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| 1 | CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta,alpha,beta,and gamma显示文摘SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing antibodies.An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants.Here,we identified CD147 as a universal receptor for SARS-CoV-2 and its variants.Meanwhile,Meplazeumab,a humanized anti-CD147 antibody,could block cellular entry of SARS-CoV-2 and its variants-alpha,beta,gamma,and delta,with inhibition rates of 68.7,75.7,52.1,52.1,and 62.3%at 60μg/ml,respectively.Furthermore,humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants,alpha and beta.When infected,these mice developed exudative alveolar pneumonia,featured by immune responses involving alveoli-infiltrated macrophages,neutrophils,and lymphocytes and activation of IL-17 signaling pathway.Mechanistically,we proposed that severe COVID-19-related cytokine storm is induced by a'spike protein-CD147-CyPA signaling axis':Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway,which further induced expression of cyclophilin A(CyPA);CyPA reciprocally bound to CD147 and triggered MAPK pathway.Consequently,the MAPK pathway regulated the expression of cytokines and chemokines,which promoted the development of cytokine storm.Importantly,Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants.Therefore,our findings provided a new perspective for severe COVID-19-related pathogenesis.Furthermore,the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment. | Jiejie Geng Liang Chen Yufeng Yuan Ke Wang Youchun Wang Chuan Qin Guizhen Wu Ruo Chen Zheng Zhang Ding Wei Peng Du Jun Zhang Peng Lin Kui Zhang Yongqiang Deng Ke Xu Jiangning Liu Xiuxuan Sun Ting Guo Xu Yang Jiao Wu Jianli Jiang Ling Li Kun Zhang Zhe Wang Jing Zhang Qingguo Yan Hua Zhu Zhaohui Zheng Jinlin Miao Xianghui Fu Fengfan Yang Xiaochun Chen Hao Tang Yang Zhang Ying Shi Yumeng Zhu Zhuo Pei Fei Huo Xue Liang Yatao Wang Qingyi Wang Wen Xie Yirong Li Mingyan Shi Huijie Bian Ping Zhu Zhi-Nan Chen | 2021 | Signal Transduction and Targeted Therapy2021,6,10: | 6 |
| 2 | A Non-Redundant Benchmark for Symmetric Protein Docking显示文摘Symmetric proteins play important roles in many biological processes, such as signal transduction and molecular transportation. Therefore, determining the symmetric oligomeric structure of subunits is crucial to investigate the molecular mechanism of the related processes. Due to the high cost and technical difficulties associated with many experimental methods, computational approaches, such as molecular docking, have played an important complementary role in the determination of symmetric complex structures, in which a benchmark data set is pressingly needed. In the present work, we develop a comprehensive and non-redundant benchmark for symmetric protein docking based on the structures in the Protein Data Bank(PDB). The diverse dataset consists of 251 targets, including 212 cases with cyclic groups symmetry, 35 cases with dihedral groups symmetry, 3 cases with cubic groups symmetry, and 1 case with helical symmetry. According to the conformational changes in the interface between bound and unbound structures, the 251 targets were classified into three groups: 176 'easy',37 'medium', and 38 'difficult' cases. A preliminary docking test on the targets of cyclic groups symmetry with MZDOCK indicated that symmetric multimer docking remains challenging. The benchmark will be beneficial for the development of symmetric protein docking algorithms. The proposed benchmark data set is available for download at http://gffzz2d5067a24f40451dh0xbfw5qu0c0o66on.ffgz.tsg.suse.edu.cn/SDBenchmark/. | Yumeng Yan Sheng-You Huang | 2019 | Big Data Mining and Analytics2019,2,2: | 2 |
| 3 | Glycosyltransferases:Mining,engineering and applications in biosynthesis of glycosylated plant natural products显示文摘UDP-Glycosyltransferases(UGTs)catalyze the transfer of nucleotide-activated sugars to specific acceptors,among which the GT1 family enzymes are well-known for their function in biosynthesis of natural product glycosides.Elucidating GT function represents necessary step in metabolic engineering of aglycone glycosylation to produce drug leads,cosmetics,nutrients and sweeteners.In this review,we systematically summarize the phylogenetic distribution and catalytic diversity of plant GTs.We also discuss recent progress in the identifi-cation of novel GT candidates for synthesis of plant natural products(PNPs)using multi-omics technology and deep learning predicted models.We also highlight recent advances in rational design and directed evolution engineering strategies for new or improved GT functions.Finally,we cover recent breakthroughs in the appli-cation of GTs for microbial biosynthesis of some representative glycosylated PNPs,including flavonoid glycosides(fisetin 3-O-glycosides,astragalin,scutellarein 7-O-glucoside),terpenoid glycosides(rebaudioside A,ginseno-sides)and polyketide glycosides(salidroside,polydatin). | Bo He Xue Bai Yumeng Tan Wentao Xie Yan Feng Guang-Yu Yang | 2022 | Synthetic and Systems Biotechnology2022,7,1: | 2 |
| 4 | Soil microbial communities as potential regulators of N2O sources in highly acidic soils显示文摘●Soil pH was a key driver of N2O emission and sources in acidic soils.●N2O emission was significantly positively associated with the ratio of ITS to 16S.●N2O was significantly correlated with bacterial and fungal community composition.●Fungi contributed to N2O in highly acidic tea plantations and vegetable fields.Acidic soil is a main source of global nitrous oxide(N2O)emissions.However,the mechanism behind the high N2O emissions from acidic soils remains a knowledge gap.The objective of this microcosm incubation study was to pin-point the microbial mechanisms involved in N2O production processes in acidic soils.For that purpose,the isotopic signatures and microbial community structure and composition of four soil samples were examined.The results showed that highly acid soils(pH=3.51)emitted 89 times more N2O than alkaline soils(pH=7.95)under the same nitrogen(N)inputs.Fungal denitrification caused high N2O emissions in acidic soils.ITS to 16S abundance ratio was positively correlated with cumulative N2O emissions from the tested soils.The highly acid soils(pH<4.5)showed greater fungal nirK gene abundance and lower abundance of AOA-amoA,AOB-amoA,nirK,nosZ I and nosZ II genes.The unclassified Aspergillaceae fungi(63.65%)dominated the highly acidic soils and was the most strongly correlated genus with N2O emissions.These findings highlight that soil microbial community structures,denitrifying fungi in particular,shaped by low pH(pH<4.5)lead to high N2O emissions from acidic soils. | Junhui Yin Huaihai Chen Pengpeng Duan Kun Zhu Naihui Li Yan Ma Yumeng Xu Jingheng Guo Rui Liu Qing Chen | 2023 | Soil Ecology Letters2023,5,4: | 1 |
| 5 | Primary malignant tumours and malignant transformation of cysts in the retrorectal space:MRI diagnosis and treatment outcomes显示文摘Background:There are no clear guidelines for the diagnosis and treatment of malignant retrorectal tumours.The purpose of this study was to increase preoperative diagnostic knowledge and to describe the outcomes of treatment for these patients.Methods:This retrospective study was conducted on patients who underwent complete retrorectal tumour resection between May 2006 and July 2018,and had confirmed post-operative pathology reports.Demographic and clinical data(including imaging,perioperative,pathological,and prognostic data)were collected and analysed.Results:Malignant lesions were identified in 15(9[60%],female)patients.The median age of the patients was 59 years(range,34–72 years).Primary malignant tumours were identified in seven patients with solid tumours,in which gastrointestinal stromal tumours accounted for 71.4%(five of seven)and the remainder were chordoma or mucinous adenocarcinoma.Malignant transformation of cysts occurred in another eight patients with heterogeneous tumours,while histopathological features were present in 75%(six of eight)of patients with mucinous adenocarcinoma,and the remainder were squamouscell carcinoma or neuroendocrine tumour(Grade 2).The malignant characteristics of the solid portions observed using magnetic resonance imaging(MRI)were as follows:the cyst wall of the tumour was irregularly thickened;the surface was convex or lobed;the solid tumour had no capsule,or the capsule was destroyed;and the surface had a gyrus-like morphology.At a median follow-up time of 52 months(range,13–100 months),the overall recurrence-free survival rate was 40.0%and the survival rate was 46.7%.Conclusion:Some MRI features can be used to distinguish malignant retrorectal tumours from benign retrorectal tumours.The survival rate of patients with malignant retrorectal tumours is poor. | Jing Gong Yumeng Xu Yan Zhang Lichao Qiao Haixia Xu Ping Zhu Bolin Yang | 2022 | Gastroenterology Report2022,10,1: | 1 |
| 6 | An inactivated recombinant rabies virus chimerically expressed RBD induces humoral and cellular immunity against SARS-CoV-2 and RABV显示文摘Many studies suggest that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can infect various animals and transmit among animals,and even to humans,posing a threat to humans and animals.There is an urgent need to develop inexpensive and efficient animal vaccines to prevent and control coronavirus disease 2019(COVID-19)in animals.Rabies virus(RABV)is another important zoonotic pathogen that infects almost all warmblooded animals and poses a great public health threat.The present study constructed two recombinant chimeric viruses expressing the S1 and RBD proteins of the SARS-CoV-2 Wuhan01 strain based on a reverse genetic system of the RABV SRV9 strain and evaluated their immunogenicity in mice,cats and dogs.The results showed that both inactivated recombinant viruses induced durable neutralizing antibodies against SARS-CoV-2 and RABV and a strong cellular immune response in mice.Notably,inactivated SRV-nCoV-RBD induced earlier antibody production than SRV-nCoV-S1,which was maintained at high levels for longer periods.Inactivated SRV-nCoV-RBD induced neutralizing antibodies against both SARS-CoV-2 and RABV in cats and dogs,with a relatively broadspectrum cross-neutralization capability against the SARS-CoV-2 pseudoviruses including Alpha,Beta,Gamma,Delta,and Omicron,showing potential to be used as a safe bivalent vaccine candidate against COVID-19 and rabies in animals. | Haili Zhang Hongli Jin Feihu Yan Yumeng Song Jiaxin Dai Cuicui Jiao Yujie Bai Jingxuan Sun Di Liu Shen Wang Mengyao Zhang Jilong Lu Jingbo Huang Pei Huang Yuanyuan Li Xianzhu Xia Hualei Wang | 2023 | Virologica Sinica2023,38,2: | 0 |
| 7 | Stability evaluation method of large cross-section tunnel considering modification of thickness-span ratio in mechanized operation显示文摘Purpose-This study aims to research the large cross-section tunnel stability evaluation method corrected after considering the thickness-span ratio.Design/methodology/approach-First,taking the Liuyuan Tunnel of Huanggang-Huangmei High-Speed Railway as an example and taking deflection of the third principal stress of the surrounding rock at a vault after tunnel excavation as the criterion,the critical buried depth of the large section tunnel was determined.Then,the strength reduction method was employed to calculate the tunnel safety factor under different rock classes and thickness-span ratios,and mathematical statistics was conducted to identify the relationships of the tunnel safety factor with the thickness-span ratio and the basic quality(BQ)index of the rock for different rock classes.Finally,the influences of thickness-span ratio,groundwater,initial stress of rock and structural attitude factors were considered to obtain the corrected BQ,based on which the stability of a large cross-section tunnel with a depth of more than 100 m during mechanized operation was analyzed.This evaluation method was then applied to Liuyuan Tunnel and Cimushan No.2 Tunnel of Chongqing Urban Expressway for verification.Findings-This study shows that under different rock classes,the tunnel safety factor is a strict power function of the thickness-span ratio,while a linear function of the BQ to some extent.It is more suitable to use the corrected BQ as a quantitative index to evaluate tunnel stability according to the actual conditions of the site.Originality/value-The existing industry standards do not consider the influence of buried depth and span in the evaluation of tunnel stability.The stability evaluation method of large section tunnel considering the correction of overburden span ratio proposed in this paper achieves higher accuracy for the stability evaluation of surrounding rock in a full or large-section mechanized excavation of double line high-speed railway tunnels. | Junru Zhang Yumeng Liu Bo Yan | 2023 | Railway Sciences2023,2,2: | 0 |
| 8 | Therapy of replenishing Yin and regulating Yang for manic episode in bipolar disorder:study protocol for a prospective,double-blind,randomized controlled trial显示文摘Bipolar disorder(BD) is a chronic and recurrent disorder characterized by biphasic mood episodes of mania or hypomania and depression.It affects more than 1% of the global population and is a leading cause of disability in young people.Currently available treatments for BD are still fairly limited in terms of efficacy,with high rates of non-adherence,non-response,and undesirable side effects.Traditional Chinese medicine(TCM) has a long history and rich experience in stabilizing mania and improving quality of life.Aiming at rebalancing Yin and Yang in BD,therapy of replenishing Yin and regulating Yang(RYRY therapy) has been in clinical use for years in China.The present prospective,double-blind,randomized controlled trial is designed to investigate the efficacy and safety of RYRY therapy for bipolar mania and its possible mechanism from the point of regulating gut microbiota and anti-inflammation.A total of 60 eligible participants will be recruited from Beijing Anding Hospital.They will be randomized to either the study group or the control group in a ratio of 1∶1.Participants allocated to the study group will receive RYRY granule,while placebo granule will be applied in the control group.Participants in both groups will be prescribed conventional therapy for manic episode in BD.Four scheduled visits will be conducted over 4 weeks.Outcome measurements include Young Mania Rating Scale,TCM Symptom Pattern Rating Scale,Treatment Emergent Symptom Scale,levels of C-reactive protein,interleukin-6 and tumor necrosis factor-α and the gut microbial community profile of stool samples.Safety outcomes and adverse events will also be recorded.In this study,we set a number of scientific and objective assessments to evaluate the efficacy of RYRY therapy and study into its possible mechanism,hopefully offering clinicians an alternative approach to BD. | YANG Yang YUAN Haining JIA Hongxiao NING Yanzhe WANG Di ZHANG Lei YAN Kaijuan GUO Yumeng WANG Fei SUN Weishuang CHEN Pei | 2023 | Journal of Traditional Chinese Medicine2023,43,3: | 0 |
| 9 | Trimetaphosphate-induced chiral selection between amino acid and nucleoside using ^(15)N-^(31)P coupling NMR显示文摘Life on Earth uses a common set of L-amino acids(L-aa)to construct proteins and D-nucleosides(D-Nu)to form nucleic acids,which serve as the carrier of genetic information.Herein,we reveal the in-trinsic mechanism of chiral selection of L-aa and D-Nu from the perspective of chemical origin of life.This work employed^(15)N-labeled L-aa and performed one-pot synthesis of nucleotide amidate of amino acid(N-aa-NMP)using equal amounts of L-^(15)N-aa and D-^(14)N-aa with D-/L-Nu in the aqueous solution of trimetaphosphate,generating L-^(15)N-aa-NMP and D-^(14)N-aa-NMP,respectively.The ^(31)P-NMR data indicated that L-aa was preferentially selected during the formation of N-aa-NMP in the presence of D-Nu.Surpris-ingly,D-aa was preferred over L-aa in the presence of L-Nu.Further analysis revealed that L-^(15)N-aa-D-NMP vs.D-^(14)N-aa-L-NMP and D-^(14)N-aa-D-NMP vs.L-^(15)N-aa-L-NMP were mirror isomers of each other,respec-tively.These data suggest that there could be a set of chiral systems opposite to that on Earth,which infers there might be a world of life that is a mirror image of the Earth. | Jianxi Ying Ruiwen Ding Yumeng Zhang Bowen Han Yeting Guo Ning Wang Dandan Guo Yile Wu Junwei Huang Yan Liu Feng Ni Shaohua Huang Yufen Zhao | 2022 | Chinese Chemical Letters2022,33,2: | 0 |
| 10 | E3 ligase MG53 suppresses tumor growth by degrading cyclin D1显示文摘Due to the essential role of cyclin D1 in regulating transition from G1 to S phase in cell cycle,aberrant cyclin D1 expression is a major oncogenic event in many types of cancers.In particular,the dysregulation of ubiquitination-dependent degradation of cyclin D1 contributes to not only the pathogenesis of malignancies but also the refractory to cancer treatment regiments with CDK4/6 inhibitors.Here we show that in colorectal and gastric cancer patients,MG53 is downregulated in more than 80%of tumors compared to the normal gastrointestinal tissues from the same patient,and the reduced MG53 expression is correlated with increased cyclin D1 abundance and inferior survival.Mechanistically,MG53 catalyzes the K48-linked ubiquitination and subsequent degradation of cyclin D1.Thus,increased expression of MG53 leads to cell cycle arrest at G1,and thereby markedly suppresses cancer cell proliferation in vitro as well as tumor growth in mice with xenograft tumors or AOM/DSS induced-colorectal cancer.Consistently,MG53 deficiency results in accumulation of cyclin D1 protein and accelerates cancer cell growth both in culture and in animal models.These findings define MG53 as a tumor suppressor via facilitating cyclin D1 degradation,highlighting the therapeutic potential of targeting MG53 in treating cancers with dysregulated cyclin D1 turnover. | Meng Fang Hong-Kun Wu Yumeng Pei Yan Zhang Xiangyu Gao Yanyun He Gengjia Chen Fengxiang Lv Peng Jiang Yumei Li Wenwen Li Peng Jiang Lin Wang Jiafu Ji Xinli Hu Rui-Ping Xiao | 2023 | Signal Transduction and Targeted Therapy2023,8,8: | 0 |
| 11 | CHDOCK: a hierarchical docking approach for modeling Cn symmetric homo-oligomeric complexes显示文摘Protein-protein interactions are crucial in many biological processes. Therefore, determining the complex structure between proteins is valuable for understanding the molecular mechanism and developing drugs. Many proteins like ion channels are formed by symmetric homo-oligomers. In this study, we have proposed a hierarchical docking algorithm to predict the structure of Cn symmetric protein complexes, which is referred to as CHDOCK. The symmetric binding modes were first constructed by an FFT-based docking algorithm and then optimized by our iterative scoring function for protein-protein interactions. When tested on a symmetric protein docking benchmark of 212 homooligomeric complexes with Cn symmetry, CHDOCK obtained a significantly better performance in binding mode predictions than three state-of-the-art symmetric docking methods, M-ZDOCK, SAM, and SymmDock. When the top 10 predictions were considered, CHDOCK achieved a success rate of 44.81% and 72.17% for unbound docking and bound docking, respectively in comparison to those of 36.79% and 65.09% for M-ZDOCK, 31.60% and 54.25% for SAM, and 30.66% and 31.60% for SymmDock. CHDOCK is computationally efficient and can normally complete a symmetric docking calculation within 30 min. The CHDOCK can be freely accessed by a web server at http://gffzz0528586739cb4ac5h0xbfw5qu0c0o66on.ffgz.tsg.suse.edu.cn. cn/hsymdock/. | Yumeng Yan Sheng-You Huang | 2019 | Biophysics Reports2019,5,2: | 0 |
| 12 | Multimodal channel cancer chemotherapy by 2D functional gadolinium metal-organic framework显示文摘2D nanomaterials generally exhibit enhanced physiochemical and biological functions in biomedical applications due to their high surface-to-volume ratio and surface charge.Conventional cancer chemotherapy based on nanomaterials has been hindered by their low drug loading and poor penetration in tumor tissue.To overcome these difficulties,novel materials systems are urgently needed.Hereby,the lanthanide-based porphyrin metal-organic framework(MOF)nanosheets(NSs)with promising cancer imaging/chemotherapy capacities are fabricated,which display superior performance in the drug loading and tumor tissue penetration.The biodegradable PPF-Gd NSs deliver an ultrahigh drug loading(>1500%)and demonstrate the stable and highly sensitive stimuli-responsive degradation/release for multimodal tumor imaging and cancer chemotherapy.Meanwhile,PPF-Gd NSs also exhibit excellent fluorescence and magnetic resonance imaging capability in vitro and in vivo.Compared to the traditional doxorubicin(DOX)chemotherapy,the in vivo results confirm the evident suppression of the tumor growth by the PPF-Gd/DOX drug delivery system with negligible side effects.This work further supports the potential of lanthanide-based MOF nanomaterials as biodegradable systems to promote the cancer theranostics technology development in the future. | Jiale Xia Yumeng Xue Bo Lei Lingling Xu Mingzi Sun Na Li Hongyang Zhao Min Wang Meng Luo Chao Zhang Bolong Huang Yaping Du Chun-Hua Yan | 2021 | National Science Review2021,8,7: | 0 |