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Synthesis and potential osteogenic applications of Wnt3a-loaded ZIF-8 nanoparticles

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Chinese Chemical Letters 2024年第3期35卷 399-405页

作者： Hengfei Wang song Chen zihan He Junyu Chen Zhou Zhu Qianbing Wan Jian Wang Xibo Pei State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of ProsthodonticsWest China Hospital of StomatologySichuan UniversityChengdu 610041China Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationStomatological Hospital of Chongqing Medical UniversityChongqing 400016China

The Wnt signaling pathway plays a critical role in bone homeostasis,and the related protein therapy strategies have been reported to have great potential in osseointegration;however,they face formidable challenges such as complex external environments and unavoidable protein denaturation.In this work,we report a novel approach combining the synthesis of metal–organic frameworks(MOFs)and protein encapsulation in a one-pot process based on zeolitic imidazolate framework-8(ZIF-8)and Wnt3a protein,with improved biomechanical behavior and enhanced protein biological response.This combination was designed to enhance the Wnt3a protein function through the improved chemical stability provided by the ZIF-8 crystals.Additionally,the zinc ions contained in the ZIF-8 crystals induced bone homeostasis,further favoring the osteogenesis.The results showed that the Wnt3a protein-loaded ZIF-8 crystals served as efficient drug delivery vehicles to promote osteogenesis,preventing protein denaturation.In particular,Wnt3a-loaded ZIF-8 nanoparticles(Wnt3a@ZIF-8 NPs)had higher efficacy on bone marrow mesenchymal stem cells(BMSCs)than ZIF-8 NPs or Wnt3a proteins,contributing to the osteogenesis through ZIF-8 crystals and intracellular Wnt3a proteins released from Wnt3a@ZIF-8 NPs.Furthermore,polymerase chain reaction(PCR)analysis showed that the osteogenic pathways were upregulated.Overall,the present one-pot process can open up new avenues to develop signaling protein-delivery systems for applications in protein therapy strategies.

关键词： Metal–organic frameworks Nanoparticle Drug release Osteogenesis Bone defects

Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer

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National Science Review 2024年第1期11卷 107-119页

作者： Shuren Zhang Dongfan song Wenhao Yu Ji Li Xiaoyu Wang Yachao Li zihan Zhao Qi Xue Jing Zhao Jie P.Li Zijian Guo State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center (ChemBIC) Nanjing University Department of Urology Afflliated Drum Tower HospitalMedical SchoolNanjing University Nanchuang (Jiangsu)Institute of Chemistry and Health

Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes(STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two PtIV-MSA-2 conjugates(Ⅰand Ⅱ) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immuneactivating STING agonist MSA-2; these conjugates showed great potential as multispecific small-molecule drugs against pancreatic cancer. Mechanistic studies revealed that conjugate Ⅰ upregulated the expression of transcripts associated with innate immunity and metabolism in cancer cells, significantly differing from cisplatin and MSA-2. An analysis of the tumor microenvironment demonstrated that conjugate I could enhance the infiltration of natural killer(NK) cells into tumors and promote the activation of T cells, NK cells and dendritic cells in tumor tissues. These findings indicated that conjugate I, which was created by incorporating a Pt chemotherapeutic drug and STING agonist into one molecule, is a promising and potent anticancer drug candidate, opening new avenues for small-molecule-based cancer metalloimmunotherapy.

关键词： platinum drug STING agonist single-molecule multitarget metalloimmunology

No tillage increases soil microarthropod(Acari and Collembola)abundance at the global scale

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Soil Ecology Letters 2024年第2期6卷 5-19页

作者： Yulin Liu Lihong song Donghui Wu zihan Ai Qian Xu Xin Sun Liang Chang State Key Laboratory of Black Soil Conservation and Utilization Northeast Institute of Geography and AgroecologyChinese Academy of SciencesChangchun130102China University of Chinese Academy of Sciences Beijing100049China College of Agriculture Guizhou UniversityGuiyang550025China Key Laboratory of Urban Environment and Health Ningbo Observation and Research StationFujian Key Laboratory of Watershed EcologyInstitute of Urban EnvironmentChinese Academy of SciencesXiamen361021China Zhejiang Key Laboratory of Urban Environmental Processes and Pollution Control CAS Haixi Industrial Technology Innovation Center in BeilunNingbo315830China

Conservation tillage increases soil microarthropod abundance at the global scale.The effect of conservative tillage on microarthropods is soil texture-dependent.This positive effect of conservation tillage is particularly evident in nutrient-poor soil areas.In temperate humid regions,however,this positive effect of conservation tillage is limited.The effect of conservative tillage on microarthropods varies with fauna group and climate regions.

关键词： no tillage soil microarthropod Acari Collembola meta-analysis

Spatial continuous modeling of early Cenozoic carbon cycle and climate

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National Science Review 2024年第4期11卷 30-32页

作者： Yonggang Liu Jian Zhang Haoyue Zuo Zhilin He Jiaqi Guo Qifan Lin Haonan Yu Jiawenjing Lan Jing Han Zhihong song zihan Yin Liang Zhao Yongyun Hu Zhengtang Guo Laboratory for Climate and Ocean-Atmosphere Studies Department of Atmospheric and Oceanic Sciences School of Physics Peking University Key Laboratory of Cenozoic Geology and Environment Institute of Geology and GeophysicsChinese Academy of Sciences State Key Laboratory of Lithospheric Evolution Institute of Geology and Geophysics Chinese Academy of Sciences

The partial pressure of atmospheric CO2（pCO2） is determined by the carbon cycle that involves climate, biogeochemistry, and plate tectonics. In this cycle,atmospheric CO2is converted into organic carbon and carbonates by biological activities and silicate weathering, and buried as sediments. The sediments on the ocean floor are subducted into the Earth’s interior, and subsequently converted back into CO2and outgassed into the atmosphere.

关键词： ATMOSPHERIC CO2

Simple and versatile in situ thermo-sensitive hydrogel for rectal administration of SZ-A to alleviate inflammation and repair mucosal barrier in ulcerative colitis

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Chinese Chemical Letters 2024年第6期35卷 462-468页

作者： Yu Yan Jiawei song Dongdong Liu zihan Liu Jialing Cheng Zhiyang Chen Yanfang Yang Weizhe Jiang Hongliang Wang Jun Ye Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China College of Pharmacy Guangxi Medical UniversityNanning 530021China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.

关键词： Ulcerative colitis SZ-A Thermo-sensitive hydrogel Rectal administration Alleviation of inflammation Mucosal barrier repair

Synchrotron Characterisation of Ultra-Fine Grain TiB_(2)/Al-Cu Composite Fabricated by Laser Powder Bed Fusion

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Acta Metallurgica Sinica(English Letters) 2022年第1期35卷 78-92页

作者： Sheng Li Biao Cai Ranxi Duan Lei Tang zihan song Dominic White Oxana V.Magdysyuk Moataz M.Attallah School of Metallurgy and Materials University of BirminghamEdgbastonBirminghamB152TTUK Department of Materials Science and Engineering Southern University of Science and TechnologyShenzhen518055China ZEISS House Building 1030Cambourne Business ParkCambourneCambridgeCB236DWUK Diamond Light Source Ltd Harwell Science and Innovation CampusDidcotOX110DEOxfordshireUK

Isotropy in microstructure and mechanical properties remains a challenge for laser powder bed fusion(LPBF)processed materials due to the epitaxial growth and rapid cooling in LPBF.In this study,a high-strength TiB_(2)/Al-Cu composite with random texture was successfully fabricated by laser powder bed fusion(LPBF)using pre-doped TiB_(2)/Al-Cu composite powder.A series of advanced characterisation techniques,including synchrotron X-ray tomography,correlative focussed ion beam-scanning electron microscopy(FIB-SEM),scanning transmission electron microscopy(STEM),and synchrotron in situ X-ray diffraction,were applied to investigate the defects and microstructure of the as-fabricated TiB_(2)/Al-Cu composite across multiple length scales.The study showed ultra-fine grains with an average grain size of about 0.86μm,and a random texture was formed in the as-fabricated condition due to rapid solidification and the TiB_(2)particles promoting heterogeneous nucleation.The yield strength and total elongation of the as-fabricated composite were 317 MPa and 10%,respectively.The contributions of fine grains,solid solutions,dislocations,particles,and Guinier-Preston(GP)zones were calculated.Failure was found to be initiated from the largest lack-of-fusion pore,as revealed by in situ synchrotron tomography during tensile loading.In situ synchrotron diffraction was used to characterise the lattice strain evolution during tensile loading,providing important data for the development of crystal-plasticity models.

关键词： Aluminium metal matrix composite Laser powder bed fusion Heterogeneous nucleation Synchrotron characterisation

Lack of ethylene does not affect reproductive success and synergid cell death in Arabidopsis

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Molecular Plant 2022年第2期15卷 354-362页

作者： Wenhao Li Qiyun Li Mohan Lyu Zhijuan Wang zihan song Shangwei Zhong Hongya Gu Juan Dong Thomas Dresselhaus Sheng Zhong Li-Jia Qu State Key Laboratory for Protein and Plant Gene Research Peking-Tsinghua Center for Life Sciences at College of Life SciencesPeking UniversityBeijing 100871People's Republic of China The National Plant Gene Research Center(Beijing) Beijing 100101People's Republic of China The Waksman Institute of Microbiology Rutgers the State University of New JerseyPiscatawayNJ 08854USA Cell Biology and Plant Biochemistry University of Regensburg93053 RegensburgGermany

The signaling pathway of the gaseous hormone ethylene is involved in plant reproduction,growth,devel-opment,and stress responses.During reproduction,the two synergid cells of the angiosperm female gametophyte both undergo programmed cell death(PCD)/degeneration but in a different manner:PCD/degeneration of one synergid facilitates pollen tube rupture and thereby the release of sperm cells,while PCD/degeneration of the other synergid blocks supernumerary pollen tubes.Ethylene signaling was postu-lated to participate in some of the synergid cell functions,such as pollen tube attraction and the induction of PCD/degeneration.However,ethylene-mediated induction of synergid PCD/degeneration and the role of ethylene itself have not been firmly established.Here,we employed the CRISPR/Cas9 technology to knock out the five ethylene-biosynthesis 1-aminocyclopropane-1-carboxylic acid oxidase(ACO)genes and created Arabidopsis mutants free of ethylene production.The ethylene-free mutant plants showed normal triple responses when treated with ethylene rather than 1-aminocyclopropane-1-carboxylic acid,but had increased lateral root density and enlarged petal sizes,which are typical phenotypes of mutants defective in ethylene signaling.Using these ethylene-free plants,we further demonstrated that production of ethylene is not necessarily required to trigger PCD/degeneration of the two synergid cells,but certain com-ponents of ethylene signaling including transcription factors ETHYLENE-INSENSITIVE 3(EIN3)and EIN3-LIKE 1(EIL1)are necessary for the death of the persistent synergid cell.

关键词： ethylene ACC PCD synergid cells triple response Arabidopsis

The egg cell is preferentially fertilized in Arabidopsis double fertilization

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Journal of Integrative Plant Biology 2022年第11期64卷 2039-2046页

作者： Ling Li Saiying Hou Wei Xiang zihan song Yuan Wang Li Zhang Jing Li Hongya Gu Juan Dong Thomas Dresselhaus Sheng Zhong Li-Jia Qu State Key Laboratory for Protein and Plant Gene Research Peking‐Tsinghua Center for Life Sciences at College of Life SciencesPeking UniversityBeijing 100871China Beijing Advanced Innovation Center for Tree Breeding by Molecular Design College of Bioscience and Resources EnvironmentBeijing University of AgricultureBeijing 102206China The National Plant Gene Research Center Beijing 100101China The Waksman Institute of Microbiology Rutgers the State University of New JerseyPiscatawayNJ"2"08854USA Cell Biology and Plant Biochemistry University of RegensburgRegensburg 93053Germany

In flowering plants(angiosperms),fertilization of the egg cell by one sperm cell produces an embryo,whereas fusion of a second sperm cell with the central cell generates the endosperm.In most angiosperms like Arabidopsis,a pollen grain contains two isomorphic sperm cells required for this double fertilization process.A long-standing unsolved question is whether the two fertilization events have any preference.A tool to address this question is the usage of the cyclin-dependent kinase a1(cdka;1)mutant pollen,which produces a single sperm-like cell(SLC).Here,we first adopt a complementation-based fluorescence-labeling method to successfully separate and collect cdka;1 mutant pollen containing a single SLC.Single-cell RNA-sequencing analysis revealed that cdka;1 SLCs show a gene expression profile highly similar to that of sperm cells and not to the generative cell,precursor of the two sperm cells.Pollination assays using a limited number of cdka;1 mutant pollen revealed that in 98.2%of the ovules,single fertilization of the egg cell occurred.Pollination of pistils with excessive cdka;1 mutant pollen allowed the delivery of a second SLC via fertilization recovery,which fertilized the central cell,resulting in 20.7%double-fertilized ovules.This indicates that cdka;1 SLCs are able to fertilize both the egg and the central cell.Taken together,our findings have answered a long-standing question and support that preferential fertilization of the egg cell is evident in Arabidopsis.

关键词： Arabidopsis double fertilization egg cell preferential fertilization

Gas-phase synthesis of Ti_(2)CCl_(2) enables an efficient catalyst for lithiumsulfur batteries

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The Innovation 2024年第1期5卷 33-40页

作者： Maoqiao Xiang zihan Shen Jie Zheng Miao song Qiya He Yafeng Yang Jiuyi Zhu Yuqi Geng Fen Yue Qinghua Dong Yu Ge Rui Wang Jiake Wei Weiliang Wang Haiming Huang Huigang Zhang Qingshan Zhu Chuanfang John Zhang State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of the Chinese Academy of SciencesBeijing 100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China China Nuclear Power Engineering Co. Ltd.117 West Third Ring RoadNorth SectionBeijing 100840China College of Materials Science&Engineering Sichuan UniversityChengdu 610065China State Key Laboratory of Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China School of Physics Guangdong Province Key Laboratory of Display Material and TechnologyCenter for Neutron Science and TechnologySun Yat-sen UniversityGuangzhou 510275China Solid State Physics&Material Research Laboratory School of Physics and Materials ScienceGuangzhou UniversityGuangzhou 510006China

MXenes have aroused intensive enthusiasm because of their exotic properties and promising applications.However,to date,they are usually synthesized by etching technologies.Developing synthetic technologies provides more opportunities for innovation and may extend unexplored applications.Here,we report a bottom-up gas-phase synthesis of Cl-terminated MXene(Ti_(2)CCl_(2)).The gas-phase synthesis endows Ti_(2)CCl_(2) with unique surface chemistry,high phase purity,and excellent metallic conductivity,which can be used to accelerate polysulfide conversion kinetics and dramatically prolong the cyclability of Li-S batteries.In-depth mechanistic analysis deciphers the origin of the formation of Ti_(2)CCl_(2) and offers a paradigm for tuning MXene chemical vapor deposition.In brief,the gas-phase synthesis transforms the synthesis of MXenes and unlocks the hardly achieved potentials of MXenes.

关键词： synthesis phase lithium