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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.

BackgroundPhysical exercise has been recommended as an important nonpharmacological therapeutic strategy for managing attention deficit hyperactivity disorder (ADHD). We conducted a network meta-analysis (NMA) to assess the comparative impact of different physical exercise modalities on enhancing executive functions (EFs) and alleviating symptoms in children and adolescents with ADHD.MethodsWe searched Web of Science, PubMed, Embase, Cochrane Central Register of Controlled Trials, SPORTDiscus, PsycINFO, CNKI, and clinical trials databases from inception to October 20, 2022. Randomized controlled trials (RCTs) and quasi-experimental studies investigating physical exercise for ADHD-related symptoms of hyperactivity/impulsivity and inattention, and executive functions were included. The frequentist random-effect NMA method was applied to pool the results.ResultsA total of 59 studies (including 39 RCTs, 5 quasi-RCTs, and 15 self-controlled trials) published between 1983 and 2022 were incorporated into the systematic review, of which 44 studies with 1757 participants were eligible for meta-analysis. All types of physical exercise were effective in improving EFs (SMD = 1.15, 95% CI: 0.83 to 1.46), and open-skill activities which require participants to react in a dynamically changing and externally paced environment induced the most incredible benefits for executive functions (SUCRA = 98.0%, SMD = 1.96, and 95% CI: 1.15 to 2.77). Subgroup analyses for EFs revealed varied findings that open-skill activities were the most promising physical exercise type for improving inhibitory control (SUCRA = 99.1%, SMD = 1.94, and 95% CI: 1.24 to 2.64), and closed-skill activities dominated by aerobic exercises had a slightly higher probability of being the most promising physical exercise intervention for working memory (SUCRA = 75.9%, SMD = 1.21, and 95% CI: −0.22 to 2.65), and multicomponent physical exercise tended to be the most effective in cognitive flexibility (SUCRA = 70.3%, SMD = 1.44, and 95% CI: −0.19 to 3.07). Regarding ADHD-related symptoms, closed-skill activities dominated by aerobic exercises might be more advantageous for hyperactivity/impulsivity (SUCRA = 72.5%, SMD = -1.60, and 95% CI: −3.02 to −0.19) and inattention (SUCRA = 96.3%, SMD = -1.51, and 95% CI: −2.33 to −0.69) improvement.ConclusionPhysical exercise can significantly help to alleviate the symptoms of ADHD and improve executive functions in children and adolescents with ADHD. Most of all, to promote adherence to treatment, they should be encouraged to perform the physical exercises that they enjoy most.

Obesity is strongly associated with metabolic diseases, which have become a global health problem. Exploring the underlying mechanism of adipogenesis is crucial for the treatment of excess white fat. Oncogene YBX1 is a multifunctional DNA- and RNA-binding protein that regulates brown adipogenesis. However, the role of YBX1 in white adipogenesis and adipose tissue expansion remains unknown. Here, we showed that YBX1 deficiency inhibited murine and porcine adipocyte differentiation. YBX1 positively regulated adipogenesis through promoting ULK1- and ULK2-mediated autophagy. Mechanistically, we identified YBX1 serves as a 5-methylcytosine (m5C)-binding protein directly targeting m5C-containing Ulk1 mRNA by using RNA immunoprecipitation. RNA decay assay further proved that YBX1 upregulated ULK1 expression though stabilizing its mRNA. Meanwhile, YBX1 promoted Ulk2 transcription and expression as a transcription factor, thereby enhancing autophagy and adipogenesis. Importantly, YBX1 overexpression in white fat enhanced ULK1/ULK2-mediated autophagy and promoted adipose tissue expansion in mice. Collectively, these findings unveil the post-transcriptional and transcriptional mechanism and functional importance of YBX1 in autophagy and adipogenesis regulation, providing an attractive molecular target for therapies of obesity and metabolic diseases.

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

Artemisinin resistance in Plasmodium falciparum has been associated with a mutation in the NLI-interacting factor-like phosphatase PfNIF4, in addition to the mutations in the Kelch13 protein as the major determinant. We found that PfNIF4 was predominantly expressed at the schizont stage and localized in the nuclei of the parasite. To elucidate the functions of PfNIF4 in P. falciparum, we performed PfNIF4 knockdown (KD) using the inducible ribozyme system. PfNIF4 KD attenuated merozoite invasion and affected gametocytogenesis. PfNIF4 KD parasites also showed significantly increased

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.

Grain weight is a major determinant in rice yield, which is tightly associated with grain size. However, the underlying molecular mechanisms that control this trait remain unclear. Here, we report a rice (

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.

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

Background The Plasmodium zygote-to-ookinete developmental transition is an essential step for establishing an infection in the mosquito vector, and antigens expressed during this stage are potential targets for transmission-blocking vaccines (TBVs). The secreted ookinete protein 26 (PSOP26) is a newly identified ookinete surface protein. The anti-PSOP26 serum has moderate transmission-blocking activity, indicating the benefit of further investigating this protein as a target for TBVs. Methods The function of psop26 was analyzed by targeted gene disruption. A chimeric PSOP25-PSOP26 protein was expressed in the Escherichia coli system. The PSOP25-PSOP26 fusion protein, along with mixed (PSOP25 + PSOP26) or single proteins (PSOP26 or PSOP25), were used for the immunization of mice. The antibody titers and immunogenicity of individual sera were analyzed by enzyme-linked immunoassay (ELISA), indirect immunofluorescence assay (IFA), and Western blot. The transmission-blocking activity of sera from different immunization schemes was assessed using in vitro and in vivo assays. Results PSOP26 is a surface protein expressed in Plasmodium gametes and ookinetes. The protein is dispensable for asexual blood-stage development, gametogenesis, and zygote formation, but is essential for the zygote-to-ookinete developmental transition. Specifically, both the prevalence of infections and oocyst densities were decreased in mosquitoes fed on psop26-null mutants. Mixtures of individual PSOP25 and PSOP26 fragments (PSOP25 + PSOP26), as well as chimeras (PSOP25-PSOP26), elicited high antibody levels in mice, with no immunological interference. Antisera against the mixed and fusion proteins elicited higher transmission-reducing activity (TRA) than antisera against the single PSOP26 antigen, but comparable to antisera against PSOP25 antigen alone. Conclusions PSOP26 plays a critical role in the zygote-to-ookinete developmental transition. PSOP25 is a promising TBV candidate that could be used alone to target the ookinete stage.

Environmental changes from humans to mosquitoes activate gametogenesis of the malaria parasite, an obligative process for parasite transmission, but how the signals are relayed remains poorly understood. Here, we show the identification of a Plasmodium G-protein-coupled receptor, GPR180, and the characterization of its function in gametogenesis.

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

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.

Weight-bearing exercise such as walking may increase risk of foot ulcers in people with diabetes mellitus (DM) because of plantar ischemia due to repetitive, high plantar pressure. Applications of local vibrations on plantar tissues as a preconditioning intervention before walking may reduce plantar tissue ischemia during walking. The objective of this study was to explore whether preconditioning local vibrations reduce reactive hyperemia after walking. A double-blind, repeated-measures, and crossover design was tested in 10 healthy participants without DM. The protocol included 10-minute baseline, 10-minute local vibrations (100 Hz or sham), 10-minute walking, and 10-minute recovery periods. The order of local vibrations was randomly assigned. Skin blood flow (SBF) was measured over the first metatarsal head during baseline and recovery periods. SBF responses were characterized as peak SBF, total SBF, and recovery time of reactive hyperemia. SBF was expressed as a ratio of recovery to baseline SBF to quantify the changes. Peak SBF in the vibration protocol (6.98 ± 0.87) was significantly lower than the sham control (9.26 ± 1.34, P < .01). Total SBF in the vibration protocol ([33.32 ± 7.98] × 103) was significantly lower than the sham control ([48.09 ± 8.9] × 103, P < .05). The recovery time in the vibration protocol (166.08 ± 32.71 seconds) was not significantly different from the sham control (223.53 ± 38.85 seconds, P = .1). Local vibrations at 100 Hz could reduce walking-induced hyperemic response on the first metatarsal head. Our finding indicates that preconditioning local vibrations could be a potential preventive intervention for people at risk for foot ulcers.

As one of the key points related to meat quality, skeletal muscle fibre type is determined by energy metabolism and genetic factors, but its transformation could be also greatly influenced by many factors. Thymol, the primary effective ingredients of thyme, is well known for its anti-oxidation and anti-inflammatory, while little is known about its effect on skeletal muscle oxidative metabolism and fibre type switch. Therefore, in order to investigate its effects and possibility to be applied in livestock production, 36 150-day-old fattening Pigs were fed with different diet for six-week experiment. As a result, the drip loss ratio of longissimus dorsi (LD) was significantly reduced (p < .05). Oxidative metabolism-related enzyme activity, the mRNA levels and protein expression of COX5B and PGC1α, mRNA level of myosin heavy chain I (MyHC I) and protein level of MyHC IIa were significantly upregulated (p < .05). While compared with control group, the protein expression of MyHC IIb was significantly decreased (p < .05). The result revealed that thymol could promote the oxidative metabolism in the muscle of pigs and improve the meat quality to a certain extent.

This study aimed to investigate the effects of conjugated linoleic acid (CLA) on intestinal epithelial barrier function and explore the underlying mechanisms. IPEC-J2 cells and mice were treated with different CLA isomers. The intestinal epithelial barrier function determined by transepithelial electrical resistance (TEER), the expression of tight junction proteins, and the involvement of G-protein coupled receptor 120 (GPR120), intracellular calcium ([Ca2+]i) and myosin light chain kinase (MLCK) were assessed. In vitro, c9, t11-CLA, but not t10, c12-CLA isomer, impaired epithelial barrier function in IPEC-J2 by downregulating the expression of tight junction proteins. Meanwhile, c9, t11-CLA isomer enhanced GPR120 expression, while knockdown of GPR120 eliminated the impaired epithelial barrier function induced by c9, t11-CLA isomer. In addition, c9, t11-CLA isomer increased [Ca2+]i and activated the MLCK signaling pathway in a GPR120-dependent manner. However, chelation of [Ca2+]i reversed c9, t11-CLA isomer-induced MLCK activation and the epithelial barrier function impairment of IPEC-J2. Furthermore, inhibition of MLCK totally abolished the impairment of epithelial barrier function induced by c9, t11-CLA. In vivo, dietary supplementation of c9, t11-CLA rather than t10, c12-CLA isomer decreased the expression of intestinal tight junction proteins and GPR120, increased intestinal permeability, and activated the MLCK signaling pathway in mice. Taken together, our findings showed that c9, t11-CLA, but not t10, c12-CLA isomer, impaired intestinal epithelial barrier function in IPEC-J2 cells and mice through activation of GPR120-[Ca2+]i and the MLCK signaling pathway. These data provided new insight into the regulation of the intestinal epithelial barrier by different CLA isomers and more references for CLA application in humans and animals.

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).

Bipolar disorders (BDs) have high morbidity. The first onset of 27.7% of BDs occurs in children under 13 years and of 37.6% occurs in adolescents between 13 and 18 years. However, not all of the pediatric and adolescent patients with BD receive therapy in time. Therefore, studies about pediatric and adolescent patients with disorders have aroused increased attention in the scientific community. Pediatric and adolescent patients with BD present with a high prevalence rate (0.9–3.9%), and the pathogenic factors are mostly due to genetics and the environment; however, the pathological mechanisms remain unclear. Pediatric and adolescent patients with BD manifest differently from adults with BDs and the use of scales can be helpful for diagnosis and treatment evaluation. Pediatric and adolescent patients with BDs have been confirmed to have a high comorbidity rate with many other kinds of disorders. Both medication and psychological therapies have been shown to be safe and efficient methods for the treatment of BD. This review summarizes the research status related to the epidemiology, pathogenic factors, clinical manifestations, comorbidities, diagnostic and treatment scales, medications, and psychological therapies associated with BDs.

Promoting the thermogenic function of brown adipose tissue (BAT) is a promising strategy to combat obesity and metabolic disorders. While much is known about the transcriptional regulation of BAT activation, however, the underlying mechanism of post-transcriptional control by RNA binding proteins remains largely unknown. Here, we found that RNA binding protein Y-box binding protein 1 (YBX1) expression was abundant in BAT and induced by cold exposure and a β-adrenergic agonist in mice. Loss-of-function experiments showed that YBX1 deficiency inhibited mouse primary brown adipocyte differentiation and thermogenic function. Further study showed that YBX1 positively regulates thermogenesis through enhancing mitophagy. Mechanistically, RNA immunoprecipitation identified that YBX1 directly targeted the transcripts of PTEN-induced kinase 1 (Pink1) and parkin RBR E3 ubiquitin-protein ligase (Prkn), two key regulators of mitophagy. RNA decay assay proved that loss of YBX1 decreased mRNA stability of Pink1 and Prkn, leading to reduced protein expression, thereby alleviating mitophagy and inhibiting thermogenic program. Importantly, in vivo experiments demonstrated that YBX1 overexpression in BAT promoted thermogenesis and mitophagy in mice. Collectively, our results reveal novel insight into the molecular mechanism of YBX1 in post-transcriptional regulation of PINK1/PRKN-mediated mitophagy and highlight the critical role of YBX1 in brown adipogenesis and thermogenesis.

The accurate estimation of coastal water quality parameters (WQPs) is crucial for decision-makers to manage water resources. Although various machine learning (ML) models have been developed for coastal water quality estimation using remote sensing data, the performance of these models has significant uncertainties when applied to regional scales. To address this issue, an ensemble ML-based model was developed in this study. The ensemble ML model was applied to estimate chlorophyll-a (Chla), turbidity, and dissolved oxygen (DO) based on Sentinel-2 satellite images in Shenzhen Bay, China. The optimal input features for each WQP were selected from eight spectral bands and seven spectral indices. A local explanation strategy termed Shapley Additive Explanations (SHAP) was employed to quantify contributions of each feature to model outputs. In addition, the impacts of three climate factors on the variation of each WQP were analyzed. The results suggested that the ensemble ML models have satisfied performance for Chla (errors = 1.7%), turbidity (errors = 1.5%) and DO estimation (errors = 0.02%). Band 3 (B3) has the highest positive contribution to Chla estimation, while Band Ration Index2 (BR2) has the highest negative contribution to turbidity estimation, and Band 7 (B7) has the highest positive contribution to DO estimation. The spatial patterns of the three WQPs revealed that the water quality deterioration in Shenzhen Bay was mainly influenced by input of terrestrial pollutants from the estuary. Correlation analysis demonstrated that air temperature (Temp) and average air pressure (AAP) exhibited the closest relationship with Chla. DO showed the strongest negative correlation with Temp, while turbidity was not sensitive to Temp, average wind speed (AWS), and AAP. Overall, the ensemble ML model proposed in this study provides an accurate and practical method for long-term Chla, turbidity, and DO estimation in coastal waters.

Background This study examined the effects of a solid-state fermented feed additive (FFA) on the small intestine histology/morphology, immunity and microbiota of broilers. Two hundred eighty-eight day-old Arbor Acre chicks, were randomly assigned to one of four groups (each group has 6 replicates, with each replicate containing 12 chickens). The negative control (NC; basal diet), the positive control (PC; basal diet +antibiotic 15 ppm), the fermented feed additive low dose (FFL; basal diet + 0.3 kg/t FFA), and the fermented feed additive high dose (FFH; 3 kg/t FFA) with Lactobacillus casei (L.casei). Results The study found that the FFH and FFL groups gained more weight (1-21d) and the FFL and PC diets had better feed conversion ratio (P P P P P P P P P Delsulfobacterota and class Desulfovibriona and Negativicutes was also significantly reduced in the group treated with FFH and PC while microorganisms having beneficial properties like Lactobacillaceae family, Lactobacillus aviarus genus and Lactobacillus spp were also tended to increase in the FFH and FFL fermented feed groups compared to the PC and NC groups. Conclusion These findings suggested that the FFA diet may modulate cecal microbiota by reducing pathogenic microorganisms such as phylum Delsulfobacterota and class Desulfovibriona and Negativicutes improve beneficial microorganisms like Lactobacillaceae family, Lactobacillus aviarus genus and Lactobacillus spp. While FFA diet also affect immunity, and gene expression related to immunity.

The mechanisms whereby fish oil rich in EPA and DHA promotes BAT thermogenesis and WAT browning are not fully understood. Thus, this study aimed to investigate the effects of cytochrome P450 (CYP) epoxygenase-derived EPA and DHA oxylipins 17,18-EpETE and 19,20-EpDPE on BAT thermogenesis and WAT browning and explore the underlying mechanism. Stromal vascular cells (SVCs) were subjected to 17,18-EpETE or 19,20-EpDPE treatment and mice were treated with the CYP epoxygenase inhibitor, the thermogenic marker genes were detected and the involvement of GPR120 and AMPKα were assessed. The