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| 1 | Cationic nanocarriers induce cell necrosis through impairment of Na^+/K^+-ATPase and cause subsequent inflammatory response显示文摘有积极表面费用的 Nanocarriers 以他们限制了他们的临床的应用的毒性著名。位于他们的毒性下面的机制例如煽动性的反应的正式就职,仍然保持大部分未知。在我们发现了 cationic nanocarriers 的那注射的现在的学习,包括 cationic liposomes, PEI,和 chitosan,导致了坏死的房间的快速的外观。cationic nanocarriers 导致的房间坏死依赖于他们的积极表面费用,但是不要求 RIP1 和 Mlkl。相反,细胞内部的 Na + 超载被发现伴随房间死亡。在文化媒介或有 Na +/K+-ATPase 阳离子绑定地点禁止者 ouabain 的房间的预告的处理的 Na + 的弄空,从房间坏死的保护的房间。而且,有 cationic nanocarriers 的处理在 vitro 并且在 vivo 禁止了 Na +/K+-ATPase 活动。计算模拟证明 cationic 搬运人能与 Na +/K+-ATPase 的阳离子绑定地点交往。有 ouabain 的小剂量的老鼠 pretreated 在 cationic nanocarriers 的致命的剂量的注射以后显示出改进幸存。进一步的分析建议 cationic nanocarriers 和 mitochondrial DNA 的产生的漏导致的那房间坏死能在 vivo 触发严重发炎,它被包含 TLR9 并且 MyD88 发信号的一条小径调停。一起拿,我们的结果揭示由此的新奇机制 cationic nanocarriers 通过和 mitochondrial 的随后的暴露的和 Na +/K+-ATPase, 的相互作用导致尖锐房间坏死是的联系损坏的分子的模式调停的一个关键事件煽动性的回答。我们的学习为评估 nanocarriers 的 biocompatibility 并且为药交货设计更好、更安全的有重要含意。 | Xiawei Wei Bin Shao Zhiyao He Tinghong Ye Min Luo Yaxiong Sang Xiao Liang Wei Wang Shuntao Luo Shengyong Yang Shuang Zhang Changyang Gong Maling Gou Hongxing Deng Yinglan Zhao Hanshuo Yang Senyi Deng Chengjian Zhao Li Yang Zhiyong Qian Jiong Li Xun Sun Jiahuai Han Chengyu Jiang Min Wu Zhirong Zhang | 2015 | Cell Research2015，25，2： | 21 |
| 2 | Molecular mechanisms and clinical management of cancer bone metastasis显示文摘As one of the most common metastatic sites of malignancies,bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish.The fenestrated capillaries in the bone,bone matrix,and bone cells,including osteoblasts and osteoclasts,together maintain the homeostasis of the bone microenvironment.In contrast,tumor-derived factors act on bone components,leading to subsequent bone resorption or excessive bone formation.The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases.In this review,we summarize the current understanding of the mechanism of bone metastases.Based on the general process of bone metastases,we specifically highlight the complex crosstalk between tumor cells and the bone microenvironment and the current management of cancer bone metastases. | Manni Wang Fan Xia Yuquan Wei Xiawei Wei | 2020 | Bone Research2020，8，3： | 7 |
| 3 | Spontaneous apoptosis of cells in therapeutic stem cell preparation exert immunomodulatory effects through release of phosphatidylserine显示文摘Mesenchymal stem cell(MSC)-mediated immunomodulation has been harnessed for the treatment of human diseases,but its underlying mechanism has not been fully understood.Dead cells,including apoptotic cells have immunomodulatory properties.It has been repeatedly reported that the proportion of nonviable MSCs in a MSC therapeutic preparation varied from 5-50%in the ongoing clinical trials.It is conceivable that the nonviable cells in a MSC therapeutic preparation may play a role in the therapeutic effects of MSCs.We found that the MSC therapeutic preparation in the present study had about 5%dead MSCs(DMSCs),characterized by apoptotic cells.Namely,1×10^(6) MSCs in the preparation contained about 5×10^(4) DMSCs.We found that the treatment with even 5×10^(4) DMSCs alone had the equal therapeutic effects as with 1×10^(6) MSCs.This protective effect of the dead MSCs alone was confirmed in four mouse models,including concanavalin A(ConA)-and carbon tetrachloride(CCI4)-induced acute liver injury,LPS-induced lung injury and spinal cord injury.We also found that the infused MSCs died by apoptosis in vivo.Furthermore,the therapeutic effect was attributed to the elevated level of phosphatidylserine(PS)upon the injection of MSCs or DMSCs.The direct administration of PS liposomes(PSLs)mimic apoptotic cell fragments also exerted the protective effects as MSCs and DMSCs.The Mer tyrosine kinase(MerTK)deficiency or the knockout of chemokine receptor C-C motif chemokine receptor 2(CCR2)reversed these protective effects of MSCs or DMSCs.These results revealed that DMSCs alone in the therapeutic stem cell preparation or the apoptotic cells induced in vivo may exert the same immunomodulatory property as the'living MSCs preparation'through releasing PS,which was further recognized by MerTK and participated in modulating immune cells. | Xuemei He Weiqi Hong Jingyun Yang Hong Lei Tianqi Lu Cai He Zhenfei Bi Xiangyu Pan Yu Liu Lunzhi Dai Wei Wang Canhua Huang Hongxin Deng Xiawei Wei | 2021 | Signal Transduction and Targeted Therapy2021，6，8： | 6 |
| 4 | Acidity of Aerosols during Winter Heavy Haze Events in Beijing and Gucheng, China显示文摘We investigated the acidity and concentrations of water-soluble ions in PM_(2.5) aerosol samples collected from an urban site in Beijing and a rural site in Gucheng, Hebei Province from November 2016 to January 2017 to gain an insight into the formation of secondary inorganic species. The average SO_4^(2–), NO_3~–, and NH_4^+ concentrations were 8.3,12.5, and 14.1 μg m^(–3), respectively, at the urban site and 14.0, 14.2, and 24.2 μg m^(–3), respectively, at the rural site.The nitrogen and sulfur oxidation ratios in urban Beijing were correlated with relative humidity(with correlation coefficient r = 0.79 and 0.67, respectively) and the aerosol loadings. Based on a parameterization model, we found that the rate constant of the heterogeneous reactions for SO_2 on polluted days was about 10 times higher than that on clear days, suggesting that the heterogeneous reactions in the aerosol water played an essential role in haze events.The ISORROPIA II model was used to predict the aerosol pH, which had a mean(range) of 5.0(4.9–5.2) and 5.3(4.6–6.3) at the urban and rural site, respectively. Under the conditions with this predicted pH value, oxidation by dissolved NO_2 and the hydrolysis of N_2O_5 may be the major heterogeneous reactions forming SO_4^(2–) and NO_3~– in haze.We also analyzed the sensitivity of the aerosol p H to changes in the concentrations of SO_4^(2–), NO_3~–, and NH_4^+ under haze conditions. The aerosol p H was more sensitive to the SO_4^(2–) and NH_4^+ concentrations with opposing trends, than to the NO_3~– concentrations. The sensitivity of the p H was relatively weak overall, which was attributed to the buffering effect of NH_3 partitioning. | Xiyuan CHI Pengzhen HE Zhuang JIANG Xiawei YU Fange YUE Longquan WANG Bokun LI Hui KANG Cheng LIU Zhouqing XIE | 2018 | Journal of Meteorological Research2018，32，1： | 4 |
| 5 | Hot deformation behavior and microstructure evolution of the laser solid formed TC4 titanium alloy显示文摘Hot compressive experiments of the laser solid formed(LSFed)TC4 titanium alloy were conducted at a wide temperature range of 650-950℃and strain rate of 0.01-10 s^(-1).The Arrheniustype constitutive models of the LSFed TC4 alloy were established at the temperature range of 800-950℃and of 650-800℃,respectively.The average relative error between the predicted stresses and experimental values in those two temperature ranges are 10.4%and 8.3%,respectively,indicating that the prediction models constructed in this paper are in a good agreement with experimental data.Processing maps were established by the principle of dynamic materials modeling on the basis of the data achieved from the hot compression experiments.The processing parameters corresponding to the stable and unstable regions of material deformation can be determined from the processing maps.The microstructure evolution of the stable and unstable regions of the samples after tests were observed.Finally,the effect of hot compressive parameters on the microstructure were investigated to research the dynamic recrystallization and the texture of the deformed LSFed TC4 alloy. | Xiawei YANG Yanying WANG Xiurong DONG Chong PENG Baijin JI Yaxin XU Wenya LI | 2021 | Chinese Journal of Aeronautics2021，34，5： | 3 |
| 6 | In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures显示文摘 | Chao Ni Yuhui Chen Musheng Zeng Rongjuan Pei Yong Du Linquan Tang Mengyi Wang Yazhuo Hu Hanyu Zhu Meifang He Xiawei Wei Shan Wang Xiangkai Ning Manna Wang Jufang Wang Li Ma Xinwen Chen Qiang Sun Hong Tang Ying Wang Xiaoning Wang | 2015 | Cell Research2015，25，7： | 3 |
| 7 | Oxidized mitochondrial DNA sensing by STING signaling promotes the antitumor effect of an irradiated immunogenic cancer cell vaccine显示文摘Exposure to ionizing radiation,a physical treatment that inactivates live tumor cells,has been extensively applied to enhance the antitumor responses induced by cancer cell vaccines in both animal research and human clinical trials.However,the mechanisms by which irradiated cells function as immunogenic tumor vaccines and induce effective antitumor responses have not been fully explored.Here,we demonstrate that oxidized mitochondrial DNA(mtDNA)and stimulator of interferon genes(STING)signaling play a key roles in the enhanced antitumor effect achieved with an irradiated tumor cell vaccine.Elevations in ROS and oxidized mtDNA 8-OHG content could be induced in irradiated tumor cells.Oxidized mtDNA derived from irradiated tumor cells gained access to the cytosol of dendritic cells(DCs).Oxidized mtDNA,as a DAMP or adjuvant,activated the STING-TBK1-IRF3-IFN-β pathway in DCs,which subsequently cross-presented irradiated tumor cell-derived antigens to CD8^(+)T cells and elicited antitumor immunity.The results of our study provide insight into the mechanism by which an irradiated cell vaccine mediates antitumor immunity,which may have implications for new strategies to improve the efficacy of irradiated vaccines. | Chunju Fang Fei Mo Li Liu Jing Du Min Luo Ke Men Feifei Na Wei Wang Hanshuo Yang Xiawei Wei | 2021 | Cellular & Molecular Immunology2021，18，9： | 2 |
| 8 | Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells显示文摘Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host defense.Contrary to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model.The histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids.Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein.Moreover,histones enhance cell-cell fusion.Finally,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model.These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19. | Weiqi Hong Jingyun Yang Jun Zou Zhenfei Bi Cai He Hong Lei Xuemei He Xue Li Aqu Alu Wenyan Ren Zeng Wang Xiaohua Jiang Kunhong Zhong Guowen Jia Yun Yang Wenhai Yu Qing Huang Mengli Yang Yanan Zhou Yuan Zhao Dexuan Kuang Junbin Wang Haixuan Wang Siyuan Chen Min Luo Ziqi Zhang Tiangi Lu Li Chen Haiying Que Zhiyao He Qiu Sun Wei Wang Guobo Shen Guangwen Lu Zhiwei Zhao Li Yang Jinliang Yang Zhenling Wang Jiong Li Xiangrong Song Lunzhi Dai Chong Chen Jia Geng Maling Gou Lu Chen Haohao Dong Yong Peng Canhua Huang Zhiyong Qian Wei Cheng Changfa Fan Yuquan Wei Zhaoming Su Aiping Tong Shuaiyao Lu Xiaozhong Peng Xiawei Wei | 2022 | Cellular & Molecular Immunology2022，19，5： | 2 |
| 9 | Role of tumor gene mutations in treatment response to immune checkpoint blockades显示文摘Early studies shed light on the immune suppression of immune checkpoint molecules in the cancer microenvironment,with later studies applying immune checkpoint blockade(ICB)in treatment of various malignancies.Despite the encouraging efficacy of ICBs in a substantial subset of cancer patients,the treatment response varies.Gene mutations of both tumor cells and immune cells in the tumor microenvironment have recently been identified as potential predictors of the ICB response.Recent developments in gene expression profiling of tumors have allowed identification of a panel of mutated genes that may affect tumor cell response to ICB treatment.In this review,we discuss the association of the ICB response with gene expression and mutation profiles in tumor cells,which it is hoped will help to optimize the clinical application of ICBs in cancer patients. | Manni Wang Liu Yu Xiawei Wei Yuquan Wei | 2019 | Precision Clinical Medicine2019，2，2： | 2 |
| 10 | DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer显示文摘A significant proportion of non-small cell lung cancer(NSCLC) patients experience accumulating chemotherapy-related adverse events,motivating the design of chemosensitizating strategies.The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks(DSB).It is thus conceivable that DNA-dependent protein kinase(DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy.The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC.We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis.M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549,H460 and H1703 NSCLC cell lines.In the four combinations based on two NSCLC xenograft models and two chemotherapy,we also observed tumor regression at tolerated doses in vivo.Moreover,we identified a P53-dependent accelerated senescence response by M3814 following treatment with paclitaxel/etoposide.The present study provides a theoretical basis for the use of M3814 in combination with paclitaxel and etoposide in clinical practice,with hope to aid the optimization of NSCLC treatment. | Manni Wang Siyuan Chen Yuquan Wei Xiawei Wei | 2021 | Acta Pharmaceutica Sinica B2021，11，12： | 2 |
| 11 | Ecological functions of uncultured microorganisms in the cobaltrich ferromanganese crust of a seamount in the central Pacific are elucidated by fosmid sequencing显示文摘Cobalt-rich ferromanganese is an important seafloor mineral and is abundantly present in the seamount crusts.Such crusts form potential hotspots for biogeochemical activity and microbial diversity, yet our understanding of their microbial communities is lacking. In this study, a cultivation-independent approach was used to recover genomic information and derive ecological functions of the microbes in a sediment sample collected from the cobalt-rich ferromanganese crust of a seamount region in the central Pacific. A total of 78 distinct clones were obtained by fosmid library screening with a 16 SrRNA based PCR method. Proteobacteria and MGI Thaumarchaeota dominated the bacterial and archaeal 16 SrRNA gene sequence results in the microbial community. Nine fosmid clones were sequenced and annotated. Numerous genes encoding proteins involved in metabolic functions and heavy metal resistance were identified, suggesting alternative metabolic pathways and stress responses that are essential for microbial survival in the cobalt-rich ferromanganese crust. In addition, genes that participate in the synthesis of organic acids and exoploymers were discovered. Reconstruction of the metabolic pathways revealed that the nitrogen cycle is an important biogeochemical process in the cobalt-rich ferromanganese crust. In addition, horizontal gene transfer(HGT) events have been observed, and most of them came from bacteria, with some occurring in archaea and plants. Clone W4-93 a, belonging to MGI Thaumarchaeota, contained a region of gene synteny. Comparative analyses suggested that a high frequency of HGT events as well as genomic divergence play important roles in the microbial adaption to the deep-sea environment. | HUO Yingyi CHENG Hong Anton F.Post WANG Chunsheng JIANG Xiawei PAN Jie WU Min XU Xuewei | 2015 | Acta Oceanologica Sinica2015，34，4： | 2 |
| 12 | Recent developments in regenerative ophthalmology显示文摘Regenerative medicine(RM)is one of the most promising disciplines for advancements in modern medicine,and regenerative ophthalmology(RO)is one of the most active fields of regenerative medicine.This review aims to provide an overview of regenerative ophthalmology,including the range of tools and materials being used,and to describe its application in ophthalmologic subspecialties,with the exception of surgical implantation of artificial tissues or organs(e.g.,contact lens,artificial cornea,intraocular lens,artificial retina,and bionic eyes)due to space limitations.In addition,current challenges and limitations of regenerative ophthalmology are discussed and future directions are highlighted. | Ye Shen He Shen Dongyu Guo Xinghuai Sun Yuan Sun Nan Hong Xiawei Wang Chen Xie Yuan Zhao Qin He Le Jin Yingying Wen Bo Jiang Chenying Yu Miaomiao Zhu Feng Cai Jianwu Dai | 2020 | Science China(Life Sciences)2020，63，10： | 2 |
| 13 | Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection显示文摘The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants.In Chengdu,China,an infection wave was predominantly induced by the BA.5 subvariant.It is crucial to determine whether the hybrid anti-SARS-CoV-2 immunity following BA.5 infection. | Jingyun Yang Weiqi Hong Hong Lei Cai He Wenwen Lei Yanan Zhou Tingmei Zhao Aqu Alu Xuelei Ma Jiong Li Li Yang Zhenling Wang Wei Wang Guangwen Lu Guobo Shen Shuaiyao Lu Guizhen Wu Huashan Shi Xiawei Wei | 2023 | Signal Transduction and Targeted Therapy2023，8，7： | 1 |
| 14 | Ammonia promotes the proliferation of bone marrow-derived mesenchymal stem cells by regulating the Akt/mTOR/S6k pathway显示文摘Ammonia plays an important role in cellular metabolism.However,ammonia is considered a toxic product.In bone marrow-derived mesenchymal stem cells,multipotent stem cells with high expression of glutamine synthetase(GS)in bone marrow,ammonia and glutamate can be converted to glutamine via glutamine synthetase activity to support the proliferation of MSCs.As a major nutritional amino acid for biosynthesis,glutamine can activate the Akt/mTOR/S6k pathway to stimulate cell proliferation.The activation of mTOR can promote cell entry into S phase,thereby enhancing DNA synthesis and cell proliferation.Our studies demonstrated that mesenchymal stem cells can convert the toxic waste product ammonia into nutritional glutamine via GS activity.Then,the Akt/mTOR/S6k pathway is activated to promote bone marrow-derived mesenchymal stem cell proliferation.These results suggest a new therapeutic strategy and potential target for the treatment of diseases involving hyperammonemia. | Yu Liu Xiangxian Zhang Wei Wang Ting Liu Jun Ren Siyuan Chen Tianqi Lu Yan Tie Xia Yuan Fei Mo Jingyun Yang Yuquan Wei Xiawei Wei | 2022 | Bone Research2022，10，4： | 1 |
| 15 | Nanoparticles targeting tumor-associated macrophages:A novel anti-tumor therapy显示文摘The immunosuppressive tumor microenvironment(TME)is crucial in the occurrence of tumorigenesis,metastasis,and drug resistance.Among all stromal cells,tumor-associated macrophages(TAMs)are recognized as vital components causing the TME to be favorable for cancer cells and are also main targets in cancer immunotherapy.To date,nanoparticle(NP)-based drug delivery systems,as new technology platforms,have exhibited considerable advantages,such as targeted drug delivery at tumor sites,enhanced drug transport efficiency,and controllable drug release profiles,which provide new approaches for cancer therapy.Regarding TAM-targeting nanoparticles,various therapeutic strategies have been developed by varying their design,namely,by blocking TAM recruitment,promoting TAM transformation,and directly diminishing existing TAMs.In the current review,we provide a brief overview of the role of TAMs in the tumor microenvironment and their functions and highlight strategies for TAM targeting.Moreover,the applications of nanoparticles in targeting TAMs to improve cancer therapeutic efficiency are summarized. | Siyuan Chen Furong Qin Manni Wang Yuquan Wei Zhiyong Qian Xiawei Wei | 2022 | Nano Research2022，15，3： | 1 |
| 16 | Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials显示文摘Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence.Epigenetic dysregulation is often linked to human disease,notably cancer.With the development of various drugs targeting epigenetic regulators,epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical trials.In this review,we summarize the aberrant functions of enzymes in DNA methylation,histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes. | Yuan Cheng Cai He Manni Wang Xuelei Ma Fei Mo Shengyong Yang Junhong Han Xiawei Wei | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 1 |
| 17 | Intranasal administration of a recombinant RBD vaccine induces long-term immunity against Omicron-included SARS-CoV-2 variants显示文摘The outbreak of coronavirus disease 2019(COVID-19)has posed great threats to global health and economy.Several effective vaccines are available now,but additional booster immunization is required to retain or increase the immune responses owing to waning immunity and the emergency of new variant strains.The deficiency of intramuscularly delivered vaccines to induce mucosal immunity urged the development of mucosal vaccines.Here,we developed an adjuvanted intranasal RBD vaccine and monitored its long-term immunogenicity against both wild-type and mutant strains of severe acute respiratory syndrome coronavirus-2(SARSCoV-2),including Omicron variants,in mice.Three-dose intranasal immunization with this vaccine induced and maintained high levels of neutralizing IgG antibodies in the sera for at least 1 year.Strong mucosal immunity was also provoked,including mucosal secretory IgA and lung-resident memory T cells(TRM).We also demonstrated that the long-term persistence of lung TRM cells is a consequence of local T-cell proliferation,rather than T-cell migration from lymph nodes.Our data suggested that the adjuvanted intranasal RBD vaccine is a promising vaccine candidate to establish robust,long-lasting,and broad protective immunity against SARS-CoV-2 both systemically and locally. | Hong Lei Aqu Alu Jingyun Yang Wenyan Ren Cai He Tianxia Lan Xuemei He Li Yang Jiong Li Zhenling Wang Xiangrong Song Wei Wang Guangwen Lu Xiawei Wei | 2022 | Signal Transduction and Targeted Therapy2022，7，6： | 1 |
| 18 | Jumonji domain-containing 6 (JMJD6) identified as a potential therapeutic target in ovarian cancer显示文摘Jumonji domain-containing 6(JMJD6)is a candidate gene associated with tumorigenesis,and JMJD6 overexpression predicts poor differentiation and unfavorable survival in some cancers.However,there are no studies reporting the expression of JMJD6 in ovarian cancer,and no JMJD6 inhibitors have been developed and applied to targeted cancer therapy research.In the present study,we found that the high expression of JMJD6 in ovarian cancer was correlated with poor prognosis in ovarian cancer.A potential inhibitor(SKLB325)was designed based on the crystal structure of the jmjC domain of JMJD6.This molecule significantly suppressed proliferation and induced apoptosis in a dose-dependent manner in SKOV3 cell lines as detected by CCK-8 cell proliferation assays and flow cytometry.A Matrigel endothelial tube formation assay showed that SKLB325 inhibited capillary tube organization and migration in HUVECs in vitro.We also observed that JMJD6 colocalized with p53 protein in the nucleus,with mRNA and protein expression of p53 as well as its downstream effectors significantly increasing both in vitro and in intraperitoneal tumor tissues treated with SKLB325.In addition,SKLB325 significantly reduced the intraperitoneal tumor weight and markedly prolonged the survival of tumor-bearing mice.Taken together,our findings suggest that JMJD6 may be a marker of poor prognosis in ovarian cancer and that SKLB325 may be a potential candidate drug for the treatment of ovarian cancer. | Heng Zheng Yan Tie Zhen Fang Xiaoai Wu Tao Yi Shuang Huang Xiao Liang Yanping Qian Xi Wang Ruyu Pi Siyuan Chen Yong Peng Shengyong Yang Xia Zhao Xiawei Wei | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 1 |
| 19 | Cationic nanocarriers as potent adjuvants for recombinant S-RBD vaccine of SARS-CoV-2显示文摘Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vaccine,targeting receptor binding domain(RBD)of the spike protein(S-RBD)of SARS-CoV-2,which could induce a potent antibody response and protect non-human primates from SARS-CoV-2 challenge.1 The recombinant RBD protein is proved as a potent antigen and a novel adjuvant is in demand for the effective stimulation of adaptive immunity.Therefore,to improve the efficacy of the vaccine and seek a novel adjuvant that can stimulate both humoral and cellular immunity,we investigated the potential of series of cationic nanocarriers as adjuvants of the recombinant S-RBD vaccine for SARS-CoV-2.As the surface charge of a nanocarrier might dramatically affect the immunogenicity of a vaccine and enhance and/or shape antigen-specific immune responses,we also used anionic nanocarriers and neutral nanocarriers as controls(Supplementary Table S1).S-RBD vaccines with adjuvant candidates were administered intranasally or intramuscularly in the present study. | Hong Lei Aqu Alu Jingyun Yang Cai He Weiqi Hong Zesheng Cheng Li Yang Jiong Li Zhenling Wang Wei Wang Guangwen Lu Xiawei Wei | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 20 | S19W,T27W,and N33OY mutations in ACE2 enhance SARS-CoV-2 S-RBD binding toward both wild-type and antibody-resistant viruses and its molecular basis显示文摘SARS-CoV-2 recognizes,via its spike receptor-binding domain(S-RBD),human angiotensin-converting enzyme 2(ACE2)to initiate infection.Ecto-domain protein of ACE2 can therefore function as a decoy.Here we show that mutations of S19W,T27W,and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding.Y330 could be synergistically combined with either W19 or W27,whereas W19 and W27 are mutually unbeneficial.The structures of SARS-CoV-2S-RBD bound to the ACE2 mutants reveal that the enhan ced binding is mainly con tributed by the van der Waals interactio ns mediated by the aromatic side-chai ns from W19,W27,and Y330.While Y330 and W19/W27 are distantly located and devoid of any steric interference,W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts,explai ning their in compatibility.Finally,using pseudotyped SARS-CoV-2 viruses,we dem on strate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses.Taken together,our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W,T27W,and N330Y mutations in ACE2,paving the way for potential application of these mutants in dinical treatment of COVID-19. | Fei Ye Xi Lin Zimin Che Fanli Yang Sheng Lin Jing Yang Hua Chen Honglu Sun Lingling Wang Ao Wen Xindan Zhang Yushan Dai Yu Cao Jingyun Yang Guobo Shen Li Yang Jiong Li Zhenling Wang Wei Wang Xiawei Wei Guangwen Lu | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 0 |
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