OXR1 maintains the retromer to delay brain aging under dietary restriction.

Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function of OXR1 variants. Multi-omic analyses in flies and humans showed that decreased Mtd/OXR1 is associated with aging and neurological diseases. mtd/OXR1 overexpression rescued age-related visual decline and tauopathy in a fly model. Hence, OXR1 plays a conserved role in preserving retromer function and is critical for neuronal health and longevity.

Sustainable production of lipids from cocoa fatty acid distillate fermentation driven by adaptive evolution in Yarrowia lipolytica.

Single cell oil production using oleaginous yeasts is a promising alternative to animal and plant-derived lipids. But substrate costs for microbial fermentation are a major bottleneck. Using side streams as alternative to substrates like glucose, for growing yeast, is a potential cost-effective solution. By combining a previously reported process of growing yeasts on a solid cocoa fatty acid distillate side stream with adaptive evolution techniques, the growth of oleaginous yeast Yarrowia lipolytica was improved by 2-fold. The lipid titre was also boosted by more than 3-fold. Using transcriptomics, key genes were identified that are possibly involved in tailoring of lipid composition, side stream utilisation and enhancement of lipid titres. Candidate genes were also identified that might enable efficient growth and utilization of fatty acids and triacylglycerides found in cocoa fatty acid distillate. In summary, this research has improved the understanding of side stream utilisation for lipid production in oleaginous yeast.

Unpacking the Experiences of Health Care Professionals About the Web-Based Building Resilience At Work Program During the COVID-19 Pandemic: Framework Analysis.

BACKGROUND: The COVID-19 pandemic has resulted in a greater workload in the health care system. Therefore, health care professionals (HCPs) continue to experience high levels of stress, resulting in mental health disorders. From a preventive perspective, building resilience has been associated with reduced stress and mental health disorders and promotes HCPs' intent to stay. Despite the benefits of resilience training, few studies provided an in-depth understanding of the contextual factors, implementation, and mechanisms of impact that influences the sustainability of resilience programs. Therefore, examining target users' experiences of the resilience program is important. This will provide meaningful information to refine and improve future resilience programs. OBJECTIVE: This qualitative study aims to explore HCPs' experiences of participating in the web-based Building Resilience At Work (BRAW) program. In particular, this study aims to explore the contextual and implementational factors that would influence participants' interaction and outcome from the program. METHODS: A descriptive qualitative approach using individual semistructured Zoom interviews was conducted with participants of the web-based resilience program. A framework analysis was conducted, and it is guided by the process evaluation framework. RESULTS: A total of 33 HCPs participated in this qualitative study. Three themes depicting participants' experiences, interactions, and impacts from the BRAW program were elucidated from the framework analysis: learning from web-based tools, interacting with the BRAW program, and promoting participants' workforce readiness. CONCLUSIONS: Findings show that a web-based asynchronous and self-paced resilience program is an acceptable and feasible approach for HCPs. The program also led to encouraging findings on participants' resilience, intent to stay, and employability. However, continued refinements in the components of the web-based resilience program should be carried out to ensure the sustainability of this intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05130879; https://clinicaltrials.gov/ct2/show/NCT05130879.

Hydroxysafflor yellow A promotes α-synuclein clearance via regulating autophagy in rotenone-induced Parkinson's disease mice.

Autophagy is an intracellular degradation process that is involved in α-synuclein (α-syn) homeostasis and Parkinson's disease (PD). The purpose of this study was to investigate whether hydroxysafflor yellow A (HSYA) could promote α-syn clearance via regulating autophagy in PD mice. Male C57BL/6 mice were intraperitoneally treated with HSYA. Thirty minutes later, they were intragastrically administered with rotenone at a dose of 30 mg/kg. The hanging wire test was performed at 14 and 28 days. Then, autophagosomes and ultrastructural changes were examined by transmission electron microscopy. The expression of tyrosine hydroxylase (TH), α-syn, JNK1, p-JNK1, Bcl-2, p-Bcl-2, Beclin1, autophagy-related proteins (Atg) 7 and 12-5, and the LC3-II/LC3-I ratio were investigated by western blot. The hanging time of HSYA-treated PD mice was significantly increased compared with that of rotenone-induced PD mice (p < 0.05 or p < 0.01). Compared with rotenone-induced PD mice, treatment with HSYA augmented the formation of autophagosomes. The expression of TH, p-JNK1/JNK1, Beclin1, Atg7, Atg12-5, p-Bcl-2/Bcl-2, and the LC3-II/LC3-I ratio were significantly increased, whereas the expression of α-syn was reduced in the rotenone plus HSYA group. These results indicate that HSYA promoted α-syn clearance via regulating autophagy in rotenone-induced PD mice.