Unsaturation of very-long-chain ceramides protects plant from hypoxia-induced damages by modulating ethylene signaling in Arabidopsis.

Lipid remodeling is crucial for hypoxic tolerance in animals, whilst little is known about the hypoxia-induced lipid dynamics in plants. Here we performed a mass spectrometry-based analysis to survey the lipid profiles of Arabidopsis rosettes under various hypoxic conditions. We observed that hypoxia caused a significant increase in total amounts of phosphatidylserine, phosphatidic acid and oxidized lipids, but a decrease in phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Particularly, significant gains in the polyunsaturated species of PC, PE and phosphatidylinositol, and losses in their saturated and mono-unsaturated species were evident during hypoxia. Moreover, hypoxia led to a remarkable elevation of ceramides and hydroxyceramides. Disruption of ceramide synthases LOH1, LOH2 and LOH3 enhanced plant sensitivity to dark submergence, but displayed more resistance to submergence under light than wild type. Consistently, levels of unsaturated very-long-chain (VLC) ceramide species (22:1, 24:1 and 26:1) predominantly declined in the loh1, loh2 and loh3 mutants under dark submergence. In contrast, significant reduction of VLC ceramides in the loh1-1 loh3-1 knockdown double mutant and lacking of VLC unsaturated ceramides in the ads2 mutants impaired plant tolerance to both dark and light submergences. Evidence that C24:1-ceramide interacted with recombinant CTR1 protein and inhibited its kinase activity in vitro, enhanced ER-to-nucleus translocation of EIN2-GFP and stabilization of EIN3-GFP in vivo, suggests a role of ceramides in modulating CTR1-mediated ethylene signaling. The dark submergence-sensitive phenotypes of loh mutants were rescued by a ctr1-1 mutation. Thus, our findings demonstrate that unsaturation of VLC ceramides is a protective strategy for hypoxic tolerance in Arabidopsis.

Arabidopsis acyl-CoA-binding protein ACBP3 participates in plant response to hypoxia by modulating very-long-chain fatty acid metabolism.

In Arabidopsis thaliana, acyl-CoA-binding proteins (ACBPs) are encoded by a family of six genes (ACBP1 to ACBP6), and are essential for diverse cellular activities. Recent investigations suggest that the membrane-anchored ACBPs are involved in oxygen sensing by sequestration of group VII ethylene-responsive factors under normoxia. Here, we demonstrate the involvement of Arabidopsis ACBP3 in hypoxic tolerance. ACBP3 transcription was remarkably induced following submergence under both dark (DS) and light (LS) conditions. ACBP3-overexpressors (ACBP3-OEs) showed hypersensitivity to DS, LS and ethanolic stresses, with reduced transcription of hypoxia-responsive genes as well as accumulation of hydrogen peroxide in the rosettes. In contrast, suppression of ACBP3 in ACBP3-KOs enhanced plant tolerance to DS, LS and ethanol treatments. By analyses of double combinations of OE-1 with npr1-5, coi1-2, ein3-1 as well as ctr1-1 mutants, we observed that the attenuated hypoxic tolerance in ACBP3-OEs was dependent on NPR1- and CTR1-mediated signaling pathways. Lipid profiling revealed that both the total amounts and very-long-chain species of phosphatidylserine (C42:2- and C42:3-PS) and glucosylinositolphosphorylceramides (C22:0-, C22:1-, C24:0-, C24:1-, and C26:1-GIPC) were significantly lower in ACBP3-OEs but increased in ACBP3-KOs upon LS exposure. By microscale thermophoresis analysis, the recombinant ACBP3 protein bound VLC acyl-CoA esters with high affinities in vitro. Further, a knockout mutant of MYB30, a master regulator of very-long-chain fatty acid (VLCFA) biosynthesis, exhibited enhanced sensitivities to LS and ethanolic stresses, phenotypes that were ameliorated by ACBP3-RNAi. Taken together, these findings suggest that Arabidopsis ACBP3 participates in plant response to hypoxia by modulating VLCFA metabolism.

Bidirectional associations and a causal mediation analysis between depressive symptoms and chronic digestive diseases: A longitudinal investigation.

BACKGROUND: Chronic digestive diseases (CDDs) and depression shared major pathogeneses. We aimed to prospectively examine the bidirectional incidence associations between depressive symptoms and CDDs and explore biologically and behaviorally relevant mediators in the bidirectional associations. METHODS: Multivariable-adjusted Cox proportional hazard models were used to examine baseline depressive symptoms in relation to incident CDDs among 10,974 adults and the relation of baseline CDDs with new-onset elevated depressive symptoms among 7489 participants in the China Health and Retirement Longitudinal Study of nationally representative middle-aged and older adults. Elevated depressive symptoms were defined as the 10-item Center for Epidemiologic Studies Depression scale (CES-D-10) score at or higher than 10 and CDDs (except for tumor and cancer) were determined by self-reported physician diagnoses. Causal mediation analysis was performed to assess the mediated effects of a priori selected blood biomarkers and lifestyle factors in the bidirectional associations. RESULTS: Prevalence of elevated depressive symptoms and nonmalignant CDDs at baseline was 33.05 % and 17.8 % respectively. During a mean of 5.47 years of follow-up, elevated depressive symptoms significantly increased hazard of CDDs by 1.66 folds (95%CI = 1.49-1.84). Having CDDs at baseline was associated with a 27 % (95%CI = 16 %-39 %) increased hazard of developing elevated depressive symptoms. Shorter sleeping duration at night nominally significantly mediated 8.76 % of the association between depressive symptoms and incident CDDs while no significant mediators were identified in the converse association. LIMITATIONS: Limited mediator information and inadequately long follow-up may reduce chance of identifying significant mediators. CONCLUSIONS: Depressive symptoms and CDDs were mutual independent risk factors. Early screening and management of depressive symptoms and sleep disturbance are suggested in the prevention of CDDs and related comorbidities.

Causal relationships of excessive daytime napping with atherosclerosis and cardiovascular diseases: a Mendelian randomization study.

STUDY OBJECTIVES: Previous observational studies have found conflicting evidence on the relationship between daytime napping and incident cardiovascular diseases (CVDs), but it remains unclear whether these associations present causality. This study aims to verify whether and why there is a causal relationship between these parameters, and whether there is an etiological basis. METHODS: A two-sample Mendelian randomization analysis was performed using 79 single nucleotide polymorphisms associated with daytime napping. Summary-level data for coronary atherosclerosis, peripheral atherosclerosis, total CVD, and five CVD outcomes were obtained from the FinnGen study. Meta-analyses were aimed at investigating the relationships of excessive daytime napping with total CVD, coronary heart disease, myocardial infarction (MI), and stroke incidence. Subgroup, network meta-analysis (NMA) and trial sequential analysis (TSA) were also performed in this study. RESULTS: The inverse-variance weighted method demonstrated that a genetic predisposition to more frequent daytime napping was significantly associated with higher odds of coronary atherosclerosis (odds ratio [OR] = 1.55, 95% confidence interval [CI]: 1.11 to 2.17), MI (OR = 1.63, 95% CI: 1.06 to 2.50), and heart failure (OR = 1.80, 95%CI: 1.28 to 2.52). In NMA, an increased risk of developing CVD in people who napped for more than 60 min a day than those who did not nap was demonstrated and then supported by TSA results (summary relative risk = 1.98, 95% CI: 1.39 to 2.82). CONCLUSION: Habitual daytime napping is causally associated with an increased risk of incident CVD primarily via the development of coronary atherosclerosis. An average napping duration of more than 60 min is associated with an elevated risk of CVD in all participants.

Diet Quality and Mortality among Chinese Adults: Findings from the China Health and Nutrition Survey.

The association between diet quality and all-cause mortality in Chinese population is unclear. We aimed to study the associations of three a priori diet quality indices-including the Diet Quality Index-International (DQI-I), Chinese Healthy Eating Index (CHEI), and energy-adjusted Dietary Inflammatory Index (E-DII)-and their included components with all-cause mortality. We used baseline data from the 2004, 2006, 2009, and 2011 waves of the China Health and Nutrition Survey (CHNS). We used a multivariable-adjusted Cox model to examine the associations between DQI-I, CHEI, and E-DII with all-cause mortality. During a mean of 7 years of follow-up, a total of 461 deaths occurred among 12,914 participants. For DQI-I, there were significant inverse associations with mortality for the variety score (HRQ4 vs. Q1 = 0.69, 95%CI = 0.52-0.92) and overall balance score (HR>0 vs. 0 = 0.81, 95%CI = 0.66-0.91). The adequacy score of CHEI was associated with 40% less risk of all-cause mortality (HRQ4 vs. Q1 = 0.60, 95%CI = 0.43-0.84). E-DII was not associated with mortality. An estimated 20.1%, 13.9%, and 31.3% of total mortality would be averted if the DQI-I variety score, DQI-I overall balance score, and CHEI adequacy score improved from the bottom to the top quartile, respectively. Improving diet quality, especially improving diet variety and adequacy, and having a more balanced diet may reduce all-cause mortality in Chinese adults.

The Isocaloric Substitution of Plant-Based and Animal-Based Protein in Relation to Aging-Related Health Outcomes: A Systematic Review.

Plant-based and animal-based protein intake have differential effects on various aging-related health outcomes, but less is known about the health effect of isocaloric substitution of plant-based and animal-based protein. This systematic review summarized current evidence of the isocaloric substitutional effect of plant-based and animal-based protein on aging-related health outcomes. PubMed and Embase databases were searched for epidemiologic observational studies published in English up to 15 March 2021. Studies that included adults ≥18 years old; use of a nutritional substitution model to define isocaloric substitution of plant protein and animal protein; health outcomes covering mortality, aging-related diseases or indices; and reported association estimates with corresponding 95% confidence intervals were included. Nine cohort studies and 3 cross-sectional studies were identified, with a total of 1,450,178 subjects included in this review. Consistent and significant inverse association of substituting plant protein for various animal proteins on all-cause mortality was observed among 4 out of 5 studies with relative risks (RRs) from 0.54 to 0.95 and on cardiovascular disease (CVD) mortality among all 4 studies with RRs from 0.58 to 0.91. Among specific animal proteins, the strongest inverse association on all-cause and CVD mortality was identified when substituting plant protein for red and/or processed meat protein, with the effect mainly limited to bread, cereal, and pasta protein when replacing red meat protein. Isocaloric substitution of plant-based protein for animal-based protein might prevent all-cause and CVD-specific mortality. More studies are needed on this topic, particularly for cancer incidence and other specific aging-related diseases.

Depressive symptoms and chronic lung disease in middle-aged and older Chinese adults: Prospective bidirectional association and mediation analysis.

BACKGROUND: We investigated the prospective bidirectional association between depressive symptoms and chronic lung disease (CLD) and explored biologically and behaviorally relevant mediators in this bidirectional association among Chinese middle-aged and older population in the China Health and Retirement Longitudinal Study. METHODS: Multivariable-adjusted Cox proportional hazard models were used to examine baseline depressive symptoms in relation to incident CLD risk among 12,546 adults and examine CLD condition in association with incidence of elevated depressive symptoms among 6,929 participants from 2011 to 2018. Elevated depressive symptoms were assessed with the 10-item Center for Epidemiologic Studies Depression scale and CLD was determined by self-reported physician diagnosis. Causal mediation analysis was performed to examine the direct and indirect effects of a priori selected nine blood biomarkers and four lifestyle factors in the bidirectional association. RESULTS: Elevated depressive symptoms significantly increased CLD risk by 68% (HR=1.68, 95%CI=1.46-1.93) after a mean follow-up of 5.9 years and the strong positive association was consistently shown in almost all the subgroups. Having positive CLD status at baseline was associated with 17% increased risk of developing elevated depressive symptoms (HR=1.17, 95%CI=1.01-1.35) during an average of 4.6 years follow-up period. Significant inflammatory, metabolic or pulmonary function related mediators were not identified. LIMITATIONS: Inadequate follow-up time and limited mediator variable information may reduce chance of identifying significant mediators. CONCLUSIONS: Elevated depressive symptoms and CLD were mutual risk factors in middle-aged and older Chinese adults. Early screening and treatment of depression is needed to reduce CLD risk and related comorbidities including new-onset depression so as to relieve substantial disease burdens of CLD and depression in China.