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| 1 | Comparative investigation on high-speed grinding of TiCp/Ti–6Al–4V particulate reinforced titanium matrix composites with single-layer electroplated and brazed CBN wheels显示文摘In order to develop the high-efficiency and precision machining technique of Ti Cp/Ti–6Al–4V particulate reinforced titanium matrix composites(PTMCs), high-speed grinding experiments were conducted using the single-layer electroplated cubic boron nitride(CBN) wheel and brazed CBN wheel, respectively. The comparative grinding performance was studied in terms of grinding force, grinding temperature, grinding-induced surface features and defects. The results display that the grinding forces and grinding temperature obtained with the brazed CBN wheel are always lower than those with the electroplated CBN wheel. Though the voids and microcracks are the dominant grinding-induced surface defects, the brazed CBN wheel produces less surface defects compared to the electroplated wheel according to the statistical analysis results. The maximum materials removal rate with the brazed CBN wheel is much higher than that with the electroplated one. All above indicate that the single-layer brazed CBN super-abrasive wheel is more suitable for high-speed grinding of PTMCs than the electroplated counterpart. | Li Zheng Ding Wenfeng Shen Long Xi Xinxin Fu Yucan | 2016 | Chinese Journal of Aeronautics2016，29，5： | 11 |
| 2 | In vitro and in vivo activity of D-serine in combination with β-lactam antibiotics against methicillin-resistant Staphylococcus aureus显示文摘As D-amino acids play important roles in the physiological metabolism of bacteria,combination of D-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate in vitro and in vivo activity of D-serine alone and in combination withβ-lactams against methicillin-resistant Staphylococcus aureus(MRSA) strains, and to explore the possible sensitization mechanisms. The activity of D-serine, β-lactams alone and in combinations was evaluated both in vitro by standard MICs, time–kill curves and checkerboard assays, and in vivo by murine systemic infection model as well as neutropenic thigh infection model. An in vitro synergistic effect was demonstrated with the combination of D-serine and β-lactams against MRSA standard and clinical strains.Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared toβ-lactam alone groups. Initial mechanism study suggested possible revision of D-alanine-D-alanine residue to D-alanine-D-serine in peptidoglycan by adding of D-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, D-serine had synergistic activity in combination with β-lactams against MRSA strains both in vitro and in vivo. Considering the relatively good safety of D-serine alone or in combination with β-lactams, D-serine is worth following up as new anti-MRSA infection strategies. | Qing Wang Yuemeng Lv Jing Pang Xue Li Xi Lu Xiukun Wang Xinxin Hu Tongying Nie Xinyi Yang Yan Q.Xiong Jiandong Jiang Congran Li Xuefu You | 2019 | Acta Pharmaceutica Sinica B2019，9，3： | 6 |
| 3 | Performance evaluation of creep feed grinding ofγ-TiAl intermetallics with electroplated diamond wheels显示文摘This paper evaluates the performance of creep feed grindingγ-TiAl intermetallic(Ti-45 Al-2 Mn-2 Nb)using electroplated diamond wheels.Firstly,a comparative analysis with the grinding results by using electroplated CBN wheels was conducted,mainly involving abrasive wheel wear behavior and maximum material removal rate below surface burn limit.It was found that the diamond wheel would produce much better grinding results including lower wheel wear rate and higher maximum material removal rate.Then the surface integrity obtained at different level of material removal rate was characterized with the utilization of the diamond wheel.The poor ductility of thisγ-TiAl intermetallic material was found to have a marginal effect on the surface integrity,as no severe surface defects such as material pullout were generated during the stable wheel wear stage.For the involved operating parameters,a deformation layer was produced with~10μm or more in thickness depending on the material removal rate used.Meanwhile,a work-hardened layer extending to more than 100μm was produced with a maximum microhardness of above 520 HV0.05(bulk value 360 HV0.05).The residual stress remained compressive,with a value of above-100 MPa and even up to-500 MPa for an elevated material removal rate.Shearing chip was the main chip type,indicating good wheel sharpness in the grinding process. | Xinxin XI Wenfeng DING Zhixin WU Lama ANGGEI | 2021 | Chinese Journal of Aeronautics2021，34，6： | 5 |
| 4 | MiR-378a-3p acts as a tumor suppressor in gastric cancer via directly targeting RAB31 and inhibiting the Hedgehog pathway proteins GLI1/2显示文摘Objective:To improve the prognosis of patients with gastric cancer(GC),more effective therapeutic targets are urgently needed.Increasing evidence indicates that miRNAs are involved in the progression of various tumors,and RAS-associated protein in the brain 31(RAB31)is upregulated and promotes the progression of multiple malignant tumors.Here,we focused on identifying RAB31-targeted miRNAs and elucidating their potential mechanism in the progression of GC.Methods:RAB31 and miR-378a-3p expression levels were detected in paired fresh GC tissues and GC cell lines.Bioinformatics analysis was used to predict the miRNAs targeting RAB31 and the relationships between RAB31 and other genes.Dual-luciferase reporter assays were applied to verify the targeted interaction relationship.CCK-8,colony formation,flow cytometry,wound healing,and Transwell assays were performed to assess the proliferation,apoptosis,migration,and invasion of GC cells.Tumorsphere formation assays were performed to assess the stemness of gastric cancer stem cells.Related proteins were detected by Western blot.Xenograft assays in nude mice were performed to explore the effect of miR-378a-3p in vivo.Results:We report the first evidence that miR-378a-3p is downregulated in GC,whereas its overexpression inhibits proliferation,invasion,and migration as well as promotes apoptosis in GC cells.Mechanistically,miR-378a-3p inhibits the progression of GC by directly targeting RAB31.Restoring RAB31 expression partially offsets the inhibitory effect of miR-378a-3p.Further research revealed that miR-378a-3p inhibits GLI1/2 in the Hedgehog signaling pathway and attenuates the stemness of gastric cancer stem cells.Finally,xenograft assays showed that miR-378a-3p inhibits GC tumorigenesis in vivo.Conclusions:MiR-378a-3p inhibits GC progression by directly targeting RAB31 and inhibiting the Hedgehog signaling pathway proteins GLI1/2. | Xinxin Xu Yang Li Guoxiao Liu Kai Li Peng Chen Yunhe Gao Wenquan Liang Hongqing Xi Xinxin Wang Bo Wei Hongtao Li Lin Chen | 2022 | Cancer Biology & Medicine2022，19，12： | 1 |
| 5 | Circulating exosome-like vesicles of humans with nondiabetic obesity impaired isletβ-cell proliferation,which was associated with decreased Omentin-1 protein cargo显示文摘The regulation ofβ-cell mass in the status of nondiabetic obesity remains not well understood.We aimed to investigate the role of circulating exosome-like vesicles(ELVs)isolated from humans with simple obesity in the regulation of isletβ-cell mass.Between June 2017 and July 2019,81 subjects with simple obesity and 102 healthy volunteers with normal weight were recruited.ELVs were isolated by ultra-centrifugation.The proliferations ofβ-cells and islets were measured by 5-ethynl-2′-deoxyuridine(EdU).Protein components in ELVs were identified by Quantitative Proteomic Analysis and verified by Western blot and ELISA.The role of specific exosomal protein was analyzed by gain-of-function approach in ELVs released by 3T3-L1 preadipocytes.Circulating ELVs from subjects with simple obesity inhibitedβ-cell proliferation in vitro without affecting its apoptosis,secretion,and inflammation.The protein levels of Rictor and Omentin-1 were downregulated in circulating ELVs from subjects with simple obesity and associated with the obesity-linked pathologic conditions.The ELV-carried Omentin-1 and Omentin-1 protein per se were validated to increaseβ-cell proliferation and activate Akt signaling pathway.Moreover,Omentin-1 in ELVs was downregulated by insulin.The circulating ELVs may act as a negative regulator forβ-cell mass in nondiabetic obesity through inhibitingβ-cell proliferation.This effect was associated with downregulated Omentin-1 protein in ELVs.This newly identified ELV-carried protein could be a mediator linking insulin resistance to impairedβ-cell proliferation and a new potential target for increasingβ-cell mass in obesity and T2DM. | Qian Ge Xinxin Xie Xiangjun Chen Rongfeng Huang Cheng-Xue Rui Qianna Zhen Renzhi Hu Min Wu Xiaoqiu Xiao Xi Li | 2022 | Genes & Diseases2022，9，4： | 1 |
| 6 | An Artemisinin Derivative ART1 Induces Ferroptosis by Targeting the HSD17B4 Protein Essential for Lipid Metabolism and Directly Inducing Lipid Peroxidation显示文摘Artemisinin and its derivatives,commonly known as antimalarial drugs,have gradually come to be regarded as potential antitumor agents,although their cytotoxic efficacy and mechanisms of action remain to be settled.Herein,we report that an artemisinin analog,ART1,can potently induce ferroptosis in a subset of cancer cell lines.Structure–activity relationship(SAR)analysis reveals that both the endoperoxide moiety and the artemisinin skeleton are required for the antitumor activity of ART1.Aided with ART1-based small-molecule tools,chemical proteomic analysis identified the HSD17B4 protein as a direct target of ART1.HSD17B4 resides in peroxisomes and is an essential enzyme in the catabolism of very-long-chain fatty acids.Our results demonstrate that ART1 initiates ferroptosis through selective oxidation of the fatty acids in peroxisomes by hijacking the HSD17B4 protein without disturbing its enzymatic function,providing a promising mechanism to develop therapeutics for cancer treatment. | Jingjing Xie Guangya Zhu Ming Gao Jie Xi Ge Chen Xinxin Ma Yu Yan Zhiyuan Wang Ze-Jun Xu Hui-Jun Chen Hong-Dong Hao Yaoyang Zhang Zhu-Jun Yao Jidong Zhu | 2022 | CCS Chemistry2022，4，1： | 0 |
| 7 | Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs显示文摘A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria.Compound 33a(IMBZ18G)is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant(MDR)Gram-negative strains,with a highly druglike nature.The checkerboard assay reveals its significant synergistic effect withβ-lactamase inhibitor avibactam,and the MIC values against MDR enterobacteria were reduced up to 4—512folds.X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and Cβ-lactamases.Accordingly,preclinical studies of 33a alone and 33a-avibactam combination as potential innovative candidates are actively going on,in the treatment ofβ-lactamase-producing MDR Gram-negative bacterial infections. | Zhiwen Li Zhihao Guo Xi Lu Xican Ma Xiukun Wang Rui Zhang Xinxin Hu Yanxiang Wang Jing Pang Tianyun Fan Yonghua Liu Sheng Tang Haigen Fu Jingpu Zhang Yinghong Li Xuefu You Danqing Song | 2023 | Acta Pharmaceutica Sinica B2023，13，7： | 0 |
| 8 | Osteopontin Promotes Macrophage M1 Polarization by Activation of the JAK1/STAT1/HMGB1 Signaling Pathway in Nonalcoholic Fatty Liver Disease显示文摘Background and Aims:Osteopontin(OPN)is reported to be associated with the pathogenesis of nonalcoholic fatty liver disease(NAFLD).However,the function of OPN in NAFLD is still inconclusive.Therefore,our aim in this study was to evaluate the role of OPN in NAFLD and clarify the involved mechanisms.Methods:We analyzed the expression change of OPN in NAFLD by bioinformatic analysis,qRT-PCR,western blotting and immunofluorescence staining.To clarify the role of OPN in NAFLD,the effect of OPN from HepG2 cells on macrophage polarization and the involved mechanisms were examined by FACS and western blotting.Results:OPN was significantly upregulated in NAFLD patients compared with normal volunteers by microarray data,and the high expression of OPN was related with disease stage and progression.OPN level was also significantly increased in liver tissue samples of NAFLD from human and mouse,and in HepG2 cells treated with oleic acid(OA).Furthermore,the supernatants of OPN-treated HepG2 cells promoted the macrophage M1 polarization.Mechanistically,OPN activated the janus kinase 1(JAK1)/signal transducers and activators of transcription 1(STAT1)signaling pathway in HepG2 cells,and consequently HepG2 cells secreted more high-mobility group box 1(HMGB1),thereby promoting macrophage M1 polarization.Conclusions:OPN promoted macrophage M1 polarization by increasing JAK1/STAT1-induced HMGB1 secretion in hepatocytes. | Zhihao Xu Feiyang Xi Xinxin Deng Yuqi Ni Changqin Pu Dan Wang Weiming Lou Xufang Zeng Ning Su Chen Chen Ziqiang Zeng Libin Deng Meixiu Jiang | 2023 | Journal of Clinical and Translational Hepatology2023，11，2： | 0 |
| 9 | Dynamic m6A-ncRNAs association and their impact on cancer pathogenesis, immune regulation and therapeutic response显示文摘Several types of modifications have been proven to participate in the metabolism and processing of different RNA types,including non-coding RNAs(ncRNAs).N-6-methyladenosine(m6A)is a dynamic and reversible RNA modification that is closely involved in the ncRNA homeostasis,and serves as a crucial regulator for multiple cancer-associated signaling pathways.The ncRNAs usually regulate the epigenetic modification,mRNA transcription and other biological processes,displaying enormous roles in human cancers.In this review,we summarized the significant implications of m6A-ncRNA interaction in various types of cancers.In particular,the interplay between m6A and ncRNAs in cancer pathogenesis and therapeutic resistance are being widely recognized.We also discussed the relevance of m6A-ncRNA interaction in immune regulation,followed by the interference on cancer immunotherapeutic procedures.In addition,we briefly highlighted the computation tools that could identify the accurate features of m6A methylome among ncRNAs.In summary,this review would pave the way for a better understanding of the biological functions of m6A-ncRNA crosstalk in cancer research and treatment. | Yuanliang Yan Jinwu Peng Qiuju Liang Xinxin Ren Yuan Cai Bi Peng Xi Chen Xiang Wang Qiaoli Yi Zhijie Xu | 2023 | Genes & Diseases2023，10，1： | 0 |
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