Astaxanthin Promotes the Survival of Adipose-Derived Stem Cells by Alleviating Oxidative Stress via Activating the Nrf2 Signaling Pathway.

The survival of free fat grafts is dependent primarily on adipose-derived stem cells (ADSCs); however, ADSCs are susceptible to oxidative stress in the recipient area. Astaxanthin (Axt) is a natural xanthophyll carotenoid with potent antioxidant properties and numerous clinical applications. To date, the therapeutic potential of Axt in fat grafting has not been explored. The purpose of this study is to investigate the effects of Axt on oxidatively stressed ADSCs. An oxidative model of ADSCs was developed to simulate the host's microenvironment. Oxidative insult decreased the protein levels of Cyclin D1, type I collagen alpha 1 (COL1A1), and type II collagen alpha 1 (COL2A1), while increasing the expression of cleaved Caspase 3 and secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in ADSCs. Axt pre-treatment significantly reduced oxidative stress, increased the synthesis of an adipose extracellular matrix, alleviated inflammation, and restored the impaired adipogenic potential in the present model. Furthermore, Axt immensely activated the NF-E2-related factor 2 (Nrf2) pathway, and ML385, an inhibitor of Nrf2, could negate Axt's protective effects. Additionally, Axt alleviated apoptosis by inhibiting bcl-2-associated X protein (BAX)/Caspase 3 signaling and improving the mitochondrial membrane potential (MMP), which could also be abolished by ML385. Our results suggest that Axt may exert its cytoprotective effect on ADSCs through the Nrf2 signaling pathway and could be therapeutic in fat grafting.

The Epoxidation of Carbonyl Compounds with a Benzyne-Triggered Sulfur Ylide.

An efficient method for the synthesis of epoxides from carbonyl compounds, sulfoxides, and benzyne is presented. The strategy involved an epoxidation by a sulfur ylide which is formed in situ from sulfoxide and benzyne through the S-O bond insertion and deprotonation. This one-pot reaction proceeds under mild and base-free conditions, providing a convenient way to introduce the substituted methylene groups onto the carbonyl carbon.

New CRISPR/Cas9-based Fgfr2C361Y/+ mouse model of Crouzon syndrome exhibits skull and behavioral abnormalities.

Crouzon syndrome (CS), a syndromic craniosynostosis, is a craniofacial developmental deformity caused by mutations in fibroblast growth factor receptor 2 (FGFR2). Previous CS mouse models constructed using traditional gene editing techniques faced issues such as low targeting efficiency, extended lineage cycles, and inconsistent and unstable phenotypes. In this study, a CRISPR/Cas9-mediated strategy was employed to induce a functional augmentation of the Fgfr2 point mutation in mice. Various techniques, including bone staining, micro-CT, histological methods, and behavioral experiments, were employed to systematically examine and corroborate phenotypic disparities between mutant mice (Fgfr2C361Y/+) and their wild-type littermates. Confirmed via PCR-Sanger sequencing, we successfully induced the p.Cys361Tyr missense mutation in the Fgfr2 IIIc isoform of the extracellular domain (corresponding to the p.Cys342Tyr mutation in humans) based on Fgfr2-215 transcript (ENSMUST00000122054.8). Fgfr2C361Y/+ mice exhibited characteristics consistent with the phenotypic features associated with CS, including skull-vault craniosynostosis, skull deformity, shallow orbits accompanied by exophthalmos, midface hypoplasia with malocclusion, and shortened skull base, notably without any apparent limb defects. Furthermore, mutant mice displayed behavioral abnormalities encompassing deficits in learning and memory, social interaction, and motor dysfunction, without anxiety-related disorders. Histopathological examination of the hippocampal region revealed structural abnormalities, suggesting possible brain development impairment secondary to craniosynostosis. In conclusion, we constructed a novel gene-edited Fgfr2C361Y/+ mice strain based on CRISPR/Cas9, which displayed skull and behavioral abnormalities, serving as a new model for studying genetic molecular mechanisms and exploring treatments for CS. KEY MESSAGES: CRISPR/Cas9 crafted a Crouzon model by enhancing Fgfr2-C361Y in mice. Fgfr2C361Y/+ mice replicate CS phenotypes-craniosynostosis and midface anomalies. Mutant mice show diverse behavioral abnormalities, impacting learning and memory. Fgfr2C361Y/+ mice offer a novel model for cranial suture studies and therapeutic exploration.

Surgical outcome and patient satisfaction after Z-epicanthoplasty and blepharoplasty.

AIM: To evaluate surgical outcomes of modified Z-epicanthoplasty with blepharoplasty that we previously reported from the patient's perspective using patient-reported outcome measures (PROMs) and patient satisfaction scores. METHODS: A total of patients (n=180) who underwent the surgery between January 2013 and June 2016 were randomly selected. Standardized patient satisfaction forms (total score, 40) and validated PROMs questionnaires (total score, 12) were sent to patients for completion. PROMs assesses the severity of scarring, pain and asymmetry, as well as functional and appearance issues. RESULTS: All patients were female, ranging from 18 to 35 years old (mean=24). The response rate was 73.3% (n=132). The majority of patients reported good or excellent outcomes based on PROM analysis. Patients reported minimum or non-visible scarring at both the double eyelid surgical scar (85.6%) and the inner canthus (80.3%). Issues concerning function and appearance were minimal as 80.3% reported satisfaction with both domains. Notably, the majority of patients reported either a high or very high satisfaction rate to yield a mean score of 104 out of 120 (P<0.05). CONCLUSION: Integration of our modified Z-epicanthoplasty with blepharoplasty produces good outcomes based on PROM results, which shows a positive linear relationship with patient satisfaction scores.

[Numerical modeling analysis of secondary organic aerosol (SOA) combined with the ground-based measurements in the Pearl River Delta region].

Two simulations were conducted with different secondary organic aerosol (SOA) methods-VBS (volatile basis set) approach and SORGAM (secondary organic aerosol model) , which have been coupled in the WRF/Chem (weather research and forecasting model with chemistry) model. Ground-based observation data from 18th to 25th November 2008 were used to examine the model performance of SOA in the Pearl River Delta(PRD)region. The results showed that VBS approach could better reproduce the temporal variation and magnitude of SOA compared with SORGAM, and the mean absolute deviation and correlation coefficient between the observed and the simulated data using VBS approach were -4.88 microg m-3 and 0.91, respectively, while they were -5.32 microg.m-3 and 0. 18 with SORGAM. This is mainly because the VBS approach considers SOA precursors with a wider volatility range and the process of chemical aging in SOA formation. Spatiotemporal distribution of SOA in the PRD from the VBS simulation was also analyzed. The results indicated that the SOA has a significant diurnal variation, and the maximal SOA concentration occurred at noon and in the early afternoon. Because of the transport and the considerable spatial distribution of O3 , the SOA concentrations were different in different PRD cities, and the highest concentration of SOA was observed in the downwind area, including Zhongshan, Zhuhai and Jiangmen.