SCN-MLTPP: A Multi-Label Classifier for Predicting Therapeutic Properties of Peptides Using the Stacked Capsule Network.

Identifying the function of therapeutic peptides is an important issue in the development of novel drugs. To reduce the time and labor costs required to identify therapeutic peptides, computational methods are increasingly required. However, most of the existing peptide therapeutic function prediction models are used for predicting a single therapeutic function, ignoring the fact that a bioactive peptide might simultaneously consist of multi-activities. Furthermore, in the few existing multi-label classification models, the feature extraction procedures are still rough. We propose a multi-label framework, called SCN-MLTPP, with a stacked capsule network for predicting the therapeutic properties of peptides. Instead of using peptide sequence vectors alone, SCN-MLTPP extracts different view representation vectors from the therapeutic peptides and learns the contributions of different views to the properties of therapeutic peptides based on the dynamic routing mechanism. Benchmarking results show that as compared with existing multi-label predictors, SCN-MLTPP achieves better and more robust performance for different peptides. In addition, some visual analyses and case studies also demonstrate the model can reliably capture features from multi-view data and predict different peptides.

High-efficiency broadband achromatic metalenses for visible full-stokes polarization imaging.

Polarization-imaging technology has important applications in target detection, communication, biomedicine, and other fields. A polarization imaging system based on metalenses, which provides new possibilities for the realization of highly integrated full-Stokes polarization imaging systems, can solve the problems of traditional polarization imaging systems, such as complex structures, large volumes, and the inability to simultaneously obtain linear and circular polarization states. However, currently designed metalens arrays that can achieve real-time full-Stokes polarization imaging can generally only be used for monochromatic detection, which significantly limits the amount of measured information of the object. Broad-spectrum polarization color imaging allows more image degrees of freedom, enabling more accurate characterization of polarization for multi-target object scenes in complex environments. To achieve broad-spectrum polarization imaging, we propose and design a metalens array that can achieve full-Stokes polarization imaging in the broadband visible range, in which the design process of metalenses for splitting and focusing broadband orthogonal circularly polarized light is emphasized. To design metalenses that can achieve polarization splitting and efficient focusing, we simulate and optimize the height and period of the nano-units and show that smaller periods and larger heights do not always result in higher-performance devices when designing multifunctional metalenses. The designed metalens array can split and diffraction-limited focus the orthogonal polarized incident light to the designated position with average focusing efficiencies of 59.2% under 460-680 nm TM linearly polarized light, 53.1% under TE linearly polarized light, 58.8% under left-handed circularly polarized light, and 52.7% under right-handed circularly polarized light. The designed metalenses can be applied to imaging systems, such as polarization imaging and polarization light-field imaging systems.

[Research Status of and Recommendations for Prevention and Control of Sleep Disorders in China].

The quality of sleep, a key physiological factor that regulates information, memory, decision making, and other vital brain functions, can affect important physiological functions of the human body. According to disease classification systems, sleep disorders can be categorized into more than 90 types, including sleep apnea, insomnia, and hypersomnia. It may cause a variety of adverse consequences, such as depression, anxiety and other emotional disorders, as well as physical diseases such as hypertension, diabetes and stroke. In addition, the relevant cardiovascular and cerebrovascular diseases and cognitive impairment not only harm physical health, but also are associated with workplace accidents and safety problems, constituting public safety hazards. Sleep disorders have become a major social and scientific problem that impacts on the national economy and the livelihood of the people. Research on sleep disorders should be given more attention by researchers and policy makers. Herein, we mainly discussed the latest findings and difficulties concerning research on the prevention and intervention of sleep disorders and proposed strategies and suggestions accordingly.

Self-Healing Coating with a Controllable Release of Corrosion Inhibitors by Using Multifunctional Zinc Oxide Quantum Dots as Valves.

As an intelligent response system, self-healing anticorrosion materials containing nanocontainers have aroused increasing demands. It is highly expected that the nanocontainers can rapidly respond on corrosion signals to efficiently release corrosion inhibitors, meanwhile to avoid an undesirable leakage before the local corrosion happening. Herein, zinc oxide quantum dot (ZnO-QD)-sealed hollow mesoporous TiO2 nanocontainers loading with 14.2% benzotriazole (BTA) inhibitor have been successfully prepared [hollow mesoporous titanium dioxide nanospheres (HMTNs)-BTA@ZnO-QDs]. ZnO-QDs play the multifunctional roles on anticorrosion of the self-healing coating. The corrosion tests of coatings on the carbon steel well demonstrate that ZnO-QDs can not only act as a valve to seal and release BTA on the time but also act as a precursor to produce the protective film of Zn(OH)2 by the reaction of Zn2+ ions with OH- around the cathode region to inhibit the corrosion of carbon steel. After being soaked in 3.5% NaCl solution for 30 days, the |Z|0.01 Hz value of the coating with HMTNs-BTA@ZnO-QDs still maintains at 2.87 × 107 Ω cm2. Once the defects are formed in the coating, the acid-responsive ZnO-QD valves are rapidly decomposed to release BTA inhibitor; meanwhile, the resulted Zn(OH)2 layer prevent the carbon steel substrate from corrosion in the cathode area. Therefore, it could be promising that the present design of the nanocontainers matching with the multifunctional ZnO-QDs can offer a valuable strategy to construct the self-healing and anticorrosion coatings with a multiresponse to the corrosion environment.

The prevalence of hypertension in Chinese adolescents aged 15-17 years: A comparison of different criteria.

This study intended to compare the prevalence of hypertension in adolescents aged 15-17 years in China according to different criteria defined by various guidelines. We included 28 715 adolescents aged 15-17 years from the China Hypertension Survey study (CHS) 2012-2015, and the 2017 American Association of Pediatrics (AAP) Clinical Practice Guideline and 2018 Chinese guidelines for children and adults were used to define hypertension. The prevalence of hypertension among Chinese adolescents aged 15-17 years was 24.4% according to the 2018 Chinese guidelines for children; the corresponding values were 18.6% according to the 2017 AAP Guidelines, and 3.5% according to 2018 Chinese guidelines for adults. The age-specific prevalence of hypertension in the age of 15, 16, and 17 years in the same population was 26.2%, 24.4%, and 23.3% according to 2018 Chinese guidelines for children; 18.8%, 17.9%, and 19.2% as per the 2017 AAP Guidelines; 3.4%, 3.4%, and 3.6% as per the 2018 Chinese guidelines for adults. A highest prevalence of hypertension was observed according to 2018 Chinese guidelines for children than the other two guidelines. Compared with the 2018 Chinese guidelines for children, a higher 95th percentile BP (systolic and diastolic) was also observed in the present study in each gender-age-height-specific group. And the height, which was key factor to influence blood pressure, was similar between adolescents aged 15-17 and adults, and a paralleled result was seen in the present study. Therefore, the 2018 Chinese guidelines for adults may also be appropriate for adolescents aged 15-17 years.

Hypertension-mediated organ damage and established cardiovascular disease in patients with hypertension: the China Hypertension Survey, 2012-2015.

Hypertension is a major health burden worldwide. However, there is limited data on the status of hypertension-mediated organ damage (HMOD) and established cardiovascular (CV) disease in Chinese hypertensive patients. The aim of this study is to determine the prevalence of HMOD and established CV disease in a nationally representative population in China. A stratified multistage random sampling method was used in the China Hypertension Survey and 21,243 participants aged 35 or older were eligible for analysis in this study. For each participant, the demographic information and a self-reported medical history were acquired. Blood pressure was measured with the electronic device 3 times on the right arm, supported at heart level, after the participant was sitting at rest for 5 min. Samples of blood and urine were tested. 2-D and Doppler echocardiography were used to assess the heart's function and structures. Sampling weights were calculated based on the 2010 China population census data. Overall, the weighted prevalence of asymptomatic HMOD was 22.1%, 28.9%, 23.1%, 6.4%, and 6.2% for wide pulse pressure, left ventricular hypertrophy, microalbuminuria, chronic kidney disease, and abnormal ankle-brachial index, respectively. For the established CV disease, the weighted prevalence was 1.8%, 1.3%, 2.0%, and 1.1% for stroke, coronary artery disease, heart failure, and atrial fibrillation, respectively. The prevalence of asymptomatic HMOD and established CV disease was greater with higher blood pressure level (P < 0.05), rather than ankle-brachial index. Compared to those with uncontrolled hypertension, the prevalence of asymptomatic HMOD was lower in patients with controlled hypertension. In summary, the prevalence of HMOD in Chinese people aged 35 or older was very common, indicating a substantial future burden of both morbidity and mortality from hypertension in China. Clinical trial registration number: ChiCTR-ECS-14004641.

Current status and etiology of valvular heart disease in China: a population-based survey.

BACKGROUND: The epidemiology of valvular heart disease (VHD) has changed markedly over the last 50 years worldwide, and the prevalence and features of VHD in China are unknown. The objective of this study was to investigate the current status and etiology of VHD in China. METHODS: We used a cross-sectional national survey with stratified multistage random sampling from the general Chinese population to estimate the VHD burden. Data on demographic characteristics, medical history, physical examination, blood tests, and potential etiology were collected. Echocardiography was used to detect VHD. RESULTS: The national survey enrolled 34,994 people aged 35 years or older across China. Overall, 31,499 people were included in the final analysis, and 1309 participants were diagnosed with VHD. The weighted prevalence was 3.8%, with an estimated 25 million patients in China. The prevalence of VHD increased with age and was higher in participants with hypertension or chronic kidney disease than in their counterparts. Among participants with VHD, 55.1% were rheumatic and 21.3% were degenerative. The proportion of rheumatic decreased with age, and the proportion of degenerative rose with age. However, the prevalence of rheumatic disease was still higher in the elderly population than in the younger population. Logistic regression revealed that age and hypertension were correlated with VHD. CONCLUSIONS: In China, rheumatic heart disease was still the major cause of the VHD, with a significant increase in degenerative heart disease. Age and hypertension are important and easily identifiable markers of VHD.

A survey on predicting microbe-disease associations: biological data and computational methods.

Various microbes have proved to be closely related to the pathogenesis of human diseases. While many computational methods for predicting human microbe-disease associations (MDAs) have been developed, few systematic reviews on these methods have been reported. In this study, we provide a comprehensive overview of the existing methods. Firstly, we introduce the data used in existing MDA prediction methods. Secondly, we classify those methods into different categories by their nature and describe their algorithms and strategies in detail. Next, experimental evaluations are conducted on representative methods using different similarity data and calculation methods to compare their prediction performances. Based on the principles of computational methods and experimental results, we discuss the advantages and disadvantages of those methods and propose suggestions for the improvement of prediction performances. Considering the problems of the MDA prediction at present stage, we discuss future work from three perspectives including data, methods and formulations at the end.

Drug-drug similarity measure and its applications.

Drug similarities play an important role in modern biology and medicine, as they help scientists gain deep insights into drugs' therapeutic mechanisms and conduct wet labs that may significantly improve the efficiency of drug research and development. Nowadays, a number of drug-related databases have been constructed, with which many methods have been developed for computing similarities between drugs for studying associations between drugs, human diseases, proteins (drug targets) and more. In this review, firstly, we briefly introduce the publicly available drug-related databases. Secondly, based on different drug features, interaction relationships and multimodal data, we summarize similarity calculation methods in details. Then, we discuss the applications of drug similarities in various biological and medical areas. Finally, we evaluate drug similarity calculation methods with common evaluation metrics to illustrate the important roles of drug similarity measures on different applications.

1,25(OH)2D3 provides protection against diabetic kidney disease by downregulating the TLR4-MyD88-NF-κB pathway.

The over-activation of Toll-like receptors (TLRs) is a typical immune response to injury. Previous work has suggested that controlling the over-activation of TLR4-MyD88-NF-κB may represent a new therapeutic option for diabetic kidney disease (DKD). 1,25(OH)2D3 has also been shown to exert a protective effect on DKD, although the mechanism involved has yet to be elucidated. The aim of this study was to investigate whether 1,25(OH)2D3 protects against DKD by down-regulating the innate immune TLR-NF-κB pathway. NRK-52E cells were cultured under normal or high-glucose conditions. We then used siRNA to knock down TLR4 expression under high-glucose conditions. NRK-52E cells cultured under high-glucose conditions, and streptozotocin (STZ)-induced diabetic rats, were treated with different doses of 1,25(OH)2D3 and used as in vitro and in vivo models, respectively. Renal biochemical indicators were then measured to evaluate the influence of 1,25(OH)2D3 treatment on DKD in diabetic rats. Histological analysis was also performed to determine the extent of infiltration by inflammatory cells and tubulointerstitial fibrosis. Using RT-qPCR, western blotting, immunohistochemistry and immunofluorescence, we determined the expression levels of TLR4, MyD88, NF-κB p65, MCP-1 and α-SMA to investigate whether 1,25(OH)2D3 could reduce the development of tubulointerstitial fibrosis. Knocking down TLR4 abolished the tubulointerstitial fibrosis caused by high-glucose conditions. High doses of 1,25(OH)2D3 consistently reduced the expression of TLR4-MyD88-NF-κB in NRK-52E cells. Moreover, high doses of 1,25(OH)2D3 had an obvious protective effect on kidney injury and inhibited the infiltration of inflammatory cells and tubulointerstitial fibrosis in diabetic rats. In conclusion, high doses of 1,25(OH)2D3 protected against tubulointerstitial fibrosis both in vitro and in vivo by downregulating the expression of TLR4-MyD88-NF-κB.

Effect of a Workplace-Based Multicomponent Intervention on Hypertension Control: A Randomized Clinical Trial.

Importance: A workplace-based intervention could be an effective approach to managing high blood pressure (BP). However, few studies to date have addressed hypertension control among the Chinese working population. Objective: To assess the effect of a workplace-based, multicomponent intervention strategy on improving BP control. Design, Setting, and Participants: A cluster randomized clinical trial of a hypertension management program was conducted from January 2013 to December 2014 in 60 workplaces across 20 urban regions in China. Workplaces were randomized to either the intervention group (n = 40) or control group (n = 20). Employee participants in each workplace were asked to complete a cross-sectional survey. Data analysis on an evaluable population was conducted from January 2016 to January 2017. Interventions: The 2-year intervention included 2 components: (1) a workplace wellness program for improving employees' cardiovascular health and (2) a guidelines-oriented hypertension management protocol with a community health center intervention accompanied by monthly visits for achieving BP control over a period of 24 months. Main Outcomes and Measures: The primary outcome was the change in BP control rate from baseline to 24 months among employees with hypertension in the intervention and control groups. The secondary outcomes were the changes in BP level and lifestyle factors by the end of the trial. Results: Overall, 4166 participants (3178 in the intervention group and 988 in the control group) were included (mean [SD] age, 46.3 [7.6] years; 3451 men [82.8%]). Blood pressure control rate at baseline was 19.5% in the intervention group and 20.1% in the control group. After 24 months of the intervention, the BP control rate for the intervention group compared with the control group was significantly higher (66.2% vs 44.0%; odds ratio, 1.77; 95% CI, 1.58-2.00; P < .001). The intervention effect on systolic BP level was -5.8 mm Hg (95% CI, -6.8 to -4.9 mm Hg; P < .001) and on diastolic BP level was -3.6 mm Hg (95% CI, -4.4 to -2.9 mm Hg; P < .001). The BP control rate showed a gradual increment throughout the whole duration in the intervention group. Moreover, greater reduction was reported in the rates of drinking (-18.4%; 95% CI, -20.6% to -16.2%; P < .001), perceived stress (-22.9%; 95% CI, -24.8% to -21.1%; P < .001), and excessive use of salt (-32.0%; 95% CI, -33.7% to -30.4%; P < .001). Conclusions and Relevance: This trial found that a workplace-based, multicomponent intervention appeared to be more effective than usual care, leading to measurable benefits such as lower blood pressure, improved hypertension control, and adoption of healthy lifestyle habits. The intervention can therefore be considered for large-scale use or inclusion in hypertension control programs in workplaces in China and other countries. Trial Registration: Chinese Clinical Trial Registry No. ChiCTR-ECS-14004641.

Prevalence of overweight and obesity in China: Results from a cross-sectional study of 441 thousand adults, 2012-2015.

OBJECTIVES: Obesity has become a global health public problem. The study aims to examine the latest prevalence of overweight and obesity in China. METHODS: Data came from the China Hypertension Survey (CHS), a nationally representative cross-sectional study among residents aged ≥18 years from October 2012 to December 2015. Overweight and obesity were defined as 25≤BMI<30kg/m2 and BMI≥30kg/m2 according to the WHO classifications, respectively. RESULTS: The data of 441 306 participants were analyzed. The prevalence of overweight and obesity was 28.1% and 5.2% respectively. The prevalence of overweight and obesity varied considerably across provinces. The prevalence of overweight was the highest in Beijing, which was 2.8 fold of the lowest in Guangxi (40.9% vs. 14.6%). The prevalence of obesity was the highest in Tianjin, which was 9.4 fold of the lowest in Hainan (12.2% vs. 1.3%). There was a striking north-south gradient with the prevalence higher in Northeast and Northwest China and lower in Southeast China. Multivariate logistic regression analysis indicated that sex, age, education, smoking, marital status and family history of cardiovascular disease were significantly associated with overweight and obesity. CONCLUSIONS: Overweight and obesity are highly prevalent among Chinese adults, and their prevalence varies greatly among different population subgroups and provinces. National and provincial obesity control and prevention strategies should be public health priorities in China.

Generation of a multiplex mutagenesis population via pooled CRISPR-Cas9 in soya bean.

The output of genetic mutant screenings in soya bean [Glycine max (L.) Merr.] has been limited by its paleopolypoid genome. CRISPR-Cas9 can generate multiplex mutants in crops with complex genomes. Nevertheless, the transformation efficiency of soya bean remains low and, hence, remains the major obstacle in the application of CRISPR-Cas9 as a mutant screening tool. Here, we report a pooled CRISPR-Cas9 platform to generate soya bean multiplex mutagenesis populations. We optimized the key steps in the screening protocol, including vector construction, sgRNA assessment, pooled transformation, sgRNA identification and gene editing verification. We constructed 70 CRISPR-Cas9 vectors to target 102 candidate genes and their paralogs which were subjected to pooled transformation in 16 batches. A population consisting of 407 T0 lines was obtained containing all sgRNAs at an average mutagenesis frequency of 59.2%, including 35.6% lines carrying multiplex mutations. The mutation frequency in the T1 progeny could be increased further despite obtaining a transgenic chimera. In this population, we characterized gmric1/gmric2 double mutants with increased nodule numbers and gmrdn1-1/1-2/1-3 triple mutant lines with decreased nodulation. Our study provides an advanced strategy for the generation of a targeted multiplex mutant population to overcome the gene redundancy problem in soya bean as well as in other major crops.

Prevalence of Abdominal Obesity in China: Results from a Cross-Sectional Study of Nearly Half a Million Participants.

OBJECTIVE: This study aimed to examine the latest prevalence of abdominal obesity in China based on nationally representative data. METHODS: A stratified, multistage, random sampling method was used to obtain a nationally representative sample of residents aged ≥ 18 years from 31 provinces in mainland China from October 2012 to December 2015. Abdominal obesity was defined as a waist circumference ≥ 90 cm for men and a waist circumference ≥ 85 cm for women. RESULTS: The data of 441,306 participants were analyzed. The prevalence of abdominal obesity was 29.1% (28.6% in men and 29.6% in women); the number of adults with abdominal obesity was estimated to be 277.8 million (approximately 140.1 million in men and 137.7 million in women). The prevalence of abdominal obesity varied considerably among provinces. In general, the prevalence of abdominal obesity was higher in the northern, lower in the southern, higher in the western, and lower in the eastern areas of China. Besides the regional disparities, the prevalence of abdominal obesity varied greatly among different population subgroups. CONCLUSIONS: Abdominal obesity is highly prevalent among Chinese adults. National and provincial obesity control and prevention strategies should be public health priorities in China. To better control obesity, the underlying reasons for the regional disparities need to be addressed.

High-Accuracy Correction of a Microlens Array for Plenoptic Imaging Sensors.

Microlens array (MLA) errors in plenoptic cameras can cause the confusion or mismatching of 4D spatio-angular information in the image space, significantly affecting the accuracy and efficiency of target reconstruction. In this paper, we present a high-accuracy correction method for light fields distorted by MLA errors. Subpixel feature points are extracted from the microlens subimages of a raw image to obtain correction matrices and perform registration of the corresponding subimages at a subpixel level. The proposed method is applied for correcting MLA errors of two different categories in light-field images, namely form errors and orientation errors. Experimental results show that the proposed method can rectify the geometric and intensity distortions of raw images accurately and improve the quality of light-field refocusing. Qualitative and quantitative comparisons between images before and after correction verify the performance of our method in terms of accuracy, stability, and adaptability.

Responsibility and Sustainability in Brain Science, Technology, and Neuroethics in China-a Culture-Oriented Perspective.

The China Brain Project is in development. Integrating an ethical framework to identify and assess ethical challenges and plan for solutions is a priority. Here Wang et al. discuss ethical questions emerging from brain research in the context of traditional Chinese culture and juxtapose the legacy of Confucianism with contemporary thinking.

Prevalence and risk factors associated with hyperuricemia among working population at high altitudes: a cross-sectional study in Western China.

Chronic exposure to high altitude may lead to hyperuricemia. We investigated the prevalence of hyperuricemia and its risk factors among employees in high-altitude areas. A cross-sectional survey with cluster sampling was performed at 23 worksites on the Qinghai-Tibet Plateau. Subjects were evaluated by using questionnaires, anthropometric and laboratory measurements, and abdominal ultrasound. A multilevel logistic regression model and restricted cubic spline were used to explore the associated factors of hyperuricemia. Of the 4198 employees included in the study, the age-standardized prevalence of hyperuricemia was 28.1% (95% confidence interval (CI) 26.7-29.5), with 31.9% (95%CI 30.2-33.6) in men and 17.9% (95%CI 15.7-20.1) in women. Hypertension, hyperlipidemia, and a meat-food pattern were positively associated with hyperuricemia in both sexes, while diabetes, shift work, body mass index, non-alcoholic fatty liver disease, and low intake of fruits and vegetables were significantly associated with hyperuricemia only in men. Furthermore, a nonlinear dose-response association between the number of cardiovascular risk factors (CRFs) and hyperuricemia was observed. Compared with those having 0 CRFs, the full-adjusted odds ratios (ORs) and 95%CIs for 1, 2, and ≥ 3 CRFs were 1.76 (95%CI 1.25-2.47), 2.54 (95%CI 1.81-3.55), and 3.05 (95%CI 2.16-4.31) in men, respectively, and 2.13 (95%CI 1.43-3.17), 2.78 (95%CI 1.71-4.53), and 3.13 (95%CI 1.50-6.55) in women, respectively. Hyperuricemia is common in employees at high-altitude areas. However, working at higher altitudes does not mean necessarily higher risk of hyperuricemia, as dietary factors and clustered CRFs are more significant. Thus, workplace-based lifestyle modifications should be promoted.

The Disease Burden of Atrial Fibrillation in China from a National Cross-sectional Survey.

Atrial fibrillation (AF) is the most common type of arrhythmia, which is a significant public health issue. We aimed to determine the disease burden of AF in China. We used a recent national survey with stratified multistage random sampling from general Chinese population to estimate the AF disease burden, which enrolled 34,994 people aged 35 years or older all over China. The AF patients were detected by electrocardiogram during the survey or medical history taking. The quality of life in AF patients was assessed by a questionnaire similar to EQ-5D to estimate the weight of disability. Disability-adjusted life years was then calculated by adding years of life lost to years lived with disability. Overall, 31,230 samples were included in the final analysis, the weighted prevalence of AF in the Chinese population aged 35 years or older was 0.71%. Thirty-four percent of AF patients were newly diagnosed in the survey and unaware of their pathological condition beforehand. The prevalence of AF significantly increased with age. The health-related quality of life was impaired in Chinese AF patients with an overall utility value of 0.53. The total disability-adjusted life years of Chinese AF patient is estimated to be 665,400. In conclusion, the disease burden of AF in the general Chinese population was a significant public health issue in China.

Rectification of Images Distorted by Microlens Array Errors in Plenoptic Cameras.

A plenoptic cameras is a sensor that records the 4D light-field distribution of target scenes. The surface errors of a microlens array (MLA) can cause the degradation and distortion of the raw image captured by a plenoptic camera, resulting in the confusion or loss of light-field information. To address this issue, we propose a method for the local rectification of distorted images using white light-field images. The method consists of microlens center calibration, geometric rectification, and grayscale rectification. The scope of its application to different sized errors and the rectification accuracy of three basic surface errors, including the overall accuracy and the local accuracy, are analyzed through simulation of imaging experiments. The rectified images have a significant improvement in quality, demonstrating the provision of precise light-field data for reconstruction of real objects.

4-(2-(4-chlorophenyl)-1-((4-chlorophenyl)amino)ethyl)benzene-1, 3-diol is a potential agent for gout therapy as a dual inhibitor of XOD and NLRP3.

BACKGOUND: Gout is an inflammatory arthritis characterized by abrupt self-limiting attacks of inflammation caused by precipitation of monosodium urate crystals (MSU) in the joint. Both anti-hyperuricemia and anti-inflammation could be gout therapeutic strategies, whereas ideal drugs for gout treatment are deficient. PURPOSE: 4-(2-(4-chlorophenyl)-1-((4-chlorophenyl)amino)ethyl)benzene-1, 3-diol (CBED) was obtained from a cluster of deoxybenzoins derivatives synthesized by our research group with potent anti-hyperuricemic and anti-inflammatory activities, which was expected to be a dual inhibitor of xanthine oxidase (XOD) and NOD-like receptor protein 3 (NLRP3). This study aimed to investigate effects of CBED on XOD and NLRP3 in vitro, as well as the possible mechanisms by which CBED improved gout in vivo. METHODS: After molecular docking detection, inhibitory effects of CBED on XOD and NLRP3 were evaluated in vitro. Subsequently, hyperuricemia and acute gouty arthritis animal models were established by potassium oxonate or MSU, respectively. After CBED treatment, serum uric acid levels, synovial interleukin (IL)-1ß concentrations, hepatic XOD activities, as well as synovial morphological changes were examined. More importantly, synovial expressions of NLRP3 inflammasome components including NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1 in rats were analyzed by immunofluorescence and western blot. RESULTS: In vitro, CBED obviously inhibited XOD activity with an IC50 value of 3.87 µM, moreover, it effectively inhibited MSU-induced NLRP3 inflammasome activation and IL-1ß over-production in THP-1 cells. In addition, CBED dose-dependently decreased serum uric acid levels suppressed hepatic XOD activities in oxonate-induced hyperuricemic mice. On the other hand, CBED significantly improved MSU-induced ankle swelling and histopathological damage with elevated IL-1ß. In addition, NLRP3 inflammasome activation could be blocked by CBED treatment in rats with acute gouty arthritis. Notbly, CBED exhibited no effects on all these indicators in normal animals, predicting its safety. CONCLUSIONS: CBED might serve as a dual XOD and NLRP3 inhibitor for treatment of gout.