Whole-transcriptome sequencing of phagocytes reveals a ceRNA network contributing to natural resistance to tuberculosis infection.

Tuberculosis (TB) is a major fatal infectious disease globally, exhibiting high morbidity rates and impacting public health and other socio-economic factors. However, some individuals are resistant to TB infection and are referred to as "Resisters". Resisters remain uninfected even after exposure to high load of Mycobacterium tuberculosis (Mtb). To delineate this further, this study aimed to investigate the factors and mechanisms influencing the Mtb resistance phenotype. We assayed the phagocytic capacity of peripheral blood mononuclear cells (PBMCs) collected from Resisters, patients with latent TB infection (LTBI), and patients with active TB (ATB), following infection with fluorescent Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Phagocytosis was stronger in PBMCs from ATB patients, and comparable in LTBI patients and Resisters. Subsequently, phagocytes were isolated and subjected to whole transcriptome sequencing and small RNA sequencing to analyze transcriptional expression profiles and identify potential targets associated with the resistance phenotype. The results revealed that a total of 277 mRNAs, 589 long non-coding RNAs, 523 circular RNAs, and 35 microRNAs were differentially expressed in Resisters and LTBI patients. Further, the endogenous competitive RNA (ceRNA) network was constructed from differentially expressed genes after screening. Bioinformatics, statistical analysis, and quantitative real-time polymerase chain reaction were used for the identification and validation of potential crucial targets in the ceRNA network. As a result, we obtained a ceRNA network that contributes to the resistance phenotype. TCONS_00034796-F3, ENST00000629441-DDX43, hsa-ATAD3A_0003-CYP17A1, and XR_932996.2-CERS1 may be crucial association pairs for resistance to TB infection. Overall, this study demonstrated that the phagocytic capacity of PBMCs was not a determinant of the resistance phenotype and that some non-coding RNAs could be involved in the natural resistance to TB infection through a ceRNA mechanism.

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.

Mining the Micro-Trajectory of Two-Wheeled Non-Motorized Vehicles Based on the Improved YOLOx.

Two-wheeled non-motorized vehicles (TNVs) have become the primary mode of transportation for short-distance travel among residents in many underdeveloped cities in China due to their convenience and low cost. However, this trend also brings corresponding risks of traffic accidents. Therefore, it is necessary to analyze the driving behavior characteristics of TNVs through their trajectory data in order to provide guidance for traffic safety. Nevertheless, the compact size, agile steering, and high maneuverability of these TNVs pose substantial challenges in acquiring high-precision trajectories. These characteristics complicate the tracking and analysis processes essential for understanding their movement patterns. To tackle this challenge, we propose an enhanced You Only Look Once Version X (YOLOx) model, which incorporates a median pooling-Convolutional Block Attention Mechanism (M-CBAM). This model is specifically designed for the detection of TNVs, and aims to improve accuracy and efficiency in trajectory tracking. Furthermore, based on this enhanced YOLOx model, we have developed a micro-trajectory data mining framework specifically for TNVs. Initially, the paper establishes an aerial dataset dedicated to the detection of TNVs, which then serves as a foundational resource for training the detection model. Subsequently, an augmentation of the Convolutional Block Attention Mechanism (CBAM) is introduced, integrating median pooling to amplify the model's feature extraction capabilities. Subsequently, additional detection heads are integrated into the YOLOx model to elevate the detection rate of small-scale targets, particularly focusing on TNVs. Concurrently, the Deep Sort algorithm is utilized for the precise tracking of vehicle targets. The process culminates with the reconstruction of trajectories, which is achieved through a combination of video stabilization, coordinate mapping, and filtering denoising techniques. The experimental results derived from our self-constructed dataset reveal that the enhanced YOLOx model demonstrates superior detection performance in comparison to other analogous methods. The comprehensive framework accomplishes an average trajectory recall rate of 85% across three test videos. This significant achievement provides a reliable method for data acquisition, which is essential for investigating the micro-level operational mechanisms of TNVs. The results of this study can further contribute to the understanding and improvement of traffic safety on mixed-use roads.

Genetic factors associated with acquired phenotypic drug resistance and its compensatory evolution during tuberculosis treatment.

OBJECTIVES: We elucidated the factors, evolution, and compensation of antimicrobial resistance (AMR) in Mycobacterium tuberculosis (MTB) isolates under dual pressure from the intra-host environment and anti-tuberculosis (anti-TB) drugs. METHODS: This retrospective case-control study included 337 patients with pulmonary tuberculosis from 15 clinics in Tianjin, China, with phenotypic drug susceptibility testing results available for at least two time points between January 1, 2009 and December 31, 2016. Patients in the case group exhibited acquired AMR to isoniazid (INH) or rifampicin (RIF), while those in the control group lacked acquired AMR. The whole-genome sequencing (WGS) was conducted on 149 serial longitudinal MTB isolates from 46 patients who acquired or reversed phenotypic INH/RIF-resistance during treatment. The genetic basis, associated factors, and intra-host evolution of acquired phenotypic INH/RIF-resistance were elucidated using a combined analysis. RESULTS: Anti-TB interruption duration of ≥30 days showed association with acquired phenotypic INH/RIF resistance (aOR = 2·2, 95% CI, 1·0-5·1) and new rpoB mutations (p = 0·024). The MTB evolution was 1·2 (95% CI, 1·02-1·38) single nucleotide polymorphisms per genome per year under dual pressure from the intra-host environment and anti-TB drugs. AMR-associated mutations occurred before phenotypic AMR appearance in cases with acquired phenotypic INH (10 of 16) and RIF (9 of 22) resistances. DISCUSSION: Compensatory evolution may promote the fixation of INH/RIF-resistance mutations and affect phenotypic AMR. The TB treatment should be adjusted based on gene sequencing results, especially in persistent culture positivity during treatment, which highlights the clinical importance of WGS in identifying reinfection and AMR acquisition before phenotypic drug susceptibility testing.

Exploring the biomarkers and potential therapeutic drugs for sepsis via integrated bioinformatic analysis.

BACKGROUND: Sepsis is a life-threatening condition caused by an excessive inflammatory response to an infection, associated with high mortality. However, the regulatory mechanism of sepsis remains unclear. RESULTS: In this study, bioinformatics analysis revealed the novel key biomarkers associated with sepsis and potential regulators. Three public datasets (GSE28750, GSE57065 and GSE95233) were employed to recognize the differentially expressed genes (DEGs). Taking the intersection of DEGs from these three datasets, GO and KEGG pathway enrichment analysis revealed 537 shared DEGs and their biological functions and pathways. These genes were mainly enriched in T cell activation, differentiation, lymphocyte differentiation, mononuclear cell differentiation, and regulation of T cell activation based on GO analysis. Further, pathway enrichment analysis revealed that these DEGs were significantly enriched in Th1, Th2 and Th17 cell differentiation. Additionally, five hub immune-related genes (CD3E, HLA-DRA, IL2RB, ITK and LAT) were identified from the protein-protein interaction network, and sepsis patients with higher expression of hub genes had a better prognosis. Besides, 14 drugs targeting these five hub related genes were revealed on the basis of the DrugBank database, which proved advantageous for treating immune-related diseases. CONCLUSIONS: These results strengthen the new understanding of sepsis development and provide a fresh perspective into discriminating the candidate biomarkers for predicting sepsis as well as identifying new drugs for treating sepsis.

EspB and HtpG interact with the type III-A CRISPR/Cas system of Mycobacterium tuberculosis.

Introduction: Mycobacterium tuberculosis (MTB) has a type III-A clustered regularly interspaced short palindromic repeat/CRISPR-associated protein (CRISPR/Cas) system consisting of a Csm1-5 and CRISPR RNA (crRNA) complex involved in the defense against invading nucleic acids. However, CRISPR/Cas system in the MTB still is clearly unknown and needs to be further explored. Methods: In our work, two non-Cas system proteins EspB and HtpG protein were found and identified by LC-MS/MS. The effect of EspB and HtpG on Type III-A CRISPR/Cas System of M. tuberculosis was examined by using Plasmid interference assay and Co-immunoprecipitation analyses. We explored that EspB could interact with the crRNA RNP complex, but HtpG could inhibit the accumulation of the MTB Csm proteins and defense the mechanism of CRISPR/Cas system. Results: The proteins ESAT-6 secretion system-1(Esx-1) secreted protein B (EspB) and high-temperature protein G (HtpG), which were not previously associated with CRISPR/Cas systems, are involved in mycobacterial CRISPR/Cas systems with distinct functions. Conclusion: EspB is a novel crRNA-binding protein that interacts directly with the MTB crRNP complex. Meanwhile, HtpG influences the accumulation of MTB Csm proteins and EspB and interferes with the defense mechanism of the crRNP complex against foreign DNA in vivo. Thereby, our study not only leads to developing more precise clinical diagnostic tool to quickly detect for MTB infection, but also knows these proteins merits for TB biomarkers/vaccine candidates.

Association between mutations in a thyX-hsdS.1 region and para-aminosalicylic acid resistance in Mycobacterium tuberculosis clinical isolates.

Although para-aminosalicylic acid (PAS) has been used to treat tuberculosis agent for decades, its mechanisms of resistance are still not thoroughly understood. Previously, sporadic studies showed that certain mutations in the thyX-hsdS.1 region caused PAS resistance in M. tuberculosis, but a comprehensive analysis is lacking. Recently, we found a G-10A mutation in thyX-hsdS.1 in a PAS-resistant clinical isolate, but it did not cause PAS resistance. SNPs in thyX-hsdS.1 in 6550 clinical isolates were analyzed, and 153 SNPs were identified. C-16 T was the most common SNP identified (54.25%, 83/153), followed by C-4T (7.19%, 11/153) and G-9A (6.54%, 10/153). Subsequently, the effects of those SNPs on the promoter activity of thyX were tested, and the results showed that mutations C-1T, G-3A, C-4T, C-4G, G-7A, G-9A, C-16T, G-18C, and C-19G led to increased promoter activity compared with the wild-type sequence, but other mutations did not. Then, thyX and wild-type thyX-hsdS.1, or thyX-hsdS.1 containing specific SNPs, were overexpressed in M. tuberculosis H37Ra. The results showed that mutations resulting in increased promoter activity also caused PAS resistance. Moreover, the results of an electrophoretic mobility shift assay showed that thyX-hsdS.1 containing the C-16T mutation had a higher binding capacity to RNA polymerase than did the wild-type sequence. Taken together, our data demonstrated that among the SNPs identified in thyX-hsdS.1 of M. tuberculosis clinical isolates, only those able to increase the promoter activity of thyX caused PAS resistance and therefore can be considered as molecular markers for PAS resistance.

Whole-genome sequencing and transcriptome-characterized in vitro evolution of aminoglycoside resistance in Mycobacterium tuberculosis.

Antibiotic resistance of Mycobacterium tuberculosis (Mtb) is a major public health concern worldwide. Therefore, it is of great significance to characterize the mutational pathways by which susceptible Mtb evolves into drug resistance. In this study, we used laboratory evolution to explore the mutational pathways of aminoglycoside resistance. The level of resistance in amikacin inducing Mtb was also associated with changes in susceptibility to other anti-tuberculosis drugs such as isoniazid, levofloxacin and capreomycin. Whole-genome sequencing (WGS) revealed that the induced resistant Mtb strains had accumulated diverse mutations. We found that rrs A1401G was the predominant mutation in aminoglycoside-resistant clinical Mtb isolates from Guangdong. In addition, this study provided global insight into the characteristics of the transcriptome in four representative induced strains and revealed that rrs mutated and unmutated aminoglycoside-resistant Mtb strains have different transcriptional profiles. WGS analysis and transcriptional profiling of Mtb strains during evolution revealed that Mtb strains harbouring rrs A1401G have an evolutionary advantage over other drug-resistant strains under the pressure of aminoglycosides because of their ultra-high resistance level and low physiological impact on the strain. The results of this study should advance our understanding of aminoglycoside resistance mechanisms.

Neutralization Effect of Sera against Delta and Omicron in Patients Recovering from COVID-19 and Inactivated Vaccine Recipients.

This study aims to analyze the serum neutralization capacity against Delta and Omicron variants in three clusters of individuals, including those who had recovered from COVID-19 and those who had received two and three doses of inactivated vaccine. Pseudovirus neutralization tests were performed on serum samples. The neutralizing titers between different groups were compared using the Wilcoxon's signed-rank test. Among the two-dose vaccinees, the neutralization titers of the Omicron variant were reduced by approximately 3.1-fold compared to the wild-type virus (p < 0.05). Meanwhile, among the three-dose vaccinees, the neutralization titers for Delta and Omicron variants were 3.5-fold (p < 0.05) and 5.0-fold (p < 0.05) lower, respectively, as compared to the wild-type virus. In addition, among the recovering patients, the neutralization titers for Delta and Omicron variants were 3.9-fold (p < 0.05) and 29.1-fold (p < 0.05) lower, respectively, as compared to the wild-type virus. Overall, only 12.0% (11/92) of participants showed neutralizing titers against Omicron above the detection limit. The ability to neutralize wild-type pseudovirus was significantly boosted in three-dose vaccinees as compared to two-dose vaccinees. Sera from recovered patients showed greater neutralizing titers for the wild-type and Delta pseudoviruses than the two- and three-dose inactivated vaccine groups. The present study revealed a loss of neutralizing activity against the Omicron variant in almost all samples. Moreover, the immunization effect obtained through natural infection is more robust than that from the active immunization method of vaccination.

Spatiotemporal dynamics of ecological security in a typical conservation region of southern China based on catastrophe theory and GIS.

Ecological security assessment can effectively reflect the ecological status of a region and reveal its level of sustainable development. In this paper, an ecological security-oriented evaluation system was constructed, and the ecological security level of the Dongjiangyuan region from 2000 to 2020 was evaluated based on catastrophe theory and GIS. The results were as follows: (1) As shown in the land use and cover maps, by 2020, the forestland area had decreased the most, and the artificial surface area had increased the most. (2) The ecological security index of the Dongjiangyuan region showed a low trend in the artificial surface area and its surrounding areas. The quite low values of the ecological security index in 2000 and 2010 were improved in 2020 due to the increase in ecological services capacity. The increased vegetation cover from 2000 to 2020 promoted the improved ecological service capacity. (3) The rapid urbanization process in the Dongjiangyuan region resulted in a lower ecological sensitivity index value. Notably, the ecological sensitivity index of the study area had a slightly decreasing trend. (4) The spatial autocorrelation showed that the proportion of hot and cold spots from 2000 to 2020 decreased by 2.96% and 6.91%, respectively. This study can provide a scientific basis and decision-making guidance for ecological management in the Dongjiangyuan region in the future.

Impact of Vaccination and Control Measures on the Fatality of COVID-19: An Ecological Study.

BACKGROUND: During the COVID-19 pandemic, reducing the case fatality rate (CFR) becomes an urgent goal. OBJECTIVE: This study explored the effect of vaccination and variants on COVID-19 fatality and provide a basis for the adjustment of control measures. METHODS: This study collected epidemiological information on COVID-19 from January to October 2021. By setting different lag times, we calculated the adjusted CFR. The Spearman correlation coefficient and beta regression were used to explore factors that may affect COVID-19 fatality. RESULTS: Every 1% increase in the percentage of full vaccinations may reduce the 3 weeks lagging CFR by 0.66%. Increasing the restrictions on internal movement from level 0 to 1, restrictions on international travel controls from level 2 to 3, and stay-at-home restrictions from level 0 to 2 were associated with an average reduction in 3 weeks lagging CFR of 0.20%, 0.39%, and 0.36%, respectively. Increasing strictness in canceling public events from level 0 to 1 and 2 may reduce the 3 weeks lagging CFR by 0.49% and 0.37, respectively. Increasing the severity of school and workplace closures from level 1 or level 0 to 3 may increase the 3 weeks lagging CFR of 0.39% and 0.83, respectively. Every 1-point increase in the Global Health Security (GHS) index score may increase the 3 weeks lagging CFR by 0.12%. CONCLUSION: A higher percentage of full vaccinations, higher levels of internal movement restrictions, international travel control restrictions, cancelations of public events, and stay-at-home restrictions are factors that may reduce the adjusted CFR.

Association between Mutations in Papain-like Protease (PLpro) of SARS-CoV-2 with COVID-19 Clinical Outcomes.

Papain-like protease (PLpro) is important for the replication and transcription of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to reveal the PLpro mutations associated with the clinical outcomes of patients. Due to the importance of the S protein in the pathogenicity of SARS-CoV-2, the mutation of the S protein was also analyzed in this study. After downloading the data from the Global Initiative on Sharing Avian Influenza Data (GISAID) database, samples were divided into two groups on the basis of patient status, namely, recovered and dead groups. This study performed a univariate analysis and further explored the association of mutations with patient outcomes through multivariate logistic regression analysis. A total of 138,492 samples were used for analysis. The patients had a mean age of 43.66 ± 21.56 years, and 51.3% of them were female. Multivariate logistic regression results showed that, compared with men, women had a lower risk of dying from coronavirus disease 2019 (COVID-19) (OR = 0.687, 95%CI: 0.638-0.740). Compared with patients aged 17 years and younger, patients aged 18-64 years (OR = 2.864, 95%CI: 1.982-4.139) and patients over 65 years old (OR = 19.135, 95%CI: 13.280-27.572) had a higher risk of death after infection. Compared with the wild type, P78L (OR = 5.185, 95%CI: 2.763-9.730) and K233Q (OR = 5.154, 95%CI: 1.442-18.416) in PLpro were associated with an increased risk of death. A synergistic interaction existed between age and mutations A146D and P78L. The results of the multivariate logistic regression analysis of the data on vaccinated patients demonstrated that, compared with the wild type, the P78L (OR = 3.376, 95%CI: 2.040-5.585) mutation was associated with an increased risk of death. In conclusion, compared with the wild-type PLpro protein, the P78L and K233Q mutations may increase the risk of death in infected individuals. In addition, a synergistic effect existed between age and P78L and K233Q that increased the risk of death in older patients.

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.

TREM-2 promotes Th1 responses by interacting with the CD3ζ-ZAP70 complex following Mycobacterium tuberculosis infection.

Triggering receptor expressed on myeloid cells 2 (TREM-2) is a modulator of pattern recognition receptors on innate immune cells that regulates the inflammatory response. However, the role of TREM-2 in in vivo models of infection and inflammation remains controversial. Here, we demonstrated that TREM-2 expression on CD4+ T cells was induced by Mycobacterium tuberculosis infection in both humans and mice and positively associated with T cell activation and an effector memory phenotype. Activation of TREM-2 in CD4+ T cells was dependent on interaction with the putative TREM-2 ligand expressed on DCs. Unlike the observation in myeloid cells that TREM-2 signals through DAP12, in CD4+ T cells, TREM-2 interacted with the CD3ζ-ZAP70 complex as well as with the IFN-γ receptor, leading to STAT1/-4 activation and T-bet transcription. In addition, an infection model using reconstituted Rag2-/- mice (with TREM-2-KO vs. WT cells or TREM-2+ vs. TREM-2-CD4+ T cells) or CD4+ T cell-specific TREM-2 conditional KO mice demonstrated that TREM-2 promoted a Th1-mediated host defense against M. tuberculosis infection. Taken together, these findings reveal a critical role of TREM-2 in evoking proinflammatory Th1 responses that may provide potential therapeutic targets for infectious and inflammatory diseases.

TARM-1 Is Critical for Macrophage Activation and Th1 Response in Mycobacterium tuberculosis Infection.

T cell-interacting activating receptor on myeloid cells 1 (TARM-1) is a novel leukocyte receptor expressed in neutrophils and macrophages. It plays an important role in proinflammatory response in acute bacterial infection, but its immunomodulatory effects on chronic Mycobacterium tuberculosis infections remain unclear. TARM-1 expression was significantly upregulated on CD14high monocytes from patients with active pulmonary tuberculosis (TB) as compared that on cells from patients with latent TB or from healthy control subjects. Small interfering RNA knockdown of TARM-1 reduced expression levels of proinflammatory cytokines IL-12, IL-18, IL-1ß, and IL-8 in M. tuberculosis-infected macrophages, as well as that of HLA-DR and costimulatory molecules CD83, CD86, and CD40. Moreover, TARM-1 enhanced phagocytosis and intracellular killing of M. tuberculosis through upregulating reactive oxygen species. In an in vitro monocyte and T cell coculture system, blockade of TARM-1 activity by TARM-1 blocking peptide suppressed CD4+ T cell activation and proliferation. Finally, administration of TARM-1 blocking peptide in a mouse model of M. tuberculosis infection increased bacterial load and lung pathology, which was associated with decreased macrophage activation and IFN-γ production by T cell. Taken together, these results, to our knowledge, demonstrate a novel immune protective role of TARM-1 in M. tuberculosis infection and provide a potential therapeutic target for TB disease.

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.

Enhanced removal of antibiotic resistance genes by nanoscale iron-cobalt particles modified with Ginkgo biloba L. leaf: Combining Illumina MiSeq sequencing and oligotyping analysis.

The addition of second metal (Co) to nanoscale iron particles (NIPs) is an attractive strategy to improve catalytic capacity. However, the nanoparticles tend to form chain-like aggregates. In this study, bacterial 16S rRNA gene, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) from secondary effluent were significantly removed by Ginkgo biloba L. modified nanoscale iron-cobalt particles (GNICPs). When the Co loading, initial pH value, DO and dosage were 10%, 7.33, 8.94 mg/L and 1.12 g/L, some ARGs and MGEs could be reduced below the detection limit at the 2nd or 3rd cycle. Illumina MiSeq sequencing demonstrated that negative correlations were found between ARGs and reaction time/cycles. The predicted microbial functions by FAPROTAX database indicated GNICPs were effective in eliminating human_pathogens_all. Furthermore, oligotyping revealed all ARGs and MGEs were positively correlated with oligotype 10, which indicated GNICPs removed oligotype 10 easily.

Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19.

Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500 mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Although randomized trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.

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.

Incidence and Predictors of Tracheobronchial Tuberculosis in Pulmonary Tuberculosis: A Multicentre, Large-Scale and Prospective Study in Southern China.

BACKGROUND: Patients with pulmonary tuberculosis (PTB) have a high risk of concomitant tracheobronchial tuberculosis (TBTB), which commonly causes severe complications such as tracheobronchial stenosis. The prevalence and predictors of TBTB in China remain unclear due to the lack of prospective and large-scale studies. OBJECTIVES: To investigate the incidence of TBTB in PTB patients in southern China, and elucidate the predictors of TBTB and related tracheobronchial stenosis. METHODS: We prospectively performed bronchoscopy in PTB patients to diagnose TBTB at four medical centres in southern China from September 2015 to August 2016. Clinical and epidemiological data were recorded and analysed to determine predictors of TBTB and related tracheobronchial stenosis. RESULTS: A total of 345 (23.9%) of the 1,442 PTB patients undergoing bronchoscopy were diagnosed with TBTB. Female sex (OR 2.53), age < 50 years (OR 1.88), living in urban (OR 2.19), diabetes (OR 1.84), coughing (OR 2.61), and symptoms ≥4 weeks (OR 1.66) were predictors of PTB concomitant with TBTB. About 59.7% TBTB patients developed tracheobronchial stenosis, of which 23.3% cases presented severe airway narrowing. Female sex (OR 2.27), age < 50 years (OR 2.11), shortness of breath (OR 1.97), and symptoms ≥4 weeks (OR 1.71) were predictors of TBTB-related tracheobronchial stenosis. CONCLUSIONS: About 23.9% of PTB patients undergoing bronchoscopy present with TBTB in Guangdong province, southern China. Young and middle-aged females with symptoms persisting for ≥4 weeks (the main predictors of TBTB and related tracheobronchial stenosis) should receive bronchoscopy immediately when diagnosed with PTB.