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Mitochondria are supposed to be involved in the early pathogenesis of general anesthesia (GA)-induced neurotoxicity and long-term cognitive deficits in developing brains. However, effective pharmacologic agents targeted on mitochondria during GA exposure are lacking. This study explores the protective effects of mitochondrion-targeted antioxidant elamipretide (SS-31) on mitochondrial morphogenesis and cognition in developing rats exposed to isoflurane. Rat pups at postnatal day (PND) 7 were exposed to 1.5% isoflurane for 6 h following intraperitoneal administration of elamipretide or vehicle with 30 min interval. The hippocampus was immediately removed for biochemical assays. Histopathological studies were conducted at PND 21, and behavioral tests were performed at PND 40 or 60. We found that early exposure to isoflurane caused remarkable reactive oxygen species (ROS) accumulation, mitochondrial deformation and neuronal apoptosis in hippocampus. The injury occurrence ultimately gave rise to long-term cognitive deficits in developing rats. Interestingly, pretreatment with elamipretide not only provided protective effect against oxidative stress and mitochondrial damages, but also attenuated isoflurane-induced cognitive deficits. Our data support the notion that mitochondrial damage is an early and long lasting event of GA-induced injury and suggest that elamipretide might have clinically therapeutic benefits for pediatric patients undertaking GA.

Low temperature is an important abiotic stress that negatively affects morphological growth and fruit development in melon (Cucumis melo L.). Chilling stress at the seedling stage causes seedling injury and poor stand establishment, prolonging vegetative growth and delaying fruit harvest. In this study, association mapping was performed for chilling tolerance at the seedling stage on an expanded melon core collection containing 212 diverse accessions by 272 SSRs and 27 CAPSs. Chilling tolerance of the melon seedlings was evaluated by calculating the chilling injury index (CII) in 2016 and 2017. Genetic diversity analysis of the whole accession panel presented two main groups, which corresponded to the two subspecies of C. melo, melo, and agrestis. Both the subspecies were sensitive to chilling but with agrestis being more tolerant. Genome-wide association study (GWAS) was conducted, respectively, on the whole panel and the two subspecies, totally detecting 51 loci that contributed to 74 markertrait associations. Of these associations, 35 were detected in the whole panel, 21 in melo, and 18 in agrestis. About half of the associations identified in the two subspecies were also observed in the whole panel, and seven associations were shared by both the subspecies. CMCT505_Chr.1 was repeatedly detected in different populations with high phenotypic contribution and could be a key locus controlling chilling tolerance in C. melo. Nine loci were selected for evaluation of the phenotypic effects related to their alleles, which identified 11 elite alleles contributing to seedling chilling tolerance. Four such alleles existed in both the subspecies and six in either of the two subspecies. Analysis of 20 parental combinations for their allelic status and phenotypic values showed that the elite alleles collectively contributed to enhancement of the chilling tolerance. Tagging the loci responsible for chilling tolerance may simultaneously favor dissecting the complex adaptability traits and elevate the efficiency to improve chilling tolerance using marker-assisted selection in melon. [ABSTRACT FROM AUTHOR]

Mitochondria are supposed to be involved in the early pathogenesis of general anesthesia (GA)-induced neurotoxicity and long-term cognitive deficits in developing brains. However, effective pharmacologic agents targeted on mitochondria during GA exposure are lacking. This study explores the protective effects of mitochondrion-targeted antioxidant elamipretide (SS-31) on mitochondrial morphogenesis and cognition in developing rats exposed to isoflurane. Rat pups at postnatal day (PND) 7 were exposed to 1.5% isoflurane for 6 h following intraperitoneal administration of elamipretide or vehicle with 30 min interval. The hippocampus was immediately removed for biochemical assays. Histopathological studies were conducted at PND 21, and behavioral tests were performed at PND 40 or 60. We found that early exposure to isoflurane caused remarkable reactive oxygen species (ROS) accumulation, mitochondrial deformation and neuronal apoptosis in hippocampus. The injury occurrence ultimately gave rise to long-term cognitive deficits in developing rats. Interestingly, pretreatment with elamipretide not only provided protective effect against oxidative stress and mitochondrial damages, but also attenuated isoflurane-induced cognitive deficits. Our data support the notion that mitochondrial damage is an early and long lasting event of GA-induced injury and suggest that elamipretide might have clinically therapeutic benefits for pediatric patients undertaking GA. [ABSTRACT FROM AUTHOR]

Background and PurposeOptimal radiation target volumes for breast cancer patients with their first isolated chest wall recurrence (ICWR) after mastectomy are controversial. We aimed to analyze the regional failure patterns and to investigate the role of prophylactic regional nodal irradiation (RNI) for ICWR.Materials and MethodsAltogether 205 patients with ICWR after mastectomy were retrospectively analyzed. Post-recurrence progression-free survival (PFS) and overall survival (OS) rates were calculated by Kaplan-Meier method and the differences were compared with Log-rank test. Competing risk model was used to estimate the subsequent regional recurrence (sRR) and locoregional recurrence (sLRR) rates, and the differences were compared with Gray test.ResultsThe 5-year sRR rate was 25.2% with median follow-up of 88.6 months. Of the 52 patients with sRR, 30 (57.7%) recurred in the axilla, 29 (55.8%) in supraclavicular fossa (SC), and five (9.6%) in internal mammary nodes. Surgery plus radiotherapy was independently associated with better sLRR and PFS rates (p