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Glucocorticoid and glycolysis inhibitors cooperatively abrogate acute graft-versus-host disease

Science China(Life Sciences) 2023年第3期66卷 528-544页

作者： Qi Wen Zheng-Li Xu Yu Wang Meng Lv Yang Song zhong-shi lyv Tong Xing Lan-Ping Xu Xiao-Hui Zhang Xiao-Jun Huang Yuan Kong Peking University People's Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationCollaborative Innovation Center of HematologyPeking UniversityBeijing 100044China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100044China

Although glucorticosteroids(GCs)are the standard first-line therapy for acute graft-versus-host disease(a Gv HD),nearly 50%of a Gv HD patients have no response to *** role of T cell metabolism in murine a Gv HD was recently ***,whether GCs and metabolism regulators could cooperatively suppress T cell alloreactivity and ameliorate a Gv HD remains to be *** glycolysis,characterized by elevated 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3),and higher rates of glucose consumption and lactate production were found in Tcells from a Gv HD *** upregulation of PFKFB3 induced T cell proliferation and differentiation into proinflammatory *** a humanized mouse model,PFKFB3-overexpressing or PFKFB3-silenced T cells aggravated or prevented a Gv HD,***,our integrated data from patient samples in vitro,in a humanized xenogeneic murine model of a Gv HD and graft-versus-leukaemia(GVL)demonstrate that GCs combined with a glycolysis inhibitor could cooperatively reduce the alloreactivity of T cells and ameliorate a Gv HD without loss of GVL ***,the current study indicated that glycolysis is critical for T cell activation and induction of human a Gv ***,the regulation of glycolysis offers a potential pathogenesis-oriented therapeutic strategy for a Gv HD *** combined with glycolysis inhibitors promises to be a novel first-line combination therapy for a Gv HD patients.

关键词： allogeneic haematopoietic stem cell transplantation graft versus host disease human T cells glycolysis

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Metal-organic frameworks with dinuclear metal centers for synergistically boosting CO2 photoreduction

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Science China Chemistry 2025年第1期68卷 201-208页

作者： Hui-Feng Wang Wen-Jie shi Yu-Xin Yang Bao-Xia Dong Tong-Bu Lu Di-Chang zhong School of Chemistry and Chemical Engineering Yangzhou University Institute for New Energy Materials and Low Carbon Technologies School of Materials Science and Engineering Tianjin University of Technology

Dinuclear metal synergistic catalysis （DMSC） has been proved powerful in boosting CO2reduction,while this has not been achieved in heterogeneous catalysts with long-range order *** this study,we,by introduction of metal catalytic centers into an indium-based metal-organic framework （MOF）,obtained a series of isostructural In-MOFs,including three MOFs with mononuclear metal catalytic center （M-In）,three MOFs with dinuclear homometallic catalytic centers （MM-In）,and three MOFs with dinuclear heterometallic catalytic centers (MM’-In,M/M’=Co（II）,Ni（II）,Zn（II）).It was found that all these MOFs can serve as catalysts for photochemical CO2reduction to *** with M-In,the catalytic activities of MM-In were obviously enhanced,and that of MM’-In was further significantly *** example,the CO yield of Co Zn-In reaches a record value of 12,700μmol g-1h-1,which is 4.0,8.1,9.4,and 18.6-fold higher than that of Co Co-In,Zn Zn-In,Co-In,and Zn-In,***,the catalytic activities of Co Ni-In and Ni Zn-In also show different fold increase than those of corresponding dinuclear homometallic and mononuclear metallic *** results of control experiments and theoretical calculation reveal that the higher catalytic activities of MM-In over M-In can be ascribed to the DMSC effect,and the higher catalytic activity of MM’-In over MM-In can be ascribed to the strengthened DMSC *** work reveals the relationship between DMSC effect and bimetal centers in CO2reduction,which provides new insights into the DMSC and paves a new way to design highly active catalysts for photochemical CO2reduction.

关键词： metal-organic frameworks dinuclear metal centers synergistic catalysis CO2 reduction photocatalysis

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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期68卷 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan zhong Yuanyuan shi Bin Hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

关键词： cbl-dependent radical SAM protein biosynthesis chuangxinmycin stereoselective methylation

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Impregnating photo-stable gold precursor onto uncalcined TS-1 to boost catalytic hydro-oxidation of propane

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Science China Chemistry 2025年

作者： Zhihua Zhang Erchuan Yang Fan Liu Kesheng Xu Yuxia zhong Jinwei Sun Shudong shi Xuezhi Duan Xinggui Zhou State Key Laboratory of Chemical Engineering East China University of Science and Technology

Immobilizing highly dispersed Au nanoparticles onto titanium silicalite-1 (TS-1) by a simple impregnation method under light is still a challenging *** this work,a high photostable Au precursor protected by thiol ligands was firstly synthesized,and the as-prepared Au precursor displayed excellent stability under light for over 30 days,while the Au precursor without thiol ligands formed precipitates after just 2 h under ***,the Au precursor protected by thiol ligands was immobilized on the external surface of uncalcined TS-1 (i.e.,TS-1-B) by the incipient wetness impregnation method (IWI method) to prepare Au/TS-1-B *** activity of as-prepared Au/TS-1-B catalyst in the hydro-oxidation of propane to acetone was 1.4 times higher than that of the catalyst prepared by the deposition-precipitation urea method (DPU method).The structures of the Au/TS-1-B catalysts prepared by different methods were analyzed by multiple *** to the Au/TS-1-B catalyst prepared by the DPU method,the Au/TS-1-B catalyst synthesized by the IWI method exhibited a narrower size distribution of Au nanoparticles and had more small Au particles (<2 nm),which is the main reason for its superior ***,the effects of gold loadings,reaction temperature and Si/Ti molar ratio on the catalytic performance of the Au/TS-1-B catalyst prepared by the IWI method were also *** addition,the Au/TS-1-B catalyst prepared by the IWI method also exhibited excellent stability for over 140 h.

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国际学界关于ChatGPT语言能力的争论与思考

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语言战略研究 2025年第1期10卷 75-86页

作者：时仲田英慧司富珍北京语言大学语言学系/乔姆斯基研究所/生物语言学与脑科学实验室北京100083 北京华文学院招生办公室北京102206

随着ChatGPT为代表的大语言模型在应用方面取得极大成功,语言官能是否为人类独有的问题引起热议,国际学界形成两个对立的阵营。一方认为,大语言模型语言理解和产出方面达到了媲美人类的水准,对乔姆斯基的语言学理论提出了挑战,甚至足以... 详细信息

随着ChatGPT为代表的大语言模型在应用方面取得极大成功,语言官能是否为人类独有的问题引起热议,国际学界形成两个对立的阵营。一方认为,大语言模型语言理解和产出方面达到了媲美人类的水准,对乔姆斯基的语言学理论提出了挑战,甚至足以取代生成语法的语言学理论地位。另一方则认为,人类语言习得“刺激贫乏”但生成能力惊人,而大语言模型“学习”语言依靠输入海量数据,因此,它无法对人类语言的本质问题给出合理性解释,在语言的核心属性方面与人类语言官能存在本质区别。不少实证测试也对夸大大语言模型在语言学理论中的地位的观点进行了批判。本文认为,对这一问题的讨论,首先应思考如下问题:(1)区分科学理论建构与工程应用;(2)对“可能的语言”与“不可能的语言”的区分做出原则性的预测与解释;(3)探讨自然语言习得“刺激贫乏”与大语言模型依靠“豪华型”海量数据之对立背后的深层原因;(4)对句法在人类语言和大语言模型中的地位进行更多维度和更系统的对比评测。

关键词： ChatGPT 大语言模型刺激贫乏可能的语言不可能的语言

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The efficacy of full-thickness endoscopic resection of subepithelial tumors in the gastric cardia

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World Journal of Gastrointestinal Oncology 2023年第12期15卷 2111-2119页

作者： En-Pan Xu Zhi-Peng Qi Bing Li zhong Ren Ming-Yan Cai shi-Lun Cai Zhen-Tao lyv Zhang-Han Chen Jing-Yi Liu Qiang shi Yun-shi zhong Endoscopy Center Zhongshan Hospital Fudan UniversityShanghai 200032China

BACKGROUND Gastric subepithelial tumors(SETs)may harbor potential *** it is well recognized that large SETs should be resected,the precise treatment strategy remains *** to surgical resection,endoscopic resection(ER)has many advantages;however,ER of SETs in the cardia is *** To evaluate the safety and efficacy of endoscopic full-thickness resection(EFTR)for the treatment of gastric cardia *** We retrospectively reviewed data from all patients with SETs originating from the muscularis propria layer in the gastric cardia that were treated by EFTR or submucosal tunneling ER(STER)at zhongshan Hospital Fudan University between November 2014 and May *** characteristics and clinical outcomes,including procedure times and complications rates,were compared between groups of patients receiving EFTR and *** A total of 171 tumors were successfully removed[71(41.5%)tumors in the EFTR and 100(58.5%)tumors in the STER group].Gastrointestinal stromal tumors(GISTs)were the most common *** en bloc resection rate was 100%in the EFTR group vs 97.0%in STER group(P>0.05).Overall,the EFTR group had a higher complete resection rate than the STER group(98.6%vs 91.0%,P<0.05).The procedure time was also shorter in the EFTR group(44.63±28.66 min vs 53.36±27.34,P<0.05).The most common major complication in both groups was electrocoagulation *** was no significant difference in total complications between the two groups(21.1%vs 22.0%,P=0.89).CONCLUSION EFTR of gastric cardia SETs is a very promising method to facilitate complete resection with similar complications and reduced operative times compared to *** cases of suspected GISTs or an unclear diagnosis,EFTR should be recommended to ensure complete resection.

关键词： Endoscopic full-thickness resection Submucosal tunneling endoscopic resection Gastrointestinal stromal tumor Gastric cardia Gastric subepithelial tumors

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An Ensemble Tree Classifier for Highly Imbalanced Data Classification

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Journal of Systems Science & Complexity 2021年第6期34卷 2250-2266页

作者： shi Peibei WANG zhong School of Computer Science and Technology Hefei Normal UniversityHefei 230601China

The performance of traditional imbalanced classification algorithms is degraded when dealing with highly imbalanced *** to deal with highly imbalanced data is a difficult *** this paper,the authors propose an ensemble tree classifier for highly imbalanced data *** ensemble tree classifier is constructed with a complete binary tree structure.A mathematical model is established based on the features and classification performance of the classifier,and it is proven that the model parameters of the ensemble classifier can be solved by ***,the AdaBoost method is used as the benchmark classifier to construct the tree structure ***,the classification cost of the model is calculated,and the quantitative mathematical description between the cost and features of the ensemble tree classifier model is ***,the cost of the classification model is transformed into an optimization problem,and the parameters of the integrated tree classifier are given through theoretical *** approach is tested on several highly imbalanced datasets in different fields and takes the AUC(area under the curve)and F-measure as evaluation *** with the traditional imbalanced classification algorithm,the ensemble tree classifier has better classification performance.

关键词： Ensemble learning F-measure imbalanced classification mathematical model

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A weighted fuzzy C-means clustering method for hardness prediction

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Journal of Iron and Steel Research International 2023年第1期30卷 176-191页

作者： Yuan Liu shi-zhong Wei School of Materials Science and Engineering Henan University of Science and TechnologyLuoyang 471003HenanChina School of Aerospace Engineering Zhengzhou University of AeronauticsZhengzhou 450015HenanChina National Joint Engineering Research Center for Abrasion Control and Molding of Metal Materials Henan University of Science and TechnologyLuoyang 471003HenanChina

The hardness prediction model was established by support vector regression(SVR).In order to avoid exaggerating the contribution of very tiny alloying elements,a weighted fuzzy C-means(WFCM)algorithm was proposed for data clustering using improved Mahalanobis distance based on random forest importance values,which could play a full role of important features and avoid clustering center *** samples were divided into two *** top 10 features of each class were selected to form two feature subsets for better performance of the *** dimension and dispersion of features decreased in such feature *** four machine learning algorithms,SVR had the best performance and was chosen to *** hyper-parameters of the SVR model were optimized by particle swarm *** samples in validation set were classified according to minimum distance of sample to clustering centers,and then the SVR model trained by feature subset of corresponding class was used for *** with the feature subset of original data set,the predicted values of model trained by feature subsets of classified samples by WFCM had higher correlation coefficient and lower root mean square *** indicated that WFCM was an effective method to reduce the dispersion of features and improve the accuracy of model.

关键词： Hardness prediction Weighted fuzzy C-means algorithm Feature selection Particle swarm optimization Support vector regression Dispersion reduction

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HIGH-RESOLUTION SEMI-DISCRETE CENTRAL SCHEME FOR DAM-BREAK PROBLEMS

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Journal of Hydrodynamics 2005年第5期17卷 585-589页

作者： CHEN Jian-zhong shi zhong-ke College of Automation Northwestern Polytechnical University Xi＇an 710072 China

A numerical model for simulating the dambreak problems was presented. The model was based on a high-resolution semi-discrete central-upwind difference scheme. In order to reduce spurious oscillation, the uniformly non-oscillatory limiter was employed. A third-order total variation diminishing Runge-Kutta method is used for time integration. The main feature of the presented method is its simplicity. It requires no Riemann solvers, no flux splitting and no flux limiter. It is explicit and does not require dimensional splitting for two dimensions. The Simpson quadrature rule was employed to compute the source term. To verify the effectiveness and accuracy of the proposed method, the 1D dambreak, circular dam-break and partial dam-break problems were simulated. The results are shown to be in good agreement with analytical solution and numerical results obtained by other methods.

关键词： dam-break shallow water equations central-upwind difference scheme

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Weakly Compact Sets and Riesz Representation Theorem in Musielak Sequence Spaces

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Acta Mathematica Sinica,English Series 2024年第2期40卷 467-484页

作者： Wan zhong GONG Si Yu shi zhong Rui shi Department of Mathematics Anhui Normal UniversityWuhu 241000P.R.China Smeal College of Business Pennsylvania State UniversityUniversity ParkPennsylwania 16802USA Department of Mathematics Shanghai UniversityShanghai 200444P.R.China

In this work,we give some criteria of the weakly compact sets and a representation theorem of Riesz's type in Musielak sequence spaces using the ideas and techniques of sequence spaces and Musielak ***,as an immediate consequence of the criteria considered in this paper,the criteria of the weakly compact sets of Orlicz sequence spaces are deduced.

关键词： Compact set weak topology Banach space dual space Musielak sequence spaces

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