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

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.

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

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.

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

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.

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

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.

Investigation and analysis of the linkage mechanism and whole process cost of livestock manure organic fertilizer

In recent years,the utilization of manure resources for livestock and poultry farming has attracted a widespread attention,and manure resources utilization models suitable for different regional characteristics have formed gradually.Among them,the production of organic fertilizer from animal manure is a vital utilization method.However,there are still some problems such as high production costs,difficult sales,and the unwillingness of farmers to use organic fertilizers which have affected the breeding cycle and the sustainability of manure treatment in livestock and poultry breeding.This article selected 371 organic fertilizer plants,related farms and farmers in China,focusing on the main links of the entire process of livestock manure-organic fertilizer-farm application,and studied the mode of animal manure collection by organic fertilizer plants.The costs of organic fertilizer production and farmland application were discussed.Moreover,suggestions were made for the promotion and implementation of large-scale organic fertilizers to make good utilization of manure resources in livestock and poultry farming.

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

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.

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

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.

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

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.

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

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.

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

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.