Microglia in the aging brain: relevance to neurodegeneration

Microglia cells are the brain counterpart of macrophages and function as the first defense in the brain. Although they are neuroprotective in the young brain, microglia cells may be primed to react abnormally to stimuli in the aged brain and to become neurotoxic and destructive during neurodegeneration. Aging-induced immune senescence occurs in the brain as age-associated microglia senescence, which renders microglia to function abnormally and may eventually promote neurodegeneration. Microglia senescence is manifested by both morphological changes and alterations in immunophenotypic expression and inflammatory profile. These changes are likely caused by microinvironmental factors, but intrinsic factors cannot yet be completely excluded. Microglia senescence appears to underlie the switching of microglia from neuroprotective in the young brain to neurotoxic in the aged brain. The hypothesis of microglia senescence during aging offers a novel perspective on their roles in aging-related neurodegeneration. In Parkinson's disease and Alzheimer's disease, over-activation of microglia may play an active role in the pathogenesis because microglia senescence primes them to be neurotoxic during the development of the diseases

Gli effetti del salicilato sulla funzione uditiva: neurotossicità ed acufene

Il salicilato, precursore dell’aspirina, è un farmaco antipiretico, analgesico ed anti-in ammatorio molto diffuso nella pratica clinica. Gli effetti del salicilato sulla funzione uditiva sono noti ed includono, quando somministrato ad alti dosaggi, acufene ed ipoacusia. In periferia, la somministrazione acuta di salicilato induce una riduzione d’ampiezza dei prodotti di distorsione delle otoemissioni acustiche (DPOAE) e del potenziale d’azione composto (CAP), prevalentemente per le basse (<10 kHz) e per le alte (>20 kHz) frequenze; è interessante come questa alterazione corrisponda alla tonalità dell’acufene indotto sperimentalmente nell’animale, che varia tra i 12 e i 16 kHz. La somministrazione cronica induce invece un aumento transitorio dell’ampiezza dei DPOAE ed una up-regulation dell’mRNA e dell’espressione proteica della prestina. In vitro la tossicità del sodio salicilato si evidenzia prevalentemente a livello dei neuroni del ganglio spirale inducendo, a dispetto delle ben note proprietà antiossidanti, un rilascio paradosso di radicale superossido che avvia la catena apoptotica. A livello centrale, il salicilato ha la capacità di alterare la trasmissione GABA e serotonino-mediata inducendo iperattività in speci che popolazioni neuronali. Molto interessanti sono gli effetti a livello della corteccia uditiva e dell’amigdala laterale dove è stata documentata, in seguito alla somministrazione sperimentale di salicilato, una variazione delle frequenze caratteristiche neuronali con una conseguente alterazione della tonotopia siologica, specialmente per le frequenze centrali (10-20 kHz). Nell’uomo gli effetti ototossici del salicilato, oltre ad ipoacusia transitoria ed acufene, includono una diminuita discriminazione verbale e dif coltà nell’integrazione temporale

A new sulfur bioconversion process development for energy- and space-efficient secondary wastewater treatment

Harvesting organic matter from wastewater is widely applied to maximize energy recovery; however, it limits the applicability of secondary treatment for acceptable effluent discharge into surface water bodies. To turn this bottleneck issue into an opportunity, this study developed oxygen-induced thiosulfatE production duRing sulfATe reductiOn (EARTO) to provide an efficient electron donor for wastewater treatment. Typical pretreated wastewater was synthesized with chemical oxygen demand of 110 mg/L, sulfate of 50 mg S/L, and varying dissolved oxygen (DO) and was fed into a moving-bed biofilm reactor (MBBR). The MBBR was operated continuously with a short hydraulic retention time of 40 min for 349 days. The formation rate of thiosulfate reached 0.12-0.18 g S/(m2.d) with a high produced thiosulfate-S/TdS-S ratio of 38-73% when influent DO was 2.7-3.6 mg/L. The sludge yield was 0.23-0.29 gVSS/gCOD, much lower than it was in conventional activated sludge processes. Then, batch tests and metabolism analysis were conducted to confirm the oxygen effect on thiosulfate formation, characterize the roles of sulfate and microbial activities, and explore the mechanism of oxygen-induced thiosulfate formation in ERATO. Results examined that oxygen supply promoted the thiosulfate-Sproduced/TdS-Sproduced ratio from 4% to 24-26%, demonstrated that sulfate and microbial activities were critical for thiosulfate production, and indicated that oxygen induces thiosulfate formation through two pathways: 1) direct sulfide oxidation, and 2) indirect sulfide oxidation, sulfide is first oxidized to S0 (dominant) which then reacts with sulfite derived from oxygen-regulated biological sulfate reduction. The proposed compact ERATO process, featuring high thiosulfate production and low sludge production, supports space- and energy-efficient secondary wastewater treatment.Comment: Written by Chu-Kuan Jiang; edited by Yang-Fan Deng, Hongxiao Guo, Guang-Hao Chen, Di Wu; Corresponding authors: Guang-Hao Chen, Di Wu; Last author (team leader): Guang-Hao Che

N-[(R)-(2-Chloro­phen­yl)(cyclo­pent­yl)meth­yl]-N-[(R)-(2-hydr­oxy-5-methyl­phen­yl)(phen­yl)meth­yl]acetamide

In the title compound, C28H30ClNO2, the cyclo­pentane ring adopts an envelope conformation. In the crystal structure, mol­ecules are linked by inter­molecular O—H⋯O hydrogen bonds, forming chains running along the a axis

2,4-Dichloro-6-((1R)-1-{[(R)-(2-chloro­phen­yl)(cyclo­pent­yl)meth­yl]amino}eth­yl)phenol

In the title compound, C20H22Cl3NO, the five-membered ring adopts an envelope conformation, and the two benzene rings are oriented at a dihedral angle of 40.44 (9)°. Intra­molecular O—H⋯N and N—H⋯Cl hydrogen bonding is present. In the crystal, the mol­ecules are linked via weak inter­molecular C—H⋯O hydrogen bonds