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

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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Robust model for tunnel squeezing using Bayesian optimized classifiers with partially missing database

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Underground Space 2023年第3期10卷 91-117页

作者： Yin Bo Xing Huang Yucong Pan yanfang feng Penghai Deng feng Gao Ping Liu Quansheng Liu Key Laboratory of Geotechnical and Structural Engineering Safety of Hubei Province School of Civil EngineeringWuhan UniversityWuhanHubei 430072China State Key Laboratory of Water Resources and Hydropower Engineering Science Wuhan UniversityWuhanHubei 430072China State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhanHubei 430071China

Accurately predicting and estimating the squeezing and ground response to tunneling remains challenging.Moreover,tunnel-squeezing hazards are much more likely to occur in deeply buried long tunnels with complex engineering-geological environments.There-fore,a high-performance predictive model for tunnel squeezing is necessary.A superior ensemble classifier is put forward in this study,which is composed of four individual classifiers(gradient boosting classifier,extra-trees classifier,AdaBoost classifier,and Logistic regression classifier)and two optimization algorithms(Bayesian optimization(BO)and sparrow search algorithm(SSA)).The training database covers five parameters:tunnel depth(H),rock tunneling quality index(Q),tunnel diameter(D),support stiffness(K),and strength stress ratio(SSR),about which the basic information is accessible at the early design phases.However,the dataset compiled from the literature is insufficient.Thus,the ten proposed methods are used to replace the missing values.During the model training pro-cess,BO shows its strong ability to optimize seventeen hyperparameters.When applied to tune the classifiers’weights,SSA achieves a fast and efficient performance.The novel Shapley Additive Explanations–LightGBM method indicates that the K is the most important input feature,followed by SSR,Q,H,and D,respectively.The ensemble classifier is then validated using the test set and additional his-torical case projects.The validation shows that the model can achieve an accuracy of 98%(i.e.,the error rate is 2%)on the test set,higher than those achieved by previous prediction models.Moreover,the predicted probability could provide warning information for timely support measures.Finally,the application results are illustrated through tests on the tunnel sections that have not yet been excavated in the line of the Sichuan–Tibet railway project.The applied predictive tendencies and laws are in line with the practical experience.In sum-mary,the proposed model’s prediction results are reasonable,and its pre

关键词： Tunnel squeezing hazard Bayesian optimization Machine learning techniques Sparrow search algorithm Ensemble classifier Incomplete database

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Hydrochar-embedded carboxymethyl cellulose-g-poly(acrylic acid)hydrogel as stable soil water retention and nutrient release agent for plant growth

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Journal of Bioresources and Bioproducts 2022年第2期7卷 34-45页

作者： Yufei Zhang Xinyue Tian Qiuyue Zhang Huifang Xie Bingyu Wang yanfang feng Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse School of Environmental and Biological EngineeringNanjing University of Science and TechnologyNanjing 210094China Key Laboratory of Agro-Environment in Downstream of Yangtze Plain Ministry of Agriculture and Rural AffairsInstitute of Agricultural Resources and EnvironmentJiangsu Academy of Agricultural SciencesNanjing 210014China

The cellulose-based hydrogel has been widely applied for soil water retention and nutrient re-lease agents for several decades.Embedding the inorganic materials into hydrogels is an excellent strategy to improve the inherent limits of the cellulose-based hydrogel.Notably,municipal sludge-derived hydrochar(HC)has reduced the environmental burden and offered a potential hydrogel carrier to control water-retention and nutrient-release.However,the above function for plant growth of hydrochar-embedded carboxymethyl cellulose-g-poly(acrylic acid)(CMC-g-PAA/HC)is unknown,and relevant reports are lacking.This study investigated the water retention,nutri-ent release behavior,and effect of germination and plant growth of CMC-g-PAA/HC hydrogel.Characterization results showed that HC was successfully incorporated into CMC-g-PAA/HC with 6.0%higher thermostability,7.2-21.0%lower swelling ratio(SR)in water,and substantial SR in phosphate solution(P-solution).The water loss rate of CMC-g-PAA/HC in P-solution or wa-ter owned a more significant temperature response(7.9-15.0 folds)than CMC-g-PAA(8.2-10.0 folds).Moreover,4.0%higher n value and more 18.5%released P for CMC-g-PAA/HC were also observed.These phenomena were due to restricting the polymer chains movement and the wa-ter molecules diffusion inside the hydrogels with HC.Phytotoxicity assessments showed that HC in CMC-g-PAA/HC could effectively alleviate the inhibition effects on rape germination retained with 78.3%germination vigor and 80.0%germination ratio,even dramatically improved plant growth to 28 d.The results of this study demonstrated a new route for developing eco-friendly CMC-g-PAA/HC hydrogel,advantageous as a water retention agent and nutrient carrier in arid and semiarid regions.

关键词： Hydrogel Hydrochar Stable phosphorus-release Water retention Plant growth

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Rhizoma Drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2210-2227页

作者： Qing Zhao Junjie feng Fubin Liu Qianxin Liang Manlin Xie Jiaming Dong yanfang Zou Jiali Ye Guilong Liu Yue Cao Zhaodi Guo Hongzhi Qiao Lei Zheng Kewei Zhao Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis the Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Guangdong Engineering Research Center of Chinese Herbal-derived Vesicles Guangzhou University of Chinese MedicineGuangzhou 510006China Department of Laboratory Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai 519000China Department of Blood Transfusion Guangdong Heyou International HospitalFoshan 528306China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.

关键词： Rhizoma Drynariae-derived nanovesicles Bone marrow mesenchymal stem cells Bone targeting Osteogenic differentiation ERαsignaling Naringin Bone morphogenetic protein 2 Runt-related transcription factor 2

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Efficient photocatalysis of tetracycline hydrochloride(TC-HCl) from pharmaceutical wastewater using AgCl/ZnO/g-C_(3)N_(4) composite under visible light: Process and mechanisms

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Journal of Environmental Sciences 2023年第4期126卷 249-262页

作者： Chenman Ding Qiurong Zhu Bei Yang Evangelos Petropoulos Lihong Xue yanfang feng Shiying He Linzhang Yang College of Resources and Environmental Sciences Nanjing Agricultural UniversityNanjing 210018China Institute of Agricultural Resources and Environment Jiangsu Academy of Agricultural SciencesNanjing 210018China School of Engineering Newcastle UniversityNewcastle upon Tyne NE17RUUK School of Chemistry and Chemical Engineering Nanjing University of Science and TechnologyNanjing 210018China

AgCl/ZnO/g-C_(3)N_(4), a visible light activated ternary composite catalyst, was prepared by combining calcination, hydrothermal reaction and in-situ deposition processes to treat/photocatalyse tetracycline hydrochloride(TC-HCl) from pharmaceutical wastewater under visible light. The morphological, structural, electrical, and optical features of the novel photocatalyst were characterized using scanning electron microscopy(SEM), UV-visible light absorption spectrum(UV–Vis DRS), X-ray diffractometer(XRD), Fourier transform infrared spectroscopy(FT-IR), X-ray photoelectron spectroscopy(XPS), and transient photocurrent techniques. All analyses confirmed that the formation of heterojunctions between AgCl/ZnO and g-C_(3)N_(4)significantly increase electron-hole transfer and separation compared to pure ZnO and g-C_(3)N_(4). Thus, AgCl/ZnO/g-C_(3)N_(4)could exhibit superior photocatalytic activity during TC-HCl assays(over 90% removal) under visible light irradiation. The composite could maintain its photocatalytic stability even after four consecutive reaction cycles. Hydrogen peroxide(H_(2)O_(2)) and superoxide radical(·O_(2)) contributed more than holes(h+) and hydroxyl radicals(·OH) to the degradation process as showed by trapping experiments. Liquid chromatograph-mass spectrometer(LC-MS) was used for the representation of the TC-HCl potential degradation pathway. The applicability and the treatment potential of AgCl/ZnO/gC_(3)N_(4)against actual pharmaceutical wastewater showed that the composite can achieve removal efficiencies of 81.7%, 71.4% and 69.0% for TC-HCl, chemical oxygen demand(COD) and total organic carbon(TOC) respectively. AgCl/ZnO/g-C_(3)N_(4)can be a prospective key photocatalyst in the field of degradation of persistent, hardly-degradable pollutants, from industrial wastewater and not only.

关键词： Photocatalyst Tetracycline degradation Pharmaceutical wastewater C_(3)N_(4)composites Degradation pathway

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FULL TIME-SPACE GOVERNANCE STRATEGY AND TECHNOLOGY FOR CROPLAND NON-POINT POLLUTION CONTROL IN CHINA

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Frontiers of Agricultural Science and Engineering 2023年第4期10卷 593-606页

作者： Lihong XUE Jingjing DUAN Pengfu HOU Shiying HE Yingliang YU yanfang feng Fuxing LIU Linzhang YANG Key Lab of Agro-environment in Downstream of Yangtze Plain of Ministry of Agriculture and Rural Areas Jiangsu Academy of Agricultural SciencesNanjing 210014China Eco-environmental Protection Research Institute Shanghai Academy of Agricultural SciencesShanghai 201403China

Ensuring food safety while reducing agricultural non-point source pollution is quite challenging,especially in developing and underdeveloped countries.Effective systematic strategies and comprehensive technologies need to be developed for agricultural non-point source pollution control at the watershed scale to improve surface water quality.In this review,a proposal is made for a full time-space governance strategy that prioritizes source management followed by endpoint water pollution control.The 4R chain technology system is specifically reviewed,including source reduction,process retention,nutrient reuse and water restoration.The 4R chain technology system with the full time-space governance strategy was applied at the scale of an administrative village and proved to be a feasible solution for reducing agricultural non-point source pollution in China.In the future,a monitoring system needs to be established to trace N and P transport.Additionally,new smart fertilizer and intelligent equipment need to be developed,and relevant governance standards and supportive policies need to be set to enhance the efficacy of agricultural non-point source pollution control.

关键词： 4R chain technology system agricultural non-point source pollution case study full time-space governance strategy

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Formable porous biochar loaded with La-Fe(hydr)oxides/montmorillonite for efficient removal of phosphorus in wastewater:process and mechanisms

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Biochar 2022年第1期4卷 296-314页

作者： Enhui Sun Yanyang Zhang Qingbo Xiao Huayong Li Ping Qu Cheng Yong Bingyu Wang yanfang feng Hongying Huang Linzhang Yang Charles Hunter Key Laboratory of Saline-Alkali Soil Improvement and Utilization(Coastal Saline-Alkali Lands) Ministry of Agriculture and Rural AffairsJiangsu Collaborative Innovation Center for Solid Organic Waste Resource UtilizationInstitute of Agricultural Resources and EnvironmentJiangsu Academy of Agricultural SciencesNanjing 210014China School of Life Sciences College of AgricultureEngineering and ScienceUniversity of KwaZulu-Natal(Pietermaritzburg Campus)Private Bag X01Scottsville 3209Republic of South Africa State Key Laboratory of Pollution Control and Resource Reuse School of the EnvironmentNanjing UniversityNanjing 210023China Institute of Germplasm Resources and Biotechnology Jiangsu Academy of Agricultural SciencesNanjing 210014China Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse School of Environmental and Biological EngineeringNanjing University of Science and TechnologyNanjing 210094China

The development of biochar-based granule-like adsorbents suitable for scaled-up application has been attracting increasing attention in the field of water treatment.Herein,a new formable porous granulated biochar loaded with La-Fe(hydr)oxides/montmorillonite(LaFe/MB)was fabricated via a granulation and pyrolysis process for enhanced phosphorus(P)removal from wastewater.Montmorillonite acted as a binder that increased the size of the granulated biochar,while the use of Fe promoted the surface charge and facilitated the dispersion of La,which was responsible for selective phosphate removal.LaFe/MB exhibited rapid phosphate adsorption kinetics and a high maximum adsorption capacity(Langmuir model,52.12 mg P g^(−1)),which were better than those of many existing granulated materials.The desorption and recyclability experiments showed that LaFe/MB could be regenerated,and maintained 76.7%of its initial phosphate adsorption capacity after four adsorption cycles.The high hydraulic endurance strength retention rate of the developed material(91.6%)suggested high practical applicability in actual wastewater.Electro-static attraction,surface precipitation,and inner-sphere complexation via ligand exchange were found to be involved in selective P removal over a wide pH range of 3-9.The thermodynamic parameters were determined,which revealed the feasibility and spontaneity of adsorption.Based on approximate site energy distribution analyses,high distribution frequency contributed to efficient P removal.The research results provide a new insight that LaFe/MB shows great application prospects for advanced phosphate removal from wastewater.

关键词： Formable porous biochar Montmorillonite Metal(hydr)oxide Wastewater phosphate removal Adsorption mechanism

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Unraveling natural aging-induced properties change of sludge-derived hydrochar and enhanced cadmium sorption site heterogeneity

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Biochar 2022年第1期4卷 615-634页

作者： Bingyu Wang Cenyao Shang Huifang Xie Haijun Sun Qiang Zhang Lihong Xue Filip M.G.Tack Deyi Hou yanfang feng Jörg Rinklebe Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse School of Environmental and Biological EngineeringNanjing University of Science and TechnologyNanjing 210094China Key Laboratory of Agro-Environment in Downstream of Yangtze Plain National Agricultural Experiment Station for Agricultural EnvironmentMinistry of Agriculture and Rural AffairsInstitute of Agricultural Resources and EnvironmentJiangsu Academy of Agricultural SciencesNanjing 210014China Co-Innovation Center for Sustainable Forestry in Southern China College of ForestryNanjing Forestry UniversityNanjing 210037China Department of Green Chemistry and Technology Ghent University9052 GhentBelgium School of Environment Tsinghua UniversityBeijing 100084China School of Architecture and Civil Engineering Institute of Foundation EngineeringWaterand Waste-ManagementLaboratory of Soiland Groundwater-ManagementUniversity of WuppertalPauluskirchstraße 742285 WuppertalGermany

Hydrochar has potential applications in soil improvement and heavy metal remediation.Hydrochar would undergo the process of aging when introduced into the soil,altering its properties.However,recent studies have focused mainly on the artificial aging of hydrochar,which could not reveal the cumulative effect of multiple environmental factors.Therefore,the periodical monitoring of the property and sorption behavior of hydrochar after amending soils is necessary to better understand the multifaceted mechanisms associated with the natural aging of hydrochar.This study selected the sludge-derived hydrochar(SLHC)as a typical hydrochar and applied a 16-month rice-wheat-rice rotation to mimic the natural aging of hydrochar,focusing on changing properties and cadmium(Cd)sorption and literature contrast between aging strategies and biochar types.The porosity,O abundance,and ash content of 16-month aged SLHC increased by 37%,47%,and 8.5%,respectively,facilitating Cd sorption due to surface complexation,pore sorption,and precipitation.The sorption percentage of Cd to SLHC was in the range of 11-14%for SLHC-A0 and increased to 17-31%for SLHC-A4 and 20-32%for SLHC-A16 after natural aging.The natural aging of SLHC induced by ash content played an essential role in Cd sorption site heterogeneity.Linear regression analysis showed that aging strategies on sorption behavior significantly differed between biochars.Thus,studies involving natural aging with multiple environmental factors are preferred over those involving chemical or biological aging.Future studies should continue to explore the mechanisms of natural aging-induced heavy metal sorption between hydrochar and pyrochar.These results improve insights to appraise the potential of SLHC as soil amendments to alleviate the adverse effects of heavy metal contamination and provide an essential basis for researchers and staff in soil management and environmental prevention.

关键词： Sludge-derived hydrochar Hydrothermal carbonization Natural aging Physicochemical properties Sorption behavior Cadmium

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超声辅助提取流苏香竹竹叶黄酮及其对亚硝化反应清除阻断作用

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西部林业科学 2024年第3期53卷 101-109,125页

作者：李翱翔谭炎坊冯武西南林业大学材料与化学工程学院云南昆明650224 云南省林业和草原科学院云南昆明650201

为了提高竹叶黄酮的得率,以流苏香竹叶为研究对象,采用响应面法优化流苏香竹竹叶黄酮超声协同乙醇提取的工艺,并测定流苏香竹叶提取物抗氧化、清除亚硝化物以及阻断亚硝化反应的能力。结果表明,响应面优化超声协同乙醇提取的最佳工艺条... 详细信息

为了提高竹叶黄酮的得率,以流苏香竹叶为研究对象,采用响应面法优化流苏香竹竹叶黄酮超声协同乙醇提取的工艺,并测定流苏香竹叶提取物抗氧化、清除亚硝化物以及阻断亚硝化反应的能力。结果表明,响应面优化超声协同乙醇提取的最佳工艺条件为:乙醇浓度为66.5%,料液比1︰30,超声功率311 W,流苏香竹叶黄酮的得率为37.146 mg/g。生物活性研究表明,流苏香竹叶提取物在一定浓度范围内对羟基自由基和超氧阴离子的清除能力强于L-抗坏血酸(Vc),DPPH自由基清除能力稍弱。对亚硝化物的清除率可达到52.59%,亚硝化反应的阻断率可达到74.75%。相关性分析表明,黄酮类化合物是流苏香竹叶中主要的抗氧化剂,亚硝化物的清除及亚硝化反应的阻断呈高度正相关。该研究发现流苏香竹竹叶黄酮作为多靶点抗癌药物或保健产品的潜力很大,可促进流苏香竹叶高附加值产品的开发。

关键词：流苏香竹竹叶黄酮响应面优化抗氧化亚硝化反应

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Impact of biochar amendment on soil aggregation varied with incubation duration and biochar pyrolysis temperature

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Biochar 2021年第3期3卷 339-347页

作者： Lanfang Han Biao Zhang Liying Chen yanfang feng Yan Yang Ke Sun Guangdong Provincial Key Laboratory of Water Quality Improvement and Ecological Restoration for Watersheds Institute of Environmental and Ecological EngineeringGuangdong University of TechnologyGuangzhou 510006China Institute of Agricultural Resources and Environment Jiangsu Academy of Agricultural SciencesNanjing 210014China State Key Laboratory of Water Environment Simulation School of EnvironmentBeijing Normal UniversityBeijing 100875China

Soil aggregation is one of the crucial processes that facilitate carbon sequestration and maintain soil fertility.So far,the effect of biochar amendment on soil aggregation remains inconclusive.Here,we tested the hypothesis that the response of soil aggregation to biochar addition varied with incubation duration and biochar chemistry.A one year microcosm experiment of soil with biochar was conducted that included biochar produced at three different temperatures(300,450,and 600°C),and three biochar application rates,i.e.,0,1,and 3 wt%.It was observed that after one and three months,biochar mainly(>90%)distributed in the micro-aggregates,and slightly reduced aggregate stability and increased proportion of micro-aggregates,which was demonstrated to result from the mechanical mixture of amended biochar with soil.Contrastingly,when the duration was prolonged to six months and one year,a significant increase in macro-aggregates(6.6-38.5%)and aggregate stability(7.3-29.4%)was detected,with the increasing extent being apparently higher for low-temperature biochar.This was related to the comparatively strong interaction of biochar particles with soil minerals or microbes after long-time incubation.The strong interaction was directly supported by the significant increase in H/C,O/C ratios of isolated biochar from treated soils,the detection of typical soil mineral elements on the surface of isolated biochar,and the increase in microbial biomass carbon of treated soils.The findings of this study highlighted the role of biochar type and amendment duration in mediating the effect of biochar application on soil aggregation.

关键词： Biochar Soil aggregation Aggregate stability Incubation duration

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