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China, with the third largest share of global tuberculosis cases, faces a substantial challenge in its healthcare system as a result of the high burden of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB). This study employs a genomic epidemiological approach to assess recent tuberculosis transmissions between individuals, identifying potential risk factors and discerning the role of transmitted resistant isolates in the emergence of drug-resistant tuberculosis in China. We conducted a population-based retrospective study on 5052 Mycobacterium tuberculosis (MTB) isolates from 70 surveillance sites using whole genome sequencing (WGS). Minimum spanning tree analysis identified resistance mutations, while epidemiological data analysis pinpointed transmission risk factors. Of the 5052 isolates, 23% (1160) formed 452 genomic clusters, with 85.6% (387) of the transmissions occurring within the same counties. Individuals with younger age, larger family size, new cases, smear positive, and MDR/RR were at higher odds for recent transmission, while higher education (university and above) and occupation as a non-physical workers emerged as protective factors. At least 61.4% (251/409) of MDR/RR-TB were likely a result of recent transmission of MDR/RR isolates, with previous treatment (crude OR = 2.77), smear-positive (cOR = 2.07) and larger family population (cOR = 1.13) established as risk factors. Our findings highlight that local transmission remains the predominant form of TB transmission in China. Correspondingly, drug-resistant tuberculosis is primarily driven by the transmission of resistant tuberculosis isolates. Targeted interventions for high-risk populations to interrupt transmission within the country will likely provide an opportunity to reduce the prevalence of both tuberculosis and drug-resistant tuberculosis.

Abstract Background Screening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT. Methods The prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov − Smirnov test and other statistical methods were used for statistical analysis, $${x}^{2}$$ x 2 was obtained using the formula $${x}^{2}=$$ x 2 = nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China. Results Among 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P

ABSTRACT Tuberculosis (TB) remains the primary cause of death from an infectious disease worldwide. The MPT64 antigen assay is an expedited diagnostic method that is increasingly adopted in many TB diagnostic laboratories and clinical settings worldwide. However, the diagnostic accuracy of the MPT64 antigen assay is influenced by the presence of 63bp deletion variants within the mpt64 gene, and the potential association of this variant with the lineage or sub-lineage of Mycobacterium tuberculosis complex (MTBC) remains unverified. In this study, we analyzed the MPT64 antigen assay using isolates from the major lineage and sub-lineage of MTBC combined with whole-genome sequencing. Notably, we found a significant association between the 63bp deletion variant in the mpt64 gene and M. tuberculosis Lineage 4.2.2 (L4.2.2) globally. Phylogenetic analysis revealed that L4.2.2 isolates were divided into two clusters (Clades A and B). Importantly, all isolates within Clade A exhibited the 63bp deletion variant in the mpt64 gene. Furthermore, using the Bayesian Skyline population model, we observed that the effective population size of Clade A has remained relatively constant. These findings highlight that MPT64-based testing should be cautiously used, and MPT64 negative results should be validated using an alternative assay in regions where L4.2.2 isolates are prevalent, such as China and Vietnam. These L4.2.2 isolates with the 63bp deletion variant in mpt64 warrant greater consideration during the development of diagnostic tests and study of their immunomodulatory role. Overall, this study provides valuable insights into a better understanding of the virulence and diagnosis of MTBC isolates based on the MPT64 protein. IMPORTANCE To date, rapid diagnostic methods based on the MPT64 antigen assay are increasingly utilized to differentiate between non-tuberculous mycobacteria and TB disease in clinical settings. Furthermore, numerous novel techniques based on the MPT64 release assay are continuously being developed and applied for the identification of both pulmonary and extrapulmonary TB. However, the diagnostic accuracy of the MPT64 antigen assay is influenced by the presence of 63 bp deletion variants within the mpt64 gene. To our knowledge, this is the first report on the association between the 63 bp deletion variant in mpt64 and Mycobacterium tuberculosis L4.2.2 globally, which highlights the need for the cautious utilization of MPT64-based testing in regions where L4.2.2 isolates are prevalent, such as China and Vietnam, and MPT64 negative results should be confirmed with another assay. In addition, further studies on vaccine development and immunology based on MPT64 should consider these isolates with 63 bp deletion variant.

Objectives: The Mycobacterium avium complex (MAC), comprising a series of subspecies, has a worldwide distribution, with differences in drug susceptibility among subspecies. This study aimed to assess the composition of MAC and susceptibility differences among subspecies in mainland China. Methods: A total of 287 MAC clinical strains were included in the study. Multitarget sequences were applied to accurately identify subspecies, and a microdilution method was used to evaluate minimum inhibitory concentrations (MICs) among subspecies using Sensititre SLOMYCO plates. Results: Mycobacterium intracellular (N = 169), Mycobacterium avium (N = 52), Mycobacterium chimaera (N = 22), Mycobacterium marseillense (N = 25), Mycobacterium colombiense (N = 14), Mycobacterium yongonense (N = 4), Mycobacterium vulneris (N = 3) and Mycobacterium timonense (N = 2) were isolated from MAC. Clarithromycin, amikacin and rifabutin showed lower MIC50 and MIC90 values than other drugs, and the resistance rates of clarithromycin, amikacin, linezolid and moxifloxacin were 6.3%, 10.5%, 51.9% and 46.3%, respectively. The resistance rates of clarithromycin and moxifloxacin in the initial treatment group were significantly lower than those in the retreatment group (4.09% vs. 12.94%; 30.41% vs. 75.29%; P < 0.05). Drug susceptibility differences were observed in clarithromycin and moxifloxacin among the five major subspecies (P < 0.05); however, those statistically significant differences disappeared when MACs were divided into two groups according to previous anti-tuberculosis (anti-TB) treatment history. Conclusion: This study revealed that MAC, primarily comprising M. intracellulare, was susceptible to clarithromycin, amikacin and rifabutin. Drug susceptibility among subspecies did not exhibit intrinsic differences in our study. Previous anti-TB treatment patients are more resistant to drugs; thus, attention should be given to those patients in the clinic.

ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) has a severe impact on public health. To investigate the drug-resistant profile, compensatory mutations and genetic variations among MDR-TB isolates, a total of 546 MDR-TB isolates from China underwent drug-susceptibility testing and whole genome sequencing for further analysis. The results showed that our isolates have a high rate of fluoroquinolone resistance (45.60%, 249/546) and a low proportion of conferring resistance to bedaquiline, clofazimine, linezolid, and delamanid. The majority of MDR-TB isolates (77.66%, 424/546) belong to Lineage 2.2.1, followed by Lineage 4.5 (6.41%, 35/546), and the Lineage 2 isolates have a strong association with pre-XDR/XDR-TB (P < 0.05) in our study. Epidemic success analysis using time-scaled haplotypic density (THD) showed that clustered isolates outperformed non-clustered isolates. Compensatory mutations happened in rpoA, rpoC, and non-RRDR of rpoB genes, which were found more frequently in clusters and were associated with the increase of THD index, suggesting that increased bacterial fitness was associated with MDR-TB transmission. In addition, the variants in resistance associated genes in MDR isolates are mainly focused on single nucleotide polymorphism mutations, and only a few genes have indel variants, such as katG, ethA. We also found some genes underwent indel variation correlated with the lineage and sub-lineage of isolates, suggesting the selective evolution of different lineage isolates. Thus, this analysis of the characterization and genetic diversity of MDR isolates would be helpful in developing effective strategies for treatment regimens and tailoring public interventions. IMPORTANCE Multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to tuberculosis prevention and control in China. This study provides insight into the drug-resistant characteristics of MDR combined with phenotypic drug-susceptibility testing and whole genome sequencing. The compensatory mutations and epidemic success analysis were analyzed by time-scaled haplotypic density (THD) method, suggesting clustered isolates and compensatory mutations are associated with MDR-TB transmission. In addition, the insertion and deletion variants happened in some genes, which are associated with the lineage and sub-lineage of isolates, such as the mpt64 gene. This study offered a valuable reference and increased understanding of MDR-TB in China, which could be crucial for achieving the objective of precision medicine in the prevention and treatment of MDR-TB.

Mycobacterial membrane proteins play a pivotal role in the bacterial invasion of host cells; however, the precise mechanisms underlying certain membrane proteins remain elusive. Mycolicibacterium smegmatis (Ms) msmeg5257 is a hemolysin III family protein that is homologous to Mycobacterium tuberculosis (Mtb) Rv1085c, but it has an unclear function in growth. To address this issue, we utilized the CRISPR/Cas9 gene editor to construct Δmsmeg5257 strains and combined RNA transcription and LC-MS/MS protein profiling to determine the functional role of msmeg5257 in Ms growth. The correlative analysis showed that the deletion of msmeg5257 inhibits ABC transporters in the cytomembrane and inhibits the biosynthesis of amino acids in the cell wall. Corresponding to these results, we confirmed that MSMEG5257 localizes in the cytomembrane via subcellular fractionation and also plays a role in facilitating the transport of iron ions in environments with low iron levels. Our data provide insights that msmeg5257 plays a role in maintaining Ms metabolic homeostasis, and the deletion of msmeg5257 significantly impacts the growth rate of Ms. Furthermore, msmeg5257, a promising drug target, offers a direction for the development of novel therapeutic strategies against mycobacterial diseases.

Abstract Triboelectric nanogenerator (TENG) is regarded as an effective strategy to convert environment mechanical energy into electricity to meet the distributed energy demand of large number of sensors in the Internet of Things (IoTs). Although TENG based on the coupling of triboelectrification and air-breakdown achieves a large direct current (DC) output, material abrasion is a bottleneck for its applications. Here, inspired by primary cell and its DC signal output characteristics, we propose a novel primary cell structure TENG (PC-TENG) based on contact electrification and electrostatic induction, which has multiple working modes, including contact separation mode, freestanding mode and rotation mode. The PC-TENG produces DC output and operates at low surface contact force. It has an ideal effective charge density (1.02 mC m−2). Meanwhile, the PC-TENG shows a superior durability with 99% initial output after 100,000 operating cycles. Due to its excellent output performance and durability, a variety of commercial electronic devices are powered by PC-TENG via harvesting wind energy. This work offers a facile and ideal scheme for enhancing the electrical output performance of DC-TENG at low surface contact force and shows a great potential for the energy harvesting applications in IoTs.

BackgroundTuberculosis may reoccur due to reinfection or relapse after initially successful treatment. Distinguishing the cause of TB recurrence is crucial to guide TB control and treatment. This study aimed to investigate the source of TB recurrence and risk factors related to relapse in Hunan province, a high TB burden region in southern China.MethodsA population-based retrospective study was conducted on all culture-positive TB cases in Hunan province, China from 2013 to 2020. Phenotypic drug susceptibility testing and whole-genome sequencing were used to detect drug resistance and distinguish between relapse and reinfection. Pearson chi-square test and Fisher exact test were applied to compare differences in categorical variables between relapse and reinfection. The Kaplan–Meier curve was generated in R studio (4.0.4) to describe and compare the time to recurrence between different groups. p 0.05). In addition, TB relapse occurs earlier in patients of Tu ethnicity compared to patients of Han ethnicity (p

Mycobacterium intracellulare is the most common cause of nontuberculous mycobacterial lung disease, with a rapidly growing prevalence worldwide. In this study, we performed comparative genomic analysis and antimicrobial susceptibility characteristics analysis of 117 clinical M. intracellulare strains in China. Phylogenetic analysis showed that clinical M. intracellulare strains had high genetic diversity and were not related to the geographical area. Notably, most strains (76.07%, 89/117) belonged to Mycobacterium paraintracellulare (MP) and Mycobacterium indicus pranii (MIP) in the genome, and we named them MP-MIP strains. These MP-MIP strains may be regarded as a causative agent of chronic lung disease. Furthermore, our data demonstrated that clarithromycin, amikacin, and rifabutin showed strong antimicrobial activity against both M. intracellulare and MP-MIP strains in vitro. Our findings also showed that there was no clear correlation between the rrs, rrl, and DNA gyrase genes (gyrA and gyrB) and the aminoglycosides, macrolides, and moxifloxacin resistance, respectively. In conclusion, this study highlights the high diversity of M. intracellulare in the clinical setting and suggests paying great attention to the lung disease caused by MP-MIP.

ABSTRACT: Objectives: The new antituberculous drugs delamanid and bedaquiline form the last line of defence against drug-resistant tuberculosis (TB). Understanding the background prevalence of resistance to new drugs can help predict the lifetime of these drugs’ effectiveness and inform regimen design. Methods: Mycobacterium tuberculosis without prior exposure to novel anti-TB drugs were analysed retrospectively. Drug susceptibility testing for bedaquiline, delamanid, linezolid, clofazimine and widely used first- and second-line anti-TB drugs was performed. All TB isolates with resistance to new or repurposed drugs were subjected to whole-genome sequencing to explore the molecular characteristics of resistance and to perform phylogenetic analysis. Results: Overall, resistance to delamanid, bedaquiline, linezolid and clofazimine was observed in 0.7% (11/1603), 0.4% (6/1603), 0.4% (7/1603) and 0.4% (6/1603) of TB isolates, respectively. Moreover, 1.0% (1/102), 2.9% (3/102), 3.9% (4/102) and 1.0% (1/102) of multidrug-resistant TB (MDR-TB) were resistant to bedaquiline, delamanid, linezolid and clofazimine, respectively. Whereas 22.2% (2/9) of extensively-drug resistant tuberculosis (XDR-TB) isolates were resistant to both delamanid and linezolid, and none was resistant to bedaquiline or clofazimine. Phylogenetic analysis showed that recent transmission occurred in two XDR-TB with additional resistance to delamanid and linezolid. None known gene mutation associated with delamanid resistance was detected. All four isolates with cross-resistance to bedaquiline and clofazimine had a detected gene mutation in Rv0678. Three of five strains with linezolid resistance had a detected gene mutation in rplC. Conclusion: Detection of resistance to new anti-TB drugs emphasises the pressing need for intensive surveillance for such resistance before their wide usage.

High reliability is a huge challenge for sliding mode triboelectric nanogenerator (TENG). Here the authors develop a floating self-excited sliding TENG achieving both high durability and output for sustainable micro mechanical energy harvesting.

ABSTRACT Multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB) is a global barrier for the Stop TB plan. To identify risk factors for treatment outcome and cluster transmission of MDR/RR-TB, whole-genome sequencing (WGS) data of isolates from patients of the Chongqing Tuberculosis Control Institute were used for phylogenetic classifications, resistance predictions, and cluster analysis. A total of 223 MDR/RR-TB cases were recorded between 1 January 2018 and 31 December 2020. Elderly patients and those with lung cavitation are at increased risk of death due to MDR/RR-TB. A total of 187 MDR/RR strains were obtained from WGS data; 152 were classified as lineage 2 strains. Eighty (42.8%) strains differing by a distance of 12 or fewer single nucleotide polymorphisms were classified as 20 genomic clusters, indicating recent transmission. Patients infected with lineage 2 strains or those with occupations listed as “other” are significantly associated with a transmission cluster of MDR/RR-TB. Analysis of resistant mutations against first-line tuberculosis drugs found that 76 (95.0%) of all 80 strains had the same mutations within each cluster. A total of 55.0% (44 of 80) of the MDR/RR-TB strains accumulated additional drug resistance mutations along the transmission chain, especially against fluoroquinolones (63.6% [28 of 44]). Recent transmission of MDR/RR strains is driving the MDR/RR-TB epidemics, leading to the accumulation of more serious resistance along the transmission chains. IMPORTANCE The drug resistance molecular characteristics of MDR/RR-TB were elucidated by genome-wide analysis, and risk factors for death by MDR/RR-TB were identified in combination with patient information. Cluster characteristics of MDR/RR-TB in the region were analyzed by genome-wide analysis, and risk factors for cluster transmission (recent transmission) were analyzed. These analyses provide reference for the prevention and treatment of MDR/RR-TB in Chongqing.

Mycobacterium kansasii can cause serious pulmonary disease. Here, the authors present a population genomics analysis of 358 environmental and clinical isolates from around the world, supporting the idea that municipal water is a main source of infection, and shedding light into the pathogen’s diversity and adaptation to the human host.

Abstract Objectives To explore the drug susceptibility of levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ) and delamanid (DLM) against multidrug resistant tuberculosis (MDR-TB) isolates from drug resistance survey of southwest China, and to illustrate the genetic characteristics of MDR-TB isolates with acquired drug resistance. Methods A total of 339 strains were collected from smear-positive TB patients in the drug resistance survey of southwest China between January 2014 and December 2016. The MICs for the above mentioned drugs were determined for MDR-TB by conventional drug susceptibility testing. Genes related to drug resistance were amplified with their corresponding pairs of primers. Results MDR was observed in 88 (26.0%; 88/339) isolates. LFX had the highest resistance rate (50.0%; 44/88), followed by MFX (38.6%; 34/88). The resistance rate to LZD, CFZ, and DLM was 4.5% (4/88), 3.4% (3/88), and 4.5% (4/88), respectively, and the lowest resistance rate was observed in BDQ (2.3%; 2/88). Of the 45 isolates resistant to LFX and MFX, the most prevalent resistance mutation was found in gyrA with the substitution of codon 94 (34/45, 75.6%). Two strains with CFZ - BDQ cross resistance had a mutation in the Rv0678 gene. Of the four LZD resistant isolates, two carried mutations in rplC gene. For the four isolates resistant to DLM, one isolate had mutations in codon 318 of fbiC gene, and two isolates were with mutations in codon 81 of ddn gene. Conclusion This study provided evidence of the usefulness of new anti-TB drugs in the treatment of MDR-TB in China.

Abstract In human-machine interaction, robotic hands are useful in many scenarios. To operate robotic hands via gestures instead of handles will greatly improve the convenience and intuition of human-machine interaction. Here, we present a magnetic array assisted sliding triboelectric sensor for achieving a real-time gesture interaction between a human hand and robotic hand. With a finger’s traction movement of flexion or extension, the sensor can induce positive/negative pulse signals. Through counting the pulses in unit time, the degree, speed, and direction of finger motion can be judged in real-time. The magnetic array plays an important role in generating the quantifiable pulses. The designed two parts of magnetic array can transform sliding motion into contact-separation and constrain the sliding pathway, respectively, thus improve the durability, low speed signal amplitude, and stability of the system. This direct quantization approach and optimization of wearable gesture sensor provide a new strategy for achieving a natural, intuitive, and real-time human-robotic interaction.

Improving the output performance of sliding mode triboelectric nanogenerators is a great challenge. Herein, a space charge accumulation effect, based on alternating shielding and blank-tribo areas, is demonstrated and effectively promotes charge density output.

Power management systems are urgently needed for maximally utilizing the energy generated from triboelectric energy devices. Here, the authors report a fractal-designed switched-capacitor-convertor as a high efficiency power management strategy for triboelectric nanogenerators.

Surface charge density is a key factor for developing high performance triboelectric nanogenerators. Herein, authors establish criteria to quantitatively evaluate the contact efficiency and air breakdown model on charge excitation triboelectric nanogenerators to maximize output charge density.

Summary: Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation.

ABSTRACT To gain a deep insight into the additional drug-resistant profiles, genetic diversity, and transmission dynamics of rifampicin-resistant tuberculosis (RR-TB) circulating in Hunan province, drug susceptibility testing and whole-genome-sequencing were performed among RR-TB strains collected from Jan. 2013 to Jun. 2018 in Hunan province. A total of 124 RR-TB strains were recovered successfully and included into the final analysis. Lineage 2.2.1 was the dominant sublineage, accounting for 72.6% (90/124), followed by lineage 4.5 (11.3%, 14/124), lineage 4.4 (8.1%, 10/124), lineage 4.2 (6.5%, 8/124) and lineage 2.2.2 (1.6%, 2/124). Overall, 83.1% (103/124) and 3.2% (4/124) of RR-TB were MDR-TB and XDR-TB, respectively. Nearly 30% of RR-TB isolates were resistant to fluoroquinolones, and 26.6% (33/124) were pre-XDR-TB. Moreover, 30.6% (38/124) of RR-TB strains were identified as phenotypically resistance to pyrazinamide. Totally, 17 clusters containing 48 (38.7%, 48/124) RR-TB strains were identified, ranging in size from 2 to 10 isolates. No significant difference was detected in clustering rate between lineage 2 and lineage 4 (χ2 = 0.027, P = 0.870). Our study revealed the complexity of RR-TB strains circulating in Hunan province with complex additional drug-resistant profile and relatively higher clustering rates. Comprehensive information based on WGS should be used to guide the design of treatment regimens and tailor public interventions. IMPORTANCE Comprehensive information such as genetic background and drug-resistant profile of MTB strains could help to tailor public interventions. However, these data are limited in Hunan province, one of the provinces with high-TB burden in China. So, this study aimed to provide us with deep insight into the molecular epidemiology of RR-TB isolates circulating in Hunan province by combining phenotypic drug susceptibility testing and whole-genome sequencing. To our knowledge, this is the first study to use whole-genome sequencing data of RR-TB strains spanning more than 5 years for molecular epidemiology analysis in Hunan province, which allows us to identify genetic background information and clustered strains more accurately. Our study revealed the complexity of RR-TB strains circulating in Hunan province with complex additional drug-resistant profile and relatively higher clustering rates. Comprehensive information based on WGS should be used to guide the design of treatment regimens and tailor public interventions.

Triboelectric nanogenerator (TENG) is a promising strategy for harvesting low frequency mechanical energy. However, the bottlenecks of limited electric output by air/dielectric breakdown and poor durability by material abrasion seriously restrict its further improvement. Herein, we propose a liquid lubrication promoted sliding mode TENG to address both issues. Liquid lubrication greatly reduces interface material abrasion, and its high breakdown strength and charge transmission effect further enhance device charge density. Besides, the potential decentralization design by the voltage balance bar effectively suppresses the dielectric breakdown. In this way, the average power density up to 87.26 W·m-2·Hz-1, energy conversion efficiency of 48%, and retention output of 90% after 500,000 operation cycles are achieved, which is the highest average power density and durability currently. Finally, a cell phone is charged to turn on by a palm-sized TENG device at 2 Hz within 25 s. This work has a significance for the commercialization of TENG-based self-powered systems.

ABSTRACT We designed this study to determine the trend of moxifloxacin resistance among multidrug-resistant tuberculosis (MDR-TB) patients from 2007 to 2013 in China to inform the composition of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment regimens. We assessed moxifloxacin resistance among MDR-TB isolates collected in national drug resistance surveys in 2007 and 2013 that included 3,634 smear-positive and 7,206 culture-positive pulmonary tuberculosis patients, respectively. Moxifloxacin susceptibility was examined by a Mycobacterium growth indicator tube (MGIT) 960 for the 2007 isolates, and by the minimum inhibitory concentration (MIC) method for the 2013 isolates, at both breakpoints 0.5 and 2.0 μg/mL. Risk factors were explored through multivariable log-binominal regression analysis. Mutations in gyrA and gyrB for part of the isolates were also studied through sequencing. Of 401 MDR strains isolated in 2007, moxifiloxacin resistance could be determined for 319 (79.6%): 41 (12.9%) and 10 (3.1%) were resistant at 0.5 and 2.0 μg/mL, respectively. Of 365 MDR strains isolated in 2013, 338 (92.6%) could be analyzed: 140 (41.4%) and 79 (23.4%) were resistant at 0.5 and 2.0 μg/mL. For patients in 2007, no characteristics were significantly associated with moxifloxacin resistance. For patients in 2013, patients aged ≥60 years (adjusted prevalence ratio [aPR], 1.46; 95% confidence interval [CI], 1.10 to 1.93) were more likely to have resistance at 0.5 μg/mL, whereas those residing in eastern China compared to those in central China had an increased risk of resistance at both 0.5 (aPR, 1.85; 95% CI, 1.38 to 2.48) and 2.0 μg/mL (aPR, 2.14; 95% CI, 1.35 to 3.40). Sequencing results were obtained for 245 and 266 MDR-TB isolates in 2007 and 2013, respectively. In total, 34 of 38 (89.5%) and 89 of 104 (85.6%) of 2007 and 2013 moxifloxacin-resistant (0.5 μg/mL) MDR-TB strains had mutations in the gyrA and gyrB gene, respectively. Asp94Gly was the most common mutation among 2007 (11 of 38, 28.9%) and 2013 isolates (24 of 104, 23.1%) and conferred high-level moxifloxacin resistance. Moxifloxacin resistance among MDR-TB patients in China increased from modest to high from 2007 to 2013. Moxifloxacin should be used carefully as a potentially effective drug for composing MDR/RR-TB regimens especially for elderly patients in China. Individual susceptibility testing especially rapid molecular-based assays should be conducted to confirm the susceptibility to moxifloxacin. IMPORTANCE China is one of the high-burden countries for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Moxifloxacin is one of the critical antituberculosis drugs for MDR/RR-TB treatment. Susceptibility to moxifloxacin is therefore very important to compose effective regimens and to provide protection against development of resistance of companion drugs such as bedaquiline and linezolid. There are, however, no nationally representative data on moxifloxacin resistance among MDR/RR-TB cases in China. Therefore, we assessed the resistance prevalence for moxifloxacin among MDR-TB strains isolated in national drug resistance surveys in 2007 and 2013 that covered 72 sites around the country. We demonstrate that the prevalence of moxifloxacin resistance in MDR-TB isolates increased from modest to high, which should prompt the national tuberculosis program to use moxifloxacin cautiously in second-line regimens to treat MDR/RR-TB unless susceptibility can be laboratory-confirmed.

Background: To contain the pandemic of COVID-19, China has implemented a series of public health interventions that impacted the tuberculosis control substantially, but these impacts may vary greatly depending on the severity of the local COVID-19 epidemic. The impact of COVID-19 on TB control in Ningxia Hui Autonomous Region is little known.Methods: Based on the national TB Information Management System (TBIMS), this study accessed the actual impact of COVID-19 on TB by comparing TB notifications, pre-treatment delays, and clinical characteristics of TB cases between 2020 COVID-19 period and 2017–2019 baseline. The data were divided into three periods based on the response started to fight against COVID-19 in Ningxia Hui Autonomous Region, including the control period (10 weeks before the pandemic), intensive period (10 weeks during the Ningxia Hui Autonomous Region lockdown), and regular (10 additional weeks after Ningxia Hui Autonomous Region reopen).Results: TB notification dropped sharply in the first week of the intensive period but took significantly longer to return to the previous level in 2020 compared with the 2017–2019 baseline. Totally, the TB notification rates decreased by more than 60% in the intensive period of COVID-19 compared with the average level of 2017–2019. The sputum smear-positive rate of TB patients diagnosed in intensive period of COVID-19 was significantly higher than that in the corresponding periods of 2017–2019 (P < 0.001). The rate of cavity on X-ray inspection of TB cases diagnosed in the intensive period of COVID-19 was significantly higher than that in period 2 of 2017–2019 (23.5 vs. 15.4%, P = 0.004). The patients' delay in the intensive period was significantly longer than that before the pandemic (P = 0.047).Conclusions: The TB notification in Ningxia was impacted dramatically by the pandemic of COVID-19. To compensate for the large numbers of missed diagnosis as well as delayed diagnosis during the intensive period of COVID-19, an urgent restoration of normal TB services, and further emphasis on enhanced active case finding and scale-up of household contact tracing and screening for TB-related symptoms or manifestation, will be essential.

Abstract Mycobacterium abscessus (M. abscessus) and Mycobacterium massiliense (M. massiliense) are major pathogens that cause post-surgical wound infection and chronic pulmonary disease. Although they are closely related subspecies of M. abscessus complex, their infections are associated with different drug-resistance and cure rate. In the present study, a loop-mediated isothermal amplification (LAMP) coupled with lateral flow dipstick (LFD) method was developed to simultaneous detect M. abscessus and M. massiliense, via specific erm(41) gene. The amplification was carried out at 65 °C for only 60 min, and the results could be visualized on a lateral flow strip. Positive results only occurred in M. abscessus and M. massiliense, no cross-reaction with other mycobacterial species was observed. Therefore, the cost-effective MABC (M. abscessus complex)–LAMP–LFD method developed here was able to correct the diagnose of M. abscessus and M. massiliense infection in a short time. Thus, this method could be used to guide clinicians in treatment of M. abscessus group infections.

CP4-EPSPS (Agrobacterium sp. strain CP4 5-enolpyruvylshikimate-3-phosphate synthase) protein showed remarkable thermostability and was highly resistant to proteases, such as trypsin. In order to eliminate the pollution of CP4-EPSPS from the accumulated straws to the surrounding environment during the winter, the present study investigated the extracellular proteases of 21 psychrophilic strains isolated from the south polar region. The results indicated that Stenotrophomonas maltophilia 780 was able to degrade CP4-EPSPS at 18 °C efficiently. Further study indicated that it was able to grow in the extract of Roundup Ready soybean at 18 °C, with CP4-EPSPS degraded to an undetectable level within 72 h. The extracellular proteases of Stenotrophomonas maltophilia 780 are thermo-sensitive, with an optimal temperature of 65 °C. The genomic sequencing result indicated that this strain had more than a hundred putative protease and peptidase coding genes, which may explain its high capability in decomposing CP4-EPSPS.

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