Morphology and classification of the second mesiobuccal canal in maxillary first molars: a cone-beam computed tomography analysis in a Chinese population.

BACKGROUND: Understanding the tooth anatomy is crucial for ensuring effective endodontic treatment. This study investigated the root canal morphology of the second mesiobuccal (MB2) canal in maxillary first molars (MFMs) in a Chinese population using cone-beam computed tomography (CBCT). METHODS: This study evaluated 486 MFMs with MB2 canals from 285 participants undergoing CBCT examination and determined the Vertucci's classification and position of the MB2 canal orifice. The prevalence of the MB2 canal was correlated with the sex, age, and tooth side. The correlations between the prevalence of the MB2 canal and sex and tooth side were assessed using the Fisher's exact test. The chi-square test was used for evaluating the correlation between the prevalence of the MB2 canal and age. RESULTS: The number of type II, III, IV, V, VI, VII, and other root canals in the MFMs was 30.9%, 0.6%, 65.0%, 1.2%, 1.2%, 0.4%, and 0.6%, respectively. Among the 201 cases with bilateral inclusion, 87.6% showed consistent canal configuration. Results of the first clear apparent position (FCAP) of the MB2 canals showed that 434, 44, and 3 teeth had FCAP at the upper, middle, and bottom one-third of the root, respectively. The FCAPs of the MB2 canal in the MFMs with types II, IV, and VI, as well as types III and V canals showed significant differences (p<0.05). The horizontal distance between the MB1 and MB2 canal orifices in the type II canals of MFMs was significantly lesser than those in the type IV canals of MFMs (p < 0.01). The longitudinal distance between the pulp chamber floor plane and MB2 canal orifice significantly correlated with age (p < 0.05). CONCLUSIONS: The morphology of the mesiobuccal root canal in the MFMs is complex. Complete understanding of the anatomical morphology of the root canal combined with the CBCT and dental operating microscope is necessary for the accurate detection of the MB2 canal and consequently improved success rate of root canal treatment. Our study findings can help endodontists improve endodontic treatment outcomes.

PDGFRß Recognizes and Binds Bacteria to Activate Src/Stat Pathway in Oysters.

The Stat signaling pathway plays important roles in mediating the secretions of a large number of cytokines and growth factors in vertebrates, which is generally triggered by the growth factor receptor, cytokine receptor, G protein coupled receptor, and receptor protein tyrosine kinase. In the current study, a platelet-derived growth factor receptor (defined as CgPDGFRß) was identified from the Pacific oyster Crassostrea gigas, with a signal peptide, three Ig domains, a transmembrane domain, and an intracellular Ser/Thr/Tyr kinase domain. The two N-terminal Ig domains of CgPDGFRß showed relatively higher binding activity to Gram-negative bacteria and LPS compared with Gram-positive bacteria and peptidoglycan. Upon binding bacteria, CgPDGFRß in hemocytes formed a dimer and interacted with protein tyrosine kinase CgSrc to induce the phosphorylation of CgSrc at Tyr416. The activated CgSrc interacted with CgStat to induce the translocation of CgStat into the nucleus of hemocytes, which then promoted the expressions of Big defensin 1 (CgBigdef1), IL17-4 (CgIL17-4), and TNF (CgTNF1). These findings together demonstrated that the Src/Stat signaling was activated after the binding of CgPDGFRß with bacteria to induce the expressions of CgBigdef1, CgIL17-4, and CgTNF1.

Integrated Analysis of miR-430 on Steroidogenesis-Related Gene Expression of Larval Rice Field Eel Monopterus albus.

The present study aims to reveal the mechanism by which miR-430s regulate steroidogenesis in larval rice field eel Monopterus albus. To this end, M. albus embryos were respectively microinjected with miRNA-overexpressing mimics (agomir430a, agomir430b, and agomir430c) or miRNA-knockdown inhibitors (antagomir430a, antagomir430b, and antagomir430c). Transcriptome profiling of the larvae indicated that a total of more than 149 differentially expressed genes (DEGs) were identified among the eight treatments. Specifically, DEGs related to steroidogenesis, the GnRH signaling pathway, the erbB signaling pathway, the Wnt signaling pathway, and other pathways were characterized in the transcriptome. We found that steroidogenesis-related genes (hydroxysteroid 17-beta dehydrogenase 3 (17ß-hsdb3), hydroxysteroid 17-beta dehydrogenase 7 (17ß-hsdb7), hydroxysteroid 17-beta dehydrogenase 12 (17ß-hsdb12), and cytochrome P450 family 19 subfamily a (cyp19a1b)) were significantly downregulated in miR-430 knockdown groups. The differential expressions of miR-430 in three gonads indicated different roles of three miR-430 (a, b, and c) isoforms in regulating steroidogenesis and sex differentiation. Mutation of the miR-430 sites reversed the downregulation of cytochrome P450 family 17 (cyp17), cyp19a1b, and forkhead box L2 (foxl2) reporter activities by miR-430, indicating that miR-430 directly interacted with cyp17, cyp19a1b, and foxl2 genes to inhibit their expressions. Combining these findings, we concluded that miR-430 regulated the steroidogenesis and the biosynthesis of steroid hormones by targeting cyp19a1b in larval M. albus. Our results provide a novel insight into steroidogenesis at the early stage of fish at the molecular level.

Multiple root canals in the maxillary molar: an unusual case report.

BACKGROUND: The objective of this report was to highlight the importance of using a dental operating microscope (DOM) to locate supernumerary canals and diagnose variations in root canals using cone-beam computed tomographic (CBCT) images. CASE PRESENTATION: A 35-year-old Chinese female had repeated swelling in the upper right posterior maxilla for 3 months and was referred to evaluate symptomatic apical periodontitis and mesotaurodonts for upper right first permanent molar and upper right second permanent molar. Root canal therapy was proposed and conducted with the use of DOM and CBCT. CONCLUSIONS: Proper diagnosis and careful clinicoradiological examination are necessary, and it is essential to reinforce the knowledge of the rare morphology of root canals for clinicians.

AP-1 regulates the expression of IL17-4 and IL17-5 in the pacific oyster Crassostrea gigas.

The activator protein-1 (AP-1) plays an important role in inducing the immune effector production in response to cellular stress and bacterial infection. In the present study, an AP-1 was identified from Pacific oyster Crassostrea gigas (designed as CgAP-1) and its function was investigated in response against lipopolysaccharide (LPS) stimulation. CgAP-1 was consisted of 290 amino acids including a Jun domain and a basic region leucine zipper (bZIP) domain. CgAP-1 shared 98.6% similarities with ChAP-1 from oyster C. hongkongensis, and assigned into the branch of invertebrates in the phylogenetic tree. The mRNA transcripts of CgAP-1 gene were detected in all tested tissues with highest expression level in hemocytes, especially in granulocytes. The mRNA expression level of CgAP-1 gene in hemocytes was significantly up-regulated (8.53-fold of that in PBS group, p < 0.01) at 6 h after LPS stimulation. CgAP-1 protein could be translocated into the nucleus of oyster hemocytes after LPS stimulation. The mRNA transcripts of interleukin17s (CgIL17-4 and CgIL17-5) in the hemocytes of CgAP-1-RNAi oysters decreased significantly at 24 h after LPS stimulation, which were 0.37-fold (p < 0.05) and 0.17-fold (p < 0.01) compared with that in EGFP-RNAi oysters, respectively. The results suggested that CgAP-1 played an important role in the immune response of oyster by regulating the expression of CgIL17s.

A novel globular C1q domain containing protein (C1qDC-7) from Crassostrea gigas acts as pattern recognition receptor with broad recognition spectrum.

The globular C1q domain containing (C1qDC) proteins are a family of versatile pattern recognition receptors (PRRs) to bind various ligands by their globular C1q (gC1q) domain. In the present study, a novel globular C1qDC (CgC1qDC-7) was characterized from Pacific oyster Crassostrea gigas. The open reading frame of CgC1qDC-7 was of 555 bp, encoding a polypeptide of 185 amino acids. Phylogenetic analysis indicated that CgC1qDC-7 shared high homology with C1qDCs from Crassostrea virginica, Mytilus galloprovincialis, and Mizuhopecten yessoensis. The mRNA transcripts of CgC1qDC-7 were widely expressed in all the tested tissues including mantle, gonad, gills, adductor muscle, hemocytes, hepatopancreas and labial palps, with the highest expression level in hemocytes and gills. The recombinant protein of CgC1qDC-7 (rCgC1qDC-7) exhibited binding activity towards Gram-negative bacteria (Vibrio splendidus, V. anguillarum, Escherichia coli, V. alginolyticus, and Aeromonas hydrophila), Gram-positive bacteria (Micrococcus luteus and Staphylococcus aureus) and fungi (Pichia pastoris and Yarrowia lipolytica), and displayed strongest binding affinity towards Gram-negative bacteria V. splendidus and V. anguillarum. It also exhibited affinity to vital pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS), peptidoglycan (PGN), mannan (MAN) and Poly (I:C) with high affinity towards LPS and PGN, and low affinity to MAN and Poly (I:C). These results collectively indicated that CgC1qDC-7 was a novel PRR in C. gigas with high binding affinity towards LPS and PGN as well as Gram-negative bacteria.

CgSOCS6 negatively regulates the expression of CgIL17s and CgDefh1 in the pacific oyster Crassostrea gigas.

As a family of negatively feedback regulating factors, the suppressor of cytokine signaling (SOCS) can depress cytokine signal transduction, and eventually modulate growth, development, differentiation, and immune response. In the present study, a SOCS homologue (designated as CgSOCS6) was identified from oyster Crassostrea gigas. The open reading frame of CgSOCS6 cDNA was of 1167 bp encoding a peptide of 388 amino acid residues with a central Src homology 2 (SH2) domain, a conserved C-terminal SOCS box, and a nucleus localization sequence (NLS) in its N-terminus. The deduced amino acid sequence of CgSOCS6 shared 37.9-45.5% similarity with other SOCS6/7 family members. In the unrooted phylogenetic tree, CgSOCS6 was clustered with EsSOCS6 from Chinese mitten crab Eriocheir sinensis and assigned into the SOCS6/7 group. The mRNA transcripts of CgSOCS6 were constitutively distributed in all the tested tissues, with the highest level in hemocytes. After lipopolysaccharide (LPS) stimulation, the mRNA expression of CgSOCS6 in hemocytes was significantly up-regulated to the highest level at 6 h (8.48-fold compared to the control group, p < 0.01), and then kept at a relatively higher level from 12 h to 72 h. CgSOCS6 protein could be translocated into the hemocyte nucleus after LPS stimulation. The mRNA expressions of interleukin 17-4 (CgIL17-4), CgIL17-5, and defensin (CgDefh1) in the hemocytes of CgSOCS6-knockdown oysters increased significantly (2.55-fold, 2.68-fold, 4.68-fold of that in EGFP-RNAi oysters, p < 0.05, p < 0.05, p < 0.001, respectively) after LPS stimulation. These findings suggested that CgSOCS6 was involved in the oyster immune response by regulating the expressions of CgIL17-4, CgIL17-5, and CgDefh1.

Glucose-induced changes in the bacterial communities of mine tailings at different acidification stages.

Ecological restoration technologies applied to tailings can influence the associated bacterial communities. However, it is unknown if the shifts in these bacterial communities are caused by increased organic carbon. Glucose-induced respiration and high-throughput sequencing were used to assess the microbial activity and bacterial communities, respectively. Glucose addition increased the microbial activity, and glucose + ammonium nitrate addition resulted in slightly higher CO2 emission than did glucose addition alone, suggesting that carbon and nitrogen limited microbial community growth. In neutral pH tailings, the bacterial taxa that increased by glucose addition were assigned to the phyla Proteobacteria, Acidobacteria, Actinobacteria, Bacteroidetes, Firmicutes, and Planctomycetes. However, the bacterial taxa that increased by glucose addition in acidic tailings only belonged to the phylum Actinobacteria (maximum increase of 43.78%). In addition, the abundances of the total nitrogen-fixing genera and of the genus Arthrobacter (representing approximately 97.89% of the total nitrogen-fixing genera) increased by glucose addition in acidic tailings (maximum increase of 46.98%). In contrast, the relative abundances of the total iron- and (or) sulfur-oxidizing bacteria decreased (maximum decrease of 10.41%) in response to the addition of glucose. These findings indicate that the addition of organic carbon is beneficial to the development of bacterial communities in mine tailings.

Response of chemical properties, microbial community structure and functional genes abundance to seasonal variations and human disturbance in Nanfei River sediments.

The Nanfei River, located in Hefei City, Anhui Province, subjected to increased nutrient loads from point and/or non-point source. Little is known about the indicators indicating heterogeneity of surface sediments. We aimed to identify the suitable indicators that can reflect the sediment heterogeneity by analyzing the sensitivity of sediment physicochemical properties group, microbial communities and diversity indices group and C, N, S-functional genes group to seasonal and regional changes. River sediments from different areas (urban area, urban-rural fringe and rural area) were collected in the level, dry and wet seasons, respectively. The chemical parameters had most significant regional heterogeneity, but no seasonal differences. Seasons had a greater impact on the overall microbial community structure than the areas. Specifically, the relative abundance of Firmicutes and Bacteroidetes were more sensitive to seasonal changes. Overall, seasonal changes showed the greatest impact on the functional genes group, with the S-functional genes (dsrB and aprA) group providing the clearest seasonal variation. Considering the seasonal distribution of functional genes and their sensitivity to environmental factors, we speculated that the sulfate-reducing gene (dsrB), the methanogenic gene (mcrA) and the anammox gene (hzo) could be identified as sensitive indicators to indicate the seasonal heterogeneity of surface sediments in different river sections of the same river in the short term. We also concluded that environmental variables were more conducive to indicating the regional heterogeneity of sediments. This study provided a valuable reference for assessing the heterogeneity or ecological stress of river sediments.

The spatial and seasonal variations of bacterial community structure and influencing factors in river sediments.

Studying the composition and structure of bacterial communities in sediments helps to understand the contribution of bacteria to environmental changes and the role of feedback in response to disturbances. However, seasonal changes in bacterial communities of river sediments with different pollution levels and sources have not been clear yet. In this study, we collected sediment samples during the dry season, wet season and level season from 40 sites with various pollution sources in three inflow rivers (Fengle-Hangbu River, Nanfei River and Zhegao River) of Chaohu Lake. Bacterial community compositions were determined based on high-throughput sequencing. The 'Bioenv' in the R package 'Vegan' and redundancy analysis was used to explore the influence of environmental factors on the bacterial community in the river sediments. Results showed that a significant deviation in bacterial communities was found among seasons and rivers. In addition, seasonal dynamics had a greater impact on shaping bacterial communities than rivers with different pollution sources. A higher diversity was found in the wet season as compared to the other seasons. The bacterial diversity was negatively correlated with nutrients (OM, TN, NH4+, IP, OP and TP) and metals (Cu and Zn). Bacterial communities were more sensitive to heavy metals pressure than nutrients. We also concluded that heavy metals (Cu and Cd) were the key contributing factors in explaining variations in bacterial communities. This study provided a valuable reference for assessing ecological stress.

Specific Inhibitor of Smad3 (SIS3) Attenuates Fibrosis, Apoptosis, and Inflammation in Unilateral Ureteral Obstruction Kidneys by Inhibition of Transforming Growth Factor ß (TGF-ß)/Smad3 Signaling.

BACKGROUND Fibrosis is the common pathological feature in most kinds of chronic kidney disease (CKD). TGF-ß/Smads signaling is the master pathway regulating kidney fibrosis pathogenesis, in which Smad3 acts as the integrator of various pro-fibrosis signals. In this study, we analyzed the role of SIS3, a specific inhibitor of Smad3, in mouse unilateral ureteral obstruction (UUO) kidneys. MATERIAL AND METHODS UUO mice were intraperitoneally injected with 0.2 mg/kg/day or 2 mg/kg/day of SIS3 or control saline for 7 days, followed by analysis of structure injury, fibrosis status, inflammation, apoptosis, and TGF-ß/Smads signaling activity. RESULTS Our results indicated that SIS3 treatment dosage-dependently relieved the gross structure injury and tubular necrosis in UUO kidneys. Masson staining, immunohistochemistry, and real-time PCR showed significantly decreased extracellular matrix deposition, fibronectin staining intensity, and RNA levels of collagen I and collagen III in SIS3-treated UUO kidneys. SIS3 treatment also suppressed the activation of myofibroblasts, as evidenced by decreased expression levels of a-SMA and vimentin in UUO kidneys. The TGF-ß/Smads signaling activity analysis showed that SIS3 inhibited the phosphorylation of Smad3 but not Smad2 and decreased the protein level of TGF-ß1, suggesting specific inhibition of the TGF-ß/Smad3 pathway in UUO kidneys. Furthermore, SIS3 treatment also ameliorated the increased pro-inflammatory TNF-α and COX2 in UUO kidneys and circulating IL-1ß in UUO mice, and inhibited caspase-3 activity and the number of apoptotic cells. CONCLUSIONS SIS3 ameliorated fibrosis, apoptosis, and inflammation through inhibition of TGF-b/Smad3 signaling in UUO mouse kidneys.

Milloux inequality of E-valued meromorphic function.

The main purpose of this paper is to establish the Milloux inequality of E-valued meromorphic function from the complex plane ℂ to an infinite dimensional complex Banach space E with a Schauder basis. As an application, we study the Borel exceptional values of an E-valued meromorphic function and those of its derivatives; results are obtained to extend some related results for meromorphic scalar-valued function of Singh, Gopalakrishna, and Bhoosnurmath.

Fixed points of difference operator of meromorphic functions.

Let f be a transcendental meromorphic function of order less than one. The authors prove that the exact difference Δf =(z+1)-f(z) has infinitely many fixed points, if a ∈ ℂ and ∞ are Borel exceptional values (or Nevanlinna deficiency values) of f. These results extend the related results obtained by Chen and Shon.

An inequality of meromorphic functions and its application.

By applying Ahlfors theory of covering surface, we establish a fundamental inequality of meromorphic function dealing with multiple values in an angular domain. As an application, we prove the existence of some new singular directions for a meromorphic function f, namely a Bloch direction and a pseudo-T direction for f.

A new dipeptide isolated from the bulb of garlic.

(R)-3-(allylthio)-2-((R)-3-(allylthio)-2-aminopropanamido)propanoic acid was isolated from the bulb of garlic, together with four known amino acids. Its structure was elucidated on the basis of 2D NMR and MS techniques. To the best of our knowledge, (R)-3-(allylthio)-2-((R)-3-(allylthio)-2-aminopropanamido)propanoic acid, which showed antibacterial activity against the Staphylococcus aureus antibiotic resistant strain, was the first example of dipeptide from garlic.

Analysis of Characteristics and Driving Mechanisms of Non-Grain Production of Cropland in Mountainous Areas at the Plot Scale-A Case Study of Lechang City.

With the continuous advancement of urbanization and industrialization, non-grain production on cropland (NGPCL) is gradually becoming more widespread. This phenomenon will compress the space for grain production and trigger a global food crisis. How to scientifically understand and effectively control NGPCL has become a scientific issue. This study, conducted at the plot scale, establishes a measurement index for NGPCL and further explores the characteristics and driving mechanisms of NGPCL in mountainous areas. The results indicate the following: (1) Compared to plots for food-growing, plots for non-grain production tend to be more dispersed, with terraces showing the most significant dispersion, while plains exhibit the highest degree of aggregation. (2) In terms of irrigation conditions, irrigated land and dry land are more likely to undergo NGPCL. In terms of topography, slope croplands have the highest probability of being used for NGPCL. (3) Regions with steeper slopes, higher elevations, greater differences in altitude from the settlement, farther distances from settlements and roads, yet closer proximity to forests, are more likely to engage in NGPCL. (4) Different plot characteristics have varying impacts on NGPCL. Plot characteristics primarily affect the costs and returns of grain production, driving farmers to change their production patterns and triggering NGPCL.

The Sulfur Conversion Functional Microbial Communities in Biogas Liquid Can Participate in Coal Degradation.

The addition of biogas liquid is a practical way to improve the yield of biological coalbed methane. The microbial composition in biogas liquid is complex, and whether it could participate in the sulfur conversion of coal remains unknown. In this study, sulfur conversion-related microbial communities were enriched from biogas liquid, which was dominated by genera Anaerosolibacter, Bacillus, Hydrogenispora, and Oxobacter. The co-culture of these groups with coal significantly changed the coal microbial community composition but did not increase the content of CH4 and H2S. The changed microbial communities mainly belonged to phyla Firmicutes, Proteobacteria, and Actinobacteriota, and increased the relative abundance of genera Bacillus, Thermicanus, Hydrogenispora, Oxobacter, Lutispora, Anaerovorax, Desulfurispora, Ruminiclostridium, and Fonticella. From the microscopic structure of coal, an increase in the number of holes and roughness on the surface of the coal was found but the change of surface functional groups was weak. In addition, the addition of S-related microbial communities increased the contents of phoxim, methylthiobenzoylglycine and glibornuride M5 in aromatic compounds, as well as the content of lauryl hydrogen sulfate in alkyl compounds. Furthermore, the dibenzothiophene degradation-related microbial communities included Bacillus, Brevibacillus, Brevundimonas, Burkholderia-Caballeronia-Paraburkholderia, and Thermicanus, which can break C-S bonds or disrupt benzene rings to degrade dibenzothiophene. In conclusion, the S-related microbial communities in biogas liquid could rebuild the coal microbial community and be involved in the conversion process of organic sulfur in coal.

Sulfur vacancy-rich (α/ß-CdS)/SiO2 photocatalysts for enhanced visible-light-driven photocatalytic degradation of rhodamine B.

The development of highly efficient photocatalysts for visible-light-driven degradation of organic pollution is of great interest for wastewater purification. In this work, a sulfur vacancy-rich (α/ß-CdS)/SiO2 (α: hexagonal & ß: cubic) photocatalyst with a high catalytic activity was novelly synthesized on a nano-SiO2 carrier by the reaction of Cd2+ with a CS2 storage material (CS2SM) as sulfur source and crystalline modifiers. The dispersion of α/ß-CdS on the nano-SiO2 carrier significantly enhanced the visible-light-driven catalytic activity of (α/ß-CdS)/SiO2 photocatalyst, and 93.37 % rhodamine B (RhB) conversion was determined over 50 mg (α/ß-CdS)/SiO2 photocatalyst for 30 mL 400 mg/L RhB solution at light intensity of 150 mW/cm2 and 298.15 K. After five cycle tests, the (α/ß-CdS)/SiO2 photocatalyst still owned excellent visible-light-driven catalytic degradation stability (>90 %). The characterizations of morphology, functional groups, and photo-electrochemistry of (α/ß-CdS)/SiO2 photocatalyst demonstrated that nano-SiO2 as a carrier played meaningful role in dispersing α/ß-CdS and reducing agglomeration, thus increasing the active site of photocatalytic degradation reaction, and the presence of α/ß hetero-phase junctions and sulfur vacancies allows the rapid separation of photo-generated carriers and inhibits photo-generated electron-holes recombination. Meanwhile, the electron paramagnetic resonance (EPR) and free radical masking test have also proved that the main active species is ·O2- for the oxidation of RhB. Therefore, the work is providing a new reference to the visible-light-driven degradation of wastewater with high RhB concentration at room temperature.

A Study on the Nanostructural Evolution of Bi/C Anode Materials during Their First Charge/Discharge Processes.

As a candidate anode material for Li-ion batteries, Bi-based materials have attracted extensive attention from researchers due to their high specific capacity, environmental friendliness, and simple synthesis methods. However, Bi-based anode materials are prone to causing large volume changes during charging and discharging processes, and the effect of these changes on lithium storage performance is still unclear. This work introduces that Bi/C nanocomposites are prepared by the Bi-based MOF precursor calcination method, and that the Bi/C nanocomposite maintains a high specific capacity (931.6 mAh g-1) with good multiplicative performance after 100 cycles at a current density of 100 mA g-1. The structural evolution of Bi/C anode material during the first cycle of charging and discharging is investigated using in situ synchrotron radiation SAXS. The SAXS results indicate that the multistage scatterers of Bi/C composite, used as an anode material during the first lithiation, can be classified into mesopores, interspaces, and Bi nanoparticles. The different nanostructure evolutions of three types of Bi nanoparticles were observed. It is believed that this result will help to further understand the complex reaction mechanism of Bi-based anode materials in Li-ion batteries.

CRISPR Screening and Comparative LC-MS Analysis Identify Genes Mediating Efficacy of Delamanid and Pretomanid against Mycobacterium tuberculosis.

Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical-genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance. Further assays show that Rv2073c might confer intrinsic resistance to DLM/PMD by interfering with inhibition of the drug target, decaprenylphophoryl-2-keto-b-D-erythro-pentose reductase (DprE2), by active nicotinamide adenine dinucleotide (NAD) adducts. Characterization of the metabolic pathways of DLM/PMD in Mtb using a combination of chemical genetics and comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM/PMD metabolites reveals that Rv0077c, which is negatively regulated by Rv0078, mediates drug resistance by metabolizing activated DLM/PMD. These results might guide development of new nitroimidazole prodrugs and new regimens for TB treatment.