 仪器是只局部性的。PAQR10/PAQR11 的 Overexpression 刺激基础、导致 EGF 的英皇家空军之阶级最低之兵 phosphorylation 并且以一种剂量依赖者方式增加英皇家空军之阶级最低之兵目标基因的表示。PAQR10/PAQR11 的 Overexpression 显著地提高 HRas, NRas 和 KRas4A 的 Golgi 本地化,然而并非 KRas4B。PAQR10 和 PAQR11 罐头也与 HRas, NRas 和 KRas4A 交往,然而并非 KRas4B。在由 PAQR10/PAQR11 的 overexpression 的 Golgi 仪器的增加的地岬蛋白质处于一个活跃状态。一致地, PAQR10 和 PAQR11 还原剂击倒在 Golgi 仪器的刺激 EGF 的英皇家空军之阶级最低之兵 phosphorylation 和地岬激活。有趣地, PAQR10 和 PAQR11 能与 RasGRP1,地岬的 guanine 核苷酸交换蛋白质,和 RasGRP1 的增加 Golgi 本地化交往。RasGRP1 的 C1 领域为和 PAQR10/PAQR11 的 RasGRP1 的相互作用必要、足够。由 overexpressed PAQR10/PAQR11 的英皇家空军之阶级最低之兵 phosphorylation 的模拟被 RasGRP1 的 downregulation 废除。而且, PC12 房间的区别被 PAQR10/PAQR11 的 overexpression 显著地提高。一起,这研究揭开由 PAQR10 和 PAQR11 在 Golgi 仪器发信号的地岬的空间规定的一个新范例。 | Ting Jin Qiurong Ding Heng Huang Daqian Xu Yuhui Jiang Ben Zhou Zhenghu Li Xiaomeng Jiang Jing He Weizhong Liu Yixuan Zhang Yi Pan Zhenzhen Wang Walter G Thomas Yan Chen | 2012 | Cell Research2012，22，4： | 6 |
| 8 | Structural basis for termination of AIM2-mediated signaling by p202显示文摘 | Heng Ru Xiangmin Ni LixiaZhao Christopher Crowle Wei Ding Li-Wei Hung Neil Shaw Genhong Cheng Zhi-Jie Liu | 2013 | Cell Research2013，23，6： | 5 |
| 9 | The Discovery of the 2.35Ga Crystalline Basement in the Southwest of the Yangtze Block and its Geological Significance显示文摘Objective Archean and Paleoproterozoic rock units crop out in the northern and southwestern portions of the Yangtze Block in the South China Craton.Archean crystalline basement outcrops are restricted to the northern part of the Yangtze Block and are represented by the Kongling Complex.The protoliths of the TTG gneisses at Kongling were emplaced at 3.3-2.7Ga (Gao et al.,2011). | ZHANG Heng GAO Linzhi ZHANG Chuanheng DING Xiaozhong LI Tingdong LIU Yanxue | 2018 | Acta Geologica Sinica(English Edition)2018，92，6： | 4 |
| 10 | Post-marketing safety surveillance and reevaluation of Motherwort injection:A clinical study of 10094 cases显示文摘OBJECTIVE:To investigate the safety profiles of Motherwort injection(MI).METHODS:A multi-center,prospective and drugderived hospital intensive monitoring method was conducted to assess the safety of MI in real world applications.This study was based on a very large population after the injection was approved and marketed in China.All patients using the injection in participating hospitals were monitored to determine the incidence,pattern,severity and outcome of associated adverse events.RESULTS:The post-marketing surveillance was performed in 10 094 female patients from April to December,2015.The incidence of adverse drug reactions(ADRs) was 0.79‰(8/10 094).Among the 8 patients,the reported adverse events mainly included systemic abnormalities,such as fever,chills and eyelid edema;skin and appendages disorders,such as pruritus and rash;gastrointestinal disorders,such as nausea,abdominal distension and pain;heart rate and rhythm disorders,such as palpitation and increased heart rate.All of these ADRs were mild in severity.CONCLUSION:In this study the ADRs incidence rate of MI is very low,which supports that it is generally safe for use in obstetric and gynecological diseases.However,the total number of 8 ADRs recorded over a relatively short time span seems limited,and the low number of reports could not represent an absolute guarantee of safety. | Cao Shan Zhang Wenhao Zhao Ziwei Heng Mingli Bu Huaien Wang Hongwu Liu Xinghui Wang Zhong Cai Yan Ma Yuyan Cui Shihong Deng Jihong Ding Guifeng Ding Yajuan Dong Linhong Duan Zhentao Fan Ling Fan Yang Fu Fen He Jing Ji Shuying Jin Lin Li Hong Li Hongying Liao Tao Lu Wei Luo Xiucui Lü Zhihui Ma Fengchun Ma Dafeng Shi Tianyun Sun Juying Sun Xiaotong Teng Hong Wang Jinhua Wang Ruihua Wang Ying Wang Zhengling Xi Jie Xu Minjuan Xu Zhihong Yan Qian Yang Cuirong Yang Yimei Yin Jie Yu Jinhua Yuan Wenjun Zhang Guanli Zhang Meihua Zhao Renfeng Zhong Yonghong Zhou Jian | 2018 | Journal of Traditional Chinese Medicine2018，38，4： | 4 |
| 11 | Comparison of the oncological,perioperative and functional outcomes of partial nephrectomy versus radical nephrectomy for clinical T1b renal cell carcinoma:A systematic review and metaanalysis of retrospective studies显示文摘Objective:To conduct a meta-analysis assessing the perioperative,functional and oncological outcomes of partial nephrectomy(PN)and radical nephrectomy(RN)for T1b tumours.The primary endpoints were the oncological outcomes.The secondary endpoints were the perioperative and functional outcomes.Methods:A systematic literature review was performed by searching multiple databases through February 2019 to identify eligible comparative studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement.Identified reports were assessed according to the Newcastle-Ottawa Scale for nonrandomized controlled trials.Results:Overall,13 retrospective cohort studies were included in the analysis.Patients undergoing PN were younger(weighted mean difference[WMD]3.49 years,95%confidence interval[CI]5.16 to1.82;p<0.0001)and had smaller masses(WMD0.45 cm,95%CI0.59 to0.31;p<0.0001).There were no differences in the oncological outcome,which was demonstrated by progression-free survival(hazard ratio[HR]0.70;pZ0.22),cancerspecific mortality(HR 0.91;pZ0.57)and all-cause mortality(HR 1.01;pZ0.96).The two procedures were similar in estimated blood loss(WMD16.47 mL;pZ0.53)and postoperative complications(risk ratio[RR]1.32;pZ0.10),and PN provided better renal function preservation and was related to a lower likelihood of chronic kidney disease onset(RR 0.38;pZ0.006).Conclusion:PN is an effective treatment for T1b tumours because it offers similar surgical morbidity,equivalent cancer control,and better renal preservation compared to RN. | Yucong Zhang Gongwei Long Haojie Shang Beichen Ding Guoliang Sun Wei Ouyang Man Liu Yuan Chen Heng Li Hua Xu Zhangqun Ye | 2021 | Asian Journal of Urology2021，8，1： | 4 |
| 12 | Co-application of energy uncoupling and ultrafiltration in sludge treatment:Evaluations of sludge reduction,supernatant recovery and membrane fouling control显示文摘Energy uncoupling is often used for sludge reduction because it is easy to operate and does not require a significant amount of extra equipments(i.e.no additional tank required).However,over time the supernatant extracted using this method can deteriorate,ultimately requiring further treatment.The purpose of this study was to determine the effect of using a low-pressure ultrafiltration membrane process for sludge water recovery after the sludge had undergone an energy uncoupling treatment(using 3,3’,4’,5-tetrachlorosalicylanilide(TCS)).Energy uncoupling was found to break apart sludge floe by reducing extracellular polymeric substances(EPS)and adenosine triphosphate(ATP)content.Analysis of supernatant indicated that when energy uncoupling and membrane filtration were coapplied and the TCS dosage was below 30 mg/L,there was no significant deterioration in organic component removal.However,ammonia and phosphate concentrations were found to increase as the concentration of TCS added increased.Additionally,due to low sludge concentrations and EPS contents,addition of 30-60 mg/L TCS during sludge reduction increased the permeate flux(two times higher than the control)and decreased the hydraulic reversible and cake layer resistances.In contrast,high dosage of TCS aggravated membrane fouling by forming compact fouling layers.In general,this study found that the co-application of energy uncoupling and membrane filtration processes represents an effective alternative method for simultaneous sludge reduction and sludge supernatant recovery. | An Ding Yingxue Zhao Zhongsen Yan Langming Bai Haiyang Yang Heng Liang Guibai Li Nanqi Ren | 2020 | Frontiers of Environmental Science & Engineering2020，14，4： | 3 |
| 13 | Geochronology, Geochemistry, Whole Rock Sr-Nd and Zircon Hf-O Isotopes of the Early Neoproterozoic Volcanic Rocks in Jiangshan, Eastern Part of the Jiangnan Orogen: Constraints on Petrogenesis and Tectonic Implications显示文摘This paper presents the results of combined studies of geochronology, geochemistry, whole rock Sr-Nd and zircon Hf-O isotopes carried out upon the rhyodacite and ignimbrite of Shangshu village, Shangyu town and Shanghupeng village of Jiangshan City in Zhejiang Province, along the northwestern side of the Jiangshan–Shaoxing suture. SHRIMP zircon U-Pb dating of samples in the three areas yielded weighted mean 206 Pb/238 U ages of 842.8 ± 6.9 Ma and 850.0 ± 7.3 Ma, 839 ± 9 Ma and 832.2 ± 8.1 Ma, 828.3 ± 8.5 Ma and 836.9 ± 9.9 Ma, respectively. These ages are older than the volcanic rocks of the Shangshu Formation dated at around 780 Ma distributed in Fuyang City, Hangzhou City, Kaihua County, etc. The volcanic rocks generally have high SiO2(54.08–76.80 wt%) and Al2 O3(12.40–21.31 wt%), low Fe2 O3(0.68–8.92 wt%), MgO(0.29–2.49 wt%), CaO(0.12–2.86 wt%), TiO2(0.10–1.59 wt%) and P2 O5(0.01–0.39 wt%), with variable total alkalis(K2 O + Na2 O =5.42–8.29 wt%). There exists a clear negative correlation between SiO2 and P2 O5. The volcanic rocks have A/CNK ratios of 1.03–2.77 and thus are peraluminous. They are characterized by enrichment in LREE, Rb, Ba, Zr, Hf, K, Th, La, U and depletion in Nb, Sr, P, Ti, with distinct LREE and HREE fractionation of(La/Yb)N values of 5.68–11.67, and with a moderate negative Eu anomaly(&Eu=0.58–0.89). Whole-rock geochemical data shows that the Jiangshan volcanic rocks are possibly I-type granitic rocks, even though they have some characteristics of A&S-type granites due to the magma fractional crystallization and water-rock interaction. Zircon δ18 O values are 3.97‰–5.49‰(average 4.50‰), 2.90‰–5.21‰(average 4.32‰) for ignimbrite from Shangshu village section, and Shanghupeng village section, respectively. They are slightly lower than the average δ18 O values of igneous zircons in equilibrium with mantle magmas(5.3 ± 0.6‰(2σ)), the lower δ18 O value also demonstrating the presence of high temperature water-rock interactions. The ignimbrite rocks have positive εNd(t)(4.02, 3.37, 3.91, 4.74, 2.85, 4.39, totals from the three areas) and εNd(t)(in-situ zircon)(4.3–14.6, a weighted mean of 8.4;6.6–12.7, a weighted mean of 9.0;8.1–12.0, a weighted mean of 9.5, respectively, from the three areas). In conjunction with the trace element studies, they indicate that the source region of the Jiangshan volcanic rocks was mainly composed of juvenile lower crustal material, mixed with some mantle-sourced magma. Detailed elemental and isotopic data suggest that the Jiangshan volcanic rocks were formed in a continental arc setting. There is a series of ca. 860–830 Ma volcanic rocks formed in a back-arc extensional setting in the southern margin of the eastern Jiangnan Orogen, along the northwest side of the Jiangshan–Shaoxing suture. The first stage rift-related anorogenic magmatism may have occurred as early as ca. 860 Ma in the eastern Jiangnan Orogen. | ZHANG Heng LIU Yanxue DING Xiaozhong GAO Linzhi YANG Chun ZHANG Jibiao GONG Chengqiang LIU Haogang | 2020 | Acta Geologica Sinica(English Edition)2020，94，4： | 3 |
| 14 | Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer显示文摘Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity.Dendritic cell(DCs)vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality.Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world.Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years,their efficacy is still unsatisfactory overall.Therefore,there is an urgent unmet clinical need for lung cancer treatment.Here,we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm,2 medical centers,pilot study initiated by the investigator(ChiCTR-ONC 16009100,NCT02956551).The patients enrolled were patients with heavily treated metastatic lung cancer.Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis.A total of 12 patients were enrolled in this study.A total of 85 vaccine treatments were administered with a median value of 5 doses/person(range:3-14 doses/person).In total,12-30 peptide-based neoantigens were selected for each patient.AIl treatment-related adverse events were grade 1-2 and there were no delays in dosing due to toxic effects.The objective effectiveness rate was 25%;the disease control rate was 75%;the median progression-free survival was 5.5 months and the median overall survival was 7.9 months.This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment. | Zhenyu Ding Qing Li Rui Zhang Li Xie Yang shu Song Gao Peipei Wang Xiaoqing Su Yun Qin Yuelan Wang Juemin Fang Zhongzheng Zhu Xuyang Xia Guochao Wei Hui Wang Hong Qian Xianling Guo Zhibo Gao Yu Wang Yuquan Wei Qing Xu Heng Xu Li Yang | 2021 | Signal Transduction and Targeted Therapy2021，6，2： | 3 |
| 15 | Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1显示文摘As a terpenoids natural product isolated from the plant Thunder God Vine,Celastrol is widely studied for its pharmacological activities,including anti-tumor activities.The clinical application of Celastrol is strictly limited due to its severe side effects,whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization.Target identification has a far-reaching influence on the development of innovative drugs,and omics data has been widely used for unbiased target prediction.However,it is difficult to enrich target of specific phenotype from thousands of genes or proteins,especially for natural products with broad promising activities.Here,we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds.Then peroxiredoxin 1(PRDX1)was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer.Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1.New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis.Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells.The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells.Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment.Our findings reveal that the side effects of Celastrol could be reduced via structural modification,and PRDX1 inhibition is promising for the treatment of colorectal cancer. | Heng Xu Hongfang Zhao Chunyong Ding Defang Jiang Zijie Zhao Yang Li Xiaoyu Ding Jing Gao Hu Zhou Cheng Luo Guoqiang Chen Ao Zhang Ying Xu Hao Zhang | 2023 | Signal Transduction and Targeted Therapy2023，8，3： | 3 |
| 16 | Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion显示文摘Ischemic stroke represents a significant danger to human beings,especially the elderly.Interventions are only available to remove the clot,and the mechanism of neuronal death during ischemic stroke is still in debate.Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs. | Qing-zhang Tuo Yu Liu Zheng Xiang Hong-Fa Yan Ting Zou Yang Shu Xu-long Ding Jin-jun Zou Shuo Xu Fei Tang Yan-qiu Gong Xiao-lan Li Yu-jie Guo Zhao-yue Zheng Ai-ping Deng Zhang-zhong Yang Wen-jing Li Shu-ting Zhang Scott Ayton Ashley I.Bush Heng Xu Lunzhi Dai Biao Dong Peng Lei | 2022 | Signal Transduction and Targeted Therapy2022，7，3： | 2 |
| 17 | Simultaneous optimization of structure together with attached tuned mass dampers considering dynamic performance显示文摘Tuned Mass Dampers(TMDs)are often attached to a main structure to reduce vibration,and the TMDs’positions are important to affect the structural dynamic performance.However,the TMDs’positions and the material layout of the structure act on each other.This paper suggests a design optimization method by combining the topology optimization of the main structure and the layout of the attached TMDs under harmonic excitations.The main structure with the attached TMDs are modeled by the continuum FEA method to consider the change of TMDs’locations.Then they are optimized simultaneously by introducing a multi-level optimization frame,which includes the structural topology optimization and the optimal tuning of TMDs.The locations and damping parameters of TMDs are optimized in every step of the SIMP-based topology optimization of the main structure,so as to fully consider the interactions between each other to improve the dynamic performance.Numerical examples of cantilever structures are studied,and the results show that when the main structure and TMDs are optimized simultaneously,the modal strain energy is more concentrated compared with that obtained by the non-simultaneous optimization approach.Therefore,the dynamic compliance of the target mode is dramatically reduced. | Lei SHEN Xiaohong DING Tiannan HU Min XIONG Heng ZHANG | 2022 | Chinese Journal of Aeronautics2022，35，2： | 2 |
| 18 | Potent in vitro Interference of Fleroxacin in DNA-binding,Unwinding and ATPase Activities of Bloom Helicase显示文摘Objective To study the effect of fleroxacin(FLRX) on biological properties of Bloom(BLM) helicase catalytic core(BLM 642-1290 helicase) in vitro and the molecular mechanism of interaction between the two molecules.Methods DNA-binding and unwinding activities of BLM 642-1290 helicase were assayed by fluorescence polarization and gel retardation assay under conditions that the helicase was subjected to different concentrations of FLRX.Effect of FLRX on helicase ATPase activity was analyzed by phosphorus-free assay based on a colorimetric estimation of ATP hydrolysis-produced inorganic phosphate.Molecular mechanism ofinteractionbetween thetwomoleculeswasassayedbyultraviolet andfluorescence spectra.Results The DNA unwinding and ATPase activities of BLM 642-1290 helicase were inhibited whereas the DNA-binding activity was promoted in vitro.A BLM-FLRX complex was formed through one binding site,electrostatic and hydrophobic interaction force.Moreover,the intrinsic fluorescence of the helicase was quenched by FLRX as a result of non-radioactive energy transfer.The biological activity of helicase was affected by FLRX,which may be through an allosteric mechanism and stabilization of enzyme conformation in low helicase activity state,disruption of the coupling of ATP hydrolysis to unwinding,and blocking helicase translocation on DNA strands.Conclusion FLRX may affect the biological activities and conformation of BLM 642-1290 helicase,and DNA helicase may be used as a promising drug target for some diseases. | LUO Heng XU Hou Qiang CHEN Xiang DING Mei YANG Qi Xin LI Kun | 2013 | Biomedical and Environmental Sciences2013，26，4： | 2 |
| 19 | Geochronology and Geochemistry of the 890 Ma I-Type Granites in the Southwestern Yangtze Block:Petrogenesis and Crustal Evolution显示文摘The tectonic evolution of the southwestern Yangtze Block during the Early Neoproterozoic period is still controversial because of the limited quantities of 1000–860 Ma magmatic rocks.In this study,our new LA-ICP-MS zircon U-Pb dating results demonstrate that the Yanbian granodiorites in the southwest Yangtze Block were emplaced at 894.6±7.4 Ma,representing the product of an 894 Ma magmatism.The Yanbian granodiorites are metaluminous to weak peraluminous with A/CNK values of 0.8–1.1,resembling Itype granitoids.They are characterized by right-inclined REE patterns with moderate to insignificant negative Eu anomalies(δEu=0.6–0.9).Their primitive mantle-normalized trace element patterns are characterized by depletion of Nb,Ta and Ti and weakly enrichment of Th.Considering the positive whole-rockεNd(t)(+5.8 to+6.8),we propose that these granodiorites originated from the partial melting of juvenile mafic lower crust.The Yanbian I-type granitoids have low Y and Nb contents similar to volcanic arc igneous rocks in the Y-Nb plot for tectonic discrimination.In conclusion,Early Neoproterozoic Yanbian granodiorites have generated in a compression setting in an active continental margin.Together with previous studies from the southwestern Yangtze Block,we suggest that the 894 Ma subduction-related Yanbian granodiorites represent the early stage of subduction at the southwestern margin of the Yangtze Block. | Jibiao Zhang Xiaozhong Ding Yanxue Liu Heng Zhang Chenglong Shi Yu Zou | 2020 | Journal of Earth Science2020，31，6： | 2 |
| 20 | Lipocalin-2-induced proliferative endoplasmic reticulum stress participates in Kawasaki disease-related pulmonary arterial abnormalities显示文摘Clinical cases have reported pulmonary arterial structural and functional abnormalities in patients with Kawasaki disease(KD);however,the underlying mechanisms are unclear.In this study,a KD rat model was established via the intraperitoneal injection of Lactobacillus casei cell wall extract(LCWE).The results showed that pulmonary arterial functional and structural abnormalities were observed in KD rats.Furthermore,proliferative endoplasmic reticulum stress(ER stress)was observed in the pulmonary arteries of KD rats.Notably,the level of lipocalin-2(Lcn 2),a trigger factor of inflammation,was remarkably elevated in the plasma and lung tissues of KD rats;increased Lcn 2 levels following LCWE stimulation may result from polymorphonuclear neutrophils(PMNs).Correspondingly,in cultured pulmonary artery smooth muscle cells(PASMCs),Lcn 2 markedly augmented the cleavage and nuclear localization of activating transcription factor-6(ATF6),upregulated the transcription of glucose regulated protein 78(GRP78)and neurite outgrowth inhibitor(NOGO),and promoted PASMCs proliferation.However,proapoptotic C/EBP homologous protein(CHOP)and caspase 12 levels were not elevated.Treatment with 4-phenyl butyric acid(4-PBA,a specific inhibitor of ER stress)inhibited PASMCs proliferation induced by Lcn 2 and attenuated pulmonary arterial abnormalities and right ventricular hypertrophy and reduced right ventricular systolic pressure in KD rats.In conclusion,Lcn 2 remarkably facilitates proliferative ER stress in PASMCs,which probably accounts for KD-related pulmonary arterial abnormalities. | Zhaoling Shi Yue Yin Chen Li Hui Ding Nan Mu Yishi Wang Shanshan Jin Heng Ma Manling Liu Jie Zhou | 2021 | Science China(Life Sciences)2021，64，6： | 1 |
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