Sequential mechanisms underlying concentration invariance in biological olfaction

Concentration invariance—the capacity to recognize a given odorant (analyte) across a range of concentrations—is an unusually difficult problem in the olfactory modality. Nevertheless, humans and other animals are able to recognize known odors across substantial concentration ranges, and this concentration invariance is a highly desirable property for artificial systems as well. Several properties of olfactory systems have been proposed to contribute to concentration invariance, but none of these alone can plausibly achieve full concentration invariance. We here propose that the mammalian olfactory system uses at least six computational mechanisms in series to reduce the concentration-dependent variance in odor representations to a level at which different concentrations of odors evoke reasonably similar representations, while preserving variance arising from differences in odor quality. We suggest that the residual variance then is treated like any other source of stimulus variance, and categorized appropriately into “odors” via perceptual learning. We further show that naïve mice respond to different concentrations of an odorant just as if they were differences in quality, suggesting that, prior to odor categorization, the learning-independent compensatory mechanisms are limited in their capacity to achieve concentration invariance

MicroRNA-575 targets BLID to promote growth and invasion of non-small cell lung cancer cells

AbstractThis study was designed to detect miR-575 expression and function in non-small cell lung cancer (NSCLC). A higher expression of miR-575 in NSCLC tissues was observed compared with adjacent non-neoplastic tissues. Furthermore, re-introduction of miR-575 significantly promoted cell proliferation, migration, and invasion in the NSCLC line. Moreover, we showed that BLID is negatively regulated by miR-575 at the posttranscriptional level, via a specific target site within the 3′UTR. Overexpression of BLID counteracted miR-575-induced proliferation and invasion in NSCLC cells. The expression of BLID is frequently downregulated in NSCLC tumors and cell lines and inversely correlates with miR-575 expression. The findings of this study contribute to the current understanding of the functions of miR-575 in NSCLC

Joint Optimization of Communication and Traffic Efficiency in Vehicular Networks

Consider single-cell downlink vehicular networks, where a base station (BS) employing massive multiple-input multiple-output simultaneously transmits information to multiple vehicles on its covered road. Taking into account both the traffic and communication performance, the Flow rate of vehicles to the Power consumption of the BS Ratio (FPR) is defined as a comprehensive metric to represent the number of vehicles supported under limited transmit power. The objective of this paper is to maximize the FPR while guaranteeing the information rate requirements of the vehicles. We first derive the average power consumption of the BS with respect to vehicle density, based on which the FPR is established by using a flow rate function that quantifies the number of passed vehicles per time unit in terms of traffic density. Then, the optimal vehicle density is given in order to maximize the FPR. Simulation results indicate that the proposed scheme can significantly improve the power efficiency of the vehicular networks.acceptedVersionPeer reviewe

ET-1 receptor type B (ETBR) overexpression associated with ICAM-1 downregulation leads to inflammatory attenuation in experimental autoimmune myocarditis

Background An experimental autoimmune myocarditis rat model was established by subcutaneous injection of porcine myocardial myosin (PCM). The effect of ET-1 receptor type B (ETBR) overexpression on autoimmune myocarditis was observed via tail vein injection of ETBR overexpression lentivirus in rats. We further investigated the mechanisms involved in the regulation of autoimmune myocarditis by ETBR overexpression. Methods Six rats were randomly selected from 24 male Lewis rats as the NC group, and the remaining 18 rats were injected with PCM on Day 0 and Day 7, to establish the experimental autoimmune myocarditis (EAM) rat model. The 18 rats initially immunized were randomly divided into three groups: the EAM group, ETBR-oe group, and GFP group. On Day 21 after the initial immunization of rats, cardiac echocardiography and serum brain natriuretic peptide (BNP) analysis were performed to evaluate cardiac function, myocardial tissue HE staining was performed to assess myocardial tissue inflammatory infiltration and the myocarditis score, and mRNA expression of IFN-γ, IL-12, and IL-17 was detected by qRT-PCR. Subsequently, immunohistochemical analysis was performed to detect the localization and expression of the ETBR and ICAM-1 proteins, and the expression of ETBR and ICAM-1 was verified by qRT-PCR and western blotting methods. Results On Day 21 after initial immunization, left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), and serum BNP concentrations increased in the hearts of rats in the EAM group compared with the NC group (P < 0.01), and ejection fraction (EF) and fractional shortening (FS) decreased compared with those of the normal control (NC) group (P < 0.01). LVEDd, LVEDs, and serum BNP concentrations decreased in the ETBR-oe group compared with the EAM group, while EF and FS increased significantly (P < 0.01). HE staining showed that a large number of inflammatory cell infiltrates, mainly lymphocytes, were observed in the EAM group, and the myocarditis score was significantly higher than that of the NC group (P < 0.01). Compared with that of the EAM group, myocardial tissue inflammatory cell infiltration was significantly reduced in the ETBR-oe group, and the myocarditis scores were significantly lower (P < 0.01). The mRNAs of the inflammatory factors IFN-γ, IL-12 and IL-17 in myocardial tissue of rats in the EAM group exhibited elevated levels compared with those of the NC group (P < 0.01) while the mRNAs of IFN-γ, IL-12 and IL-17 were significantly decreased in the ETBR-oe group compared with the EAM group (P < 0.01). Immunohistochemistry showed that the staining depth of ETBR protein in myocardial tissue was greater in the EAM group than in the NC group, and significantly greater in the ETBR-oe group than in the EAM group, while the staining depth of ICAM-1 was significantly greater in the EAM group than in the NC group, and significantly lower in the ETBR-oe group than in the EAM group. The ICAM-1 expression level was significantly higher in the EAM group than in the NC group (P < 0.01), and was significantly lower in the ETBR-oe groupthan in the EAM group (P < 0.01)

Research on drug treatment and the novel signaling pathway of chronic atrophic gastritis

Background: Chronic atrophic gastritis (CAG) is a global digestive system disease and one of the important causes of gastric cancer. The incidence of CAG has been increasing yearly worldwide. Purpose: This article reviews the latest research on the common causes and future therapeutic targets of CAG as well as the pharmacological effects of corresponding clinical drugs. We provide a detailed theoretical basis for further research on possible methods for the treatment of CAG and reversal of the CAG process. Results: CAG often develops from chronic gastritis, and its main pathological manifestation is atrophy of the gastric mucosa, which can develop into gastric cancer. The drug treatment of CAG can be divided into agents that regulate gastric acid secretion, eradicate Helicobacter. pylori (H. pylori), protect gastric mucous membrane, or inhibit inflammatory factors according to their mechanism of action. Although there are limited specific drugs for the treatment of CAG, progress is being made in defining the pathogenesis and therapeutic targets of the disease. Growing evidence shows that NF-κB, PI3K/AKT, Wnt/ β-catenin, MAPK, Toll-like receptors (TLRs), Hedgehog, and VEGF signaling pathways play an important role in the development of CAG

Factors associated with the willingness and acceptance of SARS-CoV-2 vaccine from adult subjects in China

Aim: We aimed to investigate factors affecting the willingness and acceptance of the SARS-CoV-2 vaccination among adults in China and sources of knowledge about the vaccine. Methods: A cross-sectional, web-based survey was conducted from September 8th to 15th, 2020, comprising of 23 questions. Binary logistic regression analysis was performed to examine factors associated with vaccination willingness and acceptance. Results: A total of 983 questionnaires were included and 81.3% of the participants were willing to receive the SARS-CoV-2 vaccine. With a “bachelor degree or above” (OR = 0.56, p = 0.020) and believing that the vaccine would not cause SARS-CoV-2 infection (OR = 0.50, p = 0.003) were associated with an increased willingness. Aged :30 years (OR = 0.38, p = 0.001), and believing that the vaccine would not cause SARS-CoV-2 infection (OR = 0.52, p = 0.004) were associated with higher acceptance; while from Henan province (OR = 2.49, p < 0.001), not willing to vaccinate (OR = 3.86, p < 0.001), not suffering from chronic diseases (OR = 2.25, p = 0.013), and thinking it was not safe and effective in preventing COVID-19 (OR = 1.94, p = 0.001) were correlated with a lower acceptance. Conclusions: In conclusion, age, education, and vaccine perception might be key factors affecting the vaccine willingness and acceptance. Triggering positive perception of vaccine, especially by targeting those aged <30 years, or those with below bachelor degree, or without chronic diseases might be key approaches for improving the willingness and acceptance of vaccine in China

Clinical Aspects of Gut Microbiota in Hepatocellular Carcinoma Management

Liver cancer, predominantly hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths worldwide. Emerging data highlight the importance of gut homeostasis in the pathogenesis of HCC. Clinical and translational studies revealed the patterns of dysbiosis in HCC patients and their potential role for HCC diagnosis. Research on underlying mechanisms of dysbiosis in HCC development pointed out the direction for improving the treatment and prevention. Despite missing clinical studies, animal models showed that modulation of the gut microbiota by probiotics may become a new way to treat or prevent HCC development

The Roles of Siglec7 and Siglec9 on Natural Killer Cells in Virus Infection and Tumour Progression

The function of natural killer (NK) cells, defending against virus infection and tumour progression, is regulated by multiple activating and inhibiting receptors expressed on NK cells, among which sialic acid-bind immunoglobulin-like lectins (Siglecs) act as a vital inhibitory group. Previous studies have shown that Siglec7 and Siglec9 are expressed on NK cells, which negatively regulate the function of NK cells and modulate the immune response through the interaction of sialic acid-containing ligands. Siglec7 and Siglec9 are very similar in distribution, gene encoding, protein sequences, ligand affinity, and functions in regulating the immune system against virus and cancers, but differences still exist between them. In this review, we aim to discuss the similarities and differences between Siglec7 and Siglec9 and analyze their functions in virus infection and tumour progression in order to develop better anti-viral and anti-tumor immunotherapy in the future

Targeting KRAS-mutant stomach/colorectal tumors by disrupting the ERK2-p53 complex

Summary: KRAS is widely mutated in human cancers, resulting in unchecked tumor proliferation and metastasis, which makes identifying KRAS-targeting therapies a priority. Herein, we observe that mutant KRAS specifically promotes the formation of the ERK2-p53 complex in stomach/colorectal tumor cells. Disruption of this complex by applying MEK1/2 and ERK2 inhibitors elicits strong apoptotic responses in a p53-dependent manner, validated by genome-wide knockout screening. Mechanistically, p53 physically associates with phosphorylated ERK2 through a hydrophobic interaction in the presence of mutant KRAS, which suppresses p53 activation by preventing the recruitment of p300/CBP; trametinib disrupts the ERK2-p53 complex by reducing ERK2 phosphorylation, allowing the acetylation of p53 protein by recruiting p300/CBP; acetylated p53 activates PUMA transcription and thereby kills KRAS-mutant tumors. Our study shows an important role for the ERK2-p53 complex and provides a potential therapeutic strategy for treating KRAS-mutant cancer