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Abstract Background Polycyclic aromatic hydrocarbons (PAHs) and metals were associated with decreased lung function, but co-exposure effects and underlying mechanism remained unknown. Methods Among 1,123 adults from National Health and Nutrition Examination Survey 2011–2012, 10 urinary PAHs, 11 urinary metals, and peripheral white blood cell (WBC) count were determined, and 5 lung function indices were measured. Least absolute shrinkage and selection operator, Bayesian kernel machine regression, and quantile-based g-computation were used to estimate co-exposure effects on lung function. Mediation analysis was used to explore mediating role of WBC. Results These models demonstrated that PAHs and metals were significantly associated with lung function impairment. Bayesian kernel machine regression models showed that comparing to all chemicals fixed at median level, forced expiratory volume in 1 s (FEV1)/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25 and 75% decreased by 1.31% (95% CI: 0.72%, 1.91%), 231.62 (43.45, 419.78) mL/s, and 131.64 (37.54, 225.74) mL/s respectively, when all chemicals were at 75th percentile. In the quantile-based g-computation, each quartile increase in mixture was associated with 104.35 (95% CI: 40.67, 168.02) mL, 1.16% (2.11%, 22.40%), 294.90 (78.37, 511.43) mL/s, 168.44 (41.66, 295.22) mL/s decrease in the FEV1, FEV1/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25% and 75%, respectively. 2-Hydroxyphenanthrene, 3-Hydroxyfluorene, and cadmium were leading contributors to the above associations. WBC mediated 8.22%-23.90% of association between PAHs and lung function. Conclusions Co-exposure of PAHs and metals impairs lung function, and WBC could partially mediate this relationship. Our findings elucidate co-exposure effects of environmental mixtures on respiratory health and underlying mechanisms, suggesting that focusing on highly prioritized toxicants would effectively attenuate adverse effects.

Abstract Background Change in asthma burden attributed to specific environmental risk factor has not been evaluated. Objective We aimed to explore the age, period, and cohort effects on asthma burden attributable to smoking and occupational asthmagens in different socio-demographic index (SDI) regions and the region and sex disparities. Methods Risk factor-specific asthma deaths and disability-adjusted life years (DALYs) rates were extracted from Global Burden of Disease study 2019, estimated by standard Combined Cause of Death Model and DisMod-MR 2.1 modeling tool. Age-period-cohort analysis was conducted to decompose age, period, and cohort effects on asthma burden. Results Smoking- and occupational asthmagens-related asthma deaths and DALYs rates dropped by > 45% during 1990–2019. In 2019, Africa, South and Southeast Asia had higher asthma burden than other regions. Male had higher asthma burden than female. Among nearly all age groups, low-middle SDI region had the highest smoking-related asthma burden, and low SDI region had the highest occupational asthmagens-related asthma burden. Inverse “V” shaped trend was observed in the above regions with increasing age. For smoking-related asthma deaths and DALYs rates, the most significant improvement of period rate ratio (RR) occurred in high SDI region, decreased from 1.67 (1.61, 1.74) to 0.34 (0.33, 0.36) and 1.61 (1.57, 1.66) to 0.59 (0.57, 0.61), respectively, as well as the cohort effect on smoking-related asthma burden. For occupational asthmagens-related asthma deaths and DALYs rates, the most sharply decrease of period and cohort RR appeared in the high and high-middle SDI regions. Low SDI region showed least progress in period and cohort RR of smoking- and occupational asthmagens-linked asthma burden. Conclusion Smoking- and occupational asthmagens-related asthma burden sharply decreases, but region and sex disparities exist. Policy makers from low SDI region should reinforce tobacco control and prioritize workplace protection.

Abstract Background Forced vital capacity (FVC) reflects respiratory health, but the long-term trend and heterogeneity in FVC of Chinese students were understudied. Methods Data were from Chinese National Survey on Students’ Constitution and Health 1985–2019. Super Imposition by Translation and Rotation model was used to draw FVC growth curves. Sex-, region-, and nationality-heterogeneity in FVC was evaluated. Spearman correlation and generalized additive model was used to reveal influencing factors for FVC. Results Compared to 1985, age at peak FVC velocity was 1.09, 3.17, 0.74, and 1.87 years earlier for urban male, urban female, rural male, and rural female in 2019, respectively. Peak FVC velocity first decreased and then increased during 1985–2019, only male rebounded to larger than 1985 level. FVC declined from 1985 to 2005 and then raised. Males consistently had higher FVC than females, with disparities increasing in the 13–15 age group. Urban students also had higher FVC than rural students. In 2019, FVC difference between 30 Chinese provinces and the national average showed four scenarios: consistently above national average; less than national average until age 18, then above; greater than national average until age 18, then this advantage reversed; less than national average in almost all the age. Most Chinese ethnic minority students had lower FVC levels compared to Han students. Spearman correlation and generalized additive model showed that age, sex, and height were the leading influencing factors of FVC, followed by socioeconomic and environmental factors. Conclusions Chinese students experienced advanced FVC spurt, and there was sex-, region- and nationality-heterogeneity in FVC. Routine measurement of FVC is necessary in less developed areas of China.

Abstract Computing‐in‐memory (CIM) is a promising technique for solving the ‘memory wall’ and ‘power consumption wall’ problems. However, calculations in the analog domain are limited in terms of accuracy and sensitivity to process, voltage, and temperature changes. In this study, the authors proposed a CIM multiply‐and‐accumulate (MAC) circuit in which the MAC result was reflected by the pulse edge and converted into the final digital output using a dual‐edge counter quantization circuit, thereby improving the accuracy of the MAC operation and reducing the difficulty of quantization. The performance of the proposed CIM circuit was evaluated using a 28‐nm process. It could achieve 4‐bit multiplication without errors, with an energy efficiency of 24.38 to 670.86 TOPS/W.

Abstract In‐memory computing (IMC) is a novel computing architecture that presents considerable potential in solving the data transmission and energy consumption problems faced by the von Neumann architecture. The compound Boolean logic operation (CBLO) is a crucial component of most advanced computing platforms. This study presents a static random‐access memory array structure comprising configurable embedded arithmetic logic units (ALUs), which can realize four types of CBLOs within a single cycle. The proposed structure can also form the ternary content addressable memory (TCAM) for ternary searching by configuring signal lines and sense amplifiers. The authors performed 5000 trials of the Monte Carlo simulation for four types of CBLOs. The results of all four types were observed to be accurate, and the delay of the TCAM was observed to be as low as 141 ps, which improves the parallelism of IMC, reduces power consumption, and significantly reduces calculation delay.

Evidence of the influence of prenatal phthalate exposure on childhood longitudinal obesity markers is limited. Nested on the Ma’anshan birth cohort study, 990 mother-daughter pairs were included. Seven phthalate metabolites were determined in urine collected in each trimester. Each child underwent a physical examination from birth to 6 years of age twelve times. Latent class growth models were used to identify three trajectories of girls’ body mass index (BMI). Logistic regression, quantile g-computation and Bayesian kernel machine regression models analyzed the relationships of prenatal exposure to individual and mixed phthalates with girls’ body mass index (BMI) trajectory. Compared to the “lowest trajectory” class, prenatal average concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP, ORcrude = 2.095, 95 % CI = 1.014–4.328) and di(2-ethylhexyl) phthalate (DEHP, ORcrude = 2.336, 95 % CI = 1.022–5.338) during pregnancy were associated with an increased probability of being in the “highest trajectory” class. The average concentration of DEHP (ORcrude = 1.879, 95 % CI = 1.002–3.522) was associated with an increased probability of being in the “moderate trajectory” class. Stratified analyses by trimester of pregnancy mainly showed that third-trimester exposure to monoethyl phthalate (MEP, ORadjusted = 1.584, 95 % CI = 1.094–2.292), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, ORadjusted = 2.885, 95 % CI = 1.367–6.088), MEHHP (ORadjusted = 2.425, 95 % CI = 1.335–4.407), DEHP (ORadjusted = 2.632, 95 % CI = 1.334–5.193) and high molecular weight phthalate (ORadjusted = 2.437, 95 % CI = 1.239–4.792) was associated with an increased probability of being in the “highest trajectory” class. However, the mixture of phthalates was not significantly related to the girl’s BMI trajectory. In conclusion, in utero exposure to phthalates, including MEP and DEHP metabolites (MEHHP and MEOHP), was significantly associated with early childhood high BMI trajectories in girls. The third trimester of pregnancy seemed to be the window of vulnerability to phthalate exposure for girls’ high BMI trajectory at periods of prenatal development. No evidence supported a significant relationship between combined exposure to phthalate metabolites and girls’ high BMI trajectory.

BackgroundFew studies have investigated the associations of childhood growth trajectories with the prenatal metabolic risks of mothers and their interaction with children’s genetic susceptibility.ObjectiveTo investigate the effects of gestational metabolic syndrome (GMS) risks and children’s polygenic risk scores (PRSs), and their interaction effect on the BMI trajectory and obesity risk of offspring from birth to 6 years of age.MethodsA total of 2,603 mother-child pairs were recruited from the Ma’anshan birth cohort (Anhui Province of China) study. Data on maternal prepregnancy obesity, gestational weight gain (GWG), gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP) were used to evaluate maternal GMS risk. In addition, 1,482 cord blood samples were used to genotype 11 candidate single-nucleotide polymorphisms (SNPs) to calculate children’s PRSs. The latent class growth model using the longitudinal BMI-for-age z scores (BMIz) was applied to validly capture the BMIz growth trajectory.ResultsMaternal GMS status was associated with higher BMIz scores and with an increased risk of overweight/obesity. Positive relationships were revealed between PRS and the risk of overweight/obesity among girls. Additionally, maternal GMS significantly interacted with the child’s PRS on BMIz scores and the risk of overweight/obesity among girls. Hierarchical BMI trajectory graphs by different exposure groups showed consistent findings, and both boys’ and girls’ BMIz trajectories were divided into three groups. Among girls, the higher the GMS risk or PRS they had, the higher the probability of being in the high BMIz trajectory group.ConclusionsMaternal GMS status increased BMIz scores and the risk of obesity in both boys and girls and elevated the child’s BMI trajectory from birth to 6 years of age among girls. PRSs were significantly associated with children’s BMI trajectory and the risk of obesity and modified the associations between maternal GMS status and obesity biomarkers only among girls. Thus, regarding childhood obesity, steps should be taken to decrease maternal metabolic risks before and during pregnancy, and sex discrepancies should be noted to identify high-risk populations after birth to hierarchically manage them.

Abstract Systemic immune-inflammation index (SII) emerged as a biomarker of chronic inflammation and an independent prognostic factor for many cancers. We aimed to investigate the associations of SII level with total and cause-specific mortality risks in the general populations, and the potential modification effects of lifestyle-related factors on the above associations. In this study, we included 30,521 subjects from the Dongfeng-Tongji (DFTJ) cohort and 25,761 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999–2014. Cox proportional hazards regression models were used to estimate the associations of SII with mortality from all-cause, cardiovascular diseases (CVD), cancer and other causes. In the DFTJ cohort, compared to subjects in the low SII subgroup, those within the middle and high SII subgroups had increased risks of total mortality [hazard ratio, HR (95% confidence interval, CI) = 1.12 (1.03–1.22) and 1.26 (1.16–1.36), respectively) and CVD mortality [HR (95%CI) = 1.36 (1.19–1.55) and 1.50 (1.32–1.71), respectively]; those within the high SII subgroup had a higher risk of other causes mortality [HR (95%CI) = 1.28 (1.09–1.49)]. In the NHANES 1999–2014, subjects in the high SII subgroup had higher risks of total, CVD, cancer and other causes mortality [HR (95%CI) = 1.38 (1.27–1.49), 1.33 (1.11–1.59), 1.22 (1.04–1.45) and 1.47 (1.32–1.63), respectively]. For subjects with a high level of SII, physical activity could attenuate a separate 30% and 32% risk of total and CVD mortality in the DFTJ cohort, and a separate 41% and 59% risk of total and CVD mortality in the NHANES 1999–2014. Our study suggested high SII level may increase total and CVD mortality in the general populations and physical activity exerted a beneficial effect on the above associations.

AbstractBackground Circulating white blood cell (WBC) counts have been related to lung function impairment, but causal relationship was not established. We aimed to evaluate independent effects and causal relationships of WBC subtypes with lung function.Methods The 19,159 participants from NHANES 2011–2012 (n = 3570), coke-oven workers (COW, n = 1762) and Dongfeng-Tongji (DFTJ, n = 13,827) cohorts were included in the observational studies. The associations between circulating counts of WBC subtypes and prebronchodilator lung function were evaluated by linear regression models and LASSO regression was used to select effective WBC subtypes. Summary statistics for WBC-associated SNPs were extracted from literature, and Mendelian randomization (MR) analysis with inverse-variance weighted (IVW) method was applied to estimate the causal effects of total WBC and subtypes on lung function among 4012 subjects from COW (n = 1126) and DFTJ cohorts (n = 2886).Results Total WBC counts were negatively associated with lung function among three populations and their pooled analysis indicated that per 1 × 109 cells/L increase in total WBC was associated with 36.13 (95% CI: 30.35, 41.91) mL and 25.23 (95% CI: 19.97, 30.50) mL decrease in FVC and FEV1, respectively. Independent associations with lung function were found for neutrophils, monocytes, eosinophils and basophils (all p

Speech recognition involves the ability to learn the audios which are closely related to event sequence. Although speech recognition has been widely implemented in software neural networks, a hardware implementation based on energy efficient computing architecture is still missing. Herein, W/MgO/SiO2/Mo memristor arrays with multilevel resistance states are fabricated, where the weights of the artificial synapses in the memristor array can be tuned precisely by voltage pulses. Based on the array, speech recognition in memristive spiking neural networks (SNNs) with improved supervised tempotron algorithm on Texas Instruments digit sequences (TIDIGITS) dataset is conducted, demonstrating software‐comparable accuracy for speech recognition in the memristive SNN. It is envisioned that such memristive SNNs can pave the way to building a bioinspired spike‐based neuromorphic system for audio learning.

Background: Thallium (Tl) is a cumulative high toxicant in the environment, but few longitudinal studies have investigated the respiratory impairment of Tl exposure. Objectives: This study aimed to evaluate the effect of Tl and its interaction with smoking on lung function decline, and explore the potential mechanisms. Methods: The baseline and follow-up lung functions were measured from a prospective cohort study of 1243 workers, who were followed from 2010 to 2014. Their baseline urinary levels of Tl were determined. We also measured the plasma C-reactive protein (CRP) and urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) in a randomly selected subcohort of 474 subjects. Results: The results showed that a 2-fold increase in urinary Tl was associated with 29.81 mL (95%CI: 3.83–55.80) increased decline in forced expiratory volume in 1 s (FEV1). The effect was more pronounced among heavy-smokers (≥15 pack-years) [β(95%CI) = 56.42 mL (9.66–103.19)]. In particular, compared to never-smokers with low Tl, heavy-smokers with high Tl had a separate 158.44 mL (95%CI: 54.88–262.00) and 4.58% (95%CI: 1.40–7.76) increased declines in FEV1 and percentage of predicted (ppFEV1), respectively. There was a significant interaction between Tl and smoking intensity on ppFEV1 decline (Pint = 0.034). More importantly, the increasing level of urinary Tl was correlated with elevated CRP and 8-iso-PGF2α. Conclusion: Our prospective cohort study identified that exposure to high Tl had a deleterious effect on lung function, and this effect may be enhanced by tobacco smoking. Increased inflammation may partly contribute to the joint effects of Tl and smoking on impaired lung function, but the biological mechanisms need further explorations. Keywords: Thallium, Smoking, Lung function decline, Prospective cohort study, C-reactive protein

Objective: Essential metals play important roles in the carcinogenic process. However, seldom longitudinal investigations have evaluated their roles in lung cancer development. We aimed to investigate the associations between multiple essential metals and lung cancer incidence and to explore the potential mechanisms. Methods: A nested case-control study of 440 incident lung cancer cases and 1:3 frequency matched 1320 healthy controls from the Dongfeng-Tongji Cohort was conducted. The baseline plasma concentrations of 11 essential metals (cobalt, copper, iron, manganese, molybdenum, rubidium, selenium, strontium, stannum, vanadium, and zinc) were measured, and their associations with lung cancer incidence were estimated. Effect of positive metal (zinc) on 4-year telomere attrition was then evaluated among an occupational cohort of 724 workers. We also assessed the transcriptional regulation effects of plasma zinc on mRNA expression profiles, and the expressions of zinc-related genes were further compared in pair-wised lung tumor and normal tissues. Results: Elevated plasma level of zinc was associated with lower incident risk of lung cancer [OR (95% CI) = 0.89 (0.79, 0.99)] and decreased 4-year telomere attrition [β (95% CI) = −0.73 (−1.27, −0.19)]. These effects were pronounced among males. In particularly, zinc could regulate the expressions of 8 cancer-related genes, including SOD1, APE, TP53BP1, WDR33, LAPTM4B, TRIT1, HUWE1, and ZNF813, which were over-expressed in lung tumor tissues. Conclusions: We propose that high plasma zinc could prevent incident lung cancer, probably by slowing down telomere attrition and regulating the expressions of cancer-related genes. These results provided a new insight into lung cancer prevention. Keywords: Essential metals, Zinc, Lung cancer, Cohort study, Telomere attrition, Gene expression

Abstract Bi-layer structure has been widely adopted to improve the reliability of the conductive bridge random access memory (CBRAM). In this work, we proposed a convenient and economical solution to achieve a Ta2O5/TaOx bi-layer structure by using a low-temperature annealing process. The addition of a TaOx layer acted as an external resistance suppressing the overflow current during set programming, thus achieving the self-compliance switching. As a result, the distributions of high-resistance states and low-resistance states are improved due to the suppression of the overset phenomenon. In addition, the LRS retention of the CBRAM is obviously enhanced due to the recovery of defects in the switching film. This work provides a simple and economical method to improve the reliability of CBRAM.

Objective: This study aimed to investigate the associations of multiple metals with chromosome damage, and further explore the mediation roles of microRNAs (miRNAs) and their potentials in lung cancer. Methods: We determined the urinary levels of 23 metals, lymphocytic micronucleus (MN) frequency, and ten candidate miRNAs in plasma among 365 healthy workers. Poisson and linear regression models were conducted to analyze the associations of urinary metals with MN frequency and miRNAs, respectively. The mediation effects of miRNAs on the metal-MN frequency associations were assessed by causal mediation analysis. Additionally, the levels of effective metal and miRNAs were measured in 43 pair-wised tumor and normal lung tissues. Results: The urinary level of titanium was inversely associated with MN frequency after Bonferroni correction [frequency ratio (FR) and 95% confidence interval (95%CI) = 0.88 (0.82, 0.94), p = 5.0 × 10−4]. A doubling in urinary titanium was associated with 14.72%–38.17% decrease in plasma miRNAs. After multiple comparison, miR-24-3p and miR-28-5p significantly mediated 24.8% (7.7%, 70.0%) and 20.4% (5.7%, 52.0%) of the association between titanium and MN frequency (pmediation = 0.002 and 0.004, respectively). Besides, a doubling in titanium was associated with a separate 53.4% and 47.2% decreased miR-24-3p and miR-28-5p expression in normal lung tissues. Lower titanium but higher levels of miR-24-3p and miR-28-5p were shown in tumor than normal tissues of lung squamous cell carcinoma patients (all p

Objective: Telomere is required for maintaining chromosome stability and genome integrity, while telomere length is sensitive to environmental stressors. We aimed to identify the effects of multiple metals co-exposure as well as their joint effects with TERT-CLPTM1L variants on leukocyte telomere length (LTL). Methods: This study included 842 workers from a coke-oven plant, of whom plasma concentrations of 23 metals and LTL were determined. Genetic variations in TERT-CLPTM1L were genotyped by using the Global Screening Array. Multipollutant-based statistical methods, including the Bonferroni-correction, backward elimination procedure, and LASSO penalized regression analysis, were used to select the LTL-associated metals. Generalized linear regression models were used to evaluate the joint effects of TERT-CLPTM1L variants with positive metal on LTL. Results: Each 1% increase in plasma concentration of manganese (Mn) was significantly associated with a 0.153% increase in LTL [β(95%CI) = 0.153(0.075, 0.230), P 4.21 μg/L) showed joint effects on increasing LTL. Conclusions: Our study revealed the independent and positive association between plasma Mn and LTL when accounting for co-exposure to other metals. This effect can be further enhanced by TERT-CLPTM1L variants. These results may advance our understanding of the complex interplay between genetic and environmental factors on telomere length. Further experimental studies are warranted to elucidate the underlying mechanisms.

This paper presents a design of a high performance and low power consumption triple-track magnetic sensor chip which was fabricated in TSMC 0.35 μm CMOS process. This chip is able to simultaneously sense, decode and read out the information stored in triple-track magnetic cards. A reference voltage generating circuit, a low-cost filter circuit, a power-on reset circuit, an RC oscillator, and a pre-decoding circuit are utilized as the basic modules. The triple-track magnetic sensor chip has four states, i.e., reset, sleep, swiping card and data read-out. In sleep state, the internal RC oscillator is closed, which means that the digital part does not operate to optimize energy consumption. In order to improve decoding accuracy and expand the sensing range of the signal, two kinds of circuit are put forward, naming offset correction circuit, and tracking circuit. With these two circuits, the sensing function of this chip can be more efficiently and accurately. We simulated these circuit modules with TSMC technology library. The results showed that these modules worked well within wide range input signal. Based on these results, the layout and tape-out were carried out. The measurement results showed that the chip do function well within a wide swipe speed range, which achieved the design target.