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Generation of alkenes through decarboxyolefination of alkane carboxylates has significant synthetic value in view of the easy availability of a variety of carboxylic acids and the synthetic versatility of alkenes. Herein we report that palladium catalysts under irradiation with blue LEDs (440 nm) catalyze decarboxylative desaturation of a variety of aliphatic carboxylates to generate aliphatic alkenes, styrenes, enol ethers, enamides, and peptide enamides under mild conditions. The selection of a dual phosphine ligand system is the key enabler for the successful development of this reaction. The Pd-catalyzed decarboxylative desaturation is utilized to achieve a three-step divergent synthesis of Chondriamide A and Chondriamide C in overall 68% yield from simple starting materials. Mechanistic studies suggest that, distinct from palladium catalysis under thermal condition, irradiation-induced palladium catalysis involves irradiation-induced single-electron transfer and dynamic ligand-dissociation/association process to allow two phosphine ligand to work synergistically. Production of alkenes through decarboxyolefination of carboxylates is a synthetically useful process. Here, the authors report a palladium/dual ligand-enabled decarboxylative desaturation reaction under mild irradiation conditions and apply it to the synthesis of Chondriamide A and C.

One aspect of work sustainability pertains to workers' intention to remain in their current job until reaching retirement age. Various adverse working conditions are expected to diminish work sustainability among different social groups. This study aims to examine these associations across gender and age groups.OBJECTIVESOne aspect of work sustainability pertains to workers' intention to remain in their current job until reaching retirement age. Various adverse working conditions are expected to diminish work sustainability among different social groups. This study aims to examine these associations across gender and age groups.The study participants were 19,152 economically-active adults in a national survey conducted in Taiwan. Information concerning psychosocial working conditions were obtained through interviews, using the Job Content Questionnaire. Work sustainability was evaluated by one question that asked whether the participants felt they would be able to do their current job until the age of 60. The association between psychosocial work conditions and work sustainability was examined by logistic regression analysis. We further performed stratified analysis to explore age and gender-specific associations.METHODSThe study participants were 19,152 economically-active adults in a national survey conducted in Taiwan. Information concerning psychosocial working conditions were obtained through interviews, using the Job Content Questionnaire. Work sustainability was evaluated by one question that asked whether the participants felt they would be able to do their current job until the age of 60. The association between psychosocial work conditions and work sustainability was examined by logistic regression analysis. We further performed stratified analysis to explore age and gender-specific associations.We observed that 14.2% and 17.1% of male and female workers reported low work sustainability. Workers in the electronics industries and female workers in the healthcare and education sectors reported low work sustainability. Gender-specific analyses showed that low job control among men and shift work among women were significantly associated with low work sustainability. Age-specific analyses indicated that having poor health, shift work, and long working hours in younger workers, and having low job control in older workers were associated with low work sustainability.RESULTSWe observed that 14.2% and 17.1% of male and female workers reported low work sustainability. Workers in the electronics industries and female workers in the healthcare and education sectors reported low work sustainability. Gender-specific analyses showed that low job control among men and shift work among women were significantly associated with low work sustainability. Age-specific analyses indicated that having poor health, shift work, and long working hours in younger workers, and having low job control in older workers were associated with low work sustainability.To retain older workers in the labor market, policies should aim at the improvement of psychosocial work conditions, and gender- and age-specific issues should be taken into consideration.CONCLUSIONTo retain older workers in the labor market, policies should aim at the improvement of psychosocial work conditions, and gender- and age-specific issues should be taken into consideration.

ObjectivesShift work is associated with adverse physical and psychological health outcomes. However, the independent health effects of night work and rotating shift on workers' sleep and mental health risks and the potential gender differences have not been fully evaluated.MethodsWe used data from a nationwide survey of representative employees of Taiwan in 2013, consisting of 16 440 employees. Participants reported their work shift patterns 1 week prior to the survey, which were classified into the four following shift types: fixed day, rotating day, fixed night and rotating night shifts. Also obtained were self-reported sleep duration, presence of insomnia, burnout and mental disorder assessed by the Brief Symptom Rating Scale.ResultsAmong all shift types, workers with fixed night shifts were found to have the shortest duration of sleep, highest level of burnout score, and highest prevalence of insomnia and minor mental disorders. Gender-stratified regression analyses with adjustment of age, education and psychosocial work conditions showed that both in male and female workers, fixed night shifts were associated with greater risks for short sleep duration (<7 hours per day) and insomnia. In female workers, fixed night shifts were also associated with increased risks for burnout and mental disorders, but after adjusting for insomnia, the associations between fixed night shifts and poor mental health were no longer significant.ConclusionsThe findings of this study suggested that a fixed night shift was associated with greater risks for sleep and mental health problems, and the associations might be mediated by sleep disturbance.

Aberrant activation of the epidermal growth factor receptor (EGFR/ERBB1) by erythroblastic leukemia viral oncogene homolog (ERBB) ligands contributes to various tumor malignancies, including lung cancer and colorectal cancer (CRC). Epiregulin (EREG) is one of the EGFR ligands and is low expressed in most normal tissues. Elevated EREG in various cancers mainly activates EGFR signaling pathways and promotes cancer progression. Notably, a higher EREG expression level in CRC with wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS) is related to better efficacy of therapeutic treatment. By contrast, the resistance of anti-EGFR therapy in CRC was driven by low EREG expression, aberrant genetic mutation and signal pathway alterations. Additionally, EREG overexpression in non-small cell lung cancer (NSCLC) is anticipated to be a therapeutic target for EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, recent findings indicate that EREG derived from macrophages promotes NSCLC cell resistance to EGFR-TKI treatment. The emerging events of EREG-mediated tumor promotion signals are generated by autocrine and paracrine loops that arise from tumor epithelial cells, fibroblasts, and macrophages in the tumor microenvironment (TME). The TME is a crucial element for the development of various cancer types and drug resistance. The regulation of EREG/EGFR pathways depends on distinct oncogenic driver mutations and cell contexts that allows specific pharmacological targeting alone or combinational treatment for tailored therapy. Novel strategies targeting EREG/EGFR, tumor-associated macrophages, and alternative activation oncoproteins are under development or undergoing clinical trials. In this review, we summarize the clinical outcomes of EREG expression and the interaction of this ligand in the TME. The EREG/EGFR pathway may be a potential target and may be combined with other driver mutation targets to combat specific cancers.

Background Family caregivers are important allies for healthcare providers in facilitating the recovery process among people with mental illness (PWMI). The present study examined the factors associated with quality of life (QoL) among family caregivers of PWMI. Methods A multi-center cross-sectional survey was conducted. Family caregivers of people with schizophrenia, major depressive disorder, and bipolar disorder were recruited using convenience sampling. A survey assessing their QoL, depression, anxiety, and self-esteem was completed with self-rated psychometric scales including the Rosenberg Self-Esteem Scale, Caregiver Burden Inventory, Taiwanese Depression Questionnaire, Beck Anxiety Inventory, and World Health Organization Quality of Life Instrument Short Form. A mediation model was constructed with QoL as the dependent variable, care burden as the independent variable, and psychological distress (including depression and anxiety) with self-esteem as mediating variables. Results Family caregivers of people with schizophrenia had worse QoL compared with counterparts of people with major depression and bipolar disorder. The sociodemographic of both caregivers and PWMI had less impact on QoL when psychological factors were considered. Caregivers with lower self-esteem, higher levels of psychological distress, and heavier care burdens had poorer QoL. Care burden had a significant total effect on QoL. Both self-esteem and psychological distress were significant mediators. Conclusion The findings indicated that caregivers’ psychological health and care burden influenced their QoL. Interventions that target family caregivers’ self-esteem and psychological distress may attenuate the effect from care burden, and further improve their QoL.

The past several decades have given rise to more insights into the role of astrocytes in normal brain function and diseases. Astrocytes elicit an effect which may be neuroprotective or deleterious in the process of Alzheimer’s disease (AD). Impairments in astrocytes and their other functions, as well as physiological reactions of astrocytes to external injury, can trigger or exacerbate hyperphosphorylated tau and amyloid-beta (Aβ) pathologies, leading to the formation of both amyloid plaques and neurofibrillary tangles (NFTs), as well as neuronal dysfunction. This review addresses the involvement of astrocytes in the Aβ pathology, where the main mechanisms include the generation and clearance of Aβ, and the formation of NFTs. It is also discussed that metabolic dysfunction from astrocytes acts as an initiating factor in the pathogenesis of AD and a contributor to the onset and development of clinical presentation in AD.

Studies concerning the risk of metabolic syndrome associated with night work have shown inconsistent findings, due to imprecise working time data and cross-sectional design. We used register-based daily working time data to examine the risk of incident metabolic syndrome associated with night shift work. Working time data collected between 2010 and 2018 of 5775 Taiwanese hospital workers were used to identify night shift workers and to calculate the number of night shifts. Metabolic syndrome was identified by annual occupational health examination results, which were linked to the working time data. Logistic regression models and generalized estimating equations were used to examine the association between night shift work and metabolic syndrome and the 5 components of metabolic syndrome. Night shift work is associated with a higher risk of developing metabolic syndrome (adjusted OR = 1.36, 95% CI = 1.04 to 1.78) and high waist circumference (adjusted OR = 1.27, 95% CI = 1.07 to 1.78) compared to day work. Among night shift workers, increased number of night shifts was associated with high blood pressure (adjusted OR = 1.15, 95% CI = 1.01 to 1.31). Night shift work is associated with metabolic risk factors. Long-term effects of circadian rhythm disruption on metabolic disturbances needs to be further studied.

The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a result of decreased mitophagy activity and displayed functional, transcriptomic and epigenetic characteristics of terminally exhausted T cells. Mechanistically, reduced mitochondrial fitness in TILs was induced by the coordination of T cell receptor stimulation, microenvironmental stressors and PD-1 signaling. Enforced accumulation of depolarized mitochondria with pharmacological inhibitors induced epigenetic reprogramming toward terminal exhaustion, indicating that mitochondrial deregulation caused T cell exhaustion. Furthermore, supplementation with nicotinamide riboside enhanced T cell mitochondrial fitness and improved responsiveness to anti-PD-1 treatment. Together, our results reveal insights into how mitochondrial dynamics and quality orchestrate T cell antitumor responses and commitment to the exhaustion program. Ho and colleagues report that mitochondrial dysfunction and impaired mitophagy triggered by the tumor microenvironment lead to subsequent epigenetic changes and cause permanent T cell exhaustion and dysfunction.

Essential oils (EOs) are intricate combinations of evaporative compounds produced by aromatic plants and extracted by distillation or expression. EOs are natural secondary metabolites derived from plants and have been found to be useful in food and nutraceutical manufacturing, perfumery and cosmetics; they have also been found to alleviate the phenomenon of antimicrobial resistance (AMR) in addition to functioning as antibacterial and antifungal agents, balancing menstrual cycles and being efficacious as an immune system booster. Several main aldehyde constituents can be found in different types of EOs, and thus, aldehydes and their derivatives will be the main focus of this study with regard to their antimicrobial, antioxidative, anti-inflammatory and immunomodulatory effects. This brief study also explores the activity of aldehydes and their derivatives against pathogenic bacteria for future use in the clinical setting.