Copper-binding protein modelling by single-cell transcriptome and Bulk transcriptome to predict overall survival in lung adenocarcinoma patients.

Background: Copper and copper-binding proteins are key components of tumour progression as they play an important role in tumour invasion and migration, and abnormal accumulation of copper (Cu) may be intimately linked to with lung adenocarcinoma (LUAD). Methods: Data on lung adenocarcinoma were sourced from the Cancer Genome Atlas (TCGA) database and the National Centre for Biotechnology Information (GEO). 10x scRNA sequencing, which is from Bischoff P et al, was used for down-sequencing clustering and subgroup identification using TSNE. The genes for Copper-binding proteins (CBP) were acquired from the MSigDB database. LASSO-Cox analysis was subsequently used to construct a model for copper-binding proteins (CBPRS), which was then compared to lung adenocarcinoma models developed by others. External validation was carried out in the GSE31210 and GSE50081 cohorts. The effectiveness of immunotherapy was evaluated using the TIDE algorithm and the IMvigor210, GSE78220, and TCIA cohorts. Furthermore, differences in mutational profiles and the immune microenvironment between different risk groups were investigated. The CBPRS's key regulatory genes were screened using ROC diagnostic and KM survival curves. The differential expression of these genes was then verified by RT-qPCR. Results: The six CBP genes were identified as highly predictive of LUAD prognosis and significantly correlated with it. Multivariate analysis showed that patients in the low-risk group had a higher overall survival rate than those in the high-risk group, indicating that the model was an independent predictor of LUAD. The CBPRS demonstrated superior predictive ability compared to 11 previously published models. We constructed a column-line graph that includes CBPRS and clinical characteristics, which exhibits high predictive performance. Additionally, we observed significant differences in biological functions, mutational landscapes, and immune cell infiltration in the tumour microenvironment between the high-risk and low-risk groups. It is noteworthy that immunotherapy was also significant in both the high- and low-risk groups. These results suggest that the model has good predictive efficacy. Conclusions: The CBP model demonstrated good predictive performance, revealing characteristics of the tumour microenvironment. This provides a new method for assessing the efficacy of pre-immunisation and offers a potential strategy for future treatment of lung adenocarcinoma.

The effectiveness of non-pharmacological interventions on reducing pain in patients undergoing bone marrow aspiration and biopsy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients often consider bone marrow aspiration and biopsy to be one of the most painful medical procedures. The effectiveness of non-pharmacological interventions to reduce pain during bone marrow aspiration and biopsy remains unclear. AIM: To synthesize existing evidence regarding the effectiveness of non-pharmacological interventions in mitigating procedural pain among patients undergoing bone marrow aspiration and biopsy. DESIGN: A systematic review and meta-analysis of randomized controlled trials. METHODS: Six electronic databases, including PubMed, EMBASE, CINAHL, PsycINFO, Cochrane Library and Web of Science were searched from inception to July 15, 2023. The risk of bias was assessed using the Cochrane Risk of Bias Tool Version 2.0. Meta-analysis was conducted using STATA 16. The certainty of the evidence was assessed by the GRADE approach. RESULTS: This meta-analysis included 18 studies derived from 17 articles involving a total of 1017 participants. The pooled results revealed statistically significant pain reduction effects using distraction (SMD: -.845, 95% CI: -1.344 to -.346, p < .001), powered bone marrow biopsy system (SMD: -.266, 95% CI: -.529 to -.003, p = .048), and acupoint stimulation (SMD: -1.016, 95% CI: -1.995 to -.037, p = .042) among patients undergoing bone marrow aspiration and biopsy. However, the pooled results on hypnosis (SMD: -1.228, 95% CI: -4.091 to 1.515, p = .368) showed no significant impact on pain reduction. Additionally, the pooled results for distraction did not demonstrate a significant effect on operative anxiety (MD: -2.942, 95% CI: -7.650 to 1.767, p = .221). CONCLUSIONS: Distraction, powered bone marrow biopsy system and acupoint stimulation are effective in reducing pain among patients undergoing bone marrow aspiration and biopsy. PATIENT OR PUBLIC CONTRIBUTION: Not applicable. RELEVANCE TO CLINICAL PRACTICE: This meta-analysis highlights the effectiveness of distraction, powered bone marrow biopsy system and acupoint stimulation for reducing pain in patients undergoing bone marrow biopsy. Healthcare professionals should consider integrating these interventions into pain management practices for these patients. REGISTRATION: (PROSPERO): CRD42023422854.

Serum soluble alpha-klotho klotho and cognitive functioning in older adults aged 60 and 79: an analysis of cross-sectional data of the National Health and Nutrition Examination Survey 2011 to 2014.

OBJECTIVES: Klotho, consisting of membrane klotho and soluble alpha-klotho, is found to be associated with better cognitive outcomes in small samples of the aged population. We aimed to examine the association of serum soluble alpha-klotho with cognitive functioning among older adults using a nationally representative sample of U.S. older adults. METHOD: A total of 2,173 U.S. older adults aged 60-79 years in the National Health and Nutrition Examination Survey from 2011 to 2014 were included in this cross-sectional analysis. Serum soluble alpha-klotho was measured in the laboratory and analyzed with an ELISA kit. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD-WL) immediate and delayed memory, the Animal fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated based on sample means and standard deviations. Multivariable linear regression models were applied to examine the association of quartiles and continuous value of serum soluble alpha-klotho with test-specific and global cognition z-scores. Subgroup analysis was conducted by sex. The following covariates were included in the analysis- age, sex, race/ethnicity, education, depressive symptoms, smoking status, body mass index (BMI), physical activity, stroke, prevalent coronary heart disease, total cholesterol, and systolic blood pressure. All the information was self-reported or obtained from health exams. RESULTS: Serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (beta [ß] =-0.13, 95% confidence interval [CI]: -0.25, -0.01). For subgroup analysis, serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (ß=-0.16, 95% CI: -0.32, -0.003) and global cognition (ß=-0.14, 95% CI: -0.28, -0.01) among female participants. No association was found between continuous serum soluble alpha-klotho and cognitive functioning among the participants. CONCLUSIONS: Lower serum soluble alpha-klotho quartile was associated with poorer cognitive functioning among older women. Future studies are expected to examine the longitudinal association between klotho levels and cognitive outcomes.

Prevalence and risk factors of pre-frailty and frailty in maintenance haemodialysis patients in China: A cross-sectional Study.

AIMS: To examine the prevalence and risk factors of pre-frailty and frailty in maintenance haemodialysis patients in China. DESIGN: A cross-sectional study. METHOD: From January to July 2017, using the convenience sampling method, a total of 503 maintenance haemodialysis patients from six hospitals in Lianyungang, China, were recruited for this study. The participants' socio-demographic, lifestyle factors and health information were assessed using a general information questionnaire. Frailty was evaluated based on the Fried frailty phenotype. Multi-categorical logistic regression was performed to examine factors associated with pre-frailty and frailty in this population, including age, sex, living alone, employment, educational level, body mass index, per capita monthly household income, smoking status, exercise status, primary diagnosis, dialysis age, frequency of dialysis, vascular access, congestive heart failure, other cardiac diseases, cerebrovascular disease, peripheral blood diseases, pain, albumin level and haemoglobin level. RESULTS: Among the 503 participants with an average age of 53.02 years (standard deviation 14.99), 178 had pre-frailty (35.3%) and were mostly young and middle-aged. The prevalence of pre-frailty among participants <60 years old was more than 40%. Regression analysis showed that lack of exercise, dialysis age ≤12 months, congestive heart failure and other cardiac diseases were positively associated with pre-frailty. Two hundred and eighteen participants were frail (43.3%), most of whom were aged ≥60. The prevalence of frailty in participants ≥60 was 71.4%. Regression analysis showed that advanced age, being female, obesity, low per capita monthly household income, lack of exercise, diabetes as the primary disease, dialysis age ≤12 months, congestive heart failure, other cardiac diseases, pain and low albumin level, were positively associated with frailty. In addition, more than half of the participants hardly exercised (64.6%), while lack of exercise was a risk factor for pre-frailty and frailty. A third of the participants had pain (33.4%), while pain was an independent risk factor for pre-frailty and frailty in these participants. CONCLUSION: Pre-frailty and frailty are common in patients with maintenance haemodialysis. Most of the elderly maintenance haemodialysis patients are frail, and most of the young and middle-aged patients are pre-frail. Clinicians should actively screen the pre-frailty and frailty among patients with maintenance haemodialysis, especially those with dialysis age ≤12 months. Many factors affect pre-frailty and frailty in this population. Tailored intervention measures should be designed and implemented based on these factors, giving priority to exercise guidance and pain management for patients to help them prevent or reverse pre-frailty and frailty.

Dietary Polyphenol Intake and Risk of Hypertension: An 18-y Nationwide Cohort Study in China.

BACKGROUND: Although increasing evidence suggests that polyphenol helps regulate blood pressure (BP), evidence from large-scale and long-term population-based studies is still lacking. OBJECTIVES: This study aimed to investigate the association between dietary polyphenol and hypertension risk in the China Health and Nutrition Survey (N = 11,056). METHODS: Food intake was assessed using 3-d, 24-h dietary recalls and household weighing method; polyphenol intake was calculated by multiplying consumption of each food and its polyphenol content. Hypertension was defined as BP ≥ 140/90 mmHg, physicians' diagnosis, or taking antihypertension medications. HR and 95% CI were estimated using mixed-effects Cox models. RESULTS: During 91,561 person-years of follow-up, a total of 3866 participants developed hypertension (35%). The lowest multivariable-adjusted HR (95% CI) of hypertension risk occurred in the third quartile intake, which was 0.63 (0.57, 0.70) for total polyphenol, 0.61 (0.55, 0.68) for flavonoid, 0.62 (0.56, 0.69) for phenolic acid, 0.46 (0.42, 0.51) for lignan, and 0.58 (0.52, 0.64) for stilbene, compared with the lowest quartile. The polyphenol-hypertension associations were nonlinear (all Pnonlinearity < 0.001), and different patterns were observed. U-shaped relations with hypertension were observed for total polyphenol, flavonoid, and phenolic acid, whereas L-shaped associations were observed for lignan and stilbene. Moreover, higher fiber intake strengthened the polyphenol-hypertension association, especially for lignan (P-interaction = 0.002) and stilbene (P-interaction = 0.004). Polyphenol-containing food, particularly vegetables and fruits rich in lignan and stilbene, were significantly associated with lower hypertension risk. CONCLUSIONS: This study demonstrated an inverse and nonlinear association between dietary polyphenol, especially lignan and stilbene, and hypertension risk. The findings provide implications for hypertension prevention.

Urinary tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and cognitive functioning in older adults: The National Health and Nutrition Examination Survey 2013-2014.

INTRODUCTION: Tobacco contains carcinogens called tobacco-specific nitrosamines. Among the tobacco-specific nitrosamines, is nicotine-derived nitrosamine ketone (NNK) which produces the metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). We aimed to examine the association between urinary tobacco-specific NNAL and cognitive functioning among older adults. METHODS: A total of 1673 older adults aged ≥60 years from the National Health and Nutrition Examination Survey 2013-2014 were included. Urinary tobacco-specific NNAL was analyzed in the laboratory. Cognitive functioning was measured using the Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD-WL) immediate and delayed memory tests, the Animal Fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated based on means and standard deviations of the cognitive test scores. Multivariable linear regression models were constructed to examine the independent association between quartiles of urinary tobacco-specific NNAL and cognitive test-specific and global cognition z-scores controlling for age, sex, race/ethnicity, education level, depressive symptoms, body mass index, systolic blood pressure, urinary creatinine, hypertension, diabetes, alcohol use, and smoking status. RESULTS: About half of the participants (mean age 69.8 years) were female (52.1%), non-Hispanic White (48.3%), and completed some college and above (49.7%). Multivariable linear regression results showed that participants in the 4th quartile (highest quartile) of urinary NNAL, compared with those in the 1st quartile (lowest quartile), had lower DSST z-scores (ß= -0.19; 95% CI: -0.34 - -0.04). CONCLUSIONS: Tobacco-specific NNAL was negatively associated with processing speed, sustained attention, and working memory in older adults.

Physio-psycho-social interaction mechanism in dyadic health of young and middle-aged stroke survivors and their spousal caregivers: a longitudinal observational study protocol.

INTRODUCTION: In recent years, stroke has become more common among young people. Stroke not only has a profound impact on patients' health but also incurs stress and health threats to their caregivers, especially spousal caregivers. Moreover, the health of stroke survivors and their caregivers is interdependent. To our knowledge, no study has explored dyadic health of young and middle-aged stroke survivors and their spousal caregivers from physiological, psychological and social perspectives. Therefore, this proposed study aims to explore the mechanism of how physiological, psychological and social factors affect dyadic health of young and middle-aged stroke survivors and their spousal caregivers. The findings of this study will provide implications for developing interventions to improve dyadic health of this growing population. METHODS AND ANALYSES: We will collect data from 57 dyads of young and middle-aged stroke survivors and their spousal caregivers during hospitalisation and at 1, 3, 6, 9 and 12 months after discharge. Questionnaires will be used to collect participants' demographic information, stress, depression, anxiety, benefit finding, social support, mutuality and quality of life. The following physiological reactions will be collected at baseline, including interleukin 6, tumour necrosis factor-alpha and salivary cortisol. ETHICS AND DISSEMINATION: The study was approved by the ethics review committee of life sciences of Zhengzhou University (No. ZZUIRB2020-53). Prior to being enrolled in the study, participants will be given full and detailed information about the possible risks involved, the informed consent process, confidentiality, the study procedure and secure data storage. Participants will be guaranteed that they can withdraw from the study at any time without providing a reason or leading to any consequences. Both oral and written informed consent will be obtained from all participants. The findings of this proposed study will be disseminated through peer-reviewed journals and academic conferences.

Higher blood cotinine level is associated with worse cognitive functioning in non-smoking older adults.

Introduction: Secondhand smoke (SHS) is common in older adults; however, its cognitive effect is unclear. We aimed to examine the association between serum cotinine level and cognitive functioning among non-smoking older adults. Materials and methods: A total of 2,703 older adults aged 60 and above from the National Health and Nutrition Examination (NHANES) Survey 2011-2014 were included. Serum cotinine level was analyzed in the laboratory. A level ≤10 ng/ml and a response of "no" to the question "Do you currently smoke?" were used to select non-smokers. Cognitive functioning was measured using the Consortium to Establish a Registry for Alzheimer's disease Word Learning subtest (CERAD-WL) immediate and delayed recall tests, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Multivariable linear regression models were constructed to examine the association between serum cotinine level quartile and test-specific and global cognition z scores adjusting for age, race/ethnicity, education, depressive symptoms, body mass index, alcohol use, smoking history, prevalent coronary heart disease (CHD), stroke, and systolic blood pressure. Results: About half of the participants (mean age 70.5 years) were female (53.6%), non-Hispanic White (48.3%), and completed some college and above (50.2%). Multivariate linear regressions with a reference group being those in the 1st quantile (lowest) showed that participants in the 4th quartile (highest) of serum cotinine level had lower immediate recall [ß = -0.16, 95% confidence interval (CI) = -0.29, -0.03], AFT (ß = -0.19, 95% CI = -0.33, -0.05), DSST (ß = -0.27, 95% CI = -0.39, -0.15), and global cognition (ß = -0.26, 95% CI = -0.39, -0.14) z scores. Participants in the 3rd quartile had lower immediate recall (ß = -0.16, 95% CI = -0.30, -0.02) and global cognition (ß = -0.16, 95% CI = -0.29, -0.02) z scores. Participants in the 2nd quartile had lower delayed recall z scores (ß = -0.16, 95% CI = -0.29, -0.02). Conclusion: Higher serum cotinine level was associated with worse cognitive functioning in non-smoking older adults. Prevention and reduction of SHS in older adults may help protect their cognitive functioning.

Identification of the Diagnostic Biomarker VIPR1 in Hepatocellular Carcinoma Based on Machine Learning Algorithm.

The purpose of this study was to identify the potential diagnostic biomarkers in hepatocellular carcinoma (HCC) by machine learning (ML) and to explore the significance of immune cell infiltration in HCC. From GEO datasets, the microarray datasets of HCC patients were obtained and downloaded. Differentially expressed genes (DEGs) were screened from five datasets of GSE57957, GSE84402, GSE112790, GSE113996, and GSE121248, totalling 125 normal liver tissues and 326 HCC tissues. In order to find the diagnostic indicators of HCC, the LASSO regression and the SVM-RFE algorithms were utilized. The prognostic value of VIPR1 was analyzed. Finally, the difference of immune cell infiltration between HCC tissues and normal liver tissues was evaluated by CIBERSORT algorithm. In this study, a total of 232 DEGs were identified in 125 normal liver tissues and 326 HCC tissues. 11 diagnostic markers were identified by LASSO regression and SVM-RFE algorithms. FCN2, ECM1, VIRP1, IGFALS, and ASPG genes with AUC>0.85 were regarded as candidate biomarkers with high diagnostic value, and the above results were verified in GSE36376. Survival analyses showed that VIPR1 and IGFALS were significantly correlated with the OS, while ASPG, ECM1, and FCN2 had no statistical significance with the OS. Multivariate assays indicated that VIPR1 gene could be used as an independent prognostic factor for HCC, while FCN2, ECM1, IGFALS, and ASPG could not be used as independent prognostic factors for HCC. Immune cell infiltration analyses showed that the expression of VIPR1 in HCC was positively correlated with the levels of several immune cells. Overall, VIPR1 gene can be used as a diagnostic feature marker of HCC and may be a potential target for the diagnosis and treatment of liver cancer in the future.

Temporal changes in plaque characteristics after treatment and their relationship with stroke recurrence: a quantitative study using magnetic resonance imaging.

Background: Intracranial atherosclerotic disease (ICAD) is the major cause of ischemic stroke. Despite aggressive medical therapy, around 15% of patients with ICAD experience recurrence. The aim of the present study was to evaluate the temporal changes in intracranial arteriosclerotic plaques after medical treatment based on vessel wall magnetic resonance imaging (VWMRI) and to explore their relationship with stroke recurrence. Methods: A total of 67 symptomatic patients with ICAD who underwent initial and follow-up VWMRI were recruited into this retrospective cohort study. Stroke recurrence was defined as an ipsilateral stroke symptom after the initial attack. The clinical characteristics and plaque features, including stenosis ratio (measured based on luminal diameter or area), plaque thickness, plaque burden (PB), enhancement ratio (ER), and enhancement grade, were evaluated and compared between the initial and follow-up examinations. Changes in plaque characteristics were compared between patients with or without recurrence by univariable analyses. Multivariable regression was performed to investigate imaging markers for recurrent stroke. Results: The median interval between baseline and follow-up VWMRI was 334 days. A total of 13 cases (19.4%) experienced a stroke recurrence. After treatment, significant decreases in the stenosis ratio (area), PB, and ER were observed in cases without recurrence (all P<0.05), while no significant difference in plaque features was found for cases with recurrence. Univariable analyses showed that changes in stenosis ratio (area), plaque thickness, PB, and ER were significantly different between patients with and without recurrence (all P<0.05). Multivariable regression indicated that PB change was the only significant marker associated with stroke recurrence [odds ratio (OR) =1.112 per 1% increase, 95% confidence interval (CI): 1.010 to 1.224, P=0.031]. Conclusions: Patients with arteriosclerotic plaques who benefit from medical treatment show obvious decreases in stenosis (area), PB, and ER. The progression of PB may serve as an independent marker for predicting stroke recurrence.

GPAA1 promotes the proliferation, invasion and migration of hepatocellular carcinoma cells by binding to RNA-binding protein SF3B4.

It has previously been reported that glycosylphosphatidylinositol anchor attachment 1 (GPAA1) is overexpressed in hepatocellular carcinoma (HCC); however, its role in regulating the development of HCC remains unknown. The present study aimed to examine the potential role of GPAA1 in HCC and to characterize the associated mechanism. The expression of GPAA1 was first examined using the Gene Expression Profiling Interactive Analysis 2 database, and was then determined using reverse transcription-quantitative PCR and western blotting. The effects of GPAA1 silencing on the proliferation, colony formation, migration and invasion of HuH-7 cells were measured using Cell Counting Kit-8, colony formation, wound healing and Transwell assays, respectively. The interaction between splicing factor (SF)3B4 and GPAA1 was predicted by starBase and confirmed using RNA immunoprecipitation. The results of the present study demonstrated that GPAA1 was upregulated in HCC cells, and silencing GPAA1 markedly inhibited the proliferation, migration and invasion of HCC cells, which was accompanied by reduced levels of MMP2 and MMP9. In addition, it was observed that SF3B4 could bind to GPAA1. Furthermore, to confirm whether SF3B4 binds to GPAA1 to modulate HCC cell behavior, GPAA1 was knocked down and SF3B4 was overexpressed. Overexpression of SF3B4 reversed the effects of GPAA1 knockdown on the proliferation, migration and invasion of HCC cells. In conclusion, SF3B4 may promote the proliferation, invasion and migration of HCC cells by binding to GPAA1. The present study provided novel insight into the pathogenesis of HCC.

Secondhand smoke is positively associated with pre-frailty and frailty in non-smoking older adults.

Introduction: Either exposure to secondhand smoke (SHS) or frailty has been linked to adverse health outcomes in nonsmoking adults. However, their relationship is rarely studied. The purpose of this study is to examine the association between serum cotinine level and frailty status among non-smoking older adults. Method: The study population consisted of 2,703 older adults aged ≥60 from the National Health and Nutrition Examination Survey 2011-2014. Non-smokers were included based on (1) a serum cotinine level ≤ 10 ng/mL and 2) a response of "no" to the question, "Do you currently smoke?" Frailty status was measured based on the Fried Phenotype and had three groups- robust, pre-frailty, and frailty. Multinomial logistic regression models were constructed to examine the association between serum cotinine level quartile and frailty status, controlling for age, sex, race/ethnicity, education, depressive symptoms, alcohol use, and systolic blood pressure. Results: About half of the participants (median age 70.0 years, range 64-78) were female (53.6%), non-Hispanic White (48.3%), and completed some college and above (50.1%). Multinomial logistic regression with a reference group being those in the 1st quantile (the lowest) of serum cotinine level showed that participants in the 4th quartile (the highest) of serum cotinine level had increased odds of pre-frailty vs. robust (OR 1.522, 95% confidence interval [CI] 1.060, 2.185, P = 0.023) as well as increased odds of frailty vs. robust (OR 2.349, 95% CI 1.081, 5.107, P = 0.031). Conclusions: Higher serum cotinine level is associated with increased risk of pre-frailty and frailty versus robust in non-smoking older adults. Prevention and reduction of SHS in older adults may help protect them from developing pre-frailty or frailty.

Association between Caffeine Intake and All-Cause and Cause-Specific Mortality: An Analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014 Database.

Sixty-four percent of adults in America drink coffee daily, and caffeine is the main reason people tend to drink coffee habitually. Few studies have examined the association between caffeine and all-cause and cause-specific mortality. The objective of this study was to examine the association between caffeine and all-cause and cause-specific mortality using the National Health and Nutrition Examination Survey (NHANES) 1999-2014 database. The multivariate Cox proportional hazards regression model was used to examine 23,878 individuals 20 years and older. Daily caffeine intake was measured once at baseline. A total of 2206 deaths occurred, including 394 cardiovascular (CVD) deaths and 525 cancer deaths. Compared to those with a caffeine intake of <100 mg/day, the hazard ratios (HRs) for CVD mortality were significantly lower in the participants with a caffeine intake of 100-200 mg/day (HR, 0.63; 95% confidence interval [CI], 0.45-0.88), and those with a caffeine intake of >200 mg/day (HR, 0.67; 95% CI, 0.50-0.88) after adjusting for potential confounders. The HRs for all-cause mortality were significantly lower in the participants with a caffeine intake of 100-200 mg/day (HR, 0.78; 95% CI, 0.67-0.91), and those with a caffeine intake of >200 mg/day (HR, 0.68; 95% CI, 0.60-0.78). Subgroup analyses showed that caffeine may have different effects on all-cause mortality among different age and body mass index (BMI) groups. In conclusion, higher caffeine intake was associated with lower all-cause and CVD mortality.

Augmenting ATG14 alleviates atherosclerosis and inhibits inflammation via promotion of autophagosome-lysosome fusion in macrophages.

Dysfunction of macroautophagy/autophagy in macrophages contributes to atherosclerosis. Impaired autophagy-lysosomal degradation system leads to lipid accumulation, facilitating atherosclerotic plaque. ATG14 is an essential regulator for the fusion of autophagosomes with lysosomes. Whether ATG14 plays a role in macrophage autophagy dysfunction in atherosclerosis is unknown. To investigate the effects of ATG14 on macrophage autophagy, human atherosclerotic plaque, apoe-/- mice and cultured mouse macrophages were evaluated. Overexpression of ATG14 by adenovirus was used to reveal its function in autophagy, inflammation and atherosclerotic plaque formation. Results showed that impaired autophagy function with reduction of ATG14 expression existed in macrophages of human and mouse atherosclerotic plaques. Ox-LDL impaired autophagosome-lysosome fusion with reduction of ATG14 expression in macrophages. Overexpression of ATG14 in macrophages enhanced fusion of autophagosomes with lysosomes and promoted lipid degradation, decreasing Ox-LDL-induced apoptosis and inflammatory response. Augmenting ATG14 expression reversed the autophagy dysfunction in macrophages of apoe-/- mice plaque, blunted SQSTM1/p62 accumulation, inhibited inflammation, and upregulated the population of Treg cells, resulting in alleviating atherosclerotic lesions.Abbreviations: ABCC1: ATP-binding cassette, sub-family C (CFTR/MRP), member 1; ABCA1: ATP-binding cassette, sub-family A (ABC1), member 1; Ad-Atg14: adenovirus vector carrying the mouse Atg14 gene; Ad-LacZ: adenovirus vector carrying the gene for bacterial ß-galactosidase; apoe-/-: apolipoprotein E knockout; ATG14: autophagy-related 14; CD68: CD68 antigen; DAPI: 4',6-diamidino-2-phenylindole; Dil-ox-LDL: Dil-oxidized low density lipoprotein; ELISA: enzyme-linked immunosorbent assay; HFD: high-fat diet (an atherogenic diet); IL: interleukin; LAMP2: lysosomal-associated membrane protein 2; LDL-C: low density lipoprotrein cholesterol; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; ND: normal diet; Ox-LDL: oxidized low density lipoprotein; PBMC: peripheral blood mononuclear cells; SQSTM1/p62: sequestosome 1; SREBF1/SREBP1c: sterol regulatory element binding transcription factor 1; SREBF2/SREBP2: sterol regulatory element binding factor 2; STX17: syntaxin 17; TC: serum total cholesterol; TG: triglyceride; TNF: tumor necrosis factor; IFN: interferon; Treg cell: regulatory T cell.

Genome evolution in Oryza allopolyploids of various ages: Insights into the process of diploidization.

The prevalence and recurrence of whole-genome duplication in plants and its major role in evolution have been well recognized. Despite great efforts, many aspects of genome evolution, particularly the temporal progression of genomic responses to allopolyploidy and the underlying mechanisms, remain poorly understood. The rice genus Oryza consists of both recently formed and older allopolyploid species, representing an attractive system for studying the genome evolution after allopolyploidy. In this study, through screening BAC libraries and sequencing and annotating the targeted BAC clones, we generated orthologous genomic sequences surrounding the DEP1 locus, a major grain yield QTL in cultivated rice, from four Oryza polyploids of various ages and their likely diploid genome donors or close relatives. Based on sequenced DEP1 region and published data from three other genomic regions, we investigated the temporal evolutionary dynamics of four polyploid genomes at both genetic and expression levels. In the recently formed BBCC polyploid, Oryza minuta, genome dominance was not observed and its short-term responses to allopolyploidy are mainly manifested as a high proportion of homoeologous gene pairs showing unequal expression. This could partly be explained by parental legacy, rewiring of divergent regulatory networks and epigenetic modulation. Moreover, we detected an ongoing diploidization process in this genus, and suggest that the expression divergence driven by changes of selective constraint probably plays a big role in the long-term diploidization. These findings add novel insights into our understanding of genome evolution after allopolyploidy, and could facilitate crop improvements through hybridization and polyploidization.

Smoking and Cognitive Function Among Middle-Aged Adults in China: Findings From the China Health and Retirement Longitudinal Study Baseline Survey.

BACKGROUND: Smoking is prevalent among people in China. In this study, we examined the association between smoking and cognitive function in a representative sample of adults aged 45 years and older in China. METHODS: We analyzed the baseline data of 16,892 participants from the China Health and Retirement Longitudinal Study. We measured smoking based on smoking status (never, former, and current smokers) and pack years (one pack year equals 20 cigarettes per day for 1 year). We assessed cognitive function for visuospatial ability, episodic memory, orientation/attention, and overall cognitive function. Multivariate linear and logistic regressions were used to examine the independent association between smoking and cognitive function, controlling for sociodemographic factors, domestic partner status, physical health status, and depressive symptoms. RESULTS: The study participants were, on average, 60 years old. The prevalence of former and current smoking in this population was 8.4% and 28.8%, respectively. Compared with nonsmokers, former and current smokers had better cognitive function (p < .0001). After controlling for covariates, only former smokers, compared with nonsmokers, have better orientation and attention (p = .04) and overall cognitive function (p = .01). Moreover, pack years are positively associated with orientation, attention (p = .04), and overall cognitive function among all participants (p = .02). CONCLUSIONS: This study identified that, among middle-aged and older Chinese adults, former smokers had the highest cognitive function, especially attention and orientation, followed by never smokers and current smokers. When screening for cognition impairment among Chinese middle-aged and older adults, we should encourage them to quit smoking.

Poor oral health conditions and cognitive decline: Studies in humans and rats.

BACKGROUND: The relationship between poor oral health conditions and cognitive decline is unclear. OBJECTIVE: To examine the association between oral health and cognition in humans and rats. METHODS: In humans: a cross-sectional study was conducted. Cognitive levels were evaluated by the Mini Mental State Examination (MMSE); oral conditions were reflected by the number of missing index teeth, bleeding on probing, and probing pocket depth (PD). In rats: a ligature-induced (Lig) periodontitis model and Aß25-35-induced model of Alzheimer's disease (AD) were established; tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and C-reactive protein levels in the hippocampus and cerebral cortex were detected. RESULTS: MMSE scores for the number of missing index teeth ≥ 7 group were significantly lower than those in the ≤ 6 group. A negative relationship (correlation coefficient ρ = -0.310, P = 0.002) was observed between MMSE scores and number of missing index teeth. More missing index teeth and lower education levels were independent risk factors for cognitive decline. A negative relationship (correlation coefficient ρ = -0.214, P = 0.031) was observed between MMSE scores and average PD. TNF-α and IL-6 levels in the hippocampus of the Lig+AD group were significantly higher than those of the AD group. IL-1 and IL-6 levels in the cerebral cortex of the Lig+AD group were significantly higher than those of the AD group. CONCLUSION: Poor oral health conditions including more missing index teeth and higher average PD may be risk factors for cognitive decline. Periodontitis may increase inflammatory cytokines in rat models of AD.

Depression in the context of chronic diseases in the United States and China.

Depression is not only a major global public health concern, but also a common comorbidity among patients who experience chronic diseases, such as cancer, stroke, heart disease, diabetes, and chronic obstructive pulmonary disease. Yet the recognition and treatment varies widely around the world. This study (1) provides an integrated review of the literature on the prevalence of depression among patients with chronic diseases in China and the United States and its relationship to poorer health outcomes and (2) compares the differences in the percentages of patients receiving treatments for depression between the United States and China. Given the current situation, we recommended that primary care and specialty providers should be knowledgeable and alert regarding the signs of depression. Efforts should be directed to further implement integrated care based interventions to manage depression and improve quality of life among patients suffering chronic diseases in both China and the United States.

Predictors of Depressive Symptoms Among Mid-Aged and Older Men With Diabetes in China.

BACKGROUND AND PURPOSE: Although mounting evidence has consistently shown that depressive symptoms are more common among diabetic women than among diabetic men, diabetic men are frequently overlooked in diabetes-related mental health studies, and research on predicators of depressive symptoms among diabetic men remains scarce. Therefore, the purpose of this study was to examine the gender-specific characteristics that predict depressive symptoms among mid-aged and elderly men with diabetes. METHODS: A secondary data analysis was performed using the baseline data from the China and Health Retirement Longitudinal Study. A total of 824 men aged 45 years or older with diabetes were included in the analysis. Depressive symptoms were measured with the Center for Epidemiological Studies Depression Scale short form. Age, education level, marital status, nighttime sleep duration, smoking status, duration of diabetes, treatment with insulin, and pain were based on self-reports. Information on hemoglobin A1c (HbA1c), functional impairment, weight, height, and blood lipids was also collected. RESULTS: The prevalence of depressive symptoms was 22.7%. Male-specific significant predictors of depressive symptoms included nighttime sleep duration (short sleepers [p = .019], normal sleepers [p = .001], and long sleepers [p = .000]), instrumental activities of daily living (p = .001), and pain (mild pain [p = .003], moderate pain [p = .024], and severe pain [p = .017]). IMPLICATIONS FOR PRACTICE: This study provides important findings about nighttime sleep duration, pain, and functional impairment and their relationships with presence of depressive symptoms in mid-aged and older men with diabetes. Screening tools should include these items to enable early detection and depression treatment for vulnerable men who may be otherwise missed.

FoxO1 inhibits autophagosome-lysosome fusion leading to endothelial autophagic-apoptosis in diabetes.

AIMS: Inadequate autophagy contributed to endothelial dysfunction in diabetic patients. We aimed to investigate the relationship between inadequate autophagy and endothelial cells (ECs) apoptosis in diabetes and its underlying mechanism. METHODS AND RESULTS: Aortic intima and ECs were isolated from diabetic patients. Cultured human aortic endothelial cells (HAECs) were stimulated with advanced glycation end products (AGEs). The expression of autophagy and apoptosis-related proteins were determined by western blotting. Autophagosomes were observed by electron microscopy. The fusion of autophagosome and lysosomes was detected by immunofluorescence. Compared with non-diabetic subjects, the levels of LC3-II, p62, FoxO1, and Ac-FoxO1 were increased in ECs from diabetic patients, accompanied by the decreased expressions of Atg14, STX17, and co-localization of LC3-II/LAMP2 and Atg14/STX17. Long-term stimulation with AGEs up-regulated LC3-II and p62 expression and the number of autophagosomes with decreased level of Atg14, STX17, Ras-related protein 7 (Rab7), and co-localization of LC3-II/LAMP2 and Atg14/STX17 in HAECs. The apoptosis rates were increased with elevated cleaved-caspase-3 and declined Bcl-2 expression. Inhibition of autophagy with 3-methyladenine could reduce long-term AGEs-induced apoptosis. Higher levels of FoxO1, Ac-FoxO1, and Ac-FoxO1 binding to Atg7 were detected in AGEs-treated HAECs. AGEs-induced FoxO1 enhanced Akt activity, decreased SIRT1-deacetylase activity by phosphorylation and elevated Ac-FoxO1. Knockout of FoxO1 reduced AGEs-induced autophagy and promoted the expression of Atg14 and the co-localization of LC3-II/LAMP 2 and Atg14/STX17. CONCLUSION: Inadequate autophagy with impaired autophagosome-lysosomal fusion exists in aortic intima and ECs from diabetic patients. FoxO1 mediates AGEs-induced ECs autophagic apoptosis through impairing autophagosome-lysosomes fusion by inhibiting Atg14 expression.