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Biochar alleviates apple replant disease by reducing the growth of Fusarium oxysporum and regulating microbial communities

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Horticultural Plant Journal 2024年第3期10卷 657-671页

作者： Yinghao Liu Can wang Ran Chen Weitao Jiang Yun Li Chengmiao Yin yanfang wang Zhiquan Mao College of Chemistry and Material Science Shandong Agricultural UniversityTaianShandong 271018China State Key Laboratory of Crop Biology/College of Horticultural Science and Engineering Shandong Agricultural UniversityTaianShandong 271018China

Apple replant disease(ARD)negatively affects plant growth and reduces yields in replanted orchards.In this study,biochar was applied to apple replant soil with Fusarium oxysporum.Our aim was to investigate whether biochar could promote plant growth and alleviate apple replant disease by reducing the growth of harmful soil microorganisms,changing soil microbial community structure and improving the soil environment.This experiment included five treatments:apple replant soil(CK),methyl bromide fumigation apple replant soil(FM),replant soil with biochar addition(2%),replant soil with F.oxysporum spore solution(8×10^(7)spores·mL^(-1)),and replant soil with biochar and F.oxysporum spore solution addition.Seedling biomass,the activity of antioxidant enzymes in the leaves and roots,and soil environmental variables were measured.Microbial community composition and community structure were analyzed using 16SrDNA and ITS2 gene sequencing.Biochar significantly reduced the abundance of F.oxysporum and increased soil microbial diversity and richness.Biochar also increased the soil enzyme activities(urease,invertase,neutral phosphatase,and catalase),the biomass(plant height,fresh weight,dry weight)and the activity of antioxidant enzymes(superoxide dismutase,peroxidase,and catalase).The root indexes of apple seedlings was also increased in replant soil by biochar.In sum,biochar promoted the growth of plants,improved the replant soil environment,and alleviated apple replant disease.

关键词： Biochar Fusarium oxysporum Apple replant disease Soil environment

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Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1542-1559页

作者： Xiaolan Xu Jiaming Zhang Tao wang Jing Li Yukang Rong yanfang wang Chenxia Bai Qing Yan Xiaohua Ran Yingli wang Tianhong Zhang Jin Sun Qikun Jiang Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of Education University of NottinghamNottingham NG72RDUK Department of Pharmacy Linyi People's HospitalShandong UniversityLinyi 276000China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100871China

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity against various cancer cells.Although ADCs confer certain targeting properties to the toxins,low drug loading capacity,possible immunogenicity,and other drawbacks also limit the po-tential application of ADCs.Recently,non-ADC delivery strategies for toxins have been extensively investigated.To further understand the application of toxins in anti-tumor,this paper provided an over-view of prodrugs,nanodrug delivery systems,and biomimetic drug delivery systems.In addition,toxins and their combination strategies with other therapies were discussed.Finally,the prospect and challenge of toxins in cancertreatmentwerealso summarized.

关键词： Toxins Non-antibody-drug conjugates Delivery strategies Prodrugs Nano drug delivery systems Biomimetic drugdelivery systems Combination strategies Cancer treatment

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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

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National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei Wu Jiaqi Shi yanfang wang Yuejun Yao Tao Sheng Feng Liu Wei Liu Peng Zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu Laboratory Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of Laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang University MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

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Influence of post-heat treatment on the microstructure and mechanical properties of Al-Cu-Mg-Zr alloy manufactured by selective laser melting

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Journal of Materials Science & Technology 2022年第16期111卷 35-48页

作者： yanfang wang Xin Lin Nan Kang Zihong wang Yuxi Liu Weidong Huang State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an 710072China Key Laboratory of Metal High Performance Additive Manufacturing and Innovative Design MIIT ChinaNorthwestern Polytechnical UniversityXi’an 710072China

The properties of modified conventional wrought aluminum alloys cannot be significantly enhanced by normal post-heat treatment in that the fine-grained strengthening,arising from high cooling rate in SLM,is underutilized.In this work,compared with the normal T6 heat treatment,a novel simple direct aging regime was proposed to maintain the grain-boundary strengthening and to utilize the precipitation strengthening of secondary AlZr.It was found that a heterogeneous grain structure,which consisted of ultrafine equiaxed(~0.82μm)and columnar(~1.80μm)grains at the bottom and top of molten pool,respectively,was formed in the SLM processed sample.After direct aging(DA),the ultrafine grains were maintained and a mass of spherical coherent L1-AlZr particles with a mean radius of approximately1.15 nm was precipitated.In contrast,after solution treatment and aging(STA),a significant grain coarsening occurred in the equiaxed grain region.Meanwhile,the coarsening L1-AlZr particles,nano-sized S phases and GPB zones were detected in the STA sample.This subsequently induced that the yield strength of the DA sample(~435 MPa)was higher than that of the STA sample(~402 MPa)owing to the grain boundary strengthening and precipitation strengthening.Both the STA and DA samples exhibited a higher strength than that of the other SLMed Al-Cu-Mg series alloys;this was comparable to that of the wrought AA2024-T6 alloy(~393 MPa).Both the STA and DA samples exhibited a higher strength than that of the other SLMed Al-Cu-Mg series alloys;this was comparable to that of the wrought AA2024-T6alloy(~393 MPa).

关键词： Selective laser melting Al-Cu-Mg alloy Heat treatment Microstructure Mechanical properties

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One-step base editing in multiple genes by direct embryo injection for pig trait improvement

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Science China(Life Sciences) 2022年第4期65卷 739-752页

作者： Ruigao Song Yu wang Qiantao Zheng Jing Yao Chunwei Cao yanfang wang Jianguo Zhao State Key Laboratory of Stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing100101China University of Chinese Academy of Sciences Beijing100049China State Key Laboratory of Animal Nutrition Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing100081China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing100101China The Third Hospital of Shanxi Medical University Shanxi Bethune HospitalShanxi Academy of Medical SciencesTaiyuan030032China

The precise and simultaneous acquisition of multiple beneficial alleles in the genome is in great demand for the development of elite pig breeders. Cytidine base editors(CBEs) that convert C:G to T:A have emerged as powerful tools for single-nucleotide replacement. Whether CBEs can effectively mediate C-to-T substitution at multiple sites/loci for trait improvement by direct zygote injection has not been verified in large animals. Here, we determined the editing efficiency of four CBE variants in porcine embryonic fibroblast cells and embryos. The findings showed that hA3A-BE3-Y130F and hA3A-eBE-Y130F consistently resulted in increased base-editing efficiency and low toxic effects in embryonic development. Further, we verified that using a one-step approach, direct zygote microinjection of the CBE system can generate pigs harboring multiple point mutations.Our process resulted in a stop codon in CD163 and myostatin(MSTN) and introduced a beneficial allele in insulin-like growth factor-2(IGF2). The pigs showed disrupted expression of CD163 and MSTN and increased expression of IGF2, which significantly improved growth performance and infectious disease resistance. Our approach allows immediate introduction of multiple mutations in transgene-free animals to comprehensively improve economic traits through direct embryo microinjection,providing a potential new route to produce elite pig breeders.

关键词： CBEs embryo injection pig multiple traits improvement

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An optimized prime editing system for efficient modification of the pig genome

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Science China(Life Sciences) 2023年第12期66卷 2851-2861页

作者： Yanan Qi Ying Zhang Shuangjie Tian Ruojun Zong Xinghui Yan Yu wang yanfang wang Jianguo Zhao State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China State Key Laboratory of Animal Nutrition Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100081China Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou 510642China

Prime editing(PE)is a recent gene editing technology that can mediate insertions or deletions and all twelve types of base-tobase conversions.However,its low efficiency hampers the application in creating novel breeds and biomedical models,especially in pigs and other important farm animals.Here,we demonstrate that the pig genome is editable using the PE system,but the editing efficiency was quite low as expected.Therefore,we aimed to enhance PE efficiency by modulating both exogenous PE tools and endogenous pathways in porcine embryonic fibroblasts(PEFs).First,we modified the peg RNA by extending the duplex length and mutating the fourth thymine in a continuous sequence of thymine bases to cytosine,which significantly enhanced PE efficiency by improving the expression of peg RNA and targeted cleavage.Then,we targeted SAMHD1,a deoxynucleoside triphosphate triphosphohydrolase(d NTPase)that impedes the reverse transcription process in retroviruses,and found that treatment with its inhibitor,cephalosporin C zinc salt(CPC),increased PE efficiency up to 29-fold(4-fold on average),presumably by improving the reverse transcription process of Moloney murine leukemia virus reverse transcriptase(M-MLV RT)in the PE system.Moreover,PE efficiency was obviously improved by treatment with a panel of histone deacetylase inhibitors(HDACis).Among the four HDACis tested,panobinostat was the most efficient,with an efficiency up to 122-fold(7-fold on average),partly due to the considerable HDACi-mediated increase in transgene expression.In addition,the synergistic use of the three strategies further enhanced PE efficiency in PEFs.Our study provides novel approaches for optimization of the PE system and broadens the application scope of PE in agriculture and biomedicine.

关键词： prime editing pig porcine embryonic fibroblasts editing efficiency

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Laser powder bed fusion of Zr-modified Al-Cu-Mg alloy:Processability and elevated-temperature mechanical properties

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Journal of Materials Science & Technology 2023年第5期136卷 223-235页

作者： yanfang wang Xin Lin Yufan Zhao Zihong wang Xiaobin Yu Xuehao Gao Weidong Huang State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an 710072China Key Laboratory of Metal High Performance Additive Manufacturing and Innovative Design MIIT ChinaNorthwestern Polytechnical UniversityXi’an 710072China

Zr modification is an effective method for improving hot-cracking resistance and elevated-temperature mechanical properties during laser powder bed fusion(L-PBF)of traditional medium and high strength wrought aluminum alloys.This study investigated the l-PBF processability and elevated-temperature mechanical properties of a Zr-modified 2024Al alloy.It was found that the hot-cracking susceptibility increased with the increased scanning speed,which was in reasonable agreement with the modified Rappaz-Drezet-Gremaud criterion.Furthermore,the primary L1_(2)-Al_(3)Zr precipitates,which acted as ef-ficient nucleation sites,precipitated at the fusion boundary of the melt pool,leading to the formation of a heterogeneous grain structure.The yield strength(YS)of the as-fabricated samples at 150,250,and 350℃was 363,210,and 48 MPa,respectively.Despite the slight decrease to 360 MPa of the YS when tested at 150℃,owing to the additional precipitate strengthening from the L1_(2)-Al_(3)Zr precipitates,the YS achieved yield strengths of 253 and 69 MPa,an increase of 20.5%and 30.4%,when tested at 250 and 350℃,respectively.The yield strengths in both the as-fabricated and T6-treated conditions tested at 150 and 250℃were comparable to those of casting Al-Cu-Mg-Ag alloys and superior to those of traditionally heat-resistant 2219-T6 and 2618-T6 of Al-Cu alloys.

关键词： Laser powder bed fusion Zirconium Al-Cu-Mg alloy Processability Elevated-temperature mechanical property

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Tailoring the microstructure,mechanical and tribocorrosion performance of (CrNbTiAlV)N_(x) high-entropy nitride films by controlling nitrogen flow

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Journal of Materials Science & Technology 2022年第12期107卷 172-182页

作者： Cunxiu Zhang Xiaolong Lu Cong wang Xudong Sui yanfang wang Haibin Zhou Junying Hao State Key Laboratory of Solid Lubrication Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000China School of Materials Science and Engineering China University of Petroleum(East China)Qingdao 266580China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Qingdao Center of Resource Chemistry and New Materials Qingdao 266000China

The(CrNbTiAlV)N_(x)high-entropy nitride films were fabricated by adjusting nitrogen flow via magnetron sputtering.The microstructure,mechanical,electrochemical and tribocorrosion performances of the films were studied.The results show that the films transform from amorphous to nanocrystalline structure as nitrogen flow increased.The nanocrystalline films show super hardness(>40 GPa)and adhesion strength(>50 N).The amorphous film has a pretty anti-corrosion in static corrosion,while not in tribocorrosion condition.The film deposited at nitrogen flow of 38 sccm exhibits the optimal tribocorrosion performance in artificial seawater,with the highest open circuit potential(∼−0.1 V vs.Ag/AgCl),the lowest friction coefficient(∼0.162)and wear rate(∼7.48×10^(−7)mm^(3)N^(−1)m^(−1)).

关键词： High-entropy nitride films Nitrogen flow Tribocorrosion performance Magnetron sputtering

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Solidification microstructure evolution and its correlations with mechanical properties and damping capacities of Mg-Al-based alloy fabricated using wire and arc additive manufacturing

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Journal of Materials Science & Technology 2023年第13期144卷 28-44页

作者： Zihong wang Jingfeng wang Xin Lin Nan Kang Tianchi Zhang yanfang wang Li wang Cong Dang Weidong Huang College of Materials Science and Engineering Chongqing UniversityChongqing 400045China National Engineering Research Center for Magnesium Alloys Chongqing UniversityChongqing 400044China Key Laboratory of Metal High Performance Additive Manufacturing and Innovative Design MIIT ChinaNorthwestern Polytechnical UniversityXi’an 710072China Arts et Métiers Institute of Technology MSMPHESAM UniversitéChâlons-en-Champagne F-51006France Chongqing Construction Science Research Institute Chongqing 401147China

Magnesium(Mg)alloys,as the lightest metal structural material with good damping capacities,have im-portant application prospects in realizing structural lightweight and vibration reduction.However,their engineering application is greatly limited by poor plastic formability.Wire and arc additive manufactur-ing(WAAM)provides a potential approach for fabricating large-scale Mg alloy components with high manufacturing flexibility.In this study,the evolution of the solidification microstructure of a WAAM-processed Mg-Al-based alloy was quantitatively analyzed based on the analytical models;then,the cor-relations between the solidification microstructure and mechanical properties/damping capacities were investigated.The results revealed that the WAAM-processed Mg-Al-based alloy with an equiaxed-grain-dominated microstructure displayed a simultaneous enhancement in mechanical properties and damping capacities compared to those of the cast Mg-Al-based alloy.The good combination of mechanical prop-erties and damping capacities are mainly attributed to the weakened basal texture with a relatively high Schmid factor for basalslip,the twinning-induced plasticity(TWIP)effect associated with the profuse{10-12}tensile twinning,and the relatively high dislocation density caused by the thermal stress during the WAAM process.

关键词： Wire and arc additive manufacturing Magnesium alloy Microstructure evolution Mechanical properties Damping capacities

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Serum metabolomic profiling reveals potential biomarkers in assessing the management of women with polycystic ovary syndrome:a randomized controlled trial

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Chinese Medical Journal 2022年第1期135卷 79-85页

作者： Xuesong Ding Yan Deng yanfang wang Wei Xue Shiyang Zhu Xiao Ma Ruilin Ma Aijun Sun Department of Obstetrics and Gynecology Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China

Background: As one of the most common endocrinal disorders for women at childbearing age, the diagnostic criteria of polycystic ovary syndrome (PCOS) have been defined differently among different international health organizations. Phenotypic heterogeneity of PCOS also brings about difficulties for its diagnosis and management assessment. Therefore, more efficient biomarkers representing the progression of PCOS are expected to be integrated into the monitoring of management process using metabolomic approaches.Methods: In this prospective randomized controlled trial, 117 PCOS patients were enrolled from December 2016 to September 2017. Classical diagnostic parameters, blood glucose, and metabolome were measured in these patients before and at 2 months and 3 months of different medical interventions. The receiver operating characteristic (ROC) curves were built based on multivariate statistical analysis using data at baseline and 3 months’ management, and combinational biomarkers with appreciable sensitivity and specificity were selected, which then validated with data collected at 2 months.Results: A set of metabolites including glutamic acid, aspartic acid, 1-methylnicotinamide, acetylcarnitine, glycerophosphocholine, and oleamide were filtered out with high performance in representing the improvement through 3-month management of PCOS with high sensitivity and specificity in ROC analysis and validation with other two groups showed an appreciable area under the curve over 0.96.Conclusions: The six metabolites were representative of the remission of PCOS through medical intervention, making them a set of potential biomarkers for assessing the outcome of PCOS management.Trial Registration: ClinicalTrials.gov, NCT03264638.

关键词： Polycystic ovary syndrome Metabolomic approach Management evaluation Serum metabolomic

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