Discovery of Orally Active Phenylquinoline-Based Soluble Epoxide Hydrolase Inhibitors with Anti-Inflammatory and Analgesic Activity.

Currently, there are no specific drugs for treating acute pancreatitis. Soluble epoxide hydrolase (sEH) inhibitors show promise, but face challenges like low blood drug concentrations and potential adverse effects on CYP enzymes and the human ether-a-go-go-related gene (hERG). In this study, an approach involving scaffold hopping and structure-activity guided optimization was employed to design a series of phenylquinoline-based sEH inhibitors. Among these compounds, DJ-53 exhibited potent in vitro and in vivo effects in alleviating pain and reducing inflammation. The in vivo mechanism of action involved inhibiting sEH enzyme activity, thereby increasing levels of anti-inflammatory epoxyeicosatrienoic acids (EETs) and decreasing levels of proinflammatory dihydroxyeicosatrienoic acids (DHETs). Importantly, DJ-53 showed exceptional oral bioavailability and pharmacokinetics, while avoiding inhibition of CYP enzymes or the hERG channel. These results highlight DJ-53's potential as a new lead compound for anti-inflammatory and analgesic applications and provide a safe and effective scaffold for developing sEH inhibitors.

Discovery of glycosidated glycyrrhetinic acid derivatives: Natural product-based soluble epoxide hydrolase inhibitors.

There are few reports on soluble epoxide hydrolase (sEH) structure-activity relationship studies using natural product-based scaffolds. In this study, we discovered that C-30 urea derivatives of glycyrrhetinic acid such as 33, rather than C-20/C-3 urea derivatives, possess in vitro sEH inhibitory capabilities. Furthermore, we explored the impact of stereoconfigurations at C-3 and C-18 positions, and glycosidic bonds at the 3-OH on the compound's activity. Consequently, a glycoside of 33, specifically 49Cα containing alpha-oriented mannose, exhibited promising in vivo efficacy in alleviating carrageenan-induced paw edema and acetic acid-induced writhing. Meanwhile, 49Cα demonstrated potential in mitigating acute pancreatitis by modulating the ratios of anti-inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory dihydroxyeicosatrienoic acids (DHETs). The co-crystal structure of sEH in complex with 49Cα revealed that the N-tetrahydropyranylmethylene urea hydrogen bonded with the residues within the sEH tunnel, contrasting with the mannose component that extended beyond the tunnel's confines. Our findings highlight 49Cα (coded LQ-38) as a promising candidate for anti-inflammatory and analgesic effects, and pave the way for the future rational design of triterpenoid-based sEH inhibitors.

Association between dietary vitamin A intake and risk of cardiometabolic multimorbidity.

The association between vitamin A and single cardiometabolic diseases has been extensively studied, but the relationship between dietary vitamin A intake and the risk of cardiometabolic multimorbidity (CMM) has not been studied. Therefore, the present study was conducted to explore the association with CMM risk by analyzing different sources of vitamin A. This study utilized 13,603 subjects aged ≥ 18 years from 1997 to 2015 from the China Health and Nutrition Survey (CHNS). Dietary intake was calculated from 3 consecutive 24-h dietary recalls combined with a house hold food inventory. CMM is defined as the development of at least two cardiometabolic diseases. After a median follow-up of 9.0 years, there were 1050 new cases of CMM. The risk of CMM was significantly lower in those with higher vitamin A intake (Q1 vs Q5 HR 0.66, 95% CI 0.54-0.81). ß-carotene (Q1 vs Q5 HR 0.82, 95% CI 0.66-1.02) and retinol (Q1 vs Q5 HR 0.59, 95% CI 0.48-0.73) intake had a similarly negative correlation. Using restricted cubic spline found an L-shaped relationship between retinol intake and CMM (p non-linear < 0.001). Negative associations were also found in specific CMD groups (hypertension, cardiovascular disease, stroke and diabetes). Dietary intake of vitamin A was negatively associated with CMM risk, and this protective effect was more pronounced in patients with cardiovascular disease. There was an L-shaped association between retinol intake and CMM risk.

Association between Dietary Total Vitamin A, ß-carotene, and Retinol Intake and Risk of cardiometabolic multimorbidity: Results from the China Health and Nutrition Survey, 1997-2015.

Background: The association between vitamin A and single cardiometabolic diseases has been extensively studied, but the relationship between dietary vitamin A intake and the risk of cardiometabolic multimorbidity (CMM) has not been studied. Therefore, the present study was conducted to explore the association with CMM risk by analyzing different sources of vitamin A. Methods: This study utilized 13,603 subjects aged ≥ 18 years from 1997-2015 from the China Health and Nutrition Survey (CHNS). Dietary intake was calculated from 3 consecutive 24-h dietary recalls combined with a house hold food inventory. CMM is defined as the development of at least two cardiometabolic diseases. Results: After a median follow-up of 9.1 years, there were 1050 new cases of CMM. The risk of CMM was significantly lower in those with higher vitamin A intake (Q1 vs Q5 HR 0.66, 95% CI 0.54-0.81). ß-carotene (Q1 vs Q5 HR 0.82, 95% CI 0.66-1.02) and retinol (Q1 vs Q5 HR 0.59, 95%CI 0.48-0.73) intake had a similarly negative correlation. Using restricted cubic spline found an L-shaped relationship between retinol intake and CMM (p non-linear < 0.001). In subgroup analyses, protective effects were stronger for participants aged ≥ 44 years (HR 0.72, 95%CI 0.57-0.92) and for the female group (HR 0.62, 95%CI 0.45-0.84). Conclusion: Dietary vitamin A was a protective factor for CMM, and this effect was stronger in age ≥ 44 years and in the female group. There was a ceiling effect on the protective effect of retinol intake on the risk of CMM.

Association between dietary inflammatory index and gallstones in US adults.

Introduction: Previous studies have found that diet's inflammatory potential is related to various diseases. However, little is known about its relationship with gallstones. The present study aims to investigate the relationship between dietary inflammatory index (DII) and gallstones. Methods: Data were obtained from the 2003-2020 National Health and Nutrition Examination Survey (NHANES). We used the nearest neighbor propensity score matching (PSM) with a ratio of 1:1 to reduce selection bias. Logistic regression models estimated the association between DII and gallstones. The non-linear relationship was explored with restricted cubic splines (RCS). BMI subgroup stratification was performed to explore further the connection between DII and gallstones in different populations. Results: 10,779 participants were included. Before and after PSM, gallstone group individuals had higher DII scores than non-gallstone group individuals (p < 0.05). Matched logistic regression analysis showed that DII scores were positively correlated with gallstone risk (adjusted OR = 1.14, 95% CI 1.01, 1.29). The stratified analysis showed that this association was stronger in overweight or obese people (adjusted OR = 1.18, 95% CI 1.03, 1.34). RCS analysis suggested that DII and gallstones showed a "J"-shaped non-linear dose-response relationship (p non-linear <0.001). Conclusion: Higher DII score is positively associated with the risk of gallstones, particularly in overweight or obese population, and this relationship is a "J"-shaped non-linear relationship. These results further support that avoiding or reducing a pro-inflammatory diet can be an intervention strategy for gallstone management, particularly in the overweight or obese population.

Association between indoor air pollution and depression: a systematic review and meta-analysis of cohort studies.

OBJECTIVES: Incomplete combustion of solid fuel and exposure to secondhand smoke (SHS) are the primary causes of indoor air pollution (IAP), potentially leading to detrimental effects on individual mental health. However, current evidence regarding the association between IAP and depression remains inconclusive. This study aims to systematically investigate the evidence regarding the association between IAP and the risk of depression. DESIGN: Systematic review and meta-analysis of cohort studies. DATA SOURCES: Two independent reviewers searched PubMed, the Cochrane Library, Web of Science and EMBASE for available studies published up to 13 January 2024. ELIGIBILITY CRITERIA: We included all cohort studies published in English that aimed to explore the relationship between IAP from solid fuel use and SHS exposure and the risk of depression. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the risk of bias. The association between IAP and depression was calculated using pooled relative risk (RR) with 95% CIs. Heterogeneity was assessed using the I2 value, and the effect estimates were pooled using fixed-effects or random-effects models depending on the results of homogeneity analysis. RESULTS: We included 12 articles with data from 61 217 participants. The overall findings demonstrated a significant association between IAP exposure and depression (RR=1.22, 95% CI: 1.13 to 1.31), although with substantial heterogeneity (I2=75%). Subgroup analyses based on pollutant type revealed that IAP from solid fuel use was associated with a higher risk of depression (RR=1.20, 95% CI: 1.13 to 1.26; I2=62%; 5 studies, 36 768 participants) than that from SHS exposure (RR=1.11, 95% CI: 0.87 to 1.41; I2=80%; 7 studies, 24 449 participants). In terms of fuel use, the use of solid fuel for cooking (RR: 1.23, 95% CI: 1.16 to 1.31; I2=58%; 4 studies, 34 044 participants) and heating (RR 1.15, 95% CI: 1.04 to 1.27; I2=65%; 3 studies, 24 874 participants) was associated with increased depression risk. CONCLUSIONS: The findings from this systematic review and meta-analysis of cohort studies indicated an association between exposure to IAP and depression. PROSPERO REGISTRATION NUMBER: CRD42022383285.

The mediating role of children's intergenerational support in association between grandparenting and cognitive function among middle-aged and older Chinese: findings from the CHARLS cohort study.

OBJECTIVES: With the world's population increasing in age, there has been a significant rise in the prevalence of cognitive impairment and dementia among individuals. This study aims to investigate the association between grandparenting and cognitive function among middle-aged and older Chinese using data from 2011 to 2018 China Health and Retirement Longitudinal Study (CHARLS). Additionally, the study seeks to explore the potential mediating effect of intergenerational support from children on this relationship, using data from the CHARLS 2011 database. METHODS: 5254 participants were recruited at the baseline survey in CHARLS 2011. Subsequently, a follow-up survey was conducted over 8 years, from CHARLS 2011 to 2018, with 1472 individuals completing the follow-up survey. The CHARLS included surveys on grandparenting and cognitive assessments. Grandparenting was categorized as yes and no. The assessment of cognitive function involved the evaluation of episodic memory and mental intactness. The present study used cross-sectional and longitudinal analyses to examine the relationship between grandparenting and cognitive function. The bootstrap method assessed the mediating effect of children's intergenerational support. RESULTS: The results of both cross-sectional and longitudinal studies indicated a positive association between grandparenting and cognitive function in middle-aged and older Chinese (B = 0.138, p < 0.05; B = 0.218, p < 0.05). Children's emotional and economic support played intermediary roles between grandparenting and cognitive function. CONCLUSION: The results emphasized the significance of policymakers considering the consequences of intergenerational care and family support when formulating and executing social service policies targeted at the middle-aged and older population in China.

Mobile phone problem use and depressive symptoms: the mediating role of social support and attitude to aging among Chinese older adults.

BACKGROUND: Little is known about mobile phone problem use (MPPU) among older adults. This study investigated critical factors affecting MPPU and filled the gap between MPPU and depressive symptoms in older people. METHODS: A cross-sectional study was conducted in community (n = 376) with questionnaires of Multidimensional Scale of Perceived Social Support (MSPSS), Geriatric Depression Scale (GDS-15), Attitudes to Aging Questionnaire (AAQ) and Mobile Phone Problem Use Scale (MPPUS). RESULTS: 80.9% of older people used smartphones and spend less than three hours on mobile phone per day. The average MPPU score of Chinese elderly is greater than the cut off to 41. Female (ß = -0.11, P = 0.037), living with spouse (ß = -0.17, P = 0.03), and late marriage age (ß = -0.16, P = 0.007) are less likely to develop MPPU. The relationship between MPPU and depressive symptoms was partially mediated by social support and attitude to aging. CONCLUSION: Elderly people generally have higher MPPU scores. MPPU was associated with depressive symptoms, through social support and attitude to aging.

Association between physical frailty, circadian syndrome and cardiovascular disease among middle-aged and older adults: a longitudinal study.

BACKGROUND: Physical frailty (PF) and circadian syndrome (CircS) are proposed as novel risks for cardiovascular disease (CVD), but little attention is paid to their combined impact on CVD. This study aimed to investigate the association of PF, CircS and CVD in middle-aged and older adults. METHODS: The sample comprised 8512 participants aged at least 45 years from the China Health and Retirement Longitudinal Study (CHARLS) 2011. PF was examined by the physical frailty phenotype scale. CircS was assessed by the components of the International Diabetes Federation (IDF) MetS plus short sleep duration and depression. The cut-off for CircS was set as ≥ 4. CVD was defined as the presence of physician-diagnosed heart disease and/or stroke. A total of 6176 participants without CVD recruited from CHARLS 2011 and were followed up in 2018. RESULTS: The prevalence of CVD in total populations, neither CircS or PF, PF alone, CircS alone and both CircS and PF were 13.0%, 7.4%, 15.5%, 17.4%, and 30.2%, respectively. CircS was more likely to be PF [OR (95%CI): 2.070 (1.732 ∼ 2.472)] than those without CircS. Both CircS alone [OR (95% CI): 1.954 (1.663 ∼ 2.296)], and coexisting CircS and PF [3.508 (2.739 ∼ 4.494)] were associated with CVD. Longitudinal analysis showed that individuals with both CircS and PF (HR: 1.716, 95%CI: 1.314 ∼ 2.240) and CircS alone [1.520 (1.331 ∼ 1.737)] were more likely to have new onset CVD than neither CircS or PF peers. CONCLUSION: PF and CircS together are associated with higher CVD risk, which provided new evidence for a strong relation that warrants attention to assessing PF and CircS and in community to promote healthy aging.

Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there is currently a lack of reliable diagnostic biomarkers. This meta-analysis aimed to evaluate CHIT1, CHI3L1, and CHI3L2 levels in the cerebrospinal fluid (CSF) or blood and their diagnostic potential in ALS patients. A systematic, comprehensive search was performed of peer-reviewed English-language articles published before April 1, 2023, in PubMed, Scopus, Embase, Cochrane Library, and Web of Science. After a thorough screening, 13 primary articles were included, and their chitinases-related data were extracted for systematic review and meta-analysis. In ALS patients, the CSF CHIT1 levels were significantly elevated compared to controls with healthy control (HC) (SMD, 1.92; 95% CI, 0.78 - 3.06; P < 0.001). CHIT1 levels were elevated in the CSF of ALS patients compared to other neurodegenerative diseases (ONDS) control (SMD, 0.74; 95% CI, 0.22 - 1.27; P < 0.001) and exhibited an even more substantial increase when compared to ALS-mimicking diseases (AMDS) (SMD, 1.15; 95% CI, 0.35 - 1.94, P < 0.001). Similarly, the CSF CHI3L1 levels were significantly higher in ALS patients compared to HC (SMD, 3.16; 95% CI, 1.26 - 5.06, P < 0.001). CHI3L1 levels were elevated in the CSF of ALS patients compared to ONDS (SMD, 0.75; 95% CI, 0.32 - 1.19; P = 0.017) and exhibited a more pronounced increase when compared to AMDS (SMD, 1.92; 95% CI, 0.41 - 3.42; P < 0.001). The levels of CSF chitinases in the ALS patients showed a significant increase, supporting the role of CSF chitinases as diagnostic biomarkers for ALS.

Discovery of a novel lead characterized by a stilbene-extended scaffold against sepsis as soluble epoxide hydrolase inhibitors.

Recently, some inhibitors of soluble epoxide hydrolase (sEH) showed limited potential in treating sepsis by increasing survival time, but they have unfortunately failed to improve survival rates. In this study, we initially identified a new hit 11D, belonging to a natural skeleton known as stilbene and having an IC50 of 644 nM on inhibiting murine sEH. Natural scaffold-based sEH inhibitors are paid less attention. A combination of structure-activity relationships (SARs)-guided structural optimization and computer-aided skeleton growth led to a highly effective lead compound 70P (IC50: 4.0 nM). The dose-response study indicated that 70P (at doses of 0.5-5 mg/kg, ip.) significantly increased survival rates and survival time by reducing the levels of the inflammatory factors TNF-α and IL-6 in the liver. Interestingly, 70P exhibited much higher accumulation in the liver than in plasma (AUC ratio: 175). In addition, 70P exhibits equal IC50 value (1.5 nM) on inhibiting human sEH as EC5026 (1.7 nM). In conclusion, the natural scaffold-extended sEH inhibitor 70P has the potential to become a new promising lead for addressing the unmet medical need in sepsis treatment, which highlighted the importance of natural skeleton in developing sEH inhibitors.

Effectiveness of Telecare Interventions on Depression Symptoms Among Older Adults: Systematic Review and Meta-Analysis.

BACKGROUND: Depression is the most common psychiatric disorder among older adults. Despite the effectiveness of pharmacological and psychological therapies, many patients with late-life depression (LLD) are unable to access timely treatment. Telecare has been shown to be effective in addressing patients' psychosocial issues, while its effectiveness in serving patients with LLD remains unclear. OBJECTIVE: This study aimed to evaluate the effectiveness of telecare in reducing depression and anxiety symptoms and improving quality of life (QoL) in patients with LLD. METHODS: Databases including the Cochrane Library, Web of Science, PubMed, Embase, and EBSCO were searched for randomized controlled trials (RCTs) evaluating the effectiveness of telecare for LLD from database establishment to December 28, 2022. RESULTS: A total of 12 RCTs involving 1663 participants were identified in this study. The meta-analysis showed that (1) telecare significantly reduced depressive symptoms in patients with LLD compared to those in usual care (UC; standardized mean difference [SMD]=-0.46, 95% CI -0.53 to -0.38; P<.001), with the best improvement observed within 3 months of intervention (SMD=-0.72, 95% CI -1.16 to -0.28; P<.001); (2) other scales appeared more effective than the Patient Health Questionnaire-9 for LLD in telecare interventions (SMD=-0.65, 95% CI -0.96 to -0.35; P<.001); (3) telecare was more effective than telephone-based interventions for remote monitoring of LLD (SMD=-1.13, 95% CI -1.51 to -0.76; P<.001); (4) the reduction of depressive symptoms was more pronounced in patients with LLD with chronic conditions (SMD=-0.67, 95% CI -0.89 to -0.44; P<.001); (5) telecare was more effective for LLD in Europe and the Americas than in other regions (SMD=-0.73, 95% CI -0.99 to -0.47; P<.001); (6) telecare significantly reduced anxiety symptoms in patients with LLD (SMD=-0.53, 95% CI -0.73 to -0.33; P=.02); and (7) there was no significant improvement in the psychological components of QoL in patients with LLD compared to those receiving UC (SMD=0.30, 95% CI 0.18-0.43; P=.80). CONCLUSIONS: Telecare is a promising modality of care for treatment, which can alleviate depression and anxiety symptoms in patients with LLD. Continued in-depth research into the effectiveness of telecare in treating depression could better identify where older patients would benefit from this intervention.

Enhancing HIF-1α-P2X2 signaling in dorsal raphe serotonergic neurons promotes psychological resilience.

Major depressive disorder (MDD) is a devastating condition. Although progress has been made in the past seven decades, patients with MDD continue to receive an inadequate treatment, primarily due to the late onset of first-line antidepressant drugs and to their acute withdrawal symptoms. Resilience is the ability to rebound from adversity in a healthy manner and many people have psychological resilience. Revealing the mechanisms and identifying methods promoting resilience will hopefully lead to more effective prevention strategies and treatments for depression. In this study, we found that intermittent hypobaric hypoxia training (IHHT), a method for training pilots and mountaineers, enhanced psychological resilience in adult mice. IHHT produced a sustained antidepressant-like effect in mouse models of depression by inducing long-term (up to 3 months after this treatment) overexpression of hypoxia-inducible factor (HIF)-1α in the dorsal raphe nucleus (DRN) of adult mice. Moreover, DRN-infusion of cobalt chloride, which mimics hypoxia increasing HIF-1α expression, triggered a rapid and long-lasting antidepressant-like effect. Down-regulation of HIF-1α in the DRN serotonergic (DRN5-HT) neurons attenuated the effects of IHHT. HIF-1α translationally regulated the expression of P2X2, and conditionally knocking out P2rx2 (encodes P2X2 receptors) in DRN5-HT neurons, in turn, attenuated the sustained antidepressant-like effect of IHHT, but not its acute effect. In line with these results, a single sub-anesthetic dose of ketamine enhanced HIF-1α-P2X2 signaling, which is essential for its rapid and long-lasting antidepressant-like effect. Notably, we found that P2X2 protein levels were significantly lower in the DRN of patients with MDD than that of control subjects. Together, these findings elucidate the molecular mechanism underlying IHHT promoting psychological resilience and highlight enhancing HIF-1α-P2X2 signaling in DRN5-HT neurons as a potential avenue for screening novel therapeutic treatments for MDD.

Intermittent Hypobaric Hypoxia Ameliorates Autistic-Like Phenotypes in Mice.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and stereotyped behaviors. Although major advances in basic research on autism have been achieved in the past decade, and behavioral interventions can mitigate the difficulties that individuals with autism experience, little is known about the many fundamental issues of the interventions, and no specific medication has demonstrated efficiency for the core symptoms of ASD. Intermittent hypobaric hypoxia (IHH) is characterized by repeated exposure to lowered atmospheric pressure and oxygen levels, which triggers multiple physiological adaptations in the body. Here, using two mouse models of ASD, male Shank3B -/- and Fmr1 -/y mice, we found that IHH training at an altitude of 5,000 m for 4 h per day, for 14 consecutive days, ameliorated autistic-like behaviors. Moreover, IHH training enhanced hypoxia inducible factor (HIF) 1α in the dorsal raphe nucleus (DRN) and activated the DRN serotonergic neurons. Infusion of cobalt chloride into the DRN, to mimic IHH in increasing HIF1α expression or genetically knockdown PHD2 to upregulate HIF1α expression in the DRN serotonergic neurons, alleviated autistic-like behaviors in Shank3B -/- mice. In contrast, downregulation of HIF1α in DRN serotonergic neurons induced compulsive behaviors. Furthermore, upregulating HIF1α in DRN serotonergic neurons increased the firing rates of these neurons, whereas downregulation of HIF1α in DRN serotonergic neurons decreased their firing rates. These findings suggest that IHH activated DRN serotonergic neurons via upregulation of HIF1α, and thus ameliorated autistic-like phenotypes, providing a novel therapeutic option for ASD.

Association between pro-inflammatory diet and liver cancer risk: a systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to investigate the association between dietary inflammatory potential and liver cancer to provide evidence regarding scientific dietary health education. DESIGN: Systematic review and meta-analysis. SETTING: A comprehensive literature review was conducted to identify case-control or cohort studies that involved dietary inflammation index (DII)/empirical dietary inflammation pattern (EDIP) and liver cancer in PubMed, EMBASE, Cochrane, and Web of Science databases. Using a combination of DII/EDIP and liver cancer as the search terms, the associations between DII/EDIP and liver cancer were then assessed. PARTICIPANTS: Three case-control studies and two cohort studies were brought into the meta-analysis, with 225 713 enrolled participants. RESULTS: Meta-analysis of categorical variables showed that DII/EDIP in the highest category increased the risk of liver cancer compared to DII/EDIP in the lowest category (relative risk (RR) = 2·35; 95 % CI 1·77, 3·13; P = 0·000) and with low heterogeneity across studies (I2 = 40·8 %, P = 0·119). Meta-analysis of continuous variables showed that significant positive association between liver cancer and DII/EDIP scores (RR = 1·24; 95 % CI 1·09, 1·40; P = 0·001), and no heterogeneity (I² = 0·0 %, P = 0·471). Stratified according to the study design, there was a significant positive association between liver cancer and DII/EDIP scores in both cohort studies (RR = 2·16; 95 % CI 1·51, 3·07; P = 0·000) and case-control studies (RR = 2·75; 95 % CI 1·71, 4·41; P = 0·000). CONCLUSION: The higher the DII/EDIP score, the higher the risk of liver cancer. This finding may have prominent implications for the general population.

Exploring associations between social media addiction, social media fatigue, fear of missing out and sleep quality among university students: A cross-section study.

BACKGROUND: Social media use has been linked to poor sleep outcomes among university students in the cyber age, but the association between the negative consequences of social media use and sleep problems is not yet well understood. The present study investigated the relationships among social media usage, social media fatigue (SMF), fear of missing out (FoMO), social media addiction (SMA) and sleep quality in university students. METHOD: An online survey was administered to 2744 respondents that included the Pittsburgh Sleep Quality Index (PSQI); questionnaires evaluating FoMO, SMF, and SMA; and questions regarding sleep duration, social media use, health status, and demographic information. RESULT: A total of 19.9% of respondents suffered from sleep disturbance. A total of 15.6% of participants had sleep durations less than 5 h, and 21.6% of subjects had sleep durations longer than 9 h. Sleep quality was positively associated with SMF (OR = 1.387, 95% CI: 1.103~1.743), and SMA (OR = 1.415, 95% CI: 1.118~1.791). The relationship between FoMO and sleep disturbance was not significant. Compared to a sleep duration > 9 h, SMF increased the risk of shorter sleep durations [5-6 h sleep (OR = 2.226, 95% CI: 1.132~4.375), 6-7 h sleep (OR = 1.458, 95% CI: 1.061~2.002), and 7-8 h sleep (OR = 1.296, 95% CI: 1.007~1.670)]. FoMO and SMA did not significantly affect sleep duration. In addition, SMA (OR = 3.775, 95% CI: 3.141~4.537), FoMO (OR = 3.301, 95% CI: 2.753~3.958), and sleep disorders (OR = 1.284, 95% CI: 1.006~1.638) increased SMF. CONCLUSION: Upon experiencing negative consequences of social media use, such as SMF and SMA, university students were likely to experience sleep problems. Further research exploring the interventions that improve sleep and alleviate negative consequences of social media use should be conducted.

Abdominal obesity mediates the causal relationship between depression and the risk of gallstone disease: retrospective cohort study and Mendelian randomization analyses.

OBJECTIVE: Our study aimed to explore the causal effect of depression on the risk of gallstone disease, and the mediation effects of metabolic traits. METHODS: A retrospective cohort study on Chinese elderly from the Dongfeng-Tongji cohort (including 18,141 individuals) was conducted to estimate the adverse effect of probable depression on the risk of gallstone disease. Two-sample Mendelian randomization was performed in European and East-Asian ancestries, to verify the causal relationship between major depression and gallstone disease. We further applied two-step Mendelian randomization to explore the mediation effects of metabolic traits. RESULTS: In the cohort study, probable depression was associated with an increased risk of gallstone disease within 5 years, with RR (95% CI) of 1.33 (1.12, 1.58) in multivariable regression, and 1.34 (1.11, 1.61) following propensity score weighting. Bidirectional Mendelian randomization in European ancestry revealed a positive causal effect (OR: 1.21; 95% CI: 1.07 to 1.37) of genetically predicted major depression liability on gallstone disease, based on the inverse variance weighted method. Little evidence was presented from other complementary approaches, and the analysis in East-Asian ancestry (IVW estimated OR: 1.03; 95% CI: 0.92 to 1.15). The indirect effect via waist circumference and HDL-C were 1.06 (95% CI: 1.02 to 1.10) and 1.01 (95% CI: 1.00 to 1.01) respectively, which mediated 25.8% and 3.78% of the causal relationship. CONCLUSIONS: Our study suggested a higher risk of gallstone disease in the population with probable depression, while the two-sample Mendelian randomization provided weak evidence for the causal relationship, which was moderately mediated by abdominal obesity.

Association of cognitive frailty and abdominal obesity with cardiometabolic multimorbidity among middle-aged and older adults: A longitudinal study.

BACKGROUND: Cognitive frailty and abdominal obesity are deemed to be important targets for disease prevention. However, a possible cardiometabolic multimorbidity (CMM) link with cognitive frailty and abdominal obesity is unknown. The aim of this study was to investigate the association of cognitive frailty and abdominal obesity with CMM in the middle-aged and older people. METHODS: The sample comprised 11,503 participants aged 45 and over from the China Health and Retirement Longitudinal Study (CHARLS) 2011. Cognitive frailty was defined as the coexisting cognitive impairment and physical frailty. Abdominal obesity was assessed using waist circumference. CMM was defined as the presence of two or more cardiometabolic diseases (CMDs), including diabetes, heart disease, and stroke. A total of 9177 participants without CMM recruited from CHARLS 2011 and were followed up in 2018. RESULTS: Compared with 0 CMD, coexisting cognitive frailty and abdominal obesity was associated with the risk of 1 CMD (OR: 1.734, 95 % CI: 1.133-2.655), and ≥ 2 CMDs (OR: 7.218, 95%CI: 3.216-16.198). Longitudinal analysis showed that individuals with both cognitive frailty and abdominal obesity (HR: 2.162, 95%CI: 1.032-4.531) were more likely to have new onset CMM than cognitive frailty alone peers (HR: 1.667, 95 % CI: 0.721-3.853). Among the participants with first CMD, the likelihood of CMM was substantially higher in the co-existence of cognitive frailty and abdominal obesity (HR: 3.073, 95%CI: 1.254-7.527) than in the abdominal obesity alone (HR: 1.708, 95%CI: 1.201-2.427). Cognitive frailty alone was not significantly associated with CMM. CONCLUSION: Cognitive frailty is not independently associated with the risk of CMM, but cognitive frailty and abdominal obesity together has a greater risk of CMM.

Hepatic soluble epoxide hydrolase activity regulates cerebral Aß metabolism and the pathogenesis of Alzheimer's disease in mice.

Alzheimer's disease (AD) is caused by a complex interaction between genetic and environmental factors. However, how the role of peripheral organ changes in response to environmental stimuli during aging in AD pathogenesis remains unknown. Hepatic soluble epoxide hydrolase (sEH) activity increases with age. Hepatic sEH manipulation bidirectionally attenuates brain amyloid-ß (Aß) burden, tauopathy, and cognitive deficits in AD mouse models. Moreover, hepatic sEH manipulation bidirectionally regulates the plasma level of 14,15-epoxyeicosatrienoic acid (-EET), which rapidly crosses the blood-brain barrier and modulates brain Aß metabolism through multiple pathways. A balance between the brain levels of 14,15-EET and Aß is essential for preventing Aß deposition. In AD models, 14,15-EET infusion mimicked the neuroprotective effects of hepatic sEH ablation at biological and behavioral levels. These results highlight the liver's key role in AD pathology, and targeting the liver-brain axis in response to environmental stimuli may constitute a promising therapeutic approach for AD prevention.

Exploring associations between eHealth literacy, cyberchondria, online health information seeking and sleep quality among university students: A cross-section study.

Background: University students are increasingly inclined to use the Internet for health-related purposes, and their sleep problems are becoming increasingly prominent. Currently, the relationship between sleep quality and online health-related searches is poorly understood. The aim of this study was to exam the associations of sleep quality, Internet use, eHealth literacy, online health information seeking and cyberchondria in the sample of Chinese university students. Methods: A total of 2744 students completed self-reported questionnaires online containing the Pittsburgh Sleep Quality Index (PSQI), eHealth Literacy Scale, Online Health Information Seeking, Cyberchondria Severity Scale (CSS) and questions regarding sleep duration, Internet use, health status, and demographic information. Results: The prevalence of poor sleep quality (PSQI >7) among the university students was 19.9% and 15.6% students slept less than 7 h per day. As time spent on online daily and playing phone before bed increased, the prevalence of sleep disturbance gained. Sleep disturbance was significantly associated with cyberchondria (OR = 1.545, p = 0.001), health status [good (OR = 0.625, p = 0.039), poor (OR = 3.128, p = 0.010), and fair (OR = 1.932, p = 0.001)]. Sleep quality, online health information seeking and eHealth literacy positively influenced with cyberchondria. Compared to 7-8 h sleep duration, online health information seeking (OR = 0.750, p = 0.012) was significantly associated with ≥8 h sleep duration. Conclusion: Our findings highlighted poor health status, too much time spent on online daily and high cyberchondria level might decrease sleep quality in the sample of Chinese university students, further suggesting the need for developing interventions based on online health-related searches for improving sleep quality among university students.