Integrative analysis of genetics, epigenetics and RNA expression data reveal three susceptibility loci for smoking behavior in Chinese Han population.

Despite numerous studies demonstrate that genetics and epigenetics factors play important roles on smoking behavior, our understanding of their functional relevance and coordinated regulation remains largely unknown. Here we present a multiomics study on smoking behavior for Chinese smoker population with the goal of not only identifying smoking-associated functional variants but also deciphering the pathogenesis and mechanism underlying smoking behavior in this under-studied ethnic population. After whole-genome sequencing analysis of 1329 Chinese Han male samples in discovery phase and OpenArray analysis of 3744 samples in replication phase, we discovered that three novel variants located near FOXP1 (rs7635815), and between DGCR6 and PRODH (rs796774020), and in ARVCF (rs148582811) were significantly associated with smoking behavior. Subsequently cis-mQTL and cis-eQTL analysis indicated that these variants correlated significantly with the differential methylation regions (DMRs) or differential expressed genes (DEGs) located in the regions where these variants present. Finally, our in silico multiomics analysis revealed several hub genes, like DRD2, PTPRD, FOXP1, COMT, CTNNAP2, to be synergistic regulated each other in the etiology of smoking.

Evaluating the impact of multiple factors on the control of COVID-19 epidemic: A modelling analysis using India as a case study.

The currently ongoing COVID-19 outbreak remains a global health concern. Understanding the transmission modes of COVID-19 can help develop more effective prevention and control strategies. In this study, we devise a two-strain nonlinear dynamical model with the purpose to shed light on the effect of multiple factors on the outbreak of the epidemic. Our targeted model incorporates the simultaneous transmission of the mutant strain and wild strain, environmental transmission and the implementation of vaccination, in the context of shortage of essential medical resources. By using the nonlinear least-square method, the model is validated based on the daily case data of the second COVID-19 wave in India, which has triggered a heavy load of confirmed cases. We present the formula for the effective reproduction number and give an estimate of it over the time. By conducting Latin Hyperbolic Sampling (LHS), evaluating the partial rank correlation coefficients (PRCCs) and other sensitivity analysis, we have found that increasing the transmission probability in contact with the mutant strain, the proportion of infecteds with mutant strain, the ratio of probability of the vaccinated individuals being infected, or the indirect transmission rate, all could aggravate the outbreak by raising the total number of deaths. We also found that increasing the recovery rate of those infecteds with mutant strain while decreasing their disease-induced death rate, or raising the vaccination rate, both could alleviate the outbreak by reducing the deaths. Our results demonstrate that reducing the prevalence of the mutant strain, improving the clearance of the virus in the environment, and strengthening the ability to treat infected individuals are critical to mitigate and control the spread of COVID-19, especially in the resource-constrained regions.

Probiotic Lactobacillus plantarum GUANKE effectively alleviates allergic rhinitis symptoms by modulating functions of various cytokines and chemokines.

Background: Currently, the prevalence of allergic rhinitis (AR) remains high and there is a great need to develop better and safer ways to alleviate AR symptoms. The Lactobacillus plantarum GUANKE probiotic was reported as an immunomodulator through maintaining Th1/Th2 balance. This study aimed to determine the efficacy of GUANKE in AR subjects. Methods: Adults aged from 18 to 60 years old and previously suffered from AR were recruited and received GUANKE probiotics treatment for 4 weeks. The questionnaires of Total nasal symptom scores (TNSS), total non-nasal symptom score (TNNSS), and rhinitis control assessment test (RCAT) were used to assess the effectiveness before and after treatment. The serum allergen-specific IgE and cytokines were also determined at baseline and after 4 weeks of probiotics administration. Results: The results showed that TNSS and TNNSS were significantly reduced and the RCAT score was significantly increased compared to baseline. The sub-symptom score of rhinorrhea, itching, sneezing, and tearing in each questionnaire also showed significant changes, and the serum IgE level was markedly decreased. We further measured inflammatory-related proteins in serum and found that a total of 20 proteins (6 upregulated and 14 downregulated) were significantly changed compared to baseline, including IL-4, IL-7, IL-20, IL-33, CXCL1, CXCL5, CXCL6, CXCL11, CCL4, CCL23, TGF-alpha, LAP-TGF-beta-1, MMP-1, MMP-10, AXIN1, NT-3, OSM, SCF, CD6, and NRTN. Enrichment analysis showed that these significantly altered proteins were mainly enriched in cytokine and chemokine-related signaling pathways. Conclusion: Taken together, this study demonstrated the Lactobacillus plantarum GUANKE can serve as an effective immunobiotic for the treatment of AR, which is realized through maintaining the Th1/Th2 balance by modulating the functions of various cytokines and chemokines.

The distribution of some extremum on the risk process whose income depend on the current reserve.

This paper considers the distribution of some extremum on the risk process whose income depend on the current reserve. We first construct the defective renewal sequence and obtain the density function of them. By the presented renewal measure and the strong Markov property, the distribution of the first hitting time is obtained explicitly. Then, the ruin probability and the probability that the surplus process less than x is obtained. Furthermore, the distribution of supreme profits before ruin, the joint distributions of the supreme profit and the deficit before the time of the surplus process first up-crossing level zero after ruin, and the joint distributions of the supreme profit and the deficit before the surplus process leave zero ultimately are derived. Finally, the exact calculating results for them are obtained when the individual claim amounts in the compound Poisson risk model are exponentially distributed.