The importance of alterations in bidirectional communication between gut and brain has become obvious in neuropsychiatric disorders. Gastrointestinal (GI) disturbances are very common in autism spectrum disorders (ASD), and the GI microbiota profiles in children with ASD are significantly different from those in the general population. Fragile X syndrome (FXS) is an inheritable developmental disability in humans, and patients with FXS exhibit autistic behaviors such as mental retardation and impaired social communication or interaction. We hypothesized that an increase in specific gut microbiota by fecal microbiota transplantation (FMT) would mitigate autistic-like behaviors. To test this hypothesis, we measured the effects of FMT from normal mice to Fmr1 KO mice on autistic-like behaviors using several behavioral tests. Because the amounts of A. muciniphila in Fmr1 KO mice was very low, we assessed A. muciniphila population, tested the expression of MUC2, and analyzed goblet cells in the gut after the FMT. We found that FMT ameliorated autistic-like behaviors, especially memory deficits and social withdrawal, and we observed that the levels of A. muciniphila were normalized to wild-type levels. In addition, FMT attenuated the increased levels of TNFα and Iba1 in the brains of Fmr1 KO mice. These results suggest that FMT could be a useful tool for the treatments of cognitive deficits and social withdrawal symptoms observed in FXS or ASD because it increases the population of A. muciniphila and decreases TNFα and Iba1 levels.
  The Von Hippel-Lindau (VHL) E3 ubiquitin ligase, which mediates its substrate hypoxia-inducible factor 1α (HIF-1α) for ubiquitination and subsequent degradation, is an attractive drug target in various diseases, such as anemia, inflammation, neurodegeneration and cancer. Proteolysis targeting chimeras (PROTACs) containing a VHL ligand that can hijack the E3 ligase activity to degrade the target protein has also been studied in academic and in industry areas recently.
 
  Herein, by developing and optimizing the Bayesian Model, we report ensemble-based virtual screening as an effective strategy to discover potential VHL inhibitors from Specs database.
 
  The virtual screening protocol was developed, ten representative molecules were obtained and five compounds were selected for subsequent binding mode analysis to be potent VHL inhibitors.
 The virtual screening protocol was developed, ten representative molecules were obtained and five compounds were selected for subsequent binding mode analysis to be potent VHL inhibitors.The infection epidemic event of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was formally declared a pandemic by World Health Organization on March 11th, 2020. Corona Virus Disease 2019 (COVID-19) is caused by SARS-CoV-2, a new type of coronavirus, which has high contagion and mainly causes respiratory symptoms. With the increase in confirmed cases, however, the infection symptoms turn to be diverse with secondary or first clinical symptoms relating to damage of the cardiovascular system and changes of myocardial enzyme spectrum, cardiac troponin I, electrocardiogram, cardiac function. The occurrence of extra-pulmonary manifestations, including immediately and long-term damage, means that the overall health burden caused by SARS-CoV-2 infection may be under-estimated because COVID-19 patients developed cardiovascular system injury are more likely to become serious. The factors such as directly pathogen-mediated damage to cardiomyocytes, down-regulated angiotensin-converting enzyme 2 (ACE2) expression, excessive inflammatory response, hypoxia and adverse drug reaction, are closely related to the occurrence and development of the course of COVID-19. In combination with recently published medical data of patients having SARS-CoV-2 infection and the latest studies, the manifestations of damage to cardiovascular system by COVID-19, possible pathogenic mechanisms and advances of the treatment are proposed in this article.Environmental enrichment (EE) has been studied as a protocol that can improve brain plasticity and may protect against negative insults such as chronic stress. The aim of this study was to evaluate the effects of EE on the hormonal and behavioral responses induced by chronic mild unpredictable stress (CMS) in rats, considering the involvement of the renin-angiotensin system. Male adult rats were divided into 4 groups control, CMS, EE, and CMS + EE, and the experimental protocol lasted for 7 weeks. EE was performed during 7 weeks, 5 days per week, 2 h per day. CMS was applied during weeks 3, 4, and 5. After the CMS (week 6), depression-like behavior was evaluated by forced swimming and sucrose consumption tests, anxiety level was evaluated using the elevated plus-maze test, and memory was evaluated using the Y-maze test. On week 7, the animals were euthanized and basal plasma levels of corticosterone and catecholamines were determined. The hypothalamus was isolated and tissue levels of angiotensin peptides were evaluated. CMS increased plasma corticosterone, norepinephrine, and epinephrine basal concentrations, induced depression-like behaviors, impaired memory, and increased hypothalamic angiotensin I, II, and IV concentrations. EE decreased stress hormones secretion, depression-like behaviors, memory impairment, and hypothalamic angiotensin II induced by stress. Reductions of anxiety-like behavior and norepinephrine secretion were observed in both stressed and unstressed groups. The results indicated that EE seemed to protect adult rats against hormonal and behavioral CMS effects, and that the reduction of angiotensin II could contribute to these effects.There is a lack of studies regarding the reliability of the event-related components (ERPs) of an electroencephalogram (EEG) used to assess cognitive processing in human subjects. To explore the reliability scores for the P1 and N1 components in two sessions (separated by an average of 116 days), twenty subjects performed a visual lateralized detection paradigm and EEG recording (58 channels) were employed. The session factor did not modulate the P1/N1 latencies. The visual field factor (left (LVF) or right (RVF)) was a determinant for the P1 and N1 topographical distributions as shown in previous studies. Moreover, topographical maps of the grand average showed a very strong correlation level between sessions (>0.9). Finally, individual maps demonstrated that the classic contralateral pattern for the P1 and N1 components was not always present in all subjects.  https://www.selleckchem.com/products/10-dab-10-deacetylbaccatin.html  In particular, compared to the N1 component, the P1 component exhibited a more complex set of individual topographical distributions, revealing that some steps are more heterogeneous among human subjects in early visual processing.