Physical activity and health-related quality of life in older adults: depression as a mediator.

BACKGROUND: Physical activity(PA) is associated with health-related quality of life (HRQoL) among older adults, and both are associated with mood, such as depression. However, the indirect effects of PA on HRQoL in older adults have not been clearly established. This study explained how different types and intensities of PA were associated with HRQoL while considering the effects of depression in older adults. METHODS: A cross-sectional study was conducted with 7,518 community-dwelling older adults aged 60 years and older. PA (leisure-time, household, and work-related), depression, and HRQoL were measured using the Physical Activity Scale for the Elderly (PASE), the 30-item Geriatric Depression Scale (GDS-30), and the 36-Item Short-Form Health Survey (SF-36), respectively. Information on age, gender, education, monthly income, activities of daily living, smoking, and alcohol drinking was also collected. Regression analysis was used to explore the relationship between PA, depression and HRQoL, and a mediation effect test process was used to verify the mediating mechanism of the depression on this relationship. RESULTS: The study showed that after adjusting for a set of covariates, SF-36 Physical Component Summary (PCS) scores were negatively associated with depression (B = -2.046, 95% CI [2.584, -1.509]) and positively with PA (p < 0.001). Similarly, SF-36 Mental Component Summary (MCS) scores were negatively associated with depression (B = -11.657, 95% CI [-12.190, -11.124]). In mediation analyses, we found that depression partially mediated the relationship between different types and intensities PA and PCS (moderate leisure-time PA: B = 0.223, 95%CI [0.153,0.293], P < 0.001; vigorous leisure-time PA: B = 0.323, 95%CI [0.232,0.413], P < 0.001; moderate household PA: B = 0.092, 95%CI [0.045,0.139], P < 0.001; vigorous household PA: B = 0.137, 95%CI [0.085,0.190], P < 0.001; work-related PA: B = 0.193, 95%CI [0.658,0.190], P < 0.001) and MCS (moderate leisure-time PA: B = 1.243, 95%CI [1.008,1.479], P < 0.001; vigorous leisure-time PA: B = 1.800, 95%CI [1.585,2.015], P < 0.001; moderate household PA: B = 0.496, 95%CI [0.274,0.718], P < 0.001; vigorous household PA: B = 0.742, 95%CI [0.521,0.963], P < 0.001; work-related PA: B = 1.026, 95%CI [0.819,1.234], P < 0.001). CONCLUSIONS: This study suggested that leisure-time, household, and work-related PA were negatively associated with depression, while positively affecting HRQoL in Chinese older adults. The relationships between different types and intensities of PA and HRQoL were mediated by depression. Interventions aimed at promoting purposeful exercise and different types of PA may have mental health benefits. It is recommended that geriatric health managers and healthcare planners prioritize interventions to help improve PA intensities, alleviate depressive symptoms to promote beneficial effects on HRQoL in older adults.

Gene co-expression network based on part mutual information for gene-to-gene relationship and gene-cancer correlation analysis.

BACKGROUND: Finding correlation patterns is an important goal of analyzing biological data. Currently available methods for correlation analysis mainly use non-direct associations, such as the Pearson correlation coefficient, and focus on the interpretation of networks at the level of modules. For biological objects such as genes, their collective function depends on pairwise gene-to-gene interactions. However, a large amount of redundant results from module level methods often necessitate further detailed analysis of gene interactions. New approaches of measuring direct associations among variables, such as the part mutual information (PMI), may help us better interpret the correlation pattern of biological data at the level of variable pairs. RESULTS: We use PMI to calculate gene co-expression networks of cancer mRNA transcriptome data. Our results show that the PMI-based networks with fewer edges could represent the correlation pattern and are robust across biological conditions. The PMI-based networks recall significantly more important parts of omics defined gene-pair relationships than the Pearson Correlation Coefficient (PCC)-based networks. Based on the scores derived from PMI-recalled copy number variation or DNA methylation gene-pairs, the patients with cancer can be divided into groups with significant differences on disease specific survival. CONCLUSIONS: PMI, measuring direct associations between variables, extracts more important biological relationships at the level of gene pairs than conventional indirect association measures do. It can be used to refine module level results from other correlation methods. Particularly, PMI is beneficial to analysis of biological data of the complicated systems, for example, cancer transcriptome data.

Patterns of physical activity and their relationship with depression among community-dwelling older adults in Shanghai, China: a latent class approach.

BACKGROUND: Few studies have explored patterns of physical activity (PA) and examined their relationship with depression among community-dwelling older adults. We aimed to identify the patterns of PA through a person-centered analytical approach and examine the association between quantity and patterns of PA, and depression among community-dwelling older adults. METHODS: We conducted a cross-sectional survey study in the Minhang district, Shanghai, China, in August 2019, and used a self-administered questionnaire to collect data through home visits. The total sample included 2525 older adults. This study used the Physical Activity Scale for the Elderly (PASE) to assess the quantity of PA in older adults. Depression was evaluated with the Geriatric Depression Scale (GDS). Latent class analysis (LCA) was used to identify subpopulations by shared item response patterns. Logistic regressions were performed to estimate the relationship between PASE score, patterns of PA, and depression. An exploratory analysis of joint levels and patterns of PA effects on depression was based on sample subgroups with combinations of levels and patterns of PA. Logistic regression was used to calculate the odds ratio for combined subgroups. RESULTS: Four latent classes were identified: "domestic types," "athletic types," "gardening/caring types," and "walkers." PASE scores and patterns of PA both were associated with depression. Older adults who were the most active (PASE quartile: 75-100%) and the athletic types had the strongest significant association with depression (OR = 0.19, 95% CI: 0.06-0.65), followed by those who were the most active (PASE quartile: 75-100%) and the walkers (OR = 0.28, 95% CI: 0.14-0.57) when compared with older adults with the least activity (PASE quartile: 0-25%) and domestic types. CONCLUSION: This study suggests both the quantity and patterns of physical activity are associated with depressive symptoms among community-dwelling older adults. Population-level intervention should encourage community-dwelling older adults to increase their quantity of PA to reduce the risk of depression. Athletics and walkers are recommended. To develop individual-level tailored interventions, more attention should be paid to older adults who are highly engaged in gardening/caring for others.

Spatial transcriptomics reveals prognosis-associated cellular heterogeneity in the papillary thyroid carcinoma microenvironment.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study. METHODS: In conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC-associated cells within the tissue sections. The spatial RNA-clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand-receptor analysis and Gene Ontology enrichment analysis. RESULTS: The spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse-free survival in PTC patients. We discovered key ligand-receptor interactions, including LAMB3-ITGA2, FN1-ITGA3 and FN1-SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse-free survival. In the tumour immune microenvironment, reduced interaction between myeloid-derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA-clinical analysis method developed here revealed prognosis-associated cellular heterogeneity in the PTC microenvironment. CONCLUSIONS: The occurrence of tumour foci No. 2 and three enhanced ligand-receptor interactions in the AFC area/tumour foci reduced the relapse-free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients.

Shanghai Community-Based Schizophrenia Cohort (SCS): a protocol for establishing a longitudinal cohort and research database of patients with schizophrenia receiving community-based mental health treatment.

INTRODUCTION: Drivers for remission, relapse and violence-related behaviour among patients with schizophrenia are the most complicated issue. METHODS AND ANALYSIS: This study aims to recruit a longitudinal cohort of patients with schizophrenia. Two suburban districts and two urban districts were randomly selected according to health service facilities, population, geographical region and socioeconomic status. Individuals (>18 years old) who received a diagnosis of schizophrenia following the International Classification of Diseases (10th edition) criteria within the past 3 years will be invited as participants. Assessments will be carried out in local community health centres. Data will be used to (1) establish a community-based schizophrenia cohort and biobank, (2) prospectively determine the course of multidimensional functional outcomes of patients with schizophrenia who are receiving community-based mental health treatment, and (3) map the trajectories of patients with schizophrenia and prospectively determine the course of multidimensional outcomes based on the differential impact of potentially modifiable moderators. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Human Research Ethics Committee of Shanghai Mental Health Center (2021-67). Results of the study will be disseminated through peer-reviewed journals. If effective, related educational materials will be released to the public.

Effects of a Multicomponent Intervention With Cognitive Training and Lifestyle Guidance for Older Adults at Risk of Dementia: A Randomized Controlled Trial.

Objective: This study examined the effects of a multicomponent intervention program on cognitive function in community-dwelling older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD).Methods: This was a 2-arm, randomized controlled trial in which a multicomponent intervention was applied. Participants were recruited from June 2020 to August 2020, randomization and intervention began in August 2020, and the entire program ended in January 2021. It included cognitive training (mnemonic strategy training) and lifestyle guidance (diet, sleep, and exercise guidance) for 7 weeks. A total of 123 Chinese community-dwelling older adults experiencing MCI or SCD were randomly divided into a multicomponent intervention group (n = 62) and a health education group (n = 61). The global cognitive function was measured using the Mini-Mental State Examination (MMSE). The cognitive domains outcomes included memory functions measured using the immediate and delayed tests of the Auditory Verbal Learning Test (AVLT) and Logical Memory Test (LMT), and executive function and attention measured using the Digital Symbol Substitution Test (DSST) and Digit Span Test (DST). Data were collected at baseline and postintervention.Results: For cognitive outcome, the results of linear mixed-effect model showed significant time × group effects in the MMSE (Cohen d =0.63 [95% CI, 0.27 to 1.00], F = 10.25, P = .002). This study found significant time × group effects in AVLT-immediate (Cohen d = 0.47 [95% CI, 0.11 to 0.83], F = 8.18, P = .005), AVLT delayed (Cohen d = 0.45 [95% CI, 0.10 to 0.81], F = 4.59, P = .034), LMT-delayed (Cohen d = 0.71 [95% CI, 0.34 to 1.07], F = 4.59, P = .034), DSST (Cohen d = 0.27 [95% CI, -0.08 to 0.63], F = 4.83, P = .030), and DST (Cohen d =0.69 [95% CI, 0.33 to 1.05], F = 8.58, P = .004).Conclusions and Implications: The results support the feasibility and effectiveness of the multicomponent intervention program in improving cognitive function in community dwelling older adults at risk of dementia. The high adherence of this program shows its potential for promotion in the community and supports a larger and longer trial.Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200061420).

VGluT2 neuron subtypes in the paraventricular thalamic nucleus regulate depression in paraquat-induced Parkinson's disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disease and approximately one third of patients with PD are estimated to experience depression. Paraquat (PQ) is the most widely used herbicide worldwide and PQ exposure is reported to induce PD with depression. However, the specific brain region and neural networks underlying the etiology of depression in PD, especially in the PQ-induced model, have not yet been elucidated. Here, we report that the VGluT2-positive glutamatergic neurons in the paraventricular thalamic nucleus (PVT) promote depression in the PQ-induced PD mouse model. Our results show that PVTVGluT2 neurons are activated by PQ and their activation increases the susceptibility to depression in PD mice. Conversely, inhibition of PVTVGluT2 neurons reversed the depressive-behavioral changes induced by PQ. Similar to the effects of intervention the soma of PVTVGluT2 neurons, stimulation of their projections into the central amygdaloid nucleus (CeA) also strongly influenced depression in PD mice. PQ induced malfunctioning of the glutamate system and changes in the dendritic and synaptic morphology in the CeA through its role on PVTVGluT2 neuronal activation. In summary, our results demonstrate that PVTVGluT2 neurons are key neuronal subtypes for depression in PQ-induced PD and promote depression processes through the PVTVGluT2-CeA pathway.

Signaling pathway of targeting the pancreas in the treatment of diabetes under the precision medicine big data evaluation system.

Diabetes is a chronic noncommunicable disease, which is related to lifestyle, environmental and other factors. The main disease of diabetes is the pancreas. Inflammation, oxidative stress and other factors can interfere with the conduction of various cell signaling pathways, thus inducing pancreatic tissue lesions and diabetes. Precision medicine covers epidemiology, preventive medicine, rehabilitation medicine and clinical medicine. On the basis of precision medicine big data analysis, this paper takes pancreas as the target to analyze the signal pathway of diabetes treatment. This paper analyzes from the five aspects of the age structure of diabetes, the blood sugar control standard of type 2 elderly diabetes mellitus, the changes in the number of diabetic patients, the ratio of patients using pancreatic species and the changes in blood sugar using the pancreas. The results of the study showed that targeted pancreatic therapy for diabetes reduced the diabetic blood glucose rate by approximately 6.94%.

Rucaparib cocrystal: Improved solubility and bioavailability over camsylate.

Rucaparib (Ruc) is a drug used to treat advanced ovarian cancer associated with deleterious BRCA mutations. Its commercial form, the camsylate salt (Ruc-Cam), suffers from poor aqueous solubility and thus causes low and erratic oral bioavailability. In this work, we aimed to improve the oral exposure of Ruc through cocrystallization. Liquid-assisted grinding, slurry, and solvent evaporation methods were employed to prepare new solid forms of Ruc. Cocrystals of rucaparib-theophylline monohydrate (Ruc-Thp MH), rucaparib-maltol (Ruc-Mal), and rucaparib-ethyl maltol (Ruc-Emal) were obtained. Powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and dynamic vapor sorption were utilized to characterize these multi-component systems. All cocrystals dissolve faster than Ruc-Cam at pH 2.0 and 4.5, and Ruc-Thp MH displays the highest apparent solubility in pH 4.5 and 6.8 buffers. Pharmacokinetic studies in rats show that Ruc-Thp MH exhibits 2.4 times the Cmax and 1.4 times the AUC0-24h at a single dose compared with Ruc-Cam. The enhanced solubility and bioavailability of Ruc-Thp MH showcase the power of cocrystallization in addressing absorption issues in drug development.

Circular RNA PIP5K1A Promotes Glucose and Lipid Metabolism Disorders and Inflammation in Type 2 Diabetes Mellitus.

Disorders of glucose and lipid metabolism are an important cause of type 2 diabetes mellitus (T2DM). Identifying the molecular mechanism of metabolic disorders is key to the treatment of T2DM. The study was to investigate the effect of circRNA PIP5K1A (circPIP5K1A) on glucose and lipid metabolism and inflammation in T2DM rats. A T2DM rat model was established, and then the T2DM rats were injected with lentiviral vectors that interfere with circPIP5K1A, miR-552-3p, or ENO1 expression. Fasting blood glucose (FBG) and fasting insulin (FINS) levels of rats were detected by an automatic analyzer and insulin detection kit, and HOMA-IR was calculated. Lipid metabolism was assessed by measuring serum levels of TG, TC, LDL-C, leptin, and resistin. Serum levels of inflammatory factors (TNF-α and IL-6) were detected by ELISA. The pathological conditions of pancreatic tissue were observed by HE staining. circPIP5K1A, miR-552-3p and ENO1 levels were recorded. The experimental results showed that circPIP5K1A and ENO1 were up-regulated, and miR-552-3p was down-regulated in T2DM rats. Down-regulating circPIP5K1A or up-regulating miR-552-3p reduced blood glucose and lipid levels, inhibited inflammation, and improved pancreatic histopathological changes in T2DM rats. In addition, up-regulating ENO1 rescued the ameliorating effects of down-regulated circPIP5K1A on T2DM rats. In general, downregulating circPIP5K1A improves insulin resistance and lipid metabolism disorders and inhibits inflammation by targeting miR-552-3p to mediate ENO1 expression.

Single-cell and spatial transcriptome analysis reveals the cellular heterogeneity of liver metastatic colorectal cancer.

In this study, we comprehensively charted the cellular landscape of colorectal cancer (CRC) and well-matched liver metastatic CRC using single-cell and spatial transcriptome RNA sequencing. We generated 41,892 CD45- nonimmune cells and 196,473 CD45+ immune cells from 27 samples of six CRC patients, and found that CD8_CXCL13 and CD4_CXCL13 subsets increased significantly in liver metastatic samples that exhibited high proliferation ability and tumor-activating characterization, contributing to better prognosis of patients. Distinct fibroblast profiles were observed in primary and liver metastatic tumors. F3+ fibroblasts enriched in primary tumors contributed to worse overall survival by expressing protumor factors. However, MCAM+ fibroblasts enriched in liver metastatic tumors might promote generation of CD8_CXCL13 cells through Notch signaling. In summary, we extensively analyzed the transcriptional differences of cell atlas between primary and liver metastatic tumors of CRC by single-cell and spatial transcriptome RNA sequencing, providing different dimensions of the development of liver metastasis in CRC.

The specificity of T cell regulation that enables self-nonself discrimination in the periphery.

It was recently shown that perceiving the avidity of T cell activation can be translated into peripheral T cell regulation to control autoimmune disease. This regulation is achieved by CD8(+) T cells that recognize a common surrogate target structure, Qa-1/Hsp60sp, preferentially expressed by activated T cells of intermediate but not high avidity. A truncated self-reactive repertoire, devoid of high-avidity T cells, generated by thymic negative selection, allows selective down-regulation of intermediate-avidity T cells to accomplish self-nonself discrimination in the periphery. Identification of the common surrogate target structure expressed on intermediate-avidity T cells opens up a conceptual theme to understand the relationship between the specificity of peripheral immune regulation and self-nonself discrimination. Here, we investigated peptide vaccination induced cross-protection mediated by CD8(+) T cells in two autoimmune disease models, experimental allergic encephalomyelitis (EAE) and type 1 diabetes (T1D). We show that Qa-1 restricted CD8(+) T cells cross-protect animals from either EAE or T1D without abrogating the immune response to foreign antigens. Cross-protection occurs because potentially pathogenic self-reactive T cells included in the pool of intermediate-avidity T cells are capable of preferentially expressing common surrogate target structures on their surface to render themselves subject to the down-regulation, independent of the specificity of the antigens that they are triggered by. Thus, like in the thymus, the immune system discriminates self from nonself, during adaptive immunity in the periphery, not by recognizing the structural differences between self and foreign antigens, but rather by perceiving the avidity of T cell activation.

Effects of cognitive impairment and depressive symptoms on health-related quality of life in community-dwelling older adults: The mediating role of disability in the activities of daily living and the instrumental activities of daily living.

The objective of this study was to estimate the joint effects of cognitive impairment and depressive symptoms on health-related quality of life (HRQoL) and to explore the mediating role of disability among Chinese community-dwelling older adults. A cross-sectional study was conducted with 2525 community-dwelling older adults aged ≥60 years and living in Shanghai, China in 2019. Participants were divided into four groups: (1) non-depressed without dementia, (2) non-depressed with probable MCI, (3) depressed without dementia and (4) depressed with probable mild cognitive impairment (MCI). HRQoL was assessed using the 36-Item Short-Form Health Survey. Cognitive impairment and depressive symptoms were evaluated with the AD8 and the Geriatric Depression Scale respectively. Activities of daily living (ADL) and instrumental activities of daily living (IADL) disability and other sociodemographic variables were also assessed. The results of this study showed that controlling for sociodemographic characteristics, significant differences in a physical component score (PCS) and a mental component score (MCS) of HRQoL were found across the four groups. Compared to those who were non-depressed without dementia, older adults who were depressed with probable MCI reported the lowest level of PCS and MCS, followed by older adults who were depressed without dementia. Both ADL and IADL disabilities played mediating roles in the relationship between cognitive impairment and depressive symptoms and PCS. Based on this study, we suggest that the early detection and adequate management of depressive symptoms and cognitive status-as well as efforts to improve individuals' ability to manage their ADLs and IADLs-may help to maintain or improve their HRQoL.

Dehydroepiandrosterone Cocrystals with Improved Solubility and Bioavailability.

Dehydroepiandrosterone (DHEA) is an FDA-approved food supplement used as an assisted reproductive sex hormone. The bioavailability is severely limited by its poor solubility (23 µg/mL). Herein, we aimed to modulate its solubility through cocrystallization. Eight cocrystals of DHEA with pyrocatechol (CAT), hydroquinone (HQ), resorcinol (RES), phloroglucinol (PG), 1,5-dihydroxy naphthalene (DHN), p-hydroxybenzoic acid (PHBA), gallic acid (GA), and 5-hydroxyisophthalic acid (5HIPA) were designed and synthesized. Some basic characterization tools, including powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, and Fourier transform infrared spectroscopy, were also applied in our work for basic analyses of cocrystals. It is indicated that DHEA-GA exhibits its superiority in dissolution and pharmacokinetic behaviors. While the area under the curve values of DHEA-GA is improved at the ratio of 2.2, the corresponding bioavailability of DHEA is expected to be accordingly increased.

Lactate score predicts survival, immune cell infiltration and response to immunotherapy in breast cancer.

Background: Tumor-derived lactate can modulate the function of infiltrating immune cells to establish an immunosuppressive microenvironment that favors tumor progression. However, possible effects of lactate-related genes (LRGs) on the tumor microenvironment (TME) of breast cancer (BRCA) are still unknown. Methods: LRGs were comprehensively screened from lactate metabolism-related pathways. We correlated the expression of these LRGs with immune cell infiltrating characteristics in the TME and clinicopathological features of patients. We also established a lactate score for quantifying lactate metabolism patterns of cancers and to predict of recurrence-free survival (RFS). Results: We successfully constructed a lactate score that was an independent prognostic factor in BRCA. A low lactate score, which was associated with immune activation with increased CD8+ T cells infiltration levels, indicated an inflamed TME. Consistently, higher expression levels of inhibitory immune checkpoints, including PD-L1, LAG3, CTLA4, and TIM3, as observed from high lactate score subgroup, suggested an immune-desert phenotype as well as poor prognosis. Moreover, a low lactate score predicted the increased chemotherapeutic drug sensitivity and enhanced anti-PD-1 immunotherapy responses. Conclusion: The present study analyzed the potential roles of LRGs in the TME diversity and prognosis. These results will help to improve our understanding of the characteristics of TME immune cell infiltration and guide the development of more effective immunotherapy strategies.

Association between physical activity and mild cognitive impairment in community-dwelling older adults: Depression as a mediator.

Introduction: Dementia has become a public health priority and is irreversible. Mild cognitive impairment (MCI), an intermediate state between normal cognition and dementia, is the prime time for early diagnosis and intervention. The activities of daily living of dementia patients are usually insufficient. Therefore, continuing to explore the risk factors of MCI, especially the influence of physical activity on MCI and its mechanism can enrich the relevant research fields in China. Materials and methods: For this cross-sectional study, 2,518 adults aged 60 years or older in Xinzhuang, Minhang District, Shanghai were recruited between July 2019 and April 2019, using a multistage, cluster-sampling method. A binary unconditional logistic regression model was used with MCI status as the dependent variable. Different types of physical activity were separately included in the multifactor model to test their correlations. Sensitivity analysis was performed using BADL as a stratification factor. The mediating effect of depression between physical activity and MCI was examined using the Bootstrap method. Results: This research includes 271 (10.8%) MCI. Old age (odds ratio 2.967 [95%CI 2.063∼4.269]), having diabetes (1.816 [1.302∼2.534]), and depression (3.012 [2.209∼4.108]) were possible risk factors for MCI. High education level (0.722 [0.523∼0.999]), medium level of physical activity (0.459 [0.326∼0.645]), and high level of physical activity (0.396 [0.270∼0.580]) were possible protective factors. Medium (0.548 [0.396∼0.757]) and high levels (0.557 [0.366∼0.846]) of physical exercise and medium (0.433 [0.318∼0.590]) and high levels (0.487 [0.296∼0.801]) of household chores are possible protective factors of MCI and their significance remained in the mutually adjusted model. Sensitivity analysis showed that physical activity and household chores were possible protective factors in all strata (P < 0.05). Physical exercise and work-related activities showed a protective effect in fully independent older adults, but the effect disappeared in those who cannot be fully independent. Depression played a partially mediating role with an indirect effect of 6.67%. Discussion: Overall, our results highlight that physical activity is a possible protective factor for MCI. Physical exercise and household chores have strong protective effects and future interventions could be targeted from this perspective. Depression plays a partially mediating role and more attention should be paid to the mental health of older adults.

Starburst triarylamine donor-acceptor-donor quadrupolar derivatives based on cyano-substituted diphenylaminestyrylbenzene: tunable aggregation-induced emission colors and large two-photon absorption cross sections.

In this work, we have developed a new class of aggregation-induced emission (AIE) active compounds, in which three electron-donating diphenylamine, phenothiazine, or carbazole groups are connected to the 1, 4-positions of the benzene through bis(α-cyano-4-diphenylaminostyryl) conjugation bridges to form three triarylamine quadrupolar derivatives (3 a-c). Their one- and two-photon absorption properties have been investigated. The two-photon absorption (2PA) cross sections measured by the open-aperture Z-scan technique were determined to be 1016, 1484, and 814 GM for 3 a-c, respectively. From this result, the high 2PA properties of these molecules are attributed to the extended π system and enhanced intramolecular charge transfer from the starburst triarylamine to the cyano group. Moreover, cyano-substituted diphenylamine styrylbenzene (CNDPASB)-based compounds are very weakly fluorescent in THF, but their intensities increase by almost 230, 70, and 5 times, respectively, in water/THF (v/v 90 %) mixtures, in which they exhibit strongly enhanced red, orange, and deep yellow fluorescence emissions, respectively. This result indicates that the intramolecular vibration and rotation of these dyes is considerably restricted in nano-aggregates formed in water, leading to significant increases in fluorescence. It was found that the color tuning of the CNDPASB-based compounds could be conveniently accomplished by changing the starburst triarylamine donor moiety. Multilayer electroluminescence devices with TPBI (2,2',2''-(benzene-1,3,5-triyl)-tri(1-phenyl-1H-benzimidazole)) electron-transporting layers have been made, with 3 a and 3 c as a non-doping red-yellow emitter. The preliminary results for these multilayer devices show a maximum efficiency of 0.25 %, and electroluminescence (EL) wavelengths around 568 nm. The excellent 2PA and AIE properties of these compounds make them potential materials for biophotonic applications.

Smoothing spline ANOVA frailty model for recurrent event data.

Gap time hazard estimation is of particular interest in recurrent event data. This article proposes a fully nonparametric approach for estimating the gap time hazard. Smoothing spline analysis of variance (ANOVA) decompositions are used to model the log gap time hazard as a joint function of gap time and covariates, and general frailty is introduced to account for between-subject heterogeneity and within-subject correlation. We estimate the nonparametric gap time hazard function and parameters in the frailty distribution using a combination of the Newton-Raphson procedure, the stochastic approximation algorithm (SAA), and the Markov chain Monte Carlo (MCMC) method. The convergence of the algorithm is guaranteed by decreasing the step size of parameter update and/or increasing the MCMC sample size along iterations. Model selection procedure is also developed to identify negligible components in a functional ANOVA decomposition of the log gap time hazard. We evaluate the proposed methods with simulation studies and illustrate its use through the analysis of bladder tumor data.

Expression of G3BP1 in benign and malignant human prostate tissues.

BACKGROUND: Prostate cancer (PCa) is the world's leading type of cancer in men. GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is overexpressed in a variety of tumors. However, there are limited studies in PCa concerning G3BP1. This present study was to investigates the expression of G3BP1 and the mechanism of action on PCa. METHODS: We explored the G3BP1 expression in PCa using the TCGA database and verified it using clinical samples by immunohistochemistry (IHC) methods. G3BP1 and Androgen receptor (AR) status of 104 human PCa and 50 benign prostate hyperplasia (BPH) samples were analyzed by IHC and the association between G3BP1 expression and biochemical recurrence was determined. Moreover, we generated G3BP1 knockdown cell lines in human PCa LNCaP cell lines, to observe AR changes. RESULTS: G3BP1 and AR were overexpressed in PCa compared to BPH tissues. The expression of G3BP1 and AR was positively correlated with the malignant degree of the tumor. Higher G3BP1 expression showed a trend toward biochemical recurrence. Western blot showed downregulation of G3BP1 affected AR expression levels. CONCLUSIONS: Our study suggested that G3BP1 was frequently upregulated in PCa and closely related to AR expression and tumor metastasis. Besides, G3BP1 might be associated with biochemical recurrence. These results supply potential target for the management of the PCa.

Knowledge, Attitudes, and Stigma Related to Dementia Among Illiterate and Literate Older Adults in Shanghai.

BACKGROUND: China has the largest population of patients with dementia worldwide, no assessment of illiterate old population's dementia knowledge, attitudes, stigma have been conducted so far in China. AIM: This study focused on the impact of education on knowledge, attitudes, and stigma related to dementia. METHODS: The community-based sample used in this study was recruited using multi-stage random sampling from residents aged ≥60 years registered in Shanghai. We used the Geriatric Depression Scale (GDS-30) to identify depression, and the Ascertain Dementia 8 questionnaire (AD8) for evaluating participants' cognitive impairment. Knowledge, Attitude, Belief, and Practice scale, Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) were used for measuring dementia knowledge, attitudes, stigma. We separated the population into illiterate and literate group, propensity score matching based on age, sex, depression, and cognitive impairment. We calculated the difference of knowledge, attitudes, and stigma related to dementia between illiterate and literate groups. RESULTS: Two thousand five hundred and eighteen participants completed the survey. After propensity score matching, 186 pairs of matched participants left. The overall correct rate of dementia knowledge was 70.34%. The illiterate group had a lower percentage of correct answers for each knowledge item. The item "Dementia is not a disease, it is forgetfulness due to aging" had the lowest accuracy rate in both groups (38.71% vs. 50.54%, p=0.022). Illiterate older adults were less accepting of dementia than literate older adults. The majority of participants did not agree that: "There is no need to visit a doctor when older people have memory loss, difficulty communicating, or finding words" (56.99% vs. 68.28%). Illiterate older adults had higher scores for the items assessing stigma toward dementia than literate older adults. CONCLUSION: Dementia-related knowledge and attitudes among community-dwelling older adults in Shanghai may be related to literacy.