Esophagopleural fistula (EPF) is an abnormal pathological communication between the esophagus and the pleural space. While EPF is typically associated with malignancy or iatrogenic injury, tuberculosis (TB) is a rare cause, with only a limited number reported cases. Here, we present a case of TB related EPF that developed following diagnostic surgery and was successfully treated with anti-TB therapy alone, without the need for surgical intervention.

A 58-year-old male presented with a three-month history of a six-kilogram weight loss, chronic cough and sputum production. Chest computed tomography (CT) revealed necrotic lymphadenopathy with air bubbles within the 2R lymph node, located in the paratracheal region just below the origin of subclavian artery, raising suspicion for primary lung cancer. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed, but histopathological analysis revealed only non-neoplastic bronchial tissue and lymphoid aggregates. Given the detection of a hypermetabolic lesion in the 2R lymph node on positron emission tomography-computed tomography (PET-CT), raising suspicion of malignancy, a surgical biopsy was performed. However, histopathological examination revealed only chronic active inflammation. One-month postoperatively, the patient developed EPF, which was initially managed with nasogastric tube feeding and antibiotics for aspiration pneumonia. Microbiological tests, including sputum and bronchoscopic washing, were unremarkable. The patient was discharged after approximately 40 days at his request, despite persistent EPF without clinical improvement. Four months later, he was re-admitted due to worsening aspiration symptoms and progressive lung lesions. Repeat microbiological testing ultimately confirmed pulmonary TB, with positive acid-fast bacilli (AFB) staining and Xpert MTB/RIF assay results. Standard four-drug anti-TB therapy led to significant clinical improvement, with complete resolution of the EPF on follow-up CT after six months. The patient fully recovered without surgical intervention.

This case highlights the diagnostic challenges of TB presenting as isolated lymphadenopathy and underscores the importance of repeated testing for accurate diagnosis. Furthermore, it demonstrates that TB-related EPF can be successfully managed with medical therapy alone, even in cases of advanced disease.

Tuberculosis (TB) is a transmissible disease that causes severe infections in adults as well as in infants, as they have immature immune systems. Lungs are the main site for pulmonary TB infection, although TB can affect other parts like lymph nodes, bone, joints, etc., which is known as extrapulmonary TB. M. tuberculosis is becoming one of the world's most severe pathogens due to growing multidrug resistance (MDR) and extensively drug resistance (XDR), rendering treatment medications useless. GpgP was chosen as the promising drug target protein in this study because it is primarily involved in the catalysis of the second step in the production of Methylglucose lipopolysaccharides (MGLPs), which regulate the synthesis of mycolic acids, which are an essential component for building the mycobacterial cell envelope. The cell envelope of M. tuberculosis is unique and is responsible for the bacteria's flexibility and pathogenicity. An in-house library of phytochemicals was utilized for screening in AutoDock Vina, and then the ligands were docked using AutoDock with the drug target protein for further validation. Then, four ligands were filtered out using SwissADME that were further studied by performing molecular dynamic simulations. After a thorough analysis, CID_446611 and CID_5282146 ligands were identified as potential inhibitors of GpgP.

This study aims to evaluate the capability of Large Language Models (LLMs) in responding to questions related to tuberculosis. Three large language models (ChatGPT, Gemini, and Copilot) were selected based on public accessibility criteria and their ability to respond to medical questions. Questions were designed across four main domains (diagnosis, treatment, prevention and control, and disease management). The responses were subsequently evaluated using DISCERN-AI and NLAT-AI assessment tools. ChatGPT achieved higher scores (4 out of 5) across all domains, while Gemini demonstrated superior performance in specific areas such as prevention and control with a score of 4.4. Copilot showed the weakest performance in disease management with a score of 3.6. In the diagnosis domain, all three models demonstrated equivalent performance (4 out of 5). According to the DISCERN-AI criteria, ChatGPT excelled in information relevance but showed deficiencies in providing sources and information production dates. All three models exhibited similar performance in balance and objectivity indicators. While all three models demonstrate acceptable capabilities in responding to medical questions related to tuberculosis, they share common limitations such as insufficient source citation and failure to acknowledge response uncertainties. Enhancement of these models could strengthen their role in providing medical information.

The current research includes the study of 28 new 2-hydrazineyl-2-oxoethyl-4-(1H-pyrrol-1-yl) benzoate derivatives as antitubercular, antibacterial, and enoyl-ACP reductase enzyme inhibitors. SYBYL-X.2.0 was used to investigate the molecular docking of ENR-ACP reductase/InhA in complex with 1-cyclohexyl-N-(3,5-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide (PDB ID:4TZK) and MtDHFR in complex with methotrexate (PDB ID:1DF7). All of the reported derivatives have two or more H-bonding interactions with TYR158 and the cofactor NAD + , which fit snugly into InhA's binding pocket, with MIC values of 0.8-3.12 µg/mL, 0.4-3.12 µg/mL, and 1.6-12.5 µg/mL [4(a-e), 5(a-p), 6(a-e)]. Also, the molecular H-bonding interactions of reported molecules with amino acids ARG32 and ARG60 of MtDHFR showed the interaction of molecules with targeted site. All of the reported compounds showed good activity against M. tuberculosis H37Rv, Gram-negative E.coli, and Gram-positive S. aureus, respectively. Compounds 5b and 6d showed highest antitubercular activity with the MIC value of 0.8 µg/mL. InhA inhibition was good to moderate in the tested compounds, with IC50 inhibition ranging from 9 to 51% at 50μM; and MtDHFR inhibition was good with IC50 values ranging from 23 to 153 µM compared to trimethoprim at 92 µM. The most potent compounds exhibiting dual enzyme inhibition were further evaluated for cytotoxicity in mammalian cells using the human lung cancer cell line A549. These compounds demonstrated significant cytotoxic effects, with IC50 values ranging from 255 to 319 µg/mL. In comparison, the standard antitubercular drug isoniazid exhibited an IC50 value greater than 450 µg/mL, while the anticancer drug cisplatin showed an IC50 value of 9.9 µg/mL. These molecules represent excellent future therapeutic possibilities with potential use in the biological and medical sciences due to the compounds' pronounced docking properties and biological activity.

Single nucleotide polymorphisms (SNP) in genes encoding cytokines influence tuberculosis (TB) outcomes.

To characterise genotypes of the SNPs IFN-gamma +874 T > A, TNF-alpha -308 G > A, IL-6 -174 G > C, IL-10 -1082A > G, TGF-beta codon 10 T > C, and TGF-beta codon 25 G > C in patients with pulmonary (PTB) and extrapulmonary TB (EPTB).

82 PTB and 45 EPTB cases were compared, concerning genotype distribution of the mentioned SNPs, characterised via sequence-specific primer polymerase chain reaction (PCR).

Regarding IFN-gamma +874 T > A, AA genotype was the most frequent in both groups, TA was more frequent in PTB and TT in EPTB, with no statistical significance. For SNP TNF-alpha -308 G > A, GG was more frequent in both groups of patients. Regarding the IL-6 -174 G > C polymorphism, GG predominated in both groups, while CG and GG were significantly more frequent in patients with PTB and EPTB, respectively. Concerning IL-10 -1082 A > G, AA predominated in both PTB and EPTB. Concerning TGF-beta codon 10 T > C, CC predominated in PTB while TC predominated in EPTB, but the differences were not statistically significant. Genotype GG of TGF-beta codon 25 G > C predominated among PTB and EPTB patients.

Except for IL-6, the genotype profile could not differentiate PTB and EPTB. Hence, the studied SNPs are not significantly associated with the extrapulmonary involvement of TB.

Exosomes, small extracellular vesicles with lipid bilayer membranes, play a crucial role in cellular communication and can transfer diverse biological cargo, including proteins, lipids, and nucleic acids, from donor to recipient cells. Exosomes possess diverse immunological properties, such as antigen delivery and immune activation, along with excellent drug delivery capabilities, making them promising candidates for vaccine development. For different diseases, exosome-based vaccines can be designed as therapeutic or prophylactic vaccines by leveraging cellular immunity or humoral immunity. With the emergence of precision medicine, exosome-based personalized vaccines demonstrate exceptional therapeutic potential. This review systematically introduces the sources, biogenesis mechanisms, and components of exosomes and describes their regulatory roles in the immune system. Subsequently, the preparation, administration, and personalized therapy of exosome-based vaccines are discussed. Finally, the applications and clinical trials of exosome-based vaccines in the fields of anti-infection and anti-tumor therapies are particularly highlighted, with an analysis of the potential challenges in future vaccine development.

Bedaquiline is employed to treat multidrug-resistant and extensive drug-resistant tuberculosis by inhibiting the proton pump of adenosine triphosphate synthase in Mycobacterium tuberculosis. This study aims to investigate the effect of high-fat diets on the pharmacokinetics of bedaquiline through a single-center, open-label, randomized trial in healthy Chinese participants. Bedaquiline fumarate tablets were administered at a dosage of 100 mg under both fasted conditions and high-fat diet conditions. The concentrations were determined using liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated using a noncompartmental model. The high-fat diet group showed a maximum plasma concentration that exceeded that of the fasted group by more than 4-fold and an area under the concentration-time curve from time 0 to the last measurable point that was more than twice as high. Moreover, compared to the fasted group, the high-fat diet group exhibits significantly lower levels of apparent clearance, indicating that the high-fat diet markedly enhances the rate and extent of gastrointestinal absorption of bedaquiline. To optimize drug bioavailability and absorption and ensure safety, the administration of bedaquiline with food is recommended in accordance with clinical usage guidelines and expert consensus.

Infections can mimic Primary Systemic Vasculitis. Many clinical features and investigations maybe very similar between the two conditions. It is very important for the clinician to be aware of the various infections which mimic vasculitis, since inadvertent immunosuppression in these patients can be fatal. Infections can mimic small, medium or large vessel vasculitis. Infections can produce autoantibodies such as Anti-neutrophil cytoplasmic antibody through molecular mimicry and could confound clinical judgement. In addition to the many infections causing vasculitis, more recently COVID-19 associated vasculitis has been described. The exact pathogenesis of infection associated vasculitis is not clear although direct spread, immune complex deposition and T/B cell activation are proposed. Infection as an etiological agent for primary systemic vasculitis has long been debated but definite evidence for the same is lacking. Many drugs used in daily clinical practice can rarely cause vasculitis. More recently Immune-check point inhibitors-induced vasculitis has been described.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health challenge, particularly in developing nations. Side effects and increasing drug resistance often limit conventional pharmaceutical treatments for TB. This has highlighted the urgent need for novel therapeutic agents. Traditional medicine offers a promising avenue for discovering effective and safer alternatives. In silico approaches play a crucial role in pharmaceutical research by facilitating the identification of novel therapeutic compounds. These techniques are widely employed to explore potential treatments for diverse diseases. This study aims to identify lead molecules with anti-tuberculosis potential that could be further studied for their inhibitory potential and possible optimization for the treatment of tuberculosis. Chlorophytum borivilianum and Asparagus racemosus were selected for their diverse phytochemical profiles and proven pharmacological activities, including significant antimicrobial properties that make them promising candidates for in silico exploration of anti-tuberculosis therapeutics. The drug-likeness and pharmacokinetics of phytochemicals from the plants were evaluated using Lipinski's rule of five, and ADMET predictions. Phytochemicals meeting these criteria were subjected to molecular docking against Mycobacterium tuberculosis targets: CYP51, InhA, and EthR, using Vina (PyRx)platform to calculate binding affinities and assess interaction stability. Molecular dynamics simulations (100 ns) were performed to validate the stability of the docked complexes, focusing on key parameters such as RMSD, RMSF, and Rg. This approach identified hecogenin, sarsasapogenin, and isoflavone as potential inhibitors of CYP51 with high binding affinities and stable interactions, suggesting their promise as lead compounds for tuberculosis treatment.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), still remains one of the leading causes of mortality worldwide. The elusive nature of this pathogen and its ability to develop drug resistance makes it a serious threat to global health. BCG, the only preventive vaccine for TB, has a limited efficacy and provides partial protection against the disease. A new effective recombinant vaccine capable of producing a stronger and more comprehensive immune response is required to address this global threat. In the present study, we adopted an in-silico approach to develop a multi-epitope vaccine by screening 198 "regulatory proteins" of Mtb H37Rv strain. Epitopes generated from these proteins were screened on the basis of antigenicity, cytokine profile, allergenicity, toxicity, conservancy and population coverage. Selected epitopes were docked with predominant MHC alleles that were used to develop a vaccine construct using suitable linkers and adjuvant. The construct was subjected to homology modelling, tertiary structure validation and refinement and was eventually docked with Toll-like receptor 2 receptor. Molecular dynamic simulation studies revealed stable interactions between the vaccine construct and TLR-2 receptor. The construct also displayed a high probability to elicit a protective immune response involving both humoral and cell-mediated components. In conclusion, the findings suggest that the constructed vaccine has the potential to induce a robust immune response against Mtb. However, further in-vitro and in-vivo studies are required to assess the safety, efficacy, and long-term protective effects of the vaccine construct.

The online version contains supplementary material available at 10.1007/s40203-025-00322-8.

In vitro models serve as valuable tools for understanding the complex cellular and molecular interactions involved in granuloma formation, providing a controlled environment to explore the underlying mechanisms of their development and function. Various models have been developed to replicate granulomatous diseases, even though they may lack the sophistication needed to fully capture the variability present in clinical spectra and environmental influences. Traditional cultures of PBMCs have been widely used to generate granuloma models, enabling the study of aggregation responses to various stimuli. However, growing cells on a two-dimensional (2D) plastic surface as a monolayer can lead to altered cellular responses and the modulation of signaling pathways, which may not accurately represent in vivo conditions. In response to these limitations, the past decade has seen significant advancements in the development of three-dimensional (3D) in vitro models, which more effectively mimic in vivo conditions and provide better insights into cell-cell and cell-microenvironment interactions. Meanwhile, the use of in vivo animal models in biomedical research must adhere to the principle of the three Rs (replacement, reduction, and refinement) while ensuring that the models faithfully replicate human-specific processes. This review summarizes and compares the main models developed to investigate granulomas, focusing on their contribution to advancing our understanding of granuloma biology. We also discuss the strengths and limitations of each model, offering insights into their biological relevance and practical applications.

Tuberculosis (TB) is a major global health concern, causing 1.5 million deaths in 2020. Diagnostic tests for TB are often inaccurate, expensive, and inaccessible, making chest x-rays augmented with artificial intelligence (AI) a promising solution. However, whether providers are willing to adopt AI is not apparent.

The study seeks to understand the attitude of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) and informal health care providers, who we jointly call AIPs, toward adopting AI for TB diagnosis. We chose to study these providers as they are the first point of contact for a majority of TB patients in India.

We conducted a cross-sectional survey of 406 AIPs across the states of Jharkhand (162 participants) and Gujarat (244 participants) in India. We designed the survey questionnaire to assess the AIPs' confidence in treating presumptive TB patients, their trust in local radiologists' reading of the chest x-ray images, their beliefs regarding the diagnostic capabilities of AI, and their willingness to adopt AI for TB diagnosis.

We found that 93.7% (270/288) of AIPs believed that AI could improve the accuracy of TB diagnosis, and for those who believed in AI, 71.9% (194/270) were willing to try AI. Among all AIPs, 69.4% (200/288) were willing to try AI. However, we found significant differences in AIPs' willingness to try AI across the 2 states. Specifically, in Gujarat, a state with better and more accessible health care infrastructure, 73.4% (155/211) were willing to try AI, and in Jharkhand, 58.4% (45/77) were willing to try AI. Moreover, AIPs in Gujarat who showed higher trust in the local radiologists were less likely to try AI (odds ratio [OR] 0.15, 95% CI 0.03-0.69; P=.02). In contrast, in Jharkhand, those who showed higher trust in the local radiologists were more likely to try AI (OR 2.11, 95% CI 0.9-4.93; P=.09).

While most AIPs believed in the potential benefits of AI-based TB diagnoses, many did not intend to try AI, indicating that the expected benefits of AI measured in terms of technological superiority may not directly translate to impact on the ground. Improving beliefs among AIPs with poor access to radiology services or those who are less confident of diagnosing TB is likely to result in a greater impact of AI on the ground. Additionally, tailored interventions addressing regional and infrastructural differences may facilitate AI adoption in India's informal health care sector.

Extrapulmonary tuberculosis (EPTB) is an important public health problem due to its diverse clinical presentations, diagnostic complexities, and significant impact on patient outcomes and public health. Our study aimed to understand the sociodemographic, clinical, and laboratory characteristics as well as diagnostic and treatment modalities of adult patients with EPTB. This is a multicentric retrospective study that covers patients with EPTB cases followed up from January 2015 to December 2022 among tuberculosis (TB) dispensaries and Infectious Diseases and Clinical Microbiology clinics of 15 hospitals located in various regions of Turkey. The study included 64.6% women with a mean age of 44 years and a mortality rate of 3.5% within 1 year of diagnosis. Initial constitutional symptoms were predominantly fatigue (57%) and anorexia (53.7%). The most commonly affected sites were the lymph nodes (49.1%) and pleura (9.7%). The lumbar region was particularly involved in cases with spinal TB. Diagnostic findings included acid-fast bacilli positivity in 27.5% of cases, tuberculosis polymerase chain reaction positivity in 41%, elevated adenosine deaminase levels in 91.2% (especially in pleural and peritoneal fluids), and mycobacterial culture positivity in 40.9%. Pathology slides showed granulomatous inflammation in 97.7%. Increased C-reactive protein (CRP) levels correlated with the number of organs affected. Anti-TB treatment-related hepatotoxicity was detected in 8.9% of patients. In this study, it is important to note that the lumbar region is predominantly affected with involvement in spinal region. CRP level was consistent with the number of organ involvements and was one of the most critical results of this study.

Tuberculosis (TB) remains a significant global health challenge, with multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains posing severe threats to treatment efficacy. Linezolid, a key component of the BPaL (Bedaquiline, Pretomanid and Linezolid) regimen, has demonstrated substantial efficacy against MDR-TB and XDR-TB. However, its clinical utility is often limited by side effects such as myelosuppression and monoamine oxidase (MAO) inhibition, linked to its mechanism of action. This perspective centres on the structural toxicity relationship (STR) of Linezolid and its analogues, exploring modifications to the C-ring and C-5 position that aim to reduce these toxicities while maintaining or enhancing antibacterial activity. Several promising analogues have been identified that exhibit reduced myelosuppression and MAO inhibition, highlighting the potential for developing safer Linezolid derivatives. The findings underscore the importance of continued research into the structure toxicity relationships of oxazolidinones to improve the therapeutic profiles of these essential drugs in combating drug-resistant TB.

Mycobacteria have several mechanisms for evasion of protective responses mounted by the host. In this study, we unravel yet another mechanism that is mediated by Toll-Like Receptors TLR2, TLR4, and TLR7 in epithelial cells. We show that mycobacterial infection of epithelial cells increases the expression of TLR2, TLR4, and TLR7. Stimulation of either TLR along with mycobacterial infection results in an inhibition of oxidative burst resulting in increased survival of mycobacteria inside epithelial cells. TLR stimulation along with mycobacterial infection also inhibits activation of epithelial cells for T cell responses by differentially regulating the activation of ERK-MAPK and p38-MAPK along with inhibition of co-stimulatory molecule CD86 expression. Furthermore, stimulation of either TLR inhibits the induction of apoptosis and autophagy. Knockdown of either TLR by specific siRNAs reverses the inhibition by ROS and apoptosis by mycobacteria and results in reduced intracellular survival of mycobacteria in a MyD88-dependent manner. These results point towards a negative role for TLR2, TLR4, and TLR7 in regulating protective responses to M. bovis BCG infection in epithelial cells.

Tuberculosis (TB) is a chronic respiratory infectious disease and is induced by Mycobacterium tuberculosis (M.tb) infection. Macrophages serve as the cellular home in immunoreaction against M.tb infection, which is tightly regulated through Toll-like receptor 4 (TLR4) expression. Therefore, this study is designed to explore the role and mechanism of TLR4 in mycobacterial injury in human macrophages (THP-1 cells) after M.tb infection. Cell proliferation and apoptosis were assessed using MTT, EdU, and flow cytometry assays. ELISA kits were utilized to assess the levels of Interleukin-6 (IL-6), IL-1β, and tumor necrosis factor α (TNF-α). The binding between Yin-Yang-1 (YY1) and TLR4 promoter was predicted by JASPAR and verified using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. M.tb infection might repress THP-1 cell proliferation, and induce cell apoptosis and inflammatory response in a multiplicity of infection (MOI)-dependent manner. Moreover, M.tb infection increased the expression of TLR4 in HTP-1 cells in an MOI-dependent way, and its downregulation might overturn M.tb infection-mediated HTP-1 cell damage and inflammatory response. At the molecular level, YY1 was a transcription factor of TLR4 and promoted TLR4 transcription via binding to its promoter region. Besides, YY1 might activate the NF-kB signaling pathway via regulating TLR4. Meanwhile, TLR4 inhibitor BAY11-7082 might overturn the repression effect of TLR4 on M.tb-infected HTP-1 cell damage. YY1-activated TLR4 might aggravate mycobacterial injury in human macrophages after M.tb infection by the NF-kB pathway, providing a promising therapeutic target for TB treatment.

Unveiling novel pathways for drug discovery forms the foundation of a new era in the combat against tuberculosis. The discovery of a novel drug, bedaquiline, targeting mycobacterial ATP synthase highlighted the targetability of the energy metabolism pathway. The significant potency of bedaquiline against heterogeneous population of Mycobacterium tuberculosis marks ATP synthase as an important complex of the electron transport chain. This review focuses on the importance and unique characteristics of mycobacterial ATP synthase. Understanding these distinctions enables the targeting of ATP synthase subunits for drug discovery, without aiming at the mammalian counterpart. Furthermore, a brief comparison of the structural differences between mycobacterial and mitochondrial ATP synthase is discussed. Being a complex multi-subunit protein, ATP synthase offers multiple sites for potential inhibitors, including the a, c, ε, γ, and δ subunits. Inhibitors targeting these subunits are critically reviewed, providing insight into the design of better and more potent chemical entities with the potential for effective treatment regimens.

In clinical practice, an accurate and efficient detection approach for pulmonary tuberculosis (PTB) is highly needed. The fluorescence in situ hybridization (FISH) assay for PTB might be a suitable alternative to current tests. However, a systematic assessment of the diagnostic performance of this new approach is not available. Our study aimed to determine the diagnostic accuracy of FISH for PTB.

We examined PubMed and three more databases including Embase, Cochrane Library, and Web of Science databases from their establishment to November 10, 2023, for published articles on the diagnostic performance of FISH on individuals with clinical suspicion of tuberculosis (TB). QUADAS-2 was used to evaluate the literature's quality. We used Meta-DiSc software to create forest plots.

The search yielded 7 studies, involving 1,224 sputum samples that could be included in our meta-analysis. The combined FISH sensitivity and specificity were 0.89 (95% CI 0.86-0.92) and 0.98 (95% CI 0.97-0.99), respectively. Furthermore, subgroup analysis was performed based on probes and PTB incidence.

FISH may be useful in the diagnosis of pulmonary tuberculosis. The sensitivity and specificity of FISH are high for most sputum specimens. Additionally, FISH has better diagnostic performance in countries with low PTB prevalence than in high PTB prevalence countries. We hope this study will find a new and effective tool for the early diagnosis of PTB.

This study was conducted to investigate the trend of some tuberculosis (TB) indices and identify existing gaps in addressing this important public health issue in Hamadan province over a long time period. Study Design: A registry-based cross-sectional study.

In this study, we examined the trend of 10 TB indicators separately in males and females, including the incidence rates of smear-positive pulmonary TB (SPPT), extra-pulmonary TB (EPT), and smear-negative pulmonary TB (SNPT), co-infection with AIDS, relapse rate, smear conversion rate two months after treatment initiation, TB mortality rate, diagnosis rate of pulmonary TB with a smear grade of 3+, treatment success rate, and TB diagnosis rate by the private sector in Hamadan province during 2011-2022. The trend analysis of TB was conducted using Joinpoint regression model, and the annual percentage change (APC) and the average annual percentage change (AAPC) were calculated.

A total of 481 females and 554 males were eligible for analysis. The incidence of SPPT in females showed a decreasing trend (AAPC: -7.72; 95% CI: -15.63, -1.10; P=0.008). The rates of EPT and treatment success showed a significant downward trend in both genders. In contrast, the recurrence rate among females exhibited a notable upward trend during the specified time period (AAPC: 18.45; 95% CI: 3.23, 46.47; P=0.0002).

The findings of this study suggest that the epidemiological profile of TB has exhibited a relatively favorable trend in some of the examined indicators since 2011, with declines observed in both SPPT and EPT.

Aim: To evaluate the anti-Mycobacterium tuberculosis (Mtb) potential of the hybrid oxadiazol-4-methoxynaphthalene (6n) derived from N-acylhydrazone (4k).Materials & methods: The study determined the minimal inhibitory concentration of (6n) against Mtb H37Rv and Mtb clinical isolates, potential combination of (6n) with anti-tuberculosis drugs and carried out time kill curve assay of Mtb H37Rv. Additional contribution for the analysis of (6n) was explored by in silico pharmacokinetics, and in vitro and in vivo cytotoxicity determinations.Results: The newly synthesized molecule (6n) demonstrated anti-Mtb activity, low cytotoxicity and selectivity for Mtb.Conclusion: The derivative (6n) emerges as a potential anti-TB drug candidate.

Bacterial infections have accompanied humanity for centuries. The discovery of the first antibiotics and the subsequent golden era of their discovery temporarily shifted the balance in this confrontation to the side of humans. Nevertheless, the excessive and improper use of antibacterial drugs and the evolution of bacteria has gotten the better of humans again. Therefore, today, the search for new antibacterial drugs or the development of alternative approaches to the prevention and treatment of bacterial infections is relevant and topical again. Vaccination is one of the most effective strategies for the prevention of bacterial infections. The success of new-generation vaccines, such as mRNA vaccines, in the fight against viral infections has prompted many researchers to design mRNA vaccines against bacterial infections. Nevertheless, the biology of bacteria and their interactions with the host's immunity are much more complex compared to viruses. In this review, we discuss structural features and key mechanisms of evasion of an immune response for nine species of bacterial pathogens against which mRNA vaccines have been developed and tested in animals. We focus on the results of experiments involving the application of mRNA vaccines against various bacterial pathogens in animal models and discuss possible options for improving the vaccines' effectiveness. This is one of the first comprehensive reviews of the use of mRNA vaccines against bacterial infections in vivo to improve our knowledge.

The global push to eliminate tuberculosis (TB) as a public health threat is increasingly urgent, particularly in high-burden areas like the Oliver Reginald Tambo District Municipality, South Africa. Drug-resistant TB (DR-TB) poses a significant challenge to TB control efforts and is a leading cause of TB-related deaths. This study aimed to assess DR-TB transmission patterns and predict future cases using geospatial and predictive modeling techniques.

A retrospective cross-sectional study was conducted across five decentralized DR-TB facilities in the O.R. Tambo District Municipality from January 2018 to December 2020. Data were obtained from Statistics South Africa, and patient GPS coordinates were used to identify clusters of DR-TB cases via DBSCAN clustering. Hotspot analysis (Getis-Ord Gi) was performed, and two predictive models (Linear Regression and Random Forest) were developed to estimate future DR-TB cases. Analyses were conducted using Python 3.8 and R 4.1.1, with significance set at p < 0.05.

A total of 456 patients with DR-TB were enrolled, with 56.1% males and 43.9% females. The mean age was 37.5 (±14.9) years. The incidence of DR-TB was 11.89 cases per 100,000 population, with males being disproportionately affected. Key risk factors included poverty, lack of education, and occupational exposure. The DR-TB types included RR-TB (60%), MDR-TB (30%), Pre-XDR-TB (5%), XDR-TB (3%), and INHR-TB (2%). Spatial analysis revealed significant clustering in socio-economically disadvantaged areas. A major cluster was identified, along with a distinct outlier. The analyses of DR-TB case trends using historical data (2018-2021) and projections (2022-2026) from Linear Regression and Random Forest models reveal historical data with a sharp decline in DR-TB case, from 186 in 2018 to 15 in 2021, highlighting substantial progress. The Linear Regression model predicts a continued decline to zero cases by 2026, with an R2 = 0.865, a mean squared error (MSE) of 507.175, and a mean absolute error (MAE) of 18.65. Conversely, the Random Forest model forecasts stabilization to around 30-50 cases annually after 2021, achieving an R2 = 0.882, an MSE of 443.226, and an MAE of 19.03. These models underscore the importance of adaptive strategies to sustain progress and avoid plateauing in DR-TB reduction efforts.

This study highlights the need for targeted interventions in vulnerable populations to curb DR-TB transmission and improve treatment outcomes.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis bacteria, which is more prevalent among immunocompromised individuals. According to the distribution of affected organs, this infection can be categorized as either pulmonary or extrapulmonary TB. Immunodeficiency states resulting from rheumatological disorders and the use of immunosuppressive medications, such as in Behçet's disease (BD), are potential predisposing factors for TB, particularly in cases involving multiple organs. These situations can introduce challenges in both the diagnosis and treatment of patients. We describe a 43-year-old man with a history of BD who presented with symptoms of weight loss, abdominal pain, and shortness of breath. His chest X-ray revealed cavities and calcifications, while an abdominal X-ray demonstrated signs of intestinal obstruction and adhesions. Subsequent TB diagnosis led to a 6-month course of a TB treatment regimen. Despite treatment initiation, the patient developed a brain abscess 1 year later, necessitating surgical intervention. Following the procedure, he received another 1-year course of a TB treatment regimen and experienced full recovery without any complications during a 2-year follow-up period. Notably, the patient recently received a Sinopharm COVID-19 vaccine and subsequently developed seizures that are currently being managed with anticonvulsant therapy. This case report emphasizes the significance of including pulmonary TB in complex medical cases, especially in individuals with autoimmune diseases. Early diagnosis and treatment are crucial for improving outcomes and reducing the risk of complications. Furthermore, it highlights the possible correlation between TB and BD, along with the potential adverse reactions to COVID-19 vaccines in this population, which necessitate special consideration by healthcare professionals.

To address the clinical diagnostic value of CRISPR-Cas13a-based molecular technology for tuberculosis (TB).

The 189 suspected TB patients were simultaneously sent for acid-fast staining smear of bronchoalveolar lavage fluid, MGIT 960 cultures, Xpert MTB/RIF assay, and CRISPR-Cas13a assay. Using the final clinical diagnosis as the gold standard, the TB and non-TB groups were determined, and the diagnostic values of the four assays and the combined test in TB were compared. Using MGIT 960 culture as the gold standard, the diagnostic value of CRISPR-Cas13a assay was explored in TB, and the concordance between the CRISPR-Cas13a assay and MGIT 960 culture was compared.

The 189 preliminary diagnosed patients with suspected TB were diagnosed, with 147 in the TB group and 42 in the non-TB group. Taking the final clinical diagnosis as the gold standard, the sensitivity, negative predictive value, and accuracy of CRISPR-Cas13a assay, MGIT 960 culture, and XpertMTB/RIF assay were higher than those of acid-fast staining smear; by comparing the area under the ROC curve, the diagnostic value of the CRISPR-Cas13a assay, MGIT 960 culture, and XpertMTB/RIF assay was superior to that of acid-fast staining smear (all P < 0.05). Using the MGIT 960 culture results as the gold standard, there was a moderate concordance between the CRISPR-Cas13a assay and the MGIT 960 culture (kappa = 0.666).

Bronchoalveolar lavage fluid CRISPR-Cas13a assay has high application value in the clinical diagnosis of TB and can be recommended for the initial screening of patients with suspected TB.

Aim: JBD0131, a novel anti-multidrug-resistant tuberculosis (MDR-TB) drug, can target and inhibit the synthesis of mycolic acids, which are crucial components of the cell wall of the Mycobacterium tuberculosis complex. To support the results of this clinical trial in healthy subjects, development of a specific and accurate quantification method for detecting JBD0131 and its metabolite DM131 in human plasma is needed.Materials & methods: Samples with prior added stabilizer were pretreated by protein precipitation method and the extracts were subjected to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The m/z transitions for the precursor/product ion pairs were 402.1/273 for JBD0131, 333.1/273 for DM131 and 386.1/257 for the internal standard (IS).Results: This method showed good linearity from 1 to 2000 ng/ml for JBD0131 and 0.25 to 500 ng/ml for DM131 and was validated in terms of selectivity, linearity, accuracy, precision, matrix effect, recovery of pretreament and stability.Conclusion: This method was sensitive and specific for measuring the plasma concentrations of JBD0131 and its metabolites. And it was applied for the investigation of the pharmacokinetics of JBD0131 and DM131 in a clinical trial.

Pulmonary infections have a profound influence on global mortality rates. Medicinal plants offer a promising approach to address this challenge, providing nontoxic alternatives with higher levels of public acceptance and compliance, particularly in regions where access to conventional medications or diagnostic resources may be limited. Understanding the pathophysiology of viruses and bacteria enables researchers to identify biomarkers essential for triggering diseases. This knowledge allows the discovery of biological molecules capable of either preventing or alleviating symptoms associated with these infections. In this review, medicinal plants that have an effect on COVID-19, influenza A, bacterial and viral pneumonia, and tuberculosis are discussed. Drug delivery has been briefly discussed as well. It examines the effect of bioactive constituents of these plants and synthesizes findings from in vitro, in vivo, and clinical studies conducted over the past decade. In conclusion, many medicinal plants can be used to treat pulmonary infections, but further in-depth studies are needed as most of the current studies are only at preliminary stages. Extensive investigation and clinical studies are warranted to fully elucidate their mechanisms of action and optimize their use in clinical practice.

This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in DPF3 and susceptibility to pulmonary tuberculosis (PTB) in the Northwest Chinese Han population.

Genotyping of four DPF3 SNPs (rs10140566, rs75575287, rs202075571, and rs61986330) was performed using Agena MassARRAY from 488 PTB patients and 488 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Multifactor dimensionality reduction (MDR) analysis was employed to investigate the effect of SNP-SNP interactions on PTB risk. The GSE54992 dataset was analyzed using R software to ascertain DPF3 expression levels.

Overall analysis revealed that rs202075571 (allele: OR = 1.31, p = 0.015; CC vs. TT: OR = 1.97, p = 0.049; dominant: OR = 1.33, p = 0.032) and rs61986330 (allele: OR = 1.38, p = 0.010; CA vs. CC: OR = 1.35, p = 0.044; dominant: OR = 1.40, p = 0.019) were associated with an increased PTB risk. Stratified analysis showed that rs10140566 was a PTB risk factor in females, those aged ≤40 and non-smokers, and rs202075571 was associated with PTB risk in individuals aged >40 and smokers, and rs61986330 was associated with PTB risk in males, those aged >40 and smokers. The four SNPs model demonstrated significant predictive potential for PTB risk. Furthermore, DPF3 exhibited higher expression in PTB compared to healthy controls.

DPF3 polymorphisms (rs10140566, rs202075571, and rs61986330) are associated with an increased risk of PTB, providing valuable new insights into the mechanism of PTB.

Tuberculosis (TB) remains a major global health threat. Despite ongoing efforts to control and eradicate TB, various factors including socioeconomic issues, policy modifications, and unexpected public health crises like COVID-19 pandemic have posed new obstacles to achieving TB elimination. This study aims to analyze the changes in global tuberculosis burden over the past 32 years, and provide scientific support for global initiatives targeting the eradication of TB in the post-pandemic period.

The data for this study were obtained from the Global Burden of Disease (GBD) 2021 database, with age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASDR), and disability-adjusted life years (DALYs) as the primary assessment indicators. Dynamic changes in the TB burden were analyzed by estimating the annual percentage changes (EAPCs). The attributable ratios of six main risk factors to TB burden were calculated, and the correlation between the Socio-Demographic Index (SDI) and the TB burden was analyzed using Pearson correlation tests.

The global TB incidence decreased from 8.6 million cases in 1990 to 8.4 million cases in 2021, with a corresponding decline in deaths. However, the TB burden remains higher among men than women. The highest incidence and mortality rates were observed in the age group of 15-69 years, with a notable gender disparity, especially in Eastern Europe. These rates were generally elevated in low-income and lower-middle-income regions, with significantly higher Age-Standardized Incidence Rates and Age-Standardized Death Rates in males compared to females. A significant negative correlation was found between SDI values and TB burden. Analyzing risk factors from the Global Burden of Disease study, it was determined that globally, dietary risks, high body-mass index, high fasting plasma glucose, low physical activity, tobacco, and alcohol use were the main contributors to TB age-standardized Disability-Adjusted Life Years, with tobacco and alcohol use having the most significant impact. Analysis of risk factors suggests that tailored public health interventions for specific genders and regions can effectively lessen the TB burden.

The study aimed to analyze the clinical effect of MRZE chemotherapy combined with cluster nursing intervention and treatment of pulmonary tuberculosis patients and its influence on CT signs. A total of 94 patients treated in our hospital from March 2020 to October 2021 were selected as the research object. Both groups were treated with MRZE chemotherapy regimen. Patients in the control group received routine nursing mode on this basis, and patients in the observation group received cluster nursing on the basis of the control group. The clinical efficacy, adverse reactions, compliance and nursing satisfaction, detection rate of immune function pulmonary oxygen index and pulmonary function CT signs and the level of inflammatory factors before and after nursing were compared between the two groups. The total effective rate of the observation group was significantly higher than that of the control group. The compliance rate and nursing satisfaction of the observation group were significantly higher than those of the control group. The differences of adverse reactions between the observation and control groups were statistically significant. After nursing, the scores of tuberculosis prevention and control of tuberculosis infection route, tuberculosis symptoms, tuberculosis policy and tuberculosis infection awareness in the observation group were significantly higher than those in the control group, and the differences were statistically significant. MRZE chemotherapy combined with cluster nursing intervention model for pulmonary tuberculosis patients can effectively improve the treatment compliance and nursing satisfaction of patients, and it is worthy of clinical promotion and application.

Recent publications have featured immunohistochemistry (IHC) as a sensitive tool for detecting Mycobacterium tuberculosis and nontuberculous mycobacteria, but performance is limited to cases suspected to have mycobacterial infection.

To examine cross-reactivity of a polyclonal antimycobacterial antibody with various types of pathogens, tissues, and inflammatory patterns.

Surgical pathology files during a period of 6 years were searched, and 40 cases representing a variety of pathogens, tissue types, and inflammatory responses were retrieved. Cases were stained with a rabbit polyclonal antimycobacterial antibody (Biocare Medical, Pacheco, California). The cases and associated histochemical stains, culture, and molecular results were reviewed by 3 pathologists.

All 8 cases of mycobacterial infection previously diagnosed by other methods were positive for mycobacteria by IHC. In addition, multiple bacterial and fungal organisms and 1 case of Leishmania amastigotes were also immunoreactive with the mycobacterial IHC.

Although highly sensitive for mycobacteria, the polyclonal antibody shows significant cross-reactivity with other organisms. This is a sensitive but nonspecific stain that can be used as an alternative confirmation method for mycobacteria, but attention should be paid to inflammatory reaction and organism morphology when IHC is positive to avoid misdiagnosis.

This case report presents a diagnostic challenge encountered in a 65-year-old male admitted with fever, dyspnea, chest pain, and hemoptysis, alongside constitutional symptoms including weight loss, night sweats, and fatigue. Despite initial suspicion for pulmonary thromboembolism and empirical antibiotic therapy for pneumonia, subsequent bronchoscopic evaluation revealed acute necrotizing granulomatous bronchitis, strongly indicative of endobronchial tuberculosis (TB). This diagnosis emphasizes the importance of considering TB in patients with chronic respiratory symptoms, particularly in high-risk populations. Management involves initiating multidrug antitubercular therapy, close monitoring, infection control measures, and patient education. Prompt diagnosis and appropriate management are crucial in optimizing outcomes and reducing disease burden in TB.

We aimed to determine the incidence of TB among immigrants and non-immigrants in Sanliurfa, Türkiye between 2018 and 2022 and to examine the effect of COVID-19 on the incidence, location, and drug resistance patterns of tuberculosis.

This study was a retrospective review of patients diagnosed with tuberculosis in Şanlıurfa Tuberculosis Dispensary between January-2018 and May-2022. Patients were assessed in terms of age, sex, site of tuberculosis, and drug resistance profiles before and during the COVID-19 pandemic.

A total of 887 patients with TB were included in the study. The mean age of patients diagnosed with tuberculosis was 40.63 ± 17.50 years. Of the total number of patients diagnosed, 50.7% were women, 85.8% were Turkish citizens, and 91.9% were new cases. Comparing the rate of positive cultures between the pre-COVID-19 and COVID-19 periods revealed a statistically significant rate of positive culture during the COVID-19 period (p < 0.001). In terms of mortality, the mean age of the patients who died was 60.2 ± 18.4 years and that of the survivors was 39.1 ± 16.6 years; these values were statistically significant (p < 0.001). Among the patients who survived, the rate of pulmonary tuberculosis was statistically significantly higher than that of extrapulmonary tuberculosis (p < 0.001).

The prevalence of pulmonary TB is high and the proportion of women is increasing. During the COVID-19 period, the number of patients diagnosed with TB decreased, but interestingly, the rate of positive cultures remained high, and the rate of resistance to INH also decreased. The results revealed rates similar to those reported by the World Health Organization.

Accurate identification of Mycobacterium tuberculosis (M. tuberculosis) is a critical step in the diagnosis of tuberculosis. Existing object detection methods struggle with the challenges posed by the varied morphology and size of M. tuberculosis in sputum smear images, which makes precise targeting difficult. To solve these problems, an improved YOLOv8s model is proposed. Specifically, an additional detection head is added to focus on small target information. Second, a multi-scale feature fusion module is introduced to adapt the model to different sizes of M. tuberculosis. In addition, a convolutional layer is added to the Coordinate Attention (CA) module to extract more advanced semantic features. Finally, a self-attention mechanism is added after the CA module to enhance the model's ability to accurately understand and localize the varied morphology of M. tuberculosis. Our model performed well with an average precision of 85.7 % when tested on a publicly available dataset. This clearly demonstrates the effectiveness of our proposed model in M. tuberculosis detection.

Tuberculosis (TB) remains an important public health concern in western China. This study aimed to explore and analyze the spatial and temporal distribution characteristics of TB reported incidence in 12 provinces and municipalities in western China and to construct the optimal models for prediction, which would provide a reference for the prevention and control of TB and the optimization of related health policies.

We collected monthly data on TB reported incidence in 12 provinces and municipalities in western China and used ArcGIS software to analyze the spatial and temporal distribution characteristics of TB reported incidence. We applied the seasonal index method for the seasonal analysis of TB reported incidence and then established the SARIMA and Holt-Winters models for TB reported incidence in 12 provinces and municipalities in western China.

The reported incidence of TB in 12 provinces and municipalities in western China showed apparent spatial clustering characteristics, and Moran's I was greater than 0 (p < 0.05) over 8 years during the reporting period. Among them, Tibet was the hotspot for TB incidence in 12 provinces and municipalities in western China. The reported incidence of TB in 12 provinces and municipalities in western China from 2004 to 2018 showed clear seasonal characteristics, with seasonal indices greater than 100% in both the first and second quarters. The optimal models constructed for TB reported incidence in 12 provinces and municipalities in western China all passed white noise test (p > 0.05).

As a hotspot of reported TB incidence, Tibet should continue to strengthen government leadership and policy support, explore TB intervention strategies and causes. The optimal prediction models we developed for reported TB incidence in 12 provinces and municipalities in western China were different.

Tuberculosis (TB) remains an impactful infectious disease, leading to millions of deaths every year. Mycobacterium tuberculosis causes the formation of granulomas, which will determine, through the host-pathogen relationship, if the infection will remain latent or evolve into active disease. Early TB diagnosis is life-saving, especially among immunocompromised individuals, and leads to proper treatment, preventing transmission. This review addresses different approaches to diagnosing TB, from traditional methods such as sputum smear microscopy to more advanced molecular techniques. Integrating these techniques, such as polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP), has significantly improved the sensitivity and specificity of M. tuberculosis identification. Additionally, exploring novel biomarkers and applying artificial intelligence in radiological imaging contribute to more accurate and rapid diagnosis. Furthermore, we discuss the challenges of existing diagnostic methods, including limitations in resource-limited settings and the emergence of drug-resistant strains. While the primary focus of this review is on TB diagnosis, we also briefly explore the challenges and strategies for diagnosing non-tuberculous mycobacteria (NTM). In conclusion, this review provides an overview of the current landscape of TB diagnostics, emphasizing the need for ongoing research and innovation. As the field evolves, it is crucial to ensure that these advancements are accessible and applicable in diverse healthcare settings to effectively combat tuberculosis worldwide.

To determine the usefulness of LINC00152 and LARS2-AS1 as potential biomarkers for latent tuberculosis (LTB) and active tuberculosis (ATB), as well as their effect on Mycobacterium (Mtb) infection.

The expression levels of LINC00152 and LARS2-AS1 in the health, patients with LTB and ATB were detected by qRT-PCR. The ROC curves were constructed to show their potential as biomarkers. The intracellular survival assays for Mtb and the levels of immune-related cytokines were determined to discover the effect of LINC00152 and LARS2-AS1 on Mtb infection. The relationships of miR-485-5p with LINC00152 and LARS2-AS1 were explored.

LINC00152 and LARS2-AS1 levels were significantly elevated in patients with ATB and LTB, and Mtb-infected macrophages. LINC00152 and LARS2-AS1 can distinguish the LTB from the health and ATB from LTB. LARS2-AS1 and LINC00152 knock-down reduced the intracellular Mtb survival and induced cellular immune response after Mtb challenge. miR-485-5p was a targeting miRNA for LINC00152 and LARS2-AS1.

LINC00152 and LARS2-AS1 can be considered as potential biomarkers for tuberculosis disease. LINC00152 and LARS2-AS1 have anti-Mtb effects.

To explore the diagnostic value of third-generation nanopore sequencing technology in patients with diabetes mellitus suspected of pulmonary tuberculosis.

Samples, including sputum and bronchoalveolar lavage fluid(BALF), were collected from patients with diabetes mellitus suspected of pulmonary tuberculosis who were admitted from October 2021 to August 2023. Nanopore sequencing, acid-fast bacilli (AFB) smear, mycobacterial solid culture, Xpert MTB/RIF, and DNA detection were performed, and their diagnostic efficacy was compared.

Third-generation nanopore sequencing technology exhibited high accuracy in diagnosing pulmonary tuberculosis in patients with diabetes mellitus. Compared to traditional methods, nanopore sequencing showed significantly improved sensitivity (76.80 %), negative predictive value (30.40 %), coincidence (77.92 %), and diagnostic accuracy (AUC = 0.822). Combined detection with Xpert achieved the highest diagnostic performance, with increased sensitivity (81.20 %), positive predictive value (98.20 %), negative predictive value (35.00 %), coincidence (81.82 %), and AUC (0.843). Although acid-fast staining had limitations, its combination with nanopore sequencing improved screening effectiveness.

Compared to established diagnostic modalities such as acid-fast staining, mycobacterial solid culture, Xpert MTB/RIF, and DNA detection, third-generation nanopore sequencing technology demonstrates a significant improvement in sensitivity for detecting suspected pulmonary tuberculosis in diabetic patients. Notably, the combined application of nanopore sequencing with Xpert testing offers a further enhancement in diagnostic accuracy.

Tuberculosis (TB) remains a critical global health challenge, with the emergence of drug-resistant strains heightening concerns. The development of effective drugs targeting both wild-type (WT) and mutant Escherichia coli RNA polymerase β subunit (RpoB) is crucial for global TB control, aiming to alleviate TB incidence, mortality, and transmission. This study employs molecular docking and ADMET analyses to screen echinoderm metabolites for their potential inhibition of Escherichia coli RNA polymerase, focusing on wild-type and mutant RpoB variants associated with TB drug resistance. The evaluation of docking results using the glide gscore led to the selection of the top 10 compounds for each protein receptor. Notably, CMNPD2176 demonstrated the highest binding affinity against wild-type RpoB, CMNPD13873 against RpoB D516V mutant, CMNPD2177 against RpoB H526Y mutant, and CMNPD11620 against RpoB S531L mutant. ADMET screening confirmed the therapeutic potential of these selected compounds. Additionally, MM-GBSA binding free energy calculations and molecular dynamics simulations provided further support for the docking investigations. While the results suggest these compounds could be viable for tuberculosis treatment, it is crucial to note that further in-vitro research is essential for the transition from prospective inhibitors to clinical drugs.

The principal motive of this work is to evolve and initiate an extension from interval-valued fuzzy sets to type-2 interval-valued fuzzy sets (T2IVFS) related to weighted aggregation functions containing the Einstein operator. The chief reason for this extension is that the constancy of the terms can also be taken into data during the aggregation operation. The main goal of this article is to compose the aggregation operators and their characteristics such as the Type-2 interval-valued fuzzy Einstein weighted arithmetic aggregating operator (T2IVFEWA), Type-2 interval-valued fuzzy Einstein weighted geometric aggregating operator (T2IVFEWG), and the characteristics are expressed. At last, to intimate the effectiveness of the suggested approach and explicate the purpose of these operators, a hybrid multi-criteria decision-making problem (MCDM) to select the best risk factor for Tuberculosis (TB) is considered and the result is compared with the outcome of the existing operators and methods. Additionally, a sensitivity analysis was conducted to verify the robustness of the proposed decision-making process.

Tuberculosis is a serious global health burden, resulting in millions of deaths each year. Several circulating cell subsets in the peripheral blood are known to modulate the host immune response to Mycobacterium tuberculosis (Mtb) infection in different ways. However, the characteristics and functions of these subsets to varying stages of tuberculosis infection have not been well elucidated. Peripheral blood immune cells (PBICs) were isolated from healthy donors (HD group), individuals with mild tuberculosis (MI group), and individuals with severe tuberculosis (SE group). CD4+ naive T cells and CD8+ T cells were decreased in the SE and MI groups, while CD14+ monocytes were increased in the SE group. Further analysis revealed increased activated CD4+ T cells, transitional CD8+ T cells, memory-like NK cells, and IGHG3highTTNhighFCRL5high B cells were increased in all patients with tuberculosis (SE and MI group). In contrast, Th17 cells, cytotoxic NK cells, and cytotoxic CD4+ T cells were decreased. Moreover, the increase of CD14+CD16+ monocytes correlated with severe tuberculosis, and the GBP5highRSAD2high neutrophils were unique to patients with severe tuberculosis. Cellular communication analysis revealed that CD8+ T cells exhibited the highest incoming interaction strength in the SE group. The increased CD8+ T cell incoming interactions are associated with the MHC-I and LCK pathways, with HLA-(A-E)-CD8A, HLA-(A-E)-CD8B, and LCK-(CD8A+CD8B) being ligand-receptor pairs. Patients with tuberculosis, especially severe tuberculosis, have profound changes in peripheral blood immune cell profiles. CD8+ T cells showed the highest incoming interaction strength in patients with severe tuberculosis, with the main signals being MHC-I and LCK pathways.