Poor pulmonary function is associated with mild cognitive impairment, its progression to dementia, and brain pathologies: A community-based cohort study.

INTRODUCTION: The relationship between pulmonary function (PF) and mild cognitive impairment (MCI), dementia, and brain pathologies remains unclear. METHODS: A total of 1312 dementia-free participants, including a cognitively intact group (n = 985) and an MCI group (n = 327), were followed for up to 21 years to detect incident MCI and dementia. PF was assessed at baseline with a composite score and tertiled. Over follow-up, 540 participants underwent autopsies for neuropathological assessment. RESULTS: Compared to the highest PF, the hazard ratios (95% confidence intervals [CIs]) of the lowest PF were 1.95 (1.43-2.66) for MCI in the cognitively intact group and 1.55 (1.03-2.33) for dementia in the MCI group. Low PF was further related to Alzheimer's disease pathology (odds ratio [OR] 1.32, 95% CI 1.19-1.47) and vascular pathology (OR 3.05, 95% CI 1.49-6.25). DISCUSSION: Low PF increases MCI risk and accelerates MCI progression to dementia. Both neurodegenerative and vascular mechanisms may underlie the PF-dementia association.

Pulmonary function is associated with cognitive decline and structural brain differences.

The association of poor pulmonary function (PF) with cognitive trajectories and structural brain differences remains unclear. Within the Rush Memory and Aging Project, 1377 dementia-free subjects were followed up to 21 years. PF was assessed with a composite score measured at baseline. Global and domain-specific cognitive function was assessed annually constructed from 19 cognitive tests. A subsample of 351 participants underwent brain magnetic resonance imaging to investigate the cross-sectional association between PF and structural brain volumes. We found that low PF was related to faster decline in global cognition, and domain-specific function including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed. In addition, low PF was associated with smaller volumes of total brain, white matter and gray matter, and larger white matter hyperintensities volume. Our results suggest that low PF is associated with faster cognitive decline, and both neurodegeneration and vascular brain lesions may underlie the association.

Association of cardiovascular risk burden with risk of dementia and brain pathologies: A population-based cohort study.

INTRODUCTION: The impact of cardiovascular risk burden on brain pathologies remains unclear. We aimed to examine the association of the Framingham General Cardiovascular Risk Score (FGCRS) with dementia risk, and brain pathologies. METHODS: Within the Rush Memory and Aging Project, 1588 dementia-free participants were assessed on FGCRS at baseline and followed up to 21 years. During the follow-up, 621 participants died and underwent autopsies. RESULTS: The multi-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of FGCRS were 1.03 (1.00-1.07) for dementia and 1.04 (1.01-1.07) for Alzheimer's disease (AD) dementia. Further, a higher FGCRS was associated with higher gross chronic cerebral infarctions (odds ratio [OR] 1.08, 95% CI 1.02-1.14), cerebral atherosclerosis (OR 1.10, 95% CI 1.03-1.17), and global AD pathology (OR 1.06, 95% CI 1.01-1.12). CONCLUSIONS: A higher FGCRS is associated with an increased risk of dementia and AD dementia. Both vascular and AD pathologies in the brain may underlie this association.

Association of life-course depression with the risk of dementia in late life: A nationwide twin study.

INTRODUCTION: Whether depression is a prodromal phase or risk factor for dementia is under debate. We aimed to unveil the nature of depression-dementia association by looking into the time window of depression occurrence. METHODS: Dementia-free twins (n = 41,727) from the Swedish Twin Registry were followed-up for 18 years. Data were analyzed using generalized estimating equation (GEE) for all individuals and conditional logistic regression for co-twin matched pairs. RESULTS: In the GEE model, multi-adjusted odds ratios (ORs; 95% confidence intervals [CIs]) of dementia were 1.46 (1.09-1.95) for mid-life, 2.16 (1.82-2.56) for late-life, 2.24 (1.49-3.36) for mid- to late-life, and 2.65 (1.17-5.98) for lifelong depression. The ORs in conditional logistic regression and in GEE did not differ significantly (P = 0.60). Education ≥8 years attenuated dementia risk associated with mid-life depression. DISCUSSION: Not only late-life depression, but also mid-life depression is associated with dementia. Genetic and early-life environmental factors could not account for this association. Education ≥8 years might buffer the impact of mid-life depression on dementia.

Association of lifespan cognitive reserve indicator with the risk of mild cognitive impairment and its progression to dementia.

INTRODUCTION: The association of lifespan cognitive reserve (CR) with mild cognitive impairment (MCI) remains controversial. We aimed to examine the association of lifespan CR indicator with the risk of MCI and its progression to dementia, taking brain pathologies into account. METHODS: In a community-based cohort study (mean age, 79 years) with annual follow-up (median, 5.16 years; maximum, 20 years), a cognitively intact group (n = 1182) and an MCI group (n = 420) were identified at baseline. During the follow-up, 611 participants died and underwent autopsies. CR indicator encompassing education, early life to late-life cognitive and social activities were obtained and tertiled. RESULTS: The multi-adjusted hazard ratio (HR) of MCI was 0.72 (95% confidence interval [CI] 0.58 to 0.90) in the cognitively intact group, and the HR of dementia was 0.66 (95% CI 0.45 to 0.97) in the MCI group for participants with the highest CR indicator (reference: the lowest CR indicator). Among MCI participants with brain pathologies, dementia incidence was about 50% lower in people with the highest CR indicator than the lowest CR indicator. DISCUSSION: High lifespan CR indicator reduces risk of MCI, and delays its progression to dementia.

Near-Infrared Light-Triggered Chlorine Radical (. Cl) Stress for Cancer Therapy.

Free radicals with reactive chemical properties can fight tumors without causing drug resistance. Reactive oxygen species (ROS) has been widely used for cancer treatment, but regrettably, the common O2 and H2 O2 deficiency in tumors sets a severe barrier for sufficient ROS production, leading to unsatisfactory anticancer outcomes. Here, we construct a chlorine radical (. Cl) nano-generator with SiO2 -coated upconversion nanoparticles (UCNPs) on the inside and Ag0 /AgCl hetero-dots on the outside. Upon near-infrared (NIR) light irradiation, the short-wavelength emission UCNP catalyzes . Cl generation from Ag0 /AgCl with no dependence on O2 /H2 O2 . . Cl with strong oxidizing capacity and nucleophilicity can attack biomolecules in cancer cells more effectively than ROS. This . Cl stress treatment will no doubt broaden the family of oxidative stress-induced antitumor strategies by using non-oxygen free radicals, which is significant in the development of new anticancer agents.

Type 2 diabetes in midlife and risk of cerebrovascular disease in late life: a prospective nested case-control study in a nationwide Swedish twin cohort.

AIMS/HYPOTHESIS: We aimed to examine the association between midlife type 2 diabetes mellitus and cerebrovascular disease (CBD) in late life, and further to explore whether genetic and early-life familial environmental factors (such as shared childhood socioeconomic status and adolescent environment) play a role in this association. METHODS: In this prospective nested case-control study based on the Swedish Twin Registry, 33,086 twin individuals who were born in 1958 or earlier and were CBD-free before the age of 60 were included. Midlife (40-59 years) type 2 diabetes was ascertained from self-report, the National Patient Registry (NPR) and glucose-lowering medication use. CBD diagnosis (cerebral infarction, occlusion of cerebral arteries, subarachnoid haemorrhage, intracerebral haemorrhage and unspecified CBD) and onset age were identified from the NPR. Late-life CBD was defined as CBD onset age ≥60 years. Generalised estimating equation (GEE) models were used to analyse unmatched case-control data (adjusted for the clustering of twins within a pair). Conditional logistic regression was used in co-twin matched case-control analyses in CBD-discordant twin pairs. RESULTS: Of all the participants, 1248 (3.8%) had midlife type 2 diabetes and 3121 (9.4%) had CBD in late life. In GEE models adjusted for age, sex, education, BMI, smoking, alcohol consumption, marital status, hypertension and heart disease, the ORs (95% CIs) of type 2 diabetes were 1.29 (1.03, 1.61) for cerebral infarction, 2.03 (1.20, 3.44) for occlusion of cerebral arteries, 0.52 (0.12, 2.21) for subarachnoid haemorrhage and 0.78 (0.45, 1.36) for intracerebral haemorrhage. In multi-adjusted conditional logistic regression, the OR of the type 2 diabetes-cerebral infarction association was 0.96 (0.51, 1.80). The differences in ORs from the GEE and co-twin control analyses were not statistically significant (p = 0.780). CONCLUSIONS/INTERPRETATION: Midlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. Genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes-cerebral infarction association, but further clarification is needed.

Overweight in midlife and risk of cancer in late life: A nationwide Swedish twin study.

Our study examined whether midlife overweight (body mass index [BMI] ≥25) is associated with late-life cancer risk and explored the role of genetic and early-life environmental factors in this association. The study included 14,766 individuals from the Swedish Twin Registry, whose midlife (30-50 years) height and weight were recorded. Information on cancer diagnoses in late life (>65 years) was derived from the National Patient Registry and Cancer Registry. Generalized estimating equation (GEE) models were used to analyze unmatched case-control data (controlled for the clustering of twins within a pair). A co-twin matched case-control analysis used conditional logistic regression to compare cancer-discordant twins. Of all participants, 3968 (26.9%) were overweight and 4253 (28.8%) had cancer. In multi-adjusted GEE models using normal-weight (BMI 18.5-24.9) participants as the reference group, overweight was related to higher risk of colon cancer (OR 1.36, 95% CI: 1.00-1.84, p = 0.049), liver cancer (OR 2.00, 95% CI: 1.11-3.62), cervix uteri cancer (OR 2.86, 95% CI: 1.19-6.91) and corpus uteri cancer (OR 1.78, 95% CI: 1.14-2.78) but lower risk of nonmelanoma skin cancer (OR 0.77, 95% CI: 0.66-0.90). In conditional logistic regression analysis, these associations were attenuated becoming nonsignificance. The difference in ORs from the unmatched and matched analyses was not significant. In conclusion, midlife overweight is associated with increased risk of late-life colon, liver and uterine cancer but reduced risk of late-life nonmelanoma skin cancer. Further investigations are warranted to explore the role of genetic and early-life environmental factors in these associations.

Flocculation characteristics of a bioflocculant produced by the actinomycete Streptomyces sp. hsn06 on microalgae biomass.

BACKGROUND: Microbial flocculation is a good choice for harvest of microalgae biomass, which has gained extensive attention. There have been carried out massive studies in bacterial flocculation, many bacterial strains with flocculation activity were isolated and different types of bioflocculants were produced. However, harvest of algal biomass by bioflocculants which produced from actinomycete are deficiency. In this study, the bioflocculant from an actinomycete Streptomyces sp. hsn06 could be used to harvest Chlorella vulgaris biomass. RESULTS: Consecutive treatment with 20 mg·L- 1 bioflocculant and 5 mM CaCl2 for 5 min showed the highest flocculating activity. The bioflocculant was a nonprotein substance with thermal stability and pH stability, which can be used in comprehensive applications. Chemical analysis of the bioflocculant indicated that it is a small molecule substance of moderate polarity with containing triple bond and cumulated double bonds. Algal temperature, pH, and metal ions showed great effects on the flocculation efficiency of the bioflocculant. CONCLUSIONS: The bioflocculant produced by Streptomyces sp. hsn06 possesses the potential to harvest algal biomass with high-efficiency.

In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4 -TAT Nanoprobes.

Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T-cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T-cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T-cell immunotherapy targeting glioma. In this work, ultrasmall T1 MR-based nanoprobes, NaGdF4 -TAT, as molecular probes with high longitudinal relaxivity (8.93 mm-1 s-1 ) are designed. By means of HIV-1 transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled with the NaGdF4 -TAT nanoprobes without any measurable side effects on the labeled T-cells, which is remarkably superior to that of the control fluorescein isothiocyanate-NaGdF4 concerning labeling efficacy. Labeled adoptive T-cell clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h after intravenous infusion of 107 labeled T-cells by T1 -weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF4 -TAT nanoprobes labeling of T-cells may be a promising method to track adoptive T-cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas.

Developmental toxicity and inhibition of the fungicide hymexazol to melanin biosynthesis in zebrafish embryos.

Hymexazol is an efficacious and widely used fungicide. However, its environmental toxicological assessment has not been well documented. It had no report of its toxicity to fish embryo. Fish embryo acute toxicity tests are highly predictive of aquatic embryotoxicity outcome. In this study, zebrafish (Danio rerio) embryos were exposed to hymexazol at varying concentrations for the study of the developmental toxicity, melanin biosynthesis, biochemical and transcriptional endpoints. The embryotoxicity tests indicated that the 96h LC50 value of hymexazol was 649mg/L with a 95% confidence interval range of 632-667mg/L. Hymexazol at concentrations of 417-738mg/L decreased the heart rate and increased the voluntary swing. Hymexazol inhibited normal development at concentrations above 554mg/L. the 96h EC50 was 411mg/L. Hymexazol in a concentration range of 417-738mg/L induced cardiac edema and yolk sac edema. Exposure of hymexazol at such concentrations to zebrafish embryos for 48h decreased the pigment area density compared with the no hymexazol control. Tyrosinase activity was inhibited by hymexazol relative to the untreated control. The P53 mRNA expression level in embryos upon exposure to 480mg/L or greater of hymexazol was significantly higher than that of the control. The results indicated that hymexazol has quite low acute toxicity and low embryotoxicity to zebrafish.

Identification of important modules and biomarkers in tuberculosis based on WGCNA.

Background: Tuberculosis (TB) is a significant public health concern, particularly in China. Long noncoding RNAs (lncRNAs) can provide abundant pathological information regarding etiology and could include candidate biomarkers for diagnosis of TB. However, data regarding lncRNA expression profiles and specific lncRNAs associated with TB are limited. Methods: We performed ceRNA-microarray analysis to determine the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs). Weighted gene co-expression network analysis (WGCNA) was then conducted to identify the critical module and genes associated with TB. Other bioinformatics analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and co-expression networks, were conducted to explore the function of the critical module. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to validate the candidate biomarkers, and receiver operating characteristic analysis was used to assess the diagnostic performance of the candidate biomarkers. Results: Based on 8 TB patients and 9 healthy controls (HCs), a total of 1,372 differentially expressed lncRNAs were identified, including 738 upregulated lncRNAs and 634 downregulated lncRNAs. Among all lncRNAs and mRNAs in the microarray, the top 25% lncRNAs (3729) and top 25% mRNAs (2824), which exhibited higher median expression values, were incorporated into the WGCNA. The analysis generated 16 co-expression modules, among which the blue module was highly correlated with TB. GO and KEGG analyses showed that the blue module was significantly enriched in infection and immunity. Subsequently, considering module membership values (>0.85), gene significance values (>0.90) and fold-change value (>2 or < 0.5) as selection criteria, the top 10 upregulated lncRNAs and top 10 downregulated lncRNAs in the blue module were considered as potential biomarkers. The candidates were then validated in an independent validation sample set (31 TB patients and 32 HCs). The expression levels of 8 candidates differed significantly between TB patients and HCs. The lncRNAs ABHD17B (area under the curve [AUC] = 1.000) and ENST00000607464.1 (AUC = 1.000) were the best lncRNAs in distinguishing TB patients from HCs. Conclusion: This study characterized the lncRNA profiles of TB patients and identified a significant module associated with TB as well as novel potential biomarkers for TB diagnosis.

Evaluation of the IP-10 mRNA release assay for diagnosis of TB in HIV-infected individuals.

HIV-infected individuals are susceptible to Mycobacterium tuberculosis (M.tb) infection and are at high risk of developing active tuberculosis (TB). Interferon-gamma release assays (IGRAs) are auxiliary tools in the diagnosis of TB. However, the performance of IGRAs in HIV-infected individuals is suboptimal, which limits clinical application. Interferon-inducible protein 10 (IP-10) is an alternative biomarker for identifying M.tb infection due to its high expression after stimulation with M.tb antigens. However, whether IP-10 mRNA constitutes a target for the diagnosis of TB in HIV-infected individuals is unknown. Thus, we prospectively enrolled HIV-infected patients with suspected active TB from five hospitals between May 2021 and May 2022, and performed the IGRA test (QFT-GIT) alongside the IP-10 mRNA release assay on peripheral blood. Of the 216 participants, 152 TB patients and 48 non-TB patients with a conclusive diagnosis were included in the final analysis. The number of indeterminate results of IP-10 mRNA release assay (13/200, 6.5%) was significantly lower than that of the QFT-GIT test (42/200, 21.0%) (P = 0.000026). IP-10 mRNA release assay had a sensitivity of 65.3% (95%CI 55.9% - 73.8%) and a specificity of 74.2% (95%CI 55.4% - 88.1%), respectively; while the QFT-GIT test had a sensitivity of 43.2% (95%CI 34.1% - 52.7%) and a specificity of 87.1% (95%CI 70.2% - 96.4%), respectively. The sensitivity of the IP-10 mRNA release assay was significantly higher than that of QFT-GIT test (P = 0.00062), while no significant difference was detected between the specificities of these two tests (P = 0.198). The IP-10 mRNA release assay showed a lower dependence on CD4+ T cells than that of QFT-GIT test. This was evidenced by the fact that the QFT-GIT test had a higher number of indeterminate results and a lower sensitivity when the CD4+ T cells counts were decreased (P < 0.05), while no significant difference in the number of indeterminate results and sensitivity were observed for the IP-10 mRNA release assay among HIV-infected individuals with varied CD4+T cells counts (P > 0.05). Therefore, our study suggested that M.tb specific IP-10 mRNA is a better biomarker for diagnosis of TB in HIV-infected individuals.

Fine and coarse particulate air pollution and out-of-hospital cardiac arrest onset: a nationwide case-crossover study in China.

Out-of-hospital cardiac arrest (OHCA) is a global public health concern. Nationwide studies on the effects of short-term exposure to particulate matter (PM) on OHCA risk are rare in regions with high PM levels, and evidence for coarse PM (PM2.5-10) is limited and inconsistent. To evaluate the associations between fine PM (PM2.5) and PM2.5-10 and OHCA onset, a time-stratified case-crossover study was conducted on 77,261 patients with cardiac OHCA in 26 cities across China in 2020. Daily PM2.5 and PM2.5-10 concentrations were assessed with high-resolution and full-coverage PM estimations. Conditional logistic regression models were applied in analyses. Each interquartile range of PM increase in 3-day moving average was associated with an increased risk of cardiac OHCA onset of 2.37% (95% CI, 1.20-3.56%) for PM2.5 and 2.12% (95% CI, 0.70-3.56%) for PM2.5-10. Stratified analyses showed higher susceptibility in patients over 75 years for PM2.5 exposure and with diabetes for PM2.5-10. This first nationwide study in region with high PM levels and great PM variability found not only PM2.5 but also PM2.5-10 were associated with a higher risk of OHCA onset, which could add powerful epidemiological evidence to this field and provide new evidence for the formulation of air quality guidelines.

Incidence, process of care, and outcomes of out-of-hospital cardiac arrest in China: a prospective study of the BASIC-OHCA registry.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is an important global public health issue, but its epidemiology and outcomes in low-income and middle-income countries remain largely unknown. We aim to comprehensively describe the incidence, process of care, and outcomes of OHCA in China. METHODS: In the prospective, multicentre, population-based Baseline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA) registry study, participating sites were selected from both urban and rural areas in all seven geographical regions across China. All patients with OHCA assessed by emergency medical service (EMS) staff were consecutively enrolled from Aug 1, 2019, to Dec 31, 2020. Patients with suspected cardiac arrest assessed by bystanders whose return of spontaneous circulation was achieved without the need for defibrillation or EMS personnel cardiopulmonary resuscitation were excluded. Patients with all key variables missing were excluded, including resuscitation attempt, age, sex, witnessed status, cause, all process of care indicators, and all outcome measures. In this analysis, we included data for EMS agencies serving 25 monitoring sites (20 urban and five rural) that included the entire serving population, data for the whole of 2020, and at least 50 OHCA patients in 2020. Data were collected and reported using the Utstein template. We calculated the crude incidence of EMS-assessed OHCA in 2020. We also report data on baseline characteristics (including sex, cause, location of OHCA, and presence of shockable rhythm), process of care (including EMS response time, cardiopulmonary resuscitation, defibrillation, and advanced life support), and outcomes of non-traumatic OHCA between Aug 1, 2019, and Dec 31, 2020, including survival and survival with favourable neurological outcomes at discharge or 30 days, and at 6 and 12 months. FINDINGS: Of 115·1 million people served by the 25 participating sites, 132 262 EMS-assessed patients with OHCA were enrolled, and resuscitation was attempted for 42 054 (31·8%) patients between Aug 1, 2019, and Dec 31, 2020. The crude incidence of EMS-assessed OHCA was 95·7 per 100 000 population (95% CI 95·6-95·8) in 2020. Among 38 227 individuals with non-traumatic OHCA, 25 958 (67·9%) were male, 30 282 (79·2%) had a cardiac arrest at home, 32 523 (85·1%) had a presumed cardiac cause, and 2297 (6·0%) presented with an initial shockable rhythm. 4049 (11·5%) of 35 090 patients with an unwitnessed or bystander-witnessed OHCA received dispatcher-assisted cardiopulmonary resuscitation and 7121 (20·3%) received bystander cardiopulmonary resuscitation; only 14 (<0·1%) patients were assessed by bystanders with an automated external defibrillator. The median EMS response time was 12 min (IQR 9-16). At hospital discharge or 30 days, 441 (1·2%) of 38 227 survived, 304 (0·8%) survived up to 6 months, and 269 (0·7%) up to 12 months. At hospital discharge or 30 days, 309 (0·8%) survived with favourable neurological outcomes, 257 (0·7%) had favourable neurological outcomes at 6 months, and 236 (0·6%) at 12 months. INTERPRETATION: Our findings revealed a high burden of EMS-assessed OHCA with a low proportion of resuscitation attempts. The suboptimal implementation of chain of survival and unsatisfactory prognosis call for national efforts to improve the care and outcomes of patients with OHCA in China. FUNDING: The National Science & Technology Fundamental Resources Investigation Program of China, the State Key Program of the National Natural Science Foundation of China, Taishan Pandeng Scholar Program of Shandong Province, the Key Research & Development Program of Shandong Province, the Interdisciplinary Young Researcher Groups Program of Shandong University, the Clinical Research Center of Shandong University, the ECCM Program of Clinical Research Center of Shandong University, and the Natural Science Foundation of Shandong Province.

Sevoflurane diminishes neurogenesis and promotes ferroptosis in embryonic prefrontal cortex via inhibiting nuclear factor-erythroid 2-related factor 2 expression.

OBJECTIVE: Prenatal sevoflurane exposure may pose neurotoxicity to embryonic brain development and lead to cognitive dysfunction in offspring, but the underlying mechanism is still unclear. We aimed to investigate whether sevoflurane could cause neurogenesis abnormality and ferroptosis in embryonic prefrontal cortex (PFC) and to identify the role of nuclear factor-erythroid 2-related factor 2 (Nrf2) in the sevoflurane-related neurotoxicity. METHODS: We used the rodents and primary neural stem cells to examine whether sevoflurane impacted proliferation, differentiation, ferroptosis and apoptosis in the neural stem cells of embryonic PFC. In addition, the expression of Nrf2 and the intensity of reactive oxygen species (ROS) were also assessed to explore the underlying molecular mechanism. RESULTS: Our results showed that sevoflurane exposure in third trimester could lead to neurogenesis inhibition and ferroptosis in-vivo embryonic PFC, with little influence on apoptosis. Moreover, a significant decrease in the expression of Nrf2 as well as an increase in ROS accumulation were also found in neural stem cells after sevoflurane anesthesia. CONCLUSION: We conclude that Nrf2-related neurogenesis inhibition and ferroptosis are a central mechanism contributing to sevoflurane-induced neurotoxicity in embryonic brain. The results of the present study are the first to demonstrate that ferroptosis and the expression of Nrf2 are involved in sevoflurane-related neurotoxicity in embryonic brain, which provides new vision for consideration in anesthesia-associated neurological abnormalities.

Integrins in the Regulation of Mesenchymal Stem Cell Differentiation by Mechanical Signals.

Mesenchymal stem cells (MSCs) can sense and convert mechanical stimuli signals into a chemical response. Integrins are involved in the mechanotransduction from inside to outside and from outside to inside, and ultimately affect the fate of MSCs responding to different mechanical signals. Different integrins participate in different signaling pathways to regulate MSCs multi-differentiation. In this review, we summarize the latest advances in the effects of mechanical signals on the differentiation of MSCs, the importance of integrins in mechanotransduction, the relationship between integrin heterodimers and different mechanical signals, and the interaction among mechanical signals. We put forward our views on the prospect and challenges of developing mechanical biology in tissue engineering and regenerative medicine.

Influence of Cardiovascular Risk Burden on Motor Function Among Older Adults: Mediating Role of Cardiovascular Diseases Accumulation and Cognitive Decline.

Purpose: This study aimed to investigate the association of the cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) with the trajectories of motor function over time and to assess the mediating effects of cardiovascular diseases (CVDs) accumulation and cognitive decline in such association. Methods: In Rush Memory and Aging Project, a total of 1,378 physical health participants (mean age: 79.3 ± 7.3 years) were followed up for up to 22 years. FGCRS at baseline was assessed and categorized into tertiles (lowest, middle, and highest). Global motor function (including dexterity, gait, and hand strength) was assessed annually with 10 motor tests. CVDs (including stroke, congestive heart failure, and other heart diseases) were ascertained at baseline and follow-ups, and the number of CVDs accumulation over time was assessed. Global cognitive function was tested annually by 19 tests. Data were analyzed using the linear mixed-effects models and mediation analysis. Results: At baseline, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Over the follow-up (median: 5.3 years; interquartile range: 2.9-9.0 years), in multi-adjusted mixed-effects models, the highest FGCRS was associated with faster decline in global motor function (ß = -0.0038; 95% confidence interval [CI]: -0.0069 to -0.0008), dexterity (ß = -0.0056; 95% CI: -0.0093 to -0.0020), gait (ß = -0.0039; 95% CI: -0.0077 to -0.0001), and hand strength (ß = -0.0053; 95% CI: -0.0098 to -0.0008) compared with the lowest tertile. In mediation analysis, CVDs accumulation and cognitive decline mediated 8.4% and 42.9% of the association between FGCRS and global motor function over time, respectively. Conclusion: Higher cardiovascular risk burden is associated with a faster decline in motor function including dexterity, gait, and hand strength. CVDs accumulation and cognitive decline may partially mediate the association between cardiovascular risk burden and global motor function decline.

Influence of cardiovascular risk burden on pulmonary function trajectory: role of physical and social activities.

The impact of cardiovascular risk burden on long-term trajectories of pulmonary function (PF) remains unclear. We examined the association of cardiovascular risk burden assessed by Framingham general cardiovascular risk score (FGCRS) with PF decline and explored whether cardiovascular diseases (CVD), physical and social activities play a role in the association. Within the Rush Memory and Aging Project, 1,442 participants (mean age:79.83) were followed up to 22 years. FGCRS at baseline was calculated and categorized into tertiles. Composite PF was measured annually based on peak expiratory flow, forced expiratory volume in one second, and forced vital capacity. We found that the highest FGCRS was associated with faster PF decline (ß: -0.013, 95% CI: -0.023 to -0.003) compared with the lowest FGCRS. There were significant interactions between higher FGCRS and low level of physical/social activity (ß: -0.014, 95% CI: -0.026 to -0.003)/(ß: -0.020, 95% CI:-0.031 to -0.009) or CVD(ß: -0.023, 95% CI:-0.034 to -0.011) compared to the low FGCRS with high level of physical/social activity or without CVD (P-interaction<0.05). Our results suggest that higher cardiovascular risk burden is associated with a faster PF decline, especially among people with CVD. High level of physical activity and social activity appears to mitigate this association.

Association of low birth weight with cardiometabolic diseases in Swedish twins: a population-based cohort study.

OBJECTIVES: To examine the association between low birth weight (LBW) and cardiometabolic diseases (CMDs, including heart disease, stroke and type 2 diabetes mellitus) in adulthood, and to explore whether genetic, early-life environmental and healthy lifestyle factors play a role in this association. DESIGN: A population-based twin study. SETTING: Twins from the Swedish Twin Registry who were born in 1958 or earlier participated in the Screening Across the Lifespan Twin (SALT) study for a full-scale screening during 1998-2002 and were followed up until 2014. PARTICIPANTS: 19 779 twin individuals in Sweden with birthweight data available (mean age: 55.45 years). PRIMARY AND SECONDARY OUTCOME MEASURES: CMDs were assessed based on self-reported medical records, medication use and records from the National Patient Registry. A lifestyle index encompassing smoking status, alcohol consumption, exercise levels and Body Mass Index was derived from the SALT survey and categorised as unfavourable, intermediate or favourable. Data were analysed using generalised estimating equation (GEE) models and conditional logistic regression models. RESULTS: Of all participants, 3998 (20.2%) had LBW and 5335 (27.0%) had incident CMDs (mean age at onset: 63.64±13.26 years). In GEE models, the OR of any CMD was 1.39 (95% CI 1.27 to 1.52) for LBW. In conditional logistic regression models, the LBW-CMD association became non-significant (OR=1.21, 95% CI 0.94 to 1.56). The difference in ORs from the two models was statistically significant (p<0.001). In the joint effect analysis, the multiadjusted OR of CMDs was 3.47 (95% CI 2.72 to 4.43) for participants with LBW plus an unfavourable lifestyle and 1.25 (95% CI 0.96 to 1.62) for those with LBW plus a favourable lifestyle. CONCLUSION: LBW is associated with an increased risk of adult CMDs, and genetic and early-life environmental factors may account for this association. However, a favourable lifestyle profile may modify this risk.