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Abstract The development of wearable bioelectronic systems is a promising approach for optimal delivery of therapeutic treatments. These systems can provide continuous delivery of ions, charged biomolecules, and an electric field for various medical applications. However, rapid prototyping of wearable bioelectronic systems for controlled delivery of specific treatments with a scalable fabrication process is challenging. We present a wearable bioelectronic system comprised of a polydimethylsiloxane (PDMS) device cast in customizable 3D printed molds and a printed circuit board (PCB), which employs commercially available engineering components and tools throughout design and fabrication. The system, featuring solution-filled reservoirs, embedded electrodes, and hydrogel-filled capillary tubing, is assembled modularly. The PDMS and PCB both contain matching through-holes designed to hold metallic contact posts coated with silver epoxy, allowing for mechanical and electrical integration. This assembly scheme allows us to interchange subsystem components, such as various PCB designs and reservoir solutions. We present three PCB designs: a wired version and two battery-powered versions with and without onboard memory. The wired design uses an external voltage controller for device actuation. The battery-powered PCB design uses a microcontroller unit to enable pre-programmed applied voltages and deep sleep mode to prolong battery run time. Finally, the battery-powered PCB with onboard memory is developed to record delivered currents, which enables us to verify treatment dose delivered. To demonstrate the functionality of the platform, the devices are used to deliver H $$^+$$ + in vivo using mouse models and fluoxetine ex vivo using a simulated wound environment. Immunohistochemistry staining shows an improvement of 35.86% in the M1/M2 ratio of H $$^+$$ + —treated wounds compared with control wounds, indicating the potential of the platform to improve wound healing.

Abstract Background Exposure to air pollution is associated with elevated cardiovascular risk. Evidence shows that omega-3 polyunsaturated fatty acids (omega-3 PUFA) may attenuate the adverse cardiovascular effects of exposure to fine particulate matter (PM2.5). However, it is unclear whether habitual dietary intake of omega-3 PUFA protects against the cardiovascular effects of short-term exposure to low-level ambient air pollution in healthy participants. In the present study, sixty-two adults with low or high dietary omega-3 PUFA intake were enrolled. Blood lipids, markers of vascular inflammation, coagulation and fibrinolysis, and heart rate variability (HRV) and repolarization were repeatedly assessed in 5 sessions separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily PM2.5 and maximum 8-h ozone (O3) concentrations were obtained from nearby air quality monitoring stations. Linear mixed-effects models were used to assess the associations between air pollutant concentrations and cardiovascular responses stratified by the omega-3 intake levels. Results The average concentrations of ambient PM2.5 and O3 were well below the U.S. National Ambient Air Quality Standards during the study period. Significant associations between exposure to PM2.5 and changes in total cholesterol, von Willebrand factor (vWF), tissue plasminogen activator, D-dimer, and very-low frequency HRV were observed in the low omega-3 group, but not in the high group. Similarly, O3-associated adverse changes in cardiovascular biomarkers (total cholesterol, high-density lipoprotein, serum amyloid A, soluable intracellular adhesion molecule 1, and vWF) were mainly observed in the low omega-3 group. Lag-time-dependent biphasic changes were observed for some biomarkers. Conclusions This study demonstrates associations between short-term exposure to PM2.5 and O3, at concentrations below regulatory standard, and subclinical cardiovascular responses, and that dietary omega-3 PUFA consumption may provide protection against such cardiovascular effects in healthy adults.

Abstract Background Short-term exposure to ambient nitrogen dioxide (NO2) is associated with adverse respiratory and cardiovascular outcomes. Supplementation of omega-3 polyunsaturated fatty acids (PUFA) has shown protection against exposure to fine particulate matter. This study aims to investigate whether habitual omega-3 PUFA intake differentially modify the associations between respiratory and cardiovascular responses and short-term exposure to ambient NO2. Methods Sixty-two healthy participants were enrolled into low or high omega-3 groups based on their habitual omega-3 PUFA intake. Each participant was repeatedly assessed for lung function, blood lipids, markers of coagulation and fibrinolysis, vascular function, and heart rate variability (HRV) in up to five sessions, each separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily ambient NO2 concentrations were obtained from an area air quality monitoring station on the day of outcome assessment (Lag0), 4 days prior (Lag1-4), as well as 5-day moving average (5dMA). The associations between short-term exposure to NO2 and the measured indices were evaluated using linear mixed-effects models stratified by omega-3 levels and adjusted by covariates including relative humidity and temperature. Results The average concentration of ambient NO2 during the study periods was 5.3±3.8 ppb which was below the National Ambient Air Quality Standards (NAAQS). In the high omega-3 group, an interquartile range (IQR) increase in short-term NO2 concentrations was significantly associated with increased lung function [e.g. 1.2% (95%CI: 0.2%, 2.2%) in FVC at lag1, 2.6% (95%CI: 0.4%, 4.8%) in FEV1 at 5dMA], decreased blood lipids [e.g. -2.6% (95%CI: -4.4%, -0.9%) in total cholesterol at lag2, -3.1% (95%CI: -6.1%, 0.0%) in HDL at 5dMA, and -3.1% (95%CI: -5.5%, -0.7%) in LDL at lag2], improved vascular function [e.g. 8.9% (95%CI: 0.6%, 17.2%) increase in FMD and 43.1% (95%CI: -79.8%, -6.3%) decrease in endothelin-1 at 5dMA], and changed HRV parameters [e.g. -7.2% (95%CI: -13.6%, -0.8%) in HFn and 13.4% (95%CI: 0.2%, 28.3%) in LF/HF ratio at lag3]. In the low omega-3 group, an IQR increase in ambient NO2 was associated with elevations in coagulation markers (von Willebrand Factor, D-dimer) and a decrease in HRV (very-low frequency); however, null associations were observed between short-term NO2 exposure and changes in lung function, blood lipids, and vascular function. Conclusions The results in this study imply that dietary omega-3 PUFA consumption may offer respiratory and vascular benefits in response to short-term exposure of healthy adults to NO2 levels below the NAAQS. Trial registration ClinicalTrials.gov ( NCT02921048 ).

Background: Over one-third of the U.S. population is exposed to unsafe levels of ozone (O3). Dietary supplementation with fish oil (FO) or olive oil (OO) has shown protection against other air pollutants. This study evaluates potential cardiopulmonary benefits of FO or OO supplementation against acute O3 exposure in young healthy adults. Methods: Forty-three participants (26 ± 4 years old; 47% female) were randomized to receive 3 g/day of FO, 3 g/day OO, or no supplementation (CTL) for 4 weeks prior to undergoing 2-hour exposures to filtered air and 300 ppb O3 with intermittent exercise on two consecutive days. Outcome measurements included spirometry, sputum neutrophil percentage, blood markers of inflammation, tissue injury and coagulation, vascular function, and heart rate variability. The effects of dietary supplementation and O3 on these outcomes were evaluated with linear mixed-effect models. Results: Compared with filtered air, O3 exposure decreased FVC, FEV1, and FEV1/FVC immediately post exposure regardless of supplementation status. Relative to that in the CTL group, the lung function response to O3 exposure in the FO group was blunted, as evidenced by O3-induced decreases in FEV1 (Normalized CTL −0.40 ± 0.34 L, Normalized FO −0.21 ± 0.27 L) and FEV1/FVC (Normalized CTL −4.67 ± 5.0 %, Normalized FO −1.4 ± 3.18 %) values that were on average 48% and 70% smaller, respectively. Inflammatory responses measured in the sputum immediately post O3 exposure were not different among the three supplementation groups. Systolic blood pressure elevations 20-h post O3 exposure were blunted by OO supplementation. Conclusion: FO supplementation appears to offer protective effects against lung function decrements caused by acute O3 exposure in healthy adults.

We thank Kuo et al. for their comments [...]

Background: Obesity is a growing epidemic among university students, and the high levels of stress reported by this population could contribute to this issue. Singular relationships between perceived stress; engagement in restrained, uncontrolled, and emotional eating; sleep; dietary risk; and body mass index (BMI) have been reported in the current body of literature; however, these constructs interact with each other, and the complex relationships among them are infrequently examined. Therefore, the aim of the present study was to explore the complex relationships between these constructs using mediation and moderation analyses stratified by gender. Methods: A cross-sectional study, enrolling university students from the United States (U.S.), the Netherlands, South Korea, Malaysia, Ireland, Ghana, and China, was conducted between October 2020 and January 2021 during the COVID-19 pandemic. Perceived stress; maladaptive eating behaviors including restrained, uncontrolled, and emotional eating; sleep duration and quality; dietary risk; and BMI were assessed using validated questionnaires, which were distributed through an online platform. Results: A total of 1392 students completed the online survey (379 male, 973 female, and 40 who self-identified as “other”). Uncontrolled and emotional eating mediated the relationship between perceived stress and dietary risk for both males and females; higher sleep quality weakened this relationship among female students but not males. Emotional eating mediated the relationship between perceived stress and BMI for both males and females, but higher sleep quality weakened this relationship only among females. Conclusions: Our findings suggest that students in higher education are likely to benefit from interventions to reduce uncontrolled and emotional eating. Programs that improve sleep quality, especially during highly stressful periods, may be helpful.

To evaluate the impact of different momentum control variable (CV) schemes (CV5, the momentum control variable option with ψχ and CV7, the momentum control variable option with UV) on radar data assimilation (DA) in weather research and forecasting model data-assimilation (WRFDA) systems, a heavy snowfall in central and eastern regions of China, which started on 6 February 2022, was taken as a case in this study. The results of the wind-field increments from the single observation tests indicated that the wind-field increments had a larger range of influence when stream function and velocity potential (ψχ) were used as momentum control variables in CV5. Some spurious increments were also generated in the wind-field analysis, since CV5 tended to maintain the integrated value of the wind field. When U-wind and V-wind were used as control variables in CV7, the wind-field increments had a smaller impact range, and there was less dependence among different locations on the wind increments. For the heavy snow case, the CV7 schemes displayed some improvements in simulating the composite reflectivity compared to the other two experiments, since the composite reflectivity in the CV5 and control experiments were overestimated to some level. It was also found that the RMSEs were lower in the CV7 compared to those in the CV5 in the short-term forecasts during the data-assimilation cycles. Results also indicated that the CV7 had a more significant effect on the 6 h accumulated precipitation forecasts. Meanwhile, the experiment Exp_CV7 achieved the best ETS and FSS scores among the three groups of experiments, while Exp_CV5 appeared to be generally superior to the CTRL. In summary, the precipitation of Exp_CV7 yielded the rainfall intensity and location most close to the observation compared to those from both the CTRL and Exp_CV5 experiments. [ABSTRACT FROM AUTHOR]

Objective·To explore the predictive capability of retinal vascular features in preeclampsia (PE) based on artificial intelligence (AI) models.Methods·This retrospective study enrolled 789 pregnant women who registered from June 2020 to January 2021 at Shanghai First Maternity and Infant Hospital of Tongji University in the first 16 weeks of gestation. These women underwent regular prenatal examinations, had retinal fundus images captured, and delivered singleton live births at the hospital. According to whether they developed hypertensive disorders of pregnancy (HDP), they were divided into unaffected group (n=685) and HDP group (n=104). Within the HDP group, pregnancies were further categorized into gestational hypertension (GH) group (n=36) and PE group (n=68) based on the occurrence of PE. Based on the gestational age at onset, the PE group was further divided into early-onset PE group (gestational age

Rationale: Exposure to air pollution is associated with adverse respiratory effects. Polyunsaturated omega 3 (n-3) fatty acids (FAs) appear to attenuate the health effects of air pollution. Objectives: This panel study evaluated whether n-3 FA intake and blood levels of polyunsaturated omega 6 (n-6) FAs can modulate the associations between respiratory effects and short-term exposure to ambient air pollution in healthy adults. Methods: Sixty-two healthy adults were enrolled into either high or low n-3 FA groups on the basis of n-3 FA intake and erythrocyte n-3 FA concentrations. Low and high n-6 FA groups were dichotomized on the basis of blood n-6 FA levels. Participants underwent three to five testing sessions separated by at least 7 days. At each session, the forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and plasma markers of inflammation (IL-6 [interleukin-6]) and oxidative stress (ox-LDL [oxidized low-density lipoprotein]) were measured. Associations between the ambient ozone and fine particulate matter (PM) (PM with an aerodynamic diameter ⩽2.5 μm [PM2.5]) levels and the lung function and blood markers were assessed by using mixed-effect models stratified by FA levels. Results: Average levels of ozone (40.8 ± 11.1 ppb) and PM2.5 (10.2 ± 4.1 μg/m3) were below national ambient air quality standards during the study period. FVC was positively associated with ozone at a lag of 0 days (lag0) in the high n-3 FA group, whereas the association was null in the low n-3 FA group (for an interquartile range increase in ozone of 1.8% [95% confidence interval (CI): 0.5% to 3.2%] vs. 0.0% [95% CI: -1.4% to 1.5%]); however, the association shifted to being negative at lag4 (-1.9% [95% CI: -3.2 to -0.5] vs. 0.2% [95% CI: -1.2% to 1.5%]) and lag5 (-1.2% [95% CI: -2.4% to 0.0%] vs. 0.9% [95% CI: -0.4% to 2.3%]). A similar pattern was observed in the low n-6 FA group compared with the high n-6 FA group (lag0: 1.7% [95% CI: 0.3% to 3.0%] vs. 0.5% [95% CI: -0.9% to 2.0%] and lag4: -1.4% [95% CI: -2.8% to 0.0%] vs. -0.5% [95% CI: -1.8% to 0.9%]). The associations between FEV1 and ozone and between FVC and PM2.5 also followed a similar pattern. Elevated ozone levels were associated with an immediate decrease in ox-LDL in the high n-3 FA group at lag0 (-12.3% [95% CI: -24.8% to 0.1%]), whereas there was no change in the low n-3 FA group (-7.5% [95% CI: -21.4% to 6.5%]) and there was a delayed increase in IL-6 in the high n-3 FA group compared with the low n-3 FA group (lag4: 66.9% [95% CI: 27.9% to 106.0%] vs. 8.9% [95% CI: -31.8% to 49.6%], lag5: 58.2% [95% CI: 22.4% to 94.1%] vs. -7.4% [95% CI: -48.8% to 34.0%], and lag6: 45.8% [95% CI: 8.7% to 82.9%] vs. -8.5% [95% CI: -49.7% to 32.6%]). Conclusions: We observed lag-dependent associations between short-term ambient air pollutants and lung function that were differentially modulated by n-3 and n-6 FAs, suggesting that n-3 and n-6 FAs counteract the respiratory response to low levels of ambient air pollution in healthy adults.Clinical trial registered with clinicaltrials.gov (NCT02921048). [ABSTRACT FROM AUTHOR]

Northeastern China is one of the regions where are experiencing the most significant global warming trend. Revealing the effects of anticipated warming on nitrogen absorption and utilization of rice in northeastern China can provide reference for regional sustainable production of rice and optimal management of nitrogen fertilizer. In this study, the field and pot experiments were setup based on free air temperature increase (FATI) system in Harbin, Heilongjiang province during 2019 to 2020, combined with 15N isotope tracer technique, to investigate the effects of anticipated warming (+1.5°C) on rice yield, nitrogen utilization, and the fate of fertilizer nitrogen. The results showed that warming treatment (W) promoted rice above-ground dry-matter accumulation. The mean grain yields in field and pot experiments during 2019 and 2020 under warming treatment were higher by 10.4% and 10.8% than those under control (CK), respectively. Compared with CK, the mean total nitrogen uptake of two years under W treatment significantly increased by 21.3%, however, the nitrogen utilization efficiency of rice grains showed a decreased trend. Under W treatment, the nitrogen absorbed from fertilizer decreased significantly, while the nitrogen absorbed by rice from soil increased by 31.1%, resulting in the reduction of 12.5% in fertilizer nitrogen recovery rate and the increase of 14.2% in fertilizer nitrogen loss rate. Overall, warming tended to increase rice grain yield, but decreased the proportion of fertilizer nitrogen uptake by plant, which leading to the decrease in nitrogen use efficiency and the significant increase in nitrogen loss rate. Under the background of climate warming, it was suggested to reasonably increase the transplanting density of rice to make full use of the positive effect of global warming on rice yield, as well as appropriately reduce the amount of nitrogen fertilizer application and optimize the management of nitrogen fertilizer operation to improve the nitrogen use efficiency of rice. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether ghrelin affected the autophagy and inflammatory response of intestinal intraepithelial lymphocytes (IELs) by regulating the NOD2/Beclin-1 pathway in an intestinal ischemia–reperfusion (I/R) injury model. Twenty hours after implementing the intestinal I/R injury rat model, the small intestine and both lungs were collected for histological analysis. The morphological changes in the intestinal mucosa epithelium and lung tissues were evaluated using hematoxylin-eosin staining. The activity of autophagic vacuoles and organ injury were evaluated using electron microscopy. The cytokine levels (IL-10 and TNF-α) in IEL cells and lung tissue were determined using enzyme-linked immunosorbent assay. RT-qPCR and western blot assays were conducted to check the NOD2, Beclin-1, and ATG16 levels. Ghrelin relieved the I/R-induced destruction of the intestinal mucosa epithelium and lung tissues. Moreover, ghrelin enhanced autophagy in the intestinal epithelium and lungs of I/R rats. In addition, the levels of autophagy-associated proteins (Beclin-1, ATG16, and NOD2) were higher in the ghrelin treatment group than in rats with I/R. Ghrelin reduced significantly the IL-10 and TNF-α levels. However, these changes were reversed by the NOD2 antagonist. In conclusion, ghrelin may relieve I/R-induced acute intestinal mucosal damage, autophagy disorder, and inflammatory response in IELs by regulating the NOD2/Beclin-1 pathway.

Artemisinin is an important drug for resistance against malaria. Artemisinin is derived from the glandular trichome of leaves, stems, or buds of the Chinese traditional herb Artemisia annua. Increasing the trichome density may enhance the artemisinin content of A. annua. It has been proven that cyclins are involved in the development of trichomes in tomato, Arabidopsis, and tobacco, but it is unclear whether the cyclins in A. annua influence trichome development. In this study, we showed that AaCycTL may regulate trichome development and affect the content of artemisinin. We cloned AaCycTL and found that it has the same expression files as the artemisinin biosynthesis pathway gene. We overexpressed AaCycTL in Arabidopsis, and the results indicated that AaCycTL changed the wax coverage on the surface of Arabidopsis leaves. The trichome density decreased as well. Using yeast two-hybrid and BiFC assays, we show that AaCycTL can interact with AaTAR1. Moreover, we overexpressed AaCycTL in A. annua and found that the expression of AaCycTL was increased to 82–195%. Changes in wax coverage on the surface of transgenic A. annua leaves or stems were found as well. We identified the expression of the artemisinin biosynthesis pathway genes ADS, CYP71AV1, and ALDH1 has decreased to 88–98%, 76–97%, and 82–97% in the AaCycTL-overexpressing A. annua lines, respectively. Furthermore, we found reduced the content of artemisinin. In agreement, overexpression of AaCycTL in A. annua or Arabidopsis may alter waxy loading, change the initiation of trichomes and downregulate trichome density. Altogether, AaCycTL mediates trichome development in A. annua and thus may serve to regulate trichome density and be used for artemisinin biosynthesis.

Introduction: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by bone abnormalities, vascular calcification, and some other complications. Although there are diagnostic criteria for CKD-MBD, in situations when conducting target feature examining are unavailable, there is a need to investigate and discover alternative biochemical criteria that are easy to obtain. Moreover, studying the correlations between the newly discovered biomarkers and the existing ones may provide insights into the underlying molecular mechanisms of CKD-MBD., Methods: We collected a cohort of 116 individuals, consisting of three subtypes of CKD-MBD: calcium abnormality, phosphorus abnormality, and PTH abnormality. To identify the best biomarker panel for discrimination, we conducted six machine learning prediction methods and employed a sequential forward feature selection approach for each subtype. Additionally, we collected a separate prospective cohort of 114 samples to validate the discriminative power of the trained prediction models., Results: Using machine learning under cross validation setting, the feature selection method selected a concise biomarker panel for each CKD-MBD subtype as well as for the general one. Using the consensus of these features, best area under ROC curve reached up to 0.95 for the training dataset and 0.74 for the perspective dataset, respectively., Discussion/conclusion: For the first time, we utilized machine learning methods to analyze biochemical criteria associated with CKD-MBD. Our aim was to identify alternative biomarkers that could serve not only as early detection indicators for CKD-MBD, but also as potential candidates for studying the underlying molecular mechanisms of the condition., (© 2024. The Author(s).)