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The balance between inflammatory T helper type 17 (Th17) and immunosuppressive regulatory T (Treg) cells is critical for maintaining immune homeostasis in the human body and is tightly regulated under healthy conditions. An increasing number of studies have reported that deubiquitinases (DUBs) play a vital role in regulating Th17- and Treg-cell differentiation. However, the biological functions of only a small fraction of DUBs in Th17- and Treg-cell differentiation are well defined. In this study, we identified ubiquitin-specific peptidase 1 (USP1) as a vital regulator of CD4

This work provides intermolecular insight to help design novel IL solvents for the efficient dissolution of insoluble natural drugs via MD simulations and DFT calculations.

In today's society, obesity is becoming increasingly serious, and controlling food intake and maintaining weight balance have become increasingly important. Here, we found that a stearic acid diet can increase food intake without causing obesity in mice compared with an oleic acid diet. Stearic acid increases food intake in mice by reducing serum leptin and increasing NPY neuronal excitability through the JAK2/STAT3 pathway. The impaired anorexic effect of leptin is probably due to repressive cholesterol-oxysterol-LXR-α/SREBP-1c-mediated leptin expression in mouse iWAT. At the same time, we found that stearic acid was not only poorly absorbed by itself in the small intestine but also reduced the entire absorption system of the small intestine. In conclusion, we have proven that a stearic acid diet can increase food intake in mice and avoid obesity, but whether a stearic acid diet could cause adverse reactions in the body remains to be studied.

To address the pollution problem of acid mine drainage (AMD) characterized by high concentrations of Fe2+, Mn2+, and SO42−, a combination of coal gangue (CG) and sulfate-reducing bacteria (SRB) was employed. The effects of coal-gangue dosage, SRB inoculation concentration, and temperature on AMD treatment with coal-gangue-loaded SRB were determined through single-factor experiments and response surface methodology (RSM) experiments. By considering the principles of adsorption isotherms, adsorption kinetics, and reduction kinetics, the removal mechanisms of SO42−, Fe2+, and Mn2+ in AMD using coal gangue-loaded SRB in the the Haizhou open-pit mine was revealed. The results showed that the overall effectiveness of the four types of coal-gangue-loaded SRB in repairing AMD was as follows: 3# CG-loaded SRB > 2# CG-loaded SRB > 1# CG-loaded SRB > 4# CG-loaded SRB, with coal-gangue-loaded SRB in the the Haizhou open-pit mine showing the best performance. According to the RSM test, the optimum conditions for repairing AMD with coal-gangue-loaded SRB in the open-pit mine were a coal-gangue dosage of 52 g, SRB inoculation concentration of 11.7%, and temperature of 33.4 °C. The order of factors affecting the removal of SO42− and Fe2+ from AMD by SRB loaded on coal gangue was SRB inoculation concentration > temperature > coal-gangue dosage. For Mn2+, the order of influence was temperature > SRB inoculation concentration > coal-gangue dosage. In the process of repairing Fe2+ with coal-gangue-loaded SRB in the the Haizhou open-pit mine, the biological activity metabolism of SRB played a leading role, while the adsorption isotherm of Mn2+ followed the Freundlich model. The adsorption kinetics of coal-gangue-loaded SRB in the the Haizhou open-pit mine for Fe2+ and Mn2+ in AMD conformed to Lagergren’s second-order kinetic model, while the reduction kinetics of SO42− conformed to a first-order reaction model.

This article reports the findings from a small-scale, qualitative and phenomenological institutional research project, undertaken during the COVID-19 pandemic, on the experiences of undergraduate students from groups who are traditionally under-represented in higher education in the United Kingdom. Documenting the first two phases of a longitudinal study carried out at one university in England, the over-arching research question investigated here using semi-structured interviews was: How has the ongoing COVID-19 pandemic impacted student experiences and learning at university? Key themes identified included worry, a sense of loss, feelings of connection and support, a sense of a new geography of campus life and students' need to feel "in the loop". Evidence of changes with longer-term implications were also found, namely, an evolution in the relationship between students and their institution. A series of suggestions are presented based on the findings aimed at mitigating some of the ongoing negative effects of the pandemic on students.

Background It was an effective method and research focus to remove recalcitrant organic pollutants by advanced oxidation processes based on persulfate activation with composite material as heterogeneous catalysts. Methods Fe/N co-doped biochar (Fe/N-BC) was synthesized via one-pot calcination method with anhydrous FeCl3, melamine, and grape skin powder as precursors. Characterization results showed that biomass and melamine could anchor iron species on BC matrixes by coordination. Significant findings The Fe/N0.1-BC exhibited significant activities toward peroxymonosulfate (PMS) activation, and 20 mg/L RhB can be degraded completely in 10 min with 0.05 g/L of the material and 0.5 g/L PMS. Electron paramagnetic resonance (EPR) study and free radical quenching experiments indicated that singlet oxygen (1O2), sulfate radicals (SO4•−), and hydroxyl radicals (•OH) were the main reactive oxidizing species, and non-radical mechanism and free radical process were considered to be involved in the degradation of the pollutants. Control experiments revealed that the enhanced active sites were mainly ascribed to rich defects as well as the synergistic effect among Fe and N doping into carbon substrate. The Fe/N-BC owned the merits of environmentally friendly raw materials, easy synthesis, and high activation efficiency, exhibiting splendid prospect for environmental application.

BACKGROUND: Local vibration has shown promise in improving skin blood flow and wound healing. However, the underlying mechanism of local vibration as a preconditioning intervention to alter plantar skin blood flow after walking is unclear. OBJECTIVE: The objective was to use wavelet analysis of skin blood flow oscillations to investigate the effect of preconditioning local vibration on plantar tissues after walking. METHODS: A double-blind, repeated measures design was tested in 10 healthy participants. The protocol included 10-min baseline, 10-min local vibrations (100 Hz or sham), 10-min walking, and 10-min recovery periods. Skin blood flow was measured over the first metatarsal head of the right foot during the baseline and recovery periods. Wavelet amplitudes after walking were expressed as the ratio of the wavelet amplitude before walking. RESULTS: The results showed the significant difference in the metabolic (vibration 10.06 ± 1.97, sham 5.78 ± 1.53, p

Nutritional diarrhea and subsequent performance degradation in weaned piglets are major challenges for the pig industry. Bile acids (BA) can be added to the diet as emulsifiers. This experiment was conducted to investigate the effects of chenodeoxycholic acid (CDCA), a major primary BA, on growth performance, serum metabolic profiles and gut health in weaned piglets. A total of 72 healthy weaned piglets were randomly assigned to the control (CON) and the CDCA groups, which were feed a basal diet and the basal diet supplemented with 200 mg/kg CDCA for 30 d, respectively. Our results demonstrated that CDCA significantly increased final BW and average daily gain (ADG), decreased feed-to-gain (F:G) ratio and tended to reduce diarrhea incidence. In addition, CDCA increased the villus height-to-crypt depth (V:C) ratio, elevated goblet cell numbers and the expression of tight junction proteins, suggesting the enhancement of intestinal barrier function. As an emulsifier, CDCA increased jejunal lipase activity and the mRNA expression of pancreatic lipases. CDCA supplementation also altered the serum metabolic profiles, including increasing the levels of indole 3-acetic acid, N′-formylkynurenine and theobromine that were beneficial for gut health. Moreover, the relative abundance of 2 beneficial gut bacteria, Prevotella 9 and Prevotellaceae TCG-001, were increased, whereas the relative abundance of a harmful bacteria, Dorea, was decreased in the gut of weaned piglets supplemented with CDCA. Importantly, the altered serum metabolic profiles showed a strong correlation with the changed gut bacteria. In conclusion, CDCA improved the growth performance of weaned piglets by improving intestinal morphology and barrier function, and enhancing lipid digestion, accompanied by alterations of serum metabolic profiles, and changes in relative abundance of certain gut bacteria.

Background and Objectives: The main issues should be solved in Chinese hospital management process are illustrated as long registration time and waiting list, extensive prescription dealing period and short duration of General Practitioner consultation. In order to improve healthcare process and patients’ satisfactory level, a large amount of hospitals is engaging in developing mobile health applications. However, the research on the impact of mobile health applications use (MHAU) on patients’ satisfactory level and treatment quality are quite few. This research is concentrated on evaluating patients’ satisfaction and healthcare service quality via empirical analysis.Methods: We established one model based on literature review, which related to MHAU, clinical process change perceived by patient, service quality, and patient satisfaction. Additionally, the mature scale were selected and revised as a survey instrument in this study, and was conducted at Shenzhen Ophthalmic Hospital using a paper questionnaire. In terms of the survey, patients are randomly selected to fill out the form during December 2018 to January 2019. Further, the research model and hypotheses has been verified with assistance of regression analysis.Results: The results demonstrated that the MHAU on the patient’s satisfaction is significant and direct (b=.162, p=.000Conclusions: Hospital managers should not only pay attention to the management of system usage, but also to organizational factors that affect the results of system usage, such as the clinical process change perceived by patients. The dimension of convenience should be considered when evaluating the service quality of hospital, especially for large hospitals with large outpatient service. In addition, the managers should pay attention to enhancing the initiative of physician-patient interaction, as it is an important factor affecting patients' perception of the services quality. This study provides a reference for investigations in ophthalmic hospital scene and needs to be confirmed further in other hospital scenarios.

It has been demonstrated that vascular endothelial growth factor B (VEGFB) and vascular endothelial growth factor receptor 1 (VEGFR1) play a vital role in regulating vascular biological function. However, the role of VEGFB and VEGFR1 in regulating fat deposition and skeletal muscle growth remains unclear. Therefore, this study was conducted to investigate the effects of VEGFB and VEGFR1 on fat deposition and skeletal muscle growth in mice. Our results showed that knockdown of VEGFB decreased body weight and iWAT index, stimulated the browning of mice iWAT with increased expression of UCP1, decreased the diameters of adipocytes, and elevated energy expenditure. In contrast, knockdown of VEGFB increased gastrocnemius (GAS) muscle index with increased proliferation of GAS muscle by expression of PCNA and Cyclin D1. Meanwhile, knockdown of endothelial VEGFR1 induced the browning of iWAT with increased expression of UCP1 and decreased diameters of adipocytes. By contrast, knockdown of endothelial VEGFR1 inhibited GAS muscle differentiation with decreased expression of MyoD. In conclusion, these results suggested that the loss of VEGFB/VEGFR1 signaling is associated with enhanced browning of inguinal white adipose tissue and skeletal muscle development. These results provided new insights into the regulation of skeletal muscle growth and regeneration, as well as fat deposition, suggesting the potential application of VEGFB/VEGFR1 as an intervention for the restriction of muscle diseases and obesity and related metabolic disorders.

Remote sensing has long been an effective method for water quality monitoring because of its advantages such as high coverage and low consumption. For non-optically active parameters, traditional empirical and analytical methods cannot achieve quantitative retrieval. Machine learning has been gradually used for water quality retrieval due to its ability to capture the potential relationship between water quality parameters and satellite images. This study is based on Sentinel-2 images and compared the ability of four machine learning algorithms (eXtreme Gradient Boosting (XGBoost), Support Vector Regression (SVR), Random Forest (RF), and Artificial Neural Network (ANN)) to retrieve chlorophyll-a (Chl-a), dissolved oxygen (DO), and ammonia-nitrogen (NH

For a large number of Higher Education institutions in the UK, the recruitment of international students remains vital for economic, political, cultural and educational benefits. Increasing competition within the international student market has encouraged many Higher Education institutions to pay closer attention to the quality of their educational offer, as well as the expectations and experiences of international students themselves. With an aim to present a more insightful picture of this position, this article examines the ‘service quality’ of UK Higher Education through the lens of one group of international students at a single Russell Group institution while also engaging the academic perspective in direct comparison. To achieve this, a mixed-methods research study was carried out at a location in the South East of England, with quantitative survey data collected from a convenience sample of 139 Chinese students and 27 academics, with 11 qualitative follow-up interviews. Results show both consistency and inconsistency between participant perceptions and where those consistencies and inconsistencies may exist. The findings suggest caution when assuming, as is currently prevalent in the context of highly marketised UK Higher Education, that ‘service quality’ of Higher Education can be comprehensively understood and efficiently improved from the student perspective alone.

With the rapid development of miniaturization and high integration of electronic devices, increasing attention has been paid to the exploration of dielectric composites with further improved dielectric permittivities. Herein, a unique design of high dielectric permittivity composites consisting of three-dimensional porous W-WO3/BaTiO3 foams hosted in epoxy matrix is proposed. It is demonstrated that the introduction of W-WO3/BaTiO3 foams into the epoxy matrix results in substantially improved dielectric permittivities in comparison with the epoxy matrix. Meanwhile, low loss which is comparable to that of the epoxy matrix is well maintained. Interestingly, obviously enhanced dielectric permittivities and greatly depressed loss are concurrently achieved via increasing the oxidation temperature. In particular, the composite with 53.1 wt% W-WO3/BaTiO3 foam oxidized at 1300 °C exhibits a high dielectric permittivity of ~ 536 and a low loss tangent of ~ 0.05@10 kHz which are about 149 and 1.5 times those of the epoxy matrix, respectively. It is believed that the strong interfacial polarization and the numerous equivalent micro-capacitors result in the significantly improved dielectric permittivities. The finite element simulation results reveal that the formation of the WO3 shell on the surface of W can effectively weaken the leakage current density, yielding the sharply depressed loss. This work provides a new strategy to design polymer composites with simultaneous high dielectric permittivity and low loss, and the strategy could also be applicable to the exploration of other high-performance dielectric composites.

Obesity is currently a worldwide phenomenon. The consumption of calorie-rich foods is responsible for most obesity cases, but not all humans exposed to high-calorie diets develop obesity. According to recent studies, exposure to fat-rich diets may be the actual cause of obesity. Dietary long-chain fatty acids affect brain function and are linked to food intake and motivation-related behaviors. Recently, many studies have shown that different types of fatty acids play different roles in animals. In our study, the effects of stearic acid (a saturated fatty acid) and oleic acid (a monounsaturated fatty acid) in diets on hedonic feeding behaviors were investigated, and changes of feeding-related protein levels in the brain were detected to explore the possible mechanism underlying the effects of these fatty acids. As a result, mice fed a diet containing stearic acid, compared to a diet containing oleic acid, exhibited increased food intake, hedonic eating, and an operant response to sucrose and locomotor activity. Furthermore, stearic acid corresponded to a higher level of leptin in serum than oleic acid. In addition, the stearic acid treated group had lower protein levels of p-JAK2 and p-STAT3 in the VTA and a higher dopamine concentration in the NAc than the oleic acid-treated group. Meanwhile, the protein level of TH in the NAc was higher and the protein level of the DA transporter in the VTA was lower in the stearic acid-fed group than in the oleic acid-fed group. In conclusion, these findings indicated that a diet containing stearic acid can increase hedonic feeding behavior and affect mesolimbic dopamine system signals in mice. Moreover, the lowering of serum leptin and leptin signaling in the VTA may contribute to this effect.

This study examined product use among pregnant women and new mothers in New York City during the COVID-19 pandemic (July 2020–June 2021). Women reported use of personal care and household cleaning products within the previous month, changes in antibacterial product use, receipt of healthcare provider advice, and opinions on environmental chemicals (n = 320). On average, women used 15 personal care products and 7 household cleaning products. Non-Hispanic Black women used nearly two more personal care products; non-Hispanic Black women, those with a college degree, and essential workers used 1–3 more household cleaning products. Women who were Hispanic or reported their race and ethnicity as Other were two times more likely to use antibacterial personal care products. Non-Hispanic Black, Hispanic, and women who reported their race and ethnicity as Other were 1.5 times more likely to increase antibacterial product use during the pandemic. Nearly all women agreed that environmental chemicals pose health risks and are impossible to avoid, while less than one quarter received advice regarding product use. Product use is a modifiable source of chemical exposures. Results from this study suggest that women may have increased their product use during the pandemic. Healthcare providers may use the current focus on health hygiene to promote discussion and assessment of environmental chemical exposures with patients.

Anaerobic ammonium oxidation (anammox) is a promising technology applied to treat industrial wastewater, while the commonly coexistent heavy metals and salinity usually become a challenging issue to be addressed. In this study, the responses of anammox sludge in terms of performance, activity, functional enzyme and extracellular polymeric substance (EPS) to the combined stress of Ni(II) and salinity (20 ‰) were investigated holistically. It turned out that low Ni(II) concentration (0.2 mg·L

The precise estimation of seawater quality parameters is crucial for decision-makers to manage coastal water resources. Although various machine learning (ML)-based algorithms have been developed for seawater quality retrieval using remote sensing technology, the performance of these models in the application of specific regions remains significant uncertainty due to the different properties of coastal waters. Moreover, the prediction results of these ML models are unexplainable. To address these problems, an ML-based ensemble model was developed in this study. The model was applied to estimate chlorophyll-a (Chla), turbidity, and dissolved oxygen (DO) based on Sentinel-2 satellite imagery in Shenzhen Bay, China. The optimal input features for each seawater quality parameter were selected from the nine simulation scenarios which generated from eight spectral bands and six spectral indices. A local explanation method called SHapley Additive exPlanations (SHAP) was introduced to quantify the contributions of various features to the predictions of the seawater quality parameters. The results suggested that the ensemble model with feature selection enhanced the performance for three types of seawater quality parameters estimations (The errors were 1.7%, 1.5%, and 0.02% for Chla, turbidity, and DO, respectively). Furthermore, the reliability of the model performance was further verified for mapping the spatial distributions of water quality parameters during the model validation period. The spatial-temporal patterns of seawater quality parameters revealed that the distributions of seawater quality were mainly influenced by estuary input. Correlation analysis demonstrated that air temperature (Temp) and average air pressure (AAP) exhibited the closest relationship with Chla. The DO was most relevant with Temp, and turbidity was not sensitive to Temp, average wind speed (AWS), and AAP. This study enhanced the prediction capability of seawater quality parameters and provided a scientific coastal waters management approach for decision-makers.

Remote sensing is important for aquatic environment monitoring. The Operational Land Imager (OLI) sensor onboard Landsat-8 has been proved to be able to monitor water quality of inland and coastal waters. Atmospheric correction (AC) is a crucial step in the quantitative research of remote sensing, and its accuracy is the key to the quantitative analysis of inland and coastal waters. However, the optical complexity of inland and coastal waters remains a major challenge for AC of Landsat-8 imagery, which in turn affects the retrieval accuracy of optically active constituents (OACs). A variety of AC algorithms had developed specifically for water application. However, comprehensive comparative studies of AC methods for both inland and coastal waters with a gradient of turbidity levels are lacking. Meanwhile the comparation of different AC algorithms coupled with Landsat-8 Chlorophyll-a (Chl-a) retrieval algorithm are also limited. In this study, the performances of six water-based AC methods were evaluated by using multiple global datasets (N = 139). The AC methods include the default and Management Unit Mathematics Models (MUMM) algorithms integrated into Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) Data Analysis System (SeaDAS), the Dark Spectrum Fitting (DSF) and Exponential Extrapolation (EXP) algorithms integrated into the Atmospheric Correction for OLI ‘lite’ (ACOLITE), image correction for atmospheric effects (iCOR), and the Case 2 Regional CoastColour processor (C2RCC). Four evaluation strategies were applied in this study including spectral similarity and Chl-a retrieval. The results showed that SeaDAS and DSF performed the best in term of analytical match, band ratio, Chl-a retrieval and spectral similarity for all matchups. SeaDAS had the lowest root-mean-square-error (RMSE) in the blue-green bands of 0.0036 sr-1 and 0.0043 sr-1 respectively. SeaDAS also showed good consistency across the spectra with the lowest median spectral angle of 7°. It should note that DSF performed best in high turbid waters, but was not as accurate as SeaDAS for remote sensing reflectance (Rrs) retrievals in most low-to-moderately turbid waters. For the retrieval of Chl-a using OC3 and Clark algorithm, all AC methods except iCOR and EXP gave similar performance compared to in-situ measurements. SeaDAS coupled with OC3 and Clark algorithms had the lowest RMSE of 1.3359 and 1.4250 mg m-3 respectively, which showed the advantage of SeaDAS in Chl-a retrieval. This study provides scientific basis for choosing AC methods of Landsat-8 OLI data for aquatic environment monitoring.

The estimation of water quality parameters (WQPs) using remote sensing is difficult due to the complex correlation between WQPs and water optical properties, the interactions of WQPs, and the impacts of climate. We proposed enhanced multimodal deep learning (EMDL) models for Chlorophyll-a (Chla), total phosphorous (TP), total nitrogen (TN), Secchi disk depth (SDD), dissolved organic carbon (DOC), and dissolved oxygen (DO) estimation in Lake Simcoe, Canada. The EMDL models were developed and validated using the remote sensing reflectance derived from the harmonized Landsat and Sentinel-2 images, synchronized in-situ water quality measurements, water surface temperature, and climate data (N = 950). Using the EMDL models, the spatiotemporal water quality patterns of Lake Simcoe from 2013 to 2019 were reconstructed. Besides, we quantitatively analyzed the impacts of 12 potential natural and anthropogenic factors on the water quality of Lake Simcoe. The results showed that the EMDL models had the potential to detect the spatiotemporal dynamics of water quality with the Slope being close to 1 (0.84−0.95), normalized mean absolute error ≤ 20.17%, and Bias ≤ 14.68%. Human activities such as urban development and agricultural activities mainly affected the water quality of Lake Simcoe. This study provides a practical approach to supporting the environmental management of regional inland watersheds.

We previously described the discovery of a novel indole series compounds as oral SERD for ER positive breast cancer treatment. Further SAR exploration focusing on substitutions on indole moiety of compound 12 led to the discovery of a clinical candidate LX-039. We report herein its profound anti-tumor activity, desirable ER antagonistic characteristics combined with favorable pharmacokinetic and preliminary safety properties. LX-039 is currently in clinical trial (NCT04097756).