Hsa_circ_0004831 serves as a blood-based prognostic biomarker for colorectal cancer and its potentially circRNA-miRNA-mRNA regulatory network construction.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promising prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. Here, we explored the role of hsa_circ_0004831 in blood extracellular vesicles and its prognostic value in CRC. METHODS: The circRNA and mRNA expression level matrix in extracellular vesicles of CRC and normal samples were obtained from the exoRBase database. The corresponding miRNA expression level matrix in extracellular vesicles was downloaded from the BBCancer database. Differentially expressed circRNAs, miRNAs and mRNAs were identified using the limma package of R software at the cut-off criteria of fold change (FC) > 2 and adj. p < 0.05. RT-qPCR assay was conducted to measure hsa_circ_0004831 expression level in CRC blood samples. A circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on competitive endogenous RNA mechanism and differentially expressed genes. The mRNAs co-expressed with hsa_circ_0004831 were screened at the cut-off criteria of pearson |r| > 0.3 and p < 0.05. Gene set enrichment analysis (GSEA) based on co-expressed mRNAs was used to explore the potential molecular function of hsa_circ_0004831. RESULTS: Differentially expressed circRNAs, miRNAs and mRNAs were identified and hsa_circ_0004831 had a FC value of 3.92 in CRC blood extracellular vesicles. The RT-qPCR assay showed that the hsa_circ_0004831 was up-regulated in CRC blood samples. The overall survival analysis found that high expression of hsa_circ_0004831 was linked with poorer prognosis. Finally, a circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on down-regulated miR-4326 and 12 up-regulated mRNAs. GSEA indicated that mRNAs co-expressed with hsa_circ_0004831 were involved in EMT, WNT and p53 signaling pathways. CONCLUSIONS: The study confirmed the up-regulation of hsa_circ_0004831 in CRC, and it may act as a vital prognostic biomarker. The circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 could be used to uncover the tumorigenesis and progression of CRC.

Regioselective Chlorolactonization of Styrene-Type Carboxylic Esters and Amides via PhICl2-Mediated Oxidative C-O/C-Cl Bond Formations.

A facile method employing styrene-type carboxylic esters or amides in the presence of PhICl2 in CH3CN was developed to achieve the synthesis of 6-endo products 3,4-dihydroisocoumarins or 3,4-dihydroisocoumarin-1-imines in good to high yields. This metal-free regioselective intramolecular chlorolactonization process was proposed to involve a PhICl2-mediated oxidative C-O bond formation followed by C-Cl bond formation.

An improved Bayesian network method for reconstructing gene regulatory network based on candidate auto selection.

BACKGROUND: The reconstruction of gene regulatory network (GRN) from gene expression data can discover regulatory relationships among genes and gain deep insights into the complicated regulation mechanism of life. However, it is still a great challenge in systems biology and bioinformatics. During the past years, numerous computational approaches have been developed for this goal, and Bayesian network (BN) methods draw most of attention among these methods because of its inherent probability characteristics. However, Bayesian network methods are time consuming and cannot handle large-scale networks due to their high computational complexity, while the mutual information-based methods are highly effective but directionless and have a high false-positive rate. RESULTS: To solve these problems, we propose a Candidate Auto Selection algorithm (CAS) based on mutual information and breakpoint detection to restrict the search space in order to accelerate the learning process of Bayesian network. First, the proposed CAS algorithm automatically selects the neighbor candidates of each node before searching the best structure of GRN. Then based on CAS algorithm, we propose a globally optimal greedy search method (CAS + G), which focuses on finding the highest rated network structure, and a local learning method (CAS + L), which focuses on faster learning the structure with little loss of quality. CONCLUSION: Results show that the proposed CAS algorithm can effectively reduce the search space of Bayesian networks through identifying the neighbor candidates of each node. In our experiments, the CAS + G method outperforms the state-of-the-art method on simulation data for inferring GRNs, and the CAS + L method is significantly faster than the state-of-the-art method with little loss of accuracy. Hence, the CAS based methods effectively decrease the computational complexity of Bayesian network and are more suitable for GRN inference.

Roles of the TonB1 and TonB2 proteins in haemin iron acquisition and virulence in Riemerella anatipestifer.

Two TonB systems in Riemerella anatipestifer were found and characterized as ExbB1-ExbD1-TonB1 and ExbB2-ExbD2-ExbD2'-TonB2, but the significance of two sets of TonB complexes in R. anatipestifer is not clear. In this study, by deleting the tonB1 or tonB2 gene of R. anatipestifer strain CH3, we investigated the roles of the TonB1 and TonB2 proteins in iron acquisition and virulence. The results showed that strain CH3 could utilize haemin as the sole iron source in the presence of l-cysteine, but haemin iron acquisition was defective in the CH3ΔtonB1 mutant, and the deletion of either tonB1 or tonB2 significantly reduced adhesion to and invasion of Vero cells. Animal experiments indicated that the LD50 of the CH3ΔtonB1 and CH3ΔtonB2 mutants in ducklings was ∼224- and ∼87-fold, respectively, higher than that of the WT CH3 strain. Additional analysis indicated that blood bacterial loading of ducklings infected with CH3ΔtonB1 or CH3ΔtonB2 decreased significantly compared with that found for WT CH3-infected ducklings. Thus, our results indicated that the TonB1, but not TonB2 protein, is involved in haemin iron acquisition and that both TonB proteins are necessary for optimal bacterial virulence.

Stereoselective Chlorination and Bromination of Enamides and Enamines via an Electrostatic Attraction Effect Using (1,1-Diacetoxyiodo)benzene and a Halide Source.

The direct chlorination and bromination of (E)-enamines and (Z)-enamides to the corresponding (Z)-configurated α-chloroenamines, α-bromoenamines, and α-chloroenamides have been realized using NiCl2·6H2O or tetrabutyl ammonium bromide as a halide source and (1,1-diacetoxyiodo)benzene as an oxidant. The high stereoselective reactions which produce products with only (Z)-configurations can be attributed to the structure of the intermediates, the conformations of which are controlled by the electrostatic attractions between the positively charged nitrogen atoms and the oxygen atoms of the carbonyl group. This type of electrostatic effect has never been reported in olefin halogenations. For this reason, the three-membered bromonium ion is only a minor intermediate in the enamine bromination pathway. These methods open pathways to prepare α-chloroenamines and α-chloroenamides, which are not accessible via the currently used methods.

LNETWORK: an efficient and effective method for constructing phylogenetic networks.

MOTIVATION: The evolutionary history of species is traditionally represented with a rooted phylogenetic tree. Each tree comprises a set of clusters, i.e. subsets of the species that are descended from a common ancestor. When rooted phylogenetic trees are built from several different datasets (e.g. from different genes), the clusters are often conflicting. These conflicting clusters cannot be expressed as a simple phylogenetic tree; however, they can be expressed in a phylogenetic network. Phylogenetic networks are a generalization of phylogenetic trees that can account for processes such as hybridization, horizontal gene transfer and recombination, which are difficult to represent in standard tree-like models of evolutionary histories. There is currently a large body of research aimed at developing appropriate methods for constructing phylogenetic networks from cluster sets. The Cass algorithm can construct a much simpler network than other available methods, but is extremely slow for large datasets or for datasets that need lots of reticulate nodes. The networks constructed by Cass are also greatly dependent on the order of input data, i.e. it generally derives different phylogenetic networks for the same dataset when different input orders are used. RESULTS: In this study, we introduce an improved Cass algorithm, Lnetwork, which can construct a phylogenetic network for a given set of clusters. We show that Lnetwork is significantly faster than Cass and effectively weakens the influence of input data order. Moreover, we show that Lnetwork can construct a much simpler network than most of the other available methods. AVAILABILITY: Lnetwork has been built as a Java software package and is freely available at http://nclab.hit.edu.cn/∼wangjuan/Lnetwork/. CONTACT: maozuguo@hit.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Activated carbon enhanced ozonation of oxalate attributed to HO oxidation in bulk solution and surface oxidation: effect of activated carbon dosage and pH.

Ozonation of oxalate in aqueous phase was performed with a commercial activated carbon (AC) in this work. The effect of AC dosage and solution pH on the contribution of hydroxyl radicals (HO) in bulk solution and oxidation on the AC surface to the removal of oxalate was studied. We found that the removal of oxalate was reduced by tert-butyl alcohol (tBA) with low dosages of AC, while it was hardly affected by tBA when the AC dosage was greater than 0.3g/L. tBA also inhibited ozone decomposition when the AC dosage was no more than 0.05g/L, but it did not work when the AC dosage was no less than 0.1g/L. These observations indicate that HO in bulk solution and oxidation on the AC surface both contribute to the removal of oxalate. HO oxidation in bulk solution is significant when the dosage of AC is low, whereas surface oxidation is dominant when the dosage of AC is high. The oxalate removal decreased with increasing pH of the solution with an AC dosage of 0.5g/L. The degradation of oxalate occurs mainly through surface oxidation in acid and neutral solution, but through HO oxidation in basic bulk solution. A mechanism involving both HO oxidation in bulk solution and surface oxidation was proposed for AC enhanced ozonation of oxalate.

GEFormerDTA: drug target affinity prediction based on transformer graph for early fusion.

Predicting the interaction affinity between drugs and target proteins is crucial for rapid and accurate drug discovery and repositioning. Therefore, more accurate prediction of DTA has become a key area of research in the field of drug discovery and drug repositioning. However, traditional experimental methods have disadvantages such as long operation cycles, high manpower requirements, and high economic costs, making it difficult to predict specific interactions between drugs and target proteins quickly and accurately. Some methods mainly use the SMILES sequence of drugs and the primary structure of proteins as inputs, ignoring the graph information such as bond encoding, degree centrality encoding, spatial encoding of drug molecule graphs, and the structural information of proteins such as secondary structure and accessible surface area. Moreover, previous methods were based on protein sequences to learn feature representations, neglecting the completeness of information. To address the completeness of drug and protein structure information, we propose a Transformer graph-based early fusion research approach for drug-target affinity prediction (GEFormerDTA). Our method reduces prediction errors caused by insufficient feature learning. Experimental results on Davis and KIBA datasets showed a better prediction of drugtarget affinity than existing affinity prediction methods.

Clinical Features, Diagnosis, and Treatment of Congenital and Neonatal Tuberculosis: A Retrospective Study.

INTRODUCTION: Limited studies have explored the clinical features, treatment, and prognosis of neonatal tuberculosis (TB). Here, we attempted to delineate the clinical characteristics of neonatal TB, which may help clinicians further understand this disease. METHODS: A retrospective analysis of neonates diagnosed with congenital and/or neonatal TB disease from January 2010 to December 2020 was performed. Information on the demographic and epidemiological features, clinical symptoms, laboratory and imaging examinations, therapeutic regimens, and outcomes was collected. Kaplan-Meier analysis was used to present the time to disease onset, time to diagnosis, etc. Results: Forty-eight cases of neonatal TB were classified into congenital (n = 33) and postnatal (n = 15). The median time to disease onset in postnatal group was significantly longer than that in congenital group. Positive results for gastric fluid acid-fast bacilli, TB culture, Xpert MTB/RIF, interferon-γ release assay (IGRA), and tuberculin skin test were detected in 26/48 (54.2%), 14/34 (41.2%), 11/18 (61.1%), 19/29 (65.5%), and 8/24 (33.3%) patients, respectively. For lymphadenopathy, computed tomography (CT) scans showed a higher detection rate than did X-ray (80.0% vs. 0). Of the 48 infants, 44/48 (91.7%) received anti-TB therapy, and 33/44 (75%) were clinically improved or cured after 22.1 months (interquartile range: 12.4-27.7) of follow-up. Drug-induced liver injury occurred in 14/44 (31.8%) patients. DISCUSSION/CONCLUSION: IGRA and Xpert MTB/RIF showed good positive rate in neonatal TB infection/disease. In cases where TB is presumed but etiological evidence is lacking, low-dose CT could be considered. Prompt treatment under careful surveillance is important for preventing mortality and avoiding severe adverse effects.

Attention-Based Sentiment Region Importance and Relationship Analysis for Image Sentiment Recognition.

Image sentiment recognition has attracted considerable attention from academia and industry due to the increasing tendency of expressing opinions via images and videos online. Previous studies focus on multilevel representation from global and local views to improve recognition performance. However, it is insufficient to research the importance and relationship of visual regions for image sentiment recognition. This paper proposes an attention-based sentiment region importance and relationship (ASRIR) analysis method, including important attention and relation attention for image sentiment recognition. First, we extract spatial region features using a multilevel pyramid network from the image. Second, we design important attention to exploring the sentiment semantic-related regions and relation attention to investigating the relationship between regions. In order to release the excessive concentration of attention, we employ a unimodal function as the objective function for regularization. Finally, the region features weighted by the attention mechanism are fused and input into a fully connected layer for classification. Extensive experiments on various commonly used image sentiment datasets demonstrate that our proposed method outperforms the state-of-the-art approaches.

Association Between Passive Smoking and Menstrual Discomfort: A Cross-Sectional Study of 2,571 Non-smoking Chinese Nurses.

Introduction: Menstrual discomfort affects women's quality of life, which is an important public health issue. Evidence confirming the link between passive smoking and menstrual discomfort is limited. Therefore, the aim of this study is to investigate the aforementioned topic on the basis of a cross-sectional study of 2,571 non-smoking Chinese nurses. Methods: Demographic information and passive smoking were assessed using a self-administered questionnaire. Menstrual discomfort was characterized as dysmenorrhea, illness or weakness, bed rest, and restlessness during menstruation, which was assessed using a modified version of the Cornell Medical Index-Health Questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence intervals (CIs) were estimated using the logistic regression model. Results: A total of 1:195 nurses (46.48%) were exposed to passive smoking. Compared with non-passive smoking nurses, passive smoking nurses were more likely to have menstrual discomfort symptoms (72.38 vs. 64.39%), especially symptoms of dysmenorrhea (49.54 vs. 42.08%), illnesses or weakness (48.28 vs. 42.08%), and restlessness during menstruation (53.05 vs. 46.22%). Exposure to passive smoking was significantly associated with menstrual discomfort (OR = 1.41, 95%CI: 1.19-1.67), especially symptoms of dysmenorrhea (OR = 1.32, 95%CI: 1.13-1.56), illness or weakness (OR = 1.24, 95%CI: 1.06-1.46), and restlessness (OR = 1.26, 95%CI: 1.08-1.48) during menstruation. The subgroup analyses, stratified by age, children, and marital status, agreed with the main findings. Conclusions: Exposure to passive smoking was related to symptoms of dysmenorrhea and menstrual discomfort.

Usefulness of mycobacterial interspersed repetitive-unit locus PCR amplification in rapid diagnosis of Beijing lineage strain infection among pediatric tuberculosis patients.

We assessed the usefulness of mycobacterial interspersed repetitive-unit-variable-number tandem-repeat loci 26, 31, ETR-A, Mtub30, and Mtub02 and a deletion-targeted multiplex PCR in identifying pediatric Mycobacterium tuberculosis Beijing lineage strain infection. We found that the Beijing lineage isolates accounted for ∼ 62% (130/210) of the study isolates.

Association Between Passive Smoking and Health Among Chinese Nurses: A Cross-Sectional Study.

This study aimed to investigate the association between passive smoking and physical and psychological health in Chinese nurses. Participants of this cross-sectional study comprised 2,484 non-smoking nurses. Passive smoking and demographic information were assessed using a self-administered questionnaire. Physical, psychological, and overall health status of nurses were measured using the Cornell Medical Index (CMI) health questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for nurses' health were estimated by exposure to passive smoking using unconditional logistic regression models. A total of 1,219 nurses (49.07%) were exposed to passive smoking. Of these, 609 (24.52%), 160 (6.44%), and 587 (23.63%) nurses had poorer physical, mental, and overall health, respectively. After adjusting for other confounding factors, compared with the non-passive smoking group, passive smoking was associated with poor physical (OR = 1.51, 95% CI: 1.25-1.83), mental (OR = 1.48, 95% CI: 1.07-2.07), and overall (OR = 1.58, 95% CI: 1.30-1.93) health of nurses, respectively. We also carried out subgroup analyses stratified by age, department, and professional title, which showed that most findings supported the main results. This study demonstrated that exposure to passive smoking was a risk factor for overall decreased physical and mental health status among Chinese nurses.

Synthesis of 4-Chloroisocoumarins via Intramolecular Halolactonization of o-Alkynylbenzoates: PhICl2-Mediated C-O/C-Cl Bond Formation.

A series of 4-chloroisocoumarins were conveniently synthesized from o-alkynylbenzoates via PhICl2-mediated intramolecular cyclization under metal-free conditions. PhICl2 plays the role of both the oxidant and the chlorine source to enable oxidative C-O bond formation and introduction of the chlorine atom. The utility and practicability of this protocol have been exemplified by virtue of mild reaction conditions, high-yielding products, simplified purification, and gram-scale synthesis.

In Situ Formation of RSCl/ArSeCl and Their Application to the Synthesis of 4-Chalcogenylisocumarins/Pyrones from o-(1-Alkynyl)benzoates and ( Z)-2-Alken-4-ynoates.

The reaction of diorganyl disulfides or diselenides with PhICl2 in acetonitrile was found for the first time to lead to the in situ formation of organosulfenyl chloride or selenenyl chloride, which enables the regioselective intramolecular chalcogenylacyloxylation of alkynes resulting in the formation of 4-chalcogenylisocumarins/pyrones in good to excellent yields under metal-free conditions.

Ozonation catalyzed by iron- and/or manganese-supported granular activated carbons for the treatment of phenol.

Iron- and/or manganese-supported catalysts on granular activated carbons (Fe and/or Mn/GACs) were prepared, and their catalytic activities were evaluated by using them to treat phenol and secondary petrochemical effluent via ozonation. The presence of Fe and/or Mn/GACs significantly improved the degradation and degree of phenol mineralization. Changes in dissolved ozone concentrations and the effects of carbonate and tert-butyl alcohol (TBA) indicated that the prepared catalyst enhanced the decomposition of ozone into hydroxyl radicals (·OH), which was determined to be a key factor in catalyzing the ozonation of phenol. Typical intermediate products were identified by GC-MS and HPLC analysis, and a possible degradation pathway of phenol via catalytic ozonation was proposed. The results of XPS, CV, and other experimental data indicated that introducing Fe and/or Mn increased the rate of ozone decomposition into ·OH, and also enhanced the interfacial electron transfer by Fe2+-Fe3+ and Mn2+-Mn3+-Mn4+ redox cycles, resulting in higher catalytic activity. However, the Fe-Mn/GAC surface was shown to undergo galvanic corrosion between Fe3O4 and MnO2, decreasing the catalytic activity. In addition, catalytic ozonation was used to treat secondary petrochemical effluent. The results demonstrated that the Mn/GAC/O3 system significantly improved the quality of phenol-containing wastewater in terms of its COD, TOC, NH4+-N, water color, and ecotoxicity. This study gives a better understanding of the phenol treatment by catalytic ozonation using Fe and/or Mn/GAC.

Gene Regulatory Networks Reconstruction Using the Flooding-Pruning Hill-Climbing Algorithm.

The explosion of genomic data provides new opportunities to improve the task of gene regulatory network reconstruction. Because of its inherent probability character, the Bayesian network is one of the most promising methods. However, excessive computation time and the requirements of a large number of biological samples reduce its effectiveness and application to gene regulatory network reconstruction. In this paper, Flooding-Pruning Hill-Climbing algorithm (FPHC) is proposed as a novel hybrid method based on Bayesian networks for gene regulatory networks reconstruction. On the basis of our previous work, we propose the concept of DPI Level based on data processing inequality (DPI) to better identify neighbors of each gene on the lack of enough biological samples. Then, we use the search-and-score approach to learn the final network structure in the restricted search space. We first analyze and validate the effectiveness of FPHC in theory. Then, extensive comparison experiments are carried out on known Bayesian networks and biological networks from the DREAM (Dialogue on Reverse Engineering Assessment and Methods) challenge. The results show that the FPHC algorithm, under recommended parameters, outperforms, on average, the original hill climbing and Max-Min Hill-Climbing (MMHC) methods with respect to the network structure and running time. In addition, our results show that FPHC is more suitable for gene regulatory network reconstruction with limited data.

Practical Glucosylations and Mannosylations Using Anomeric Benzoyloxy as a Leaving Group Activated by Sulfonium Ion.

One obstacle for practical glycosylations is the high cost of promoters and low-temperature equipment. This problem has been at least partially solved by using MeSCH2Cl/KI as a low-cost promoter system. MeSCH2Cl has an estimated cost of <$1/mol compared with $1741/mol for AgOTf and $633/mol for TMSOTf. This new promoter system is capable of activating various leaving groups including anomeric Cl, F, trichloroacetimidate, and acyloxy groups. Stable and easy-to-prepare anomeric benzoloxy carbohydrate donors were investigated in the glycosylations of carbohydrates, aliphatic alcohols, amino acids, steroids, and nucleoside acceptors. Most of these glycosylations were operationally simple with fast reaction rates and moderate yields of 35-79%. In addition, direct glycosylations of nucleosides using less than 2 equiv of anomeric benzoloxy donors and high stereoselective mannosylation have been achieved. From an economic point of view, this glycosylation method should be highly applicable to industrial processes.

Constructing an integrated gene similarity network for the identification of disease genes.

BACKGROUND: Discovering novel genes that are involved human diseases is a challenging task in biomedical research. In recent years, several computational approaches have been proposed to prioritize candidate disease genes. Most of these methods are mainly based on protein-protein interaction (PPI) networks. However, since these PPI networks contain false positives and only cover less half of known human genes, their reliability and coverage are very low. Therefore, it is highly necessary to fuse multiple genomic data to construct a credible gene similarity network and then infer disease genes on the whole genomic scale. RESULTS: We proposed a novel method, named RWRB, to infer causal genes of interested diseases. First, we construct five individual gene (protein) similarity networks based on multiple genomic data of human genes. Then, an integrated gene similarity network (IGSN) is reconstructed based on similarity network fusion (SNF) method. Finally, we employee the random walk with restart algorithm on the phenotype-gene bilayer network, which combines phenotype similarity network, IGSN as well as phenotype-gene association network, to prioritize candidate disease genes. We investigate the effectiveness of RWRB through leave-one-out cross-validation methods in inferring phenotype-gene relationships. Results show that RWRB is more accurate than state-of-the-art methods on most evaluation metrics. Further analysis shows that the success of RWRB is benefited from IGSN which has a wider coverage and higher reliability comparing with current PPI networks. Moreover, we conduct a comprehensive case study for Alzheimer's disease and predict some novel disease genes that supported by literature. CONCLUSIONS: RWRB is an effective and reliable algorithm in prioritizing candidate disease genes on the genomic scale. Software and supplementary information are available at http://nclab.hit.edu.cn/~tianzhen/RWRB/ .

Epidemiology and Clinical Characteristics of Pediatric Drug-Resistant Tuberculosis in Chongqing, China.

To gain insight into the epidemiology of childhood drug resistant tuberculosis (DR-TB) in China that has the second largest burden of TB and the largest number of multidrug resistant (MDR) TB cases in the world, we performed the cross-sectional study to investigate drug resistance of four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) using Mycobacterium tuberculosis isolates from 196 culture-confirmed pediatric TB cases diagnosed in the Children's Hospital of Chongqing Medical University, China during 2008-2013. Univariate and multivariate logistic regression analyses were performed to assess the associations between patient demographic and clinical characteristics and DR-and MDR-TB, respectively. Twenty-eight percent (56/196) of the study patients exhibited resistance to at least one of the four first-line anti-TB drugs tested. MDR was found in 4.6% (9/196) of the study patients. More than half (5/9, 55.6%) of the MDR cases were from a single county of Chongqing. A significant association was found between being acid-fast bacilli-smear negative and DR-TB (adjusted OR, 2.33; 95% CI, 1.13-4.80) and between having concurrent thoracic-extrathoracic involvement and MDR-TB (adjusted OR, 9.49; 95% CI, 1.05-85.92), respectively. The findings of this study indicate that the rate of DR is high among pediatric TB patients in Chongqing and suggest an urgent need for studies to identify MDR transmission hotspots in Chongqing, thereby contributing to the control DR- and MDR-TB epidemics in China. The study also generates new insight into the pathogenesis of DR and MDR M. tuberculosis strains and highlights the importance of studying childhood TB to the goal of global TB control.