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A mutation in TBXT causes congenital vertebral malformations in humans and mice

journal of genetics and genomics 2024年第4期51卷 433-442页

作者： shuxia chen Yunping Lei Yajun Yang chennan liu Lele Kuang Li jin Richard hFinnell Xueyan Yang hongyan Wang Obstetrics and gynecology hospital State Key Laboratory of Genetic Engineering at School of Life SciencesKey Laboratory of Reproduction Regulation of NPFPCInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200438China shanghai Key Laboratory of Metabolic Remodeling and health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Center for Precision Environmental health Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonTX 77030USA MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200438China Department of Assisted Reproduction Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Children’s hospital Fudan University399 Wanyuan RoadShanghai 201102China

T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal *** it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well ***,we report a family with 15 CVM patients distributed across 4 *** affected individuals carry a heterozygous mutation,T c.596A>g(p.q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and *** vitro assays show that T p.q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the *** determine the pathogenicity of this mutation in vivo,we generated a q199R knock-in mouse model that recapitulates the human CVM *** heterozygous q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral ***,we show that the q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.

关键词： Congenital vertebral malformation TBXT T gene Loss-of-function mutation

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A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

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Acta Pharmaceutica sinica B 2024年第1期14卷 223-240页

作者： Lei sun Arabella h.Wan shijia Yan Ruonian liu jiarui Li Zhuolong Zhou Ruirui Wu Dongshi chen Xianzhang Bu jingxing Ou Kai Li Xiongbin Lu guohui Wan Zunfu Ke Department of Pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Local joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(Cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Department of Medical and Molecular genetics Indiana University School of MedicineIndianapolisIN 46202USA Department of Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Department of hepatic surgery and Liver Transplantation Center Third Affiliated HospitalOrgan Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong ProvinceGuangdong Province Engineering Laboratory for Transplantation MedicineGuangzhou 510630China guangdong Provincial Key Laboratory of Liver Disease Research Guangzhou 510630China Department of Ultrasound Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Melvin and Bren simon Comprehensive Cancer Center Indiana UniversityIndianapolisIN 46202USA

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug ***,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant *** and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing *** screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO ***,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EgFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX ***,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

关键词： Lenvatinib Drug resistance high-throughput screening Drug discovery Patient-derived model Romidepsin EgFR Liver cancer

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supported Atomically Dispersed Pd Catalyzed Direct Alkoxylation and Allylic Alkylation

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Chinese journal of Chemistry 2024年第7期42卷 719-724页

作者： Ruixuan qin Ziwen chen qingyuan Wu Nanfeng Zheng Pengxin liu New Cornerstone science Laboratory State Key Laboratory for Physical Chemistry of Solid SurfacesCollaborative Innovation Center of Chemistry for Energy Materialsand National&Local Joint Engineering Research Center of Preparation Technology of NanomaterialsCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamenFujian 361005China Innovation Laboratry for scences and Technoogies of Energy Materials of Fujan Province(IKKM) Xiamen Fujian 361102China school of Physical science and Technology Shanghai Tech UniversityShanghai 201210China Fujian Key Laboratory of Rare-earth Functional Materials Fujian Shanhai Collaborative Innovation Center of Rare-earth Functional MaterialsLongyanFujian 366300China

A new approach to allylic alkylation is realized using an atomically dispersed palladium catalyst(Pd1/TiO2-Eg).Unlike conventional methods that require derivation of substrates and utilization of additives,this method allows for direct allylic alkylation from allylic alcohols,producing h2O as the sole *** catalyst's high efficiency is attributed to the local hydrogen bonding at the or-ganic-inorganic interface(Pd-Eg interface),facilitating hydroxyl group activation forη3π-allyl complex *** system demonstrates successful direct C—O and C—C coupling reactions with high selectivity,requiring no *** study highlights the potential of supported atomically dispersed catalysts for greener and more efficient catalysis,meanwhile,offers unique insights into the distinct behavior of atomically dispersed catalysts in comparison to homogeneous or nanoparticle-based catalysts.

关键词： Atomically dispersed catalyst Alkylation C—C coupling Organic-inorganic Interface hydrogen bond Tsuji-Trost reaction green catalysis

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Abalone shell-derived Mg-doped mesoporous hydroxyapatite microsphere drug delivery system loaded with icariin for inducing apoptosis of osteosarcoma cells

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Biomaterials Translational 2024年第2期5卷 185-196页

作者： liu K. cheng M. huang h. Yu h. Zhao s. Zhou j. Tie D. Wang j. Pan P. chen j. Marine College Shandong University Shandong Province Weihai China state Key Laboratory of Mineral Processing Beijing China College of Biological science and Technology Fuzhou University Fujian Province Fuzhou China

hydroxyapatite (hAP) porous microspheres with very high specific surface area and drug loading capacity, as well as excellent biocompatibility, have been widely used in tumour therapy. Mg2+ is considered to be a key factor in bone regeneration, acting as an active agent to stimulate bone and cartilage formation, and is effective in accelerating cell migration and promoting angiogenesis, which is essential for bone tissue repair, anti-cancer, and anti-infection. In this study, abalone shells from a variety of sources were used as raw materials, and Mg2+-doped abalone shell-derived mesoporous hAP microspheres (Mg-hAP) were prepared by hydrothermal synthesis as Mg2+/icariin smart dual delivery system (ICA-Mg-hAP, IMhA). With increasing of Mg2+ doping, the surface morphology of hAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous, which may be due to Mg2+ substitution or coordination in the hAP lattice. At 30% Mg2+ doping, the Mg-hAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area (186.06 m2/g). The IMhA microspheres showed high drug loading (7.69%) and encapsulation rate (83.29%), sustained Mg2+ release for more than 27 days, sustained and stable release of icariin for 60 hours, and good responsiveness to ph (ph 6.4 > ph 5.6). In addition, the IMhA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in Mg63 cells by blocking the g2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes (Bcl-2, caspase-3,-8,-9). This suggests that the abalone shell-based IMhA may have potential applications in drug delivery and tumour therapy. © 2024, Chinese Medical Multimedia Press Co Ltd. All rights reserved.

关键词： abalone shell drug delivery hydroxyapatite microspheres magnesium doping osteosarcoma

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Fe-N-C core-shell catalysts with single low-spin Fe(Ⅱ)-N_(4)species for oxygen reduction reaction and high-performance proton exchange membrane fuel cells

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journal of Energy Chemistry 2024年第6期93卷 538-546,I0013页

作者： Yan Wan Linhui Yu Bingxin Yang Caihong Li chen Fang Wei guo Fang-Xing Xiao Yangming Lin Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstituteChinese Academy of SciencesXiamen 361021FujianChina CAs Key Laboratory of Urban Pollutant Conversion Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021FujianChina Fujian Institute of Research on the structure of Matter Chinese Academy of SciencesFuzhou 350002FujianChina College of Materials science and Engineering Fuzhou UniversityNew CampusMinhou 350108FujianChina College of Chemistry and Materials science Fujian Normal UniversityFuzhou 350117FujianChina

Fe-N-doped carbon materials(Fe-N-C)are promising candidates for oxygen reduction reaction(ORR)relative to Pt-based catalysts in proton exchange membrane fuel cells(PEMFCs).however,the intrinsic contributions of Fe-N_(4)moiety with different chemical/spin states(e.g.D1,D2,D3)to ORR are unclear since various states coexist *** the present work,Fe-N-C core-shell nanocatalyst with single lowspin Fe(Ⅱ)-N_(4)species(D1)is synthesized and identified with ex-situ ultralow temperature Mossbauer spectroscopy(T=1.6 K)that could essentially differentiate various Fe-N_(4)states and invisible Fe-O *** quantifying with CO-pulse chemisorption,site density and turnover frequency of Fe-N-C catalysts reach 2.4×10^(-9)site g^(-1)and 23 e site~(-1)s^(-1)during the ORR,***-wave potential(0.915V_(RhE))of the Fe-N-C catalyst is more positive(approximately 54 mV)than that of Pt/***,we observe that the performance of PEMFCs on Fe-N-C almost achieves the 2025 target of the Us Department of Energy by demonstrating a current density of 1.037 A cm^(-2)combined with the peak power density of 0,685 W cm^(-2),suggesting the critical role of Fe(Ⅱ)-N_(4)site(D1).After 500 h of running,PEMFCs still deliver a power density of 1.26 W cm^(-2)at 1.0 bar h_(2)-O_(2),An unexpected rate-determining step is figured out by isotopic labelling experiment and theoretical *** work not only offers valuable insights regarding the intrinsic contribution of Fe-N_(4)with a single spin state to alkaline/acidic ORR,but also provides great opportunities for developing high-performance stable PEMFCs.

关键词： Fuel cells Oxygen reduction reaction Non-platinum group metals(PgMs) Isotopic labelling Active site TOF

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stabilizing semi-transparent perovskite solar cells with a polymer composite hole transport layer

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Nano Research 2024年第3期17卷 1500-1507页

作者： Yongbin jin huiping Feng Zheng Fang liu Yang Kaikai liu Bingru Deng jingfu chen Xueling chen Yawen Zhong jinxin Yang chengbo Tian Liqiang Xie Zhanhua Wei Xiamen Key Laboratory of Optoelectronic Materials and Advanced Manufacturing Institute of Luminescent Materials and Information DisplaysCollege of Materials Science and EngineeringHuaqiao UniversityXiamen 361021China

semi-transparent perovskite solar cells(sT-PsCs)have broad applications in building integrated ***,the stability of sT-PsCs needs to be improved,especially in n-i-p sT-PsCs since the doped 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenyl-amine)-9,9'-spirobifluorene(spiro-OMeTAD)is unstable at elevated temperatures and high *** this work,aπ-conjugated polymer poly[(2,6-(4,8-bis(5-(2-ethylhexyl)thiophene-2-yl)-benzo[1,2-b:4,5-b']dithiophene))-alt-(5,5-(1',3'-di-2-thienyl-5',7'-bis(2-ethylhexyl)benzo[1',2'-c:4',5'-c']dithiophene-4,8-dione)](PBDB-T)is selected to form a polymer composite hole transport layer(hTL)with *** sulfur atom of the thiophene unit and the carbonyl group of the polymer interact with the undercoordinated Pb2+at the perovskite surface,which stabilizes the perovskite/hTL interface and passivates the interfacial *** incorporation of the polymer also increases the glass transition temperature and the moisture resistance of *** a result,we obtain sT-PsCs with a champion efficiency of 13.71%and an average visible light transmittance of 36.04%.Therefore,a high light utilization efficiency of 4.94%can be ***,the encapsulated device can maintain 84%of the initial efficiency after 751 h under continuous one-sun illumination(at 30%relative humidity)at the open circuit and the unencapsulated device can maintain 80%of the initial efficiency after maximum power tracking for more than 1250 h under continuous one-sun illumination.

关键词： semi-transparent solar cells π-conjugated polymer composite hole transport layer building integrated photovoltaics

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Breaking the Fe_(3)O_(4)-wrapped copper microstructure to enhance copper-slag separation

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International journal of Minerals,Metallurgy and Materials 2024年第10期31卷 2312-2325页

作者： Xiaopeng Chi haoyu liu jun Xia hang chen Xiangtao Yu Wei Weng shuiping Zhong Zijin school of geology and Mining Fuzhou UniversityFuzhou 350108China Fujian Key Laboratory of green Extraction and high-Value Utilization of New Energy Metals Fuzhou UniversityFuzhou 350108China Zijin Mining group Co. Ltd.Longyan 364200China Collaborative Innovation Center of steel Technology University of Science and Technology BeijingBeijing 100083China

The precipitation of Fe_(3)O_(4)particles and the accompanied formation of Fe_(3)O_(4)-wrapped copper structure are the main obstacles to copper recovery from the molten slag during the pyrometallurgical smelting of copper ***,the commercial powdery pyrite or anthracite is replaced with pyrite-anthracite pellets as the reductants to remove a large amount of Fe_(3)O_(4)particles in the molten slag,resulting in a deep fracture in the Fe_(3)O_(4)-wrapped copper microstructure and the full exposure of the copper matte *** 1wt%composite pellet is used as the reductant,the copper matte droplets are enlarged greatly from 25μm to a size observable by the naked eye,with the copper content being enriched remarkably from 1.2wt%to 4.5wt%.Density functional theory calculation results imply that the formation of the Fe_(3)O_(4)-wrapped copper structure is due to the preferential adhesion of Cu_(2)s on the Fe_(3)O_(4)particles.X-ray photoelectron spectroscopy,Fourier transform infrared spectrometer(FTIR),and Raman spectroscopy results all reveal that the high-efficiency conver-sion of Fe_(3)O_(4)to FeO can decrease the volume fraction of the solid phase and promote the depolymerization of silicate network *** a consequence,the settling of copper matte droplets is enhanced due to the lowered slag viscosity,contributing to the high efficiency of copper-slag separation for copper *** results provide new insights into the enhanced in-situ enrichment of copper from mol-ten slag.

关键词： pyrometallurgical smelting process slag cleaning reductants copper matte

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A stable Copper-based Metal-Azolate Framework for Efficient Electroreduction of CO_(2)to C_(2+)Products

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Chemical Research in Chinese Universities 2024年第4期40卷 664-669页

作者： liu Yuan-Yuan ZhU hao-Lin LIAO Pei-qin chen Xiao-Ming Key Laboratory of Bioinorganic and synthetic Chemistry Ministry of EducationGBRCE for Functional Molecular EngineeringSchool of ChemistryIGCMESun Yat-sen UniversityGuangzhou510275P.R.China Chemistry and Chemical Engineering guangdong Laboratory Shantou515031P.R.China

Driven by renewable or excess electrical energy,electrochemical CO_(2)reduction reaction(eCO_(2)RR)represents a promising carbon-neutral approach to generating valuable low-carbon fuels by consuming CO_(2)and h_(2)O.C_(2+)products are one of the most economically valuable products among the reduction species of eCO_(2)RR,but there are still some challenges,such as low selectivity or low current *** this work,we showed that a copper-based metal-azolate framework(MAF),denoted as MAF-203,exhibits the high performance of eCO_(2)RR to yield C_(2+)products with the Faradaic efficiency(C_(2+))of 52.5%and a current density of 660 mA/cm^(2)at-1.2 V *** in a flow cell device under alkaline *** experiment,in situ infrared spectroscopy and the density functional theory(DFT)calculations showed that the electron donating effect of methyl substituents on organic ligands of the copper-based MAF could enhance the ligand field and activation of key intermediates(*CO and*ChO species),thus promoting the coupling of*CO and*ChO for yielding C_(2+)products.

关键词： Metal-organic framework Carbon dioxide Electroreduction C_(2+)product Metal-azolate framework

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Anti-abrasion collagen fiber-based membrane functionalized by UiO-66-Nh_(2)with ultra-high efficiency and stability for oil-in-water emulsions separation

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Chinese journal of Chemical Engineering 2024年第2期66卷 285-297页

作者： Xiaoxia Ye Rixin huang Zhihong Zheng juan liu jie chen Yuancai Lv College of Environmental and safety Engineering Fuzhou UniversityFuzhou 350108China College of Chemical Engineering Fuzhou UniversityFuzhou 350108China

Membrane separation strategies offer promising platform for the emulsion ***,the low mechanical strength of membrane separation layers and the trade-off between separation flux and efficiency present significant *** this study,we report a CFM@UiO-66-Nh_(2)membrane with high separation flux,efficiency and stability,through utilizing a robust anti-abrasion collagen fiber membrane(CFM)as the multifunctional support and UiO-66-Nh_(2)by an in-situ growth as the separation *** high mechanical strength of the CFM compensated for the weakness of the separation layer,while the charge-breaking effect of UiO-66-Nh_(2),along with the size sieving of its constituent separating layers and the capillary effect of the collagen fibers,contributed to the potential for efficient ***,the CFM@UiO-66-Nh_(2)membrane exhibited superhydrophilic properties,making it suitable for separating oil-in-water microemulsions and nanoemulsions stabilized by anionic *** membrane demonstrated remarkable separation efficiencies of up to 99.960%and a separation flux of370.05 L·m^(-2)·h^(-1).Moreover,it exhibits stability,durability,and abrasion resistance,maintaining excellent separation performance even when exposed to strong acids and alkalis without any damage to its structure and *** six cycles of reuse,it achieved a separation flux of 417.97 L·m^(-2)·h^(-1)and a separation efficiency of 99.747%.Furthermore,after undergoing 500 cycles of strong abrasion,the separation flux remained at 124.39 L·m^(-2)·h^(-1),with a separation efficiency of 99.992%.These properties make it suitable for the long-term use in harsh operating *** attribute these properties to the electrostatic effect resulting from the amino group on UiO-66-Nh_(2)and its in-situ growth on the CFM,which forms a size-screening separation *** work highlights the potential of the CFM@UiO-66-Nh_(2)membrane as an environmentally friendly size-screening

关键词： Collagen fibers Metal-organic frameworks Oil-in-water emulsion separation size sieving

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Optical two-dimensional coherent spectroscopy of excitons in transition-metal dichalcogenides

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Frontiers of physics 2024年第2期19卷 141-148页

作者： YanZuo chen shaogang Yu Tao jiang Xiaojun liu XinBin cheng Di huang state Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Wuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhan 430071China MOE Key Laboratory of Advanced Micro-structured Materials Shanghai Frontiers Science Center of Digital OpticsInstitute of Precision Optical Engineeringand School of Physics Science and EngineeringTongji UniversityShanghai 200092China shanghai Institute of Intelligent science and Technology Tongji UniversityShanghai 200092China

Exciton physics in atomically thin transition-metal dichalcogenides(TMDCs)holds paramount importance for fundamental physics research and prospective ***,the experimental exploration of exciton physics,including excitonic coherence dynamics,exciton many-body interactions,and their optical properties,faces challenges stemming from factors such as spatial heterogeneity and intricate many-body *** this perspective,we elaborate upon how optical two-dimensional coherent spectroscopy(2DCs)emerges as an effective tool to tackle the challenges,and outline potential directions for gaining deeper insights into exciton physics in forthcoming experiments with the advancements in 2DCs techniques and new materials.

关键词： monolayer transition-metal dichalcogenides two-dimensional coherent spectroscopy

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