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Background Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. Methods The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 10 8 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. Results Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 10 9 /L vs. 1.78 × 10 9 /L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. Conclusions Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 10 9 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. Trial Registration : MEXCOVID, NCT04276987.

Empathy promotes positive physician-patient communication and is associated with improved patient satisfaction, treatment adherence and clinical outcomes. It has been suggested that personality traits should be taken into consideration in programs designed to enhance empathy in medical education due to the association found between personality and empathy among medical students. However, the associations between empathy and big five personality traits in medical education are still underrepresented in the existing literature and relevant studies have not been conducted among medical students in China, where tensions in the physician-patient relationship have been reported as outstanding problems in the context of China's current medical reform. Thus, the main objective of this study was to examine the associations between empathy and big five personality traits among Chinese medical students. A cross-sectional study was conducted in a medical university in Northeast China in June 2016. Self-reported questionnaires including the Interpersonal Reactivity Index (IRI) and Big Five Inventory (BFI) and demographic characteristics were distributed. A total of 530 clinical medical students became our final subjects. Hierarchical regression analysis was performed to explore the effects of big five personality traits on empathy. Results of this study showed that big five personality traits accounted for 19.4%, 18.1%, 30.2% of the variance in three dimensions of empathy, namely, perspective taking, empathic concern and personal distress, respectively. Specifically, agreeableness had a strong positive association with empathic concern (β = 0.477, P<0.01), and a moderate association with perspective taking (β = 0.349, P<0.01). Neuroticism was strongly associated with personal distress (β = 0.526, P<0.01) and modestly associated with perspective taking (β = 0.149, P<0.01). Openness to experience had modest associations with perspective taking (β = 0.150, P<0.01) and personal distress (β = -0.160, P<0.01). Conscientiousness had a modest association with perspective taking (β = 0.173, P<0.01). This study revealed that big five personality traits were important predictors of self-reported measures of both cognitive and affective empathy among Chinese medical students. Therefore, individualized intervention strategies based on personality traits could be integrated into programs to enhance empathy in medical education.

Parkinson's disease (PD) is a progressive movement disorder with multiple non-motor symptoms. Although family genetic mutations only account for a small proportion of the cases, these mutations have provided several lines of evidence for the pathogenesis of PD, such as mitochondrial dysfunction, protein misfolding and aggregation, and the impaired autophagy-lysosome system. Recently, vesicle trafficking defect has emerged as a potential pathogenesis underlying this disease. Rab GTPases, serving as the core regulators of cellular membrane dynamics, may play an important role in the molecular pathway of PD through the complex interplay with numerous factors and PD-related genes. This might shed new light on the potential therapeutic strategies. In this review, we emphasize the important role of Rab GTPases in vesicle trafficking and summarize the interactions between Rab GTPases and different PD-related genes.

Sleep deprivation (SD) is increasingly common in modern society, which can lead to the dysregulation of inflammatory responses and cognitive impairment, but the mechanisms remain unclear. Emerging evidence suggests that gut microbiota plays a critical role in the pathogenesis and development of inflammatory and psychiatric diseases, possibly via gut microbiota–brain interactions and neuroinflammation. The present study investigated the impact of SD on gut microbiota composition and explored whether alterations of the gut microbiota play a causal role in chronic inflammatory states and cognitive impairment that are induced by SD. We found that SD-induced gut dysbiosis, inflammatory responses, and cognitive impairment in humans. Moreover, the absence of the gut microbiota suppressed inflammatory response and cognitive impairment induced by SD in germ-free (GF) mice. Transplantation of the “SD microbiota” into GF mice activated the Toll-like receptor 4/nuclear factor-κB signaling pathway and impaired cognitive function in the recipient mice. Mice that harbored “SD microbiota” also exhibited increases in neuroinflammation and microglial activity in the hippocampus and medial prefrontal cortex. These findings indicate that gut dysbiosis contributes to both peripheral and central inflammatory processes and cognitive deficits that are induced by SD, which may open avenues for potential interventions that can relieve the detrimental consequences of sleep loss.

Circular RNAs (circRNAs) produced from back-spliced exons are widely expressed, but individual circRNA functions remain poorly understood owing to the lack of adequate methods for distinguishing circRNAs from cognate messenger RNAs with overlapping exons. Here, we report that CRISPR–RfxCas13d can effectively discriminate circRNAs from mRNAs by using guide RNAs targeting sequences spanning back-splicing junction (BSJ) sites featured in RNA circles. Using a lentiviral library that targets sequences across BSJ sites of highly expressed human circRNAs, we show that a group of circRNAs are important for cell growth mostly in a cell-type-specific manner and that a common oncogenic circRNA, circFAM120A, promotes cell proliferation by preventing the mRNA for family with sequence similarity 120A (FAM120A) from binding the translation inhibitor IGF2BP2. Further application of RfxCas13d–BSJ-gRNA screening has uncovered circMan1a2, which has regulatory potential in mouse embryo preimplantation development. Together, these results establish CRISPR–RfxCas13d as a useful tool for the discovery and functional study of circRNAs at both individual and large-scale levels.This paper describes a CRISPR–Cas13 system to effectively target circRNAs and screen their functions in vitro and in vivo, which enables the study of relevant circRNA phenotypes in human cell proliferation and in mouse embryogenesis.

In order to improve the personalized recommendation effect of online shopping products, this article combines online fast learning through latent factor model to construct a personalized virtual planning recommendation system for online shopping products. Moreover, this article improves on the ONMTF model. In the problem of cross-domain recommendation, this article clusters users and items in each data domain with hidden scoring patterns and learns common scoring patterns that can be shared between different data domains to deal with the data sparse problem that often occurs in recommender systems. The experimental research results show that cross-domain recommendation can indeed use the implicit semantics or topics between domains to share information and knowledge, thereby improving the accuracy of recommendation.

We study the Hawking evaporation of a class of black hole solutions in dRGT massive gravity, in which the graviton mass gives rise to an effective negative cosmological constant. We found that the effective emission surface can be either proportional to the square of the effective AdS length scale, or corresponds to the square of the impact parameter of the null geodesic that falls onto the photon orbit of the black hole. Furthermore, depending on the black hole parameters, the emission surface could switch from one to another as the black hole loses mass during the evaporation process. Furthermore, the black holes can either evaporate completely or become a remnant at late time. Our result is more generally applicable to any asymptotically anti-de Sitter-like black hole solution in any theory whose metric function has a term linear in the coordinate radius, with massive gravity being only a concrete example.

Trichothecenes are the most common mycotoxins contaminating small grain cereals worldwide. The C12,13 epoxide group in the trichothecenes was identified as a toxic group posing harm to humans, farm animals, and plants. Aerobic biological de-epoxidation is considered the ideal method of controlling these types of mycotoxins. In this study, we isolated a novel trichothecene mycotoxin-de-epoxidating bacterium, Desulfitobacterium sp. PGC-3-9, from a consortium obtained from the soil of a wheat field known for the occurrence of frequent Fusarium head blight epidemics under aerobic conditions. Along with MMYPF media, a combination of two antibiotics (sulfadiazine and trimethoprim) substantially increased the relative abundance of Desulfitobacterium species from 1.55% (aerobic) to 29.11% (aerobic) and 28.63% (anaerobic). A single colony purified strain, PGC-3-9, was isolated and a 16S rRNA sequencing analysis determined that it was Desulfitobacterium. The PGC-3-9 strain completely de-epoxidated HT-2, deoxynivalenol (DON), nivalenol and 15-acetyl deoxynivalenol, and efficiently eliminated DON in wheat grains under aerobic and anaerobic conditions. The strain PGC-3-9 exhibited high DON de-epoxidation activity at a wide range of pH (6–10) and temperature (15–50 °C) values under both conditions. This strain may be used for the development of detoxification agents in the agriculture and feed industries and the isolation of de-epoxidation enzymes.

There are some examples in the literature, in which despite the fact that the underlying theory or model does not impose a lower bound on the size of black holes, the final temperature under Hawking evaporation is nevertheless finite and nonzero. We show that under some loose conditions, the black hole is necessarily an effective remnant, in the sense that its evaporation time is infinite. That is, the final state that there is nonzero finite temperature despite having no black hole remaining cannot be realized. We discuss the limitations, subtleties, and the implications of this result, which is reminiscent of the third law of black hole thermodynamics, but with the roles of temperature and size interchanged. We therefore refer to our result as the “complementary third law” for black hole thermodynamics.

The optimal planning of grid-connected microgrids (MGs) has been extensively studied in recent years. While most of the previous studies have used fixed or time-of-use (TOU) prices for the optimal sizing of MGs, this work introduces real-time pricing (RTP) for implementing a demand response (DR) program according to the national grid prices of Iran. In addition to the long-term planning of MG, the day-ahead operation of MG is also analyzed to get a better understanding of the DR program for daily electricity dispatch. For this purpose, four different days corresponding to the four seasons are selected for further analysis. In addition, various impacts of the proposed DR program on the MG planning results, including sizing and best configuration, net present cost (NPC) and cost of energy (COE), and emission generation by the utility grid, are investigated. The optimization results show that the implementation of the DR program has a positive impact on the technical, economic, and environmental aspects of MG. The NPC and COE are reduced by about USD 3700 and USD 0.0025/kWh, respectively. The component size is also reduced, resulting in a reduction in the initial cost. Carbon emissions are also reduced by 185 kg/year.