Decreased Methylenetetrahydrofolate Reductase Activity Leads to Increased Sensitivity to para-Aminosalicylic Acid in Mycobacterium tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the most fatal diseases in the world. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the production of 5-methyltetrahydrofolate (5-CH3-THF), which is required for the de novo biosynthesis of methionine in bacteria. Here, we identified Rv2172c as an MTHFR in M. tuberculosis through in vitro and in vivo analyses and determined that the protein is essential for the in vitro growth of the bacterium. Subsequently, we constructed rv2172c R159N and L214A mutants in M. tuberculosis and found that these mutants were more sensitive to the antifolates para-aminosalicylic acid (PAS) and sulfamethoxazole (SMX). Combining biochemical and genetic methods, we found that rv2172c R159N or L214A mutation impaired methionine production, leading to increased susceptibility of M. tuberculosis to PAS, which was largely restored by adding exogenous methionine. Moreover, overexpression of rv2172c in M. tuberculosis could increase methionine production and lead to PAS resistance. This research is the first to identify an MTHFR in M. tuberculosis and reveals that the activity of this enzyme is associated with susceptibility to antifolates. These findings have particular value for antitubercular drug design for the treatment of drug-resistant TB.

Impact of different grade roads on ecological networks: A case study of Fuzhou City, China.

The expansion of roads exacerbates the fragmentation of ecological networks and obstructs landscape connectivity. Scientific analysis of the impacts of different grades of roads on landscape connectivity and ecological networks is crucial for guiding road planning and ecological conservation. Based on the data of 2020 road network, land cover types, and digital elevation models, we used morphological spatial pattern analysis and circuit theory to construct ecological networks within different species dispersal distances (1, 3, 5, 10 km) in Fuzhou. We analyzed the impacts of roads of different grades (motorway, urban expressway, primary and secondary highway) on landscape connectivity at the landscape-patch-corridor scale. The results showed that at the landscape scale, overall landscape connectivity was significantly positively correlated with species dispersal distance. The motorway, urban expressway, primary and secondary highway had the lowest decline rate of overall landscape connectivity within a 10 km species dispersal range, being reduced by 15.6%, 5.3%, 1.5% and 5.2%, respectively. At the patch scale, in the comparison of roads of different grades, motorway led to the highest decline rate of patch connectivity within 1 and 5 km species dispersal range, while primary highway led to the highest decline rate of patch connectivity within 3 and 10 km species dispersal range. At the corridor scale, urban expressway led the highest increase rate of indices. The cost-weighted distance of the overall least-cost path, the ratio of cost-weighted distance to length, ove-rall effective resistance, and total corridor length within 5 km species dispersal range were increased by 43.4%, 33.2%, 57.3%, and 7.3%, respectively. As the distance of species dispersal increased, the patches with high importance were reduced from the northern, central, and northwestern regions to the northern regions, leading to a decrease in the living space of species, and the key corridors were gradually extending from the northwestern and southern regions to the central regions. Our results can guide the construction and optimization of Fuzhou's ecological network from an overall perspective, and provide a scientific basis for biodiversity conservation, ecological restoration, and road network planning under the context of limited land resource utilization.

Risk of prevalence of latent tuberculosis infection in health care workers-an idiographic meta-analysis from a Chinese perspective.

BACKGROUND: China is one of the countries sharing the major burden of tuberculosis (TB) in the world. Health care workers (HCWs) are subject to a high risk of occupational latent tuberculosis infection (LTBI)-an asymptomatic state of TB disease. However, the heterogenic composition of healthcare professionals in terms of nature of their work leads to the inconsistency in predicting the prevalence of LTBI amongst them. Furthermore, the global statistics do not account for the analysis conducted within the Chinese population. Our study reflects a systemic and epidemiological meta-analysis to investigate the risk of contracting LTBI by the HCWs of China. METHODS: A systematic review of the literature was performed to identify studies reporting LTBI prevalence or incidence among HCWs and a control groups in China. Risk of infection, as well as subgroup analysis was calculated by pooled effect estimates. Review Manager 5.0 was used to perform the meta-analyses. RESULTS: Twenty studies containing 9,654 HCWs met the inclusion criteria. The average prevalence of LTBI among HCWs was 51.5%, ranging from 27.9-88.8%. HCWs had a higher risk of prevalence of LTBI than the control groups [odds ratio (OR), 1.78, 95% confidence interval (CI), 1.46-2.16]. In the subgroup analysis, the prevalence of LTBI in HCWs with respect to the control groups was observed to be highest in Eastern China (OR, 2.05; 95% CI, 1.35-3.11). Furthermore, the pooled OR for LTBI was 1.90 and 1.65 separately from the results of the tuberculin skin test (TST) and the interferon-gamma release assay. Lastly, upon comparing the HCWs with the control groups from the community and the nosocomial source, it was observed that the pooled OR favored for the prevalence of LTBI, which was primarily community-sourced (3.12 and 1.54). HCWs had an increased risk of prevalence of LTBI than the control groups, both in general hospitals and TB specific hospitals (pooled OR 2.4 and 1.57). CONCLUSIONS: Risk of LTBI infection among HCWs is relatively high in China, especially in the eastern region, predisposed by the cumulative exposure to Mycobacterium tuberculosis from the community and the general hospitals. Overall, our data reflects an alarming risk posed to our HCWs, and calls for immediate reforms at the policy levels, so as to implement effective screening and treatment of affected HCWs in China.

Simultaneous adsorption and degradation of triclosan by Ginkgo biloba L. stabilized Fe/Co bimetallic nanoparticles.

Triclosan (TCS), an antimicrobial agent added in many pharmaceutical and personal care products, can cause some environmental problems due to its bioaccumulation, toxicity and potential antibiotic cross-resistance. In this study, Ginkgo biloba L. leaf extract was used as the green stabilizing agent to synthesize Fe/Co bimetallic nanoparticles (G-Fe/Co NPs), which were applied to remove TCS from aqueous solution. G-Fe/Co NPs were characterized by TEM, EDS, SEM, BET, FTIR, XRD and XPS. G. biloba L. leaf extract improved the dispersion and reduced the passivation of NPs. The TCS removal efficiency followed the order of G-Fe/Co NPs > G-Fe NPs > Co NPs > Fe/Co NPs > Fe NPs. G-Fe/Co NPs can be reused at least eight times. The Co leaching under different initial pH values was negligible. The factors affecting the TCS removal were investigated. The results indicated that the removal of TCS followed pseudo-second-order kinetics, and the removal rate constant decreased with increasing the initial pH value and the initial TCS concentration, and decreasing the Co loading of G-Fe/Co NPs and NPs dosage. The mass balance of TCS removal by G-Fe/Co NPs indicated that adsorption was dominant process and TCS degradation was an accumulative process.