The potential mechanism of the progression from latent to active tuberculosis based on the intestinal microbiota alterations.

INTRODUCTION: Tuberculosis (TB) poses a serious challenge to global health systems. The altered intestinal microbiota is associated with the pathogenesis of TB, but the exact links remain unclear. METHODS: 16 S rDNA sequencing was performed to comprehensively detect the changes in the intestinal microbiota of feces from active TB (ATB), latent TB infection (LTBI) and healthy controls (HC). RESULTS: The rarefaction curves demonstrated the sequencing results' validity. The alpha diversity was lowest in ATB, while highest in HC. Boxplot of beta diversity showed significant differences in every two groups. LDA Effect Size (LEfSe) Analysis revealed differences in probiotic bacteria like Romboutsia, Bifidobacterium and Lactobacillus in LTBI, and pro-inflammatory bacteria like R. gnavus, Streptococcus and Erysipelatoclostridium in ATB, corresponding to the cluster analysis. PICRUST2 analysis revealed the pentose phosphate pathway was active in ATB and LTBI (more active in ATB). The differences between the groups are statistically significant at the P<0.05 level. CONCLUSION: Our study indicated that from LTBI to ATB, some intestinal microbiota inhibit the synthesis of interferon (INF)-γ and interleukin (IL)-17, promoting the survival and spread of Mycobacterium tuberculosis (M. tb). In addition, the metabolites secreted by intestinal microbiota and dysbiosis in intestine also have an effect on the development of LTBI to ATB.

Untargeted Metabolomics of Feces Reveals Diagnostic and Prognostic Biomarkers for Active Tuberculosis and Latent Tuberculosis Infection: Potential Application for Precise and Non-Invasive Identification.

Purpose: Distinguishing latent tuberculosis infection (LTBI) from active tuberculosis (ATB) is important to control the prevalence of tuberculosis; however, there is currently no effective method. The aim of this study was to discover specific metabolites through fecal untargeted metabolomics to discriminate ATB, individuals with LTBI, and healthy controls (HC) and to probe the metabolic perturbation associated with the progression of tuberculosis. Patients and Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to comprehensively detect compounds in fecal samples from HC, LTBI, and ATB patients. Differential metabolites between the two groups were screened, and their underlying biological functions were explored. Candidate metabolites were selected and enrolled in LASSO regression analysis to construct diagnostic signatures for discriminating between HC, LTBI, and ATB. A receiver operating characteristic (ROC) curve was applied to evaluate diagnostic value. A nomogram was constructed to predict the risk of progression of LTBI. Results: A total of 35 metabolites were found to exist differentially in HC, LTBI, and ATB, and eight biomarkers were selected. Three diagnostic signatures based on the eight biomarkers were constructed to distinguish between HC, LTBI, and ATB, demonstrating excellent discrimination performance in ROC analysis. A nomogram was successfully constructed to evaluate the risk of progression of LTBI to ATB. Moreover, 3,4-dimethylbenzoic acid has been shown to distinguish ATB patients with different responses to etiological tests. Conclusion: This study constructed diagnostic signatures based on fecal metabolic biomarkers that effectively discriminated HC, LTBI, and ATB, and established a predictive model to evaluate the risk of progression of LTBI to ATB. The results provide scientific evidence for establishing an accurate, sensitive, and noninvasive differential diagnosis scheme for tuberculosis.

Hexaaqua-zinc(II) 4,4'-(1,2-dihy-droxy-ethane-1,2-di-yl)dibenzoate monohydrate.

The title compound, [Zn(H(2)O)(6)](C(16)H(12)O(6))·H(2)O, consists of one 4,4'-(1,2-dihy-droxy-ethane-1,2-di-yl)dibenzoate anion lying on an inversion centre, one [Zn(H(2)O)(6)](2+) dication lying on a mirror plane and one solvent water mol-ecule located on a mirror plane. The octahedral [Zn(H(2)O)(6)](2+) cations, solvent water mol-ecules and anions inter-act via O-H⋯O hydrogen bonds, forming a three-dimensional network.

[µ-1,3-Bis(3,5-dimethyl-1H-pyrazol-1-yl-κN)propan-2-olato-κO:O]bis-[(ethanol-κO)zinc(II)] bis-(perchlorate).

In the centrosymmetric dinuclear title complex, [Zn(2)(C(13)H(19)N(4)O)(2)(C(2)H(5)OH)(2)](ClO(4))(2), the Zn(II) atom is in a distorted trigonal-bipyramidal coordination geometry. The equatorial plane is constructed by one N atom and one O atom from two 1,3-bis-(3,5-dimethyl-pyrazol-1-yl)propan-2-olate (bppo) ligands and one O atom from an ethanol mol-ecule. One N atom and one O atom from the two bppo ligands occupy the axial positions. Inter-molecular O-H⋯O hydrogen bonds between the ethanol mol-ecules and perchlorate anions, and O⋯π inter-actions between the perchlorate anions and pyrazole rings [O⋯centroid distances = 3.494 (3) and 3.413 (3) Å], lead to a chain structure along [010].

catena-Poly[[diaqua-dichlorido-manganese(II)]-µ-1,1'-bis-(1H-1,2,4-triazol-1-ylmeth-yl)ferrocene].

In the title complex, [FeMn(C(8)H(8)N(3))(2)Cl(2)(H(2)O)(2)](n), the Mn(II) atom, located on an inversion center, is octa-hedrally coordinated by two N atoms from two adjacent 1,1'-bis-(1H-1,2,4-triazol-1-ylmeth-yl)ferrocene (btmf) ligands and two Cl atoms forming the equatorial plane, with the axial positions occupied by two O atoms of coordinated water mol-ecules. The btmf ligands link adjoining Mn(II) atoms into a zigzag chain along the a axis. The crystal structure is stabilized by inter-molecular O-H⋯N hydrogen bonds, which link the chains, forming a two-dimensional layer parallel to (10); O-H⋯Cl inter-actions link the layers, forming a three-dimensional network.