Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury.Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury.Thus,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease.To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,respectively.Using bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S100 calcium binding protein A9(S100A9)as a potential regulator of mitochondrial function and determined its possible interacting proteins.Interactions between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in vitro.Our data showed that:(1)mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3)in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4)S100A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory effects.Taken together,our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis,and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.

Hydrogen evolution reaction activity enhancement from active site turnover mechanism

Although heteroatom doping is an effective way to improve the catalytic activity of transition metal phosphides(TMPs),the mechanism of activity enhancement needs to be further refined.To this end,we synthesized a Co-doped Ni_(2)P catalyst as a research model and found that the introduction of heterogeneous Co reconstructed the charge distribution around the P site,which effectively enhanced the hydrogen evolution reaction(HER)activity of the pure Ni_(2)P.Based on in-situ Raman real-time monitoring technology,we monitored for the first time that Co doping triggered a switch of the active site(from the original Co-active site to the P-active site),which promoted the adsorption of H_(2)O to enhance the HER activity.The density functional theory(DFT)calculations indicated that the P site of Co-Ni_(2)P expressed the highest activity and the Ni site of pure Ni_(2)P expressed the highest activity,which further confirms the in-situ Raman monitoring results.The active site turnover mechanism discovered in this study will undoubtedly provide more rational and targeted ideas for future catalyst design.

Identification and validation of a major gene for kernel length at the P1 locus in Triticum polonicum

Kernel size, one of the traits that determine wheat yield, is controlled by multiple quantitative trait loci.Polish wheat(Triticum polonicum) has elongated and plump kernel and is a valuable material for breeding high-yielding wheat cultivars. However, genes or loci determining kernel length(KL) in Polish wheat are unknown. We identified and validated a major KL gene, KL-PW, at the P1 locus in Polish wheat. KL-PW is VRT-A2, which encodes a MIKC-type MADS-box protein(MADS55). An insertion/deletion mutation in intron 1 of VRT-A2;led to an alternatively spliced transcript, VRT-A2;. Quantitative PCR analysis showed that VRT-A2;was more highly expressed in developing seeds than was VRT-A2 Ailanmai.Brassinosteroid(BR) sensitivity experiment and the expression of BR-related genes indicated that VRTA2;functions as a positive regulator of BR responses. VRT-A2;significantly increased KL of wheat.These findings not only reveal the molecular basis of KL-PW in controlling KL, but also provide a valuable genetic resource for increasing kernel size in wheat.

3D urchin like V-doped CoP in situ grown on nickel foam as bifunctional electrocatalyst for efficient overall water-splitting

Cobalt phosphide (CoP) is considered to be a potential candidate in the field of electrocatalysis due to its low-cost, abundant resources and high electrochemical stability. However, there is a great space for further improvement of its electrocatalytic performance since its charge transfer rate and catalytic activity have not reached a satisfactory level. Herein, we design and fabricate a three dimensional urchins like V-doped CoP with different amounts of V-doping on nickel foam electrode. The V-doped CoP/NF electrode with optimized amounts of V-doping (10%) exhibits outstanding hydrogen evolution reaction (HER) performance under universal-pH conditions and preeminent oxygen evolution reaction (OER) performance in alkaline media. Notably, the assembled water-splitting cell displays a cell voltage of only 1.53 V at 10 mA·cm−2 and has excellent durability, much better than many reported related bifunctional catalysts. The experiment results and theoretical analysis revealed that vanadium atoms replace cobalt atoms in CoP lattice. Vanadium doping can not only raise the density of electronic states near the Fermi level enhancing the conductivity of the catalyst, but can also optimize the free energy of hydrogen and oxygen-containing intermediates adsorption over CoP, thus promoting its catalytic activity. Moreover, the unique nanostructure of the catalyst provides the various shortened channels for charge transfer and reactant/electrolyte diffusion, which accelerates the electrocatalytic process. Also, the in situ growth strategy can improve the conductivity and stability of the catalyst.

Abatement of sulfide generation in sewage by glutaraldehyde supplementation and the impact on the activated sludge accordingly

Hydrogen sulfide emission in sewer systems is associated with toxicity, corrosion, odour nuisance and high costs treatment. In this study, a novel method to inhibit sulfide generation from sewage by means of glutaraldehyde supplementation has been suggested and evaluated under anaerobic conditions. Different concentra- tions of glutaraldehyde at 10, 15, 20, 30 and 40mg.L1 have been investigated. Besides, the possible impacts of glutaraldehyde supplementation on an activated sludge system and an appraisal of the economic aspects are presented as well. As observed from the experimental results, a dosage of 20 mg. L-1 glutaraldehyde resulted in a significant decrease of the sulfide production by 70%-80% in the simulated sewage. Moreover, the impacts of additional glutaraldehyde at 20mg·L^-1 on activated sludge, in terms of chemical oxygen demand removal and oxygen uptake rates, were negligible. From an economical point of view, the cost of the commercial glutaraldehyde products required in the operation, which was calculated on the basis of activated sulfide removal avoidance, was around ε3.7-4.6 S·kg^-1. Therefore it is suggested that glutaraldehyde supplementation is a feasible technique to abate the sulfide problems in sewer systems. Yet further research is required to elucidate the optimum ＂booster＂ dosage and the dosing frequency in situ accordingly.

Design, Synthesis and Biological Evaluation of Potent and Selective S1PR1 Agonists for the Treatment of Ulcerative Colitis

The binding of Sphingosine-1-phosphate(S1P)with the S1PR1-5 plays a fundamental physiological role in a number of processes including vascular development and stabilization,lymphocyte migration and distribution.S1P-S1PR1 signal axis established roles in immune cell trafficking thus playing a therapeutic role in multiple sclerosis and inflammatory bowel disease.In this study,a series of oxadiazole derivatives were designed and synthesized as S1PR1 agonists based on rational drug design.Among them,compound 9i was identified as a potent and selective S1PR1 agonist with activities onβ-arrestin recruitment(EC50=0.36 nmol/L)and receptor internalization(EC50=8.09 nmol/L).Meanwhile,compound 9i displayed an oral bioavailability up to 93.6%.Based on its excellent activity to S1PR1 and pharmacokinetic properties,compound 9i effectively alleviated dextran sulfate sodium(DSS)-induced ulcerative colitis in mice at a dose of 0.1 mg/kg.