Expression and significance of SIRT6 in human peritoneal dialysis effluents and peritoneal mesothelial cells.

Sirtuin 6 (SIRT6) can inhibit the fibrosis of many organs. However, the relationship between SIRT6 and peritoneal fibrosis (PF) in peritoneal dialysis (PD) remains unclear. We collected 110 PD patients with a duration of PD for more than 3 months and studied the influence of PD duration and history of peritonitis on SIRT6 levels in PD effluents (PDEs). We also analyzed the relationship between SIRT6 levels in PDEs and transforming growth factor beta 1 (TGF-ß1), IL-6, PD duration, peritoneal function, PD ultrafiltration (UF), and glucose exposure. We extracted human peritoneal mesothelial cells (HPMCs) from PDEs and measured the protein and gene expression levels of SIRT6, E-cadherin, vimentin, and TGF-ß1 in these cells. Based on the clinical results, we used human peritoneal mesothelial cells lines (HMrSV5) to observe the changes in SIRT6 levels and mesothelial-to-mesenchymal transition (MMT) after intervention with PD fluid. By overexpressing and knocking down SIRT6 expression, we investigated the effect of SIRT6 expression on E-cadherin, vimentin, and TGF-ß1 expression to elucidate the role of SIRT6 in mesothelial-to-epithelial transition in PMCs. Results: (1) With the extension of PD duration, the influence of infection on SIRT6 levels in PDEs increased. Patients with the PD duration of more than 5 years and a history of peritonitis had the lowest SIRT6 levels. (2) SIRT6 levels in PDEs were negatively correlated with PD duration, total glucose exposure, TGF-ß1, IL-6 levels, and the dialysate-to-plasma ratio of creatinine (Cr4hD/P), but positively correlated with UF. This indicates that SIRT6 has a protective effect on the peritoneum. (3) The short-term group (PD ≤ 1 year) had higher SIRT6 and E-cadherin gene and protein levels than the mid-term group (1 year < PD ≤ 5 years) and long-term group (PD > 5 years) in PMCs, while vimentin and TGF-ß1 levels were lower in the mid-term group and long-term group. Patients with a history of peritonitis had lower SIRT6 and E-cadherin levels than those without such a history. (4) After 4.25% PD fluid intervention for HPMCs, longer intervention time resulted in lower SIRT6 levels. (5) Overexpressing SIRT6 can lead to increased E-cadherin expression and decreased vimentin and TGF-ß1 expression in HPMCs. Knocking down SIRT6 expression resulted in decreased E-cadherin expression and increased vimentin and TGF-ß1 expression in HPMCs. This indicates that SIRT6 expression can inhibit MMT in HPMCs, alleviate PF associated with PD, and have a protective effect on the peritoneum.

Interactive deformable electroluminescent devices enabled by an adaptable hydrogel system with optical/photothermal/mechanical tunability.

Deformable electroluminescent devices (DELDs) with mechanical adaptability are promising for new applications in smart soft electronics. However, current DELDs still present some limitations, including having stimuli-insensitive electroluminescence (EL), untunable mechanical properties, and a lack of versatile stimuli response properties. Herein, a facile approach for fabricating in situ interactive and multi-stimuli responsive DELDs with optical/photothermal/mechanical tunability was proposed. A polyvinyl alcohol (PVA)/polydopamine (PDA)/graphene oxide (GO) adaptable hydrogel exhibiting optical/photothermal/mechanical tunability was used as the top ionic conductor (TIC). The TIC can transform from a viscoelastic state to an elastic state via a special freezing-salting out-rehydration (FSR) process. Meanwhile, it endows the DELDs with a photothermal response and thickness-dependent light shielding properties, allowing them to dynamically demonstrate "on" or "off" or "gradually change" EL response to various mechanical/photothermal stimuli. Thereafter, the DELDs with a viscoelastic TIC can be utilized as pressure-responsive EL devices and laser-engravable EL devices. The DELDs with an elastic TIC can withstand both linear and out-of-plane deformation, enabling the designs of various interactive EL devices/sensors to monitor linear sliders, human finger bending, and pneumatically controllable bulging. This work offers new opportunities for developing next-generation EL-responsive devices with widespread application based on adaptable hydrogel systems.

River ecological flow early warning forecasting using baseflow separation and machine learning in the Jiaojiang River Basin, Southeast China.

Ecological flow early warning is crucial for the rational management of watershed water resources. However, determining of accurate ecological flow threshold and choosing the appropriate forecasting model are challenging tasks. In this study, we initially developed a baseflow separation and Tennant method-based technique for calculating ecological river flow. Then an ecological flow early warning model was created using the machine learning technique based on distributed gradient enhancement framework (LightGBM). Finally, we utilized the framework of Shapley Additive Planning (SHAP) to explain how various hydrometeorological factors affect the variations in ecological flow conditions. The Jiaojiang River basin in southeast China is selected as the study area, and the hydrological stations in upstream of Baizhiao (BZA) and Shaduan (SD) are chosen for key analysis. The results of these applications show that the monthly baseflow frequency of the river ecological flow conditions of the two stations in the dry season is 20 % (7.49 m3/s) and 30 % (4.79 m3/s), respectively. The ecological flow level early warning forecasting accuracy is close to 90 % in the BZA and SD stations during dry and wet seasons. The variations of ecological flow are most affected by evaporation and base flow index. The results of this study can serve as a strong basis for the effective allocation and utilization of locally available water resources.

Prevalence of smoking among nurses and its association with blood pressure: A cross-sectional study in 11 cities of China.

AIM: Smoking is harmful to human health. However, the relationship between smoking and blood pressure (BP) has not been consistent. This study aimed to analyse nurses' smoking behaviours and their relationship with BP. METHODS: This cross-sectional study recruited 128 009 nurses in 11 cities in China. They were surveyed with questionnaires including BP measurements. The main contents of the questionnaire included smoking status and other factors that might be associated with hypertension. Multiple linear regression analyses and binary logistic regression analyses were used to analyse the data. RESULTS: The results showed there was a significant difference in the smoking rate among nurses with different characteristics (P < 0.05). For both male and female nurses, smoking was associated with increased diastolic BP and mean arterial pressure, but only with increased systolic BP of male nurses. The prevalence of hypertension among male and female nurses was not related to smoking. CONCLUSION: Despite a relatively low overall smoking rate, rates among some groups are high. Different cities, hospitals, and departments can combine local data and conditions to formulate targeted tobacco control measures to improve nurses' physical and mental health.

A piecewise sine waveguide for terahertz traveling wave tube.

In this paper, a piecewise sine waveguide (PWSWG) is proposed as the slow-wave structure (SWS) to develop high-power terahertz (THz) traveling wave tubes (TWTs). The PWSWG is an improvement over the rectangular waveguide wherein its two E-planes simultaneously oscillate up and down along the longitudinal direction. The oscillation curve in the H-plane is a piecewise sine curve formed by inserting line segments into the peaks and troughs of the sine curve. The simulation analysis and experimental verification show that the PWSWG offers the advantages of large interaction impedance and excellent electromagnetic transmission performance. Furthermore, the calculation results of beam-wave interaction show that the TWT based on PWSWG SWS can generate a radiated power of 253.1 W at the typical frequency of 220 GHz, corresponding to a gain of 37.04 dB and an interaction efficiency of 6.92%. Compared with the conventional SWG TWTs, the PWSWG TWT has higher interaction efficiency and shorter saturation tube length. In conclusion, the PWSWG proposed in this paper can be considered a suitable SWS for high-power THz radiation sources.

D2A U-Net: Automatic segmentation of COVID-19 CT slices based on dual attention and hybrid dilated convolution.

Coronavirus Disease 2019 (COVID-19) has become one of the most urgent public health events worldwide due to its high infectivity and mortality. Computed tomography (CT) is a significant screening tool for COVID-19 infection, and automatic segmentation of lung infection in COVID-19 CT images can assist diagnosis and health care of patients. However, accurate and automatic segmentation of COVID-19 lung infections is faced with a few challenges, including blurred edges of infection and relatively low sensitivity. To address the issues above, a novel dilated dual attention U-Net based on the dual attention strategy and hybrid dilated convolutions, namely D2A U-Net, is proposed for COVID-19 lesion segmentation in CT slices. In our D2A U-Net, the dual attention strategy composed of two attention modules is utilized to refine feature maps and reduce the semantic gap between different levels of feature maps. Moreover, the hybrid dilated convolutions are introduced to the model decoder to achieve larger receptive fields, which refines the decoding process. The proposed method is evaluated on an open-source dataset and achieves a Dice score of 0.7298 and recall score of 0.7071, which outperforms the popular cutting-edge methods in the semantic segmentation. The proposed network is expected to be a potential AI-based approach used for the diagnosis and prognosis of COVID-19 patients.

Optimization of Serial Modular Continuous Mixing Process Parameters for Natural Rubber Composites Reinforced by Silica/Carbon Black.

In the tire industry, the combination of carbon black and silica is commonly utilized to improve the comprehensive performance of natural rubber so as to realize the best performance and cost-effectiveness. The corresponding mixing is divided into three processes (initial mixing, delivery, reactive mixing) by the serial modular continuous mixing method, thus achieving more accurate control of the mixing process, higher production efficiency and better performance. Moreover, the optimization of serial modular continuous mixing process parameters can not only improve the performance of composite materials, but help people understand the physical and chemical changes and the reinforcing mechanism of fillers in the mixing process. In this paper, the relationship among the parameters of eight processes and filler network structure, tensile strength, chemical reinforcing effect and tear resistance was explored through experiments. The deep causes of performance changes caused by parameters were analyzed. Consequently, the best process condition and the ranking of the influencing factors for a certain performance was obtained. Furthermore, the best preparation process of natural rubber (NR)/carbon black/silica composite was achieved through comprehensive analysis.

Multiclass and multiresidue screening of veterinary drugs and pesticides in infant formula using Quadrupole-Orbitrap MS with PRM scan mode.

A multiclass and multiresidue method for screening veterinary drugs and pesticides in infant formula was developed and validated using ultrahigh-performance liquid chromatography coupled to Quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-HRMS). A total of 49 veterinary drugs and pesticides investigated belong to 11 classes including antivirals, anticoccidials, macrolides, pyrethroids, insecticides, sulfonamides, beta-agonists, sedatives, thyreostats, nonsteroidal anti-inflammatory drugs, and other pharmacologically active substances. A generic sample preparation and highly selective acquisition mode of parallel reaction monitoring (PRM) were deliberately incorporated to perform efficient screening analysis. As a result, the screening target concentrations of the analytes varied from 1 to 500 µg/kg with ≤5% of false compliant rate as specified in Decision 2002/657/EC for screening analysis. The average recoveries ranged from 40.7 to 124.9% as well as the relative standard deviations from 4.2 to 26.6%, respectively. The matrix effects and interferences were effectively controlled by integrated application of dispersive solid phase extraction, PRM scan mode, and matrix-matched standard calibration. The proposed method will be helpful to provide applicable strategy for screening residues in infant formula with surveillance purpose.

Understanding the cholesterol metabolism-perturbing effects of docosahexaenoic acid by gas chromatography-mass spectrometry targeted metabonomic profiling.

PURPOSE: Over the past few decades, docosahexaenoic acid (DHA) has gained special attention for management of cholesterol-associated metabolic disorders and neurodegenerative diseases such as Alzheimer's disease (AD) owing to its neuroprotective, anti-inflammatory and hypolipidemic properties. Several epidemiological studies have reported the effect of DHA in reducing the risk of developing AD by lowering cholesterol. Hypercholesterolemia is a pro-amyloidogenic factor influencing the enzymatic processing of amyloid-ß precursor protein (AßPP) to toxic ß-amyloid. However, the mechanism by which DHA modulates the cholesterol pathway has not been established. Thus, the objective of this study was to investigate the mechanism of regulation of cholesterol metabolism by DHA in an AßPP695 overexpressing AD cell model. METHODS: A gas chromatography/mass spectrometry method was developed and validated for the targeted profiling of 11 cholesterol metabolites in DHA-treated Chinese hamster ovary wild-type (CHO-wt) and AßPP695 overexpressing (CHO-AßPP695) cells. The differential metabolite profiles between DHA- and vehicle-treated groups were further analyzed using fold change values of the ratio of concentration of metabolites in CHO-AßPP695 to CHO-wt cells. Effect of DHA on key rate-limiting enzymatic activities within the cholesterol pathway was established using biochemical assays. RESULTS: Our results showed that DHA reduced the levels of key cholesterol anabolites and catabolites in CHO-AßPP695 cells as compared to CHO-wt cells. Further enzymatic studies revealed that the cholesterol-lowering effect of DHA was mediated by regulating HMG-CoA reductase and squalene epoxidase enzyme activities. CONCLUSION: We demonstrate for the first time the dual effects of DHA in inhibiting HMG-CoA reductase and squalene epoxidase and modulating the sterol biosynthesis axis of the cholesterol pathway in AßPP695 overexpressing AD. Our novel findings underscore the potential of DHA as a multi-target hypocholesterolemic agent for the prophylaxis of AD and other cholesterol-associated diseases.

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict.

Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine (DA) system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4 (TLR4), an important pattern-recognition receptor in the innate immune system, can be directly activated by substances of abuse, resulting in an increase of the extracellular DA level in the nucleus accumbens. We thus hypothesized that TLR4-dependent signaling might regulate approach-avoidance behavior. To test this hypothesis, we compared the novelty-seeking and social interaction behaviors of TLR4-deficient (TLR4(-/-)) and wild-type (WT) mice in an approach-avoidance conflict situation in which the positive motivation to explore a novel object or interact with an unfamiliar mouse was counteracted by the negative motivation to hide in exposed, large spaces. We found that TLR4(-/-) mice exhibited reduced novelty-seeking and social interaction in the large open spaces. In less stressful test apparatuses similar in size to the mouse cage, however, TLR4(-/-) mice performed normally in both novelty-seeking and social interaction tests. The reduced exploratory behaviors under approach-avoidance conflict were not due to a high anxiety level or an enhanced fear response in the TLR4(-/-) mice, as these mice showed normal anxiety and fear responses in the open field and passive avoidance tests, respectively. Importantly, the novelty-seeking behavior in the large open field induced a higher level of c-Fos activation in the nucleus accumbens shell (NAcSh) in TLR4(-/-) mice than in WT mice. Partially inactivating the NAcSh via infusion of GABA receptor agonists restored the novelty-seeking behavior of TLR4(-/-) mice. These data suggested that TLR4 is crucial for positive motivational behavior under approach-avoidance conflict. TLR4-dependent activation of neurons in the NAcSh may contribute to this phenomenon.

Wnt co-receptor LRP5/6 overexpression confers protection against hydrogen peroxide-induced neurotoxicity and reduces tau phosphorylation in SH-SY5Y cells.

Emerging studies have suggested the involvement of dysregulated Wnt/ß-catenin cascade in the etiology of Alzheimer's disease (AD). Recently, genetic variations in Wnt co-receptor low density lipoprotein receptor-related protein (LRP) 6 causing reduced Wnt signaling has been linked to late-onset AD. Here, we hypothesized that overexpression of Wnt co-receptors LRP5 and LRP6 would serve as an effective new approach in reducing neurotoxicity induced by oxidative stress and decreasing tau phosphorylation in SH-SY5Y human neuroblastoma cells. Our results showed that overexpression of LRP5 and LRP6 in SH-SY5Y cells activates Wnt signaling and downstream proliferation genes, whereas knockdown of the co-receptors represses Wnt signaling and the transcription of proliferative markers. We further demonstrated that overexpression of LRP5 and LRP6 protects SH-SY5Y from cell death caused by hydrogen peroxide-induced oxidative stress, inhibits GSK3ß activity and subsequently reduces tau phosphorylation. Together, our findings suggest that rescuing LRP5/6-mediated Wnt signaling improves neuronal cell survival and reduces tau phosphorylation, which support the hypothesis that Wnt signaling might be an attractive therapeutic strategy for managing AD.

Metabotyping of docosahexaenoic acid - treated Alzheimer's disease cell model.

BACKGROUND: Despite the significant amount of work being carried out to investigate the therapeutic potential of docosahexaenoic acid (DHA) in Alzheimer's disease (AD), the mechanism by which DHA affects amyloid-ß precursor protein (AßPP)-induced metabolic changes has not been studied. OBJECTIVE: To elucidate the metabolic phenotypes (metabotypes) associated with DHA therapy via metabonomic profiling of an AD cell model using gas chromatography time-of-flight mass spectrometry (GC/TOFMS). METHODS: The lysate and supernatant samples of CHO-wt and CHO-AßPP695 cells treated with DHA and vehicle control were collected and prepared for GC/TOFMS metabonomics profiling. The metabolic profiles were analyzed by multivariate data analysis techniques using SIMCA-P+ software. RESULTS: Both principal component analysis and subsequent partial least squares discriminant analysis revealed distinct metabolites associated with the DHA-treated and control groups. A list of statistically significant marker metabolites that characterized the metabotypes associated with DHA treatment was further identified. Increased levels of succinic acid, citric acid, malic acid and glycine and decreased levels of zymosterol, cholestadiene and arachidonic acid correlated with DHA treatment effect. DHA levels were also found to be increased upon treatment. CONCLUSION: Our study shows that DHA plays a role in mitigating AßPP-induced impairment in energy metabolism and inflammation by acting on tricarboxylic acid cycle, cholesterol biosynthesis pathway and fatty acid metabolism. The perturbations of these metabolic pathways by DHA in CHO-wt and CHO-AßPP695 cells shed further mechanistic insights on its neuroprotective actions.