Fasting produces antidepressant-like effects via activating mammalian target of rapamycin complex 1 signaling pathway in ovariectomized mice

Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test.Howeve r,whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established.Therefore,in this study,we simulated perimenopausal depression via an ovariectomy in mice,and subjected them to a single 9-hour fasting 7 days later.We found that the ovariectomy increased the time spent immobile in the forced swimming test,inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefro ntal cortex,and decreased the density of dendritic spines in the hippocampus.The 9-hour acute fasting alleviated the above-mentioned phenomena.Furthermore,all of the antidepressant-like effects of 9-hour fasting were reve rsed by an inhibitor of the mammalian to rget of rapamycin complex 1.Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting.These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus.Thus,fasting may be a potential treatment for depression.

Cyclic Dinucleotide Self-Assembled Nanoparticles as a Carrier-Free Delivery Platform for STING-Mediated Cancer Immunotherapy

Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy target.Currently,CDNs and their derivatives are being investigated clinically.However,the poor bioavailability of exogenous CDNs has limited their application in immunotherapy.Although nanocarriers are widely used for cytosolic delivery of CDNs,their loading capacity is insufficient,and their complicated composition and purification process raises bio-compatibility concerns.Herein,we report a super-simplified CDN self-assembly strategy for carrier-free delivery of CDNs.In the presence of excess K^(+),CDNs form oligomers which further self-assemble with divalent metal ions(such as Mn^(2+))to form nanoparticles(NPs)in aqueous solution.We demonstrate that the self-assembled CDN NPs promote cellular uptake of CDNs and enhance tumor immunogenicity by remodeling the tumor microenvironment,inducing immunogenic tumor cell death and increasing tumorinfiltrating lymphocytes,which is conducive to the generation of tumor neoantigen-specific T-cell responses.We also demonstrate that the use of CDN NPs alone or in combination with immune checkpoint blockades inhibits tumor growth,highlighting the fact that CDN NPs are a potent platform for cancer immunotherapy.

Selective introduction of surface defects in anatase TiO2 nanosheets for highly efficient photocatalytic hydrogen generation

Defect engineering greatly enhances the cat-alytic activity of transition metal semiconductor photocat-alysts.Recently,localized surface defects engineering has been intensively researched,but it still remains challenges on how to tilt the balance to the controllable construction of surface defects rather than bulk ones.Here,we report a facile room-temperature solution processing strategy on(001)facet exposed anatase TiO_(2) nanosheets(ATO),in which localized defects are generated on the surface selectivity with high concentration.To achieve the aspect,lithium-ethylenediamine(Li-EDA)treatment is carried out on(001)facet exposed ATO under a mild condition.The optimized sample exhibits outstanding photocatalytic H_(2) production rates of 9.28 mmol·g^(-1)·h^(-1) with loading 0.5 wt%Pt as co-catalyst(AM 1.5),which is nearly 7.5 times higher than that of the pristine ATO.This defect engi-neering strategy of ATO photocatalyst will spark the ideas for the defects engineering and semiconductor photocata-lyst,which is with important application prospect in solar energy conversion,including hydrogen generation and carbon dioxide reduction.