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Cell division is critical for the survival, growth, pathogenesis, and antibiotic susceptibility of Mycobacterium tuberculosis (Mtb). However, the regulatory networks governing the transcription of genes involved in cell growth and division in Mtb remain poorly understood. This study aimed to investigate the impact of BlaI overexpression on cell division and growth in Mtb and elucidate the underlying mechanisms. Mycobacterium smegmatis mc2155 was used as the model organism. Recombinant strains overexpressing BlaI were constructed. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), ethidium bromide and Nile red uptake assays, minimum inhibitory concentration (MIC) determination, drug resistance analysis, quantitative real-time PCR (qRT-PCR) assays, and electrophoretic mobility shift assay (EMSA) were employed to assess changes in bacterial morphology, cell wall permeability, antibiotic susceptibility, gene transcription levels, and the interaction between BlaI and its target genes. Overexpression of BlaI disrupted bacterial division in M. smegmatis, leading to growth delay, cell elongation, and formation of multi-septa. It also altered the lipid permeability of the cell wall and enhanced the sensitivity of M. smegmatis to β-lactam antibiotics. BlaI overexpression affected the transcription of cell division-related genes, particularly downregulating ftsQ. Additionally, BlaI negatively regulated the transcription of Rv1303—a gene co-transcribed with ATP synthase-encoding genes—inhibiting ATP synthesis. This impaired the phosphorylation of division complex proteins, ultimately affecting cell division and cell wall synthesis. Overexpression of BlaI in Mtb interferes with bacterial division, slows growth, and alters gene expression. Our findings identify a novel role for BlaI in regulating mycobacterial cell division and β-lactam susceptibility, providing a foundation for future mechanistic studies in M. tuberculosis, with validation required to assess relevance to clinical tuberculosis—though validation in M. tuberculosis and preclinical models is required.

Tuberculosis caused by Mycobacterium tuberculosis remains a major global health concern; M. tuberculosis drug resistance and persistence further fueled the situation. Nutrient supportive therapy was intensively pursued to complement the conventional treatment, as well as their synergy with current antibiotics. To explore whether l-alanine can synergize with fluoroquinolones against M. tuberculosis, M. smegmatis was used as a surrogate in this study. We found that l-alanine can boost the bactericidal efficacy of fluoroquinolones, increasing the production of intracellular reactive oxygen species. This effect is very significant for persisters. Accelerated tricarboxylic acid cycle and/or nucleotide metabolism were observed after the addition of l-alanine. M. smegmatis MSMEG2660 is a homolog of the alanine dehydrogenase (Rv2780, MSMEG2659) negative regulator Rv2779c and involved in the l-alanine potentiation of fluoroquinolone via funneling more alanine into tricarboxylic acid. Deletion mutant of the MSMEG2660 (∆Ms2660) became more susceptible, and more readily revived from persistence. We firstly found that l-alanine can synergize with fluoroquinolones against Mycobacterium, especially the persisters via promoting metabolism. This will inspire new avenue to eliminate Mycobacterium persisters.

IntroductionYolk sac tumor (YST) is a rare malignant germ cell tumor, which usually affects young males. Because of the low incidence, few studies on YST have been published. In our study, we aim to investigate the clinical characteristics, survival and risk factors of male YST patients based on the Surveillance, Epidemiology, and End Results (SEER) program.MethodsWe identified 569 male YST patients from the SEER-18 database with additional treatment fields. Clinical characteristics, survival and prognostic factors were described in the study. Chi-square tests were applied to analyze categorical and continuous variables between different groups. Univariate and multivariate Cox proportional hazard model were performed to assess the relative impacts of risk factors on cancer-specific survival (CSS) in YST patients. Kaplan–Meier method and the log-rank test were used to analyze differences in survival that were significant.ResultsThe major primary sites of YST were testis (74.69%), mediastinum (15.47%), retroperitoneum (2.64%) and central nervous system (1.24%). The 3-year and 5-year CSS was 70.0%, 56.5% vs. 97.2%, 96.0% for the mediastinal and testicular YST patients, respectively (p < 0.001). Primary site of mediastinum, distant SEER Summary stage were independent factors of poor prognosis (hazard ratio (HR) = 2.010 (1.094–3.695), p = 0.025; HR = 6.501 (2.294–18.424), p < 0.001, respectively). Receiving surgery was a good prognosis factor for all patients (HR = 0.495 (0.260–0.940), p = 0.032) and for the mediastinal group (p = 0.0019). Being treated with chemotherapy indicated poor outcome in all patients (HR = 3.624 (1.050–12.507), p = 0.042) and in the localized testicular YST patients (p = 0.0077).ConclusionFor the first time, our study revealed the primary site distribution of male YST, and summarized the clinical characteristics, survival and prognostic factors based on the SEER database, which provided important epidemiological evidence for clinical practice.

Purpose: Phage is a new choice for the treatment of multi-drug-resistant bacteria, and phage resistance is also an issue of concern. SWU1 is a mycobacteriophage, and the mechanism of its resistance remain poorly understood. Methods: The mutant strains which were stably resistant to SWU1 were screened by transposon mutation library. The stage of phage resistance was observed by transmission electron microscope (TEM). The insertion site of transposon was identified by thermal asymmetric interlaced PCR (TAIL-PCR). The possible relationship between insertion site and phage resistance was verified by gene knockout technique. The fatty acid composition of bacterial cell wall was analyzed by Gas Chromatography-Mass Spectrometer (GCMS). Through the amplification and sequencing of target genes and gene complement techniques to find the mechanism of SWU1 resistance. Results: The transposon mutant M12 which was stably resistant to mycobacteriophage SWU1 was successfully screened. It was confirmed that resistance occurred in the adsorption stage of bacteriophage. It was verified that the insertion site of the transposon was located in the MSMEG 3705 gene, but after knocking out the gene in the wild type M. smegmatis [mc.sup.22] 155, the resistance of the knockout strain to SWU1 was not observed. Through the amplification and sequencing of the target gene MSMEG0392, it was found that there was an adenine insertion mutation at position 817. After complementing MSMEG0392 in M12, it was found that M12 returned to sensitivity to SWU1. Conclusion: We confirmed that the resistance of M12 to SWU1 was related to the functional inactivation of MSMEG0392 and this phenomenon may be caused by the change of cell wall of M. smegmatis. Keywords: phage resistance M. smegmatis, mycobacteriophage, SWU1, insertion mutation

Purpose: Phage is a new choice for the treatment of multi-drug-resistant bacteria, and phage resistance is also an issue of concern. SWU1 is a mycobacteriophage, and the mechanism of its resistance remain poorly understood. Methods: The mutant strains which were stably resistant to SWU1 were screened by transposon mutation library. The stage of phage resistance was observed by transmission electron microscope (TEM). The insertion site of transposon was identified by thermal asymmetric interlaced PCR (TAIL-PCR). The possible relationship between insertion site and phage resistance was verified by gene knockout technique. The fatty acid composition of bacterial cell wall was analyzed by Gas Chromatography-Mass Spectrometer (GCMS). Through the amplification and sequencing of target genes and gene complement techniques to find the mechanism of SWU1 resistance. Results: The transposon mutant M12 which was stably resistant to mycobacteriophage SWU1 was successfully screened. It was confirmed that resistance occurred in the adsorption stage of bacteriophage. It was verified that the insertion site of the transposon was located in the MSMEG 3705 gene, but after knocking out the gene in the wild type M. smegmatis [mc.sup.22] 155, the resistance of the knockout strain to SWU1 was not observed. Through the amplification and sequencing of the target gene MSMEG0392, it was found that there was an adenine insertion mutation at position 817. After complementing MSMEG0392 in M12, it was found that M12 returned to sensitivity to SWU1. Conclusion: We confirmed that the resistance of M12 to SWU1 was related to the functional inactivation of MSMEG0392 and this phenomenon may be caused by the change of cell wall of M. smegmatis. Keywords: phage resistance M. smegmatis, mycobacteriophage, SWU1, insertion mutation

Kr atoms were produced in their metastable states 4p55s [3/2]2 and 4p55s’ [1/2]0 in a pulsed DC dis-charge in a beam,and subsequently excited to the even-parity autoionizing Rydberg states 4p5np’ [3/2]1,2,[1/2]1 and 4p5nf’ [5/2]3 using single photon excitation.The excitation spectra of the even-parity autoionizing resonance series from the metastable Kr were obtained by recording the autoionized Kr+ ions with time-of-flight ion detection in the photon energy range of 29000-40000 cm1.A wealth of autoionizing resonances were newly observed,from which more precise and more systematic spec-troscopic data of the level energy and quantum defects were derived.

Phage is a new choice for the treatment of multi-drug-resistant bacteria, and phage resistance is also an issue of concern. SWU1 is a mycobacteriophage, and the mechanism of its resistance remain poorly understood. The mutant strains which were stably resistant to SWU1 were screened by transposon mutation library. The stage of phage resistance was observed by transmission electron microscope (TEM). The insertion site of transposon was identified by thermal asymmetric interlaced PCR (TAIL-PCR). The possible relationship between insertion site and phage resistance was verified by gene knockout technique. The fatty acid composition of bacterial cell wall was analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). Through the amplification and sequencing of target genes and gene complement techniques to find the mechanism of SWU1 resistance. The transposon mutant M12 which was stably resistant to mycobacteriophage SWU1 was successfully screened. It was confirmed that resistance occurred in the adsorption stage of bacteriophage. It was verified that the insertion site of the transposon was located in the gene, but after knocking out the gene in the wild type mc2 155, the resistance of the knockout strain to SWU1 was not observed. Through the amplification and sequencing of the target gene , it was found that there was an adenine insertion mutation at position 817. After complementing in M12, it was found that M12 returned to sensitivity to SWU1. We confirmed that the resistance of M12 to SWU1 was related to the functional inactivation of and this phenomenon may be caused by the change of cell wall of .

biofilm is associated with the virulence and persistence capability. Our aim is to delineate factors involved in biofilms development. We performed transposon mutants screen and found that mutation of MSMEG_3641, a homolog of Rv1836c, can change colony morphology and biofilm. MSMEG_3641 contains a vWA domain that is highly conserved among . The phenotypes of MSMEG_3641 mutants include disrupted biofilm, weakened migration ability and changed colony morphology. All phenotypes might be contributed to the enhanced cell wall permeability and declined cell aggregation ability. To our knowledge, this is the first report concerning the mycobacteria Von Willebrand factor domain function, especially in colony morphology and biofilm development.

Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1–3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the JamesWebb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.