Yi Song

Retinal pigment epithelial (RPE) dysfunction contributes to diabetic retinopathy (DR), but the upstream molecular mediators linking hyperglycemia to mitochondrial injury in RPE cells remain incompletely defined. This study investigated whether p66Shc regulates high glucose (HG)-induced injury in human RPE cells (HRPECs), with a focus on Son of Sevenless 1 (Sos1)–Rac1 signaling. HRPECs were exposed to increasing glucose concentrations or an osmotic control. p66Shc was silenced using siRNA. Protein expression and protein–protein interactions were assessed by Western blotting and co-immunoprecipitation, and subcellular co-localization was evaluated by immunofluorescence. Mitochondrial membrane potential (ΔΨm) and apoptosis were quantified using 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and flow cytometry, respectively. HG exposure increased p66Shc and Rac1 expression in a concentration-and time-dependent manner, whereas osmotic control did not induce comparable changes. HG enhanced Sos1–Rac1 complex formation and increased the co-localization of Sos1 with Rac1. p66Shc knockdown significantly reduced Rac1's abundance, attenuated Sos1–Rac1 interactions, restored ΔΨm, and decreased apoptosis under HG conditions. These findings indicate that p66Shc contributes to HG-induced cellular stress. It promotes Sos1-dependent Rac1 signaling. This process is associated with mitochondrial depolarization and apoptosis in HRPECs. Targeting the p66Shc/Sos1–Rac1 axis may help protect the outer blood–retinal barrier in DR.

Aims: To investigate the association between socioeconomic position (SEP) and sensory impairments (SIs).Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS) (2015). Logistic regressions estimated the odds ratio for associations of SEP with SIs. In addition, Mendelian randomization (MR) analysis was conducted to assess the causal relationship between them with the inverse variance weighting (IVW) estimator. MR-Egger, simple median, weighted median, maximum likelihood, and robust adjusted profile score were employed for sensitivity analyses.Results: In the observational survey, we enrolled 19,690 individuals aged 45 and above. SEP was negatively associated with SIs. Adjusted odds of vision impairment were higher for illiterate (1.50; 95%CI: 1.19, 1.91), less than elementary school diploma (1.76; 95%CI: 1.39, 2.25), middle school diploma (1.53; 95%CI: 1.21, 1.93) and lower income (all p < 0.001). The odds of hearing impairment were significantly higher for people with less than a high school diploma than those with a college degree or higher diploma, for agricultural workers than non-agricultural workers, and for people in low-income families (p < 0.01). The MR analysis also showed that occupation was associated with HI (1.04, 95%CI: 1.01, 1.09, p < 0.05) using IVW.Conclusion: We found that both observational and causal evidence supports the theory that SEP can result in SIs and that timely discovery, targeted management, and education can prevent SIs among middle-aged and older adults.

Background: The purpose of this study was to investigate whether acupuncture is effective at treating dry eye disease among postmenopausal women and to identify the possible mechanisms. Methods: Twenty-eight postmenopausal women with dry eye disease were randomly divided into two groups: an acupuncture plus artificial tears (AC + AT) group and an artificial tears (AT) only group. After baseline examination of clinical parameters and tear sample collection, each patient received the designated modality of topical therapy for 2 months. Posttreatment documentation of clinical parameters was recorded, and tear samples were collected. Tear samples from the AC + AT group were subjected to two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry (2D nano-LC-MS/MS). Western blot analysis was also performed on tear samples from both groups. Results: After treatment, the Ocular Surface Disease Index scores, symptom assessment scores, scores of sign assessment, and tear break-up time were significantly improved in both groups (P=0.000). Symptom assessment scores were significantly improved in the AC + AT group (P=0.000) compared with the AT group. 2D nano-LC-MS/MS identified 2,411 proteins, among which 142 were downregulated and 169 were upregulated. After combined AC + AT treatment, the abundance of secreted proteins was increased, whereas that of cytoplasmic proteins decreased (Pearson’s χ² test, P=0.000, P=0.000, respectively). Proteins involved in immunity and regulation were also more abundant (Pearson’s χ² test, P=0.040, P=0.016, respectively), while components and proliferation-related proteins were downregulated (Pearson’s χ² test, P=0.003, P=0.011, respectively). Conclusion: AC + AT treatment increased protein synthesis and secretion, and improved clinical symptoms. These results indicate that acupuncture may be a complimentary therapy for treating postmenopausal dry eye disease.