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Alzheimer’s disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling

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The Innovation 2024年第1期5卷 118-126页

作者： Qing-Qing Tao Xue Cai yan-yan Xue Weigang Ge Liang Yue Xiao-yan Li Rong-Rong Lin Guo-Ping Peng Wenhao Jiang Sainan Li Kun-Mu Zheng Bin Jiang Jian-Ping Jia Tiannan Guo Zhi-Ying Wu Department of Neurology and Research Center of Neurology in the Second Affiliated Hospital and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of MedicineHangzhou 310009China Liangzhu Laboratory Zhejiang UniversityHangzhou 311100China Westlake Laboratory of Life Sciences and Biomedicine Key Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake UniversityHangzhou 310024China Institute of Basic Medical Sciences Westlake Institute for Advanced StudyHangzho 310024China Department of Neurology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Neurology First Affiliated HospitalSchool of MedicineXiamen UniversityXiamen 361009China Innovation Center for Neurological Disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijing 100053China MOE Frontier Science Center for Brain Science and Brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031China

Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic *** ADspecific early diagnostic and disease staging biomarkers are *** this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 *** biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 *** quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,*** the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,*** 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,*** 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative ***,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD *** findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.

关键词： cerebrospinal Alzheimer fluid

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Understanding and Detecting Inefficient Image Displaying Issues in Android Apps

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Journal of Computer Science & Technology 2024年第2期39卷 434-459页

作者：李文杰马骏蒋炎岩许畅马晓星 State Key Laboratory of Novel Software Technology Nanjing UniversityNanjing 210023China Department of Computer Science and Technology Nanjing UniversityNanjing 210023China

Mobile applications(apps for short)often need to display ***,inefficient image displaying(IID)issues are pervasive in mobile apps,and can severely impact app performance and user *** paper first establishes a descriptive framework for the image displaying procedures of IID *** on the descriptive framework,we conduct an empirical study of 216 real-world IID issues collected from 243 popular open-source Android apps to validate the presence and severity of IID issues,and then shed light on these issues’characteristics to support research on effective issue *** the findings of this study,we propose a static IID issue detection tool TAPIR and evaluate it with 243 real-world Android ***,49 and 64 previously-unknown IID issues in two different versions of 16 apps reported by TAPIR are manually confirmed as true positives,respectively,and 16 previously-unknown IID issues reported by TAPIR have been confirmed by developers and 13 have been ***,we further evaluate the performance impact of these detected IID issues and the performance improvement if they are *** results demonstrate that the IID issues detected by TAPIR indeed cause significant performance degradation,which further show the effectiveness and efficiency of TAPIR.

关键词： Android application(app) inefficient image displaying(IID) performance empirical study static analysis

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Portable fluorogenic probe for monitoring of volatile amine vapour and food spoilage

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Chinese Chemical Letters 2024年第3期35卷 257-261页

作者： Jian-Hao Zhao Wen-Xing Xu Bin Li Wei Xu Wu-Kun Zhang Ming-Shuai Yuan Hui-Zi Li Qing-Guo He Xiang Ma Jian-Gong Cheng yan-yan Fu State Key Lab of Transducer Technology Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghai 200050China Center of Materials Science and Optoelectronics Engineering University of the Chinese Academy of SciencesBeijing 100039China School of Physical Science and Technology ShanghaiTech UniversityShanghai 201210China Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghai 200237China

There are urgent needs of volatile amine gas sensors with high-performance in food quality control,disease monitoring and environmental ***-film fluorescent probe is suitable for amine vapour sensing due to its high sensitivity,high selectivity,and no polluting ***,a novel fluorescent probe based on indacenodithiophene structure withπconjugated system was designed and *** experimental results show that the films prepared by this material exhibit rapid and distinct fluorescence quenching after being exposed to saturated vapours of primary amine,secondary amine and tertiary amine represented by n-propylamine,diethylamine and trimethylamine,*** quenching of fluorescence is 84%,87%and 96%,respectively,within 10 *** detection mechanism of probe for primary amine is based on specific chemical reaction,while the detection mechanism for secondary amine and tertiary amine is intramolecular charge *** experiments show that the detection limit of the fluorescent probe for trimethylamine,an important marker of food spoilage,could reach 4.610 ***-site detection based on spoilage of small yellow croaker suggests the material possesses the potential for food freshness *** simple fluorogenic probe is an original approach to simplify real-time visual monitoring of volatile amine vapour.

关键词： Fluorescent probe Volatile amine Gas sensing Trimethylamine Food spoilage

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Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification

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World Journal of Diabetes 2024年第3期15卷 530-551页

作者： Meng-Ying Che Ling Yuan Jiao Min Duo-Jie Xu Dou-Dou Lu Wen-Jing Liu Kai-Li Wang yan-yan Wang Yi Nan Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina College of Pharmacy Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Traditional Chinese Medicine College Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina School of Clinical Medicine Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Department of Endocrinology Yinchuan Hospital of Traditional Chinese MedicineYinchuan 750004Ningxia Hui Autonomous RegionChina

BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's *** Chinese medicine has been validated for its efficacy in DKD after many years of clinical ***,the specific mechanism by which it works is still *** the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new *** To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro *** The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of *** for DKD were obtained based on the Genecards,OMIM,and TTD *** VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"*** String database was used to construct protein interaction *** Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID *** selecting the targets and the active ingredients,Autodock software was used to perform molecular *** experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic *** cytometry was used to detect the cell cycle progression and *** blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and *** A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for *** analysis of KEGG pathways was performed to determ

关键词： Nardostachyos Radix et Rhizoma-rhubarb Diabetic kidney disease Molecular docking Network pharmacology Experimental validation

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The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes:findings from a prospective,nationwide,and multicenter registry

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Journal of Geriatric Cardiology 2024年第5期21卷 523-533页

作者： Rui FU Ying-Xuan ZHU Kong-Yong CUI Jin-Gang yanG Hai-yan XU Dong YIN Wei-Hua SONG Hong-Jian WANG Cheng-Gang ZHU Lei FENG Wei WU Kai-HongCHEN yan-yan ZHAO Ye LU Ke-Fei DOU Yue-Jin yanG on behalf of the CAMI Registry Investigators Cardiometabolic Medicine Center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical Research&Biometrics Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Coronary Heart Disease Center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Guangzhou Traditional Chinese Medical College First Affiliated HospitalGuangdong ProvinceChina Department of Cardiology Longyan Hospital First HospitalFujian ProvinceChina 不详

OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism *** We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were *** were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,*** primary endpoint was in-hospital *** Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,*** with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not ***-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic *** FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic *** This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without *** might be useful to stratify patients with AMI.

关键词： patients fasting infarction

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Prevalence,Characteristics and Treatment of Knee Osteoarthritis in Urban Residents of Beijing,China:A Community-Based Cross-Sectional Study

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Biomedical and Environmental Sciences 2024年第4期37卷 418-422页

作者： ZHOU Jun yan yan DONG Ya Wei LIU Xiao Yu WANG Ping LIN Jia Ming DONG Peng Xuan QUAN Rui WANG Rong Tian MI Bao Hong CHEN Wei Heng Beijing University of Chinese Medicine Third Affiliated Hospital Beijing 100029China Engineering Research Center of Chinese Orthopaedics and Sports Rehabilitation Artificial Intelligent Ministry of EducationBeijing 100029China Beijing Hepingli Community Health Service Center Beijing 100013China Minimally Invasive Joint Surgery Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China

Knee osteoarthritis(KOA)is a common progressive joint disease with chronic pain and movement disorders as the main clinical *** is a major public health problem worldwide and it imposes serious medical and economic *** accounts for nearly four-fifths of the global Osteoarthritis burden and increases with rising obesity and age[1].There are many reasons for the change in disease prevalence and risk factors,such as urbanization,lifestyle changes,population aging,and sex imbalances.

关键词： Osteoarthritis clinical obesity

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Effectiveness of Extended Care in Preventing Falls in Disabled Elderly and Its Impact on Quality of Life

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Journal of Clinical and Nursing Research 2024年第6期8卷 154-159页

作者： Chun Tian Na Li yan yan The First Hospital of Shanxi Medical University Taiyuan 030001Shanxi ProvinceChina School of Nursing Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina

Objective:To analyze the value of extended care interventions for disabled elderly in preventing falls and optimizing quality of ***:A sample of 60 cases of disabled elderly in a tertiary hospital from May 2022 to May 2023 was selected and grouped by the random number table *** observation group received extended care,while the control group adopted routine *** differences in complication rate,fall rate,36-Item Short Form Health Survey(SF-36)score,health knowledge awareness score,and nursing satisfaction were ***:The complication rate and fall rate of the disabled elderly in the observation group were lower than those in the control group,P<0.05;the SF-36 score,health knowledge score,and nursing satisfaction of the observation group were higher than those of the control group,P<***:Extended care for the disabled elderly can reduce the risk of falls and complications related to disability,as well as optimize their cognition and improve their quality of life,which is efficient and feasible.

关键词： Disabled elderly Extended care Falls Quality of life

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Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3471-3480页

作者： Wei-yang Shu yan-yan Shi Jiu-Tian Huang Ling-Mei Meng He-Jun Zhang Rong-Li Cui Yuan Li Shi-Gang Ding Department of Gastroenterology Peking University Third HospitalBeijing 100191China Research Center of Clinical Epidemiology Peking University Third HospitalBeijing 10019China Department of Gastroenterology Pathology Laboratory Peking University Third HospitalBeijing 100191China Department of Gastroenterology Peking University International HospitalBeijing 102206China

BACKGROUND The intrapapillary capillary loop(IPCL)characteristics,visualized using magnifying endoscopy,are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma(ESCC).Japan Esophageal Society(JES)classification is the most widely used *** structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor:tortuosity,dilatation,irregular caliber,and different ***,the pathological characteristics of IPCLs have not been thoroughly investigated,especially the microvascular structures corresponding to the deepest parts of the lesions'*** To investigate differences in pathological microvascular structures of ESCC,which correspond to the deepest parts of the lesions'*** Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April *** first underwent magnified endoscopic examination,followed by endoscopic submucosal dissection or surgical *** images were scanned using a threedimensional slice scanner,and the pathological structural differences in different types,according to the JES classification,were analyzed using nonparametric tests and *** The 35 lesions were divided into four groups according to the JES classification:A,B1,B2,and *** analyses revealed significant differences(aP0.05).However,significant differences in the short calibers,long calibers,and area of IPCL were observed between types B1 and B3(aP0.05).CONCLUSION Pathological structures of IPCLs in the deepest infiltrating regions differ among va

关键词： Esophageal squamous cell carcinoma Intrapapillary capillary loop The Japan Esophageal Society classification Magnifying endoscopy Pathological characteristics

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西北内陆区降水稳定同位素时空分布特征及其水汽来源

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环境科学 2024年第4期45卷 2080-2095页

作者：张炎炎辛存林郭小燕张博陈宁史延飞西北师范大学地理与环境科学学院兰州730070 中国科学院西北生态环境资源研究院兰州730000

综合分析西北内陆区97个研究站点的降水稳定同位素数据,并结合相关气象资料,揭示了西北内陆区降水稳定同位素δ^(18)O、δD和d-excess时空分布特征,明确了海拔、经纬度、温度和降雨量对降水δ^(18)O的影响;利用水汽通量和HYSPLIT模型追... 详细信息

综合分析西北内陆区97个研究站点的降水稳定同位素数据,并结合相关气象资料,揭示了西北内陆区降水稳定同位素δ^(18)O、δD和d-excess时空分布特征,明确了海拔、经纬度、温度和降雨量对降水δ^(18)O的影响;利用水汽通量和HYSPLIT模型追踪了大气降水的水汽来源.同时,根据关键自然地理要素的空间差异将西北内陆区划分为4个子区域,对上述内容分区域进行系统分析和对比.结果表明:(1)西北内陆区降水δ^(18)O和δD的变化范围分别为-21.20‰~1.70‰和-144.20‰~5.21‰,d-excess波动范围为-20.37‰~46.48‰,δ^(18)O、δD和d-excess均存在显著的空间变化和季节变化特征,河西内陆区和塔里木地区δ^(18)O和δD值相对偏正,柴达木-青海湖区和准噶尔-吐哈地区δ^(18)O和δD偏负.(2)西北内陆区大气降水线方程的斜率和截距均小于中国和全球大气降水线,4个子区域亦低于全球水线,其中塔里木地区斜率最低.(3)西北内陆区海拔效应为-0.04‰·(100 m)^(-1),其中河西内陆区和塔里木地区呈显著负相关;降水δ^(18)O与经度呈显著正相关,而与纬度呈不显著负相关.(4)西北内陆区普遍存在显著的温度效应,呈西北高东南低的空间特征;受气温和地形影响,降雨量效应较微弱.(5)西北内陆区水汽来源全年主要为西风水汽输送,冬季受到极地气团影响,夏季受季风水汽的入侵,部分区域会出现极端降水事件;过量氘夏季贫化、冬季富集,与相对湿度呈正相关,表明西北内陆区降水还受局地水汽再循环影响.

关键词：西北内陆区大气降水稳定同位素水汽来源过量氘

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不同比例硫酸铵替代尿素对玉米根际土壤环境及微生物群落的影响

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环境科学 2024年第6期45卷 3584-3594页

作者：张延慧刘宇韩莹董馨宇郭探文闫秋艳闫双堆山西农业大学资源环境学院太谷030801 山西农业大学小麦研究所临汾041000 山西农业大学农业资源与环境国家级实验教学示范中心太谷030801

为了探究工业副产物硫酸铵以不同比例替代尿素做为氮肥施入土壤后对土壤养分以及微生物群落的影响,进行了盆栽玉米试验.试验采用完全随机设计方法,共设置5个处理:CK(不施肥)、U_(10)S_(0)(100%尿素)、U_(8)S_(2)(80%尿素+20%硫酸铵)、U_... 详细信息

为了探究工业副产物硫酸铵以不同比例替代尿素做为氮肥施入土壤后对土壤养分以及微生物群落的影响,进行了盆栽玉米试验.试验采用完全随机设计方法,共设置5个处理:CK(不施肥)、U_(10)S_(0)(100%尿素)、U_(8)S_(2)(80%尿素+20%硫酸铵)、U_(6)S_(4)(60%尿素+40%硫酸铵)和U_(0)S_(10)(100%硫酸铵).应用常规方法进行土壤基本理化性质以及玉米植株干重的测定,通过Illumina Nova Seq平台进行微生物测序.结果表明:①在玉米的各个生育期,施肥处理土壤p H(7.85~8.15)与CK(8.1~8.21)相比都有所下降,并且随着硫酸铵比例的增加p H呈不断下降的趋势;②在玉米各生育期土壤碱解氮含量随着硫酸铵比例的增加呈逐渐增加的趋势,U_(0)S_(10)处理比CK和U_(10)S_(0)处理分别提高了30.56%~63.68%和13.22%~38.43%;有机碳含量变化趋势为:U_(8)S_(2)>U_(6)S_(4)>U_(0)S_(10),但除苗期以外其他生育期添加硫酸铵的处理都仍高于U_(10)S_(0)处理;③所有的施肥处理蛋白酶活性都高于对照,并且随着玉米的不断生长和硫酸铵比例的增加蛋白酶活性逐渐增强,U_(0)S_(10)处理在玉米各生育期都高于U_(10)S_(0)处理,提高了10.54%~100%;各施肥处理土壤蔗糖酶活性范围为0.04~0.24 mg·(g·24 h)^(-1),并在所有生育期U_(0)S_(10)处理都显著高于U_(10)S_(0)和CK处理,分别提高了20.32%~99.16%、24.31%~79.33%;④所有施肥处理的玉米根际细菌和真菌物种丰富度都低于CK处理,U_(10)S_(0)处理仅低于CK,硫酸铵替代尿素的3个处理细菌群落物种多样性趋势为:U_(8)S_(2)>U_(0)S_(10)>U_(6)S_(4),真菌为:U_(6)S_(4)>U_(8)S_(2)>U_(0)S_(10);⑤U_(0)S_(10)和U_(10)S_(0)处理玉米植株干重最大,分别比CK处理提高了39.47%和36.16%,U_(0)S_(10)处理高于U_(10)S_(0)处理但差异不显著;Pearson模型表明相关环境变量对土壤根际真菌和细菌物种丰富度和多样性有一定影响,其中p H值和土壤碱解氮含量是影响微生物物种多样性的最主要因素.综上,在石灰性褐土的玉米种植中,以一定比例硫酸铵替代尿素比单施尿素更能提高土壤养分,在一定程度上影响了玉米生长及根际微生物群落,并且有更大的产出.

关键词：硫酸铵 pH 碳氮养分土壤酶活性根际微生物

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