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This study aims to clarify the effect of occupational stress and changes in the work environment on non-healthcare workers’ (HCWs) mental health during the third wave of the COVID-19 pandemic in Japan. A web-based, cross-sectional survey was conducted from 16 to 17 December 2020. Data from 807 non-HCWs were included. We evaluated occupational stress using the Generic Job Stress Questionnaire (GJSQ). Depressive and anxiety symptoms were assessed using the Japanese version of the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder 7-item scale, respectively. We collected demographic variables, work-related variables, and the variables associated with COVID-19. The adjusted odds ratios for depressive and anxiety groups were estimated using multivariate logistic regression analyses, adjusted for all the demographic variables, work-related variables, COVID-19-related variables, and the six subdivided GJSQ subscales. The results confirm a relationship between variance in workload, job future ambiguity, social support from coworkers, having contact with COVID-19 patients, and depressive and anxiety symptoms. Paying attention to job future ambiguity, the variance in workload at the workplace and individual perspectives, promoting contact and support among coworkers using online communication tools, and reducing contact with COVID-19 patients, will be useful for decreasing the depressive and anxiety symptoms among non-HCWs.

Most teachers have a high risk of work-related stress and mental disorders. Drunken driving and hazardous alcohol consumption (HAC) among teachers are social problems. Gender differences among teachers in burnout, occupational stress, self-efficacy and job satisfaction were reported. This study aimed to clarify gender differences in the relationships between perceived individual-level occupational stress and HAC among Japanese teachers. A cross-sectional study was conducted in 2013 and a total of 723 male and 476 female teachers remained after excluding non-drinkers. Perceived individual-level occupational stress was assessed using the Generic Job Stress Questionnaire. HAC was defined as ethanol consumption greater than or equal to 280 g in 1 week for male teachers, and greater than or equal to 210 g for female teachers. Multiple logistic regression analyses were conducted. HAC was identified in 16.6% of male and 12.4% of female teachers. The average ages (± standard deviation: SD) of male and female teachers were 46.9 ± 10.9 years and 39.9 ± 12.3 years, respectively. Schoolteacher was the most common position classification among male (48.7%) and female teachers (86.3%). For those with a moderate level of stress, \"social support from supervisors\" was associated with HAC among males (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.23-0.8), whereas for female teachers with a high level of stress, \"variance in workload\" was associated with HAC (OR = 2.09, 95% CI = 1.04-4.24), using an adjusted model. This study showed that moderate social support from supervisors was negatively related to HAC among male teachers, and high variance in workload was positively related to HAC among female teachers. Gender differences need to be considered when developing HAC prevention strategies for teachers.

The severity of major depressive disorder (MDD), which is related to the depressive symptoms, is a predictor of clinical outcomes and may be used to determine the appropriate treatment. However, there is a lack of systematic research on the relationship between early depressive symptoms and MDD severity. This study aimed to clarify the association between initial depressive symptoms and MDD severity in working patients. We assessed 118 patients aged over 20 years who visited the Neuropsychiatry Department of the Osaka City University Hospital following their first episode of MDD. Logistic regression analyses were performed to estimate the odds ratios (OR) with 95% confidence intervals (CI) for the associations between age, gender, marital status, working hours, and initial self-perceived depressive symptoms and MDD severity. Age and working hours were analyzed as continuous variables, and gender (man, woman), marital status (married, single) and severity (mild to moderate MDD, severe to very severe MDD) were analyzed as categorical variables. The most common initial self-perceived symptom was “depressed mood,” followed by “fatigue or loss of energy nearly every day.” The univariate analysis found no association between age, gender, marital status, or working hours and MDD severity. Initial self-perceived non-somatic symptoms were associated with increased odds of having severe MDD (odds ratio = 3.32, 95% confidence interval 1.46–7.58), and this association persisted in the adjusted model (odds ratio = 3.35, 95% confidence interval 1.47–7.60). Initial self-perceived non-somatic depressive symptoms are significantly associated with MDD severity at its first onset. Workplace support may lead to the early detection and treatment of working patients with non-somatic symptoms.

Background. Stigma related to mental illness can be an obstacle affecting the quality of life of people with mental illness. Although mental illness in the workplace is a public problem globally, few studies have investigated the effect of stigma on job-related problems such as burnout. Aim. This study aimed to clarify the association between mental-illness-related stigma and burnout among nonprofessional occupational mental health staff. Methods. In this cross-sectional study, nonprofessional occupational mental health staff’s perceived mental-illness-related stigma was assessed using Link’s Devaluation-Discrimination Scale, and their burnout was assessed using the Maslach Burnout Inventory. The association between stigma and burnout was analyzed by multiple linear regression analysis. Results. In total, 282 participants completed the questionnaire (response rate: 91.3%). We excluded 54 nurses from the analysis to examine strictly nonprofessional occupational mental health staff. Finally, 228 eligible respondents were surveyed. Multiple linear regression analysis revealed that mental-illness-related stigma was significantly associated with a high degree of depersonalization, which was one of the burnout dimensions. However, the impact of stigma over the depersonalization domain of burnout was minor. Conclusion. The results suggest that higher perceived mental-illness-related stigma is associated with more severe burnout. It is important to take measures against mental-illness-related stigma to avoid burnout among occupational mental health staff.

The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9 −/− and Gal-9 wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9 −/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9 wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9 −/− mice receiving Gal-9 −/− or Gal-9 wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9 wt/wt mice receiving Gal-9 −/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H 2 O 2 . The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.

Molecularly targeted cancer therapy has improved outcomes for cancer patients with targetable oncoproteins, such as mutant epidermal growth factor receptor (EGFR) in lung cancer. Yet, long-term patient survival remains limited because treatment responses are typically incomplete. One potential explanation for the lack of complete and durable responses is that oncogene-driven cancers with activating mutations in the EGFR often harbor additional co-occurring genetic alterations. This hypothesis remains untested for most genetic alterations that co-occur with mutant EGFR. Here, we report the functional impact of inactivating genetic alteration of the mRNA splicing factor RBM10 that co-occur with mutant EGFR. RBM10 deficiency decreased EGFR inhibitor efficacy in patient-derived EGFR mutant tumor models. RBM10 modulated mRNA alternative splicing of the mitochondrial apoptotic regulator Bcl-x to regulate tumor cell apoptosis during treatment. Genetic inactivation of RBM10 diminished EGFR inhibitor-mediated apoptosis by decreasing the ratio of Bcl-xS-(pro-apoptotic)-to-Bcl-xL(anti-apoptotic) Bcl-x isoforms. RBM10 deficiency was a biomarker of poor response to EGFR inhibitor treatment in clinical samples. Co-inhibition of Bcl-xL and mutant EGFR overcame resistance induced by RBM10 deficiency. This study sheds light on the role of co-occurring genetic alterations, and on the impact of splicing factor deficiency in the modulation of sensitivity to targeted kinase inhibitor cancer therapy.

Background Tertiary lymphoid structures (TLSs) maturity and cellular composition shape resistance or sensitivity to immune-checkpoint blockade (ICB) across cancers. Single-cell spatial resolution data for the endothelial compartment of TLSs are lacking; therefore, we investigated the cellular composition, endothelial dynamics, and cell-cell interactions within TLS regions. Methods We applied high-resolution Xenium In Situ spatial transcriptomics to eight samples collected from non-small-cell lung cancers (NSCLC) (four after chemoimmunotherapy, four untreated), extracted 90 TLS regions, generated approximately 320,000 single-cell profiles from those regions, and analyzed the endothelial compartment within each TLS. We independently assessed the exploratory findings using multiplex immunofluorescence and survival analysis in a separate cohort of 45 patients receiving immunotherapy. Results Spatial mapping revealed a reproducible, B-cell-dominant TLS architecture across all samples. Mature TLSs contained CXCL13-rich follicular cores and were associated with a favorable prognosis. Within the endothelial compartment, high endothelial cells (HECs) forming high-endothelial venules (HEVs) segregated from other endothelial cells; in mature TLSs these HECs exhibited high inhibitor of DNA binding 1 ( ID1 ) expression and an adhesion molecular signature, promoting lymphocyte recruitment. Patients with tumors harboring ID1-high HEVs showed higher response rates and pronounced survival advantage; multivariable analysis confirmed ID1-high status as an independent prognostic factor. Conversely, ICB exposure eventually reduced ID1 expression and adhesion molecule levels in HECs, impaired lymphocyte trafficking, and promoted a shift toward a remodeled endothelial state. Conclusions ID1expression, linked to HEC differentiation during TLS maturation or ICB exposure, marks a functionally mature, lymphocyte-recruiting HEV that predict durable response to immunotherapy. These findings provide a novel mechanistic framework and practical biomarkers for HEV-centered immuno-oncology strategies in NSCLC.

Oral streptococci are primary colonizers of tooth surfaces and Streptococcus mutans is the principal causative agent of dental caries in humans. A number of proteins are involved in the formation of monospecies biofilms by S. mutans. This study analyzed the protein expression profiles of S. mutans biofilms formed in the presence or absence of S. gordonii, a pioneer colonizer of the tooth surface, by two-dimensional gel electrophoresis (2-DE). After identifying S. mutans proteins by Mass spectrometric analysis, their expression in the presence of S. gordonii was analyzed. S. mutans was inoculated with or without S. gordonii DL1. The two species were compartmentalized using 0.2-μl Anopore membranes. The biofilms on polystyrene plates were harvested, and the solubilized proteins were separated by 2-DE. When S. mutans biofilms were formed in the presence of S. gordonii, the peroxide resistance protein Dpr of the former showed 4.3-fold increased expression compared to biofilms that developed in the absence of the pioneer colonizer. In addition, we performed a competition assay using S. mutans antioxidant protein mutants together with S. gordonii and other initial colonizers. Growth of the dpr-knockout S. mutans mutant was significantly inhibited by S. gordonii, as well as by S. sanguinis. Furthermore, a cell viability assay revealed that the viability of the dpr-defective mutant was significantly attenuated compared to the wild-type strain when co-cultured with S. gordonii. Therefore, these results suggest that Dpr might be one of the essential proteins for S. mutans survival on teeth in the presence of early colonizing oral streptococci.