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| 1 | The prognostic and therapeutic implications of circulating tumor cell phenotype detection based on epithelial-mesenchymal transition markers in the first-line chemotherapy of HER2-negative metastatic breast cancer显示文摘Background:Epithelial-mesenchymal transition(EMT)is implicated in the metastatic process and presents a chal-lenge to epithelial cell adhesion molecule-based detection of circulating tumor cells(CTCs),which have been demon-strated to be a prognostic indicator in metastatic breast cancer.Although evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression,no standard recommendations have been established for clinical practice.This study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer patients.Methods:We enrolled 108 human epidermal growth factor receptor 2-negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes(including epithelial CTCs,biphenotypic epithelial/mesenchymal CTCs,and mesenchymal CTCs)in peripheral blood samples.Receiver operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1-year progression-free survival(PFS)rate were conducted to determine the optimal cut-off values,and Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut-off values of both total CTC count and the proportion of mesenchymal CTCs in combination.Results:For predicting the 1-year PFS rate,the optimal cut-off value of total CTC count was 9.5(Area under the curve[AUC]=0.538,95%confidence interval[CI]=0.418-0.657),and that of the proportion of mesenchymal CTCs was 10.7%(AUC=0.581,95%CI=0.463-0.699).We used the two cut-off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%.Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria(6.2 vs.9.9 months,P=0.010).A nomogram was constructed based on the criteria and significant clinicopatho-logical characteristics with a C-index of 0.613(P=0.010).Conclusions: The criteria, which combine the total CTC count and the proportion of mesenchymal CTCs, may be used to monitor therapeutic resistance and predict prognosis in patients with metastatic breast cancer. | Xiuwen Guan Fei Ma Chunxiao Li Shiyang Wu Shangying Hu Jiefen Huang Xiaoying Sun Jiayu Wang Yang Luo Ruigang Cai Ying Fan Qiao Li Shanshan Chen Pin Zhang Qing Li Binghe Xu | 2019 | Cancer Communications2019，39，1： | 15 |
| 2 | Activation of calcium-sensing receptors is associated with apoptosis in a model of simulated cardiomyocytes ischemia/reperfusion显示文摘Objective:Calcium-sensing receptors(CaSRs)are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion,activation of ion channels,cell apoptosis,proliferation,and differentiation.Previous studies have shown that CaSRs induce apoptosis in isolated adult rat heart and in normal neonatal rat cardiomyocytes by G-protein-PLC-IP 3 signaling transduction.However,little knowledge is presently available concerning the role of CaSRs in the apoptosis induced by ischemia and reperfusion in neonatal cardiomyocytes.Methods:Primary neonatal rat ventricular cardiomyocytes were incubated in ischemiamimetic solution for 2 h,and then re-incubated in normal culture medium for 24 h to establish a model of simu- lated ischemia/reperfusion(I/R).Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The expression of CaSRs mRNA was detected by real-time reverse transcription polymerase chain reaction(RT-PCR).In addition,the expressions of caspase-3 and Bcl-2 were analyzed by western blot.Results:The simulated I/R enhanced the expression of CaSRs and cardiomyocyte apopto- sis.GdCl 3 ,a specific activator of CaSRs,further increased the expression of CaSRs and cardiomyocyte apoptosis, along with up-regulation of caspase-3 and down-regulation of Bcl-2.Conclusion:CaSRs are associated with I/R injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting caspase-3 expression. | Ling Yan Tlebing Zhu Tingting Sun Liansheng Wang Shiyang Pan Zhengxlan Tao Zhijian Yang Kejiang Cao | 2010 | The Journal of Biomedical Research2010，24，4： | 2 |
| 3 | Size effects of extraframework monovalent cations on the thermal stabili- ty and nitrogen adsorption of LSX zeolite 显示文摘 | Minghui Fan Jihong Sun Shiyang Bai | 2015 | Microporous and Mesoporous Materials2015，202，： | 1 |
| 4 | Identification of Cinobufagin and Resibufogenin as Inhibitors of Enterovirus 71 Infection显示文摘 | CHEN Jiawen XU Lin SUN Shiyang ZHANG Huafei MA Tonghui SU Weiheng JIANG Chunlai | 2014 | Chemical Research in Chinese Universities2014，30，6： | 1 |
| 5 | 基于上皮–间质转化标志物的循环肿瘤细胞表型检测对HER2阴性转移性乳腺癌一线化疗的预后意义显示文摘背景与目的上皮–间质转化(epithelia-mesenchymal,EMT)参与肿瘤细胞的转移,并且对基于上皮细胞黏附分子的循环肿瘤细胞(circulating tumor cells,CTCs)检测技术提出了挑战,CTCs已被证实是转移性乳腺癌的预后指标。虽然有证据表明基于EMT标志物的CTCs异质性与疾病进展相关,但在临床应用方面尚无统一的参考标准。本研究旨在评估基于EMT的动态CTCs检测对转移性乳腺癌患者的预后意义。方法我们从CAMELLIA III期前瞻性研究中招募了108例人表皮生长因子受体2阴性转移性乳腺癌患者,并应用CanPatrol CTC富集技术检测外周血中不同亚型的CTCs(包括上皮型CTCs、混合型上皮/间质CTCs和间质型CTCs)。应用1年无进展生存(progression-free survival,PFS)率作为界值分别寻找CTC总数和间质CTCs比例的受试者工作曲线来确定最佳阈值,并采用Kaplan-Meier分析和Cox比例风险回归分析验证综合考虑CTC总数和间质型CTCs比例制定的诊断标准的预后价值。结果CTC总数的最佳阈值为9.5[曲线下面积(area under the curve,AUC)=0.538,95%置信区间(confidence interval,CI=0.418–0.657)]及间质CTCs比例为10.7%(AUC=0.581,95%CI:0.463–0.699)作为预测1年PFS率的界值。我们采用CTC总数≥10/5 mL且间质CTCs比例>10.7%的联合标准预测PFS。符合联合标准的患者的中位PFS显著短于不符合标准的患者(6.2个月vs.9.9个月,P=0.010)。根据该标准和显著的临床病理学特征绘制列线图,C指数为0.613(P=0.010)。结论CTC总数和间质CTCs比例的联合标准可用于监测转移性乳腺癌患者的治疗耐药性和预测患者预后。 | Xiuwen Guan Fei Ma Chunxiao Li Shiyang Wu Shangying Hu Jiefen Huang Xiaoying Sun Jiayu Wang Yang Luo Ruigang Cai Ying Fan Qiao Li Shanshan Chen Pin Zhang Qing Li Binghe Xu | 2019 | 癌症2019，38，9： | 1 |
| 6 | A new adapted constructed flora using in tomato paste wastewater treatment 显示文摘 | Sun Shiyang Sheng Zhigang Yang Ruili | 2013 | Korean J Chem Eng2013，18，2： | 1 |
| 7 | pH-responsive ibuprofen deliveryin silane-modified poly( methylacrylic acid) coated bimodal mesoporoussilicas 显示文摘 | Huang Zhang Shiyang Bai Jihong Sun | 2014 | Materials Research Bulletin2014，53，： | 1 |
| 8 | Making the Pilot Project of Standardization as an Opportunity to Develop Shenzhen Public Meteorological Service Innovatively显示文摘The rapid development of the social economy and the urgent needs of building a low-carbon,ecologic and livable city ask for a higher requirement for urban meteorological service,which requires higher,better and more specialized service.To Shenzhen,the year of 2011 is featured by “Universiade” and “Quality”.In this year,the first national meteorological service standardization pilot and demonstration unit is stationed in Shenzhen,which has more far-reaching significance,richer connotation and heavier responsibility.In the meanwhile,it brings a historic opportunity for the innovative development of public meteorological service in Shenzhen.We will change the traditional ideas,break through the existing mode,make reforms as a forerunner,and innovatively develop the public meteorological service in Shenzhen. | Sun Shiyang | 2011 | China Standardization2011，56，5： | 0 |
| 9 | Digging out molecular markers associated with low salinity tolerance of Nannochloropsis oceanica through bulked mutant analysis显示文摘Nannochloropsis oceanica is a marine microalgal species with both economic value and biological importance.It grows fast,contains rich oils,reproduces asexually,holds a small and haploidy genome,and is easy to be modified genetically.However,the genetic study of N.oceanica is scarce.Very less genetic bases of its traits have been deciphered,and no gene has been isolated from it with the function verified simultaneously via either genetic or reverse genetic approaches or both(de novo cloned).Changing medium salinity may aid to control harmful organisms met during large scale cultivation.As a stress,it may also facilitate the accumulation of desirable chemicals including fatty acids.In order to decipher the genetic basis of the low salinity tolerance of N.oceanica,we mutated N.oceanica with Zeocin.In total,five mutant bulks were constructed at equal number of cells,100 mutants each,which were tolerant to a discontinuous serial of salinities from that of 100%of f/2 to that of a mixture of 4%of f/2 and 94%of BG11.The bulks were genotyped through whole genome re-sequencing and analyzed with bulked mutant analysis(BMA)newly modified from bulked segregant analysis(BSA).In total,47 SNPs and 112 InDels were found to associate with the low salinity tolerance,and around them a set of low salinity tolerance associating genes were identified.A set of annotatable genes commonly found between control and different salinities indicated that the genes functioning in gene expression,energy metabolism and cellular structure may be involved in the low salinity tolerance.These associating molecular markers and genes around them were not enough for outlining the physiological mechanism underlining the tolerance;however they should aid to improve N.oceanica genetically. | LIANG Sijie ZHANG Zhongyi LIU Hang GUO Li SUN Shiyang YANG Guanpin | 2020 | Journal of Oceanology and Limnology2020，38，6： | 0 |
| 10 | Dual-engineered cartilage-targeting extracellular vesicles derived from mesenchymal stem cells enhance osteoarthritis treatment via miR-223/NLRP3/pyroptosis axis:Toward a precision therapy显示文摘Osteoarthritis(OA)is the most common disabling joint disease with no effective disease modifying drugs.Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models,representing a novel therapeutic strategy.In this study,we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells(hUC-EVs)could maintain chondrocyte homeostasis and alleviate OA,and further revealed a novel molecular mechanism of this therapeutic effect.miR-223,which could directly bind with the 3′UTR of NLRP3 mRNA,was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage protecting.For enhancing the effect on mitigating osteoarthritis,exogenous miR-223 was loaded into hUC-EVs by electroporation,and a collagen II-targeting peptide(WYRGRL)was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the cartilage.The dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis,and offered excellent results for the treatment of OA.This study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment. | Weixuan Liu Anqi Liu Xujun Li Ziyang Sun Zhenghua Sun Yaru Liu Gang Wang Dan Huang Hao Xiong Shiyang Yu Xintao Zhang Cunyi Fan | 2023 | Bioactive Materials2023，，12： | 0 |
| 11 | Profiling the responsiveness of focal adhesions of human cardiomyocytes to extracellular dynamic nano-topography显示文摘Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals.Previous studies have demonstrated that cardiomyocyte focal adhesions can be modulated by surface topographic features.However,the response of focal adhesions to dynamic surface topographic changes remains underexplored.To study this dynamic responsiveness of focal adhesions,we utilized a shape memory polymer-based substrate that can produce a flat-to-wrinkle surface transition triggered by an increase of temperature.Using this dynamic culture system,we analyzed three proteins(paxillin,vinculin and zyxin)from different layers of the focal adhesion complex in response to dynamic extracellular topographic change.Hence,we quantified the dynamic profile of cardiomyocyte focal adhesion in a time-dependent manner,which provides new understanding of dynamic cardiac mechanobiology. | Huaiyu Shi Xiangjun Wu Shiyang Sun Chenyan Wang Zacharias Vangelatos Ariel Ash-Shakoor Costas P.Grigoropoulos Patrick T.Mather James H.Henderson Zhen Ma | 2022 | Bioactive Materials2022，7，4： | 0 |
| 12 | Ferrodifferentiation regulates neurodevelopment via ROS generation显示文摘Iron is important for life,and iron deficiency impairs development,but whether the iron level regulates neural differentiation remains elusive.In this study,with iron-regulatory proteins(IRPs)knockout embryonic stem cells(ESCs)that showed severe iron deficiency,we found that the Pax6-and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1^(-/-)IRP2^(-/-)ESCs were significantly decreased after inducing neural differentiation.Consistently,in vivo study showed that the knockdown of IRP1 in IRP2^(-/-)fetal mice remarkably affected the differentiation of neuronal precursors and the migration of neurons.These findings suggest that low intracellular iron status significantly inhibits neurodifferentiation.When supplementing IRP1^(-/-)IRP2^(-/-)ESCs with iron,these ESCs could differentiate normally.Further investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species(ROS)production caused by the substantially low level of iron and the downregulation of iron-sulfur cluster protein ISCU,which,in turn,affected the proliferation and differentiation of stem cells.Thus,the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation. | Shiyang Chang Peina Wang Yingying Han Qiang Ma Zeyuan Liu Suijuan Zhong Yufeng Lu Ruiguo Chen Le Sun Qian Wu Guofen Gao Xiaoqun Wang Yan-Zhong Chang | 2023 | Science China(Life Sciences)2023，66，8： | 0 |
| 13 | Transcriptome Responses of Hygromycin B Resistance Gene-Transformed, Hygromycin B-Adaptive and Wild Nannochloropsis oceanica Strains to Hygromycin B显示文摘In order to decipher the hygromycin B tolerance and resistance mechanisms of Nannochloropsis oceanica,the transcriptome profiles of a transgenic strain carrying a randomly integrated hygromycin B resistant gene,a hygromycin B-adaptive strain and a wild type strain of N.oceanica were compared by transcriptome sequencing(RNA-seq)without referring to a high quality genome sequence.The results showed that the adaptive strain adapts to the hygromycin B existing environments mainly by intensifying the expressions of the efflux pump ABC and MFS superfamily transporter genes,thus reducing the intracellular concentration of hygromycin B.The transgenic strain obtains the hygromycin B resistance ability solely by expressing exogenous resistance gene.Accordingly,the screening and maintenance of N.oceanica transformants should be carried out at an antibiotics concentration higher than the adaptive threshold.Our findings can help the genetic modification of N.oceanica with the application of hygromycin B. | LIU Hang ZHANG Zhongyi LIANG Sijie GUO Li SUN Shiyang PAN Kehou YANG Guanpin | 2020 | Journal of Ocean University of China2020，19，2： | 0 |
| 14 | Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with MET alterations显示文摘Various c-mesenchymal-to-epithelial transition(c-MET) inhibitors are effective in the treatment of non-small cell lung cancer;however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras(PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC_(50) values and achieved picomolar DC_(50) values and>99% of maximum degradation(D_(max)) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion.Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^(Y1230H) and c-MET^(D1228N) mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations. | Pengyun Li Changkai Jia Zhiya Fan Xiaotong Hu Wenjuan Zhang Ke Liu Shiyang Sun Haoxin Guo Ning Yang Maoxiang Zhu Xiaomei Zhuang Junhai Xiao Zhibing Zheng Song Li | 2023 | Acta Pharmaceutica Sinica B2023，13，6： | 0 |
| 15 | Heterogeneous lamella design to tune the mechanical behaviour of a new cost-effective compositionally complicated alloy显示文摘A heterogeneous lamella(HL)design strategy was applied to manipulate mechanical properties of a new cost-effective Fe_(35)Ni_(35)Cr_(25)Mo_(5)compositionally complicated alloy(CCA).The HL structure was produced by single-step heat treatment(800℃for 1 h)after cold rolling.This HL structure consists of alternative lamellae regions of coarse-grained FCC matrix(5-20μm),and regions containing ultra-fine grains or subgrains(200-500 nm)together with nanoprecipitates(20-500 nm)and annealing twins.As compared with other cost-effective CCAs,the 800℃annealed sample with HL structure demonstrated a comparable tensile property,with yield strength over 1.0 GPa and total elongation of~13%.Formation of the annealing twins and nanoprecipitates decorated HL structure was a result of the concurrent partial recrystallization and precipitation ofσphase at the shear bands with a high density of lattice defects(e.g.high-density dislocation walls and deformation twins).The latter restricted the growth of recrystallized grains,leading to the formation of ultrafine subgrains within the HL structure.The high yield strength resulted from the multistage hetero-deformation induced(HDI)strengthening and precipitation strengthening associated with heterogeneous lamella structures containing nanoprecipitates.The ductility was originated from the coexistence of multiple deformation mechanisms,which started with dislocation slip and formation of stacking faults at the initial stage,followed by nano-twinning at the higher strain level.This HL design strategy,comprising composition and thermomechanical process designs,and the resultant microstructure tuning,open a broader window for the development of cost-effective CCAs with enhanced performance. | Yu Yin Qiyang Tan Qiang Sun Wangrui Ren Jingqi Zhang Shiyang Liu Yingang Liu Michael Bermingham Houwen Chen Ming-Xing Zhang | 2022 | Journal of Materials Science & Technology2022，，1： | 0 |
| 16 | Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study显示文摘Thoracic aortic dissection(TAD)without familial clustering or syndromic features is known as sporadic TAD(STAD).So far,the genetic basis of STAD remains unknown.Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population(N=637).After population structure and genetic relationship and ancestry analyses,we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD.We found that COL3A1 was significantly relevant to STAD(P=7.35×10^(−6))after 10000 times permutation test(P=2.49×10^(−3)).Moreover,another independent cohort,including 423 cases and 734 non-STAD subjects(N=1157),replicated our results(P=0.021).Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues,and its expression was related to the extracellular matrix(ECM)pathway.Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway.We wanted to expand the knowledge of the genetic basis and pathology of STAD,which may further help in providing better genetic counseling to the patients. | Yanghui Chen Yang Sun Zongzhe Li Chenze Li Lei Xiao Jiaqi Dai Shiyang Li Hao Liu Dong Hu Dongyang Wu Senlin Hu Bo Yu Peng Chen Ping Xu Wei Kong Dao Wen Wang | 2021 | Frontiers of Medicine2021，15，3： | 0 |
| 17 | Serum metabolomic profiling reveals potential biomarkers in assessing the management of women with polycystic ovary syndrome:a randomized controlled trial显示文摘Background: As one of the most common endocrinal disorders for women at childbearing age, the diagnostic criteria of polycystic ovary syndrome (PCOS) have been defined differently among different international health organizations. Phenotypic heterogeneity of PCOS also brings about difficulties for its diagnosis and management assessment. Therefore, more efficient biomarkers representing the progression of PCOS are expected to be integrated into the monitoring of management process using metabolomic approaches.Methods: In this prospective randomized controlled trial, 117 PCOS patients were enrolled from December 2016 to September 2017. Classical diagnostic parameters, blood glucose, and metabolome were measured in these patients before and at 2 months and 3 months of different medical interventions. The receiver operating characteristic (ROC) curves were built based on multivariate statistical analysis using data at baseline and 3 months’ management, and combinational biomarkers with appreciable sensitivity and specificity were selected, which then validated with data collected at 2 months.Results: A set of metabolites including glutamic acid, aspartic acid, 1-methylnicotinamide, acetylcarnitine, glycerophosphocholine, and oleamide were filtered out with high performance in representing the improvement through 3-month management of PCOS with high sensitivity and specificity in ROC analysis and validation with other two groups showed an appreciable area under the curve over 0.96.Conclusions: The six metabolites were representative of the remission of PCOS through medical intervention, making them a set of potential biomarkers for assessing the outcome of PCOS management.Trial Registration: ClinicalTrials.gov, NCT03264638. | Xuesong Ding Yan Deng Yanfang Wang Wei Xue Shiyang Zhu Xiao Ma Ruilin Ma Aijun Sun | 2022 | Chinese Medical Journal2022，，1： | 0 |
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