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OBJECTIVES: This study investigated the transmission patterns of tuberculosis and its associated risk factors in Hunan province to inform the development of prevention and control strategies in the region. METHODS: An 8-year retrospective population-based genomic epidemiological study was conducted. Genomic clusters were defined using distance thresholds of 12-single-nucletide-polymorphisms. Risk factors associated with TB transmission were analyzed using logistic regression model. Kernel Density analysis was used to locate hotspots where transmission occurred. RESULTS: Among 2649 TB cases included in this study, 275 clusters were identified, with an overall clustering rate of 24.7% (654/2649). Nearly 95% (620/654) of clustered strains were isolated from the same county. Of the 275 clusters, 23 (8.4%, 23/275) had differences in drug-resistant profiles, with FQs resistance mutations occurring most frequently (52.2%, 12/23). Multivariate analysis identified male TB patients, those aged 30-60 years, ethnic minorities, non-farmers, retreated TB patients, and individuals infected with MDR/RR-TB as independent risk factors for TB transmission (P<0.05). CONCLUSION: Recent transmission in the region is predominantly occurring within counties. The risk factors related to the TB transmission and the hotspots where transmission occurs can provide a scientific basis for the formulation of targeted tuberculosis prevention and control strategies.
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Importance: Despite posing a significant challenge to global tuberculosis (TB) elimination efforts, recurrent TB remains understudied due to the challenges of long-term observation. Objective: To investigate the burden of recurrent TB using data from patients with pulmonary TB (PTB) in China. Design, Setting, and Participants: This retrospective cohort study included all bacteriologically confirmed or clinically diagnosed PTB cases reported to the Tuberculosis Information Management System with completed or successful treatment outcomes from January 1, 2005, to December 31, 2021. Data were analyzed from July 15, 2022, to October 28, 2023. Exposures: Newly diagnosed PTB was classified into primary, hematogenous disseminated, or secondary PTB. Main Outcomes and Measures: The primary outcome was the annual recurrence rate, stratified by disease classification, over the 17-year observation period. The recurrence rate for year n was calculated by dividing the number of patients with recurrent TB in year n by observed person-years in year n. The secondary outcome was the annual proportion of recurrent TB among reported cases and associated risk factors. Results: Of 13 833 249 patients with TB reported to the Tuberculosis Information Management System, 10 482 271 with PTB met the inclusion criteria. Of these, 68.9% were male, 22.3% were 65 years or older, 89.6% were of Han ethnicity, and 68.4% were agricultural workers. A total of 413 936 patients experienced a recurrent TB episode after successful treatment, resulting in an overall recurrence rate of 0.47 (95% CI, 0.47-0.48) per 100 person-years. The recurrence rate for patients with primary PTB was 0.24 (95% CI, 0.22-0.26) per 100 person-years; for hematogenous disseminated PTB, 0.37 (95% CI, 0.36-0.38) per 100 person-years; and for secondary PTB, 0.48 (95% CI, 0.47-0.48) per 100 person-years. The cumulative proportion of recurrences within the first 2 years accounted for 48.9% of all recurrent cases. The proportion of recurrent cases among notified incident cases increased 1.9-fold from 4.7% in 2015 to 8.8% in 2021. Among other factors, ages 45 to 64 years (adjusted hazard ratio, 1.77 [95% CI, 1.65-1.89]) and having completed treatment (adjusted hazard ratio, 1.16 [95% CI, 1.14-1.18]) were identified as associated with recurrence. Conclusions and Relevance: In this retrospective cohort study, the PTB recurrence rate was substantially higher than the incidence, and the proportion of recurrent cases increased. Almost half of the recurrence occurred within the first 2 years, suggesting that routine posttreatment follow-up may represent an important strategy for accelerating TB elimination.
Subject(s)
Recurrence , Tuberculosis, Pulmonary , Humans , China/epidemiology , Male , Female , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/drug therapy , Retrospective Studies , Middle Aged , Adult , Aged , Young Adult , Risk Factors , Adolescent , Aged, 80 and overABSTRACT
[This corrects the article DOI: 10.1371/journal.pgph.0001788.].
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Background: Tuberculosis remains a major public health concern in China, with varying prevalence and drug resistance profiles across regions. This study explores the genetic diversity and drug-resistant profiles of MTB strains in Hinggan League, a high TB burden in Inner Mongolia, China. Methods: This population-based retrospective study, encompassing all culture-positive TB cases from Jun. 2021 to Jun. 2023 in Hinggan League. Drug resistant profiles and genetic diversity of MTB strains were assessed using phenotypic drug susceptibility testing and whole-genome sequencing. Risk factors associated with drug resistance were analyzed using univariate and multivariate logistic regression models. Results: A total of 211 MTB strains were recovered successfully and included into final analysis. Lineage 2.2.1 (88.6%, 187/211) was the dominant sub-lineage, followed by lineage 4.5 (7.1%, 15/211) and lineage 4.4 (4.3%, 9/211). MTB strains exhibited the highest resistance rates to isoniazid (16.1%, 34/211), followed by rifampicin (10.0, 21/211). In addition, the MTB strains also showed relatively high rates of resistance against new and repurposed anti-TB drugs, with resistant rates of 2.4% (5/211) to delamanid and 1.9% (4/211) to bedaquiline. Overall, 25.6% (54/211) of MTB strains were DR-TB, and 14 MTB strains met the definition of MDR-TB, including 7 strains of simple-MDR-TB, 5 of pre-XDR-TB, and 2 of XDR-TB. Genetic analysis revealed that the dominant mutations of isoniazid-, rifampin-, ethambutol-, levofloxacin-/moxifloxacin-, and ethionamide- resistance were katG_Ser315Thr(46.4%), rpoB_Ser450Leu (47.4%), embB_Met306Val (25.0%), gyrA_Asp94Ala (40.0%), and fabG1_c15t (42.9%), respectively. Previously treated patients (AOR = 2.015, 95% CI: 1.052-4.210) and male patients (AOR = 3.858, 95% CI: 1.416-10.511) were identified as independent risk factors associated with DR-TB. Conclusion: Our study offers crucial insights into the genetic diversity and drug-resistant profiles of TB strains circulating in Hinggan League. These findings are valuable for DR-TB surveillance and for guiding treatment regimens and public health interventions in the region.
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BACKGROUND: Tuberculosis is a chronic infectious disease that endangers people's health, and China is a country with a high burden of tuberculosis. To accelerate the progress towards ending TB, the Chinese government implemented the End TB Action Plan (2019-2022), which consists of six actions. Among the End TB Action Plan, health promotion was conducted to improve the awareness of TB knowledge among Chinese people. The purpose of this study is to evaluate the effectiveness of implementing TB health promotion activities outlined in the End TB Action Plan, and to provide recommendations for future TB prevention and control plan. METHODS: A cross-sectional study was conducted in nine Chinese provinces in 2022. A total of 11,920 Chinese people filled out the questionnaire. Logistic regression analysis was used to explore that overall awareness of TB core information is associated with whether they received TB health education. RESULTS: The study involved 11,920 Chinese participants. The overall awareness rate of the core information of TB was 84.2%, which does not reach the 85% goal of the End TB Action Plan. The single awareness rate that TB is a chronic infectious disease and that the vast majority of TB patients can be cured were 75.3% and 76.0%. Participants who received TB health education had a higher awareness rate of TB core information. Participants who were elderly, retired or had a primary school education or below had poor awareness of the core information of TB. Participants who were elderly, lived in urban areas, were equipment operators or had a primary school education or below received less TB health education. Participants mainly received TB health education through TV (44.6%) and Internet (37.8%), preferred TV, broadcasts or movies (58.9%) and Internet advertising (54.7%). Participants preferred illustrated (46.2%) and audio-visual (44.8%) advertising materials. The common sources used to answer health-related questions on the internet were We-Medias (48.3%) and search engines (38.9%). Participants preferred to use short-form videos (66.8%) and illustrations (53.1%) to answer health-related questions. CONCLUSIONS: Health promotion action for TB had a positive effect in China, but the awareness of TB was inadequate among Chinese people, and it is necessary to strengthen TB health education for those people. Moreover, TB prevention and control institutions should advertise TB more in audio-visual and illustrated forms on the Internet and audio-visual media. Health-related questions should be published in short-form video and illustrated forms in the We-Media and search engine more.
Subject(s)
Health Knowledge, Attitudes, Practice , Health Promotion , Tuberculosis , Humans , China/epidemiology , Male , Cross-Sectional Studies , Female , Health Promotion/methods , Adult , Middle Aged , Tuberculosis/prevention & control , Tuberculosis/epidemiology , Young Adult , Surveys and Questionnaires , Aged , Adolescent , Health EducationABSTRACT
Tuberculosis (TB) is the leading infectious cause of morbidity and mortality globally. Despite available tools for preventing, finding, and treating TB, many people with TB remain undiagnosed. In high-incidence settings, TB transmission is ubiquitous within the community, affecting both high-risk groups and the general population. In fact, most people who develop TB come from the general population. To disrupt the chain of transmission that sustains the TB epidemic, we need to find and treat everyone with infectious TB as early as possible, including those with minimal symptoms or subclinical TB who are unlikely to present for care. Important elements of an effective active case-finding strategy include effective social mobilisation and community engagement, using sensitive screening tools that can be used at scale, and embracing population-wide screening in high-incidence ('hot spot') areas. We require a better description of feasible delivery models, 'real-life' impact and cost effectiveness to enable wider implementation.
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Objective: To detect levofloxacin (LFX) and moxifloxacin (MFX) resistance among rifampicin-resistant tuberculosis (RR-TB) isolates, and predict the resistance level based on specific mutations in gyrA and gyrB genes. Methods: A total of 686 RR-TB isolates were collected from Chinese Drug Resistance Surveillance Program from 2013 to 2020. The minimum inhibitory concentrations (MICs) of 12 anti-TB drugs were acquired using the broth microdilution method, followed by whole genome sequencing (WGS) analysis. Results: Among the 686 RR isolates, the most prevalent resistance was to isoniazid (80.5 %) and ethambutol (28.4 %), followed by LFX (26.1 %) and MFX (21.9 %). The resistance rate of LFX (26.1%-99.4 %) was higher than that of MFX (21.9%-83.3 %) across various drug resistance patterns. Of the 180 fluoroquinolones (FQs) resistant isolates, 168 (93.3 %) had mutations in quinolone-resistant determining regions (QRDRs) with 21 mutation types, and Asp94Gly (32.7 %, 55/168) was the predominant mutation. Isolates with mutations in Asp94Asn and Asp94Gly were associated with high levels of resistance to LFX and MFX. Using broth microdilution method as gold standard, the sensitivities of WGS for LFX and MFX were 93.3 % and 98.0 %, and the specificities were 98.6 % and 95.0 %, respectively. Conclusion: The resistance rate of LFX was higher than that of MFX among various drug resistance patterns in RR-TB isolates. The gyrA Asp94Gly was the predominant mutation type underlying FQs resistance. However, no significant difference was observed between mutation patterns in gyrA gene and resistance level of FQs.
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Bacteriophages play an essential role in shaping the diversity and metabolism of bacterial communities. Marine Roseobacter group is an abundant heterotrophic bacterial group that is involved in many major element cycles, especially carbon and sulfur. Members of the Roseobacter CHUG (Clade Hidden and Underappreciated Globally) lineage are globally distributed and are activated in pelagic marine environments. In this study, we isolated and characterized a phage, CRP-810, that infects the CHUG strain FZCC0198. The genome of CRP-810 was dissimilar to those of other known phages. Additionally, 251 uncultured viral genomes (UViGs) closely related to CRP-810 were obtained from the uncultivated marine viral contig databases. Comparative genomic and phylogenetic analyses revealed that CRP-810 and these related UViGs exhibited conserved genome synteny, representing a new phage family with at least eight subgroups. Most of the CRP-810-type phages contain an integrase gene, and CRP-810 can be integrated into the host genome. Further analysis revealed that three CRP-810-type members were prophages found in the genomes of marine SAR11, Poseidonocella, and Sphingomonadaceae. Finally, viromic read-mapping analysis showed that CRP-810-type phages were globally distributed and displayed distinct biogeographic patterns related to temperature and latitude. Many members with a lower G + C content were mainly distributed in the trade station, whereas members with a higher G + C content were mainly distributed in polar and westerlies station, indicating that the niche differentiation of phages was subject to host adaptation. Collectively, these findings identify a novel phage family and expand our understanding of phylogenetic diversity, evolution, and biogeography of marine phages. IMPORTANCE: The Roseobacter CHUG lineage, affiliated with the Pelagic Roseobacter Cluster (PRC), is widely distributed in the global oceans and is active in oligotrophic seawater. However, knowledge of the bacteriophages that infect CHUG members is limited. In this study, a CHUG phage, CRP-810, that infects the CHUG strain FZCC0198, was isolated and shown to have a novel genomic architecture. In addition, 251 uncultured viral genomes closely related to CRP-810 were recovered and included in the analyses. Phylogenomic analyses revealed that the CRP-810-type phages represent a new phage family containing at least eight genus-level subgroups. Members of this family were predicted to infect various marine bacteria. We also demonstrated that the CRP-810-type phages are widely distributed in global oceans and display distinct biogeographic patterns related to latitude. Collectively, this study provides important insights into the genomic organization, diversity, and ecology of a novel phage family that infect ecologically important bacteria in the global ocean.
Subject(s)
Bacteriophages , Genome, Viral , Phylogeny , Roseobacter , Roseobacter/virology , Roseobacter/genetics , Roseobacter/classification , Bacteriophages/genetics , Bacteriophages/classification , Bacteriophages/isolation & purification , Prophages/genetics , Prophages/classification , Prophages/isolation & purification , Seawater/microbiology , Seawater/virology , GenomicsABSTRACT
The biaxial compression experiments of rock-like materials with two flaws are carried out under different flaw inclination angle, rock bridge ligament angle, lateral stress. The experimental studies show that crack propagation modes of rock-like material are as follows: wing crack through mode (Y mode), shear crack through mode (J mode), mixed crack through mode (wing shear JY mode), longitudinal extension of crack and transverse shear splitting. prefabricated fractured rock specimens have experienced the closing stage of prefabricated fractures, the elastic deformation stage, the generation and expansion of cracks (or plastic strengthening), and the residual loading stage. The peak strength of the specimen is increases with the increase of flaw inclination angle and lateral stress. With the increase of the rock bridge ligament angle, the failure of the rock bridge region changes from the shear crack failure to composite failure of shear crack and the wing type tensile crack failure, and then to the wing crack failure. With the increase of the lateral pressure, the failure of the specimen changes from the wing type tensile crack failure to the wing type and shear crack failure, and then to shear crack failure. The flaw inclination angle mainly changes the form of crack growth but does not effect on the failure modes. The counting number of acoustic emission events at the center of the sample is relative large, indicating that the cacks appear in the part of the rock bridge firstly. With the increasing of loads, the cracks of the rock bridge expanding constantly and connecting finally. The changes of acoustic emission event counts is consistent with the macroscopic damage form obtained from the experiments.
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To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency testing performed DST, and the sensitivity, specificity, reproducibility, and accordance rate were calculated from data of 13 rounds proficiency testing results for DST from 2008 to 2021. A total of 30 and 20 strains of Mycobacterium tuberculosis with known susceptibility results were sent to each laboratory in 2008 to 2019, 2020 and 2021, respectively. The number of participating laboratories ranged from 30 in 2009 to 546 in 2021. L-J DST was the predominant method. The specificity presented relatively higher than sensitivity. Improvement of specificity were observed for all drugs through the years, while sensitivity did not show improvement for amikacin and capreomycin. Accordance rate of pyrazinamide and kanamycin and reproducibility of capreomycin and pyrazinamide were not significantly improved through the years. Most of the participating laboratories significantly improved the quality of their DST through the consecutive rounds of proficiency testing except for second-line injectable drugs and pyrazinamide. The results highlight the importance of developing novel and/or improving existing methods for phenotypic DST for certain drugs.
Subject(s)
Antitubercular Agents , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Mycobacterium tuberculosis/drug effects , China , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Humans , Laboratory Proficiency Testing , Reproducibility of Results , Phenotype , Amikacin/pharmacology , Amikacin/therapeutic use , Pyrazinamide/therapeutic useABSTRACT
BACKGROUND: Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. METHODS: To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. RESULTS: We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2-4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. CONCLUSIONS: Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.
Subject(s)
Antitubercular Agents , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , China/epidemiology , Humans , Antitubercular Agents/pharmacology , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/epidemiology , Prevalence , Nitroimidazoles/pharmacology , Genotype , Mutation , Whole Genome SequencingABSTRACT
Phages play an essential role in controlling bacterial populations. Those infecting Pelagibacterales (SAR11), the dominant bacteria in surface oceans, have been studied in silico and by cultivation attempts. However, little is known about the quantity of phage-infected cells in the environment. Using fluorescence in situ hybridization techniques, we here show pelagiphage-infected SAR11 cells across multiple global ecosystems and present evidence for tight community control of pelagiphages on the SAR11 hosts in a case study. Up to 19% of SAR11 cells were phage-infected during a phytoplankton bloom, coinciding with a ~90% reduction in SAR11 cell abundance within 5 days. Frequently, a fraction of the infected SAR11 cells were devoid of detectable ribosomes, which appear to be a yet undescribed possible stage during pelagiphage infection. We dubbed such cells zombies and propose, among other possible explanations, a mechanism in which ribosomal RNA is used as a resource for the synthesis of new phage genomes. On a global scale, we detected phage-infected SAR11 and zombie cells in the Atlantic, Pacific, and Southern Oceans. Our findings illuminate the important impact of pelagiphages on SAR11 populations and unveil the presence of ribosome-deprived zombie cells as part of the infection cycle.
Subject(s)
Bacteriophages , Ribosomes , Ribosomes/metabolism , Bacteriophages/genetics , Bacteriophages/physiology , Phytoplankton/virology , Phytoplankton/genetics , Phytoplankton/metabolism , In Situ Hybridization, Fluorescence , Alphaproteobacteria/genetics , Alphaproteobacteria/metabolism , Ecosystem , Seawater/microbiology , Seawater/virology , Oceans and SeasABSTRACT
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.
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The ubiquitous and abundant marine phages play critical roles in shaping the composition and function of bacterial communities, impacting biogeochemical cycling in marine ecosystems. Autographiviridae is among the most abundant and ubiquitous phage families in the ocean. However, studies on the diversity and ecology of Autographiviridae phages in marine environments are restricted to isolates that infect SAR11 bacteria and cyanobacteria. In this study, ten new roseophages that infect marine Roseobacter strains were isolated from coastal waters. These new roseophages have a genome size ranging from 38â917 to 42â634 bp and G+C content of 44.6-50â%. Comparative genomics showed that they are similar to known Autographiviridae phages regarding gene content and architecture, thus representing the first Autographiviridae roseophages. Phylogenomic analysis based on concatenated conserved genes showed that the ten roseophages form three distinct subgroups within the Autographiviridae, and sequence analysis revealed that they belong to eight new genera. Finally, viromic read-mapping showed that these new Autographiviridae phages are widely distributed in global oceans, mostly inhabiting polar and estuarine locations. This study has expanded the current understanding of the genomic diversity, evolution and ecology of Autographiviridae phages and roseophages. We suggest that Autographiviridae phages play important roles in the mortality and community structure of roseobacters, and have broad ecological applications.
Subject(s)
Bacteriophages , Roseobacter , Humans , Bacteriophages/genetics , Roseobacter/genetics , Ecosystem , Genome, Viral , GenomicsABSTRACT
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.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Whole Genome Sequencing , Humans , China/epidemiology , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/classification , Male , Adult , Female , Middle Aged , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/transmission , Tuberculosis, Multidrug-Resistant/microbiology , Cross-Sectional Studies , Retrospective Studies , Young Adult , Risk Factors , Adolescent , Aged , Rifampin/pharmacology , Antitubercular Agents/pharmacology , Genome, Bacterial , Drug Resistance, Multiple, BacterialABSTRACT
An innovative molecularly imprinted polymer membrane (MIPM) was prepared with polyvinylidene difluoride (PVDF) as the support, phenytoin (PHT) as the single template, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linking reagent, azobisisobutyronitrile as the initiator, and acetonitrile-dimethylformamide (1 : 1.5, v/v) as the porogen. These materials were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller measurements and X-ray photoelectron spectroscopy. Their adsorption performances were evaluated through a series of experiments including isothermal adsorption, kinetic adsorption, selective adsorption, adsorption-desorption, reusability, and preparation reproducibility. Additionally, the application was explored by investigating the extraction recovery of MIPMs towards PHT, phenobarbital (PHB) and lamotrigine (LTG) in different matrices including methanol, normal saline (NS), phosphate buffer solution (PBS) and plasma. The results showed that MIPMs with rough and porous surfaces were successfully constructed, which offered good preparation reproducibility, reusability and selectivity. The adsorption capacities of MIPMs towards PHT, PHB and LTG were 2.312, 2.485 and 2.303 mg g-1, respectively, while their corresponding imprinting factors were 8.538, 12.122 and 4.562, respectively. The adsorption equilibrium of MIPMs was achieved within 20 min at room temperature without stirring or ultrasonication. The extraction recoveries of MIPMs for PHT, PHB or LTG in methanol, NS and PBS were more than 80% with an RSD% value of less than 3.64. In the case of plasma, the extraction recovery of MIPMs for PHT and PHB was more than 80% with an RSD% value of less than 2.41, while that of MIPMs for LTG was more than 65% with an RSD% value of less than 0.99. All the results indicated that the preparation method for MIPMs was simple, stable, and reliable, and the prepared MIPMs possessed excellent properties to meet the extraction application of PHT, PHB and LTG in different matrices.
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Tuberculosis (TB) is one of the top ten causes of death worldwide, taking the lives of over a million people annually. In addition to being a serious health issue, TB is also closely linked to eradicating poverty according to the Sustainable Development Goals (SDGs) of the United Nations (UN). All UN members have committed to ending the TB epidemic by 2030. China has one of the highest TB loads worldwide, ranking third in the world on many TB burden indices. The national strategy for TB control is aimed at creating a collaborative network and integrating TB treatment into the medical system. According to the WHO's global TB report, China is expected to have 748,000 new cases of TB in 2022 and an incidence of 52 cases per 100,000 people. Ending TB remains a huge challenge and requires comprehensive control strategies in China. In this work, we have discussed the challenges of TB prevention and control in China and proposed specific measures to end TB.
Subject(s)
Tuberculosis , Humans , Tuberculosis/epidemiology , Tuberculosis/prevention & control , China/epidemiologyABSTRACT
Background: Tuberculosis (TB) remains a severe public health problem globally, and it is essential to comprehend the transmission pattern to control tuberculosis. Herein, we evaluated the drug-resistant characteristics, recent transmission, and associated risk factors of TB in Golmud, Qinghai, China. Methods: In this study, we performed a population-based study of patients diagnosed with TB in Golmud from 2013 to 2018. Drug-susceptibility testing and whole-genome sequencing were performed on 133 Mycobacterium tuberculosis strains. The genomic clustering rate was calculated to evaluate the level of recent transmission. Risk factors were identified by logistic regression analysis. Results: Our results showed that 46.97% (62/132) of strains were phylogenetically clustered and formed into 23 transmission clusters, suggesting a high recent transmission of TB in the area. 12.78% (17/133) strains were multidrug-resistant/rifampicin tuberculosis (MDR/RR-TB), with a high drug-resistant burden. Based on drug resistance gene analysis, we found 23 strains belonging to genotype MDR/RR-TB, where some strains may have borderline mutations. Among these strains, 65.2% (15/23) were found within putative transmission clusters. Additionally, risk factor analysis showed that recent transmission of TB happened more in patients with Tibetan nationality or older age. Conclusion: Overall our study indicates that the recent transmissions of MTB strains, especially genotypic MDR/RR strains, drive the tuberculosis epidemic in Golmud, which could contribute to developing effective TB prevention and control strategies.
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ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry (Morus alba L.) leaf is a well-known herbal medicine and has been used to treat diabetes in China for thousands of years. Our previous studies have proven mulberry leaf water extract (MLWE) could improve type 2 diabetes mellitus (T2D). However, it is still unclear whether MLWE could mitigate T2D by regulating gut microbiota dysbiosis and thereof improve intestinal permeability and metabolic dysfunction through modulation of lipopolysaccharide (LPS) and endocannabinoid system (eCBs). AIM OF STUDY: This study aims to explore the potential mechanism of MLWE on the regulation of metabolic function disorder of T2D mice from the aspects of gut microbiota, LPS and eCBs. MATERIALS AND METHODS: Gut microbiota was analyzed by high-throughput 16S rRNA gene sequencing. LPS, N-arachidonoylethanolamine (AEA) and 2-ararchidonylglycerol (2-AG) contents in blood were determined by kits or liquid phase chromatography coupled with triple quadrupole tandem mass spectrometry, respectively. The receptors, enzymes or tight junction protein related to eCBs or gut barrier were detected by RT-PCR or Western blot, respectively. RESULTS: MLWE reduced the serum levels of AEA, 2-AG and LPS, decreased the expressions of N-acylphophatidylethanolamine phospholipase D, diacylglycerol lipase-α and cyclooxygenase 2, and increased the expressions of fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA), alpha/beta hydrolases domain 6/12 in the liver and ileum and occludin, monoacylglycerol lipase and cannabinoid receptor 1 in the ileum of T2D mice. Furthermore, MLWE could change the abundances of the genera including Acetatifactor, Anaerovorax, Bilophila, Colidextribacter, Dubosiella, Gastranaerophilales, Lachnospiraceae_NK4A136_group, Oscillibacter and Rikenella related to LPS, AEA and/or 2-AG. Moreover, obvious improvement of MLWE treatment on serum AEA level, ileum occludin expression, and liver FAAH and NAAA expression could be observed in germ-free-mimic T2D mice. CONCLUSION: MLWE could ameliorate intestinal permeability, inflammation, and glucose and lipid metabolism imbalance of T2D by regulating gut microbiota, LPS and eCBs.
Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Morus , Mice , Animals , Diabetes Mellitus, Type 2/drug therapy , Endocannabinoids/metabolism , Lipopolysaccharides , Morus/chemistry , Gastrointestinal Microbiome/genetics , Dysbiosis/drug therapy , Occludin , RNA, Ribosomal, 16S , Plant Leaves/metabolismABSTRACT
Colorectal cancer (CRC) presents a landscape of intricate molecular dynamics. In this study, we focused on the role of the leukotriene B4 receptor (LTB4R) in CRC, exploring its significance in the disease's progression and potential therapeutic approaches. Using bioinformatics analysis of the GSE164191 and the Cancer Genome Atlas-colorectal adenocarcinoma (TCGA-COAD) datasets, we identified LTB4R as a hub gene influencing CRC prognosis. Subsequently, we examined the relationship between LTB4R expression, apoptosis, and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway through cellular and mice experiments. Our findings revealed that LTB4R is highly expressed in CRC samples and is pivotal for determining prognosis. In vitro experiments demonstrated that silencing LTB4R significantly impeded CRC cell viability, migration, invasion, and colony formation. Correspondingly, in vivo tests indicated that LTB4R knockdown led to markedly slower tumor growth in mice models. Further in-depth investigation revealed that LTB4R knockdown significantly amplified the apoptosis in CRC cells and upregulated the expression of apoptosis-related proteins, such as caspase-3 and caspase-9, while diminishing p53 expression. Interestingly, silencing LTB4R also resulted in a significant downregulation of the PI3K/AKT/mTOR signaling pathway. Moreover, pretreatment with the PI3K activator 740Y-P only partially attenuated the effects of LTB4R knockdown on CRC cell behavior, emphasizing LTB4R's dominant influence in CRC cell dynamics and signaling pathways. LTB4R stands out as a critical factor in CRC progression, profoundly affecting cellular behavior, apoptotic responses, and the PI3K/AKT/mTOR signaling pathway. These findings not only shed light on LTB4R's role in CRC but also establish it as a potential diagnostic biomarker and a promising target for therapeutic intervention.