Tokyo Metropolitan University

Supersulfides, sulfur species containing catenated sulfur atoms, are potent reducing agents produced by diverse organisms. Although their intracellular functions are increasingly recognized, the ecological and physiological importance of gut microbial supersulfides remains poorly understood. In this study, we explored two complementary aspects of gut microbiota-derived supersulfide. First, by assessing the reducing activity, we found that bacterial supersulfides contribute to the enhancement of the extracellular reducing capacity. In particular, Dorea longicatena and Enterocloster bolteae exhibit strong cystine-dependent supersulfide production, which is associated with protection against oxidative stress. Second, beyond their ecological roles, supersulfides influence protein supersulfidation, which is a reversible post-translational modification. Supersulfidated proteins have been detected across multiple commensal taxa with species-specific profiles. This modification is redox-sensitive and modulated by extracellular supersulfides. Members of the Lactobacillaceae family are particularly susceptible to exogenous supersulfides. Supersulfidation involves proteins linked to core microbial processes, including bile acid metabolism, suggesting their potential role in tuning bacterial functions. Together, these findings suggest that microbial supersulfides act as dual regulators: (i) contributing to a protective reducing milieu and (ii) modulating bacterial protein function through supersulfidation. By highlighting post-translational control in gut bacteria and their sensitivity to the local redox environment, this work broadens the current models of microbial redox biology and provides a basis for linking bacterial sulfur metabolism with gut ecosystem stability and host-microbe interactions.

Solar UV comprises UVA and UVB; each exerts distinct biological effects, while their combined impact is not yet fully understood. We previously reported that human keratinocytes exposed to UVA1 followed by UVB irradiation exhibited severe cell death accompanied by DNA double-strand break (DSB) formation. In this study, we confirmed the DSB formation following sequential exposure to UVA1 and UVB and investigated the underlying mechanisms. The occurrence of DSBs was validated by biased sinusoidal field gel electrophoresis and the detection of phosphorylated histone H2AX and RPA. Notably, DSB induction was absent in xeroderma pigmentosum (XP) mutant cell lines, suggesting that nucleotide excision repair (NER) of UVB-induced pyrimidine dimers serves as a trigger for DSB formation. RPA, which binds to single-stranded DNA (ssDNA) gaps, and the replication factor PCNA rapidly accumulated at UV-damaged sites and persisted for an extended period in cells pre-irradiated with UVA1, indicating that NER-mediated ssDNA gaps were stabilized by UVA1 exposure. Furthermore, DSB formation was markedly suppressed by knockdown of the nucleases, EXO1 and MRE11. Inhibition of MRE11 endonuclease activity with PFM01 suppressed DSB formation after sequential exposure to UVA1 and UVB, whereas inhibition of its exonuclease activity with Mirin had no significant effect. These findings suggest that ssDNA gaps stabilized by UVA1 pre-irradiation are extended by EXO1, while MRE11 introduces a nick, ultimately leading to DSB formation.

In this nationwide retrospective study, we sought to evaluate the oncologic and functional outcomes and safety of transoral surgery (TOS) for hypopharyngeal and laryngeal squamous cell carcinomas in Japan and to clarify the appropriate indications for various TOS modalities. Data were obtained from the Head and Neck Cancer Registry of Japan. Patients who underwent transoral or endoscopic resection between 2011 and 2016 were selected. Detailed clinical information was collected from 55 institutions using web-based case report forms. Surgical modalities analyzed included endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), endoscopic laryngopharyngeal surgery (ELPS), transoral laser microsurgery (TLM), and transoral videolaryngoscopic surgery (TOVS). In total, 1825 patients were included (hypopharyngeal cancer, 62.5 %; laryngeal cancer, 37.5 %). Most cases (77.5 %) were T1 or lower, and 90.8 % were Stage II or earlier. TLM is predominantly used for glottic cancers, ELPS/ESD for superficial hypopharyngeal lesions, and TOVS for more advanced tumors, reflecting distinct indications for each modality. The 5-year disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) were 97.1 %, 84.3 %, and 85.4 %, respectively. The laryngeal preservation rate was 98.2 %. Tracheostomy was performed in 5.0 % of cases, mainly for airway protection; major complications, including pneumonia (2.4 %), hemorrhage (1.1 %), fistula formation (0.4 %), and vocal cord fixation (2.6 %), occurred in <3 % of patients. Postoperative functional outcomes were favorable, with persistent dysphagia (Functional Outcome Swallowing Scale stage ≥ 3) in 1.6 % and tube feeding dependence in 1.8 %. Non-robot-assisted TOS demonstrated excellent oncologic control and functional preservation of the larynx with low complication rates in early-stage hypopharyngeal and laryngeal cancers. Each surgical modality has distinct indications depending on the tumor site, depth of invasion, and institutional expertise. These findings support the use of TOS as a safe and effective treatment option for selected patients. Further procedural standardization and data accumulation are required to refine the indications and facilitate their broader adoption in clinical practice.

Accurate delineation of tumor extent is essential for curative endoscopic resection of esophageal squamous cell carcinomas (ESCCs). This study aimed to clarify the efficacy of the combined use of magnifying narrow-band imaging (NBI)/blue laser imaging (BLI) observation with Lugol chromoendoscopy (LCE) for evaluating the extent of ESCCs during endoscopic resection. This prospective, single-center study enrolled patients with ESCCs scheduled for endoscopic resection (ER). Tumor margins were initially assessed using NBI/BLI with magnification, followed by LCE. ER was performed based on the combined diagnosis. The primary outcome was the proportion of lesions demonstrating a positive effect, defined as a decrease in either overestimation or underestimation of tumor extent when using the combined diagnostic strategy compared to LCE alone. A total of 62 patients with 82 ESCCs underwent endoscopic treatment. After excluding two lesions due to inadequate pathological evaluation, 80 lesions in 60 patients were analyzed. R0 resection was achieved in 96.3% (77/80). A positive effect was observed in 8.8% (7/80; 95% confidence interval [CI] 3.6-17.2%), all associated with multiple Lugol-voiding lesions (LVLs), in which overestimation by LCE was mitigated using the combined diagnostic strategy. Among lesions with multiple LVLs, the positive effect rate was 18.9% (7/37; 95% CI 8.0-35.2%). Overestimation by magnifying NBI/BLI occurred in one lesion, while LCE-added areas contained SCC in 3 lesions and intraepithelial neoplasia in two lesions. Combined use of magnifying NBI/BLI and LCE is a simple and effective strategy during ER for ESCCs, particularly in cases with multiple LVLs.

In this study, the effects of compressive residual stress and work hardening introduced by multifunction cavitation (MFC) treatment on the ductile–brittle transition for carburized steel were investigated. Prior to Charpy impact tests, variations in surface properties with processing time were evaluated. Both surface hardness and compressive residual stress increased rapidly and reached saturation at approximately 10 min, which was determined as the optimal treatment condition. Depth profile analysis under this condition revealed that the hardness and compressive stress increased to a depth of approximately 75 µm from the surface. The Charpy impact test results showed that the absorbed energy and lateral expansion of the MFC-treated specimens were substantially higher than those of the untreated ones in the intermediate temperature range (473–573 K). A strong linear correlation (Δ h = kE ) was observed between the absorbed energy ( E ) and the lateral expansion (Δ h ), and the proportional coefficient k increased from 1.438 × 10 −2 cm/J for untreated steel to 1.544 × 10 −2 cm/J after the MFC treatment. These results indicate that the compressive residual stress induced by MFC treatment relaxes the stress concentration at crack tips and enhances plastic deformation. Consequently, MFC treatment was found to be an effective surface modification method for reducing the ductile–brittle transition temperature of carburized steel. • MFC treatment formed a strengthened surface layer extending to ∼75 µm in depth. • Hardness and compressive residual stress increased within the MFC-affected layer. • Brittle fracture dominated at 183–303 K, with ductile transition at 473–573 K. • At 623–773 K, MFC-treated specimens showed higher absorbed energy. • A linear Δh–E relationship confirmed enhanced plastic deformation by MFC.

Infections are a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although humoral immunity is essential, the phase-specific role of IgG remains unclear. We analyzed 579 allo-HCT recipients, stratified into early, intermediate, and late post-transplant phases. The incidence of bacterial infections during the intermediate phase decreased with increasing IgG trough levels (incidence rate ratio [IRR], 0.85; 95% confidence interval [CI]: 0.78-0.94, p < 0.01), whereas no association was observed in the early or late phases. During the intermediate phase, multivariable analyses demonstrated that hypogammaglobulinemia (IRR, 1.70; 95% CI: 1.11-2.62, p = 0.02) and acute graft-versus-host disease with grade II-IV (IRR, 2.10; 95% CI: 1.39-3.18, p < 0.01) were associated with bacterial infections. In models including high-dose steroid exposure, steroid therapy was independently associated with bacterial infections, whereas the effect of hypogammaglobulinemia was attenuated. There was a trend toward an interaction between hypogammaglobulinemia and high-dose steroid exposure. A stratified analysis suggested that hypogammaglobulinemia had a more pronounced impact among patients without high-dose steroids (IRR 1.86; 95% CI: 1.09-3.16; p = 0.02). These findings suggest the clinical relevance of hypogammaglobulinemia is phase-specific and influenced by the intensity of immunosuppressive therapy. Monitoring IgG during this period may help identify candidates for targeted immunoglobulin replacement therapy.