5- methylcytidine effectively improves spermatogenesis recovery in busulfan-induced oligoasthenospermia mice.

The function and regulatory mechanisms of 5-methylcytidine (m5C) in oligoasthenospermia remain unclear. In this study, we made a mouse model of oligoasthenospermia through the administration of busulfan (BUS). For the first time, we demonstrated that m5C levels decreased in oligoasthenospermia. The m5C levels were upregulated through the treatments of 5-methylcytidine. The testicular morphology and sperm concentrations were improved via upregulating m5C. The cytoskeletal regenerations of testis and sperm were accompanying with m5C treatments. m5C treatments improved T levels and reduced FSH and LH levels. The levels of ROS and MDA were significantly reduced through m5C treatments. RNA sequencing analysis showed m5C treatments increased the expression of genes involved in spermatid differentiation/development and cilium movement. Immunofluorescent staining demonstrated the regeneration of cilium and quantitative PCR (qPCR) confirmed the high expression of genes involved in spermatogenesis. Collectively, our findings suggest that the upregulation of m5C in oligoasthenospermia facilitates testicular morphology recovery and male infertility via multiple pathways, including cytoskeletal regeneration, hormonal levels, attenuating oxidative stress, spermatid differentiation/development and cilium movement. m5C may be a potential therapeutic agent for oligoasthenospermia.

Sound-localization-related activation and functional connectivity of dorsal auditory pathway in relation to demographic, cognitive, and behavioral characteristics in age-related hearing loss.

Background: Patients with age-related hearing loss (ARHL) often struggle with tracking and locating sound sources, but the neural signature associated with these impairments remains unclear. Materials and methods: Using a passive listening task with stimuli from five different horizontal directions in functional magnetic resonance imaging, we defined functional regions of interest (ROIs) of the auditory "where" pathway based on the data of previous literatures and young normal hearing listeners (n = 20). Then, we investigated associations of the demographic, cognitive, and behavioral features of sound localization with task-based activation and connectivity of the ROIs in ARHL patients (n = 22). Results: We found that the increased high-level region activation, such as the premotor cortex and inferior parietal lobule, was associated with increased localization accuracy and cognitive function. Moreover, increased connectivity between the left planum temporale and left superior frontal gyrus was associated with increased localization accuracy in ARHL. Increased connectivity between right primary auditory cortex and right middle temporal gyrus, right premotor cortex and left anterior cingulate cortex, and right planum temporale and left lingual gyrus in ARHL was associated with decreased localization accuracy. Among the ARHL patients, the task-dependent brain activation and connectivity of certain ROIs were associated with education, hearing loss duration, and cognitive function. Conclusion: Consistent with the sensory deprivation hypothesis, in ARHL, sound source identification, which requires advanced processing in the high-level cortex, is impaired, whereas the right-left discrimination, which relies on the primary sensory cortex, is compensated with a tendency to recruit more resources concerning cognition and attention to the auditory sensory cortex. Overall, this study expanded our understanding of the neural mechanisms contributing to sound localization deficits associated with ARHL and may serve as a potential imaging biomarker for investigating and predicting anomalous sound localization.

Comparison of the efficiency of anti-VEGF drugs intravitreal injections treatment with or without retinal laser photocoagulation for macular edema secondary to retinal vein occlusion: A systematic review and meta-analysis.

Objective: To compare the efficiency of anti-VEGF drugs intravitreal injections(IVI) treatment with or without retinal laser photocoagulation(LPC) for macular edema(ME) secondary to retinal vein occlusion(RVO). Methods: The randomized controlled trials and retrospective studies including anti-VEGF drug IVI combined with retinal LPC and single IVI in the treatment of macular edema secondary to RVO were collected in PubMed, Medline, Embase, Cochrane Library, and Web of Science. We extracted the main outcome indicators including the best corrected visual acuity (BCVA), central macular thickness(CMT), the number of injections and the progress of retinal non-perfusion areas(NPAs) for systematic evaluation, to observe whether IVI + LPC could be more effective on the prognosis of RVO. We use Review Manager 5.4 statistical software to analyze the data Results: 527 articles were initially retrieved. We included 20 studies, with a total of 1387 patients who were divided into the combination(IVI + LPC) treatment group and the single IVI group. All the patients completed the ocular examination including BCVA, slit-lamp test, fundus examination and Optical Coherence Tomography(OCT) test before and after each treatment. There was no statistical difference between the combination treatment group and single IVI group on BCVA(WMD = 0.12,95%CI = -3.54-3.78,p = 0.95),CMT(WMD = -4.40,95%CI = -21.33-12.53,p = 0.61) and NPAs(WMD = 0.01,95%CI = -0.28-0.30,p = 0.94).However, the number of IVI was decreased significantly in the combination treatment group in BRVO patients, compared to that in the single IVI group(WMD = -0.69,95%CI = -1.18∼-0.21,p = 0.005). Conclusion: In the treatment of RVO patients with macular edema, the combination of IVI and retinal LPC neither improves BCVA nor reduces CMT significantly compared with the single IVI treatment. However, the combination treatment can decrease the number of intravitreal injections in patients with BRVO, while it is not observed in CRVO patients.