A large study of metabolomics reveals common and distinct metabolic biomarkers for type 2 diabetes, coronary heart disease, and stroke.

We aimed at examining the shared and unique associations of metabolites with multiple cardiometabolic diseases (CMD), i.e. type 2 diabetes (T2D), coronary heart disease (CHD) and stroke. In this study, a total of 168 plasma metabolites were measured by targeted high-throughput nuclear magnetic resonance spectroscopy among 98,162 participants free of T2D, CHD, and stroke at baseline. Cox proportional hazard models estimated hazard ratios for one SD increase in metabolite concentration levels, and false discovery rate (at 10%) was used to correct for multiple comparisons. Over 12.1 years of follow-up on average, 3,463 T2D, 6,186 CHD, and 1,892 stroke events were recorded. Most lipoprotein metabolites were associated with risks of T2D and CHD but not with the risk of stroke, with stronger associations for T2D than for CHD. Phospholipids within intermediate-density lipoprotein or large low-density lipoprotein particles showed positive associations with CHD and inverse associations with T2D. Metabolites indicating very small very low-density lipoprotein, histidine, creatinine, albumin, and glycoprotein acetyls were associated with risks of all three conditions. This large-scale metabolomics study revealed common and distinct metabolic biomarkers for T2D, CHD and stroke, providing instrumental information to possibly implement precision medicine for preventing and treating these conditions.

Heterodimers of Aromadendrane Sesquiterpenoid with Benzoquinone from the Chinese Liverwort Mylia nuda.

Mylnudones A-G (1-7), unprecedented 1,10-seco-aromadendrane-benzoquinone-type heterodimers, and a highly rearranged aromadendrane-type sesquiterpenoid (8), along with four known analogs (9-12), were isolated from the liverwort Mylia nuda. Compounds 1-6 and 7, bearing tricyclo[6.2.1.02,7] undecane and tricyclo[5.3.1.02,6] undecane backbones, likely formed via a Diels-Alder reaction and radical cyclization, respectively. Their structures were determined by spectroscopic analysis, computational calculation, and single-crystal X-ray diffraction analysis. Dimeric compounds displayed cytoprotective effects against glutamic acid-induced neurological deficits.

Associations of liver function with plasma biomarkers for Alzheimer's Disease.

BACKGROUND: Blood-based biomarkers for Alzheimer's disease (AD) are promising to be used in clinical settings. The liver is an important degradation organ of the body. Whether liver function affects the levels of AD biomarkers needs to be studied. OBJECTIVE: To investigate the associations between liver function and the plasma levels of AD biomarkers. METHODS: We conducted an ADNI cohort-based cross-sectional study. Thirteen liver function markers commonly used in clinical settings were analyzed: total protein (TP), albumin (AL), globulin (GL), AL/GL ratio (A/G), total bilirubin (TB), direct bilirubin (DB), indirect bilirubin (IB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyltransferase (GGT). Liquid chromatography-tandem mass spectrometry was used to detect the plasma Aß42 and Aß40 concentrations. Single Molecule array technique was used to measure the plasma p-tau181 and NfL concentrations. We used linear regression models to analyze the associations between liver function markers and the levels of AD plasma biomarkers. RESULTS: ALP was positively associated with the levels of plasma Aß42 (ß = 0.16, P = 0.018) and Aß40 (ß = 0.21, P = 0.004). LDH was positively associated with the levels of plasma p-tau181 (ß = 0.09, P = 0.022). While NfL was correlated with multiple liver function markers, including AL, A/G, ALT, AST/ALT, and LDH. CONCLUSION: Liver function was associated with the plasma levels of AD biomarkers. It needs to consider the potential influence of liver function on the reference ranges and the interpretation of results for AD biomarkers before clinical use.

Global, regional, and national burden of cardiovascular diseases in youths and young adults aged 15-39 years in 204 countries/territories, 1990-2019: a systematic analysis of Global Burden of Disease Study 2019.

BACKGROUND: Understanding the temporal trends in the burden of overall and type-specific cardiovascular diseases (CVDs) in youths and young adults and its attributable risk factors is important for effective and targeted prevention strategies and measures. We aimed to provide a standardized and comprehensive estimation of the prevalence, incidence, disability-adjusted life years (DALY), and mortality rate of CVDs and its associated risk factors in youths and young adults aged 15-39 years at global, regional, and national levels. METHODS: We applied Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 analytical tools to calculate the age-standardized incidence, prevalence, DALY, and mortality rate of overall and type-specific CVDs (i.e., rheumatic heart disease, ischemic heart disease, stroke, hypertensive heart disease, non-rheumatic valvular heart disease, cardiomyopathy and myocarditis, atrial fibrillation and flutter, aortic aneurysm, and endocarditis) among youths and young adults aged 15-39 years by age, sex, region, sociodemographic index and across 204 countries/territories from 1990 to 2019, and proportional DALY of CVDs attributable to associated risk factors. RESULTS: The global age-standardized DALY (per 100,000 population) for CVDs in youths and young adults significantly decreased from 1257.51 (95% confidence interval 1257.03, 1257.99) in 1990 to 990.64 (990.28, 990.99) in 2019 with an average annual percent change (AAPC) of - 0.81% (- 1.04%, - 0.58%, P < 0.001), and the age-standardized mortality rate also significantly decreased from 19.83 (19.77, 19.89) to 15.12 (15.08, 15.16) with an AAPC of - 0.93% (- 1.21%, - 0.66%, P < 0.001). However, the global age-standardized incidence rate (per 100,000 population) moderately increased from 126.80 (126.65, 126.95) in 1990 to 129.85 (129.72, 129.98) in 2019 with an AAPC of 0.08% (0.00%, 0.16%, P = 0.040), and the age-standardized prevalence rate significantly increased from 1477.54 (1477.03, 1478.06) to 1645.32 (1644.86, 1645.78) with an AAPC of 0.38% (0.35%, 0.40%, P < 0.001). In terms of type-specific CVDs, the age-standardized incidence and prevalence rate in rheumatic heart disease, prevalence rate in ischemic heart disease, and incidence rate in endocarditis increased from 1990 to 2019 (all P < 0.001). When stratified by sociodemographic index (SDI), the countries/territories with low and low-middle SDI had a higher burden of CVDs than the countries/territories with high and high-middle SDI. Women had a higher prevalence rate of CVDs than men, whereas men had a higher DALY and mortality rate than women. High systolic blood pressure, high body mass index, and low-density lipoprotein cholesterol were the main attributable risk factors for DALY of CVDs for all included countries and territories. Household air pollution from solid fuels was an additional attributable risk factor for DALY of CVDs in low and low-middle SDI countries compared with middle, high-middle, and high SDI countries. Compared with women, DALY for CVDs in men was more likely to be affected by almost all risk factors, especially for smoking. CONCLUSIONS: There is a substantial global burden of CVDs in youths and young adults in 2019. The burden of overall and type-specific CVDs varied by age, sex, SDI, region, and country. CVDs in young people are largely preventable, which deserve more attention in the targeted implementation of effective primary prevention strategies and expansion of young-people's responsive healthcare systems.

Handgrip strength is associated with risks of new-onset stroke and heart disease: results from 3 prospective cohorts.

BACKGROUND: Stroke and heart disease are two major contributors to the global disease burden. We aimed to evaluate and compare the roles of different handgrip strength (HGS) expressions in predicting stroke and heart disease in three nationally representative cohorts. METHODS: This longitudinal study used data from the Health and Retirement Study (HRS), the Survey of Health, Ageing, and Retirement in Europe (SHARE), and the China Health and Retirement Longitudinal Study (CHARLS). The Cox proportional hazard model was applied to analyze the relationship between HGS and stroke and heart disease, and Harrell's C index was used to assess the predictive abilities of different HGS expressions. RESULTS: A total of 4,407 participants suffered from stroke and 9,509 from heart disease during follow-up. Compared with the highest quartile, participants in the lowest quartile of dominant HGS, absolute HGS and relative HGS possessed a significantly higher risk of new-onset stroke in Europe, America, and China (all P < 0.05). After adding HGS to office-based risk factors, there were minimal or no differences in the increases of Harrell's C indexes among three HGS expressions. In contrast, the modest association between HGS and heart disease was only seen in SHARE and HRS, but not in CHARLS. CONCLUSION: Our findings support that HGS can be used as an independent predictor of stroke in middle-aged and older European, American and Chinese populations, and the predictive ability of HGS may not depend on how it is expressed. The relationship between HGS and heart disease calls for further validation.

Associations of handgrip strength with morbidity and all-cause mortality of cardiometabolic multimorbidity.

BACKGROUND: Cardiometabolic multimorbidity (CM) is an increasing public health and clinical concern. However, predictors for the development and prognosis of CM are poorly understood. The aims of this study were to investigate the relation between handgrip strength (HGS) and the risk of CM and to examine the association of HGS with all-cause mortality risk among patients with CM. METHODS: This prospective cohort study involved 493,774 participants from the UK Biobank. CM was defined as the simultaneous occurrence of two or more of the following conditions: type 2 diabetes, stroke, and coronary heart disease (CHD). Cox proportional hazards models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During a median follow-up of 12.1 years, 4701 incident CM cases were documented among participants with none cardiometabolic disease at baseline. Compared with the fourth quartile (Q4), the multivariable adjusted HR (95% CI) value of Q1 of HGS for developing CM was 1.46 (1.34-1.60). In participants with one cardiometabolic disease at baseline, participants in Q1 of HGS also possessed higher risk of CM than those in Q4, with HRs (95% CIs) being 1.35 (1.23-1.49) in patients with type 2 diabetes, 1.23 (1.04-1.46) in patients with stroke, and 1.23 (1.11-1.36) in patients with CHD. For participants with CM at recruitment, HGS was also associated with the risk of all-cause mortality (Q1 vs. Q4 HR: 1.57, 95% CI: 1.36-1.80). CONCLUSIONS: Our study provided novel evidence that HGS could be an independent predictor of morbidity and all-cause mortality of CM.

Pinguisane Sesquiterpenoids from the Chinese Liverwort Trocholejeunea sandvicensis and Their Anti-Inflammatory Activity.

Nine new pinguisane sesquiterpenoid compounds, 1-9, including a highly oxygenated compound (1) and two amides (7 and 8), along with three known compounds (10, 11, and 12), were isolated from the Chinese liverwort Trocholejeunea sandvicensis Mizut (Lejeuneaceae). The structures of these compounds were determined by analysis of IR, UV, HRESIMS, NMR spectroscopic data, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Inhibitory effects against lipopolysaccharide (LPS)-induced NO production in RAW 264.7 murine macrophages indicated that the maximum inhibition rates of NO production of compounds 1, 9, and 10 were 83.15%, 83.54%, and 96.28% under the nontoxic tested concentration, respectively. Compound 9 also displayed moderate anti-inflammatory activity in vivo in a CuSO4-induced transgenic zebrafish model.

Bidirectional association between depression and multimorbidity in middle-aged and elderly Chinese adults: a longitudinal cohort study.

BACKGROUND: Few studies have investigated the bidirectional association between depression and multimorbidity from a longitudinal perspective. We aimed to explore the bidirectional relationship between depression and multimorbidity in a middle-aged and elderly Chinese population. METHODS: Participants aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) were included. Depression was measured with a 10-item version of the Center for Epidemiological Studies Depression Scale (CESD-10). In stage I, we assessed the association of baseline depression with follow-up multimorbidity. In stage II, we examined whether multimorbidity increases the risk of depression. Logistic regression models were used to estimate the odds ratios (ORs) and confidence intervals (CIs). The ORs were then converted to risk ratios (RRs) using a proposed formula. RESULTS: A total of 7056 subjects without multimorbidity and 7587 subjects without depression at baseline were included in stage I and stage II. In stage I, the adjusted RRs (95% CIs) of depressed participants developing one disease, two diseases, three diseases, and ≥4 diseases were 1.15 (0.96-1.35), 1.64 (1.36-1.99), 1.84 (1.44-2.35) and 2.42 (1.75-3.34), respectively. In stage II, compared with individuals without any disease, the adjusted RRs (95% CIs) of developing depression for individuals carrying one disease, two diseases, three diseases, and ≥4 diseases were 1.08 (0.96-1.22), 1.39 (1.22-1.57), 1.46 (1.23-1.70) and 1.62 (1.34-1.93), respectively. CONCLUSIONS: Baseline depression increases the risk of future multimorbidity, and multimorbidity also contributes to an increased risk of incident depression in middle-aged and elderly Chinese adults.

Nutrient Removal by Floating Treatment Wetlands Under Different Spatial Arrangement Modes: a Field Study.

Floating treatment wetlands (FTWs) are a management method to improve urban rivers, but most studies have been carried out at laboratory, micro, and meso levels, so it is necessary to study full-scale FTWs as a method to improve urban water bodies. In this experiment, the purification effects of water temperature (WT), dissolved oxygen (DO), ammonia nitrogen (NH4+-N), nitrate nitrogen (NO3--N), total phosphorus (TP), chemical oxygen demand (CODMn), and chlorophyll-a (Chl-a) under staggered arrangement (SA) and centered arrangement (CA) were evaluated. It was found that the DO concentration and removal rate of CODMn, Chl-a, and TP in the SA were significantly higher than those in the CA in months with heavy rainfall. However, interestingly, for TP, August showed the opposite trend. The removal rates of NH4+-N and NO3--N were significantly different throughout the test period. The biomass growth values of shoots and roots of plants in the FTWs were 0.40 ± 0.03 kg/m2 and 1.38 ± 0.07 kg/m2 in the SA and 0.32 ± 0.07 kg/m2 and 1.26 ± 0.30 kg/m2 in the CA. The increments of N absorbed by plants in the SA and CA were 7.08 ± 0.49 g/kg and 6.83 ± 0.07 g/kg, respectively, and the increments of P were 0.57 ± 0.02 g/kg and 0.32 ± 0.07 g/kg, respectively, which indicated that the growth status of plants in the FTWs in the SA was slightly better than that in the CA. In summary, the hybrid-constructed FTWs of both arrangements can effectively improve the water quality of urban rivers, and the effect of the SA was greater than that of the CA. The purification effect of in situ tests under different arrangement modes of hybrid-constructed FTWs was evaluated, which provides guidance and support for the field layout of FTWs in rivers in the future.

Dolabrane Diterpenoids from the Chinese Liverwort Notoscyphus lutescens.

Nine new dolabrane-type diterpenoids, notoscarins A-I (1-9), including an unprecedented 6,18-cyclo-dolabrane-type diterpenoid (1) obtained through intramolecular cyclization, two rare 19-nor-2-chloro-dolabrane diterpenoids (2 and 3), six new related dolabrane-type diterpenoids (4-9), and one new butyrolactone derivative (10), were isolated from the Chinese liverwort Notoscyphus lutescens. The 6,18-cyclo-dolabrane and 19-nor-dolabrane carbon skeletons are reported for the first time. The structures of these compounds were determined on the basis of MS and NMR spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Preliminary bioassays showed that compounds 1-10 exhibited moderate to weak quinone reductase-inducing activity in Hepa-1c1c7 cells.

Diverse Prenylated Bibenzyl Enantiomers from the Chinese Liverwort Radula apiculata and Their Cytotoxic Activities.

An EtOH extract of the Chinese liverwort Radula apiculata showed cytotoxic activity against the A549 lung cancer cell line. Bioassay-guided fractionation led to the isolation of 19 prenylated bibenzyls, including eight previously unknown dimeric prenylated bibenzyls [radulapins A-H (1-8)], four new prenylated bibenzyls (9-12), and seven known compounds (13-19). Compounds 1-11 were analyzed as racemates by chiral-phase separation. Their structures were determined by detailed analysis of their spectroscopic data and by single-crystal X-ray diffraction, chiral resolutions, and electronic circular dichroism measurements. Using an MTT assay, these dimers (1-8) showed significant cytotoxic activity against a panel of human cancer cell lines. Further investigation revealed that compound 4 induces PC-3 cell death via mitochondrial-derived apoptosis.

Terpenoids from Chinese Liverworts Scapania spp.

An investigation of the chemical composition of Chinese liverworts led to the isolation of six new caged clerodane-type diterpenoids, scaparins A-C (1-3) from Scapania koponenii and scaparins D-F (4-6) from S. verrucosa. An unknown ent-trachylobane diterpenoid (7) and three known terpenoid derivatives (8-10) were obtained from S. verrucosa. The structures of the compounds were established on the basis of physical data (IR, UV, HRESIMS, and 1D and 2D NMR), and the absolute configurations were unequivocally confirmed by comparison of the experimental and calculated electronic circular dichroism spectra. Preliminary bioassays showed that compounds 1-7 exhibited moderate to weak quinone reductase-inducing activity in Hepa-1c1c7 cells.

Waist-to-height ratio, waist circumference, body mass index, waist divided by height0.5 and the risk of cardiometabolic multimorbidity: A national longitudinal cohort study.

BACKGROUND AND AIMS: Cardiometabolic multimorbidity (CM) is an increasing public health burden. This study aimed to evaluate the association of waist-to-height ratio (WHtR), waist circumference (WC), waist divided by height0.5 (WHT.5R) and body mass index (BMI) with the risk of CM. METHODS AND RESULTS: We used data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 10,521 participants aged 45 years and over were recruited, including 8807 individuals with 0 cardiometabolic diseases at baseline (stage I) and 1714 individuals with 1 cardiometabolic disease at baseline (stage II). CM was defined as self-reporting of two or more of the following conditions: stroke, diabetes and heart disease. Logistic regression was conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to evaluate the incremental predictive value beyond conventional factors. In stage I, an increased risk of CM was observed among participants with WHtR ≥0.5 (OR: 1.76, 95% CI: 1.05-2.97), WC ≥ 90 cm (men) + WC ≥ 80 cm (women) (OR: 2.06, 95% CI: 1.29-3.27), WHT.5R ≥ 6.54 cm0.5 (OR: 1.81, 95% CI: 1.16-2.83) or BMI ≥24 kg/m2 (OR: 1.48, 95% CI: 0.98-2.24). Furthermore, the NRI and IDI of WHtR, WC and WHT.5R were all higher than those of BMI. In stage II, the adjusted ORs (95% CIs) of WHtR, WC, WHT.5R and BMI were 2.04 (1.24-3.35), 1.89 (1.29-2.77), 1.86 (1.24-2.78) and 1.47 (1.06-2.04), respectively. In addition, WC exhibited the highest NRI and IDI. CONCLUSION: WHtR, WC, WHT.5R and BMI are independent predictors of CM in the middle-aged and older Chinese population. WHtR, WC and WHT.5R show better abilities in predicting CM than BMI.

Association between visceral adipose index and risk of hypertension in a middle-aged and elderly Chinese population.

BACKGROUND AND AIMS: Visceral adipose index (VAI) had been widely used to predict the risks of several diseases. However, few studies have clarified the association between VAI and the risk of hypertension in Chinese population. Thus, we investigate the association between VAI and the increased risk of hypertension in a nationwide cohort of middle-aged and elderly adults in China. METHODS AND RESULTS: Data were obtained from the China Health and Retirement Longitudinal Study from 2011 to 2015. A total of 5200 Chinese participants aged 45 years and older were included. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of hypertension, with the lowest quartile of VAI score group as the reference. During the 4-years follow-up, 979 cases of hypertension were recorded. Compared with those in the lowest VAI score group, the participants with the highest quartile of VAI score were at a higher risk level of hypertension (HR: 1.454; 95% CI 1.204 to 1.755), especially subjects living in the urban area (2.142, 1.522 to 3.014). Furthermore, VAI can improve the ability of both BMI and WC in predicting the risk of hypertension by 12.72% (95% CI: 5.78%-19.67%) and 10.12% (95% CI: 3.17%-17.07%), respectively. CONCLUSION: In summary, VAI was positively associated with an increased risk of hypertension among a middle-aged and elderly Chinese population; VAI score can improve the ability of BMI and WC in predicting risk of hypertension.

Longitudinal Follow-Up Studies on the Bidirectional Association between ADL/IADL Disability and Multimorbidity: Results from Two National Sample Cohorts of Middle-Aged and Elderly Adults.

BACKGROUND AND OBJECTIVES: Few studies have investigated the bidirectional relationship between disability and multimorbidity, which are common conditions among the older population. Based on the data from the China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Ageing and Retirement in Europe (SHARE), we aimed to investigate the bidirectional relationship between disability and multimorbidity. METHODS: The activities of daily living (ADLs) and the instrumental activities of daily living (IADLs) scales were used to measure disability. In stage I, we used multinomial logistic regression to assess the longitudinal association between ADL/IADL disability and follow-up multimorbidity. In stage II, binary logistic regression was used to evaluate the multimorbidity effect on future disability. RESULTS: Compared with those free of disability, people with disability possessed ascending risks for developing an increasing number of diseases. For ADL disability, the odds ratio (OR) (95% confidence interval [CI]) values of developing ≥4 diseases were 4.10 (2.58, 6.51) and 6.59 (4.54, 9.56) in CHARLS and SHARE; for IADL disability, the OR (95% CI) values were 2.55 (1.69, 3.84) and 4.85 (3.51, 6.70) in CHARLS and SHARE. Meanwhile, the number of diseases at baseline was associated, in a dose-response manner, with future disability. Compared with those without chronic diseases, participants carrying ≥4 diseases had OR (95% CI) values of 4.82 (3.73, 6.21)/4.66 (3.65, 5.95) in CHARLS and 3.19 (2.59, 3.94)/3.28 (2.71, 3.98) in SHARE for developing ADL/IADL disability. CONCLUSION: The consistent findings across 2 national longitudinal studies supported a strong bidirectional association between disability and multimorbidity among middle-aged and elderly adults. Thus, tailored interventions should be taken to prevent the mutual development of disability and multimorbidity.

Role of handgrip strength in predicting new-onset diabetes: findings from the survey of health, ageing and retirement in Europe.

BACKGROUND: Diabetes is a major concern for the global health burden. This study aimed to investigate the relationship between handgrip strength (HGS) and the risk of new-onset diabetes and to compare the predictive abilities between relative HGS and dominant HGS. METHODS: This longitudinal study used data from the Survey of Health, Ageing and Retirement in Europe (SHARE), including 66,100 European participants aged 50 years or older free of diabetes at baseline. The Cox proportional hazard model was used to analyze the relationship between HGS and diabetes, and the Harrell's C index, net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the predictive abilities of different HGS expressions. RESULTS: There were 5,661 diabetes events occurred during follow-up. Compared with individuals with lowest quartiles, the hazard ratios (95 % confidence intervals) of the 2nd-4th quartiles were 0.88 (0.81-0.94), 0.82 (0.76-0.89) and 0.85 (0.78-0.93) for dominant HGS, and 0.95 (0.88-1.02), 0.82 (0.76-0.89) and 0.60 (0.54-0.67) for relative HGS. After adding dominant HGS to an office-based risk score (including age, gender, body mass index, smoking, and hypertension), the incremental values of the Harrell's C index, NRI, IDI of relative HGS were all slightly higher than those of dominant HGS in both training and validation sets. CONCLUSIONS: Our findings supported that HGS was an independent predictor of new-onset diabetes in the middle-aged and older European population. Moreover, relative HGS exhibited a slightly higher predictive ability than dominant HGS.

Estimation of losses of quality-adjusted life expectancy attributed to the combination of cognitive impairment and multimorbidity among Chinese adults aged 45 years and older.

OBJECTIVES: This study aims to estimate the losses of quality-adjusted life expectancy (QALE) due to the joint effects of cognitive impairment and multimorbidity, and to further confirm additional losses attributable to this interaction among middle-aged and elderly Chinese people. METHODS: The National Cause of Death Monitoring Data were linked with the China Health and Retirement Longitudinal Study (CHARLS). A mapping and assignment method was used to estimate health utility values, which were further used to calculate QALE. Losses of QALE were measured by comparing the differences between subgroups. All the losses of QALE were displayed at two levels: the individual and population levels. RESULTS: At age 45, the individual-level and population-level losses of QALE attributed to the combination of cognitive impairment and multimorbidity were 7.61 (95% CI: 5.68, 9.57) years and 4.30 (95% CI: 3.43, 5.20) years, respectively. The losses for cognitive impairment alone were 3.10 (95% CI: 2.29, 3.95) years and 1.71 (95% CI: 1.32, 2.13) years at the two levels. Similarly, the losses for multimorbidity alone were 3.53 (95% CI: 2.53, 4.56) years and 1.91 (95% CI: 1.24, 2.63) years at the two levels. Additional losses due to the interaction of cognitive impairment and multimorbidity were indicated by the 0.98 years of the individual-level gap and 0.67 years of the population-level gap. CONCLUSION: Among middle-aged and elderly Chinese people, cognitive impairment and multimorbidity resulted in substantial losses of QALE, and additional QALE losses were seen due to their interaction at both individual and population levels.

Longitudinal research on the bidirectional association between depression and arthritis.

PURPOSE: Studies evaluating the mutual relation between depression and arthritis have been limited and yielded inconsistent results. The aim of this study was to investigate the bidirectional relationship between depression and arthritis in a middle-aged and elderly Chinese population. METHODS: Participants ≥ 45 years of age were included from the China Health and Retirement Longitudinal Study (CHARLS). In stage I, we assessed the association of baseline depression with follow-up arthritis. In stage II, we examined whether the onset of arthritis predicted future depression. Logistic regression analyses were conducted to estimate the odds ratios (ORs) and confidence intervals (CIs) in stage I and stage II, respectively. RESULTS: In stage I, 24.3% (679/2794) of the depression group and 15.4% (1000/6482) of the non-depression group developed new arthritis cases. Compared with non-depression individuals, the risk of developing arthritis in depression patients was significantly higher (OR: 1.56, 95% CI 1.37-1.79). In stage II, 39.7% (973/2453) subjects in the arthritis group and 26.7% (1667/6236) subjects in the non-arthritis group developed depressive symptoms. The adjusted OR (95% CI) for depression in the arthritis group was 1.64 (1.45-1.86) times higher than that in the non-arthritis group. In the subgroup analyses according to sex, age, household income, residence, body mass index, smoking and drinking, all sub-groups yielded consistent associations. CONCLUSION: The onset of depression increased the risk of incident arthritis; in addition, baseline arthritis predicted future depression in middle-aged and elderly Chinese adults.

An Investigation into the Interaction between Double Hydroxide-Based Antioxidant Benzophenone Derivatives and Cyclooxygenase 2.

Cyclooxygenases 2 (COX2) is a therapeutic target for many inflammation and oxidative stress associated diseases. A high-throughput technique, biolayer interferometry, was performed to primarily screen the potential COX2 binding activities of twelve newly synthesized double hydroxide-based benzophenone derivatives. Binding confirmation was achieved by molecular docking and multi-spectroscopy studies. Such a combined method provided a comprehensive understanding of binding mechanism and conformational changes. Compounds DB2, SC2 and YB2 showed effective COX2 binding activity and underlined the benefits of three phenolic hydroxyl groups adjacent to each other on the B ring. The twelve tested derivatives were further evaluated for antioxidant activity, wherein compound SC2 showed the highest activity. Its concentration for the 50% of maximal effect (EC50) value was approximately 1000 times greater than that of the positive controls. SC2 treatment effectively improved biochemical indicators caused by oxidative stress. Overall, compound SC2 could serve as a promising candidate for further development of a new potent COX2 inhibitor.

Identification and evolutionary analysis of chalcone isomerase-fold proteins in ferns.

The distribution of type I and II chalcone isomerases (CHIs) in plants is highly family specific. We have previously reported that ancient land plants, such as the liverworts and Selaginella moellendorffii, harbor type II CHIs. To better understand the function and evolution of CHI-fold proteins, transcriptomic data obtained from 52 pteridophyte species were subjected to sequence alignment and phylogenetic analysis. The residues determining type I/II CHI identity in the pteridophyte CHIs were identical to those of type I CHIs. The enzymatic characterization of a sample of 24 CHIs, representing all the key pteridophyte lineages, demonstrated that 19 of them were type I enzymes and that five exhibited some type II activity due to an amino acid mutation. Two pteridophyte chalcone synthases (CHSs) were also characterized, and a type IV CHI (CHIL) was demonstrated to interact physically with CHSs and CHI, and to increase CHS activity by decreasing derailment products, thus enhancing flavonoid production. These findings suggest that the emergence of type I CHIs may have coincided with the divergence of the pteridophytes. This study deepens our understanding of the molecular mechanism of CHIL as an enhancer in the flavonoid biosynthesis pathway.