ABSTRACT
Aflatoxins (AFs) are produced by fungi such as Aspergillus flavus and A. parasiticus and are one of the most toxic mycotoxins found in agricultural products and food. Aflatoxin contamination, which requires the control of A. flavus, remains problematic because of the lack of effective strategies and the exploration of new compounds that can inhibit A. flavus growth and mycotoxin production is urgently required to alleviate potential deleterious effects. Acetohydroxy acid synthase (AHAS) and dihydroxy acid dehydratase are important enzymes in the biosynthetic pathways of branched-chain amino acids (BCAAs), including isoleucine, leucine, and valine. Enzymes involved in BCAA biosynthesis are present in bacteria, plants, and fungi, but not in mammals, and are therefore, attractive targets for antimicrobial and herbicide development. In this study, we characterized AflaILVB/G/I and AflaILVD, which encode the catalytic and regulatory subunits of AHAS and dihydroxy acid dehydratase, from the pathogenic fungus Aspergillus flavus. The AflaILVB/G/I and AflaILVD deletion mutant grew slower and produced smaller colonies than the wild-type strain when grown on glucose minimal medium, potato dextrose agar, and yeast extract medium for three days at 28°C, and disruption of AflaILVB/G/I caused a significant reduction in conidia production when grown on all kinds of media. Cellular stress assays determined that all strains were sensitive to H2O2. Importantly, the pathogenicity and aflatoxin production were affected when AflaILVB/G/I and AflaILVD were knocked out, particularly AflaILVB/G/I. A series of genes that encoded enzymes involved in aflatoxin synthesis were downregulated, meaning that the knockout of AflaILVB/G/I influenced aflatoxin synthesis in A. flavus strain WT. Collectively, our results demonstrate the potential value of antifungals targeting AflaILVB/G/I in A. flavus.
Subject(s)
Aflatoxins , Aspergillus flavus , Animals , Aspergillus flavus/genetics , Virulence , Hydrogen Peroxide/metabolism , Hydro-Lyases , MammalsABSTRACT
Aspergillus flavus is an important fungus that produces aflatoxins, among which aflatoxin B1 (AFB1) is the most toxic and contaminates food and poses a high risk to human health. AFB1 interacts with another mycotoxin sterigmatocystin (STC), which is also a precursor of AFB1. Herein, we determined the effect of STC on AFB1 by evaluating A. flavus transcriptomic and proteomic profiles in the presence or absence of STC by RNA-seq and isobaric tagging, respectively. Overall, 3377 differentially expressed genes were identified by RNA-seq. These genes were mainly associated with the cellular component organisation and biosynthesis, the synthesis of valine, leucine, and isoleucine, and the synthesis of aflatoxin. Clustered genes responsible for AFB1 biosynthesis exhibited varying degrees of downregulation, and norB expression was completely suppressed in the experimental group. During proteomic analysis, 331 genes were differentially expressed in response to STC. These differentially expressed proteins were associated with cell parts and catalytic and antioxidant activities. Differentially expressed proteins predominantly participated in metabolic pathways associated with aflatoxin biosynthesis, glycolysis/gluconeogenesis, glutathione metabolism, and carbon metabolism. Notably, the upregulated and downregulated enzymes in carbohydrate and glutathione metabolisms may serve as potential gateways for inhibiting aflatoxin biosynthesis. Moreover, twelve proteins including seven downregulated ones involved in aflatoxin biosynthesis were identified; among them, AflG was the most downregulated, suggesting that it may be the key enzyme responsible for inhibiting aflatoxin synthesis. These findings provide novel insights into A. flavus control and the mechanisms regulating mycotoxin production.
ABSTRACT
This study examined whether older people with epicenter travel experiences in the event of the novel coronavirus disease epidemic suffered from stigmatization, which in turn affected subsequent behavior, including fear of disclosure and social avoidance. A three-wave survey was conducted using a time-lagged design of older people who had travel experiences in Hubei, China on the eve of the outbreak. Results reveal positive associations between stigmatization and stress, social avoidance, and fear of disclosure, in addition to positive associations between stress and social avoidance and fear of disclosure. Findings thus suggest that the effects of stigmatization on social avoidance and fear of disclosure is mediated, in part, by stress. De-stigmatization and psychological supports should be prioritized for epidemic prevention and control among older people in quarantine.
Subject(s)
COVID-19 , Disclosure , Fear/psychology , Public Policy , Social Isolation , Stereotyping , Aged , China , Female , Humans , Male , Middle Aged , Public Health , Quarantine , TravelABSTRACT
OBJECTIVE: The practice of parallel multiple jobs has increasingly become a global trend. However, the effects of parallel multiple jobs on physical and mental health have not been well understood. METHOD: Data come from China Health and Retirement Longitudinal Study published by CHARLS in 2015. The agricultural population aged 45 years old and above are selected through stratified random sampling (Nâ=â10,118). Robust regression method is used to give robust estimation. RESULTS: U-shape relations are found. The modest increase in the number of parallel multiple jobs can alleviate the difficulty in physical activities functioning and can reduce mental health problems. However, these beneficial effects could turn detrimental with the number of parallel multiple jobs beyond the modest level, leading to work overload. CONCLUSION: Parallel multiple jobs could be considered a double edge sword for physical and mental health.
Subject(s)
Mental Health , Retirement , Agriculture , Exercise , Humans , Longitudinal Studies , Middle AgedABSTRACT
BACKGROUND: The Civil Aviation Administration of China (CAAC) declares the airline transport regulation in January 2020 to help retard the spread of the novel coronavirus disease in China. This study is to examine the effect of airline transport regulation on confirmed cases of the novel coronavirus disease in megacities in China. METHODS: This study combines the multi-source data from the health data platform DXY, the airline data platform Airsavvi, the China Economic Internet Statistical Database and the China Railway website. The megacities whose airports have a passenger throughput of over 30 million per year (11 megacities: Wuhan, Beijing, Shanghai, Guangzhou, Chengdu, Shenzhen, Kunming, Xi'an, Chongqing, Hangzhou, Nanjing) are included in the analysis. The regression analysis is conducted in this study. RESULTS: The curvilinear relationship between the limitation on air traffic and confirmed cases of the novel coronavirus disease is identified (coefficient of the linear term = -4.650, p-value < 0.01; coefficient of the quadratic term = 4.089, p-value < 0.01). CONCLUSIONS: This study confirms the effectiveness of airline transport regulation in suppressing the development of this pandemic. The limitation on air traffic is found to negatively affect the confirmed cases in China's megacities. However, such effect marginally recedes as the strength of limitation intensifies. It suggests that comprehensive policy intervention is in need and air traffic can be one of important determinants that affect the epidemic development.