Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

Water Role and Its Influence on Hydrogen Isotopic Composition of Natural Gas during Gas Generation

In order to discuss the role and influence of water during the generation of natural gas,the participation mechanism of water during the evolution of organic matter and its influences were summarized.In addition,we carried out an anhydrous cracking experiment of oil extracted from the Feixianguan Formation source rock in a closed system,which led to the establishment of the kinetic models for describing carbon and hydrogen isotopic fractionation during gas generation from organic matter.The models were calibrated and then applied to the northeastern Sichuan Basin.By combining a series of gas generation experiments from octadecane pyrolysis without water or with distilled water in varying mass proportions,several results were proved:(1) the hydrogen isotopic composition of natural gas becomes lighter with the participation of formation water;(2) we can quantitatively study the hydrogen isotopic fractionation with the kinetic model for describing carbon isotopic fractionation; (3) more abundant and reliable geological information can be obtained through the combined application of carbon and hydrogen isotopic indices.

Homochiral design of titanium-organic cage for circularly polarized luminescence-based molecular detection

Post-assembly modification strategy is used as an effective approach to improve the functional applications of metal-organic cages. The active vertex of the racemic tetrahedral Ti4L6(L = embonate) cages traps four chiral diamine chelated dinuclear silver ions, obtaining homochiral cages which exhibit helical perovskite stacks. Such a surface modification engineering enables the structural precise cages presenting homochirality and circularly polarized luminescence(CPL) response, further achieving enantioselective recognition toward chiral Camphorquinone molecules and displaying enhanced temperature-dependent effects of CPL output.

Activated PKB/GSK-3β synergizes with PKC-δ signaling in attenuating myocardial ischemia/reperfusion injury via potentiation of NRF2 activity: Therapeutic efficacy of dihydrotanshinone-Ⅰ

Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury(MIRI).NRF2,the endogenous antioxidant regulator,might provide therapeutic benefits.Dihydrotanshinone-Ⅰ(DT)is an active component in Salvia miltiorrhiza with NRF2 induction potency.This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation.DT potently induced NRF2 nuclear accumulation,ameliorating post-reperfusion injuries via redox alterations.Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT.Mechanistically,DT phosphorylated NRF2 at Ser40,rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation.Importantly,we identified PKC-δ-(Thr505)phosphorylation as primary upstream event triggering NRF2-(Ser40)phosphorylation.Knockdown of PKC-δdramatically retained NRF2 in cytoplasm,convincing its pivotal role in mediating NRF2 nuclear-import.NRF2 activity was further enhanced by activated PKB/GSK-3βsignaling via nuclear-export signal blockage independent of PKC-δactivation.By demonstrating independent modulation of PKC-δand PKB/GSK-3β/Fyn signaling,we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations.Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo,further supporting the potential applicability of this rationale.