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MAGED4B Promotes Glioma Progression via Inactivation of the TNF-α-induced Apoptotic Pathway by Down-regulating TRIM27 Expression

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Neuroscience Bulletin 2023年第2期39卷 273-291页

作者： Can Liu Jun Liu Juntang Shao Cheng Huang Xingliang Dai yujun shen Weishu Hou Yuxian shen Yongqiang Yu Department of Radiology The First Afliated Hospital of Anhui Medical UniversityHefei 230022China Biopharmaceutical Research Institute Anhui Medical UniversityHefei 230032China School of Basic Medical Sciences Anhui Medical UniversityHefei 230032China Department of Pathology The First Afliated Hospital of Anhui Medical UniversityHefei 230022China Department of Neurosurgery The First Afliated Hospital of Anhui Medical UniversityHefei 230022China

MAGED4B belongs to the melanoma-associated antigen family;originally found in melanoma,it is expressed in various types of cancer,and is especially enriched in glioblastoma.However,the functional role and molecular mechanisms of MAGED4B in glioma are still unclear.In this study,we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue,and the level was positively correlated with glioma grade,tumor diameter,Ki-67 level,and patient age.The patients with higher levels had a worse prognosis than those with lower MAGED4B levels.In glioma cells,MAGED4B overexpression promoted proliferation,invasion,and migration,as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide.On the contrary,MAGED4B knockdown in glioma cells inhibited proliferation,invasion,and migration,as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide.MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain.The interaction between MAGED4B and tripartite motif-containing 27(TRIM27)in glioma cells was detected by co-immunoprecipitation assay,which showed that MAGED4B was co-localized with TRIM27.In addition,MAGED4B overexpression down-regulated the TRIM27 protein level,and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine(MG132),an inhibitor of the proteasome.On the contrary,MAGED4B knockdown up-regulated the TRIM27 level.Furthermore,MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132.Accordingly,MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7(USP7)involved in the tumor necrosis factor-alpha(TNF-α)-induced apoptotic pathway.These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1(RIP1)-dependent TNF-α-induced apoptotic pathway,which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.

关键词： Glioma MAGE family member D4B Tripartite motif-containing Apoptosis

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MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4234-4252页

作者： Chao Hou Dong Wang Mingxia Zhao Petek Ballar Xinru Zhang Qiong Mei Wei Wang Xiang Li Qiang sheng Jun Liu Chuansheng Wei yujun shen Yi Yang Peng Wang Juntang Shao Sa Xu Fuyan Wang Yang Sun Yuxian shen School of Basic Medical Sciences Anhui Medical UniversityHefei 230032China Biopharmaceutical Research Institute Anhui Medical UniversityHefei 230032China Department of Biochemistry Faculty of PharmacyEge UniversityIzmir 35100Turkey State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210023China

The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

关键词： Hepatic fibrosis Mesencephalic astrocyte-derived neurotrophic factor Macrophage differentiation Ly6C^(high)macrophages S100A8/S100A9 TLR4 NF-κB pathway HSCs activation

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Endoplasmic reticulum stress is involved in okadaic acid-induced tau phosphorylation and neurotoxic effects of okadaic acid

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Neural Regeneration Research 2010年第20期5卷 1534-1540页

作者： Lijie Feng Yuxian shen Aimin Sun yujun shen shengyun Fang Jun Li School of Pharmacy Anhui Medical University Hefei 230032 Anhui Province China Key Laboratory of Gene Resource Utilization for Genetic Diseases of Educational Ministry and Anhui Province Anhui Medical University Hefei 230032 Anhui Province China Institute of Medical and Pharmaceutical Biotechnology Anhui Medical University Hefei 230032 Anhui Province China

The role of the endoplasmic reticulum in Alzheimer＇s disease pathogenesis remains poody understood.The present study investigated the correlation of okadaic acid-induced tau hyperphosphorylation and neurotoxicity with endoplasmic reticulum stress.Following co-culture of various concentrations of okadaic acid （25,50,100,and 200 nmol/L） and human neuroblastoma SH-SY5Y cells,okadaic acid,a selective protein phosphatase （PP-1,PP-2A） inhibitor,reduced cell viability in a concentration-dependent manner,which was closely associated with okadaic acid-induced tau phosphorylation.In addition,expressions of the unfolded protein response activation marker glucose-regulated protein 78 （BiP/Grp78） and the CCAAT/enhancer binding protein homologous protein （CHOP）/Gadd153 increased following okadaic acid treatment.Furthermore,the unfolded protein response was activated in human embryonic kidney 293 （HEK 293） cells overexpressing tau following okadaic acid treatment,but untransfected HEK 293 cells did not exhibit activation of the unfolded protein response.These data indicate that endoplasmic reticulum stress is involved in mechanisms underlying tau phosphorylation and the cytotoxic effects of okadaic acid.

关键词： tau phosphorylation endoplasmic reticulum stress unfolded protein response

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Study on dynamic sorption characteristics of modified biochars for ammonium in biogas slurry

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International Journal of Agricultural and Biological Engineering 2020年第1期13卷 234-240页

作者： Jingtao Ding yujun shen Yanru Ma Haibo Meng Hongsheng Cheng Xi Zhang Jian Wang Pengyue Zhang Institute of Energy and Environmental Protection Academy of Agricultural Planning&EngineeringMinistry of Agriculture and Rural AffairsBeijing 100125China Key Laboratory of Technologies and Models for Cyclic Utilization from Agricultural Resources Ministry of Agriculture and Rural AffairsBeijing 100125China College of Engineering Huazhong Agricultural UniversityWuhan 430070China

The objective of this study was to investigate the relationship between ammonium(NH^(+)_(4)-N)dynamic sorption capacity and physicochemical properties of modified biochars.Biochars,producing from three species of agricultural wastes of cornstalk(A),corncob(B)and sawdust(C)at 550°C,600°C and 650°C,were modified by four methods of NaOH plus microwave(NaM),KOH(K),FeCl 3(Fe)and HNO 3(H).The static and dynamic adsorption experiments were conducted to investigate sorption characteristics of modified biochars on NH^(+)_(4)-N in slurry of piggery manure anaerobic digestate.Four modified biochars with better NH^(+)_(4)-N adsorption rates were selected through static kinetics adsorption tests,which showed that chemical reactions might have occurred during the NH^(+)_(4)-N sorption process and the maximum NH^(+)_(4)-N removal rates of B-550-Fe,A-550-NaM,A-550-K and C-600-NaM were 66.64%,57.50%,52.39%and 45.20%,respectively.The dynamic adsorption column experiment was conducted in a three-stage adsorption column packed with the selected three modified biochars.NH^(+)_(4)-N dynamic adsorption depended on the slurry inflow flow rate,the type of biochar and the depth of packed biochar.The optimal adsorption process was elected by the method of orthogonal experiment.The data showed that using deeper packed biochar and applying lower flow rates could be a better strategy to increase NH^(+)_(4)-N adsorption.The maximum NH^(+)_(4)-N removal rate in the slurry could reach 85.60%in the three-stage adsorption process.It concluded that NH^(+)_(4)-N adsorption in three-stage adsorption process could be an effective method to recover nitrogen from piggery manure anaerobic digestate.

关键词： modified biochar biogas slurry ammonium adsorption sorption characteristics

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Airflow field simulation model building and application for aerobic compost using CFD

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International Journal of Agricultural and Biological Engineering 2021年第4期14卷 245-254页

作者： Qiongyi Cheng Haibo Meng Haibin Zhou yujun shen Hongsheng Cheng Jingtao Ding Shihao Zhao Shance Hou Academy of Agricultural Planning and Engineering Key Laboratory of Technologies and Models for Cyclic Utilization from Agricultural ResourcesMinistry of Agriculture and Rural AffairsBeijing 100125China

Composting is a suitable low-cost strategy to transform animal waste into a stabilized end product,and the airflow field in the pile affects the fermentation states.For piles in the aeration weak zone,anaerobic fermentation may happen as the lack of oxygen.While in practice,due to the extremely low speed and harsh condition,the airflow field was scarcely researched.This study adopted Computational Fluid Dynamics(CFD)to investigate the airflow field in the compost pile.A three-dimensional CFD model was built;the compost pile in this model was simplified as porous media;unstructured mesh was adopted to discretize the geometric model;standard k-εmodel and SIMPLE scheme were employed for numerical methods.The CFD model was validated with the field experiment in the cooling period.Then the model was applied to research the airflow field in the pile with increased pipe diameter.Results showed that it was feasible to investigate the airflow field in the pile with CFD.For boundary conditions in the CFD model,treating the compost pile as a homogeneous porous media is reasonable.The CFD model was successfully validated by the field measurement(the average relative difference between the simulated and measured air speed was within 10%).Airflow in the existing compost pile showed nonuniform distribution with stagnation and vortex zones;the turbulence intensities were 3.57 and 1.43 for the airflow in the pile and the reactor,respectively.When pipe diameter increased,the airflow distribution uniformity in the pile was improved significantly.With diameter raising to 0.04 m,the turbulence intensity decreased to 1.54 and 0.42 for the airflow in the pile and the reactor,respectively.The CFD model developed in this research can provide qualitative and quantitative analyses of the airflow field in compost piles,and can be a theoretical basis for the aeration system design.

关键词： CFD model building compost airflow field pile

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Survey on heavy metal concentrations and maturity indices of organic fertilizer in China

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International Journal of Agricultural and Biological Engineering 2018年第6期11卷 172-179页

作者： Xi Zhang Haibo Meng yujun shen Ji Li Jiarui Wang Haibin Zhou Jingtao Ding Jian Wang Liqiu Song Institute of Energy and Environmental Protection Chinese Academy of Agricultural Engineering Planning and DesignBeijing 100125China Key Laboratory of Technologies and Models for Cyclic Utilization from Agricultural Resources Ministry of Agriculture and Rural AffairsBeijing 100125China Beijing Key Laboratory of Farmland Soil Pollution Prevention and Remediation College of Resources and Environmental ScienceChina Agricultural UniversityBeijing 100193China

A nationwide survey of organic fertilizer was carried out in China,and 263 samples were collected to be analyzed for maturity indices(moisture content(MC),pH,electrical conductivity(EC),E4/E6,and germination index(GI))and 7 heavy metals(Cu,Zn,Cd,Pb,Cr,As and Ni).The MC,pH,EC,E4/E6 and GI showed large variations among the organic fertilizer samples with ranges of 6.9%-66.68%,4.40-9.19,0.76-13.38 mS/cm,1.07-9.40,and 10%-150%,respectively.The concentrations of 7 heavy metals(Cu,Zn,Cd,Pb,As,Cr,Ni)were also with large variations at 7.53-580.4,0-2818,0.02-149.3,0(not detected)-1321,0.14-26.9,3.70-1237,and 0(not detected)-214.6 mg/kg dry weight.Compared with the limit values of the Chinese standard for organic fertilizers(NY525-2012),9.51%,73.4%,3.19%,and 3.04%of the samples exceeded the limit values of Cd,Pb,As and Cr,respectively.No limits have been set for Cu,Zn and Ni in China,and 35.0%,13.3%and 16.7%of the samples exceeded the Cu,Zn and Ni limits for composts in Germany,respectively.Monte Carlo simulations indicated that with the continuous application of organic fertilizer,Cu,Zn,Cd,Pb and Cr would accumulate to the risk control standard for soil contamination of agricultural land(GB15618-2018)within a relatively short period.It is urgent to establish suitable limits of heavy metals in organic fertilizer in China to control the risk of heavy metal pollution in agricultural land.

关键词： heavy metal organic fertilizer risk assessment maturity indices

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Metagenome analysis reveals potential microbial functions in topsoil of wheat-maize rotation system with five-year application of fertilizers

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International Journal of Agricultural and Biological Engineering 2019年第6期12卷 177-184页

作者： yujun shen Lixin Zhao Haibo Meng Hongsheng Cheng Jingtao Ding Jiarui Wang Shanshan Dong Xi Zhang Liqiu Song shengwei Zheng Institute of Energy and Environmental Protection Chinese Academy of Agricultural EngineeringBeijing 100125China Key Laboratory of Technologies and Models for Cyclic Utilization from Agricultural Resources Ministry of AgricultureBeijing 100125China Key Laboratory of Energy Resource Utilization from Agriculture Residue Ministry of AgricultureBeijing 100125China

Fertilization mode affects soil quality and ecological health.The effects of four fertilization regimens on lignocellulose content,readily degradable carbohydrate decomposition,and potential microbial functions in the topsoil of a wheat-maize rotation system between 2012 and 2017 were investigated.The fertilization regimens of control(control NFNB),high chemical fertilizer(HCF),high biochar plus low chemical fertilizer(HBLCF),and biochar-based fertilizer(BBF)were compared on soil fundamental properties,microbial structure,and potential function in soil carbohydrate degradation based on metagenome analysis.The diversity of carbohydrate-active enzyme genes in the topsoil microbial consortia in the four trials was primarily distributed within the ten ecologically most dominant phyla.Application of BBF was associated with the lowest decline in total nitrogen and P2O5(2012-2017:6.5%and 28.1%,respectively)and the most effective carbohydrate decomposition(2015-2017:67.0%for cellulose and 59.9%for readily degradable carbohydrate).Carbohydrate transport and metabolism accounted for 6.0%of reads assigned functional classification under the BBF regimen.These findings reveal the ecologically functional diversity of topsoil microorganisms and suggest BBF application as a promising strategy for sustainable agriculture and beneficial to soil health.

关键词： biochar-based fertilizer carbohydrate decomposition genetic function microbial community topsoil

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Effects of different biochars on antibiotic resistance genes during swine manure thermophilic composting

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International Journal of Agricultural and Biological Engineering 2018年第6期11卷 166-171页

作者： Jian Wang Bin Sui yujun shen Haibo Meng Lixin Zhao Haibin Zhou Ran Li Jingtao Ding Hongsheng Cheng Xi Zhang Institute of Energy and Environmental Protection Chinese Academy of Agricultural Engineering Planning and DesignBeijing 100125China Key Laboratory of Technologies and Models for Cyclic Utilization from Agricultural Resources Ministry of Agriculture and Rural Affairs of the People's Republic of ChinaBeijing 100125China Chinese Academy of Agricultural Engineering Planning and Design Beijing 100125China

Elimination of antibiotic resistance genes(ARGs)in animal manure from concentrated animal feeding operations by thermophilic composting has drawn increasing attention.This study investigated the effects of sawdust biochar,corn stover biochar and peanut hull biochar with three spiked levels on ARGs in swine manure during thermophilic composting.Thirteen ARGs corresponding to four classes of antibiotics(tetracyclines,sulfonamides,macrolides and quinolones)were determined in the composting piles.Results indicated that the ten tested composting groups became fully mature after 30-day thermophilic composting process.tetM,tetO and ermB were reduced in all tested groups;tetC and tetG,tetX,sul1,sul2,ermF,qnrD and aac(6’)-Ib were mostly reduced under low level biochar addition but increased under higher level biochar addition;gyrA increased under medium biochar addition and reduced in other groups;oqxB remained comparatively stable throughout the composting process.The addition levels of spiked biochar are more important than types of spiked biochar on the removal of ARGs in the composting pile.The average removal rates of ARGs in the control group,low,medium and high level biochar addition groups were 0.24 logs,0.52-0.72 logs,-0.52-0.18 logs and-0.19-0.21 logs,respectively.In summary,low level biochar addition could enhance the elimination of studied ARGs in swine manure during the composting process,while medium level biochar addition to the composting piles would increase the risk of ARGs’propagation.

关键词： biochar antibiotic resistance genes thermophilic composting swine manure

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不同工艺对牛粪堆沤肥过程气体排放的影响

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农业工程学报 2024年第2期40卷 323-331页

作者：邵浩宸衣淑娟沈玉君孟海波丁京涛程红胜周海宾张冬丽农业农村部规划设计研究院农村能源与环保研究所北京100125 农业农村部资源循环利用技术与模式重点实验室北京100125 黑龙江八一农垦大学工程学院大庆163319

堆沤肥是中国畜禽粪便处理利用的最主要方式。为探究不同堆沤肥方式对温室气体和氨气排放规律和温室效应,在北京市密云区开展了为期71 d的堆沤肥试验,以牛粪和玉米秸秆为原料,分析了静态堆沤(T1)、堆沤+翻抛(T2)、堆沤+覆膜(T3)、翻抛+... 详细信息

堆沤肥是中国畜禽粪便处理利用的最主要方式。为探究不同堆沤肥方式对温室气体和氨气排放规律和温室效应,在北京市密云区开展了为期71 d的堆沤肥试验,以牛粪和玉米秸秆为原料,分析了静态堆沤(T1)、堆沤+翻抛(T2)、堆沤+覆膜(T3)、翻抛+覆膜(T4)等4种方式对堆沤肥过程中腐熟度、温室气体和氨气等指标的影响。结果表明,4个处理的种子发芽指数分别达到131.33%、134.49%、108.76%和136.24%,均满足堆肥产品的腐熟度要求(≥70%)。翻抛有利于CO_(2)、N_(2)O和NH3的排放,而覆膜抑制了N2O的生成,T2处理的增温潜势最高,T3处理的增温潜势最低,较对照组T1处理减排20.14%。因此,T3处理在能够保证堆肥产品的腐熟度要求的前提下,还可有效减少增温潜势。该研究可为中小养殖场户堆沤肥的工艺优化实践提供技术指导。

关键词：粪便堆肥氨气温室气体增温潜势

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Heavy metals and community structure of microorganism changes during livestock manure composting with inoculation of effective microorganisms

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International Journal of Agricultural and Biological Engineering 2020年第6期13卷 125-132页

作者： Haibin Zhou yujun shen Ran Li Haibo Meng Xi Zhang Jian Wang Hongsheng Cheng Shanshan Dong Liqiu Song Jingtao Ding Qiongyi Cheng Academy of Agricultural Planning&Engineering Ministry of Agriculture and Rural Affairs of the People's Republic of ChinaBeijing 100125China Key Laboratory of Technologies and Models for Cyclic Utilization from Agricultural Resources Ministry of Agriculture and Rural Affairs of the People's Republic of ChinaBeijing 100125China

Effective microorganisms(EM)is usually used in composting to improve the composting process.However,the effect of EM on heavy metals evolution was still unclear.This study was performed to illustrate the microbial community changes that occur during composting with the addition of EM and to determine the evolution of heavy metal speciation during this process.The requirement of harmlessness for pig manure was met after the addition of EM at a dosage of 0.5%,with a germination index of 96.42%.The bacterial and fungal diversity were both found to decrease during the composting process.Additionally,the bioavailability of Cu and Pb decreased significantly during composting.Significant correlations were observed between the microbial composition and the percentage of different heavy metals fractions;however,the mechanism responsible for this correlation requires further investigation.This study has the potential to contribute to control of heavy metal contamination during the process of recycling pig manure through the controlled addition of EM.

关键词： effective microorganisms heavy metal microbial communities pig manure composting

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