Effect of aerobic intermittent exercise on the decreased cognitive ability induced by PM_(2.5)exposure in rats

Objectives:This study aimed to investigate the protective effects and underlying mechanisms of aerobic intermittent exercise on cognitive impairment by PM_(2.5)exposure.Methods:Thirty-two rats were randomly divided into four groups:sedentary,exercise,sedentary+PM_(2.5)exposure,and exercise+PM_(2.5)exposure.The exercise groups underwent 8 weeks of exercise training(5 days of exercise per week).Subsequently,PM_(2.5)exposure groups were subjected to PM_(2.5)for three weeks.Post-exposure,we assessed cognitive abilities(shuttle box test),hippocampal tissue structure,related inflammatory factors(TNF-α,IL-6,IL-1β),the protein of inflammatory responses mechanism(P65,IκκB)and cognitiverelated protein levels(BDNF,Aβ-42).Results:PM_(2.5)exposure caused cognitive impairment,abnormal histopathological changes,reduced cognitive related protein and increased pro-inflammatory cytokine levels.Analysis of shuttle box test data revealed significant main effects on the passive avoidance latency times measured in rats(p<0.05).Aerobic intermittent exercise improves spatial learning decline in rats induced by PM_(2.5).Conversely,the Exercise+PM_(2.5)group demonstrated a significant reduction in latency of 24.9%compared to the Sedentary+PM_(2.5)group(p<0.05,ES=1.41).Conclustion:Aerobic intermittent exercise may help in protecting against the decrease of cognitive ability induced by PM_(2.5)exposure.

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.

Ubiquitin-mediated NFκB degradation pathway

The nuclear factor κB （NFκB） transcription factor plays critical roles in inflammation and immunity. The dysregulation of NFKB is associated with inflammatory and autoimmune diseases and cancer. NFKB activation is negatively regulated by the ubiquitin-dependent proteasomal degradation pathway. In the present review, we discuss recent advances in our understanding of how ubiquitin ligases regulate the NFκB degradation pathway.

Huoxin Pill Reduces Myocardial Ischemia Reperfusion Injury in Rats via TLR4/NFκB/NLRP3 Signaling Pathway

Objective:To explore the protective effect of Huoxin Pill(HXP)on acute myocardial ischemia-reperfusion(MIRI)injury in rats.Methods:Seventy-five adult SD rats were divided into the sham-operated group,model group,positive drug group(diltiazem hydrochloride,DH),high dose group(24 mg/kg,HXP-H)and low dose group(12 mg/kg,HXP-L)of Huoxin Pill(n=15 for every group)according to the complete randomization method.After 1 week of intragastric administration,the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h.Serum was separated and the levels of creatine kinase(CK),creatine kinase isoenzyme(CK-MB)and lactate dehydrogenase(LDH),superoxide dismutase(SOD),and malondialdehyde(MDA),hypersensitive C-reactive protein(hs-CRP)and interleukin-1β(IL-1β)were measured.Myocardial ischemia rate,myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride(TTC).Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN)databases were used to screen for possible active compounds of HXP and their potential therapeutic targets;the results of anti-inflammatory genes associated with MIRI were obtained from GeneC ards,Drugbank,Online Mendelian Inheritance in Man(OMIM),and Therapeutic Target Datebase(TTD)databases was performed;Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment were used to analyze the intersected targets;molecular docking was performed using AutoD ock Tools.Western blot was used to detect the protein expression of Toll-like receptor 4(TLR4)/nuclear factor kappa-B(NFκB)/NOD-like receptor protein 3(NLRP3).Results:Compared with the model group,all doses of HXP significantly reduced the levels of LDH,CK and CK-MB(P<0.05,P<0.01);HXP significantly increased serum activity of SOD(P<0.05,P<0.01);all doses of HXP significantly reduced the levels of hs-CRP and IL-1β(P<0.05,P<0.01)and the myocardial infarction rate and myocardial no-reflow rate(P<0.01).GO enrichment analysis mainly involved positive regulation of gene expression,extracellular space and identical protein binding,KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis.Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4,NFκB and NLRP3 molecules.The protein expressions of TLR4,NFκB and NLRP3 were reduced in the HXP group(P<0.01).Conclusions:HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats,and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4/NFκB/NLRP3 signaling pathway.

通过共掺杂策略优化氮化物电极的反应路径以促进碱性析氢反应动力学

通过优化氮化物的析氢反应(HER)途径来提高反应动力学是氮化物改性的重点.本工作创造性地采用P-阴离子和Ce-阳离子的共掺杂策略构建了P,Ce-FeNi_(3)N/NF电极.该P,Ce-FeNi_(3)N/NF电极在200 mV过电位下的电流密度(340 mA cm^(−2))是商业Pt/C@NF电流密度(174 mA cm^(−2))的两倍.理论计算表明,与FeNi_(3)N/NF的单个Ni活性位点不同,P,Ce-FeNi_(3)N/NF利用双活性位点(Ni和P)机制极大地优化了碱性HER过程中的反应动力学.此外,组装的NiFeCe-LDH/NF||P,Ce-FeNi_(3)N/NF电池仅需要1.537 V的电压即可实现500 mA cm^(−2)的高电流密度.这项工作从反应路径优化和反应动力学改进的角度为实现氮化物优异的电催化性能提供了一种新策略.