Oligomerization of the mixed-lineage kinase domain-like protein (MLKL) is essential for its cation channel function in necroptosis. Here we show that the MLKL channel is an octamer comprising two previously identified tetramers most likely in their side-by-side position. Intermolecule disulfide bonds are present in the tetramer but are not required for octamer assembly and necroptosis. MLKL forms oligomers in the necrosome and is then released from the necrosome before or during its membrane translocation. We identified two MLKL mutants that could not oligomerize into octamers, although they formed a tetramer, and also, one MLKL mutant could spontaneously form a disulfide bond-linked octamer. Subsequent analysis revealed that the tetramers fail to translocate to the plasma membrane and that the MLKL octamer formation depends on ␣-helices 4 and 5. While MLKL could be detected from outside the cells, its N-and C-terminal ends could not be detected, indicating that the MLKL octamer spans across the plasma membrane, leaving its N and C termini inside the cell. These data allowed us to propose a 180°symmetry model of the MLKL octamer and conclude that the fully assembled MLKL octamers, but not the previously described tetramers, act as effectors of necroptosis.
Background: Direct exposure to natural disasters and related losses are associated with post-traumatic stress disorder (PTSD). It is less clear whether indirect media exposure is associated with PTSD.Objective: This study investigated key exposure-related risk factors for PTSD and examined the effect of media exposure on the prevalence of disaster-related PTSD.Method: Typhoon Hato directly hit Macao on 23 August 2017. It was one of the most serious natural disasters ever to strike southern China. One month after the event, 1876 Chinese university students in Macao were recruited into a cross-sectional study (mean age 20.01 years, SD = 2.63; 66.2% female). Self-reported typhoon exposure, media use and exposure to disaster-related content, and PTSD symptoms were collected using an electronic survey. Univariable analyses assessed associations between risk factors and PTSD, which were then included in a series of multivariable logistic regressions.Results: The prevalence of PTSD was 5.1%. Adjusted models demonstrated that being male (vs female) [adjusted odds ratio (aOR) = 1.68, 95% confidence interval (CI) 1.07–2.63], home damage (aOR = 2.86, 95% CI 1.71–4.78), witnessing people injured (aOR = 2.33, 95% CI 1.36–4.00), and almost drowning during the storm (aOR = 8.99, 95% CI 1.92–41.99) were associated with PTSD. After adjusting for direct exposure, indirect exposure to disaster-related social media content, including information related to drowning victims (aOR = 1.29, 95% CI 1.00–1.67) and residents’ emotional reactions (aOR = 1.98, 95% CI 1.44–2.72), was associated with PTSD. Viewing more information about the storm itself (aOR = 0.37, 95% CI 0.28–0.49) and images of heroic acts (aOR = 0.72, 95% CI 0.55–0.94) were significantly associated with lower odds of PTSD.Conclusion: These findings add to the literature demonstrating that some types of media use and certain media content following a natural disaster are associated with PTSD.
Background: A large number of Chinese suffer from common mental disorders (e.g., depression, anxiety, stress, and post-traumatic stress disorder), but treatment seeking is typically low in this population. It is unclear what barriers influence professional mental health help-seeking behavior within the Chinese population. Identifying these barriers could assist in implementation science efforts to reach this population. Objective: This review systematically synthesizes findings related to the barriers to professional mental health help-seeking among Chinese adults. Methods: Two English language databases (PubMed and PsycINFO) and two Chinese databases (WANFANGDATA and CNKI) were searched to find relevant studies. Quality assessment was conducted in identified studies. Quantitative findings were tabulated and frequently reported barriers were ranked. Primary data obtained from qualitative studies were thematically analyzed. Results: Of 6,933 citations identified, 17 met inclusion criteria. There were 11 (64%) studies that reported quantitative methods; 3 (18%) employed qualitative research, and 3 (18%) mixed methods. Results indicated that frequently reported barriers to mental health help seeking among Chinese adults included a preference on self-reliance, seeking help from alternative sources, low perceived need toward help-seeking, a lack of affordability, negative attitude toward, or poor experiences with help-seeking. Less frequently mentioned barriers included stigma, families' opposition, limited knowledge about mental illness, a lack of accessibility, unwillingness to disclose mental illness, and fear of burdening family. Conclusions: The current review identified a number of key barriers to help-seeking behavior. Effective strategies are needed to promote professional help-seeking among Chinese adults. Additional factors influencing professional mental health help-seeking need to be further investigated, as they may contribute to a better understanding the helpseeking behavior among Chinese.
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