P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

Endoplasmic reticulum stress: molecular mechanism and therapeutic targets

The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and autophagy.

Stability and interaction of biochar and iron mineral nanoparticles:effect of pH,ionic strength,and dissolved organic matter

Biochar nanoparticles(BCNPs)and iron mineral nanoparticles(IMNPs),such as ferrihydrite nanoparticles(FHNPs),magnetite nanoparticles(MTNPs),and goethite nanoparticles(GTNPs),are often combined and used in soil remediation.However,the stability and interaction of nanoparticles under various environmental conditions have not been investigated previously.In this study,settling experiments,a semi-empirical model,the Derjaguin-Landau-Verwey-Overbeek(DLVO)theory,scanning electron microscopy(SEM)observations,and quantum chemical calculations were used to study the interaction and heteroaggregation of BCNPs and IMNPs.Settling of BCNPs-FHNPs and BCNPs-GTNPs was stable at neutral and alkaline pH(relative concentration of unsettled nanoparticles C_(res’)=0.679-0.824),whereas fast settling of BCNPs-IMNPs was observed at acidic pH(C_(res’)=0.104-0.628).By contrast,BCNPs-MTNPs consistently showed moderate settling regardless of the mass of magnetite at all pH(C_(res’)=0.423-0.673).Both humic acid(HA,10 mg L^(−1))and ionic strength(IS,10 and 100 mM)facilitated the settling of BCNPs-FHNPs and BCNPs-MTNPs systems,whereas the settling of BCNPs-GTNPs was sensitive only to IS.Fulvic acid(10 mg L^(−1))had a general stabi-lizing effect on the BCNPs-IMNPs systems.The results of SEM and quantum chemical calculations suggested that the interaction between BCNPs and FHNPs(-2755.58 kJ mol^(−1))was stronger than that between BCNPs and GTNPs(−1706.23 kJ mol^(−1))or MTNPs(−1676.73 kJ mol^(−1)).The enhancement of heteroaggregation between BCNPs and IMNPs under unfavorable conditions(acidic pH,HA,and IS)was regulated by the strength of the interaction.Therefore,the enhancement of heteroaggregation of BCNPs-FHNPs was greater than that of BCNPs-MTNPs.In the BCNPs-GTNPs system,the high concentration and elongated structure of GTNPs may contribute greatly to heteroag-gregation and settling with small interactions.Our results highlight the influence of pH,IS,and HA on the interaction between BCNPs and IMNPs.These results will be helpful in the application of BCNPs and IMNPs for soil remediation.