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New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： xiao-Peng Duan Bao-dong Qin xiao-dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang Department of Medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

Artemsieverolactones A—H,Eight Guaiane-Type Sesquiterpenoid Trimers from Artemisia sieversiana

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Chinese Journal of Chemistry 2024年第10期42卷 1084-1092页

作者： Wei dong xiao-Yan Huang Tian-Ze Li Yan-Mei Weng Chang-An Geng Ji-Jun chen State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunmingYunnan 650201China University of Chinese Academyof Sciences Beijing 100049China

Eight new guaiane-type sesquiterpenoid trimers,artemsieverolactones A—H,possessing unprecedented scaffolds via biocatalyzed[4+2]Diels−Alder cycloaddition reactions were identified from Artemisia *** structures were determined by comprehensive spectroscopic data,single-crystal X-ray diffraction analyses,and ECD *** terms of structure,artemsieverolactones A—H are first examples of sesquiterpenoid trimers from guaiane-type sesquiterpenoid through four different[4+2]Diels−Alder cycloaddition *** fibrosis assay suggested that five compounds exhibited activity against HSC-LX2 with IC_(50)values ranging from 37.8 to 117.1μmol/*** most active artemsieverolactone B(2)displayed significant inhibitory activity against HSC-LX2 with IC_(50)value of 37.8μmol/L,which was 3 times more active than the positive drug silybin(IC_(50),139.7μmol/L).Preliminary mechanism study revealed that artemsieverolactone B could inhibit the deposition of human collagen typeⅠ(ColⅠ),human hyaluronic acid(HA),and human laminin(HL)with IC_(50)values of 40.4μmol/L(Col I),55.1μmol/L(HL),47.3μmol/L(HA),which was 2 to 3-fold more potent than silybin.

关键词： Artemisia sieversiana Artemsieverolactones A-H Guaiane-type sesquiterpenoid trimers Antihepatic fibrosis Extracellular matrix Cancer NMR spectroscopy X-ray diffraction

Visible-light-activated aziridination reaction enables simultaneous resolving of C=C bond location and the sn-position isomers in lipids

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Chinese Chemical Letters 2024年第4期35卷 481-485页

作者： Qiongqiong Wan Yanan xiao Guifang Feng Xin dong Wenjing Nie Ming Gao Qingtao Meng Suming chen The Institute for Advanced Studies Renmin Hospital of Wuhan UniversityWuhan UniversityWuhan 430072China

There is a close relationship between the biological functions of lipids and their structures, and various isomers greatly increases the complexity of lipid structures. The C=C bond location and sn-position are two of the essential attributes that determine the structures of unsaturated lipids. However, simultaneous identification of both attributes remains challenging. Here, we develop a visible-light-activated aziridination reaction system, which enables the dual-resolving of the C=C bond location and sn-position isomerism of in lipids when combines with liquid chromatography-mass spectrometry(LC-MS). Based on the derivatization of C=C bonds with Ph I=NTs, their location in lipids could be easily identified by tandem MS. Especially, the sn-position isomers of unsaturated phosphatidylcholine(PC) can be separated and quantified by LC-MS after the derivatization. By using the proposed method, the significant changes of the sn-position isomers ratios of PC in mouse brain ischemia were revealed. This study offers a powerful tool for deep lipid structural biology.

关键词： Aziridination Lipid isomers C=C bond location sn-Position Mass spectrometry

Possible Mechanisms and Prospects of Stem Cell Therapy for Keloids

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International Journal of Dermatology and Venereology 2019年第3期2卷 160-164页

作者： Min-Min Zhang xiao-dong chen Medical School Nantong UniversityNantongJiangsu 226001China Department of Dermatology Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China

Introduction Keloids are a benign proliferative disease of the skin caused by abnormal healing of physiological *** are similar to hypertrophic ***,keloids extend beyond the margin of the original wound and do not spontaneously regress,while hypertrophic scars are confined to the original wound and generally maintain their shape.1 Keloids cause pain,pruritus,restricted joint activity and cosmetic problems,and negatively affect quality of *** bioactivity of keloids is regulated by various factors,such as transforming growth factor (TGF)-β,connective tissue growth factor (CTGF),and hypoxia inducible factor (HIF).2-4 These inflammatory factors are involved in keloid fibrosis,collagen production,and the deposition of extracellular ***,the pathogenesis of keloids remain unclarified,and it is still one of the most challenging diseases in clinical practice.

关键词： Possible Mechanisms Stem Cell Keloids

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Research progress in CALPHAD assisted metal additive manufacturing

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China Foundry 2024年第4期21卷 295-310页

作者： Ya-qing Hou xiao-qun Li Wei-dong Cai Qing chen Wei-ce Gao Du-peng He Xue-hui chen Hang Su China Iron&Steel Research Institute Group Beijing 100081China Thermo-Calc Software AB SolnaSE-169Sweden KTH Royal Institute of Technology StockholmSE-100Sweden Central Iron and Steel Research Institute Beijing 100081China

Metal additive manufacturing(MAM)technology has experienced rapid development in recent *** both equipment and materials progress towards increased maturity and commercialization,material metallurgy technology based on high energy sources has become a key factor influencing the future development of *** calculation of phase diagrams(CALPHAD)is an essential method and tool for constructing multi-component phase diagrams by employing experimental phase diagrams and Gibbs free energy models of simple *** combining with the element mobility data and non-equilibrium phase transition model,it has been widely used in the analysis of traditional metal *** development of CALPHAD application technology for MAM is focused on the compositional design of printable materials,the reduction of metallurgical imperfections,and the control of microstructural *** endeavor carries considerable theoretical and practical *** paper summarizes the important achievements of CALPHAD in additive manufacturing(AM)technology in recent years,including material design,process parameter optimization,microstructure evolution simulation,and properties ***,the limitations of applying CALPHAD technology to MAM technology are discussed,along with prospective research directions.

关键词： metal additive manufacturing CALPHAD integrated computational material engineering powder bed fusion material design microstructure simulation

Regulated reaction pathway of CO_(2)photoreduction into CH_(4)by metal atom pair sites

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Rare Metals 2024年第9期43卷 4620-4627页

作者： dong-Po He Guang-Bing Huang Jun Hu Yang Wu xiao-dong Li Qing-Xia chen Shan Zhu Wen-Sheng Yan Jun-Fa Zhu Yang Pan Xing-chen Jiao Key Laboratory of Synthetic and Biological Colloids Ministry of EducationSchool of Chemical and Material EngineeringJiangnan UniversityWuxi 214122China Hefei National Research Center for Physical Sciences at Microscale National Synchrotron Radiation LaboratoryUniversity of Science and Technology of ChinaHefei 230026China Max Planck Institute of Microstructure Physics Weinberg 206120 HalleGermany State Grid Anhui Electric Power Research Institute Hefei 230601China

The carbon dioxide(CO_(2))reduction process involves complex protonation,making the resulting product often *** achieve the desired product,it is crucial to manipulate the reaction ***,we build the metal atom pair sites for selective CO_(2)photoreduction into *** a prototype,Ni atom pair sites loaded on the Mo S_(2)nanosheets were synthesized and verified by highresolution transmission electron microscopy(HRTEM),X-ray photoelectron spectroscopy(XPS)and X-rayabsorption near edge structure spectra(XANES).In-situ Fourier transform infrared spectroscopy(FTIR)monitors the*CHO group,a crucial intermediate in CH_(4)production,during CO_(2)photoreduction on the Ni-Mo S_(2)nanosheets,whereas this monitoring is not observed for the Mo S_(2)***,theoretical calculations disclose that over the Ni-Mo S_(2)nanosheet slab,the formation energy of*CHO intermediates is determined to be lower(0.585 e V)than the desorption energy of*CO intermediates for CO production(0.64 e V),implying the higher selectivity of CH_(4)production.

关键词： steps dioxide desired

Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma

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World Journal of Clinical Cases 2024年第2期12卷 285-292页

作者： Sha-Sha Sun xiao-Di Guo Wen-dong Li Jing-Long chen Department of Oncology Capital Medical University Affiliated Beijing Ditan HospitalBeijing 100015China

BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is *** To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced *** HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were *** patients were treated with lenvatinib every day and sintilimab once every 3 ***,TACE was performed every 4-6 wk if *** primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse *** Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January *** a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,*** ORR and DCR were 45%and 90%,*** median progressive free survival and median OS were not *** complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.

关键词： Lenvatinib Sintilimab Advanced hepatocellular carcinoma Combination therapy Tumor response

Strong metal-support interactions between highly dispersed Cu^(+) species and ceria via mix-MOF pyrolysis toward promoted water-gas shift reaction

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Journal of Energy Chemistry 2024年第4期91卷 475-483页

作者： xiao-chen Sun Xing-Chi Li Ze-Wei Xie chen-Yue Yuan De-Jiu Wang Qian Zhang xiao-Yu Guo Hao dong Hai-Chao Liu Ya-Wen Zhang Beijing National Laboratory for Molecular Sciences(BNLMS) State Key Laboratory of Rare Earth Materials Chemistry and ApplicationsPKU-HKU Joint Laboratory in Rare Earth Materials and Bioinorganic ChemistryCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Beijing National Laboratory for Molecular Sciences(BNLMS) College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Beijing National Laboratory for Molecular Sciences(BNLMS) State Key Laboratory for Structural Chemistry of Stable and Unstable SpeciesCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

The modulation of metal-support interfacial interaction is significant but challenging in the design of high-efficiency and high-stability supported ***,we report a synthetic strategy to upgrade Cu-CeO_(2)interfacial interaction by the pyrolysis of mixed metal-organic framework(MOF)*** obtained highly dispersed Cu/CeO_(2)-MOF catalyst via this strategy was used to catalyze water-gas shift reaction(WGSR),which exhibited high activity of 40.5μmolCOgcat^(-1).s^(-1)at 300℃and high stability of about 120 *** on comprehensive studies of electronic structure,pyrolysis strategy has significant effect on enhancing metal-support interaction and then stabilizing interfacial Cu^(+)species under reaction *** Cu^(+)species and generated oxygen vacancies over Cu/CeO_(2)-MOF catalyst played a key role in CO molecule activation and H2O molecule dissociation,*** collaborated closely and then promoted WGSR catalytic performance in comparison with traditio nal supported *** study shall offer a robust approach to harvest highly dispersed catalysts with finely-tuned metal-support interactions for stabilizing the most interfacial active metal species in diverse heterogeneous catalytic reactions.

关键词： Cu-based catalyst MOF derivative Water-gas shift reaction Metal-support interaction

Covalency competition induced selective bond breakage and surface reconstruction in manganese cobaltite towards enhanced electrochemical charge storage

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Green Energy & Environment 2024年第5期9卷 909-918页

作者： Peng Gao Pei Tang Ying Mo Peitao xiao Wang Zhou Shi chen Hongliang dong Ziwei Li Chaohe Xu Jilei Liu College of Materials Science and Engineering Hunan Joint International Laboratory of Advanced Materials and Technology for Clean EnergyHunan Province Key Laboratory for Advanced Carbon Materials and Applied TechnologyHunan UniversityChangshaHunan410082China Department of Materials Science and Engineering National University of Defense TechnologyChangshaHunan410073China Joint Key Laboratory of the Ministry of Education Institute of Applied Physics and Materials EngineeringUniversity of MacaoAvenida da UniversidadeTaipaMacao999078China Center for High Pressure Science and Technology Advanced Research PudongShanghai201203China College of Aerospace Engineering Chongqing UniversityChongqing400044China

Manganese cobaltite(MnCo_(2)_(4))is a promising electrode material because of its attractive redox chemistry and excellent charge storage *** previous work demonstrated that the octahedrally-coordinated Mn are prone to react with the hydroxyl ions in alkaline electrolyte upon electrochemical cycling and separates on the surface of spinel to reconstruct into d-MnO_(2) nanosheets irreversibly,thus results in a change of the reaction mechanism with Kþion ***,the low capacity has greatly limited its practical ***,we found that the tetrahedrally-coordinated Co_(2) þions were leached when MnCo_(2)_(4) was equilibrated in 1 mol L^(-1) HCl solution,leading to the formation of layered CoOOH on MnCo_(2)_(4) surface which is originated from the covalency competition induced selective breakage of the CoT–O bond in CoT–O–CoO and subsequent rearrangement of free Co_(6) *** as-formed CoOOH is stable upon cycling in alkaline electrolyte,exhibits conversion reaction mechanism with facile proton diffusion and is free of massive structural evolution,thus enables utilization of the bulk electrode material and realizes enhanced speciﬁc capacity as well as facilitated charge transfer and ion *** general,our work not only offers a feasible approach to deliberate modiﬁcation of MnCo_(2)_(4)'s surface structure,but also provides an in-depth understanding of its charge storage mechanism,which enables rational design of the spinel oxides with promising charge storage properties.

关键词： Manganese cobaltite Tetrahedrally-coordinated Co^(2+)leaching Selective bond breakage Surface reconstruction Charge storage mechanisms