Additional file 1 of Identification of a new gene signature for prognostic evaluation in cervical cancer: based on cuproptosis-associated angiogenesis and multi-omics analysis

Supplementary Material 1: Figure S1: Forest plot of 66 CuRA prognostic genes by univariate COX analysis. Figure S2: Comparison of errors in ridge regression, lasso regression and elastic network regression and comprehensive comparison of the errors in three regression algorithms. Figure S3: Construction and verification of a CuRA prognostic model. Figure S4: Localization and validation of 10 modeling genes in the GSE168652 dataset. Figure S5: Immune infiltration landscape in high and low CuRA-groups calculated by CIBERSORT, EPIC, MCP, Quanti-seq, TIMER, xCell algorithms. Figure S6: Differences in mutation frequency between high and low CuRA groups. Figure S7: Survival analysis of 10 modeling genes. Figure S8: Assessment of regulatory pathways and immune microenvironment of SFT2D1. Figure S9: Visual circular and hierarchical plots showing cellular communication in the VEGF pathway. Figure S10: Cell Communication Analysi

Data_Sheet_1_Mental burden among Chinese undergraduate medical students: A prospective longitudinal study before, during, and after the COVID-19 outbreak.docx

BackgroundIncreasing evidence indicated a clear association between COVID-19 pandemic and mental health. This study aimed to assess the dynamic change of mental burden during and after the COVID-19 outbreak and related predictive factors among Chinese undergraduate medical students.MethodsThis longitudinal survey was conducted among Chinese undergraduate medical students before, during, and after the COVID-19 outbreak. We focused on COVID-19 related mental burdens including psychological distress, stress reaction, and insomnia symptoms, and defined the sum score of the three specific mental burden indexes as the overall mental burden index. The prevalence of specific and overall mental burdens and their changing patterns at two phases of the pandemic (during vs. after the COVID-19 outbreak) were measured. In addition, multinomial logistic regressions were used to assess the associations between the psychosocial status before the pandemic and specific and overall mental burden changing patterns.ResultsOur findings showed that the prevalence of overall mental burden increased (from 27.46 to 37.28%) after the COVID-19 outbreak among the 863 Chinese undergraduate medical students who participated in the surveys at baseline, during, and after the COVID-19 outbreak. Specifically, the prevalence of stress reaction symptoms decreased (from 10.90 to 3.60%), while the rates of psychological distress (from 28.06 to 37.95%) and insomnia symptoms (from 12.54 to 20.71%) increased. Participants, with obsessive-compulsive symptoms, somatic symptoms, internet addiction, childhood adversity, stressful life events, and being neurotic were found to have a higher risk of developing mental burden in at least one survey (during or after the COVID-19 outbreak). Healthy family function and being extravert were found to positively impact mental burden.ConclusionPsychological distress, stress reaction and insomnia symptoms have been prevalent among Chinese undergraduate medical students during the COVID-19 outbreak, and the prevalence of overall mental burden increased after the COVID-19 outbreak. Some students, especially those with the risk factors noted above, exhibited persistent or progression symptoms. Continued mental health care was in demand for them even after the COVID-19 outbreak.</p

Identification of ANXA2 (annexin A2) as a specific bleomycin target to induce pulmonary fibrosis by impeding TFEB-mediated autophagic flux

<p>Bleomycin is a clinically potent anticancer drug used for the treatment of germ-cell tumors, lymphomas and squamous-cell carcinomas. Unfortunately, the therapeutic efficacy of bleomycin is severely hampered by the development of pulmonary fibrosis. However, the mechanisms underlying bleomycin-induced pulmonary fibrosis, particularly the molecular target of bleomycin, remains unknown. Here, using a chemical proteomics approach, we identify ANXA2 (annexin A2) as a direct binding target of bleomycin. The interaction of bleomycin with ANXA2 was corroborated both in vitro and in vivo. Genetic depletion of <i>anxa2</i> in mice mitigates bleomycin-induced pulmonary fibrosis. We further demonstrate that Glu139 (E139) of ANXA2 is required for bleomycin binding in lung epithelial cells. A CRISPR-Cas9-engineered ANXA2^E139A mutation in lung epithelial cells ablates bleomycin binding and activates TFEB (transcription factor EB), a master regulator of macroautophagy/autophagy, resulting in substantial acceleration of autophagic flux. Pharmacological activation of TFEB elevates bleomycin-initiated autophagic flux, inhibits apoptosis and proliferation of epithelial cells, and ameliorates pulmonary fibrosis in bleomycin-treated mice. Notably, we observe lowered TFEB and LC3B levels in human pulmonary fibrosis tissues compared to normal controls, suggesting a critical role of TFEB-mediated autophagy in pulmonary fibrosis. Collectively, our data demonstrate that ANXA2 is a specific bleomycin target, and bleomycin binding with ANXA2 impedes TFEB-induced autophagic flux, leading to induction of pulmonary fibrosis. Our findings provide insight into the mechanisms of bleomycin-induced fibrosis and may facilitate development of optimized bleomycin therapeutics devoid of lung toxicity.</p