Evidence that offspring traits can be shaped by parental life experiences in an epigenetically inherited manner paves a way for understanding the etiology of depression. Here, we show that F1 offspring born to F0 males of depression-like model are susceptible to depression-like symptoms at the molecular, neuronal, and behavioral levels. Sperm small RNAs, and microRNAs (miRNAs) in particular, exhibit distinct expression profiles in F0 males of depression-like model and recapitulate paternal depressive-like phenotypes in F1 offspring. Neutralization of the abnormal miRNAs in zygotes by antisense strands rescues the acquired depressive-like phenotypes in F1 offspring born to F0 males of depression-like model. Mechanistically, sperm miRNAs reshape early embryonic transcriptional profiles in the core neuronal circuits toward depression-like phenotypes. Overall, the findings reveal a causal role of sperm miRNAs in the inheritance of depression and provide insight into the mechanism underlying susceptibility to depression.

Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks’ continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.

Background:Sleep disturbance is a common problem in liver transplant recipients, but few studies have confirmed the psychosocial factors associated with sleep quality in patients after liver transplantation. This study aimed to identify the psychosocial factors related to sleep quality among liver transplant patients during outpatient follow-up. Material/Methods:A retrospective cross-sectional study was performed in 124 liver transplant patients during outpatient followup. All participants completed a general demographic questionnaire, the Pittsburgh Sleep Quality Index (PSQI), the Generalized Anxiety Disorder-7 scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), and the perceived social support scale (PSSS). Results:The mean global PSQI score was 6.57 (SD, 4.28), which was significantly higher than the mean score for people with normal sleep quality; 50 (40.3%) recipients were classified as having poor sleep quality (PSQI >7). Among the self-reported sleep problems, 62 (50.0%) participants reported that they had to go to the bathroom at night, 58 (43.5%) woke up in the middle of the night or early morning, 84 (67.7%) reported depression symptoms, and 116 (93.5%) had low-level social support. The global PSQI score was positively correlated with anxiety and depression scores, while the global PSSS score was negatively correlated with anxiety and depression scores (p<0.01). Multiple linear regression analysis showed that the length of the post-liver transplant period, the type of residence, BMI, depressive symptoms, and anxiety symptoms were important factors affecting sleep quality among liver transplant patients (p<0.05). Conclusions:Our findings showed high prevalence and incidence of poor sleep quality in liver transplant recipients in outpatient follow-up, with significant correlations with anxiety, depression, and social support, and it was affected by multiple factors. This indicates a need for further research on the follow-up results of sleep and the benefits of comprehensive interventions involving psychosocial factors in liver transplant recipients in China.

Combined chemotherapy and radiotherapy may offer better outcome without the need for extensive resection, and surgery should be reserved to providing tissue for diagnosis. The patients with low-intermediate risk (IPI = 2) or stage IIE need be treated more aggressively.