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Background: The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB. Methods: A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment. Results: Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures. Conclusion: Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective. Plain Language Summary: This study explored a new way to treat a hard-to-treat type of tuberculosis (TB) using a medicine called Sulfasalazine, alongside usual TB treatments. Over 9 months, two groups of patients were given different sets of medicines, one including Sulfasalazine. The results, checked 12 months after treatment, showed that most patients improved, especially those given Sulfasalazine. No one in the Sulfasalazine group died or had their treatment fail, suggesting that Sulfasalazine could be a promising addition to current treatments for this tough-to-treat TB. [ABSTRACT FROM AUTHOR]

Herein, we designed and prepared the persistent luminescence nanoparticles (PLNPs) of γ-Ga2O3:Cr,Ba rationally with Cr ions to achieve the near-infrared (NIR) emission at 700 nm and Ba ions to improve the emission intensity by inducing trap distribution. Energy transfer between γ-Ga2O3 and Cr ions occurs as the emission at 508 nm decreases and that at 700 nm increases along with the increased content of Cr ions. In combination with the trap depth, band gap of the host, and energy levels of Cr ions, an emission mechanism was proposed. Thus, NIR emission (700 nm), high brightness, large Stokes shift (446 nm), and long afterglow time (90 min) were achieved with the optimal γ-Ga2O3:0.0025Cr,0.0012Ba (γGCB) under excitation at 254 nm. The emission intensity of γGCB is temperature-dependent for non-contact ratiometric temperature sensing, and temperature linearity ranging from 300 to 420 K was achieved with an absolute sensitivity of 3.4% K−1. γGCB and γ-G2O3 are white under sunlight but exhibit red and green emissions under single excitation at 254 nm. Thus, Morse and binary codes are adapted to achieve encryption information transfer with the combination of γGCB and γ-G2O3. This work provides ideas for selecting a host, emission center, and trap for PLNPs with desirable properties and thus achieves extensive applications, as validated with ratiometric temperature sensing and encryption information transfer. [ABSTRACT FROM AUTHOR]

The nasopharynx is the initial site of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, and neutrophils play a critical role in preventing viral transmission into the lower airways or lungs during the early phases of infection. However, neutrophil dynamics, functional signatures, and predictive roles in the nasopharynx of coronavirus disease 2019 (COVID‐19) patients have not yet been elucidated. In this study, we carried out RNA sequencing of nasopharyngeal swabs from a cohort of COVID‐19 patients with mild, moderate, severe outcomes and healthy donors as controls. Over 32.7% of the differentially expressed genes associated with COVID‐19 severity were neutrophil‐related, including those involved in migration, neutrophil extracellular traps formation, and inflammasome activation. Multicohort single‐cell RNA sequencing analysis further confirmed these findings and identified a population of neutrophils expressing Vacuolar‐type ATPase (V‐ATPase) and the chemokine receptor CXCR4 in the nasopharynx. This population of neutrophils preferentially expressed pro‐inflammatory genes relevant to phagosomal maturation as well as local reactive oxygen species and reactive nitrogen species production in the nasopharynx of patients with severe outcomes. A four‐gene panel defined as a neutrophil signature associated with COVID‐19 progression (NSAP) was identified as an early diagnostic predictor of severe COVID‐19, which potentially distinguished severe patients from mild cases with influenza, respiratory syncytial virus, dengue virus, or hepatitis B virus infection. NSAP is mainly expressed on CXCR4high neutrophils and exhibits a significant association with the cell fraction of this neutrophil population. This study highlights novel potential therapeutic targets or diagnostic tools for predicting patients at a higher risk of severe outcomes. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a persistent infectious disease threatening human health. The existing diagnostic methods still have significant shortcomings, including a low positivity rate in pathogen-based diagnoses and the inability of immunological diagnostics to detect active TB. Hence, it is urgent to develop new techniques to detect TB more accurate and earlier. This research aims to scrutinize and authenticate DNA methylation markers suitable for tuberculosis diagnosis. Concurrently, Providing a new approach for tuberculosis diagnosis., Methods: Blood samples from patients with newly diagnosed tuberculosis and healthy controls (HC) were utilized in this study. Examining methylation microarray data from 40 whole blood samples (22TB + 18HC), we employed two procedures: signature gene methylated position analysis and signature region methylated position analysis to pinpoint distinctive methylated positions. Based on the screening results, diagnostic classifiers are constructed through machine learning, and validation was conducted through pyrosequencing in a separate queue (22TB + 18HC). Culminating in the development of a new tuberculosis diagnostic method via quantitative real-time methylation specific PCR (qMSP)., Results: The combination of the two procedures revealed a total of 10 methylated positions, all of which were located in the promoter region. These 10 signature methylated positions facilitated the construction of a diagnostic classifier, exhibiting robust diagnostic accuracy in both cross-validation and external test sets. The LDA model demonstrated the best classification performance, achieving an AUC of 0.83, specificity of 0.8, and sensitivity of 0.86 on the external test set. Furthermore, the validation of signature methylated positions through pyrosequencing demonstrated high agreement with screening outcomes. Additionally, qMSP detection of 2 potential hypomethylated positions (cg04552852 and cg12464638) exhibited promising results, yielding an AUC of 0.794, specificity of 0.720, and sensitivity of 0.816., Conclusion: Our study demonstrates that the validated signature methylated positions through pyrosequencing emerge as plausible biomarkers for tuberculosis diagnosis. The specific methylation markers in the TSPAN4 gene, identified in whole blood samples, hold promise for improving tuberculosis diagnosis. This approach could significantly enhance diagnostic accuracy and speed, offering a new avenue for early detection and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Chen, Zhang, Chen, Mo, Yang, Zhang and Liu.)