The multiple roles of viral 3Dpol protein in picornavirus infections.

The Picornaviridae are a large group of positive-sense, single-stranded RNA viruses, and most research has focused on the Enterovirus genus, given they present a severe health risk to humans. Other picornaviruses, such as foot-and-mouth disease virus (FMDV) and senecavirus A (SVA), affect agricultural production with high animal mortality to cause huge economic losses. The 3Dpol protein of picornaviruses is widely known to be used for genome replication; however, a growing number of studies have demonstrated its non-polymerase roles, including modulation of host cell biological processes, viral replication complex assembly and localization, autophagy, and innate immune responses. Currently, there is no effective vaccine to control picornavirus diseases widely, and clinical therapeutic strategies have limited efficiency in combating infections. Many efforts have been made to develop different types of drugs to prohibit virus survival; the most important target for drug development is the virus polymerase, a necessary element for virus replication. For picornaviruses, there are also active efforts in targeted 3Dpol drug development. This paper reviews the interaction of 3Dpol proteins with the host and the progress of drug development targeting 3Dpol.

Study progress on the pipeline transportation safety of hydrogen-blended natural gas.

The core of carbon neutrality is the energy structure adjustment and economic structure transformation. Hydrogen energy, as a kind of clean energy with great potential, has provided important support for the implementation of the carbon peaking and carbon neutrality goals of China. How to achieve the large-range, safe, and reliable transportation of hydrogen energy with good economic benefits remains the key to limiting the development of hydrogen energy. Using the existing natural gas pipeline network can save many infrastructure construction costs to transport hydrogen-blended natural gas. However, due to great differences in the physical and chemical properties of hydrogen and natural gas, the transportation of hydrogen-blended natural gas will bring safety risks to the pipeline network operation to a certain extent. In this paper, the influences of pipeline transportation of hydrogen-blended natural gas on existing pipelines and parts along the pipelines are analyzed from two aspects of pipe compatibility and hydrogen blending ratio, and the safety of pipeline transportation of hydrogen-blended natural gas is summarized from two aspects of leakage and accumulation as well as combustion and explosion. In addition, the integrity management of hydrogen-blended natural gas pipelines and the existing relevant standards and specifications are reviewed. This paper points out the shortcomings of current hydrogen-blended natural gas pipeline transportation and gives some relevant suggestions. Hopefully, this work can provide a useful reference for developing a hydrogen-blended natural gas pipeline transportation system.

Pathogenicity and virulence of human respiratory syncytial virus: Multifunctional nonstructural proteins NS1 and NS2.

Human respiratory syncytial virus (hRSV) is a major cause of acute lower respiratory tract infections in children under the age of two as well as in the elderly and immunocompromised worldwide. Despite its discovery over 60 years ago and the global impact on human health, limited specific and effective prophylactic or therapeutic options have been available for hRSV infections. Part of the lack of treatment options is attributed to the legacy of vaccine failure in the 1960s using a formalin-inactivated RSV (FI-RSV), which led to enhancement of disease post exposure to hRSV infection and hampered subsequent development of vaccine candidates. Recent FDA approval of a vaccine for older adults and impending approval for a maternal vaccine are major advancements but leaves children between 6 months and 5 years of age unprotected. Part of this limitation can be attributed to a lack of complete understanding of the factors that contribute to hRSV pathogenesis. The nonstructural proteins NS1 and NS2 are multifunctional virulence factors that are unique to hRSV and that play critical roles during hRSV infection, including antagonizing interferon (IFN) signalling to modulate host responses to hRSV infection. However, the molecular mechanisms by which the nonstructural proteins mediate their IFN inhibitory functions have not been completely defined. Current progress on the characterization of NS1 and NS2 during infection provides deeper insight into their roles. Furthermore, reverse genetics systems for hRSV provide a viable strategy to generate attenuated viruses by introduction of select mutations while maintaining immunogenicity required to elicit a long-term protective response. Here we will review the current state of knowledge of the nonstructural proteins, their contributions to RSV pathogenesis, and their potential as targets for therapeutic development.

Effects of early standardized management on the growth trajectory of offspring with gestational diabetes mellitus at 0-5 years old: a preliminary longitudinal study.

To explore the application value of early standardized management in the delivery of neonates of pregnant women with gestational diabetes mellitus (GDM). Parturient diagnosed with GDM and their offspring were selected in our hospital from January 1, 2015 to December 31, 2017 to underwent early standardized management. Non-GDM pregnant women and their offspring were selected as the control group. The growth and development of children aged 0-5 years in the two groups were longitudinally followed up, and the mixed linear model was used to evaluate and compare the growth trajectories. There was no significant difference in height and weight between the two groups at 1 year old (P > 0.05), but the BMI of the GDM group was significantly higher than that in the control group. After 1 year of age, both groups of offspring were similar in height, weight, and BMI, and these similarities persisted at 2, 3, 4, and 5 years of age. After controlling for covariates, the weight, length/height of the two groups of children were slightly different in the growth trajectories between 0-1 years old, 1-2 years old, 2-3 years old, 3-4 years old, and 4-5 years old with no statistical significance (P > 0.05). Although growth differences between the two groups of children were detected within 1 year of age, there were no significant differences in growth trajectories from 1 to 5 years between two groups, which proved that early standardized management has positive significance.

The characteristic of competitive adsorption of HCHO and C6H6 on activated carbon by molecular simulation.

To explore the characteristic of competitive adsorption of formaldehyde (HCHO) and benzene(C6H6) on activated carbon, the slit models of activated carbon with different pore sizes of 1 nm, 2 nm and 4 nm were constructed by using the Visualizer module of Materials Studio molecular simulation software. The adsorption of single-component C6H6 and HCHO at three different temperatures of 288.15K,293.15K and 323.15K were conducted by the method of grand canonical Monte Carlo. Experiments were carried out to verify the accuracy of simulation results. For the single-compound adsorption, the adsorption amount of C6H6 varied little at different temperature conditions, while the pore size had a significant effect on the adsorption amount of C6H6, and the adsorption capability increased as the pore size goes up. The adsorption capacity of HCHO decreased as the temperature goes up, and the adsorption capacity of both 1 nm and 4 nm pore size activated carbon was less than that of 2 nm pore size. As for the competitive adsorption, HCHO has a better adsorption effect by activated carbon when the pore is in small size like 1 nm, while the competitive adsorption ability of C6H6 is much better than HCHO as the pore size goes up to 2 nm or 4 nm.Implications: (1) Understanding the equilibrium process of activated carbon adsorption at the molecular level based on the co-existence of multi-component VOCs. (2) The effects of concentration, temperature and humidity factors on the coupling of the dynamic equilibrium of competing adsorption of benzene and formaldehyde were analyzed. (3) The accuracy of the molecular simulations was verified using an experimental approach.

Targeting BCAA metabolism to potentiate metformin's therapeutic efficacy in the treatment of diabetes in mice.

AIMS/HYPOTHESIS: An increasing body of evidence has shown that the catabolism of branched-chain amino acids (BCAAs; leucine, isoleucine and valine) is impaired in obese animals and humans, contributing to the development of insulin resistance and type 2 diabetes. Promoting BCAA catabolism benefits glycaemic control. It remains unclear whether BCAA catabolism plays a role in the therapeutic efficacy of currently used glucose-lowering drugs such as metformin. METHODS: Mice were treated with vehicle or metformin (250 mg/kg per day) for more than 4 weeks to investigate the effects of metformin in vivo. In vitro, primary mouse hepatocytes and HepG2 cells were treated with 2 mmol/l metformin. The therapeutic efficacy of metformin in the treatment of type 2 diabetes was assessed in genetically obese (ob/ob) mice and high-fat-diet-induced obese (DIO) mice. Enhancing BCAA catabolism was achieved with a pharmacological agent, 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2). The ob/ob mice were treated with a low-BCAA diet or intermittent protein restriction (IPR) to reduce BCAA nutritional intake. RESULTS: Metformin unexpectedly inhibited the catabolism of BCAAs in obese mice, resulting in an elevation of BCAA abundance. AMP-activated protein kinase (AMPK) mediated the impact of metformin on BCAA catabolism in hepatocytes. Importantly, enhancing BCAA catabolism via a pharmacological agent BT2 significantly potentiated the glucose-lowering effect of metformin while decreasing circulating BCAA levels in ob/ob and DIO mice. Similar outcomes were achieved by a nutritional approach of reducing BCAA intake. IPR also effectively reduced the circulating BCAA abundance and enhanced metformin's glucose-lowering effect in ob/ob mice. BT2 and IPR treatments reduced the expression of fructose-1,6-bisphosphatase 1, a rate-limiting enzyme in gluconeogenesis, in the kidney but not liver, indicating the involvement of renal gluconeogenesis. CONCLUSIONS/INTERPRETATION: Metformin self-limits its therapeutic efficacy in the treatment of type 2 diabetes by triggering the suppression of BCAA catabolism. Enhancing BCAA catabolism pharmacologically or reducing BCAA intake nutritionally potentiates the glucose-lowering effect of metformin. These data highlight the nutritional impact of protein on metformin's therapeutic efficacy and provide new strategies targeting BCAA metabolism to improve metformin's effects on the clinical outcome in diabetes.

The relationship between screen time and attention deficit/hyperactivity disorder in Chinese preschool children under the multichild policy: a cross-sectional survey.

BACKGROUND: Long screen time has become a public health problem that cannot be ignored. The association between screen time and attention-deficit/hyperactivity disorder (ADHD) in preschool children has received widespread attention. METHODS: A questionnaire was used to survey 2452 people. ADHD symptoms were assessed by the Conners Child Behavior Scale. Considering that the ADHD symptoms of boys and girls might be different, we stratified the data by gender. Logistic regression model was used for regression analysis. To exclude the influence of multichild family and obesity level, we also conducted a sensitivity analysis. P values were two-tailed with a significance level at 0.05. RESULTS: The results showed that the association between screen time and ADHD symptoms in preschool children was significant (OR = 1.826, 95%CI: 1.032, 3.232). After grouping the genders, the correlation was not significant. There was an association between screen time and ADHD symptoms in children from families with multiple children. However, after excluding overweight and obese children from the overall population, the association between screen time and ADHD symptoms did not have statistical significance. CONCLUSIONS: The issue of screen time for preschoolers needs to be taken seriously. Although the results indicate a significant correlation between screen time and ADHD symptoms, clearer evidence is needed to provide recommendations to policy makers.

Association between low blood selenium concentrations and poor hand grip strength in United States adults participating in NHANES (2011-2014).

The trace element selenium, which is found in selenoproteins, plays an antioxidant role in preventing muscle tissue injury. A positive association between selenium concentrations and hand grip strength has been reported in older adults; however, the evidence of this association is scarce in general adults. In this study, we aimed to evaluate the association between blood selenium concentrations and low hand grip strength using the data from the National Health and Nutrition Examination Survey 2011-2012 and 2013-2014 in the United States (US). Logistic regression was used to calculate the odds ratio (OR) of low hand grip strength, with blood selenium level adjusted for potential confounders. Among 8158 adults (women: 51.59%) with a mean age of 47 (range: 18-80) years, women and non-Hispanic Blacks tended to have low blood selenium concentrations. Notably, participants with high blood selenium concentrations (range, 178.1-192.5 µg/L) were more likely to have a low risk of low hand grip strength after adjusting for the potential covariates (OR: 0.60, 95% confidence interval (CI): 0.38-0.95) than those with low blood selenium concentrations. After excluding participants with chronic diseases, high blood selenium concentrations were found to be associated with a low risk of low hand grip strength (OR: 0.30, 95% CI: 0.14-0.65). A J-shaped relationship was found between selenium concentrations and low hand grip strength (P for nonlinear trend <0.0001). Subgroup analyses revealed a significantly consistent relationship among women, non-Hispanic Whites and others, and individuals with overweight or obesity (P < 0.05). Our study suggests that blood selenium concentrations are inversely associated with hand grip strength in general US adults. However, further prospective studies are required to confirm the causality between selenium concentrations and hand grip strength.

Research on the Maturity Evaluation Model of Enterprise Safety Culture.

To regulate the safety behavior of employees and improve the occupational safety level of enterprises. Based on the perspective of safety culture, this paper designed an index system based on the four dimensions of safety concept, system, behavior, and physical culture, and it explored a new quantitative assessment method of safety culture level by introducing the concept of maturity into the evaluation of safety culture using the grey fuzzy comprehensive evaluation method. Combining the characteristics of enterprise safety culture, safety culture was divided into five levels, including original level, starting level, development level, completion level, and leading level, and the maturity model of enterprise safety culture was established. Finally, taking an enterprise to be evaluated as an example, the evaluation steps and application of evaluation results were introduced. The results showed that the evaluation model of enterprise safety culture maturity constructed in this paper provides systematic measurement indexes and scientific evaluation methods for evaluating the safety culture maturity of enterprises.

The Foot-and-Mouth Disease Virus Lb Protease Cleaves Intracellular Transcription Factors STAT1 and STAT2 to Antagonize IFN-ß-Induced Signaling.

Foot-and-mouth disease virus (FMDV) is the causative agent of foot-and-mouth disease, one of the most highly infectious animal viruses throughout the world. The JAK-STAT signaling pathway is a highly conserved pathway for IFN-ß-induced antiviral gene expression. Previous studies have shown that FMDV can strongly suppress the innate immune response. Moreover, although STAT1 and STAT2 (STAT1/2) have been well established in JAK-STAT signaling-induced antiviral gene expression, whether FMDV proteins inhibit IFN-ß-induced JAK-STAT signaling remains poorly understood. In this study, we described the Lb leader protease (Lbpro) of FMDV as a candidate for inhibiting IFN-ß-induced signaling transduction via directly interacting with STAT1/2. We further showed that Lbpro colocalized with STAT1/2 to inhibit their nuclear translocation. Importantly, Lbpro cleaved STAT1/2 to inhibit IFN-ß-induced signal transduction, whereas the catalytically inactive mutant of LC51A (Lbpro with cysteine substituted with alanine at amino acid residue 51) had no effect on the stability of STAT1/2 proteins. The cleavage of the STAT1/2 proteins was also determined during FMDV infection in vitro. Lbpro could cleave the residues between 252 and 502 aa for STAT1 and the site spanning residues 140 - 150 aa (QQHEIESRIL) for STAT2. The in vivo results showed that Lbpro can cleave STAT1/2 in pigs. Overall, our findings suggest that FMDV Lbpro-mediated targeting of STAT1/2 may reveal a novel mechanism for viral immune evasion.

Working memory-related alterations in neural oscillations reveal the influence of in-vehicle toluene on cognition at low concentration.

Although toluene is a typical in-vehicle pollutant, the impacts of in-vehicle toluene exposure on cognitive functions remain unestablished. Therefore, this study aimed to investigate the effects of short-term toluene exposure in vehicles on working memory based on neural oscillations. In total, 24 healthy adults were recruited. Each subject was exposed to four different concentrations of toluene and divided into 0 ppb, 17.5 ppb, 35 ppb, and 70 ppb groups for self-control studies. After 4 h of exposure to each concentration of toluene, a behavioral test of visual working memory was performed while 19-channel electroencephalogram (EEG) signals were collected. Meanwhile, the power spectral density (PSD) and spatial distribution of working memory encoding, maintenance, and extraction periods were calculated by short-time Fourier transform to clarify the characteristic frequency bands, major brain regions, and characteristic channels of each period. To compare the changes in the characteristic patterns of neural oscillations under the effect of different concentrations of toluene. There was no significant difference in working memory reaction time and correct rate between the groups at different toluene concentrations (p > 0.05). The characteristic frequency band of the working memory neural oscillations in each group was the theta frequency band; the PSD of the theta frequency band was predominantly concentrated in the frontal area, and the characteristic channel was the Fz channel. The whole brain (F = 3.817, p < 0.05; F = 4.758, p < 0.01; F = 3.694, p < 0.05), the frontal area (F = 2.505, p < 0.05; F = 2.839, p < 0.05; F = 6.068, p < 0.05), the Fz channel (F = 3.522, p < 0.05; F = 3.745, p < 0.05; F = 6.526, p < 0.05), and the PSD of working memory in the theta frequency band was significantly increased in the 70 ppb group compared with the other three groups during the coding, maintenance, and retrieval phases of working memory. When the in-vehicle toluene exposure concentration was 70 ppb, the PSD of the characteristic frequency bands of working memory was significantly increased in the whole brain, major brain regions, and characteristic channels.

Sildenafil Inhibits the Growth and Epithelial-to-mesenchymal Transition of Cervical Cancer via the TGF-ß1/Smad2/3 Pathway.

AIMS: The study aims to explore new potential treatments for cervical cancer. BACKGROUND: Cervical cancer is the second most common cancer in women, causing >250,000 deaths worldwide. Patients with cervical cancer are mainly treated with platinum compounds, which often cause severe toxic reactions. Furthermore, the long-term use of platinum compounds can reduce the sensitivity of cancer cells to chemotherapy and increase the drug resistance of cervical cancer. Therefore, exploring new treatment options is meaningful for cervical cancer. OBJECTIVE: The present study was to investigate the effect of sildenafil on the growth and epithelial-tomesenchymal transition (EMT) of cervical cancer. METHODS: HeLa and SiHa cells were treated with sildenafil for different durations. Cell viability, clonogenicity, wound healing, and Transwell assays were performed. The levels of transforming growth factor-ß1 (TGF-ß1), transforming growth factor-ß type I receptor (TßRI), phosphorylated (p-) Smad2 and p-Smad3 in cervical cancer samples were measured. TGF-ß1, Smad2 or Smad3 were overexpressed in HeLa cells, and we measured the expression of EMT marker proteins and the changes in cell viability, colony formation, etc. Finally, HeLa cells were used to establish a nude mouse xenograft model with sildenafil treatment. The survival rate of mice and the tumor size were recorded. RESULTS: High concentrations of sildenafil (1.0-2.0 µM) reduced cell viability, the number of HeLa and SiHa colonies, and the invasion/migration ability of HeLa and SiHa cells in a dose- and time-dependent manner. The expression of TGF-ß1, TßRI, p-Smad2 and p-Smad3 was significantly enhanced in cervical cancer samples and cervical cancer cell lines. Sildenafil inhibited the expression of TGF-ß1-induced EMT marker proteins (Snail, vimentin, Twist, E-cadherin and N-cadherin) and p-Smad2/3 in HeLa cells. Overexpression of TGF-ß1, Smad2, and Smad3 reversed the effect of sildenafil on EMT, viability, colony formation, migration, and invasion ability of HeLa cells. In the in vivo study, sildenafil significantly increased mouse survival rates and suppressed xenograft growth. CONCLUSION: Sildenafil inhibits the proliferation, invasion ability, and EMT of human cervical cancer cells by regulating the TGF-ß1/Smad2/3 pathway.

A model to evaluate ozone distribution and reaction byproducts in aircraft cabin environments.

Ozone and byproducts of ozone-initiated reactions are among the primary pollutants in aircraft cabins. However, investigations of the spatial distribution and reaction mechanisms of these pollutants are insufficient. This study established a computational fluid dynamics-based model to evaluate ozone and byproduct distribution, considering ozone reactions in air, adsorption onto surfaces, and byproduct desorption from surfaces. The model was implemented in an authentic single-aisle aircraft cabin and validated by measurements recorded during the aircraft cruise phase. Ozone concentrations in the supply air-dominated area were approximately 50% higher than that in the passenger breathing zone, suggesting that human surfaces represent a significant ozone sink. The deposition velocity onto human bodies was 21.83 m/h, surpassing 3.97 m/h on other cabin interior surface areas. Our model provides a mechanistic tool to analyze ozone and byproduct concentration distributions, which would be useful for assessing passenger health risks and for developing strategies for healthier aircraft cabin environments.

Prediction and Analysis of Contemporary College Students' Mental Health Based on Neural Network.

For an ordinary student who has just graduated from high school, interpersonal communication and performance evaluation on campus is also a huge challenge. In order to solve the future and current competition and pressure faced by contemporary college students, many college students have mental health problems. This paper evaluates, predicts, and analyzes the mental health status of contemporary college students based on a neural network algorithm. The computer technology of neural network algorithm is applied to the prediction of contemporary college students' mental health. Data mining technology based on a neural network algorithm is used to collect data sources. Finally, the prediction results are analyzed, and the main psychological stressor factors of contemporary college students are analyzed by cluster analysis. The results show that there is no significant correlation between college Students' inferiority complex and dependency map and the incidence of mental diseases and majors. A comprehensive physical symptom test was conducted on individuals to understand students' psychological characteristics and behavior.

Combinational Deletions of MGF360-9L and MGF505-7R Attenuated Highly Virulent African Swine Fever Virus and Conferred Protection against Homologous Challenge.

Multigene family (MGF) gene products are increasingly reported to be implicated in African swine fever virus (ASFV) virulence and attenuation of host defenses, among which the MGF360-9L and MGF505-7R gene products are characterized by convergent but distinct mechanisms of immune evasion. Herein, a recombinant ASFV mutant, ASFV-Δ9L/Δ7R, bearing combinational deletions of MGF360-9L and MGF505-7R, was constructed from the highly virulent ASFV strain CN/GS/2018 of genotype II that is currently circulating in China. Pigs inoculated intramuscularly with 104 50% hemadsorption doses (HAD50) of the mutant remained clinically healthy without any serious side effects. Importantly, in a virulence challenge, all four within-pen contact pigs demonstrated clinical signs and pathological findings consistent with ASF. In contrast, vaccinated pigs (5/6) were protected and clinical indicators tended to be normal, accompanied by extensive tissue repairs. Similar to most viral infections, innate immunity and both humoral and cellular immune responses appeared to be vital for protection. Notably, transcriptome sequencing (RNA-seq) and quantitative PCR (qPCR) analysis revealed a regulatory function of the mutant in dramatic and sustained expression of type I/III interferons and inflammatory and innate immune genes in vitro. Furthermore, infection with the mutant elicited an early and robust p30-specific IgG response, which coincided and was strongly correlated with the protective efficacy. Analysis of the cellular response revealed a strong ASFV-specific interferon gamma (IFN-γ) response and immunostaining of CD4+ T cells coupled with a high level of CD163+ macrophage infiltration in spleens of vaccinated pigs. Our study identifies a new mechanism of immunological regulation by ASFV MGFs that rationalizes the design of live attenuated vaccine for implementation of improved control strategies to eradicate ASFV. IMPORTANCE Currently, the deficiency in commercially available vaccines or therapeutic options against African swine fever constitutes a matter of major concern in the swine industry globally. Here, we report the design and construction of a recombinant ASFV mutant harboring combinational deletions of interferon inhibitors MGF360-9L and MGF505-7R based on a genotype II ASFV CN/GS/2018 strain currently circulating in China. The mutant was completely attenuated when inoculated at a high dose of 104 HAD50. In the virulence challenge with homologous virus, sterile immunity was achieved, demonstrating the mutant's potential as a promising vaccine candidate. This sufficiency of effectiveness supports the claim that this live attenuated virus may be a viable vaccine option with which to fight ASF.

FMDV 3A Antagonizes the Effect of ANXA1 to Positively Modulate Viral Replication.

The RIG-I-like receptor signaling pathway is crucial for producing type I interferon (IFN-I) against RNA viruses. The present study observed that viral infection increased annexin-A1 (ANXA1) expression, and ANXA1 then promoted RNA virus-induced IFN-I production. Compared to ANXA1 wild-type cells, ANXA1-/- knockout cells showed IFN-ß production decreasing after viral stimulation. RNA virus stimulation induced ANXA1 to regulate IFN-ß production through the TBK1-IRF3 axis but not through the NF-κB axis. ANXA1 also interacted with JAK1 and STAT1 to increase signal transduction induced by IFN-ß or IFN-γ. We assessed the effect of ANXA1 on the replication of foot-and-mouth disease virus (FMDV) and found that ANXA1 inhibits FMDV replication dependent on IFN-I production. FMDV 3A plays critical roles in viral replication and host range. The results showed that FMDV 3A interacts with ANXA1 to inhibit its ability to promote IFN-ß production. We also demonstrated that FMDV 3A inhibits the formation of ANXA1-TBK1 complex. These results indicate that ANXA1 positively regulates RNA virus-stimulated IFN-ß production and FMDV 3A antagonizes ANXA1-promoted IFN-ß production to modulate viral replication. IMPORTANCE FMDV is a pathogen that causes one of the world's most destructive and highly contagious animal diseases. The FMDV 3A protein plays a critical role in viral replication and host range. Although 3A is one of the viral proteins that influences FMDV virulence, its underlying mechanisms remain unclear. ANXA1 is involved in immune activation against pathogens. The present study demonstrated that FMDV increases ANXA1 expression, while ANXA1 inhibits FMDV replication. The results also showed that ANXA1 promotes RNA virus-induced IFN-I production through the IRF3 axis at VISA and TBK1 levels. ANXA1 was also found to interact with JAK1 and STAT1 to strengthen signal transduction induced by IFN-ß and IFN-γ. 3A interacted with ANXA1 to inhibit ANXA1-TBK1 complex formation, thereby antagonizing the inhibitory effect of ANXA1 on FMDV replication. This study helps to elucidate the mechanism underlying the effect of the 3A protein on FMDV replication.

Senecavirus a 3D Interacts with NLRP3 to Induce IL-1ß Production by Activating NF-κB and Ion Channel Signals.

Senecavirus A (SVA) infection induces inflammation in animals, such as fever, diarrhea, vesicles and erosions, and even death. The inflammatory cytokine interleukin-1ß (IL-1ß) plays a pivotal role in inflammatory responses to combat microbes. Although SVA infection can produce inflammatory clinical symptoms, the modulation of IL-1ß production by SVA infection remains unknown at present. Here, both in vitro and in vivo, SVA robustly induced IL-1ß production in macrophages and pigs. Infection performed in NOD-, LRR-, and pyrin domain-containing three (NLRP3) knockdown cells indicated that NLRP3 is essential for SVA-induced IL-1ß secretion. Importantly, we identified that the 1 to 154 amino acid (aa) portion of SVA 3D binds to the NLRP3 NACHT domain to activate NLRP3 inflammasome assembly and IL-1ß secretion. In addition, the SVA 3D protein interacts with IKKα and IKKß to induce NF-κB activation, which facilitates pro-IL-1ß transcription. Meanwhile, 3D induces p65 nucleus entry. Moreover, SVA 3D induces calcium influx and potassium efflux, which triggers IL-1ß secretion. Ion channels might be related to 3D binding with NLRP3, resulting in NLRP3-ASC complex assembly. We found that 3D protein expression induced tissue hemorrhage and swelling in the mice model. Consistently, expression of 3D in mice caused IL-1ß maturation and secretion. In the natural host of pigs, we confirmed that 3D also induced IL-1ß production. Our data reveal a novel mechanism underlying the activation of the NLRP3 inflammasome after SVA 3D expression, which provides clues for controlling pig's inflammation during the SVA infection. IMPORTANCE Inflammation refers to the response of the immune system to viral, bacterial, and fungal infections or other foreign particles in the body, which can involve the production of a wide array of soluble inflammatory mediators. The NLRP3 inflammasome is one of the best-characterized inflammasome leading to IL-1ß production and maturation. Senecavirus A (SVA) is an oncolytic virus that can cause fever, vesicles and erosions, severe fatal diarrhea, and even the sudden death of piglets. In this study, we demonstrated that 1 to 154 aa of SVA polymerase protein 3D interacts with the NACHT domain of NLRP3 to induce IL-1ß production via the NF-κB signaling pathway and ion channel signal. Our study unveils the mechanism underlying the regulation of inflammasome assembly and production of IL-1ß in response to SVA infection that will help better understand the modulation of host inflammation in pathogens invasion and development of the vaccine.

Identification of key volatile organic compounds in aircraft cabins and associated inhalation health risks.

The identification of key VOCs during flights is important in creating a satisfactory aircraft cabin environment. Two VOC databases for the building indoor environment (from 251 occupied residences) and the aircraft cabin environment (from 56 commercial flights) were compared, to determine the common compounds (detection rate (DR) > 70%) in the two environments and the characteristic VOCs (only those with high DR during flights) in aircraft cabins. Possible VOC emission sources in flights were also discussed. As TVOC is usually viewed as a general indicator of air quality, the prediction of TVOC concentration was carried out using BP neural network algorithm, and the average error between the predicted and measured values was 55.35 µg/m3 (R2 = 0.80). Meanwhile, the VOCs' inhalation cancer/non-cancer risks to crew members and passengers were calculated on the basis of detection rates, exposure concentrations, and health risk assessments. Six compounds (i.e., formaldehyde, benzene, tetrachloroethylene, trichloromethane, 1,2-dichloroethane, and naphthalene) were proposed as the key VOCs in the existing aircraft cabin environment, presenting a risk to crew members that is higher than the US EPA proposed acceptable level (evaluated mean value > 1E-06). The estimated lifetime excess cancer/non-cancer risks for passengers were all below the assessment criteria. Based on a summary of various VOC limits in five built environments, hierarchical design of VOC concentration limits is recommended for the aircraft environment.

QTL analysis of important agronomic traits and metabolites in foxtail millet (Setaria italica) by RIL population and widely targeted metabolome.

As a bridge between genome and phenotype, metabolome is closely related to plant growth and development. However, the research on the combination of genome, metabolome and multiple agronomic traits in foxtail millet (Setaria italica) is insufficient. Here, based on the linkage analysis of 3,452 metabolites via with high-quality genetic linkage maps, we detected a total of 1,049 metabolic quantitative trait loci (mQTLs) distributed in 11 hotspots, and 28 metabolite-related candidate genes were mined from 14 mQTLs. In addition, 136 single-environment phenotypic QTL (pQTLs) related to 63 phenotypes were identified by linkage analysis, and there were 12 hotspots on these pQTLs. We futher dissected 39 candidate genes related to agronomic traits through metabolite-phenotype correlation and gene function analysis, including Sd1 semidwarf gene, which can affect plant height by regulating GA synthesis. Combined correlation network and QTL analysis, we found that flavonoid-lignin pathway maybe closely related to plant architecture and yield in foxtail millet. For example, the correlation coefficient between apigenin 7-rutinoside and stem diameter reached 0.98, and they were co-located at 41.33-44.15 Mb of chromosome 5, further gene function analysis revealed that 5 flavonoid pathway genes, as well as Sd1, were located in this interval . Therefore, the correlation and co-localization between flavonoid-lignins and plant architecture may be due to the close linkage of their regulatory genes in millet. Besides, we also found that a combination of genomic and metabolomic for BLUP analysis can better predict plant agronomic traits than genomic or metabolomic data, independently. In conclusion, the combined analysis of mQTL and pQTL in millet have linked genetic, metabolic and agronomic traits, and is of great significance for metabolite-related molecular assisted breeding.

Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription.

Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on host gene expression. These data suggest that nuclear NS1 alters host responses to RSV infection by binding at regulatory elements of immune response genes and modulating host gene transcription. Our study identifies another layer of regulation by virally encoded proteins that shapes host response and impacts immunity to RSV.