Tofacitinib Mitigates the Increased SARS-CoV-2 Infection Susceptibility Caused by an IBD Risk Variant in the PTPN2 Gene.

Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, triggered a global pandemic with severe medical and socioeconomic consequences. While fatality rates are higher among the elderly and those with underlying comorbidities, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases.

A Herpes Simplex Virus Type-1-Derived Influenza Vaccine Induces Balanced Adaptive Immune Responses and Protects Mice From Lethal Influenza Virus Challenge.

Influenza virus is a major respiratory viral pathogen responsible for the deaths of hundreds of thousands worldwide each year. Current vaccines provide protection primarily by inducing strain-specific antibody responses with the requirement of a match between vaccine strains and circulating strains. It has been suggested that anti-influenza T-cell responses, in addition to antibody responses may provide the broadest protection against different flu strains.

A method for assessing the risk of rockburst based on coal-rock mechanical properties and In-Situ ground stress.

With the increase in mining depth and intensity, dynamic disasters such as rockburst in mines are becoming more severe. Deep resource extraction is characterized by a high in-situ stress geological environment, closely associated with geological dynamic disasters. However, there is currently no quantitative analysis method for the correlation between the two.

Numerical simulation of blasting behavior of rock mass with cavity under high in-situ stress.

With the shift of coal seam mining to the deep, the in-situ stress of coal and rock mass increases gradually. High ground stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different crushing states than low stress conditions. In order to study the blasting expansion rule of rock mass with cavity under high ground stress and the rock mass fracture state under different side stress coefficients.

Numerical simulation of rock blasting under different in-situ stresses and joint conditions.

High primary rock stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different rock breaking states under different primary rock stress conditions. There are a large number of naturally formed joints in rock mass, due to the limitations of laboratory tests, a numerical model of jointed rock mass was established using LS-DYNA software to investigate the evolution of blasting damage under various in-situ stresses and open joints. In this simulation, using the Lagrange-Euler (ALE) procedure and the equation of state (JWL) that defines explosive materials, the study considered different joint thicknesses (2cm, 4cm, and 6cm), joint angles (0°, 30°, 60°, and 90°), and in-situ stress conditions (lateral stress coefficients of 0.

Live-attenuated virus vaccine defective in RNAi suppression induces rapid protection in neonatal and adult mice lacking mature B and T cells.

Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs.

Research on rockburst prevention systems based on the attenuation law of coal and rock vibration wave energy.

During the coal and rock mass fracture process, elastic properties are released and vibration waves are radiated outward. The energy attenuation characteristics of these waves can describe the cumulative damage and elastic energy accumulation of the mass. To investigate coal and rock mass failure characteristics and energy attenuation rules during rockburst, numerical simulation and laboratory testing were utilized to study the energy transfer laws under various parameters.

Harnessing preexisting influenza virus-specific immunity increases antibody responses against SARS-CoV-2.

In pandemic scenarios involving novel human pathogenic viruses, it is highly desirable that vaccines induce strong neutralizing antibodies as quickly as possible. However, current vaccine strategies require multiple immunization doses to produce high titers of neutralizing antibodies and are poorly protective after a single vaccination. We therefore wished to design a vaccine candidate that would induce increased protective immune responses following the first vaccine dose.

A conformational selection mechanism of flavivirus NS5 for species-specific STAT2 inhibition.

Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ZIKV NS5s were shown to facilitate proteosome-mediated protein degradation of human STAT2 (hSTAT2). However, how flavivirus NS5s have evolved for species-specific IFN-suppression remains unclear.

Modeling the effects of cigarette smoke extract on influenza B virus infections in mice.

Influenza B virus (IBV) is a major respiratory viral pathogen. Due to a lack of pandemic potential for IBV, there is a lag in research on IBV pathology and immunological responses compared to IAV. Therefore, the impact of various lifestyle and environmental factors on IBV infections, such as cigarette smoking (CS), remains elusive.

Research on main influencing factors and complete support technology for dynamic pressure and large deformation roadway.

To determine the main factors influencing dynamic pressure and large deformation roadways, a targeted set of support technologies was designed. The 2603 air inlet roadway of the Zhangcun coal mine in Lu'an, Shanxi Province, was taken as an example. The influence of the Wenwangshan South normal fault and in situ stress field on the dynamic pressure roadway was analyzed theoretically, and the main factors influencing this dynamic pressure and large deformation roadway under natural geological conditions were determined.

Insights into fundamental problems of rockburst under the modern structure stress field.

Rockbursts are some of the most severe dynamic disasters in coal mines. In this paper, the discrimination method of the tectonic stress field is proposed by analyzing the modern stress field in China. The tectonic stress field formed by modern tectonic movement guides in situ stress measurements.

Numerical simulation of roadway deformation and failure under different degrees of dynamic disturbance.

Deformation and failure of the roadway surrounding rock under dynamic disturbance were explored, which is essential for the control of the surrounding rock. The impact of dynamic disturbance on the deformation and failure of the roadway surrounding rock was studied from a single factor perspective using numerical simulation software. The disturbance intensity, frequency, and time were determined to affect the deformation and plastic zone of the surrounding rock.

Impact of Protein Nitration on Influenza Virus Infectivity and Immunogenicity.

Influenza viruses are deadly respiratory pathogens of special importance due to their long history of global pandemics. During influenza virus infections, the host responds by producing interferons, which activate interferon-stimulated genes (ISGs) inside target cells. One of these ISGs is inducible nitric oxide synthase (iNOS).

Noncoding RNAs and Deep Learning Neural Network Discriminate Multi-Cancer Types.

Detecting cancers at early stages can dramatically reduce mortality rates. Therefore, practical cancer screening at the population level is needed. To develop a comprehensive detection system to classify multiple cancer types, we integrated an artificial intelligence deep learning neural network and noncoding RNA biomarkers selected from massive data.

Effects of Cigarette Smoking on Influenza Virus/Host Interplay.

Cigarette smoking has been shown to increase the risk of respiratory infection, resulting in the exacerbation of infectious disease outcomes. Influenza viruses are a major respiratory viral pathogen, which are responsible for yearly epidemics that result in between 20,000 and 50,000 deaths in the US alone. However, there are limited general summaries on the impact of cigarette smoking on influenza pathogenic outcomes.

Review Devil's tools: SARS-CoV-2 antagonists against innate immunity.

The unprecedented Coronavirus pandemic of 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Like other coronaviruses, to establish its infection, SARS-CoV-2 is required to overcome the innate interferon (IFN) response, which is the first line of host defense. SARS-CoV-2 has also developed complex antagonism approaches involving almost all its encoding viral proteins.

Joint Genome-Wide Association Analyses Identified 49 Novel Loci For Age at Natural Menopause.

Background: Age at natural menopause (ANM) is an important index for women's health. Either early or late ANM is associated with a series of adverse outcomes later in life. Despite being an inheritable trait, its genetic determinant has not yet been fully understood.

Two conserved oligomer interfaces of NSP7 and NSP8 underpin the dynamic assembly of SARS-CoV-2 RdRP.

Replication of the ∼30 kb-long coronavirus genome is mediated by a complex of non-structural proteins (NSP), in which NSP7 and NSP8 play a critical role in regulating the RNA-dependent RNA polymerase (RdRP) activity of NSP12. The assembly of NSP7, NSP8 and NSP12 proteins is highly dynamic in solution, yet the underlying mechanism remains elusive. We report the crystal structure of the complex between NSP7 and NSP8 of SARS-CoV-2, revealing a 2:2 heterotetrameric form.

Assessment of Causal Direction Between Gut Microbiota and Inflammatory Bowel Disease: A Mendelian Randomization Analysis.

Background: Recent studies have shown that the gut microbiota is closely related to the pathogenesis of Inflammatory Bowel Disease (IBD), but the causal nature is largely unknown. The purpose of this study was to assess the causal relationship between intestinal bacteria and IBD and to identify specific pathogenic bacterial taxa via the Mendelian randomization (MR) analysis.

Materials And Methods: MR analysis was performed on genome-wide association study (GWAS) summary statistics of gut microbiota and IBD.

Noncoding RNAs Serve as the Deadliest Universal Regulators of all Cancers.

Numerous cancer drivers have been identified, but they are specific to a given cancer type and condition; universal cancer drivers and universal cancer mechanisms still remain largely unclear. Here, we identified the deadliest universal drivers for all cancers via developing algorithms to analyze massive RNAseqs and clinical data from The Cancer Genome Atlas (TCGA). In general, noncoding RNAs primarily serve as the most important inducers and suppressors for all types of cancers.

H1 Hemagglutinin Priming Provides Long-Lasting Heterosubtypic Immunity against H5N1 Challenge in the Mouse Model.

Influenza virus infections leave a signature of immune memory that influences future responses to infections with antigenically related strains. It has been hypothesized that the first exposure in life to H1N1 influenza virus imprints the host immune system, potentially resulting in protection from severe infection with H5N1 later in life through hemagglutinin (HA) stalk-specific antibodies. To study the specific role of the HA on protection against infection without interference of cellular immunity or humoral antineuraminidase immunity, we primed mice with influenza B viruses that express an H1 HA (group 1; B-H1), H3 HA (group 2; B-H3), or wild-type influenza B virus and subsequently challenged them at different time points with an H5N1 virus.