Probable Pathway Research Articles

Most probable transition pathways and maximal likely trajectories in a genetic regulatory system

We study the most probable transition pathways and maximal likely trajectories in a genetic regulation model of the transcription factor activator’s concentration evolution, with Gaussian noise and non-Gaussian stable Lévy noise in the synthesis reaction rate taking into account, respectively. We compute the most probable transition pathways by the Onsager–Machlup least action principle, and calculate the maximal likely trajectories by spatially maximizing the probability density of the system path, i.e., the solution of the associated nonlocal Fokker–Planck equation. We have observed the rare most probable transition pathways in the case of Gaussian noise, for certain noise intensity, evolution time scale and system parameters. We have especially studied the maximal likely trajectories starting at the low concentration metastable state, and examined whether they evolve to or near the high concentration metastable state (i.e., the likely transcription regime) for certain parameters, in order to gain insights into the transcription processes and the tipping time for the transcription likely to occur. This enables us: (i) to visualize the progress of concentration evolution (i.e., observe whether the system enters the transcription regime within a given time period); (ii) to predict or avoid certain transcriptions via selecting specific noise parameters in particular regions in the parameter space. Moreover, we have found some peculiar or counter-intuitive phenomena in this gene model system, including: (a) A smaller noise intensity may trigger the transcription process, while a larger noise intensity cannot, under the same asymmetric Lévy noise. This phenomenon does not occur in the case of symmetric Lévy noise; (b) The symmetric Lévy motion always induces transition to high concentration, but certain asymmetric Lévy motions do not trigger the switch to transcription.These findings provide insights for further experimental research, in order to achieve or to avoid specific gene transcriptions, with possible relevance for medical advances.

Dual Role of Glyoxal in Metal-Free Dicarbonylation Reaction: Synthesis of Symmetrical and Unsymmetrical Dicarbonyl Imidazoheterocycles.

A practical and efficient method has been developed for the dicarbonylation of imidazoheterocycles using glyoxals as dicarbonyl precursors under metal-free conditions in acetic acid. A series of symmetrical and unsymmetrical dicarbonyl imidazoheterocycles was synthesized in good yields. Aryl and alkyl glyoxals also demonstrated excellent reactivity under similar reaction conditions and delivered corresponding dicarbonyl imidazoheterocycles in high yields. It is believed that the glyoxal plays a dual role both as a dicarbonyl source and as an oxidant in this transformation. A probable mechanistic pathway has been proposed based on control experiments and electrospray ionization high-resolution mass spectrometry analysis.

INVESTIGATIONS ON IN VITRO METABOLITES OF LINEZOLID IN VARIOUS SPECIES

Linezolid is a potent synthetic oxazolidinone used for the treatment of bacterial infections with a new mechanism of action that involves early inhibition of bacterial protein synthesis. In humans, linezolid circulates mainly as parent drug and is excreted primarily as parent drug and a major inactive, morpholine ring-opened carboxylic acid metabolite. In vitro studies were conducted to identify the hepatic enzymes responsible for the oxidative metabolism of linezolid using human liver microsomes. However the specific enzyme responsible for the oxidation of linezolid was not identified. The present study is to check with and identify the probable metabolic pathways in various species like monkey, mouse, rat, dog and human livermicrosomes and put up the best model for the contingency studies using modern analytical techniques. The current investigation on the metabolites obtained after 60 minutes incubation revealed three additional metabolites, namely, M10, M11 and M12, adding on to the list of already reported metabolites.>

Base Catalyzed Scaffold Shift from Pyranone Carboxamide to Pyrazolyl Acetamide through Intramolecular Ring Transformation

AbstractScaffold shift of biologically active pyranone carboxamide to pyrazolyl acetamide, which is another biologically important scaffold was achieved through one‐pot base catalyzed metal‐free intramolecular ring transformation. Out of the two probable mechanistic pathways (Figure 3), substitution at C‐4 by hydrazineyl leading to a pyranone intermediate followed by an intramolecular attack of hydrazineyl at C‐6 and decarboxylation to yield pyrazolyl acetamides was rationalized through LCMS, UV monitoring and computational studies.

Biodegradation of tricresyl phosphate isomers by Brevibacillus brevis: Degradation pathway and metabolic mechanism

Tricresyl phosphates (TCPs), a typical sort of organophosphate flame retardants, has received extensive concerns due to its potential adverse effects. However, limited information is available on the efficient and safe removal methods of TCPs. In this regard, TCPs were tentatively biodegraded with Brevibacillus brevis. A probable degradation pathway was further proposed with the cellular reactions discussed in detail. Experiments showed that B. brevis at 2 g L−1 could degrade 1 mg L−1 tri-m-cresyl phosphate, tri-p-cresyl phosphate, and tri-o-cresyl phosphate by 82.91%, 93.91%, and 53.92%, respectively, within five days. In the process of biodegradation, B. brevis metabolism caused the release of Na+ and Cl− as well as the absorption of some nutrient ions including K+, PO43−, Mg2+, and SO42−; the presence of oxalic acid, citric acid, acetic acid, and malonic acid was also detected. Similar metabolic pathways were found among different TCPs isomers, but tri-o-cresyl phosphate induced more reactive oxygen species than the other two did. This work develops novel insights into the potential mechanisms of TCPs biodegradation by microorganisms.

UVA and UVB radiation induce the formation of neutrophil extracellular traps by human polymorphonuclear cells

Prolonged exposure of the skin to ultraviolet radiation (UV) leads to its damage and loss of protective properties. This condition called photoaging of the skin is caused by a number of destructive factors, such as reactive oxygen species (ROS) and proteolytic enzymes that cause damage to the extracellular matrix, e.g. collagen fibers. Many cells of the immune system, including neutrophils, are involved in the photoaging process. The presence of neutrophils in the skin exposed to UV irradiation is known; however, the mechanism of neutrophil activity at these conditions remains unclear.In our study, we focused on the ability of neutrophils to release neutrophil extracellular traps (NETs) and the role of these structures in the photoaging process. NET release occurs in response to various stimuli; however, we hereby showed that the UVA and UVB radiation that reaches the Earth's surface could activate the mechanism of netosis. UV-induced netosis was much faster than that activated by chemical or biological factors; however, it also occurred due to the production of ROS, known signal mediators in netosis. In this work, we also identified the probable netosis signaling pathway involved in the neutrophil response to UV.The participation of NET components may explain the ongoing process of skin photoaging, but it is also important to indicate netosis as a potential target for skin protection therapy. Antioxidants tested in this work, such as N-acetylcysteine, ethamsylate, as well as vitamin B1 (thiamine), can successfully inhibit UV-induced netosis, and thus be used as protective components against the negative effects of solar radiation.

Preparation, structure, electrical properties and diffusional sodium pathways in the new Na5.2Cu1.9Al(AsO4)4

The novel arsenate Na5.2Cu1.9Al(AsO4)4 was synthesized using solid-state reaction route. Single crystal X-ray diffraction experiment revealed that the title compound crystallizes in a triclinic space group P-1 with a = 5.111(3) Å; b = 7.577(2) Å; c = 9.332(4) Å, α = 88.73(3)°, β = 75.74(5)°, γ = 89.56(4)° and Z = 2. The structural model was supported by bond valence sum (BVS) and charge distribution (CHARDI) validation tools. The crystal structure is based on an open 3D framework made up of CuO4 square planar units, MO5 square-based pyramids and AsO4 tetrahedra sharing corners. The framework tunnels in [100] direction accommodate the Na ions. AC impedance spectroscopy studies show that the conductivity is 1.49 × 10−5 S cm−1 at 575 °C and the activation energy is 1.14 eV. In addition, probable diffusion pathways of Na ions in the structure were simulated using the bond valence sum (BVS) maps method.

In ovo Sound Stimulation Mediated Regulation of BDNF in the Auditory Cortex and Hippocampus of Neonatal Chicks

Brain-derived neurotrophic factor (BDNF) is known to mediate activity-dependent changes in the developing auditory system. Its expression in the brainstem auditory nuclei, auditory cortex and hippocampus of neonatal chicks (Gallus gallus domesticus) in response to in ovo high intensity sound exposure at 110 dB (arrhythmic sound: recorded traffic noise, 30–3000 Hz with peak at 2700 Hz, rhythmic sound: sitar music, 100–4000 Hz) was examined to understand the previously reported altered volume and neuronal number in these regions. In the brainstem auditory nuclei, no mature BDNF, but proBDNF at the protein level was detected, and no change in its levels was observed after in ovo sound stimulation (music and noise). Increased ProBDNF protein levels were found in the auditory cortex in response to arrhythmic sound, along with decreased levels of one of the BDNF mRNA transcripts, in response to both rhythmic and arrhythmic sound stimulation. In the hippocampus, increased levels of mature BDNF were found in response to music. Expression microarray analysis was performed to understand changes in gene expression in the hippocampus in response to music and noise, followed by gene ontology analysis showing enrichment of probable signaling pathways. Differentially expressed genes like CAMK1 and STAT1 were found to be involved in downstream signaling on comparing music versus noise-exposed chicks. In conclusion, we report that BDNF is differentially regulated in the auditory cortex at the transcriptional and post-translational level, and in the hippocampus at the post-translational level in response to in ovo sound stimulation.

Inclusion of Ln(III) in the Complexes of Co(II) with a Mannich Base Ligand: Development of Atmospheric CO2 Fixation and Enhancement of Catalytic Oxidase Activities.

The reaction of the Mannich base ligand (H2L = N, N'-dimethyl- N, N'-bis(2-hydroxy-3-methoxy-5-methylbenzyl)ethylenediamine) with Co(OAc)2·4H2O and Ln(III) nitrate salts (Ln = Gd, Tb, and Dy) under basic conditions afforded three carbonato-bridged isostructural tetranuclear heterometallic Co(II)-Ln(III) complexes (Co2Gd2L2(μ4-CO3)2(NO3)2] (1), [Co2Tb2L2(μ4-CO3)2(NO3)2] (2), and [Co2Dy2L2(μ4-CO3)2(NO3)2] (3)) by atmospheric CO2 fixation. In all structures, two dinuclear [(CoIIL)LnIII(NO3)] units are linked via two μ4-carbonato groups to form the tetranuclear CoII2LnIII2 core. The geometry around two penta-coordinated Co(II) ions is distorted square pyramid, and that around two nona-coordinated Ln(III) ions is intermediate between "spherical tricapped trigonal prism" and "spherical capped square antiprism" in all complexes. The complexes (1-3) showed catecholase-like and phenoxazinone-synthase-like catalytic activities. The kcat values calculated for the catecholase-like reaction were 254.5, 272.4, and 291.3 h-1, and for the phenoxazinone-synthase-like reaction they were 2930.6, 2965.2, and 2998.5 h-1 for complexes 1-3, respectively. The probable pathways for these two oxidase reactions have been proposed by the analyses of mass spectral data. For all of the compounds, the variable temperature magnetic susceptibility and isothermal magnetization data were investigated. The complexes exhibited overall ferromagnetic behavior, which was evident from the isothermal magnetization curves. AC magnetic susceptibility measurements revealed the slow relaxation of magnetization in complexes 2 and 3 but very negligible in 1. The activation energy barriers ( Ueff) for the slow relaxation process were evaluated and found to be 1.99, 2.79, and 8.98 K for 1, 2, and 3, respectively.

Systems Approach to Identify Common Genes and Pathways Associated with Response to Selective Serotonin Reuptake Inhibitors and Major Depression Risk.

Despite numerous studies on major depressive disorder (MDD) susceptibility, the precise underlying molecular mechanism has not been elucidated which restricts the development of etiology-based disease-modifying drug. Major depressive disorder treatment is still symptomatic and is the leading cause of (~30%) failure of the current antidepressant therapy. Here we comprehended the probable genes and pathways commonly associated with antidepressant response and MDD. A systematic review was conducted, and candidate genes/pathways associated with antidepressant response and MDD were identified using an integrative genetics approach. Initially, single nucleotide polymorphisms (SNPs)/genes found to be significantly associated with antidepressant response were systematically reviewed and retrieved from the candidate studies and genome-wide association studies (GWAS). Also, significant variations concerning MDD susceptibility were extracted from GWAS only. We found 245 (Set A) and 800 (Set B) significantly associated genes with antidepressant response and MDD, respectively. Further, gene set enrichment analysis revealed the top five co-occurring molecular pathways (p ≤ 0.05) among the two sets of genes: Cushing syndrome, Axon guidance, cAMP signaling pathway, Insulin secretion, and Glutamatergic synapse, wherein all show a very close relation to synaptic plasticity. Integrative analyses of candidate gene and genome-wide association studies would enable us to investigate the putative targets for the development of disease etiology-based antidepressant that might be more promising than current ones.

A potential bioactive peptide candidate for biomaterial and tissue engineering applications

The surface modification of biomaterials with matrikines for tissue engineering application is one of the recent approaches to improve their biocompatibility. In an earlier study, a peptide containing 21 amino acid isolated from bovine tendon collagen was shown to promote good cell adhesion in HeLa cell, and a smaller region in the peptide was identified using bioinformatics tool to mediate cell-peptide interaction. Hence, the present study was undertaken to validate the cell adhesion property of the smaller region of the peptide and elucidate probable peptide-cell interaction pathway. Cell adhesion and proliferation properties of the peptide were studied on cells cultured on surfaces coated with varying concentrations of peptide. Expression of focal adhesion related proteins like paxillin and pFAK Tyr397 was confirmed by immunoblotting and immunofluorescence microscopy respectively. The anti-pFAK Tyr 397 stained confocal micrographs and mRNA transcription levels of Cdc42 and Rho further confirmed peptide mediated cell spreading. The change in the expression levels of integrin α1 and β1 indicates an integrin mediated cell–peptide interaction for cell survival and proliferation. Integrin mediated adhesion was further confirmed by anti-integrin blocking assay. The modulation of ECM components by the peptide was assessed by expression of COL1A1, TIMP mRNA levels and gelatin zymography for MMPs. The results of the study confirm the role of the small region of the larger collagen peptide in cell adhesion and proliferation and hint at the possible use of such small peptides as biocompatible surface modifiers for tissue scaffolds.

Formation of colloidal alloy semiconductor CdTeSe magic-size clusters at room temperature

Alloy semiconductor magic-size clusters (MSCs) have received scant attention and little is known about their formation pathway. Here, we report the synthesis of alloy CdTeSe MSC-399 (exhibiting sharp absorption peaking at 399 nm) at room temperature, together with an explanation of its formation pathway. The evolution of MSC-399 at room temperature is detected when two prenucleation-stage samples of binary CdTe and CdSe are mixed, which are transparent in optical absorption. For a reaction consisting of Cd, Te, and Se precursors, no MSC-399 is observed. Synchrotron-based in-situ small angle X-ray scattering (SAXS) suggests that the sizes of the two samples and their mixture are similar. We argue that substitution reactions take place after the two binary samples are mixed, which result in the formation of MSC-399 from its precursor compound (PC-399). The present study provides a room-temperature avenue to engineering alloy MSCs and an in-depth understanding of their probable formation pathway.

Prediction of Bone Metastasis in Inflammatory Breast Cancer Using a Markov Chain Model.

Inflammatory breast cancer (IBC) is a rare yet aggressive variant of breast cancer with a high recurrence rate. We hypothesized that patterns of metastasis differ between IBC and non-IBC. We focused on the patterns of bone metastasis throughout disease progression to determine statistical differences that can lead to clinically relevant outcomes. Our primary outcome of this study is to quantify and describe this difference with a view to applying the findings to clinically relevant outcomes for patients. We retrospectively collected data of patients with nonmetastatic IBC (n = 299) and non-IBC (n = 3,436). Probabilities of future site-specific metastases were calculated. Spread patterns were visualized to quantify the most probable metastatic pathways of progression and to categorize spread pattern based on their propensity to subsequent dissemination of cancer. In patients with IBC, the probabilities of developing bone metastasis after chest wall, lung, or liver metastasis as the first site of progression were high: 28%, 21%, and 21%, respectively. For patients with non-IBC, the probability of developing bone metastasis was fairly consistent regardless of initial metastasis site. Metastatic patterns of spread differ between patients with IBC and non-IBC. Selection of patients with IBC with known liver, chest wall, and/or lung metastasis would create a population in whom to investigate effective methods for preventing future bone metastasis. This study demonstrated that the patterns of metastasis leading to and following bone metastasis differ significantly between patients with inflammatory breast cancer (IBC) and those with non-IBC. Patients with IBC had a progression pattern that tended toward the development of bone metastasis if they had previously developed metastases in the liver, chest wall, and lung, rather than in other sites. Selection of patients with IBC with known liver, chest wall, and/or lung metastasis would create a population in whom to investigate effective methods for preventing future bone metastasis.

Facile synthesis of inorganic–organic Fe2W18Fe4@NiO@CTS hybrid nanocatalyst induced efficient performance in oxidative desulfurization of real fuel

In this work, a new nanocatalyst, Fe2W18Fe4@NiO@CTS, was synthesized by the reaction of sandwich‐type polyoxometalate (Fe2W18Fe4), nickel oxide (NiO), and chitosan (CTS) via sol–gel method. The assembled nanocatalyst was systematically characterized by FT‐IR, UV–vis, XRD, SEM, and EDX analysis. The catalytic activity of Fe2W18Fe4@NiO@CTS was tested on oxidative desulfurization (ODS) of real gasoline and model fuels. The experimental results revealed that the levels of sulfur content and mercaptan compounds of gasoline were lowered with 97% efficiency. Also, the Fe2W18Fe4@NiO@CTS nanocatalyst demonstrated an outstanding catalytic performance for the oxidation of dibenzothiophene (DBT) in the model fuel. The major factors that influence the desulfurization efficiency and the kinetic study of the ODS reactions were fully detailed and discussed. The probable ODS pathway was proposed via the electrophilic mechanism on the basis of the electrophilic characteristic of the metal‐oxo‐peroxo intermediates. The prepared nanocatalyst could be reused for 5 successive runs without any appreciable loss in its catalytic activity. As a result, the current study suggested the potential application of the Fe2W18Fe4@NiO@CTS hybrid nanocatalyst as an ideal candidate for removal of sulfur compounds from fuel.

Ultrafine Bi3TaO7 Nanodot-Decorated V, N Codoped TiO2 Nanoblocks for Visible-Light Photocatalytic Activity: Interfacial Effect and Mechanism Insight.

Bi3TaO7 is a potential photocatalyst because of its high chemical stability, defective fluorite-type structure, and superior mobility of photoinduced holes. However, few studies have focused on the interfacial effects of Bi3TaO7-based photocatalysts. In this work, 0D Bi3TaO7 nanodot-hybridized 3D V and N codoped TiO2 nanoblock (B/VNT) composites were first synthesized for the photocatalytic removal of oxytetracycline hydrochloride, 2,4,6-trichlorophenol, and tetrabromobisphenol A. The fabricated B/VNT had a photocatalytic performance superior to that of pristine components, and probable degradation pathways were proposed according to the primary intermediates identified by a gas chromatography-mass spectrometer. Interestingly, on B/VNT, the transfer of interfacial electrons was observed from V/N-TiO2 to Bi3TaO7, and the formed built-in electronic field led to a direct Z-scheme structure, rather than type II, as confirmed by the generated •OH and •O2- radicals and band structures from the density functional theory calculation. Therefore, the strong interfacial electronic interaction on the B/VNT was significant, which drove faster photogenerated charge transfer, more visible-light adsorption, and active •OH and •O2- generation, thus improving the photocatalytic activity.

Directing-Group-Assisted Manganese-Catalyzed Cyclopropanation of Indoles.

The first manganese-catalyzed cyclopropanation of indoles is reported in moderate to excellent yield with methyl-2-diazo-2-arylacetates. This new strategy involved acetyl (COCH3) as the directing group and exhibited exceptional functional group tolerance. In the absence of stereodirecting groups the desired products were obtained as a mixture of diastereomers (7:3 → 8:2). Control experiments and DFT studies elucidated the probable pathway for the formation of cyclopropane-fused indole product. Deacetylation of the final products afforded both C3-substituted NH-indoles.

Cypate and Cypate-Glucosamine as Near-Infrared Fluorescent Probes for In Vivo Tumor Imaging.

Near-infrared (NIR) imaging is a promising technique for use as a noninvasive and sensitive diagnostic tool. Although the NIR fluorescently labeled glucose analog glucosamine (cypate-glucosamine) has applications in preclinical imaging, the transport pathways and fate of this probe in tissues remain unaddressed. Here, we have synthesized and characterized cypate and cypate-glucosamine conjugate (cy-2-glu), and investigated the probable transport pathways of these probes in vitro and in vivo. We compared uptake of the probes in the presence and absence of excess d-glucose, "saturated cypate" and palmitic acid in two normal-cancer cell line pairs: lung cancer (A549)-normal (MRC9) and prostate cancer (DU145)-normal (BPH). Breast cancer (MDA-MB-231) and liver cancer (HepG2) cell lines were also examined. Results support use of the glucose transport pathway by cy-2-glu and fatty acid transport pathway by cypate. Mass spectrometry data on the in vitro extracts revealed deamidation of cy-2-glu in prostate and liver cells, suggesting release of glucosamine. In vivo biodistribution studies in mice engrafted with breast tumors showed a distinct accumulation of cy-2-glu in liver and tumors, and to a lesser extent in kidneys and spleen. A negligible accumulation of cypate alone in tumors was observed. Analysis of urine extracts revealed renal excretion of the cy-2-glu probe in the form of free cypate, indicating deamidation of cy-2-glu in tissues. Thus, investigation of the metabolic pathways used by NIR probes such as cy-2-glu advances their use in the detection and monitoring of tumor progression in preclinical animal studies.

A density functional theory study on ethylene decomposition to carbon monomer on Cu(410) surface

First-principles density functional theory (DFT) study has been conducted to investigate the probable reaction pathways of carbon formation from ethylene decomposition on Cu(410) surface. The geometric structures and energy information of all the species and relevant CH and CC bond scission reactions have been computed. The results indicate that the proceeding of the CH bond scission reactions is more favorable than CC bond scission reactions. With the aid of the computed results, we find two possible pathways of ethylene decomposition. Ethylene experiences complete dehydrogenation, no carbon monomer will be generated and CC is the final product. The CC species are easy to form but difficult to decompose, which indicates that CC may be another form of carbon deposition. The research may help us make further understanding on the mechanism of carbon formation and be helpful to design of Cu-based catalyst.

Cation Distributions and Anion Disorder in Ba3NbMO8.5 (M = Mo, W) Materials: Implications for Oxide Ion Conductivity

Competitive oxide ion conductivity was identified recently in members of the Ba3Nb1–y(Mo1–xWx)1+yO8.5+1/2y (0 ≤ x ≤ 1, −0.3 ≤ y ≤ 0.2) series, which adopt a disordered rhombohedral “hybrid” structure combining features of the 9R perovskite and palmierite structures. We report the first growth of Ba3NbMoO8.5 and Ba3NbWO8.5 single crystals from molten phases and their characterizations using single-crystal X-ray diffraction data between 120 and 473 K. Structure refinements reveal a previously unreported splitting of the central Nb/M cation site, rationalized by bonding considerations, which imposes limitations on the material stoichiometry and possible arrangements of cations within the face-sharing polyhedral stacks. The analysis of atomic displacement parameters and bond valence energy landscapes (BVELs) gives new insight into the probable low-energy pathways for oxide ion diffusion in the hybrid structure, indicating that they are three-dimensional and involve all crystallographically distinct oxygen sites. Evidence for considerable static disorder of the oxide ions at temperatures below the onset of significant conductivity is also discussed.

Targeted depletion of BTF3a in macrophages activates autophagic pathway to eliminate Mycobacterium tuberculosis

Aimsβ casein fragment peptide (54–59) downregulates Basic Transcription factor 3a (BTF3a) in macrophages and exhibits enhanced clearance of M. bovis BCG and several other intracellular pathogens. However, the direct effect of BTF3a downregulation on Mycobacterium tuberculosis (Mtb) survival and the probable pathways involved have not yet been studied. Therefore, the present study was undertaken to deduce the antimycobacterial significance of BTF3a in human macrophages. Main methodsCRISPR/Cas 9 gRNA was designed to downregulate BTF3a in THP1 derived macrophages. Fold change in BTF3a, p62 and Lamp 1 expression was evaluated through immune blot analysis. CFU assay was done to enumerate the intracellular burden of Mtb H37Rv. LC3B-II turnover and Lamp 1 expression was checked through immunoblotting and also visualized through confocal microscopy. Colocalization of Mtb H37Rv with LC3B, Lysotracker and Rab 7 was visualized through confocal microscopy. Key findingsThe current study identifies BTF3a as a critical host factor assisting intracellular survival of Mtb. In THP1 derived macrophages, infection with Mtb H37Rv resulted in upregulation of BTF3a and targeted depletion of BTF3a resulted in augmented Mtb clearance. Furthermore, BTF3a knockdown demonstrated increased autophagy flux and ameliorated the lysosomal targeting of Mtb containing autophagosomes for lysosomal degradation. SignificanceDeep understanding of macrophage-Mtb interactions and their roles in the pathogenesis can offer exciting new therapeutic targets for alternative host-specific adjunct therapies in tuberculosis treatment. The present study highlights a novel and significant role of BTF3a in curbing the intracellular survival of Mtb through modulation of autophagy and lysosome biogenesis.