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Abstract Background Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs. Methods Within the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts. Results At baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p

Abstracts Objective The oxidative balance score (OBS) reflects the overall burden of oxidative stress in an individual, with a higher OBS indicating greater antioxidant exposure. This study aimed to explore the association between constipation and OBS. Methods Variables were extracted from participants who completed a constipation questionnaire as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The OBS was developed based on dietary and lifestyle factors, encompassing 16 nutrients and 4 lifestyle variables. Weighted logistic regression and restricted cubic spline (RCS) analyses were employed to evaluate the association between OBS and constipation. Results After adjusting for all covariates, weighted multivariate logistic regression analysis revealed a 4% reduction in the incidence of constipation for each additional unit of OBS (OR: 0.96, 95% CI: 0.95–0.97, p

Background High cognitive reserve (CR) has been related to lower dementia risk, but its association with heart disease (HD) is unknown. We aimed to explore the relation of CR to HD and cardiac structure and function. Methods and Results Within the UK Biobank, 349 907 HD‐free participants were followed up. A composite CR indicator involving education/occupation attainment/television viewing time/confiding frequency/social connection frequency/variety of leisure activities was generated, and further categorized into low/moderate/high levels. Incident HD, including coronary HD, cardiac arrhythmia, and heart failure, was ascertained on the basis of medical records. During the follow‐up, a subsample (n=31 182) underwent cardiac magnetic resonance imaging to assess ventricular structure and function. Data were analyzed using Cox regression, Laplace regression, and linear regression. Compared with low CR, the hazard ratio and 95% CI of any HD for high CR was 0.78 (0.75–0.80) (including 0.68 [0.66–0.71] for coronary HD, 0.91 [0.87–0.95] for cardiac arrhythmia, and 0.63 [0.58–0.68] for heart failure). Furthermore, high CR was associated with delayed HD onset by 1.59 (95% CI, 1.37–1.82) years compared with low CR. In cardiac magnetic resonance imaging data analysis, compared with low CR, high CR was associated with larger left ventricular end‐diastolic volume (β, 0.13 [95% CI, 0.09–0.17]), left ventricular end‐systolic volume (β, 0.05 [95% CI, 0.01–0.10]), left ventricular stroke volume (β, 0.16 [95% CI, 0.12–0.21]), and left ventricular ejection fraction (β, 0.08 [95% CI, 0.03–0.13]). Conclusions High CR is associated with favorable HD health. Our findings suggest that the beneficial effect of CR is not limited to dementia but also HD.

Objectives: The association of the dietary inflammatory potential with cancer risk remains uncertain. We examined the relationship of the dietary inflammatory potential with risk of overall and site-specific cancers and explored its sex and age differences. Design: A community-based longitudinal study. Setting: Participants from the UK Biobank completed baseline surveys during 2006–2010 and were followed for up to 15 years to detect incident cancer. Participants: 170,899 cancer-free participants with dietary data available (mean age: 55.73 ± 7.95, 54.10% female). Measurements: At baseline, dietary intake was assessed with a 24-h dietary record for up to 5 times. The inflammatory diet index (IDI) was calculated to assess the dietary inflammatory potential as a weighted sum of 31 food groups (including 14 anti-inflammatory and 17 pro-inflammatory) based on plasma high-sensitivity C-reactive protein (hsCRP) levels, and tertiled as low (indicating low-inflammatory diet), moderate, and high IDI (as reference). Overall and site-specific cancers were ascertained via linkage to routine hospital admission, cancer registry, and death certificate data. Data were analyzed using Cox regression and Laplace regression. Results: During the follow-up (median 10.32 years, interquartile range: 9.95–11.14 years), 18,884 (11.05%) participants developed cancer. In multi-adjusted Cox regression, low IDI scores were associated with decreased risk of rectal cancer (hazard ratio [95% confidence interval, CI] 0.76 [0.61, 0.94]), thyroid cancer [0.45 (0.27, 0.74)], lung cancer [0.73 (0.61, 0.88)]. However, the association between IDI score and the risk of overall cancer was not significant. Laplace regression analysis showed that 10th percentile differences (95% CIs) of cancer onset time for participants with low IDI scores was prolonged by 1.29 (0.32, 2.27), 1.44 (0.58, 2.30), and 2.62 (0.98, 4.27) years for rectal cancer, thyroid cancer, and lung cancer, respectively, compared to those with high IDI scores. Stratified analysis revealed that low IDI scores were associated with a lower risk of rectal cancer (p interaction between IDI score and sex = 0.035) and lung cancer in males, but not in females, and with a reduced risk of thyroid cancer in females, but not in males. Moreover, low IDI scores were associated with a reduced risk of rectal cancer and lung cancer in the participants aged ≥60 years, but not in those

The fractured-vuggy carbonate reservoir comprises various types of storage and seepage spaces, and is composed of multi-scale dissolution pores and fractures. The frequent changes to working systems make the characteristics of water breakthrough complex, and the production data nonlinear and non-stationary, resulting in great difficulty in real-time prediction. Traditional production forecasting methods only consider temporal correlations, neglecting the spatial correlations between production wells and local geological features. In this paper, adopts a modular design approach that comprehensively considers the spatiotemporal characteristics by abstracting each production well in the unit as a directed graph network node. We establish a graph attention network module based on the connectivity between wells to simulate fluid motion patterns and extract spatial features. To address the autocorrelation characteristics of the production sequences, we use a self-attention mechanism module to capture the temporal dependency relationships between production sequences. Finally, considering the fusion of spatiotemporal features, a gating mechanism is designed to adaptively aggregate spatiotemporal characteristics produced by the previous two modules, enabling dynamic production forecasting. We validate our proposed model using real-world production data from the Tarim Basin in China. Our experimental results demonstrate the superiority of the new model over existing production prediction models in fractured-vuggy carbonate reservoirs.

Abstract Background Whether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes among normoglycemic and prediabetic participants. We also explored whether a low-inflammatory diet modifies genetic risk for type 2 diabetes. Methods Among 142,271 diabetes-free UK Biobank participants (aged 39–72 years), 126,203 were normoglycemic and 16,068 were prediabetic at baseline. Participants were followed for up to 15 years to detect incident type 2 diabetes. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was generated based on high-sensitivity C-reactive protein levels and was a weighted sum of 34 food groups (16 anti-inflammatory and 18 pro-inflammatory). Participants were grouped into tertiles corresponding to inflammatory level (low, moderate, and high) based on IDI scores. Prediabetes at baseline was defined as HbA1c 5.7–6.4% in diabetes-free participants. Incident type 2 diabetes and age of onset were ascertained according to the earliest recorded date of type 2 diabetes in the Primary Care and Hospital inpatient data. A diabetes-related genetic risk score (GRS) was calculated using 424 single-nucleotide polymorphisms. Data were analyzed using Cox regression and Laplace regression. Results During follow-up (median 8.40 years, interquartile range 6.89 to 11.02 years), 3348 (2.4%) participants in the normoglycemia group and 2496 (15.5%) in the prediabetes group developed type 2 diabetes. Type 2 diabetes risk was lower in normoglycemic (hazard ratio [HR] = 0.71, 95% confidence interval [CI] 0.65, 0.78) and prediabetic (HR = 0.81, 95% CI 0.73, 0.89) participants with low IDI scores compared to those with high IDI scores. A low-inflammatory diet may prolong type 2 diabetes onset by 2.20 (95% CI 1.67, 2.72) years among participants with normoglycemia and 1.11 (95% CI 0.59, 1.63) years among participants with prediabetes. In joint effect analyses, normoglycemic or prediabetes participants with low genetic predisposition to type 2 diabetes and low IDI scores had a significant 74% (HR = 0.26, 95% CI 0.21, 0.32) or 51% (HR = 0.49, 95% CI 0.40, 0.59) reduction in type 2 diabetes risk compared to those with high genetic risk plus high IDI scores. There were significant additive and multiplicative interactions between IDI and GRS in relation to type 2 diabetes risk in the normoglycemia group. Conclusions A low-inflammatory diet is associated with a decreased risk of type 2 diabetes and may delay type 2 diabetes onset among participants with normal blood glucose or prediabetes. A low-inflammatory diet might significantly mitigate the risk of genetic factors on type 2 diabetes development.

A partial space elevator (PSE) is a multi-body tethered space system in which the main satellite, typically an ultra-large spacecraft or a space station in a higher orbit, is connected to a transport spacecraft in a lower orbit via a tether, maintaining orbital synchronization. One or more climbers can move along the tether driven by electric power, enabling cross-orbital payload transportation between the two spacecraft. The climbers’ motion significantly alters the main satellite’s orbital states, compromising its safe and stable operation. The dynamic coupling and nonlinearity of the PSE further exacerbate this challenge. This study aims to preliminarily address this issue by proposing a new mission planning strategy. This strategy utilizes reinforcement learning (RL) to select the waiting interval between two transfer missions, thereby maintaining the main satellite’s orbital motion in a stable state. Simulation results confirm the feasibility and effectiveness of the proposed mission-based method.

Abstract INTRODUCTION The presence of multiple cardiometabolic diseases (CMDs) has been linked to increased dementia risk, but the combined influence of CMDs on cognition and brain structure across the life course is unclear. METHODS In the UK Biobank, 46,562 dementia‐free participants completed a cognitive test battery at baseline and a follow‐up visit 9 years later, at which point 39,306 also underwent brain magnetic resonance imaging. CMDs (diabetes, heart disease, and stroke) were ascertained from medical records. Data were analyzed using age‐stratified (middle age [

Abstract Background Cardiometabolic diseases (CMDs) including heart disease, stroke, and type 2 diabetes have been individually linked to depression. However, their combined impact on depression risk is unclear. We aimed to examine the association between cardiometabolic multimorbidity and depression and explore the role of genetic background in this association. Methods Within the Swedish Twin Registry, 40,080 depression-free individuals (mean age 60 years) were followed for 18 years. Cardiometabolic multimorbidity was defined as having ≥2 CMDs. CMDs and depression were ascertained based on the National Patient Register. Cox regression was used to estimate the CMD-depression association in a classical cohort study design and a matched co-twin design involving 176 twin pairs. By comparing the associations between monozygotic and dizygotic co-twins, the contribution of genetic background was estimated. Results At baseline, 4809 (12.0%) participants had one CMD and 969 (2.4%) had ≥2 CMDs. Over the follow-up period, 1361 participants developed depression. In the classical cohort design, the multi-adjusted hazard ratios (95% confidence interval [CIs]) of depression were 1.52 (1.31–1.76) for those with one CMD and 1.83 (1.29–2.58) for those with ≥2 CMDs. CMDs had a greater risk effect on depression if they developed in mid-life (

Introduction: Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to increased dementia risk. We examined whether high levels of cognitive (CR) can counteract the risk of dementia related to CMDs and explored the potential underlying mechanisms. Methods: Within the UK Biobank, 216,185 dementia-free participants aged ≥60 years were followed for up to 15 years to detect incident dementia cases. Dementia was identified through linkage to medical records. At baseline, each CMD was ascertained from medical records and self- reported medical history. Latent class analysis was used to generate an indicator of cognitive reserve (CR; low, moderate, and high) based on education, occupational attainment, confiding inothers, social connection, leisure activities, and television watching time. A subsample (n=13,664) underwent brain magnetic resonance imaging (MRI) scans 9 years after baseline. Volumes of total brain (TBV), white matter (WMV), gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were measured. Data were analyzed using Cox regression and linear regression. Results: At baseline, 43,403 (20.1%) participants had at least one CMD. There were 6,600 incident dementia cases over the follow-up (median 11.7 years [interquartile range 10.9-12.5 years]). In multi-adjusted Cox models, the hazard ratio (HR, 95% confidence interval) of dementia was 1.57 (1.48, 1.67) for participants with CMDs. In joint effect analysis, the HR of dementia was 2.13 (1.97, 2.30) for those with CMDs and low CR and 1.78 (1.66, 1.91) for those with CMDs and moderate to high CR (reference: CMD-free, moderate to high CR). In MRI data analysis, among people with CMDs, those with moderate to high CR had significantly higher TBV, GMV, WMV, and HV (p

Abstract Background Cognitive reserve (CR) has been linked to dementia, yet its influence on the risk of depression and related outcomes remains unknown. We aimed to examine the association of CR with depression and subsequent dementia or death, and to assess the extent to which CR is related to depression-free survival. Methods Within the UK Biobank, 436,232 participants free of depression and dementia were followed. A comprehensive CR indicator (low, moderate, and high) was created using latent class analysis based on information on education, occupation, mentally passive sedentary behavior, social connection, confiding with others, and leisure activities. Depression, dementia, and survival status were ascertained through self-reported medical history and/or linkages to medical records. Data were analyzed using multi-state Markov model and Laplace regression. Results Over a median follow-up of 12.96 years, 16,560 individuals developed depression (including 617 with subsequent dementia) and 28,655 died. In multivariable multi-state models, compared with low CR, high CR was associated with lower risk of depression (hazard ratio 0.53 [95% confidence interval 0.51–0.56]) and lower risk of post-depression dementia (0.55 [0.34–0.88]) or death (0.69 [0.55–0.88]) in middle-aged adults (aged

Summary: Background: The pattern of olfactory identification change in the early phases of dementing disorders is unclear. We aimed to assess olfactory identification trajectories preceding incident mild cognitive impairment (MCI) and dementia and explore the role of brain pathologies in these trajectories. Methods: Within the Rush Memory and Aging Project, 1318 dementia-free older adults were followed annually for up to 11 years. Olfactory identification was assessed using the Brief Smell Identification Test annually. Of 900 cognitively intact participants, incident MCI and dementia were diagnosed following standard criteria. Over follow-up, 518 participants died and underwent brain autopsies for neuropathological assessment. Data were analyzed using mixed-effect models with backward timescales. Findings: Compared to participants who remained cognitively intact, olfactory identification declined faster among those who developed MCI (β −0.09 [95% CI −0.13, −0.05]), leading to a significantly lower olfactory identification starting from five years preceding MCI diagnosis (mean difference at year −5: −0.39 [−0.71, −0.07]). Among participants with incident MCI, olfactory identification declined faster in those who developed dementia compared to those who did not (β −0.19 [−0.36, −0.01]), leading to a significantly lower olfactory identification starting from three years preceding dementia diagnosis (mean difference at year −3: −0.95 [−1.67, −0.23]). A faster decline in olfactory identification was associated with higher burdens of global Alzheimer’s disease pathology, neurofibrillary tangles, and amyloid beta load. Interpretation: Olfactory identification declined faster preceding dementia disorders and Alzheimer’s pathology may underlie these faster declines. Funding: This study was funded by the National Institutes of Health (R01AG17917) and Swedish Research Council (2021-01647).

Abstract Colon mucosae of ulcerative colitis (UC) and Crohn's disease (CD) display differences in the number and distribution of immune cells that are difficult to assess by eye. Deep learning‐based analysis on whole slide images (WSIs) allows extraction of complex quantitative data that can be used to uncover different inflammatory patterns. We aimed to explore the distribution of CD3 and γδ T cells in colon mucosal compartments in histologically inactive and active inflammatory bowel disease. By deep learning‐based segmentation and cell detection on WSIs from a well‐defined cohort of CD (n = 37), UC (n = 58), and healthy controls (HCs, n = 33), we quantified CD3 and γδ T cells within and beneath the epithelium and in lamina propria in proximal and distal colon mucosa, defined by the Nancy histological index. We found that inactive CD had significantly fewer intraepithelial γδ T cells than inactive UC, but higher total number of CD3 cells in all compartments than UC and HCs. Disease activity was associated with a massive loss of intraepithelial γδ T cells in UC, but not in CD. The total intraepithelial number of CD3 cells remained constant regardless of disease activity in both CD and UC. There were more mucosal CD3 and γδ T cells in proximal versus distal colon. Oral corticosteroids had an impact on γδ T cell numbers, while age, gender, and disease duration did not. Relative abundance of γδ T cells in mucosa and blood did not correlate. This study reveals significant differences in the total number of CD3 and γδ T cells in particularly the epithelial area between CD, UC, and HCs, and demonstrates useful application of deep segmentation to quantify cells in mucosal compartments.

Plaque rupture, plaque erosion, and COVID-19 infection can cause acute coronary syndromes (ACS). We illustrate case examples demonstrating the distinctive and characteristic pathologic findings underlying each of these various causes of acute myocardial infarction. A deeper understanding of the pathophysiology of ACS is necessary for the development of newer agents and techniques to improve outcomes after ACS. (Level of Difficulty: Advanced.)

Abstract Background Risk genes linked to the development of gout have been identified, and lifestyle factors are related to gout risk. It remains unclear whether healthy lifestyle factors can mitigate the genetic risk of gout. Therefore, we aimed to explore whether and to what extent a healthy lifestyle can mitigate the risk of gout related to genetic factors. Methods Within the UK Biobank, 416,481 gout-free participants (aged 37–74) were identified at baseline. Polygenic risk for gout was assessed and categorized as low (lowest tertile), middle (tertile 2), and high (highest tertile). Healthy lifestyle factors included no/moderate alcohol consumption, no smoking, physical activity, and a healthy diet. Participants were categorized into three groups according to their number of healthy lifestyle factors: unfavorable (0 or 1), intermediate (any 2), and favorable (3 or 4). Data were analyzed using Cox proportional hazard models. Results Over the follow-up (median: 12.1 years), 6206 participants developed gout. Compared to low genetic risk, the hazard ratios (HRs) and 95% confidence intervals (CIs) of gout was 1.44 (1.35–1.54) for middle and 1.77 (1.66–1.89) for high genetic risk. The HRs (95% CIs) of gout were 0.63 (0.59–0.67) for a favorable lifestyle and 0.79 (0.75–0.85) for an intermediate lifestyle, compared to an unfavorable lifestyle. In joint effect analysis, compared to participants with low genetic predisposition and a favorable lifestyle, the HRs (95% CIs) of gout were 2.39 (2.12–2.70)/3.12 (2.79–3.52) in those with middle and high genetic predisposition plus unfavorable lifestyle profiles, and 1.53 (1.35–1.74)/1.98 (1.75–2.24) for those with middle and high genetic predisposition plus favorable lifestyle profiles, respectively. Moreover, compared to an unfavorable lifestyle, the HRs of gout related to a favorable lifestyle was 0.64 (95% CI, 0.56–0.73) for low genetic risk, 0.65 (95% CI, 0.58–0.72) for middle genetic risk, and 0.62 (95% CI, 0.57–0.69) for high genetic risk. There was a significant additive interaction between unfavorable lifestyle and high genetic risk on gout. Conclusions Healthy lifestyle was associated with a lower risk of gout and may attenuate the risk of gout related to genetic factors by almost a third.

Vascular calcification (VC) is concomitant with atherosclerosis, yet it remains uncertain why rupture-prone high-risk plaques do not typically show extensive calcification. Intraplaque hemorrhage (IPH) deposits erythrocyte-derived cholesterol, enlarging the necrotic core and promoting high-risk plaque development. Pro-atherogenic CD163+ alternative macrophages engulf hemoglobin:haptoglobin (HH) complexes at IPH sites. However, their role in VC has never been examined to our knowledge. Here we show, in human arteries, the distribution of CD163+ macrophages correlated inversely with VC. In vitro experiments using vascular smooth muscle cells (VSMCs) cultured with HH-exposed human macrophage — M(Hb) — supernatant reduced calcification, while arteries from ApoE–/– CD163–/– mice showed greater VC. M(Hb) supernatant–exposed VSMCs showed activated NF-κB, while blocking NF-κB attenuated the anticalcific effect of M(Hb) on VSMCs. CD163+ macrophages altered VC through NF-κB–induced transcription of hyaluronan synthase (HAS), an enzyme that catalyzes the formation of the extracellular matrix glycosaminoglycan, hyaluronan, within VSMCs. M(Hb) supernatants enhanced HAS production in VSMCs, while knocking down HAS attenuated its anticalcific effect. NF-κB blockade in ApoE–/– mice reduced hyaluronan and increased VC. In human arteries, hyaluronan and HAS were increased in areas of CD163+ macrophage presence. Our findings highlight an important mechanism by which CD163+ macrophages inhibit VC through NF-κB–induced HAS augmentation and thus promote the high-risk plaque development.

The cotton aphid, Aphis gossypii Glover, is a species of polyphagous aphid with many biotypes, and its host transfer has always been the focus of research on the control of cotton aphid. An important factor affecting aphid specialization is the nutritional association with microbial symbionts that provide the host with nutrients lacking in the diet. We analyzed the microbial composition and biodiversity of reared on zucchini for 10 generations (T1–T10) and cotton as a control (CK), by high-throughput Illumina sequencing of 16S ribosomal RNA genes. The findings showed that the change in plant hosts decreased the richness and variety of microbial species. Regardless of whether the plant host is altered or not, Proteobacteria and Firmicutes are the predominate phyla in cotton-specialized aphid. Additionally, cotton-specialized aphids that live in zucchini had considerably lower relative abundances of non-dominant phyla (Bacteroidetes) than cotton hosts. At the genus level the dominant communities were Buchnera, Acinetobacter, and Arsenophonus. The relative abundance of Buchnera was significantly higher in aphids reared on zucchini than those on cotton, whereas the opposite was observed for Acinetobacter, as well as for some non-dominant communities (Stenotrophomonas, Pseudomons, Flavobacterium, Novosphingobium). Collectively, this study clarifies the dynamic changes of symbiotic bacteria in cotton-specialized aphids reared on zucchini for multiple generations. Among them, Buchnera is crucial for the cotton-specialized aphid to get nutrients during the transfer of the host and has a favorable impact on the colonization of cotton-specialized aphid populations on zucchini hosts. It not only enriches our understanding of the relationship between the bacterial microbiota of aphids and their adaptability to new hosts, zucchini, but also expands the current body of research on the mechanisms underlying the host shifting ability of cotton-specialized aphids.

Abstract Background The relation between cigarette smoking and metabolic syndrome (MetS) remains unclear, and previous studies focusing on MetS are limited in sample size. We investigated the association between life-course smoking and MetS with independent discovery and replication samples. Methods Preliminary analysis utilized data from an annual cross-sectional survey of 15,222 participants aged ≥ 60 years in Tianjin, China. Suggestive associations were followed-up in 8565 adults from the China Health and Nutrition Survey. MetS was identified according to the criteria of the Chinese Diabetes Society in 2013. Life-course smoking was assessed by a comprehensive smoking index (CSI), based on information on smoking intensity, duration, and time since cessation across life-course, collected through standard questionnaires. Participants were divided into four groups: non-smokers; and the tertiles of CSI in ever smokers. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between life-course smoking and MetS. Results In the discovery sample, ORs of MetS were 2.01 (95%CI: 1.64–2.47) and 1.76 (95%CI: 1.44–2.16) for smokers in the highest and second tertile of CSI compared with never smokers. Potential interaction was shown for age, with increased ORs for MetS associated with smoking limited to individuals who aged

Abstract The SARS‐CoV‐2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine‐elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS‐CoV‐2 receptor‐binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL‐1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.

BackgroundA deeper understanding of coronary medial thickness is important for coronary intervention because media thickness can limit the safety and effectiveness of interventional techniques. However, there is a paucity of detailed data on human coronary medial thickness so far.Materials and methodsWe investigated the thickness of the media by histologic analysis. A total of 230 sections from 10 individuals from the CVPath autopsy registry who died from non-coronary deaths were evaluated. We performed pathological analysis on 13 segments of the following primary vessels from coronary arteries: the left main trunk, proximal left anterior descending artery (LAD), mid LAD, distal LAD, proximal left circumflex artery (LCX), mid LCX, distal LCX, proximal right coronary artery (RCA), mid RCA, and the distal RCA. The following side branches were also evaluated: diagonal, obtuse margin, and posterior descending artery branches.ResultsThe average age of the studied individuals was 60.4±12.3 years. The median medial thickness for all sections was 0.202 (0.149-0.263) mm. The median medial thickness of the main branches was significantly higher compared to that of the side branches (pConclusionsThe human coronary arteries demonstrate variation in medial thickness which tends to vary depending upon an epicardial coronary artery itself, as well as its segments and branches. Understanding these variations in medial thickness can be useful for both the interventionalists and interventional product development teams.

Abstract Introduction Decline in physical function varies substantially across older individuals due to several extrinsic modifiable factors such as dietary patterns, physical activity and social support. We aimed to determine the association of these factors and their interaction with mobility and muscle strength decline. Methods We analyzed data from 1686 functionally healthy individuals aged 60 + from the population-based Swedish National study on Aging and Care in Kungsholmen (SNAC-K). The Mediterranean Diet Score (MDS) was calculated based on a validated food frequency questionnaire. Self-reported physical activity was categorized based on current recommendations, and social support was measured according to participants’ perceived material and psychological support from relatives and friends. Participants’ physical function was assessed over 12 years through changes in walking speed (m/s) and chair stand time (s). Linear mixed models adjusted for socio-demographic and clinical factors were used. In order to explore the combined effect of the different exposures, two indicator variables were created by cross-classifying individuals' levels of Mediterranean diet adherence and social support or physical activity. Results Participants with a high adherence to Mediterranean diet were primarily

BackgroundPancreatic pseudocyst (PPC) with massive gastrointestinal bleeding is rare, especially in children. Inadvertent intraoperative examination and damage to the gastric mucosa and malformed blood vessels by the fluid content of PPC can lead to massive bleeding, which may endanger the patient's life.Case presentationHere, we present a case of an 8-year-old boy who was diagnosed with a massive gastrointestinal haemorrhage caused by PPC complicated with Dieulafoy's disease. At his first admission, his complaint was being hit to the stomach by the handlebar while riding bicycle 24 h before admission. After being hospitalized, he was diagnosed with pancreatic injury by abdominal CT. Conservative treatment lasted for 1 month in the Department of Pediatric Surgery. Then, a pancreatic pseudocyst was formed. Under the guidance of ultrasonic endoscopy, cyst puncture and drainage of pseudocysts through the gastric wall were performed. Unexplained hematemesis occurred 8 days after surgery. Emergency gastroscopy was performed, and abnormal submucosal vascular haemorrhage was found at the gastric fundus. Gastric Dieulafoy's disease was diagnosed. The boy underwent gastroscopic titanium clipping of abnormal arteries. He had no complications during the 3-month follow-up. Then, the patient returned to the hospital, and the stent was removed under endoscopy. No bleeding was found, and the patient was discharged. The patient recovered smoothly and was followed up for half a year without any complications, and hematological indicators were normal.ConclusionEndoscopic ultrasonography-guided gastric puncture and internal drainage of cysts is a safe and effective surgical method for the treatment of pancreatic pseudocysts. However, at the same time, it is necessary to thoroughly and carefully explore the stomach cavity to prevent adverse consequences caused by a missed diagnosis of gastric Dieulafoy's disease or other abnormal abnormalities.

Background Although sleep disorders have been linked to cardiovascular diseases (CVDs), the association between sleep characteristics and CVDs remains inconclusive. We aimed to examine the association of nighttime sleep duration, daytime napping, and sleep patterns with CVDs and explore whether genetic and early‐life environmental factors account for this association. Methods and Results In the Swedish Twin Registry, 12 268 CVD‐free twin individuals (mean age=70.3 years) at baseline were followed up to 18 years to detect incident CVDs. Sleep duration, napping, and sleep patterns (assessed by sleep duration, chronotype, insomnia, snoring, and daytime sleepiness) were self‐reported at baseline. CVDs were ascertained through the Swedish National Patient Registry and the Cause of Death Register. Data were analyzed using a Cox model. In the multiadjusted Cox model, compared with 7 to 9 hours/night, the hazard ratios (HRs) of CVDs were 1.14 (95% CI, 1.01–1.28) for 30 minutes (HR, 1.23 [95% CI, 1.14–1.33]) were related to CVDs. Furthermore, a poor sleep pattern was associated with CVDs (HR, 1.22 [95% CI, 1.05–1.41]). The co‐twin matched control analyses showed similar results as the unmatched analyses, and there was no significant interaction between sleep characteristics and zygosity (P values >0.05). Conclusions Short or long sleep (

Abstract Background Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. Objectives AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. Results We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. Conclusion Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.

Abstract The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS‐CoV‐2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies, and cellular immune phenotypes of asymptomatic patients with acute SARS‐CoV‐2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro‐inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro‐inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus‐specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS‐CoV‐2 was observed in asymptomatic patients. In addition, asymptomatic COVID‐19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro‐inflammatory and more protective immune responses against SARS‐CoV‐2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID‐19.

COVID-19 severity is associated with cytokine levels and lymphopenia, but the role of immune cell subsets is not well understood. Here the authors immunophenotype whole blood samples from 54 COVID-19 patients and find that the immature neutrophil-to-VD2 T-cell ratio is associated with severe COVID-19.

PurposeThis 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.MethodsIn 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.ResultsAt 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 (β = −0.0038; 95% confidence interval [CI]: −0.0069 to −0.0008), dexterity (β = −0.0056; 95% CI: −0.0093 to −0.0020), gait (β = −0.0039; 95% CI: −0.0077 to −0.0001), and hand strength (β = −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.ConclusionHigher 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.

AbstractBackgroundThe differential impact of depression across different periods in life on mortality remains inconclusive. We aimed to examine the association of depression that occurs at different age with all-cause mortality, and to explore the roles of dementia, as well as genetic and early-life environmental factors, in this association.MethodsFrom the Swedish Twin Registry, 44,919 twin individuals were followed for up to 18 years. Depression was ascertained using the National Patient Registry and categorized as early-life (

MI is a leading cause of morbidity and mortality worldwide. Coronary artery thrombosis is the final pathologic feature of the most cases of acute MI primarily caused by atherosclerotic coronary artery disease. The concept of vulnerable plaque has evolved over the years but originated from early pioneering work unveiling the crucial role of plaque rupture and subsequent coronary thrombosis as the dominant cause of MI. Along with systemic cardiovascular risk factors, developments of intravascular and non-invasive imaging modalities have allowed us to identify coronary plaques thought to be at high risk for rupture. However, morphological features alone may only be one of many factors which promote plaque progression. The current vulnerable-plaque-oriented approaches to accomplish personalized risk assessment and treatment have significant room for improvement. In this review, the authors discuss recent advances in the understanding of vulnerable plaque and its management strategy from pathology and clinical perspectives.

A low guiding magnetic field facilitates the compactness of high power microwave sources, thus making it more practical. In order to reduce the guiding magnetic field, a focusing cathode is introduced in a Ka-band coaxial transit time oscillator in this paper. Based on the focusing cathode with a large impedance (>100 Ω) coaxial structure, a particle-in-cell simulation is conducted. When the diode voltage is 480 kV and the beam current is 3.62 kA, a microwave with an average power of 800 MW at 31.667 GHz is obtained under a guiding magnetic field of 0.5 T, the corresponding conversion efficiency is 46%, and the saturation time is 25 ns. Meanwhile, the maximum EZ field in the diode region is 350 kV/cm; thus, electron emission beyond the cathode region is avoided. When the guiding magnetic field is 0.5 T and the voltage varies in the range of 430–510 kV, the conversion efficiency is greater than 40%. In addition, when the voltage stays at 480 kV and the guiding magnetic field is in the range of 0.45–1.0 T, the conversion efficiency is also greater than 40%.

Summary: The elderly are an important target for influenza vaccination, and the determination of factors that underlie immune responsiveness is clinically valuable. We evaluated the immune and metabolic profiles of 205 elderly Singaporeans administered with Vaxigrip. Despite high seroprotection rates, we observed heterogeneity in the response. We stratified the cohort into complete (CR) or incomplete responders (IR), where IR exhibited signs of accelerated T cell aging. We found a higher upregulation of genes associated with the B-cell endoplasmic-reticulum stress response in CR, where XBP-1 acts as a key upstream regulator. B-cells from IR were incapable of matching the level of XBP-1 upregulation observed in CR after inducing ER stress with tunicamycin in vitro. Metabolic signatures also distinguished CR and IR – as CR presented with a greater diversity of bile acids. Our findings suggest that the ER-stress pathway activation could improve influenza vaccination in the elderly.

To execute higher-order functions, cells self-assemble into spatially coded tissue configurations. Here the authors magnetically assembly giant unilamellar vesicles into three dimensional tissue-mimic structures with collective osmotic stability.

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

In confined spaces, bacteria exhibit unexpected cellular behaviors that are related to the biogeochemical cycle and human health. Types of confined spaces include lipid vesicles, polymer vesicles, emulsion droplets, microfluidic chips, and various laboratory-made chambers. This mini-review summarizes the behaviors of living bacteria in these confined spaces, including (a) growth and proliferation, (b) cell communication, and (c) motion. Future trends and challenges are also discussed in this paper.

The design of compact, lightweight devices has become an important development direction of high-power microwave source devices, with the reduction of the external magnetic field being the leading innovation. By analyzing the transmission equation of the intense relativistic electron beam (IREB), it can be known that magnetic field strength in the diode region has great influence on the transmission quality of the IREB. In this paper, a new structure that introduces a soft magnetic material as the cathode base is proposed. Considering that soft magnetic materials have the capability to concentrate and enhance the magnetic field, the proposed structure leverages this merit to improve the magnetic field strength in the diode area under certain low external magnetic field conditions. Thus, the proposed structure is capable of effectively improving the emission and transmission quality of the IREB without any increase of the external guiding magnetic field. As for the device design, the new structure was introduced into a previously proposed C-band transit time oscillator, and the particle-in-cell simulation was carried out. The results showed that high power microwaves with a power of 2.7 GW are generated with a corresponding frequency of 40% when the electron beam voltage is 550 kV, the beam current is 12 kA, and the guiding magnetic field is 0.3 T.

Background Cardiovascular risk burden has been linked to cardiovascular disease (CVD) and cognitive decline, but its association with disability is unclear. We aimed to examined the association of cardiovascular risk burden assessed by the Framingham general cardiovascular risk score (FGCRS) with the risk and progression of disability and estimated the extent to which CVD and cognitive decline mediate this association. Methods and Results A total of 1480 older adults with no disabilities (mean age=79.32±7.38 years) from the Rush Memory and Aging Project were followed for up to 21 years. FGCRS at baseline was calculated and categorized into tertiles. Disability was assessed annually with activities of daily living. The number of CVDs was calculated by summing up the CVD events. Global cognitive function was assessed annually with a battery of 19 tests. Data were analyzed using the Cox model, linear mixed effects model, and mediation analysis. At the end of the follow‐up, 713 (48.2%) participants developed disability. Compared with the lowest tertile of the FGCRS, the multiadjusted hazards ratios of disability were 1.34 (95% CI, 1.11–1.62) for the highest tertile. In addition, the highest FGCRS was associated with a change in activities of daily living score over time (β=0.057; 95% CI, 0.021–0.093). The association between FGCRS and change in activities of daily living was 13.8% mediated by the accumulation of CVDs and 25.1% by cognitive decline, respectively. Conclusions Higher cardiovascular risk burden increased the risk of disability and accelerated its progression over time. CVD accumulation and cognitive decline may partially mediate the association.

Background: Immune adaptation with aging is a major of health outcomes. Studies in humans have mainly focus on αβ T cells while γδ T cells have been neglected despite their role in immunosurveillance. We investigated the impact of aging on γδ T cell subsets phenotypes, functions, senescence and their molecular response to stress. Methods: Peripheral blood of young and old donors in Singapore have been used to assess the phenotype, functional capacity, proliferation capacity and gene expression of the various γδ T cell subsets. Peripheral blood mononuclear cells from apheresis cones and young donors have been used to characterize the telomere length, epigenetics profile and DNA damage response of the various γδ T cell subsets phenotype. Findings: Our data shows that peripheral Vδ2+ phenotype, functional capacity (cytokines, cytotoxicity, proliferation) and gene expression profile are specific when compared against all other αβ and γδ T cells in aging. Hallmarks of senescence including telomere length, epigenetic profile and DNA damage response of Vδ2+ also differs against all other αβ and γδ T cells. Interpretation: Our results highlight the differential impact of lifelong stress on γδ T cells subsets, and highlight possible mechanisms that enable Vδ2+ to be resistant to cellular aging. The new findings reinforce the concept that Vδ2+ have an “innate-like” behavior and are more resilient to the environment as compared to “adaptive-like” Vδ1+ T cells. Keywords: Gamma Delta T cells, Immunosenescence, Innate Immunity, Immunobiology, Aging, Cellular Senescence

This work aims at improving the textural and whipping properties of whipped cream by the addition of milk fat globule membrane protein. The determination of particle size distribution and average diameter of whipped cream showed that the small particle size was shifted to a larger range after milk fat globule membrane protein was added. The average particle size (d3,2) of whipped cream reached a maximum value of 5.05 µm at 1% milk fat globule membrane protein, while slowly decreased with increasing milk fat globule membrane protein levels from 2% to 5%. In addition, the partial coalescence of fat increased with the increase of milk fat globule membrane protein levels, and the correlation between the whipping time and the overrun of whipped cream was positive. The addition of milk fat globule membrane protein also altered the rheological behaviour of whipped cream, resulting in the increase of modulus G′ and the loss modulus G″. The results also indicated that higher milk fat globule membrane protein level decreased the serum loss of whipped cream while improved its stability. While milk fat globule membrane protein levels had no significant effect on viscosity, its increasing levels effectively improved the hardness, consistency, and viscosity of whipped cream.

Background: China has been going through significant changes in social and economical aspects and with great socioeconomic disparity in different regions. However, data on the association between socioeconomic status (SES) and obesity are not available in Tianjin, China. Aim: This study aimed to investigate the association between SES and high adiposity among the adult population in Tianjin. Subjects and methods: A total of 7351 individuals aged 20–79 were included in this study. Socioeconomic information was collected through an interview following a structured questionnaire. Waist circumference, body weight and height were measured following standard procedures. Overweight and obesity were defined according to the criteria of the Working Group on Obesity in China. Data were analysed using multinomial logistic regression with adjustment for potential confounders. Results: Stratified analysis showed that higher monthly income and education were related to decreased odds of abdominal overweight/obesity in women, while high education was associated with increased odds of general overweight/obesity in men. Retirement increased the odds of abdominal overweight and obesity and non-manual work was associated with low odds of abdominal obesity in women. Conclusions: SES was associated with general and abdominal overweight/obesity and sex may play a role in such an association.

Pickled ready-to-eat meat (PRTEM) is a meat product that is treated with various seasonings and then cooked. PRTEM is a popular food consumed mostly in China and some Asian countries. Since this food is considered ‘ready to eat’, once it is contaminated by foodborne pathogens such as Salmonella, the prospect for significant morbidity, mortality, and immeasurable economic losses can occur. Here we investigated the prevalence and concentration of Salmonella in 107 PRTEM samples collected from Shaanxi, China during 2015–2016. Furthermore, we analyzed the serotype, antibiotic susceptibility, and presence of antibiotic resistance genes and amino acid mutations in 219 Salmonella isolates, followed by subtyping of 115 representative isolates. The average detection rate of Salmonella-positive PRTEM was 58.9%, and the average most probable number (MPN) of Salmonella in positive samples was 2.27 logMPN per gram of sample (range: 2.10–2.43). Ten serotypes were identified from the 219 Salmonella isolates, with S. Thompson (37.9%) and S. Indiana (20.5%) being predominant. The remaining serotypes were S. Typhi (7.8%), S. Typhimurium (7.3%), S. Mbandaka (6.9%), S. Albany (6.4%), S. Blockley (5.5%), S. Infantis (4.1%), S. Escanaba (3.2%), and S. Dusseldorf (0.5%). All isolates were resistant to ceftiofur (100%), while most of them were resistant to ciprofloxacin (99.1%), amoxicillin-clavulanic acid (97.7%), trimethoprim-sulfamethoxazole (96.4%), ampicillin (92.3%), sulfisoxazole (92.2%), tetracyclines (90.4%), and nalidixic acid (90.4%), respectively. A single mutation of Ser83Phe (27.1%) and double mutations of Ser83Phe-Asp87Gly (25.9%) in GyrA were detected in 85 isolates, whereas mutations of Thr57Ser (63.9%) and Ser80Arg (36.1%) in ParC were detected in 122 isolates. qnrB, oqxAB, aac(6′)-Ib, and qnrA were present in 50 (22.8%), 48 (21.9%), 26 (11.9%), and 1 (0.5%) isolate(s), respectively. Pulse field gel electrophoresis results revealed that those isolates recovered from the same type of PRTEM or the same sampling place shared identical or similar DNA profiles, antibiotic resistance phenotypes, and even plasmid-mediated quinolone resistance encoding genes. The findings indicate that Salmonella is commonly prevalent in PRTEMs at high concentrations in Shaanxi, China. More attention should be paid to the processing and storage of this ready-to-eat food to prevent bacterial contamination and foodborne outbreaks.

BackgroundUnfavorable psychosocial working conditions have been associated with cognitive decline and chronic diseases, both of which may subsequently accelerate functional dependence. This study aimed to investigate the association between job demand-control-support combinations and trajectories of disability in later life and to further explore the role of cognitive decline and the co-occurrence of chronic diseases in mediating this association.Methods and findingsIn this cohort study, 2,937 community dwellers aged 60+ years (mean age 73 ± 10.6; 62.9% female) residing in the Kungsholmen District of Stockholm, Sweden, participated in the baseline survey (2001-2004) and were followed up to 12 years. Lifelong occupational history was obtained through a standardized interview; job demands, job control, and social support at work in the longest-held occupation were graded with a psychosocial job-exposure matrix. Job control, demands, and social support were dichotomized using the median values from the matrix, respectively, to further generate demand-control-support combinations. Disability was measured by summing the number of impaired basic and instrumental activities of daily living. Global cognitive function was assessed by Mini-Mental State Examination. Chronic conditions were ascertained by clinical examinations, medical history, and patient clinical records; the total number of chronic diseases was summed. Data were analyzed using linear mixed-effects models and mediation analysis. Age, sex, education, alcohol consumption, smoking, leisure activity engagement, early-life socioeconomic status, occupational characteristic and physical demands, and baseline cognitive function and number of chronic diseases were adjusted for in the analyses. Compared with active jobs (high control/high demands; n = 1,807), high strain (low control/high demands; n = 328), low strain (high control/low demands; n = 495), and passive jobs (low control/low demands; n = 307) were all associated with a faster rate of disability progression (β = 0.07, 95% CI 0.02-0.13, p = 0.01; β = 0.10, 95% CI 0.06-0.15, p < 0.001; β = 0.11, 95% CI 0.05-0.18, p < 0.001). The association between high strain and disability progression was only shown in people with low social support at work (β = 0.13, 95% CI 0.07-0.19, p < 0.001), but not in those with high social support (β = 0.004, 95% CI -0.09 to 0.10, p = 0.93). Moreover, we estimated that the association between demand-control status and disability trajectories was mediated 38.5% by cognitive decline and 18.4% by accumulation of chronic diseases during the follow-up period. The limitations of this study include unmeasured confounding, self-reported work experience, and the reliance on a psychosocial job-exposure matrix that does not consider variabilities in individuals' perception on working conditions or job characteristics within occupations.ConclusionsOur findings suggest that negative psychosocial working conditions during working life may accelerate disability progression in later life. Notably, social support at work may buffer the detrimental effect of high strain on disability progression. Cognitive decline and chronic-disease accumulation, and especially the former, partially mediate the association of psychosocial working conditions with trajectories of disability. Further studies are required to explore more mechanisms that underlie the association between psychosocial working conditions and disability trajectories.

Summary: The molecular characterization of immune subsets is important for designing effective strategies to understand and treat diseases. We characterized 29 immune cell types within the peripheral blood mononuclear cell (PBMC) fraction of healthy donors using RNA-seq (RNA sequencing) and flow cytometry. Our dataset was used, first, to identify sets of genes that are specific, are co-expressed, and have housekeeping roles across the 29 cell types. Then, we examined differences in mRNA heterogeneity and mRNA abundance revealing cell type specificity. Last, we performed absolute deconvolution on a suitable set of immune cell types using transcriptomics signatures normalized by mRNA abundance. Absolute deconvolution is ready to use for PBMC transcriptomic data using our Shiny app (https://github.com/giannimonaco/ABIS). We benchmarked different deconvolution and normalization methods and validated the resources in independent cohorts. Our work has research, clinical, and diagnostic value by making it possible to effectively associate observations in bulk transcriptomics data to specific immune subsets. : Monaco et al. generate an RNA-seq dataset on 29 immune cell types and identify modules of cell type-specific, co-expressed, and housekeeping genes. The mRNA heterogeneity and abundance of the different cell types were examined. Absolute deconvolution of PBMCs was obtained by taking into account mRNA abundance when normalizing the signature matrix. Keywords: immune system, flow cytometry, transcriptome, RNA-seq, gene modules, housekeeping, mRNA composition, mRNA abundance, mRNA heterogeneity, deconvolution

A Ku-band transit-time oscillator (TTO) with compact magnetic coil and a novel collector structure is proposed. By utilizing the natural bending of the magnetic field, this TTO could decrease over 25% length of uniform magnetic field and the required energy of the solenoid. Besides, the larger radius and decreased magnetic field at the collector lead to larger collection area and less current density in collector surface, simulation shows that the energy deposition peak is 2.5 times less in this novel collector. That this novel collector also has evident advantages in suppressing the adverse effect of plasmas than traditional one in simulation, when hydrogen gas is preset on the collector surface. Particle-in-cell simulation shows that with a 2.4GW beam guided by a decreasing magnetic field of about 0.7T, 0.85GW microwave power pulse at 13.23GHz is generated in this TTO, yielding a conversion efficiency of about 35.4%.

Decorative ornamental plants have been applied as hyperaccumulators/phytoremediators to a wide spectrum of heavy metal contaminants. In this study, pot culture experiments were conducted to investigate the Sn tolerance and accumulation in Impatiens balsamina L., Mirabilis jalapa L. and Tagetes erecta L., in order to assess the possibility of these three ornamental plants to be used as phytoremediators of Sn-contaminated soil. Results show that all three plants exhibited strong tolerance to Sn contamination, and no significant visual toxicity was observed for all three plants grown under most of the Sn treatments. The amount of Sn accumulated in the three plants was positively correlated with the Sn concentration in the soil. The order of the Sn accumulative capacity was Impatiens balsamina > Mirabilis jalapa > Tagetes erecta. Impatiens balsamina and Tagetes erecta showed a low translocation ability (TF) (Impatiens balsamina showed a relatively high bioconcentration factor (BCF, Sn concentration in each part > 100 mg/kg after Sn treatment of 500 mg/kg). Meanwhile, the TF of Mirabilis jalapa was >1, and the fluorescence accumulated the most Sn. In combination with the adaptation to high concentrations of various heavy metals, these three ornamental plants are potential candidates for Sn mining tailings or contaminated soil.

Dengue is endemic in tropical countries worldwide and the four dengue virus serotypes often co-circulate. Infection with one serotype results in high titers of cross-reactive antibodies produced by plasmablasts, protecting temporarily against all serotypes, but impairing protective immunity in subsequent infections. To understand the development of these plasmablasts, we analyzed virus-specific B cell properties in patients during acute disease and at convalescence. Plasmablasts were unrelated to classical memory cells expanding in the blood during early recovery. We propose that only a small subset of memory B cells is activated as plasmablasts during repeat infection and that plasmablast responses are not representative of the memory B cell repertoire after dengue infection.

Fault components in the fault path and the non-fault path differ due to the unbalanced distribution of positive, negative and zero-sequence components in the line in the case of a single-phase earth fault in the power distribution network. Therefore, this paper proposes an improved fault section location algorithm based on phase current, which obtains the fault component current by the subtraction of currents before and after the fault and the fundamental wave amplitude of the corresponding current through Fast Fourier Transform (FFT). Meanwhile, considering that the fault section location cannot be completed accurately with the amplitude relationship alone, the Minkowski distance calculation formula is introduced to strengthen the difference between the fault path and the non-fault path, and the relationship between the calculation results of different sections and the threshold is compared by threshold setting to complete the section location. This paper proposes the specific fault section location process and criteria and verifies the feasibility of the algorithm through simulation experiment.

In the coming decades, many developed countries in the world are expecting the “greying” of their populations. This phenomenon poses unprecedented challenges to healthcare systems. Aging is one of the most important risk factors for infections and a myriad of diseases such as cancer, cardiovascular and neurodegenerative diseases. A common denominator that is implicated in these diseases is the immune system. The immune system consists of the innate and adaptive arms that complement each other to provide the host with a holistic defense system. While the diverse interactions between multiple arms of the immune system are necessary for its function, this complexity is amplified in the aging immune system as each immune cell type is affected differently—resulting in a conundrum that is especially difficult to target. Furthermore, certain cell types, such as γδ T cells, do not fit categorically into the arms of innate or adaptive immunity. In this review, we will first introduce the human γδ T cell family and its ligands before discussing parallels in mice. By covering the ontogeny and homeostasis of γδ T cells during their lifespan, we will better capture their evolution and responses to age-related stressors. Finally, we will identify knowledge gaps within these topics that can advance our understanding of the relationship between γδ T cells and aging, as well as age-related diseases such as cancer.

Background: Findings from animal and epidemiological research support the potential neuroprotective benefits from healthy diets. However, to establish diet-neuroprotective causal relations, evidence from dietary intervention studies is needed. NU-AGE is the first multicenter intervention assessing whether a diet targeting health in aging can counteract the age-related physiological changes in different organs, including the brain. In this study, we specifically investigated the effects of NU-AGE's dietary intervention on age-related cognitive decline.Materials and Methods: NU-AGE randomized trial (NCT01754012, clinicaltrials.gov) included 1279 relatively healthy older-adults, aged 65–79 years, from five European centers. Participants were randomly allocated into two groups: “control” (n = 638), following a habitual diet; and, “intervention” (n = 641), given individually tailored dietary advice (NU-AGE diet). Adherence to the NU-AGE diet was measured over follow-up, and categorized into tertiles (low, moderate, high). Cognitive function was ascertained at baseline and at 1-year follow-up with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Neuropsychological Battery and five additional domain-specific single cognitive tests. The raw scores from the CERAD subtests [excluding the Mini-Mental State Examination (MMSE)] and the single tests were standardized into Z-scores. Global cognition (measured with MMSE and CERAD-total score), and five cognitive domains (perceptual speed, executive function, episodic memory, verbal abilities, and constructional praxis) were created. Cognitive changes as a function of the intervention were analyzed with multivariable mixed-effects models.Results: After the 1-year follow-up, 571 (89.1%) controls and 573 (89.8%) from the intervention group participated in the post-intervention assessment. Both control and intervention groups showed improvements in global cognition and in all cognitive domains after 1 year, but differences in cognitive changes between the two groups were not statistically significant. However, participants with higher adherence to the NU-AGE diet showed statistically significant improvements in global cognition [β 0.20 (95%CI 0.004, 0.39), p-value = 0.046] and episodic memory [β 0.15 (95%CI 0.02, 0.28), p-value = 0.025] after 1 year, compared to those adults with lower adherence.Discussion: High adherence to the culturally adapted, individually tailored, NU-AGE diet could slow down age-related cognitive decline, helping to prevent cognitive impairment and dementia.

Objectives: The role of different body fat indicators and age in assessing the prevalence of obesity is unclear. We aimed to examine to what extent different body fat indicators including BMI, waist circumference (WC) and waist-to-hip ratio (WHR) affect the prevalence of overweight and obesity among Chinese adults taking age into account. Methods: This population-based cross-sectional study included a random sample of 7,603 adults aged 20-79 years across entire Tianjin, China. BMI, WC, and WHR were used to define overweight and obesity following standard criteria. Prevalence rates were calculated and standardized using local age- and gender-specific census data. Logistic regression was used in data analysis. Results: Using the combination of BMI, WC, and WHR, the prevalence of overweight and obesity was 69.8%, and increased with age till the age of 60 and a decline thereafter. The prevalence of overweight assessed by BMI was higher than that assessed by WC and WHR, while the prevalence of obesity defined by BMI was much lower than that defined by WC or WHR. Conclusion: The prevalence of overweight and obesity is about 70% among Chinese adults. Adiposity indicators and age play an important role in the prevalence of overweight and obesity.

Gamma-tocotrienol, a major component of tocotrienol-rich fraction of palm oil, has been suggested to exhibit bone protective effects in vivo. However, the effects of γ-tocotrienol on osteoblast cells are still unclear. In this study, the effects of γ-tocotrienol on the proliferation, differentiation, and mineralization in osteoblastic MC3T3-E1 cells were investigated. Our results showed that γ-tocotrienol (2–8 μmol/L) significantly improved the cell proliferation (p