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Decreased secretion of melatonin was reported to be associated with an enhanced risk of hypertension and diabetes. However, the effect of melatonin on gestational hypertension (GH) and the underlying mechanism remain unclear. A GH mouse model was established via electrical stimulation. The hypertensive phenotypes were indicated by systolic blood pressure (SBP) and urinary protein levels. Uterine artery (UtA) endothelial function was detected by relaxation, peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI) and pulsatility index (PI). Protein expression levels were determined using immunochemistry and Western blots. Pregnancy outcomes were indicated by the fetal live ratio, fetal weight and placental weight. Melatonin supplementation ameliorated hypertensive phenotypes in the mice with GH and enhanced UtA endothelial response to acetylcholine. The BKCa potassium channel was involved in the effect of melatonin on UtA endothelial function, and melatonin promoted BKCa potassium channel expression and function in UtAs. Finally, melatonin improved pregnancy outcomes in pregnant mice. In conclusion, melatonin ameliorates hypertension in hypertensive pregnant mice and suppresses hypertension-induced decreases in Ca2+-activated K+ channels in uterine arteries.

Background Several studies have shown that preoperative blood transfusion is associated with postoperative venous thromboembolism (VTE). In this study, a meta-analysis was performed to explore the relationship between preoperative blood transfusion and postoperative VTE. Methods Published articles were identified through a comprehensive review of PubMed and EMBASE. Data from studies reporting relative risks, odds ratios, or hazard ratios comparing the risk of postoperative VTE among participants who had preoperative blood transfusion versus those without preoperative blood transfusion were analyzed. A random-effect model was used to calculate pooled odds ratios and 95% confident intervals (CIs). Results Eight studies, which included 3,504,778 participants, aligned with our inclusion criteria and were included in the meta-analysis. Pooled analysis showed an association between preoperative blood transfusion and postoperative VTE, with an odds ratio of 2.95 (95% CI: 1.65–5.30; I2 = 89.1%). In subgroup analyses, the positive association between preoperative blood transfusion and postoperative VTE was still exist in studies with confounders adjustment. Sensitivity analysis by one-study-removed analysis confirmed the robustness of our results. Conclusions Our study indicated that preoperative blood transfusion was associated with higher odds of postoperative VTE. Further large-scale prospective cohort studies are needed to investigate the causality between preoperative blood transfusion and postoperative VTE.

Objective: Optimal dosing regimens for achieving a positive clinical outcome were simulated for seven antibiotics commonly used to treat bloodstream infections (BSIs) in adults. Methods and Results...

The combustion of fossil fuels has resulted in rapidly increasing emissions of nitrogen oxide (NOx), which has caused serious human health and environmental problems. NO capture has become a research focus in gas purification because NO accounts for more than 90% of NOx and is difficult to remove. Advanced oxidation processes (AOPs), features the little secondary pollution and the broad-spectrum strong oxidation of hydroxyl radicals (•OH), are effective and promising strategies for NO removal from coal-fired flue gas. This review provides the state of the art of NO removal by AOPs, highlighting several methods for producing •OH and SO4•-. According to the main radicals responsible for NO removal, these processes are classified into two categories: hydroxyl radical-based AOPs (HR-AOPs) and sulfate radical-based AOPs (SR-AOPs). This paper also reviews the mechanisms of NO capture by reactive oxygen species (ROS) and SO4•- in various AOPs. A HiGee (high-gravity) enhanced AOP process for improving NO removal, characterized by intensified gas-liquid mass transfer and efficient micro-mixing, is then proposed and discussed in brief. We believe that this review will be useful for workers in this field. Graphical abstract.

Introduction Invasive fungal disease (IFD) is a life-threatening infection. The epidemiology and clinical features of IFD in the elderly population are less discussed. The aim of this study was to explore the epidemiology and mortality-associated factors for IFD in the elderly inpatients. Methods A retrospective study enrolling 512 elderly inpatients from The First Affiliated Hospital of Sun Yat-sen University during the last two decades was performed. Results The annual prevalence of IFD was 0.1-0.5%. Candidiasis was the most common (236/521, 45.3%). An increasing trend was observed in aspergillosis from 11.1% in year 1998 to 28.8% in year 2018. The common infective sites of candidiasis were abdominal cavity (83/236, 35.2%) and bloodstream (55/236, 23.3%). Invasive aspergillosis mainly developed in the sinus (74/149, 49.7%) and lung (65/149, 43.6%). Patients with diabetes mellitus (DM) (59/126, 46.8%), solid organ malignancy (84/114, 73.7%), chronic kidney disease (CKD) (40/62, 64.5%) or receiving operation (109/147, 74.1%) were prone to develop candidiasis, while aspergillosis was usually complicated in patients with chronic obstructive pulmonary disease (COPD) (25/51, 49.0%). The all-cause mortality rate was 25.9% (135/521), and patients aged ≥80 years were the riskiest (20/51, 39.2%). Lymphopenia (59.5% vs 17.3%, P

Background Comorbidities, any other coexisting diseases in patients with a particular index disease, are known to increase the mortality of a stroke. However, the association of pre-existing comorbidities with stroke risk has not been fully studied. Methods This study included 16,246 adults from a prospective community-based cohort with a baseline survey conducted in 2013 in China. Participants were followed up with hospitalization records and the Cause of Death Registry. The association of eight pre-existing comorbidities (coronary heart disease, hyperlipidemia, hypertension, diabetes, previous stroke, chronic obstructive pulmonary disease, nephropathy, and cancer) with stroke risk was analyzed using the Cox proportional hazard model in 2020. Results At a median follow-up of 5.5 years, a total of 449 participants (206 men and 243 women) developed a stroke. Four pre-existing comorbidities (hypertension, congenital heart disease, previous stroke, and diabetes) were independently and positively associated with the risk for all types of stroke. The adjusted hazard ratios for participants with only 1 and ≥ 2 pre-existing comorbidities compared with those without pre-existing conditions were 1.96 (95% CI: 1.44, 2.67; P P Conclusions The number of pre-existing comorbidities was independently associated with an increased risk of stroke. There was a synergic effect between increased age and a higher number of pre-existing comorbidities on stroke occurrence. Our novel findings emphasize the importance and potential application of pre-existing comorbidities as a risk indicator in stroke prevention.

Background:Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).Methods:We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.Results:DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.Conclusions:DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.Funding:This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

ObjectivesDiabetes mellitus has been associated with stroke. However, the association between fasting blood glucose (FBG) and stroke risk in a general population remains not clear. The purpose of our study was to examine the FBG levels on subsequent stroke risk in a community-based cohort in China.DesignProspective cohort study, employing Cox proportional hazard model to analyse the association of FBG levels with stroke risk.SettingA community-based cohort study included adults participating in a baseline survey conducted in 2013 in Changshu, eastern China.Participants16 113 participants were recruited with a multistage sampling method, excluding participants with severe disability, severe cancer, severe psychiatric disturbance or previous stroke before enrolment.Primary outcome measuresStroke events.ResultsDuring a median follow-up of 5.5 years, 417 incident cases of stroke were identified. The adjusted HR for total and ischaemic stroke for participants in the fourth quartile of FBG compared with the first quartile was 1.44 (95% CI 1.07 to 1.94) and 1.57 (95% CI 1.11 to 2.21), respectively. FBG levels of ≥7.0 mmol/L were associated with an increased risk of stroke based on two clinical classifications (American Diabetes Association: 1.68 (1.24 to 2.27); WHO: 1.62 (1.21, 2.13)). In stratified analyses, risk associations existed in women (HR: 1.92, 95% CI 1.22 to 3.01) and postmenopausal women (HR: 1.68, 95% CI 1.06 to 2.68) for the fourth quartile versus the first. More importantly, the meta-analysis observed a positive association between FBG levels and stroke risk (pooled HR: 1.70, 95% CI 1.27 to 2.29; n=7)).ConclusionsHigher FBG level was independently associated with an increased risk of stroke in Chinese adults, especially significant in women.

Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions. In this study, we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheumatoid arthritis (RA). Arthritic mice displayed fracture nonunion with the absence of fracture callus, diminished angiogenesis and fibrotic scar tissue formation leading to the failure of biomechanical properties, representing the major manifestations of atrophic nonunion in the clinic. Mechanistically, we demonstrated that the angiogenesis defect observed in RA mice was due to the downregulation of SPP1 and CXCL12 in chondrocytes, as evidenced by the restoration of angiogenesis upon SPP1 and CXCL12 treatment in vitro. In this regard, we developed a biodegradable scaffold loaded with SPP1 and CXCL12, which displayed a beneficial effect on angiogenesis and fracture repair in mice despite the presence of inflammation. Hence, these findings strongly suggest that the sustained release of SPP1 and CXCL12 represents an effective therapeutic approach to treat impaired angiogenesis and fracture nonunion under inflammatory conditions.

It is indicated that lipids profiles are associated with carotid plaque and Atherosclerosis. However, studies about the relationship between serum lipid profiles and carotid plaque composition in Chinese Population is limited. We conducted a cross-sectional study among 3,214 participants between January 2015 and December 2017 in China, to investigate the association between various lipid profiles and the prevalence of carotid plaque. Logistic regression model was used to investigate the association between plasma lipid profiles and odds of carotid plaque. Analysis of covariance (ANCOVA) was used to compare the mean plasma lipid profiles among different number and composition of carotid artery plaques. HDL-C, Non-HDL-C levels, TC/HDL-C, LDL-C/HDL-C were significantly associated with the presence of carotid plaque; HDL-C, LDL-C, Non-HDL-C levels, TC/HDL-C, LDL-C/HDL-C were significantly associated with the presence of common carotid artery (CCA) plaque. Compare with participants without carotid plaque, increased level of LDL-C/HDL-C was found in those with echolucent/polytype plaque. Similarly, compared with participants without CCA plaque, increased level of LDL-C/HDL-C was found in those with echolucent plaque. In conclusion, we found that serum HDL-C, Non-HDLc level, TC/HDLc, and LDLc/HDLc were all associated with the prevalence of carotid plaque, and LDL-C/HDL-C differed among different group of carotid plaque composition.

Evidence indicates associations between higher optimism and reduced risk of age-related conditions and premature mortality. This suggests optimism is a positive health asset, but research identifying potential biological mechanisms underlying these associations remains limited. One potential pathway is slower cellular aging, which may delay age-related deterioration in health. Data were from the Women’s Health Initiative (WHI) (N=3,298) and the Veterans Affairs Normative Aging Study (NAS) (N=514), and included dispositional and explanatory style optimism measures. We evaluated whether higher optimism was associated with metrics suggestive of less cellular aging, as indicated by two DNA methylation algorithms, intrinsic (IEAA) and extrinsic epigenetic age acceleration (EEAA); these algorithms represent accelerated biologic aging that exceeds chronological age. We used linear regression models to test our hypothesis while considering several covariates (sociodemographics, depressive symptoms, health behaviors). In both cohorts, we found consistently null associations of all measures of optimism with both measures of DNA methylation aging, regardless of covariates considered. For example, in fully-adjusted models, dispositional optimism was not associated with either IEAA (WHI:β=0.02; 95% Confidence Interval [CI]:-0.15-0.20; NAS:β=-0.06; 95% CI:-0.56-0.44) or EEAA (WHI:β=-0.04; 95% CI: -0.26-0.17; NAS:β=-0.17; 95% CI: -0.80-0.46). Higher optimism was not associated with reduced cellular aging as measured in this study.

BackgroundA ‘mortality risk score’ (MS) based on ten prominent mortality-related cytosine-phosphate-guanine (CpG) sites was previously associated with all-cause mortality, but has not been verified externally. We aimed to validate the association of MS with mortality and to compare MS with three aging biomarkers: telomere length (TL), DNA methylation age (DNAmAge) and phenotypic age (DNAmPhenoAge) to explore whether MS can serve as a reliable measure of biological aging and mortality.MethodsAmong 534 males aged 55–85 years from the US Normative Aging Study, the MS, DNAmAge and DNAmPhenoAge were derived from blood DNA methylation profiles from the Illumina HumanMethylation450 BeadChip, and TL was measured by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsA total of 147 participants died during a median follow-up of 9.4 years. The MS showed strong associations with all-cause, cardiovascular disease (CVD) and cancer mortality. After controlling for all potential covariates, participants with high MS (>5 CpG sites with aberrant methylation) had almost 4-fold all-cause mortality (hazard ratio: 3.84, 95% confidence interval: 1.92–7.67) compared with participants with a low MS (0–1 CpG site with aberrant methylation). Similar patterns were observed with respect to CVD and cancer mortality. MS was associated with TL and DNAmPhenoAge acceleration but not with DNAmAge acceleration. Although the MS and DNAmPhenoAge acceleration were independently associated with all-cause mortality, the former exhibited a higher predictive accuracy of mortality than the latter.ConclusionsMS has the potential to be a prominent predictor of mortality that could enhance survival prediction in clinical settings.

Agency problems, such as moral hazard and adverse selection, are prevalent in the public service sector, and the Chinese rural e-commerce service sector is no exception. With the focus on the top-down project ‘information and communication technology for development’ implemented in the underdeveloped areas in China, the rural e-commerce service center (RESC) operation mechanism was analyzed in this study. Based on the tension between RESC operators, local governments, and e-commerce service providers that was reported in a field survey, this study further employs the principal-agent framework to analyze the problems of asymmetric information. Based on this analysis, solutions are suggested that can remedy the moral hazard issues in rural e-commerce service delivery, including developing a service evaluation system, promoting the usage of ICTs, and enhancing rural social capital. To address the problem of adverse selection, the RESC recruitment process should be improved. Moreover, by dividing the potential RESC employees into native villagers and e-commerce entrepreneurs, the optimal subsidy schemes can be designed for both types of applicants according to their ability and sensitivity to incentive.

Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.

Background and aims: Studies on associations of apolipoprotein B (ApoB), apolipoprotein A-I (ApoA-I) and the ApoB/ApoA-I ratio with stroke risk are scarce. We aimed to prospectively examine the associations of the ApoB/ApoA-I ratio and other lipid profiles with the risk of stroke using data from the China Health and Nutrition Survey (CHNS). Methods and results: A total of 7318 participants without stroke at baseline in 2009 were included in the final analysis and followed for a median of 6.1 years. The serum lipid profiles including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), ApoA-I, and ApoB were measured at baseline. Multivariable Cox proportional hazards models were used to evaluate the associations between these parameters and stroke risk. The ApoB/ApoA-I ratio was positively associated with incident stroke, yielding adjusted hazard ratio (HR) of 1.32 (95% CI: 1.09 – 1.59, P = 0.004). In comparison, ratio of ApoB and ApoA-I containing lipoproteins, the non-HDL-C/HDL-C ratio, possessed relatively weaker association with incident stroke (HR: 1.24, 95% CI: 1.01 – 1.52, P = 0.036). Furthermore, the risk associations for the ApoB/ApoA-I and non-HDL-C/HDL-C ratios were prominent among those participants aged > 51, body mass index ≤ 23, or female. There were no significant associations of other lipids and their ratios with the stroke risk. Conclusions: Higher ApoB/ApoA-I ratio was associated with an increased risk of stroke. Our findings suggest that the ApoB/ApoA-I ratio may serve as a better risk indicator of stroke than other lipid profiles and their ratios.

Background DNA methylation (DNAm) may play a role in age-related outcomes. It is not yet known which DNAm-based biomarkers of age acceleration (BoAA) has the strongest association with age-related endpoints. Methods We collected the blood samples from two independent cohorts: the Normative Ageing Study, and the Cooperative Health Research in the Region of Augsburg cohort. We measured epigenome-wide DNAm level, and generated five DNAm BoAA at baseline. We used Cox proportional hazards model to analyze the relationships between BoAA and all-cause death. We applied the Fine and Gray competing risk model to estimate the risk of BoAA on myocardial infarction (MI), stroke, and cancer, accounting for death of other reasons as the competing risks. We used random-effects meta-analyses to pool the individual results, with adjustment for multiple testing. Findings The mean chronological ages in the two cohorts were 74, and 61, respectively. Baseline GrimAgeAccel, and DNAm-related mortality risk score (DNAmRS) both had strong associations with all-cause death, MI, and stroke, independent from chronological age. For example, a one standard deviation (SD) increment in GrimAgeAccel was significantly associated with increased risk of all-cause death [hazard ratio (HR): 2.01; 95% confidence interval (CI), 1.15, 3.50], higher risk of MI (HR: 1.44; 95% CI, 1.16, 1.79), and elevated risk of stroke (HR: 1.42; 95% CI, 1.06, 1.91). There were no associations between any BoAA and cancer. Interpretation From the public health perspective, GrimAgeAccel is the most useful tool for identifying at-risk elderly, and evaluating the efficacy of anti-aging interventions. Funding National Institute of Environmental Health Sciences of U.S., Harvard Chan-NIEHS Center for Environmental Health, German Federal Ministry of Education and Research, and the State of Bavaria in Germany.

This study analyzed the pathogen distribution in bloodstream-infected (BSI) children hospitalized in Shandong Province from 2015 to 2018, to identify prevention strategies and select empiric antimicrobial therapy for BSI in children. Blood sample data from 14 107 children from 162 hospitals of Shandong Province were obtained from the China Antimicrobial Resistance Surveillance System and analyzed with WHONET 5.6 software. The results of the blood culture test showed the growth of 70.6% Gram-positive and 29.4% Gram-negative bacteria. Of the 14 107 blood isolates, 59.3% were collected from males and 40.7% were from females. Coagulase-negative staphylococci (47.1%) were the most commonly distributed pathogens. The distribution of pathogens varied according to age group and season. All Staphylococcus isolates were susceptible to vancomycin, teicoplanin and linezolid. Clinically, significant declines in penicillin-resistant Streptococcus pneumonia and carbapenem-resistant Escherichia coli were observed during the study period; however, detection rates of carbapenem-resistant Klebsiella pneumoniae increased over time (p

Knowing the number of occupants of different zones in buildings, is crucial for intelligent buildings and building energy managing system. In this paper, a two-step framework on indoor occupant counting is proposed, where the region of interest (ROI) of the target image is obtained based on a cascade classifier in the first step, and the number of indoor occupant is estimated through classifying and recognizing the ROI area based on deep learning technologies in the second step. Finally, this system framework have been implemented and real experiments are conducted to verify its effectiveness. Results show that the average of more than 91% accuracy rate on the occupant number detection can be achieved by the partly background elimination, and the binary absence or presence prediction accuracy can reach more than 93%.

For many applications in buildings, such as heating, ventilation and air conditioning (HVAC), lighting control under normal conditions and fast evacuation under emergency conditions, the real-time and reliable knowledge of the number of occupants in each area plays an important role. This paper works on a naive and ideal occupant estimation model by detecting the enter and leave occupants of boundary detection area, and the zenithal video analysis is utilized to reduce the cumulative error of the naive estimation model. Specifically, the Kalman Filter is utilized to track the targets that through the border of each area, and two key tunable pareamters that are the matching distance threshold and scaling factor are designed and tested elaborately to reduce the estimation error. Experimental results show that the proposed zenithal video analysis based indoor occupant counting approach with the careful tuning of matching distance threshold and the scaling factor,can effectively reduce the discriminant error of occupants entering and exiting, achieving the estimation of the indoor occupant number with above 92% accuracy, the occupied or unoccupied state estimation for an area with more than 99% accuracy, and the staying time of indoor occupant with more than 99% accuracy.

Background We investigated the expression and clinical significance of miR-141 and miR-340 in cervical squamous cell carcinoma (CSCC). Methods Expression of miR-141 and miR-340 in CSCC, high-grade squamous intraepithelial lesion (HSIL), and normal cervical squamous epithelium were detected by qRT-PCR. PTEN was assessed by immunohistochemistry. Their relationship with clinicopathological features was analyzed. Results The changes of miR-141 and miR-340 were different in CSCC, HSIL, and normal squamous epithelium (P = 0.030). miR-141 expression was statistically significant in gross type, differentiation, uterine corpus invasion, nerve invasion, vagina invasion, and FIGO stage in CSCC (P < 0.05). miR-340 expression was related to tumor size, differentiation, nerve invasion, lymph node metastasis, and FIGO stage in CSCC (P < 0.05). miR-141 and miR-340 expressions were statistically significant in different ages (P < 0.05) in HSIL. The AUC of miR-141 in CSCC diagnosis and that of miR-340 in HSIL diagnosis were 0.893 and 0.764, respectively. The sensitivity and the specificity of miR-141 for diagnosis of CSCC were 95.0% and 60.8%, respectively, while those of miR-340 for diagnosis of HSIL were 90.0 and 48.6%, respectively. miR-141 and miR-340 expressions are associated with PTEN expression (P = 0.002 and P < 0.001). Conclusion miR-141 and miR-340 may be associated with their target gene PTEN and involved in the carcinogenesis of cervical squamous epithelium.

Tigecycline, a new first-in-class glycylcycline antibiotic, has shown promising efficacy against a broad range of micro-organisms. It is widely prescribed for various infections, with most prescriptions being considered for off-label use. However, only a few years after its approval by the US Food and Drug Administration (FDA), tigecycline is suspected of increasing all-cause mortality. Some clinicians have suggested such unfavourable outcomes correlate with inadequate drug exposure at the infection site. The pharmacokinetic/pharmacodynamic (PK/PD) profile of a drug plays an important role in predicting its antibiotic effect, which for tigecycline is determined as the ratio of area under the concentration–time curve (AUC) to minimum inhibitory concentration (MIC). In this study, PK/PD targets based on infection sites, bacterial isolates and patient populations are discussed. Generally, a higher dosage of tigecycline for the treatment of serious infections has been recommended in previous reports. However, the latest finding of tigecycline's atypical protein binding property requires consideration when recommending further use. In addition, combination therapy with other antibiotics provides another option by potentially lowering the MICs of multidrug-resistant bacteria.

One-carbon metabolism is an important contributor to aging-related diseases; nevertheless, relationships of one-carbon metabolites with novel DNA methylation-based measures of biological aging remain poorly characterized. We examined relationships of one-carbon metabolites with 3 DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge. We measured plasma levels of 4 common one-carbon metabolites (vitamin B6, vitamin B12, folate, and homocysteine) in 715 VA Normative Aging Study participants with at least 1 visit between 1999 and 2008 (observations = 1153). DNA methylation age metrics were calculated using the HumanMethylation450 BeadChip. We utilized Bayesian Kernel Machine Regression models adjusted for chronological age, lifestyle factors, age-related diseases, and study visits to determine metabolites important to the aging outcomes. Bayesian Kernel Machine Regression models allowed for the estimation of the relationships of single metabolites and the cumulative metabolite mixture with methylation age. Log vitamin B6 was selected as important to PhenoAge (β = −1.62 years, 95% CI: −2.28, −0.96). Log folate was selected as important to GrimAge (β = 0.75 years, 95% CI: 0.41, 1.09) and PhenoAge (β = 1.62 years, 95% CI: 0.95, 2.29). Compared to a model where each metabolite in the mixture is set to its 50th percentile, the log cumulative mixture with each metabolite at its 30th (β = −0.13 years, 95% CI: −0.26, −0.005) and 40th percentile (β = −0.06 years, 95% CI: −0.11, −0.005) was associated with decreased GrimAge. Our results provide novel characterizations of the relationships between one-carbon metabolites and DNA methylation age in a human population study. Further research is required to confirm these findings and establish their generalizability.

Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up - baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.

Background Hysteroscopy is a commonly used technique for diagnosing endometrial lesions. It is essential to develop an objective model to aid clinicians in lesion diagnosis, as each type of lesion has a distinct treatment, and judgments of hysteroscopists are relatively subjective. This study constructs a convolutional neural network model that can automatically classify endometrial lesions using hysteroscopic images as input. Methods All histopathologically confirmed endometrial lesion images were obtained from the Shengjing Hospital of China Medical University, including endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyps, and submucous myomas. The study included 1851 images from 454 patients. After the images were preprocessed (histogram equalization, addition of noise, rotations, and flips), a training set of 6478 images was input into a tuned VGGNet-16 model; 250 images were used as the test set to evaluate the model’s performance. Thereafter, we compared the model’s results with the diagnosis of gynecologists. Results The overall accuracy of the VGGNet-16 model in classifying endometrial lesions is 80.8%. Its sensitivity to endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyp, and submucous myoma is 84.0%, 68.0%, 78.0%, 94.0%, and 80.0%, respectively; for these diagnoses, the model’s specificity is 92.5%, 95.5%, 96.5%, 95.0%, and 96.5%, respectively. When classifying lesions as benign or as premalignant/malignant, the VGGNet-16 model’s accuracy, sensitivity, and specificity are 90.8%, 83.0%, and 96.0%, respectively. The diagnostic performance of the VGGNet-16 model is slightly better than that of the three gynecologists in both classification tasks. With the aid of the model, the overall accuracy of the diagnosis of endometrial lesions by gynecologists can be improved. Conclusions The VGGNet-16 model performs well in classifying endometrial lesions from hysteroscopic images and can provide objective diagnostic evidence for hysteroscopists.

Humans can change their behaviors to obtain environmental rewards (e.g., money, food, and sex). However, our knowledge regarding how rewards affect human behaviors by priming and whether there are differences among types of rewards is limited. This study focused on whether monetary and social rewards have different priming effects on product rating decisions in e-commerce by using a behavioral experiment and event-related potentials (ERPs). Using cash/discount coupons as a monetary reward and greeting cards as a social reward, the behavioral data showed that unsatisfactory products with a monetary reward induced a less negative consumer attitude than those with a social reward or no reward; additionally, such products were associated with a longer reaction time while rating products than those with a social reward, reflecting that monetary rewards made it more difficult for the subjects to rate unsatisfactory products than social rewards. The P2, N2, and P3 components of the ERP data were evaluated. Unsatisfactory products caused negative emotion, which could be compensated more by the monetary reward than the social reward as reflected by a smaller P2 amplitude. Due to the compensation effect of the monetary reward, unsatisfactory products were associated with more decision conflict than the social reward as reflected by a more negative N2 amplitude, which is consistent with the behavioral results. However, in the subsequent controlled process, regardless of whether the products were satisfactory or unsatisfactory, the monetary reward caused more attention reallocation and was more motivating than the social reward as reflected by a larger P3 component. These findings have implications for the marketing strategy of online sellers and value of online reviews and suggest attaching importance to ethical issues induced by monetary rewards in rating behaviors.

Background: Previous studies have indicated that white blood cells (WBCs) might contribute to the development of atherosclerosis. However, the associations of WBCs and WBC subgroups with carotid atherosclerotic plaque (CAP) have not been compared.Methods: A cross-sectional study including 3,569 healthy Chinese adults was conducted between January 2016 and December 2018 in Zhengzhou, China, to explore the associations of WBC and WBC subtypes with the presence, severity, and types of CAPs. Fasting peripheral venous blood was collected for measurement of the total WBC and WBC subtype counts. The size, composition, and types of CAPs in the common carotid artery, the internal carotid artery, and the external carotid artery were measured bilaterally using B-mode ultrasound.Results: The total WBC, neutrophil, and monocyte counts showed significant associations with the presence of CAPs in men, but not in women, with the adjusted odds ratios (95% CI) in the highest (compared to the lowest) quartile 1.99 (1.33–2.97), 1.65 (1.10–2.47), and 2.17 (1.41–3.18) (Ptrend = 0.004, Ptrend = 0.004, and Ptrend < 0.001), respectively. The three leukocyte counts were also significantly associated with the severity of CAPs, as judged by the count of CAPs, maximal internal carotid plaque thickness, and the plaque score (all P < 0.01, Ptrend < 0.05). Compared with individuals without CAPs, those with echolucent plaques had significantly increased total WBC and neutrophil counts, whereas those with polytype plaques had a significantly increased monocyte count.Conclusion: WBC, neutrophil, and monocyte counts were significantly associated with the presence, severity, and types of CAPs in a healthy Chinese population.

Aims Diabetes mellitus has been reported to be one of the most prevalent comorbidity in patients with Coronavirus Disease 2019 (COVID-19). We aimed to assess the association of comorbid diabetes with COVID-19 severity or mortality in China. Methods We performed a systematic literature search from six electronic databases on diabetes and COVID-19. The outcome of interest was disease severity or mortality. Heterogeneity among the studies was assessed by the Cochran Q test and the I2 statistic. A random effects model was applied to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). Results Nine studies from different provinces/cities were identified according to the predefined inclusion and exclusion criteria. There were a total of 1070 patients with diabetes, out of the 8807 COVID-19 cases. The majority of the cases were derived from Hubei Province. A low degree of heterogeneity in the risk estimates was observed in the included studies. Meta-analysis showed that there was a significant association of preexisting diabetes with disease severity or death. The pooled RR was 2.96 (95% CI: 2.31–3.79; p

Background Waardenburg syndrome (WS) is a highly clinically and genetically heterogeneous disease. The core disease phenotypes of WS are sensorineuronal hearing loss and pigmentary disturbance, which are usually caused by the absence of neural crest cell‐derived melanocytes. At present, four subtypes of WS have been defined, which are caused by seven genes. Waardenburg syndrome type 2 (WS2) is one of the most common forms. Two genes, MITF and SOX10, have been found to be responsible for majority of WS2. Methods In this study, we performed a clinical longitudinal follow‐up and mutation screening for a Chinese family with Waardenburg syndrome type II. Results A diversity of clinical manifestations was observed in this WS2 family. In addition to the congenital hearing loss of most affected family members, progressive hearing loss was also found in some WS2 patients. A nonsense mutation of c.328C>T (p.R110X) in MITF was identified in all affected family members. This mutation results in a truncated MITF protein, which is considered to be a disease‐causing mutation. Conclusion These findings offer a better understanding of the spectrum of MITF mutations and highlight the necessity of continuous hearing assessment in WS patients., The present study describes a large Chinese WS2 family with a highly clinical heterogeneity. Clinical longitudinal follow‐up revealed progressive hearing loss in some patients. A nonsense mutation of c.328C>T (p.R110X) in MITF was identified.

The discrepancy of DNA methylation age (DNAmAge) with chronological age (termed as age acceleration, AA) has been identified to be associated with many aging-related health outcomes including hypertension. Since taking antihypertensive medication (AHM) could prevent aging-related diseases caused by hypertension, we hypothesized that using AHM could also reduce the AA. We examined this hypothesis among 546 males aged 55-85 years by exploring the associations of AHM use with AA and its change rate (ΔAA) in two visits with a median follow-up of 3.86 years. Horvath DNAmAge was derived from DNA methylation profiles measured by Illumina HumanMethylation450 BeadChip and information on AHM use was collected by physician interview. A general decreasing pattern of AA was observed between the two visits. After the fully adjusting for potential covariates including hypertension, any AHM use showed a cross-sectional significant association with higher AA at each visit, as well as a longitudinal association with increased ΔAA between visits. Particularly, relative to participants who never took any AHM, individuals with continuous AHM use had a higher ΔAA of 0.6 year/chronological year. This finding underlines that DNAmAge and AA may not be able to capture the preventive effects of AHMs that reduce cardiovascular risks and mortality.

Background Epidemiological studies have shown the associations of ambient temperature and particulate matter (PM) air pollution with respiratory morbidity and mortality. However, the underlying mechanisms have not been well characterized. The aim of this study is to investigate the associations of temperature and fine and coarse PM with fractional exhaled nitric oxide (FeNO), a well-established biomarker of respiratory inflammation. Methods We conducted a longitudinal panel study involving six repeated FeNO tests among 33 type 2 diabetes mellitus patients from April to June 2013 in Shanghai, China. Hourly temperature and PM concentrations were obtained from a nearby fixed-site monitoring station. We then explored the associations between temperature, PM, and FeNO using linear mixed-effect models incorporated with distributed lag nonlinear models for the lagged and nonlinear associations. The interactions between temperature and PM were evaluated using stratification analyses. Results We found that both low and high temperature, as well as increased fine and coarse PM, were significantly associated with FeNO. The cumulative relative risk of FeNO was 1.75% (95% confidence interval [CI], 1.04–2.94) comparing 15 °C to the referent temperature (24 °C) over lags 0–9 days. A 10 μg/m3 increase in fine and coarse PM concentrations were associated with 1.18% (95% CI, 0.18–2.20) and 1.85% (95% CI, 0.62–3.09) FeNO in lag 0–1 days, respectively. PM had stronger effects on cool days than on warm days. Conclusions This study suggested low ambient temperature, fine PM, and coarse PM might elevate the levels of respiratory inflammation. Our findings may help understand the epidemiological evidence linking temperature, particulate air pollution, and respiratory health., Highlights • Both low and high temperatures were significantly associated with FeNO. • The increases of fine and coarse PM concentrations were associated with FeNO. • Both fine and coarse PM had stronger effects in cool days.

Air pollution may increase cardiovascular and respiratory risk through inflammatory pathways, but evidence for acute effects has been weak and indirect. Between December 2014 and July 2015, we enrolled 36 healthy, nonsmoking college students for a panel study in Shanghai, China, a city with highly variable levels of air pollution. We measured personal exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5) continuously for 72 hours preceding each of 4 clinical visits that included phlebotomy. We measured 4 inflammation proteins and DNA methylation at nearby regulatory cytosine-phosphate-guanine (CpG) loci. We applied linear mixed-effect models to examine associations over various lag times. When results suggested mediation, we evaluated methylation as mediator. Increased PM2.5 concentration was positively associated with all 4 inflammation proteins and negatively associated with DNA methylation at regulatory loci for tumor necrosis factor alpha (TNF-α) and soluble intercellular adhesion molecule-1. A 10-μg/m3 increase in average PM2.5 during the 24 hours preceding blood draw corresponded to a 4.4% increase in TNF-α and a statistically significant decrease in methylation at one of the two studied candidate CpG loci for TNF-α. Epigenetics may play an important role in mediating effects of PM2.5 on inflammatory pathways.

There is increasing interest in quasi-experimental research to evaluate whether actions taken to improve air quality will benefit public health. We conducted a quasi-experimental study to evaluate inflammatory response to changes in air quality during the 2014 Nanjing Youth Olympics in China. We repeatedly measured 8 biomarkers of systemic inflammation in 31 healthy adults and obtained hourly air pollutant concentrations from a nearby fixed-site monitoring station. We used linear mixed-effect models to examine the associations between air quality changes and blood biomarkers. Air pollutant concentrations decreased apparently during the Youth Olympics. Concomitantly, we observed significant decreases in levels of soluble cluster of differentiation 40 (CD40) ligand and interleukin 1β (geometric means ratios were 0.45 and 0.24, respectively) from the pre-Olympic period to the intra-Olympic period. Afterwards, levels of C-reactive protein and vascular cell adhesion molecule 1 increased significantly (geometric means ratios were 2.22 and 1.29, respectively) in the post-Olympic period. Fine particulate matter and ozone were significantly associated with soluble CD40 ligand, P-selectin, interleukin 1β, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. Other pollutants showed positive but nonsignificant associations. Our study indicated that reduced air pollution, especially fine particulate matter and ozone, during the 2014 Nanjing Youth Olympics was associated with alleviated systemic inflammation in healthy adults.

The evidence is quite limited regarding the constituents of fine particulate matter (PM2.5) responsible for lung dysfunction. We designed a time-series panel study in 28 patients to examine the effects of 10 major constituents of PM2.5 on lung function with repeated daily measurements from December 2012 to May 2013 in Shanghai, China. We applied a linear mixed-effect model combined with a distributed lag model to estimate the cumulative effects of PM2.5 constituents on morning/evening forced expiratory volume in 1-s (FEV1) and peak expiratory flow (PEF) over a week. The cumulative decreases in morning FEV1, evening FEV1, morning PEF and evening PEF associated with an interquartile range (35.8 μg/m3) increase in PM2.5 concentrations were 33.49 [95% confidence interval(CI):2.45,54.53] mL, 16.80 (95%CI:3.75,29.86) mL, 4.48 (95%CI:2.30,6.66) L/min, and 1.31 (95%CI:-0.85,3.47) L/min, respectively. These results were not substantially changed after adjusting for gases in two-pollutant models. The associations o...

Besides expanding the spectrum of KCNQ1 mutations causing Jervell and Lange-Nielsen Syndrome (JLNS), the results showed diversity of its phenotypes, and emphasized the importance of molecular genetic analysis in confirming clinical diagnosis and making diagnosis possible before the emergency symptoms for deaf individuals.This study aimed to investigate four patients from three Chinese families with congenital hearing loss clinically and genetically.Genetic analysis of previously reported deafness genes based on massively parallel sequencing was conducted in more than five thousand Chinese hearing loss patients. Detailed clinical features of the patients with compound heterozygous or homozygous mutations of KCNQ1 gene were collected and analyzed.Compound mutations of KCNQ1 were found to be the genetic etiology of four patients from three families. Among the six KCNQ1 mutations, c.546C A was identified as a novel mutation, c.965C T had been reported in JLNS, while c.683 + 5G A, c.1484_1485delCT, c.905C T and c.1831G A were previously reported in LQT1. In addition to congenital profound hearing loss in all subjects, two sibling subjects showed typical JLNS cardiac phenotype of prolonged QTc and recurrent syncopal episodes. One subject presented not only JLNS, but also iron-deficiency anemia and epilepsy. The other subject did not present any cardiac phenotype.

Objectives To analyze complications associated with minimally invasive cochlear implantation by comparing data from different centers, to discuss major reasons for complications, and to refine implantation techniques to decrease them. Patients Patients who underwent cochlear implantation at our center by the same surgeon (the corresponding author of this article) from March 2006 to March 2015 were enrolled. Intervention First, a retrospective analysis of the complications associated with minimally invasive cochlear implantation at our center was performed. Second, published reports from other centers that describe complications were reviewed. Differences between complications in our cohort and other studies were evaluated. Main outcome measure Strategies for reducing complications were assessed and modifications in surgical protocol proposed accordingly. Results In total, 1,014 patients underwent 1,065 cochlear implantations. There were 28 complications (7 major, 21 minor) and only 2 reimplantations for the entire cohort, with no case of severe infection, flap necrosis, or device extrusion. The major complications were electrode misplacement, magnet displacement, implant failure secondary to trauma, and temporary cerebrospinal fluid leakage. The rates of major complications in our cohort were very low (0.6%) compared with those in the literature. Conclusion Preoperative surgical planning based on individual patient anatomy and employment of soft surgical techniques can minimize surgical complications.

To explore the clinical features and associated factors of cryptococcosis in patients with connective tissue disease (CTD) from Southern China.Demographic and clinical data were collected between 2007 and 2018. Associated factors were analyzed by logistic regression analysis.A total of 6809 inpatients with CTD were included. Cryptococcosis was diagnosed in 30 patients (prevalence, 0.4%). Cryptococcosis was predominant in patients with ANCA-associated vasculitis (AAV) (prevalence, 6/530, 1.1%). Lung was commonly involved (18/30, 60.0%), followed by meninges (6/30, 20.0%), blood stream (5/30, 16.7%), and disseminated cryptococcosis (involved blood stream and meninges) (1/30, 3.3%). Infiltrates (10/18, 55.6%) and small nodules (8/18, 44.4%) were the main radiographic manifestation of pulmonary cryptococcosis (PC). The positive rate of serum cryptococcal antigen (CrAg) in patients with PC was 88.2%. Cryptococcus spp. were found in 75% (3/4) patients who underwent lung biopsy. Most of the patients with cryptococcal meningitis (CM) had elevated cerebrospinal fluid (CSF) opening pressure (6/7, 85.7%) and decreased CSF glucose level (5/7, 71.4%). Positive blood culture confirmed the diagnosis of cryptococcal sepsis (CS). Three patients died (10.0%), including one with CM and two with PC. Multivariate logistic regression analysis showed that accumulated dose of glucocorticoid (GC) [odds ratio (OR) = 1.42, 95% confidence interval (CI) 1.04-1.93, P = 0.03] was associated with cryptococcosis in patients with CTD.Cryptococcosis develops in various organs. Typical radiological manifestation accompanied with positive serum CrAg provides helpful clues for the diagnosis. Lumbar puncture is a critical diagnostic method to distinguish CM. The accumulated dose of GC is associated with cryptococcosis in patients with CTD. Key Points • Pulmonary cryptococcosis is suspected if pulmonary nodules adjacent to the pleura are present, with serum CrAg positive. • Cryptococcal meningitis has insidious onset and the diagnosis mainly depends on lumber puncture. • Cryptococcal sepsis is not rare and needs timely blood culture in suspected patients.

Recently we demonstrated that ablation of the DNA methyltransferase enzyme, Dnmt3b, resulted in catabolism and progression of osteoarthritis (OA) in murine articular cartilage through a mechanism involving increased mitochondrial respiration. In this study, we identify 4-aminobutyrate aminotransferase (Abat) as a downstream target of Dnmt3b. Abat is an enzyme that metabolizes γ-aminobutyric acid to succinate, a key intermediate in the tricarboxylic acid cycle. We show that Dnmt3b binds to the Abat promoter, increases methylation of a conserved CpG sequence just upstream of the transcriptional start site, and inhibits Abat expression. Dnmt3b deletion in articular chondrocytes results in reduced methylation of the CpG sequence in the Abat promoter, which subsequently increases expression of Abat. Increased Abat expression in chondrocytes leads to enhanced mitochondrial respiration and elevated expression of catabolic genes. Overexpression of Abat in murine knee joints via lentiviral injection results in accelerated cartilage degradation following surgical induction of OA. In contrast, lentiviral-based knockdown of Abat attenuates the expression of IL-1β-induced catabolic genes in primary murine articular chondrocytes in vitro and also protects against murine articular cartilage degradation in vivo. Strikingly, treatment with the FDA-approved small-molecule Abat inhibitor, vigabatrin, significantly prevents the development of injury-induced OA in mice. In summary, these studies establish Abat as an important new target for therapies to prevent OA.

Limited evidence is available on the effects of various fine particulate matter (PM(2.5)) components on inflammatory cytokines and DNA methylation. We examined whether 16 PM(2.5) components are associated with changes in four blood biomarkers, that is, tumor necrosis factor-α (TNF-α), soluble cluster of differentiation 40 ligand (sCD40L), soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen, as well as their corresponding DNA methylation levels in a panel of 36 healthy college students in Shanghai, China. We used linear mixed-effect models to evaluate the associations, with controls of potential confounders. We further conducted mediation analysis to evaluate the potential mediation effects of components on inflammatory markers through change in DNA methylation. We observed that several components were consistently associated with TNF-α and fibrinogen as well as their DNA hypomethylation. For example, an interquartile range increase in personal exposure to PM(2.5)-lead (Pb) was associated with 65.20% (95% CI: 37.07, 99.10) increase in TNF-α and 2.66 (95% CI: 37.07, 99.10) decrease in TNF-α methylation, 30.51% (95% CI: 0.72, 69.11) increase in fibrinogen and 1.25 (95% CI: 0.67, 1.83) decrease in F3 methylation. PM(2.5) components were significantly associated with sICAM-1 methylation but not with sICAM-1 protein. DNA methylation mediated 19.89%–41.75% of the elevation in TNF-α expression by various PM(2.5) constituents. Our findings provide clues that personal PM(2.5) constituents exposure may contribute to increased systemic inflammation through DNA hypomethylation

Online ratings impose significant effects on the behaviors of potential customers. Thus, online merchants try to adopt strategies that affect this rating behavior, and most of these strategies are connected to money, such as the strategies of returning cash coupons if a consumer gives a five-star rating (RI strategy, an acronym for “returning” and “if”) or returning cash coupons directly with no additional requirements (RN strategy, an acronym for “returning” and “no”). The current study explored whether a certain strategy (RN or RI) was more likely to give rise to more false rating behaviors, as assessed by event-related potentials. A two-stimulus paradigm was used in this experiment. The first stimulus (S1) was the picture of a product with four Chinese characters that reflected the product quality (slightly defective vs. seriously defective vs. not defective), and the second stimulus (S2) displayed the coupon strategy (RN or RI). The participants were asked to decide whether or not to give a five-star rating. The behavioral results showed that the RI strategy led to a higher rate of five-star ratings than the RN strategy. For the electrophysiological time courses, the N1, N2 and LPP components were evaluated. The slightly defective products elicited a larger amplitude of the N1 component than the seriously defective and not-defective products, reflecting that perceptual difficulty was associated with the processing of the slightly defective products. The RI strategy evoked a less negative N2 and a more positive LPP than the RN strategy, indicating that the subjects perceived less conflict and experienced stronger incentives when processing the RI strategy. These findings will benefit future studies of fake online comments and provide evidence supporting the policy of forbidding the use of the RI strategy in e-commerce.

Elderly individuals who are never smokers but have the same height and chronological age can have substantial differences in lung function. The underlying biological mechanisms are unclear. To evaluate the associations of different biomarkers of aging (BoA) and lung function, we performed a repeated-measures analysis in the Normative Aging Study using linear mixed-effect models. We generated GrimAgeAccel, PhenoAgeAccel, extrinsic and intrinsic epigenetic age acceleration using a publically available online calculator. We calculated Zhang's DNAmRiskScore based on 10 CpGs. We measured telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) using quantitative real-time polymerase chain reaction. A pulmonary function test was performed measuring forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC), FEV1, and maximum mid-expiratory flow (MMEF). Epigenetic-based BoA were associated with lower lung function. For example, a one-year increase in GrimAgeAccel was associated with a 13.64 mL [95% confidence interval (CI), 5.11 to 22.16] decline in FEV1; a 0.2 increase in Zhang's DNAmRiskScore was associated with a 0.009 L/s (0.005 to 0.013) reduction in MMEF. No association was found between TL/mtDNA-CN and lung function. Overall, this paper shows that epigenetics might be a potential mechanism underlying pulmonary dysfunction in the elderly.

Background: The incidence of AITDs increased with the increase of iodine nutrient levels in the population. HT is one of the most common AITDs. The role of thyroid function stratification, antibody titer, Th17/Treg cells and related factors in the pathogenesis of HT under different iodine nutritional conditions is still unclear. Objective: To investigate the correlation between the thyroid function stratification, autoantibody titer and Th17 cells, Treg cells, cytokines and transcription factors in hashimoto thyroiditis patients with different iodine nutritional status. Methods: Thyroid hormone, autoantibody and urinary iodine levels were measured in 100 hashimoto's thyroiditis (HT) patients and 60 healthy subjects by electrochemical immunoluminescence and iodine-catalyzed arseniummethod. Meanwhile, the proportion and ratio of Th17 cells and Tregs cells in peripheral blood mononuclear cells (PBMC) were determined by immunofluorescence labeling and flow cytometry. The qRT-PCR was used to detect the expression of ROR-γt mRNA and Foxp3 mRNA. Serum IL-17 and TGF-β levels were detected by ELISA. Results: Th17 cell proportion, serum IL-17 and ROR-γt mRNA expression levels in PBMC of HT patients with different iodine nutritional status were all higher than those in the control group (P

Introduction: At present, studies on the role of iodine nutrition in thyroid function stratification, antibody titer, Th17/Treg cells and related factors in the pathogenesis of GD have not been carried out. Objective: The acritical aims to investigate the correlation between thyroid function and autoantibody titers of Graves' disease (GD) patients with different iodine nutritional status with Th17/Treg cells, their cytokines and transcription factors, and the role of related factors in the pathogenesis of GD. Method: The levels of serum thyroid hormone, autoantibodies and urine iodine in 100 GD patients and 60 healthy subjects are detected by electrochemiluminescence instrument and iodine-catalyzed arsenic-cerium method, respectively. The ratio of Th17 cells to Treg cells and Th17/Treg ratio in peripheral blood mononuclear cells (PBMC) are detected by immunofluorescence-labeled monoclonal antibodies and flow cytometry. Real-time fluorescence quantitative PCR is used to detect the expression levels of retinoic acid-related orphan receptor (ROR-γt) and fork head/wing-shaped spiral transcription factor 3 (Foxp3) mRNA, and the serum IL-17 and TGF-β levels are detected by ELISA. Result: As a result, the proportion of Th17 cells, serum IL-17 and ROR-γt in PBMC of GD patients with different iodine nutritional status significantly increase, while the proportion of Treg cells, the expression of Foxp3mRNA and serum TGF-β significantly decrease. The ratio of Th17/Treg cells in GD patients is significantly positively correlated with the titers of TPOAb and TgAb, and the titers of TPOAb and TgAb antibodies are significantly correlated with Th17/Treg, IL-17 and ROR-γt. Conclusion: In conclusion, thyroid hormones, autoantibodies, Th17, Treg cell ratios and dysfunctions as well as corresponding cytokines and transcription factors in GD patients with different iodine nutritional status participate in the development of GD.

A dual-gate (DG) amorphous indium–gallium–zinc-oxide thin-film transistor (TFT)-driven pixel circuit for active-matrix organic light-emitting diode displays is presented. One gate of the DGs serves as a primary gate (PG) and the other as an auxiliary gate (AG). The threshold voltage ( $V_{\mathrm {{TH}}}$ ) of the DG TFT under the PG operation is modulated by the AG bias voltage. The $V_{\mathrm {{TH}}}$ variation ( $\Delta V_{\mathrm {{TH}}}$ ) is compensated with the AG and the drain diode-connected structure. The validity of the presented pixel circuit is experimentally verified. The measured current error rates are less than 3.2% at a $\Delta V_{\mathrm {{TH}}}$ of $\text {TFT} = \pm 0.5$ V and a $\Delta V_{\mathrm {{TH}}}$ of OLED = 0.5 V with the emission current ranging from 7 nA to $1.13~\mu \text{A}$ .

Background: Practical approaches to protect individuals from ambient particulate matter (PM) are urgently needed in developing countries. Evidence on the health benefits of wearing particulate-filtering respirators is limited. Objectives: We evaluated the short-term cardiovascular health effects of wearing respirators in China. Methods: A randomized crossover trial was performed in 24 healthy young adults in Shanghai, China in 2014. The subjects were randomized into two groups and wore particulate-filtering respirators for 48 hr alternating with a 3-week washout interval. Heart rate variability (HRV) and ambulatory blood pressure (BP) were continuously monitored during the 2nd 24 hr in each intervention. Circulating biomarkers were measured at the end of each intervention. Linear mixed-effect models were applied to evaluate the effects of wearing respirators on health outcomes. Results: During the intervention periods, the mean daily average concentration of PM with an aerodynamic diameter < 2.5 μm (PM2.5) was 74.2 μg/m3. Compared with the absence of respirators, wearing respirators was associated with a decrease of 2.7 mmHg [95% confidence interval (CI): 0.1, 5.2 mmHg] in systolic BP and increases of HRV parameters, including 12.5% (95% CI: 3.8%, 21.2%) in high frequency (HF) power, 10.9% (95% CI: 1.8%, 20.0%) in the root mean square of the successive differences, and 22.1% (95% CI: 3.6%, 40.7%) in the percentage of normal RR intervals with duration > 50 msec different from the previous normal RR interval (pNN50). The presence of respirators was also associated with a decrease of 7.8% (95% CI: 3.5%, 12.1%) in the ratio of low frequency (LF)/HF power. Conclusions: Short-term wearing of particulate-filtering respirators may produce cardiovascular benefits by improving autonomic nervous function and reducing BP. Citation: Shi J, Lin Z, Chen R, Wang C, Yang C, Cai J, Lin J, Xu X, Ross JA, Zhao Z, Kan H. 2017. Cardiovascular benefits of wearing particulate-filtering respirators: a randomized crossover trial. Environ Health Perspect 125:175–180; http://dx.doi.org/10.1289/EHP73

A current source free separate frame compensated voltage-programmed AMOLED pixel circuit is proposed. In the circuit a separate frame time is periodically assigned to compensate for the variation and/or degeneration of all driving transistors and OLEDs performance simultaneously and the pixel thereby is able to have enough compensation time which is not limited by the number of the row lines and frame rate. For the rest of operation time, the pixel circuit does not perform any compensation action, allowing sufficient time for light emission. Moreover, the current error can be suppressed below 2.50% provided that the threshold voltage shift of the driving transistor and OLED is 2V.

A current comparison scheme for external compensation circuit of AMOLED displays is proposed. In this scheme, a current comparator is designed to sense the difference between the reference current and the driving current of pixels and to output a corresponding digital signal to the compensation block. For the current comparator, a sense amplifier is used to amplify the current difference, which can effectively increase the accuracy of the current comparator. Simulation results show that the accuracy of the proposed current comparator is 1nA and the sensing error is lower than 0.224 %, when the reference current is 500 nA.