Keeping cGAS in check: SPSB3 promotes nuclear cGAS degradation for maintaining immune homeostasis.

In a recent publication in Nature, Xu et al.1 discovered a role of CRL5-SPSB3 ubiquitin ligase in promoting ubiquitination and degradation of nuclear cGAS, which prevents aberrant cGAS activation by genomic DNA and contributes to the maintenance of immune homeostasis.

PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly.

Purinosomes serve as metabolons to enhance de novo purine synthesis (DNPS) efficiency through compartmentalizing DNPS enzymes during stressed conditions. However, the mechanism underpinning purinosome assembly and its pathophysiological functions remains elusive. Here, we show that K6-polyubiquitination of the DNPS enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (PAICS) by cullin-5/ankyrin repeat and SOCS box containing 11 (Cul5/ASB11)-based ubiquitin ligase plays a driving role in purinosome assembly. Upon several purinosome-inducing cues, ASB11 is upregulated by relieving the H3K9me3/HP1α-mediated transcriptional silencing, thus stimulating PAICS polyubiquitination. The polyubiquitinated PAICS recruits ubiquitin-associated protein 2 (UBAP2), a ubiquitin-binding protein with multiple stretches of intrinsically disordered regions, thereby inducing phase separation to trigger purinosome assembly for enhancing DNPS pathway flux. In human melanoma, ASB11 is highly expressed to facilitate a constitutive purinosome formation to which melanoma cells are addicted for supporting their proliferation, viability, and tumorigenesis in a xenograft model. Our study identifies a driving mechanism for purinosome assembly in response to cellular stresses and uncovers the impact of purinosome formation on human malignancies.

DNA cytosine methyltransferases differentially regulate genome-wide hypermutation and interhomolog recombination in Trichoderma reesei meiosis.

Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type and spo11Δ meiosis. DNA methyltransferases (DNMTs) perform multiple tasks in meiosis. Three DNMT genes (rid1, dim2 and dimX) differentially regulate genome-wide cytosine methylation and C:G-to-T:A hypermutations in different chromosomal regions. We have identified two types of DSBs: type I DSBs require spo11 or rid1 for initiation, whereas type II DSBs do not rely on spo11 and rid1 for initiation. rid1 (but not dim2) is essential for Rad51-mediated DSB repair and normal meiosis. rid1 and rad51 exhibit a locus heterogeneity (LH) relationship, in which LH-associated proteins often regulate interconnectivity in protein interaction networks. This LH relationship can be suppressed by deleting dim2 in a haploid rid1Δ (but not rad51Δ) parental strain, indicating that dim2 and rid1 share a redundant function that acts earlier than rad51 during early meiosis. In conclusion, our studies provide the first evidence of the involvement of DNMTs during meiotic initiation and recombination.

The Effects of Light Therapy on Sleep, Depression, Neuropsychiatric Behaviors, and Cognition Among People Living With Dementia: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Alterations in the suprachiasmatic nucleus due to underlying pathologies disrupt the circadian rhythms in people living with dementia (PLWD). Circadian rhythms significantly impact sleep, emotional, and cognitive functions, with its synchronization depending on light exposure. We performed a meta-analysis to evaluate the effects of light therapy on sleep, depression, neuropsychiatric behaviors, and cognition among PLWD. METHODS: A systematic search was conducted in Cochrane, ClinicalTrials.gov, Embase, EBSCOhost, Ovid-MEDLINE, PubMed, Scopus, Web of Science, and CINAHL databases. The pooled effect size was calculated using the Hedges' g with random-effects model adopted in comprehensive meta-analysis software. The Cochrane risk of bias (RoB 2.0) tool evaluated the quality of studies, while Cochrane's Q and I² tests assessed heterogeneity. RESULTS: A total of 24 studies with 1,074 participants were included. Light therapy demonstrated small-to-medium effects on improving sleep parameters: total sleep time (Hedges' g = 0.19), wake after sleep onset (Hedges' g = 0.24), sleep efficiency (Hedges' g = 0.31), sleep latency (Hedges' g = 0.35), circadian rhythm (acrophase: Hedges' g = 0.36; amplitude: Hedges' g = 0.43), number of night awakenings (Hedges' g = 0.37), sleep disturbance (Hedges'g = 0.45), and sleep quality (Hedges' g = 0.60). Light therapy showed small-to-medium effect on reducing depression (Hedges' g = -0.46) with medium-to-large effect on cyclical function (Hedges' g = -0.68) and mood-related signs and symptoms (Hedges' g = -0.84) subscales. Light therapy also demonstrated small effect on reducing neuropsychiatric behaviors (Hedges' g = -0.34) with medium-to-large effect on agitation (Hedges' g = -0.65), affective symptom (Hedges' g = -0.70), psychosis (Hedges' g = -0.72), and melancholic behavior (Hedges' g = -0.91) subscales. Additionally, light therapy also improved cognition (Hedges' g = 0.39). CONCLUSION: Light therapy could be used as a supportive therapy to improve sleep, depression, cognition, and neuropsychiatric behaviors among PLWD.

Prevalence of swallowing disorder in different dementia subtypes among older adults: a meta-analysis.

BACKGROUND: Ageing process and abnormal protein accumulation in dementia damage neural pathways affecting the swallowing process and leading to swallowing disorder. OBJECTIVE: To estimate the prevalence of swallowing disorder among older adults with different dementia subtypes. METHODS: We conducted a systematic search across multiple databases, including PubMed, Embase, Scopus, Web of Science and OVID Medline. The meta-analysis employed R (version 4.0.2) and utilised a generalised linear mixed model with a random-effect approach to estimate the pooled prevalence of swallowing disorder among older adults, considering various dementia subtypes. The quality of included studies was assessed using Hoy's criteria. Heterogeneity was identified through Cochrane's Q and I2 statistics. To further explore heterogeneity, moderator analysis was performed to identify the contributing variables among the included studies. RESULTS: Eighteen studies with 12,532 older adults with different dementia subtypes were enrolled in our meta-analysis. The pooled prevalence of swallowing disorder among older adults with dementia was 58%, with 46.5% for Alzheimer's dementia, 34.9% for Parkinson's dementia, 18.8% for vascular dementia, 16.3% for mixed dementia and 12.2% for Lewy body dementia. According to assessment tools, Alzheimer's dementia had the highest prevalence, with 58% in instrumental assessments and 39% in clinical assessments. Medical history, Alzheimer's dementia, moderate-to-severe Clinical Dementia Rating, delayed oral phase, delayed pharyngeal phase and poor tongue motility contributed to the heterogeneity of the included studies. CONCLUSIONS: More than half of older adults with dementia demonstrate to have swallowing disorder. Our findings offer valuable insights to healthcare professionals for the identification of swallowing disorder in ageing population with dementia.

Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination.

Autophagy, a cellular self-eating mechanism, is important for maintaining cell survival and tissue homeostasis in various stressed conditions. Although the molecular mechanism of autophagy induction has been well studied, how cells terminate autophagy process remains elusive. Here, we show that ULK1, a serine/threonine kinase critical for autophagy initiation, is a substrate of the Cul3-KLHL20 ubiquitin ligase. Upon autophagy induction, ULK1 autophosphorylation facilitates its recruitment to KLHL20 for ubiquitination and proteolysis. This autophagy-stimulated, KLHL20-dependent ULK1 degradation restrains the amplitude and duration of autophagy. Additionally, KLHL20 governs the degradation of ATG13, VPS34, Beclin-1, and ATG14 in prolonged starvation through a direct or indirect mechanism. Impairment of KLHL20-mediated regulation of autophagy dynamics potentiates starvation-induced cell death and aggravates diabetes-associated muscle atrophy. Our study identifies a key role of KLHL20 in autophagy termination by controlling autophagy-dependent turnover of ULK1 and VPS34 complex subunits and reveals the pathophysiological functions of this autophagy termination mechanism.

WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 in Drosophila.

WD40 proteins control many cellular processes via protein interactions. Drosophila Wuho (Wh, a WD40 protein) controls fertility, although the involved mechanisms are unclear. Here, we show that Wh promotion of Mei-p26 (a human TRIM32 ortholog) function maintains ovarian germ cell homeostasis. Wh and Mei-p26 are epistatically linked, with wh and mei-p26 mutants showing nearly identical phenotypes, including germline stem cell (GSC) loss, stem-cyst formation due to incomplete cytokinesis between GSCs and daughter cells, and overproliferation of GSC progeny. Mechanistically, Wh interacts with Mei-p26 in different cellular contexts to induce cell type-specific effects. In GSCs, Wh and Mei-p26 promote BMP stemness signaling for proper GSC division and maintenance. In GSC progeny, Wh and Mei-p26 silence nanos translation, downregulate a subset of microRNAs involved in germ cell differentiation and suppress ribosomal biogenesis via dMyc to limit germ cell mitosis. We also found that the human ortholog of Wh (WDR4) interacts with TRIM32 in human cells. Our results show that Wh is a regulator of Mei-p26 in Drosophila germ cells and suggest that the WD40-TRIM interaction may also control tissue homeostasis in other stem cell systems.

Comparative effectiveness of psychotherapies in adults with posttraumatic stress disorder: a network meta-analysis of randomised controlled trials.

BACKGROUND: Evidence on the long-term comparative effectiveness of posttraumatic stress disorder (PTSD) psychotherapies in adults remains unknown. Therefore, we performed an extensive network meta-analysis of randomised controlled trials (RCTs) to determine the comparative effectiveness of psychotherapies for people diagnosed with PTSD. METHODS: A comprehensive search was conducted in Cochrane library, Embase, Medline-OVID, PubMed, Scopus, and Psych-Info until March 2021. Studies on the effectiveness of cognitive processing therapy (CPT), cognitive therapy (CT), eye movement desensitisation reprocessing (EMDR), narrative exposure therapy (NET), prolonged exposure (PE), cognitive behavioural therapy (CBT), present-centred therapy (PCT), brief eclectic psychotherapies (BEP), psychodynamic therapy (PDT) or combination therapies compared to no treatment (NT) or treatment as usual (TAU) in adults with PTSD were included. Frequentist and Bayesian approaches were used for analysis in R-software. RESULTS: We included 98 RCTs with 5567 participants from 18 897 studies. CPT, EMDR, CT, NET, PE, CBT, and PCT were significant to reduce PTSD symptoms (SMD range: -1.53 to -0.75; Certainty: very low to high) at immediate post-treatment and ranked accordingly. Longitudinal analysis found EMDR (1.02) and CPT (0.85) as the significant therapies with large effect size in short-term and long-term follow-up, respectively. NET and CPT showed higher proportion of loss of PTSD diagnosis (RR range: 5.51-3.45) while there were no significant psychotherapies for retention rate compared to NT. CONCLUSIONS: Our findings provide evidence for improving current guidelines and informing clinical decision-making for PTSD management. However, the best PTSD treatment plan should be tailored to patients' needs, characteristics, and clinician expertise. REGISTRATION: PROSPERO CRD42020162143.

Efficacy of Blue LED Phototherapy on Sleep Quality and Behavioral and Psychological Symptoms of Dementia: A Double-Blind Randomized Controlled Trial.

INTRODUCTION: People with dementia often experience behavioral and psychological symptoms of dementia (BPSD), which are a major cause of caregiver burden and institutionalization. Therefore, we conducted a double-blind, parallel-group randomized controlled trial to examine the efficacy of blue-enriched light therapy for BPSD in institutionalized older adults with dementia. METHODS: Participants were enrolled and randomly allocated into blue-enriched light therapy (N = 30) or the conventional light group (N = 30) for 60 min in 10 weeks with five sessions per week. The primary outcome was sleep quality measured by actigraphy and Pittsburgh Sleep Quality Index (PSQI). The secondary outcome was overall BPSD severity (Cohen-Mansfield Agitation Inventory [CMAI] and Neuropsychiatric Inventory [NPI-NH]). The outcome indicators were assessed at baseline, mid-test, immediate posttest, 1-month, 3-month, and 6-month follow-up. The effects of the blue-enriched light therapy were examined by the generalized estimating equation model. RESULTS: Blue-enriched light therapy revealed significant differences in the objective sleep parameters (sleep efficiency: ß = 5.81, Waldχ2 = 32.60, CI: 3.82; 7.80; sleep latency: ß = -19.82, Waldχ2 = 38.38, CI:-26.09; -13.55), subjective sleep quality (PSQI: ß = -2.07, Waldχ2 = 45.94, CI: -2.66; -1.47), and overall BPSD severity (CMAI: ß = -0.90, Waldχ2 = 14.38, CI: -1.37; -0.44) (NPI-NH: ß = -1.67, Waldχ2 = 30.61, CI: -2.26; -1.08) compared to conventional phototherapy immediate posttest, 1-month, 3-month, and 6-month follow-up. Furthermore, the effects for sleep efficiency and sleep latency lasted for up to 6 months. In the subscale analysis, the differences of the behavioral symptoms changed significantly between the groups in physical/nonaggressive (CI: -1.01; -0.26) and verbal/nonaggressive (CI: -0.97; -0.29). CONCLUSIONS: Blue-enriched light therapy is a feasible low-cost intervention that could be integrated as a comprehensive therapy program for BPSD among older adults with dementia.

Effectiveness of respiratory rehabilitation in patients with COVID-19: A meta-analysis.

AIM: Examine effectiveness of respiratory rehabilitation and moderating factors on lung function and exercise capacity in post-COVID-19 patients. DESIGN: Meta-analysis. METHODS: R software 4.0.2 assessed the effectiveness of respiratory rehabilitation adopting the random-effects model and presenting standardised mean differences (SMDs). Heterogeneity was determined by Cochran's Q and I2 . The Cochrane Risk of Bias 2.0 and MINORS evaluated quality of the included studies. DATA SOURCES: A comprehensive search was undertaken in Cochrane, Embase, Ovid-MEDLINE, Scopus, NCBI SARS-CoV-2 Resources, ProQuest, Web of Science and CINAHL until March 2022. RESULTS: Of the 5703 identified studies, 12 articles with 596 post-COVID-19 patients were included. Eleven of our twelve studies had moderate to high quality and one study had high risk of bias assessed with MINORS and RoB 2 tool. Overall, respiratory rehabilitation was effective in improving forced expiratory volume in 1 s (1.14; 95%CI 0.39-1.18), forced vital capacity (0.98; 95%CI 0.39-1.56), total lung capacity (0.83; 95%CI 0.22-1.44), 6-minute walk distance (1.56; 95%CI 1.10-2.02) and quality of life (0.99; 95%CI 0.38-1.60). However, no significant differences were observed for ratio of the forced expiratory volume in 1 s to the forced vital capacity of the lungs, anxiety and depression. Respiratory rehabilitation for post-COVID-19 patients was effective in those without comorbidities, performed four types of exercise programs, frequency ≥3 times/week and rehabilitation time 6 weeks. CONCLUSIONS: Respiratory rehabilitation improved lung function, exercise capacity and quality of life in post-COVID-19 patients. The findings suggest rehabilitation programs for post-COVID-19 patients should use multiple respiratory exercise programs with frequency of ≥3 times per week for longer than 6 weeks. IMPACT: These findings will help improve the implementation of respiratory rehabilitation programs for post-COVID-19 patients. IMPLICATIONS FOR THE PROFESSION: Our findings can be used to develop patient-centred respiratory rehabilitation interventions by nurses and clinicians for post-COVID-19 patients. REPORTING METHOD: PRISMA guideline was followed. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Autophagy and cancer metabolism-The two-way interplay.

Autophagy is an intracellular catabolic process that degrades cytoplasmic components for recycling in response to stressed conditions, such as nutrient deprivation. Dysregulation of autophagy is associated with various diseases, including cancer. Although autophagy plays dichotomous and context-dependent roles in cancer, evidence has emerged that cancer cells exploit autophagy for metabolic adaptation. Autophagy is upregulated in many cancer types through tumor cell-intrinsic proliferation demands and the hypoxic and nutrient-limited tumor microenvironment (TME). Autophagy-induced breakdown products then fuel into various metabolic pathways to supply tumor cells with energy and building blocks for biosynthesis and survival. This bidirectional regulation between autophagy and tumor constitutes a vicious cycle to potentiate tumor growth and therapy resistance. In addition, the pro-tumor functions of autophagy are expanded to host, including cells in TME and distant organs. Thus, inhibition of autophagy or autophagy-mediated metabolic reprogramming may be a promising strategy for anticancer therapy. Better understanding the metabolic rewiring mechanisms of autophagy for its pro-tumor effects will provide insights into patient treatment.

Long noncoding RNA BCRP3 stimulates VPS34 and autophagy activities to promote protein homeostasis and cell survival.

BACKGROUND: Autophagy plays important roles in cell homeostasis and protein quality control. Long non-coding RNAs (lncRNAs) have been revealed as an emerging class of autophagy regulators, but the majority of them function in regulating the expression of autophagy-related genes. LncRNAs that directly act on the core autophagic proteins remain to be explored. METHODS: Immunofluorescence staining and Western blotting were used to evaluate the function of BCRP3 in autophagy and aggrephagy. RNA immunoprecipitation and in vitro RNA-protein binding assay were used to evaluate the interaction of BCRP3 with its target proteins. Phosphatidylinositol 3-phosphate ELISA assay was used to quantify the enzymatic activity of VPS34 complex. qRT-PCR analysis was used to determine BCRP3 expression under stresses, whereas mass spectrometry and Gene Ontology analyses were employed to evaluate the effect of BCRP3 deficiency on proteome changes. RESULTS: We identified lncRNA BCRP3 as a positive regulator of autophagy. BCRP3 was mainly localized in the cytoplasm and bound VPS34 complex to increase its enzymatic activity. In response to proteotoxicity induced by proteasome inhibition or oxidative stress, BCRP3 was upregulated to promote aggrephagy, thereby facilitating the clearance of ubiquitinated protein aggregates. Proteomics analysis revealed that BCRP3 deficiency under proteotoxicity resulted in a preferential accumulation of proteins acting in growth inhibition, cell death, apoptosis, and Smad signaling. Accordingly, BCRP3 deficiency in proteotoxic cells compromised cell proliferation and survival, which was mediated in part through the upregulation of TGF-ß/Smad2 pathway. CONCLUSIONS: Our study identifies BCRP3 as an RNA activator of the VPS34 complex and a key role of BCRP3-mediated aggrephagy in protein quality control and selective degradation of growth and survival inhibitors to maintain cell fitness.

K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking.

Ubiquitin chains are formed as structurally distinct polymers via different linkages, and several chain types including K33-linkage remain uncharacterized. Here, we describe a role for K33-polyubiquitination in protein trafficking. We show that the Cullin 3 (Cul3) substrate adaptor KLHL20 is localized to the trans-Golgi network (TGN) and is important for post-Golgi trafficking by promoting the biogenesis of TGN-derived transport carriers. The Cul3-KLHL20 ubiquitin E3 ligase catalyzes a nondegradable, K33-linked polyubiquitination on coronin 7 (Crn7), which facilitates Crn7 targeting to TGN through a ubiquitin-dependent interaction with Eps15. Blockage of K33-chain formation, Crn7 ubiquitination, or disruption of Crn7-Eps15 interaction impairs TGN-pool F-actin assembly, a process essential for generating transport carriers. Enforced targeting of Crn7 to TGN bypasses the requirement of K33-ubiquitination for TGN-pool F-actin assembly and post-Golgi trafficking. Our study reveals a role of KLHL20-mediated K33-ubiquitination of Crn7 in post-Golgi transport and identifies a cellular recognition mechanism for this ubiquitin chain type.

Prevalence of Oropharyngeal Dysphagia and Risk of Pneumonia, Malnutrition, and Mortality in Adults Aged 60 Years and Older: A Meta-Analysis.

INTRODUCTION: Oropharyngeal dysphagia (OD) is a serious health condition associated with poor survival and quality of life in adults aged 60 years and older. Comprehensive assessment and management of OD could lead to better and improved health outcomes for older adults. Therefore, we performed the first meta-analysis to determine the pooled prevalence of OD and risk of pneumonia, malnutrition, and mortality. METHODS: Databases including Ovid-MEDLINE, Web of Science, Embase, PubMed, Cochrane, and CINAHL were searched up to January 2021. Data analysis was conducted using logistic-normal for prevalence rate and DerSimonian-Lard random-effects models for outcomes and associated factors of OD, providing odds ratio (OR) and corresponding 95% confidence interval (CI). RESULTS: The pooled prevalence of OD in 39 studies with 31,488 participants was 46% associated with higher pooled OR for risk of pneumonia 2.07 (95% CI, 1.58-2.72), malnutrition 2.21 (95% CI, 1.43-3.41), and mortality 2.73 (95% CI, 1.62-4.60). Geriatric syndromes including fecal incontinence 6.84 (4.955-9.44), immobility syndrome 6.06 (5.28-6.96), pressure ulcers 4.02 (2.46-6.56), sarcopenia 3.10 (1.89-5.09), urinary incontinence 2.75 (1.81-4.19), frailty 2.66 (1.16-6.13), delirium 2.23 (1.73-2.87), and falls 1.47 (1.19-1.81) and comorbidities including dementia 3.69 (2.36-5.78) and stroke 1.92 (1.47-2.52) were associated with OD. CONCLUSION: Early identification and management of OD should consider geriatric syndromes and neurogenic comorbidities to prevent malnutrition and pneumonia and reduce mortality in adults aged 60 years and older.

Integrative analyses of noncoding RNAs reveal the potential mechanisms augmenting tumor malignancy in lung adenocarcinoma.

Precise noncoding RNA (ncRNA)-based network prediction is necessary to reveal ncRNA functions and pathological mechanisms. Here, we established a systemic pipeline to identify prognostic ncRNAs, predict their functions and explore their pathological mechanisms in lung adenocarcinoma (LUAD). After in silico and experimental validation based on evaluations of prognostic value in multiple LUAD cohorts, we selected the PTTG3P pseudogene from among other prognostic ncRNAs (MIR497HG, HSP078, TBX5-AS1, LOC100506990 and C14orf64) for mechanistic studies. PTTG3P upregulation in LUAD cells shortens the metaphase to anaphase transition in mitosis, increases cell viability after cisplatin or paclitaxel treatment, facilitates tumor growth that leads to poor survival in orthotopic lung models, and is associated with a poor survival rate in LUAD patients in the TCGA cohort who received chemotherapy. Mechanistically, PTTG3P acts as an ncRNA that interacts with the transcription factor FOXM1 to regulate the transcriptional activation of the mitotic checkpoint kinase BUB1B, which augments tumor growth and chemoresistance and leads to poor outcomes for LUAD patients. Overall, we established a systematic strategy to uncover prognostic ncRNAs with functional prediction methods suitable for pan-cancer studies. Moreover, we revealed that PTTG3P, due to its upregulation of the PTTG3P/FOXM1/BUB1B axis, could be a therapeutic target for LUAD patients.

Individual and family preferences of job qualities matter: association between face needs, locked-in job status, and burnout among high-tech workers in Taiwan.

BACKGROUND: Studies on the health impacts of being locked in a job are primarily conducted in Western countries, with the theory based on the value of individualism. But the socially-oriented concerns should be considered in workers' locked-in status in Chinese society. So the current study aims at evaluating socially-oriented concerns on workers' locked-in status in Taiwan. METHODS: Anonymous surveys were conducted with 1102 workers at high-tech companies in Taiwan from October 2015 to January 2016 to assess their "face" needs-- a sociological concept linked to the dignity, prestige, and reputation that a person has in terms of their social relationships, locked-in status of the job, and burnout. In addition to being separated into three groups by lock-in score, participants were categorized by the conflict of preference of the job between themselves and their family. Chi-square, ANOVA, Pearson correlation, and regression tests were conducted. RESULTS: Among the 1102 participants, 18% had jobs that they did not prefer but their family preferred. Participants with higher face needs and higher locked-in status had a significantly higher risk of developing personal and work-related burnout. However, the analysis using "locked-in job conflict of preference between themselves and their family" showed a more coherent result. Participants with a job which "self does not prefer but family do" had twice the risk of having personal and work-related burnout (OR = 2.03 and 2.34, respectively). Participants with a job which neither themselves nor their family prefer had four times the risk of having personal and work-related burnout (OR = 4.10 and 4.17, respectively). CONCLUSIONS: The current study suggests an importance in considering a socially-oriented job preference in locked-in status evaluations within the Chinese culture. Workers' whose locked-in status preference conflicted with their family's preference showed a significantly negative impact on their health.

Gamma irradiation influence on mechanical, thermal and conductivity properties of hybrid carbon nanotubes/montmorillonite nanocomposites.

A thermoplastic elastomer (TPE) based nanocomposite with the same weight ratio of hybrid nanofillers composed of carbon nanotubes (CNTs) and montmorillonite nanoclay (DK4) was prepared using a melt blending technique with an internal mixer. The TPE composite was blended from polylactic acid (PLA), liquid natural rubber (LNR) as a compatibilizer and natural rubber (NR) in a volume ratio of 70:10:20, respectively. The weight ratio of CNTs and DK4 was 2.5 wt%. The prepared samples were exposed to gamma radiation at range of 0-250 kGy. After exposure to gamma radiation, the mechanical, thermo-mechanical, thermal and electrical conductivity properties of the composites were significantly higher than unirradiated TPE composites as the irradiation doses increased up to 150 kGy. Transmission electron microscopy (TEM) micrographs revealed the good distribution and interaction between the nano-fillers and the matrix in the prepared TPE hybrid nanocomposites. In summary, the findings from this work definite that gamma irradiation might be a viable treatment to improve the properties of TPE nanocomposite for electronic packaging applications.

Using World Health Organization Disability Assessment Schedule 2.0 in people with schizophrenia: a 4-year follow-up.

Little is known about the changes of people with schizophrenia disability in Taiwan who receive routine treatments under the current mental healthcare system. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess and track changes in the degree of disability in people with schizophrenia before and after 4 years of follow-up. Data on 4497 people with schizophrenia were acquired from the Taiwan Data Bank of Persons with Disability. The WHODAS 2.0 was used for disability assessment, and the chi-square test, logistic regression and generalised estimating equations were adopted for statistical analysis. People with schizophrenia exhibited improvement in cognition, mobility and participation among the six domains as well as in the overall score. The degree of disability in all domains remained mild to moderate among people aged 18-64 years; the degree of disability in cognition declined from moderate to severe among patients aged ≥65 years. The degree of disability in all domains remained mild to moderate among people with mild to moderate impairment; among those with severe impairment, the degree of disability in the domains of cognition and life activities declined from moderate to severe and the degree of disability in the domain of mobility declined from mild to moderate. Community-dwelling patients exhibited less degree of disability in all domains than their institutionalised peers. Early detection and treatment and an emphasis on communication and social problem-solving skills in rehabilitation programmes are recommended for people with schizophrenia.

Cullin 3 and Its Role in Tumorigenesis.

Cullin 3 (Cul3) family of ubiquitin ligases comprises three components, the RING finger protein RBX1, the Cul3 scaffold, and a Bric-a-brac/Tramtrack/Broad complex (BTB) protein. The BTB protein serves as a bridge to connect Cul3 to substrate and is functionally equivalent to the combination of substrate adaptor and linker in other Cullin complexes. Human genome encodes for ~180 BTB proteins, implying a broad spectrum of ubiquitination signals and substrate repertoire. Accordingly, Cul3 ubiquitin ligases are involved in diverse cellular processes, including cell division, differentiation, cytoskeleton remodeling, stress responses, and nerve cell functions. Emerging evidence has pointed to the prominent role of Cul3 ubiquitin ligases in cancer. This chapter will describe recent advances on the roles of Cul3 E3 ligase complexes in regulating various cancer hallmarks and therapeutic responses and the mutation/dysregulation of Cul3 substrate adaptors in cancer. In particular, we will focus on several extensively studied substrate adaptors, such as Keap1, SPOP, KLHL20, and LZTR1, and will also discuss other recently identified Cul3 adaptors with oncogenic or tumor-suppressive functions. We conclude that Cul3 ubiquitin ligases represent master regulators of human malignancies and highlight the importance of developing modulating agents for oncogenic/tumor-suppressive Cul3 E3 ligase complexes to prevent or intervene tumorigenesis.

Branched Ubiquitination: Detection Methods, Biological Functions and Chemical Synthesis.

Ubiquitination is a versatile posttranslational modification that elicits signaling roles to impact on various cellular processes and disease states. The versatility is a result of the complexity of ubiquitin conjugates, ranging from a single ubiquitin monomer to polymers with different length and linkage types. Recent studies have revealed the abundant existence of branched ubiquitin chains in which one ubiquitin molecule is connected to two or more ubiquitin moieties in the same ubiquitin polymer. Compared to the homotypic ubiquitin chain, the branched chain is recognized or processed differently by readers and erasers of the ubiquitin system, respectively, resulting in a qualitative or quantitative alteration of the functional output. Furthermore, certain types of branched ubiquitination are induced by cellular stresses, implicating their important physiological role in stress adaption. In addition, the current chemical methodologies of solid phase peptide synthesis and expanding genetic code approach have been developed to synthesize different architectures of branched ubiquitin chains. The synthesized branched ubiquitin chains have shown their significance in understanding the topologies and binding partners of the branched chains. Here, we discuss the recent progresses on the detection, functional characterization and synthesis of branched ubiquitin chains as well as the future perspectives of this emerging field.