Exploration of the association between new "Life's Essential 8" with hyperuricemia and gout among US adults.

BACKGROUND: Previous researches have reported the relationship between uric acid and cardiovascular disease. We aimed to investigate the association of Life's Essential 8, a recently updated measurement of cardiovascular health, with the prevalence of hyperuricemia (HUA) and gout among US adults. Additionally, we also explored the relationship between LE8 and all-cause mortality among patients with HUA or gout. METHODS: Participants from the National Health and Nutrition Examination Survey in 2007-2016 were involved in this study. LE8 score was categorized into low, moderate, high CVH groups according to American Heart Association definitions. Multivariable logistic regression and cox regression analyses, restricted cubic spline models, subgroup analysis and sensitivity analysis were used to explore the associations. RESULTS: A total of 23,619 adult participants were included in this study, which included 4,775 hyperuricemia patients and 1,055 gout patients. Among all participants, the overall median LE8 score was 65.62 (21.25) and the prevalence of hyperuricemia and gout of were 20.2% and 4.5%, respectively. After fully adjusted the potential confounders, participants in high CVH group had a lower prevalence of hyperuricemia and gout compared with the low CVH group, with a OR (95%CI) of 0.50 (0.39-0.63) and 0.50 (0.30-0.82), respectively. The restricted cubic spline showed a significantly inverse relationship between LE8 and hyperuricemia and gout. Similar patterns were also identified in the association between LE8 scores and all-cause mortality in HUA and gout patients. CONCLUSIONS: Higher LE8 scores are associated with lower risk and lower all-cause mortality of HUA and gout among US adults. Adherence to optimal CVH metrics may be an appropriate prevention and management strategy for reducing the socioeconomic burden of hyperuricemia and gout.

Assessment of the correlation between KAP scores regarding sugar-sweetened beverage consumption and hyperuricemia amongst Chinese young adults.

BACKGROUND: The prevalence of hyperuricemia in China has been consistently increasing, particularly among the younger generation. The excessive consumption of sugar-sweetened beverages is associated with hyperuricemia. This study examined the knowledge, attitudes, and practices (KAP) of Chinese young adults regarding sugar-sweetened beverage consumption and the correlation with hyperuricemia. METHODS: This cross-sectional investigation was conducted from June 28th, 2023, to July 21st, 2023, and enrolled Chinese young adults. Demographics and KAP were evaluated using a questionnaire (Cronbach's α = 0.787). Factors influencing KAP scores were analyzed using multivariable analyses. RESULTS: A total of 1288 valid questionnaires were analyzed. The median knowledge, attitude, and practice scores were 16 (12,19)/22, 22 (20,24)/30, and 27.5 (23,31.75)/40. The multivariable analysis showed that bachelor's/associate education (OR = 1.912, 95%CI: 1.128-3.239), white collar/employee (OR = 0.147, 95%CI: 0.105-0.206), educator (OR = 0.300, 95%CI: 0.174-0.518), healthcare worker (OR = 0.277, 95%CI: 0.188-0.407), not suffering from hyperuricemia (OR = 0.386, 95%CI: 0.253-0.590), and not having gout (OR = 0.456, 95%CI: 0.282-0.736) were independently associated with knowledge. Age 26-30 (OR = 1.470, 95%CI: 1.052-2.052), age 31-35 (OR = 1.489, 95%CI: 1.097-2.022), age 36-40 (OR = 0.328, 95%CI: 1.010-1.746), age 41-44 (OR = 1.548, 95%CI: 1.091-2.198), and not having hyperuricemia (OR = 0.512, 95%CI: 0.345-0.760) were independently associated with attitude. White collar/employee (OR = 0.386, 95%CI: 0.285-0.521), educator (OR = 0.534, 95%CI: 0.317-0.899), healthcare worker (OR = 0.341, 95%CI: 0.236-0.493), having siblings (OR = 0.725, 95%CI: 0.573-0.917), and not suffering from hyperuricemia (OR = 0.442, 95%CI: 0.296-0.659), were independently associated with practice. CONCLUSION: Chinese young adults display moderate KAP toward sugar-sweetened beverages. Notably, an association was observed between hyperuricemia and each KAP dimension.

Improved anaerobic sludge fermentation mediated by a tryptophan-degrading consortium: Effectiveness assessment and mechanism deciphering.

The hydrolysis of extracellular polymeric substances (EPS) represents a critical bottleneck in the anaerobic fermentation of waste activated sludge (WAS), while tryptophan is identified as an underestimated constituent of EPS. Herein, we harnessed a tryptophan-degrading microbial consortium (TDC) to enhance the hydrolysis efficiency of WAS. At TDC dosages of 5%, 10%, and 20%, a notable increase in SCOD was observed by factors of 1.13, 1.39, and 1.88, respectively. The introduction of TDC improved both the yield and quality of short chain fatty acids (SCFAs), the maximum SCFA yield increased from 590.6 to 1820.2, 1957.9 and 2194.9 mg COD/L, whilst the acetate ratio within SCFAs was raised from 34.1% to 61.2-70.9%. Furthermore, as TDC dosage increased, the relative activity of protease exhibited significant increments, reaching 116.3%, 168.0%, and 266.1%, respectively. This enhancement facilitated WAS solubilization and the release of organic substances from bound EPS into soluble EPS. Microbial analysis identified Tetrasphaera and Soehngenia as key participants in WAS solubilization and the breakdown of protein fraction. Metabolic analysis revealed that TDC triggered the secretion of enzymes associated with amino acid metabolism and fatty acid biosynthesis, thereby fostering the decomposition of proteins and production of SCFAs.

Hyperuricemia and gout increased the risk of long-term mortality in patients with heart failure: insights from the National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of hyperuricemia, gout, and heart failure (HF) is on the rise, and these conditions often share similar risk factors. The present study aimed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. METHODS: The data on nonpregnant participants aged ≥ 20 years with or without hyperuricemia, gout, and HF from the National Health and Nutrition Examination Survey 2001-2018 and 2007-2018 were included in this study. The binary logistic regression, Kaplan-Meier curve, Cox proportional-hazards model, and restricted cubic spline analysis were employed to evaluate the relationship among hyperuricemia, gout, HF, and all-cause mortality. RESULTS: Of 204,179,060 and 223,702,171 weighted eligible participants, 40,044,228 (19.6%) and 9,158,600 (4.1%) had hyperuricemia and gout, respectively. Older age, diabetes, stroke, and coronary artery disease were the risk factors for HF among patients with hyperuricemia and gout. The median survival time was 7.00 years and 6.25 years and the 5-year survival rate was 59.9% and 55.9% for patients with HF and hyperuricemia and those with HF and gout, respectively. Patients with hyperuricemia or gout were 2.46 and 2.35 times more likely to have HF and 1.37 and 1.45 times more likely to experience all-cause mortality compared with those who did not exhibit these conditions. The restricted cubic spline showed a nonlinear correlation between uric acid levels and HF and a J-shaped correlation between uric acid levels and all-cause mortality. CONCLUSIONS: Ambulatory patients with hyperuricemia or gout were more likely to have HF compared with those without hyperuricemia or gout. Patients with HF with hyperuricemia or gout were more likely to experience all-cause mortality in the long-term follow-up.

Photoredox-Catalyzed gem-Difluoromethylenation of Aliphatic Alcohols with 1,1-Difluoroalkenes to Access α,α-Difluoromethylene Ethers.

A switchable synthesis of alcohols and ketones bearing a CF2-OR scaffold using visible-light promotion is described. The method of PDI catalysis is characterized by its ease of operation, broad substrate scopes, and the ability to switch between desired products without the need for transition metal catalysts. The addition or absence of a base plays a key role in controlling the synthesis of the major desired products.

Impaired autophagy flux by lncRNA NEAT1 is critical for inflammation factors production in human periodontal ligament stem cells with nicotine treatment.

BACKGROUND AND OBJECTIVES: Periodontitis is the top reason for tooth loss, and smoking significantly increases severe periodontitis risk. Defective autophagy has been reported to play a vital role in periodontitis. This study aimed to elucidate the relationship between autophagy and inflammation factors production in nicotine-treated periodontal ligament stem cells (PDLSCs) and the underlying mechanism. METHODS: In this study, transmission electron microscopy, immunofluorescence, and the mCherry-GFP-LC3 plasmid were used to study autophagy flux. The gene levels of inflammation factors and long noncoding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) were detected by quantitative real-time PCR (qRT-PCR). Western blot was performed to assess the protein levels of autophagic markers and α7 nicotinic acetylcholine receptor (α7nAChR). RESULTS: We found that nicotine impaired autophagosome-lysosome fusion and lysosome functions to block autophagy flux, contributing to inflammatory factors production in nicotine-treated PDLSCs. Moreover, nicotine upregulated NEAT1 by activating α7nAChR. NEAT1 decreased autophagy flux by downregulating syntaxin 17 (STX17). CONCLUSION: Our data indicate that NEAT1-decreased autophagy flux is pivotal for inflammation factors production in nicotine-treated PDLSCs.

Palmitic acid induces GSDMD-mediated pyroptosis in periodontal ligament cells via the NF-κB pathway.

OBJECTIVE: Obesity can affect periodontal tissues and exacerbate periodontitis. Pyroptosis, a newly identified type of inflammatory cell death, is involved in the development of periodontal inflammation. The saturated fatty acid palmitic acid (PA) is elevated in obese patients. The effect of PA on pyroptosis in periodontal ligament cells (PDLCs) and its underlying mechanisms remain unknown. MATERIALS AND METHODS: Human PDLCs were isolated from healthy individuals and cultured for experiments. The effects of PA on PDLC pyroptosis and the underlying mechanisms were examined by transmission electron microscopy, quantitative real-time PCR and western blotting. RESULTS: The morphology of PDLCs in the PA group indicated pyroptotic characteristics, including swollen cells, plasma membrane rupture and changes in subcellular organelles. PA induced inflammatory responses in PDLCs, as indicated by an increase in IL-1ß in the cell culture supernatant. Furthermore, we found that the pyroptosis-related proteins caspase-1, caspase-4 and GSDMD were involved in PA-induced cell death. GSDMD and caspase-4 inhibitors alleviated pyroptotic death of PDLCs. Moreover, PA promoted NF-κB P65 phosphorylation. A NF-κB inhibitor decreased IL-1ß expression and partly rescued cell death induced by PA. CONCLUSION: PA activated the NF-κB pathway and induced the inflammatory response in PDLCs. Caspase-4/GSDMD mediated PDLC pyroptosis induced by PA.

Small-scale spatiotemporal epidemiology of notifiable infectious diseases in China: a systematic review.

BACKGROUND: The prevalence of infectious diseases remains one of the major challenges faced by the Chinese health sector. Policymakers have a tremendous interest in investigating the spatiotemporal epidemiology of infectious diseases. We aimed to review the small-scale (city level, county level, or below) spatiotemporal epidemiology of notifiable infectious diseases in China through a systematic review, thus summarizing the evidence to facilitate more effective prevention and control of the diseases. METHODS: We searched four English language databases (PubMed, EMBASE, Cochrane Library, and Web of Science) and three Chinese databases (CNKI, WanFang, and SinoMed), for studies published between January 1, 2004 (the year in which China's Internet-based disease reporting system was established) and December 31, 2021. Eligible works were small-scale spatial or spatiotemporal studies focusing on at least one notifiable infectious disease, with the entire territory of mainland China as the study area. Two independent reviewers completed the review process based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 18,195 articles were identified, with 71 eligible for inclusion, focusing on 22 diseases. Thirty-one studies (43.66%) were analyzed using city-level data, 34 (47.89%) were analyzed using county-level data, and six (8.45%) used community or individual data. Approximately four-fifths (80.28%) of the studies visualized incidence using rate maps. Of these, 76.06% employed various spatial clustering methods to explore the spatial variations in the burden, with Moran's I statistic being the most common. Of the studies, 40.85% explored risk factors, in which the geographically weighted regression model was the most commonly used method. Climate, socioeconomic factors, and population density were the three most considered factors. CONCLUSIONS: Small-scale spatiotemporal epidemiology has been applied in studies on notifiable infectious diseases in China, involving spatiotemporal distribution and risk factors. Health authorities should improve prevention strategies and clarify the direction of future work in the field of infectious disease research in China.

miR-296-5p promotes autophagy in mouse LS8 cells under excessive fluoride via AMPK/ULK1 pathways.

Numerous microRNAs participate in regulating the pathological process of autophagy. We have found miR-296-5p is one of the most significantly down-regulated microRNAs in a high concentration of sodium fluoride. However, it is not clear whether miR-296-5p augments autophagy in dental fluorosis. Our purpose is to explore the function of miR-296-5p in regulating autophagy of excessive fluoride development. Thus, the cell line of ameloblasts LS8 was exposed to a 1.5 mM dose of NaF and miR-296-5p-mimics, Real-time qPCR, CCK-8 assays, Fluorescence imaging and Western blot analysis were performed. Autophagy was observed. As our results indicated, miR-296-5p overexpression in mouse LS8 cells significantly accelerated autophagy. The autophagy inhibition effect of miR-296-5p underexpression was consistent with the effect of the AMPK inhibitor. And we found that the expression of LC3II was decreased via down-regulation of AMPK. The change of ULK1 by miR-296-5p may be accomplished through AMPK. Thus, miR-296-5p may improve the secretion of autophagic mediators by activating AMPK/ULK1 expression in fluorosis, suggesting that miR-296-5p, AMPK/ULK1 may be potential therapeutic targets under the higher fluoride stimulation.

Advances in Molecular Pathology of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade.

Micro two-dimensional slit-array for super resolution beyond pixel Nyquist limits in grating spectrometers.

This paper presents a new micro 2-D slit-array device for spectral resolution enhancement in grating spectrometers. The 2-D slit-array is encoded in Hadamard matrix and the device is fabricated based on the micro-electromechanical system (MEMS) technology. By just using this 2-D slit-array to replace the single slit in the conventional grating spectrometer, real-time super spectral resolution detection beyond the pixel Nyquist limit, which is determined by the size of the detector pixel, can be realized. Furthermore, no other configuration of the spectrometer is changed, no movable parts are used, and the spectral range and instrument size remain almost unchanged while the resolution is improved. A series of experimental verifications for the feasibility of this design are included in this work.

The Effect of National Health Service Corps Clinician Staffing on Medical and Behavioral Health Care Costs in Community Health Centers.

OBJECTIVE: Prior studies of community health centers (CHCs) have found that clinicians supported by the National Health Service Corps (NHSC) provide a comparable number of primary care visits per full-time clinician as non-NHSC clinicians and provide more behavioral health care visits per clinician than non-NHSC clinicians. This present study extends prior research by examining the contribution of NHSC and non-NHSC clinicians to medical and behavioral health costs per visit. METHODS: Using 2013-2017 data from 1022 federally qualified health centers merged with the NHSC participant data, we constructed multivariate linear regression models with health center and year fixed effects to examine the marginal effect of each additional NHSC and non-NHSC staff full-time equivalent (FTE) on medical and behavioral health care costs per visit in CHCs. RESULTS: On average, each additional NHSC behavioral health staff FTE was associated with a significant reduction of 3.55 dollars of behavioral health care costs per visit in CHCs and was associated with a larger reduction of 7.95 dollars in rural CHCs specifically. In contrast, each additional non-NHSC behavioral health staff FTE did not significantly affect changes in behavioral health care costs per visit. Each additional NHSC primary care staff FTE was not significantly associated with higher medical care costs per visit, while each additional non-NHSC clinician contributed to a slight increase of $0.66 in medical care costs per visit. CONCLUSIONS: Combined with previous findings on productivity, the present findings suggest that the use of NHSC clinicians is an effective approach to improving the capacity of CHCs by increasing medical and behavioral health care visits without increasing costs of services in CHCs, including rural health centers.

Alternative Approaches to Ensuring Adequate Nurse Staffing: The Effect of State Legislation on Hospital Nurse Staffing.

OBJECTIVE: The objective of this study was to addresses the basic question of whether alternative legislative approaches are effective in encouraging hospitals to increase nurse staffing. METHODS: Using 16 years of nationally representative hospital-level data from the American Hospital Association (AHA) annual survey, we employed a difference-in-difference design to compare changes in productive hours per patient day for registered nurses (RNs), licensed practical/vocational nurses (LPNs), and nursing assistive personnel (NAP) in the state that mandated staffing ratios, states that legislated staffing committees, and states that legislated public reporting, to changes in states that did not implement any nurse staffing legislation before and after the legislation was implemented. We constructed multivariate linear regression models to assess the effects with hospital and year fixed effects, controlling for hospital-level characteristics and state-level factors. RESULTS: Compared with states with no legislation, the state that legislated minimum staffing ratios had an 0.996 (P<0.01) increase in RN hours per patient day and 0.224 (P<0.01) increase in NAP hours after the legislation was implemented, but no statistically significant changes in RN or NAP hours were found in states that legislated a staffing committee or public reporting. The staffing committee approach had a negative effect on LPN hours (difference-in-difference=-0.076, P<0.01), while the public reporting approach had a positive effect on LPN hours (difference-in-difference=0.115, P<0.01). There was no statistically significant effect of staffing mandate on LPN hours. CONCLUSIONS: When we included California in the comparison, our model suggests that neither the staffing committee nor the public reporting approach alone are effective in increasing hospital RN staffing, although the public reporting approach appeared to have a positive effect on LPN staffing. When we excluded California form the model, public reporting also had a positive effect on RN staffing. Future research should examine patient outcomes associated with these policies, as well as potential cost savings for hospitals from reduced nurse turnover rates.

Downregulated hypoxia-inducible factor 1α improves myoblast differentiation under hypoxic condition in mouse genioglossus.

The treatment of obstructive sleep apnea-hypopnea syndrome targets the narrow anatomic structure of the upper airway (UA) and lacks an effective therapy for UA dilator muscle dysfunction. Long-term hypoxia can cause damage to UA dilator muscles and trigger a vicious cycle. We previously confirmed that hypoxia-inducible factor 1α (HIF-1α) upregulation mediates muscle fatigue in hypoxia condition, but the underlying mechanism remains to be determined. The present study investigated the intrinsic mechanisms and related pathways of HIF-1α that affect myoblast differentiation, with an aim to search for compounds that have protective effects in hypoxic condition. Differentiation of myoblasts was induced under hypoxia, and we found that hypoxia significantly inhibits the differentiation of myoblasts, damages the ultrastructure of mitochondria, and reduces the expression of myogenin, PGC-1ß and pAMPKα1. HIF-1α has a negative regulation effect on AMPK. Downregulation of HIF-1α increases the expression of the abovementioned proteins, promotes the differentiation of myoblasts, and protects mitochondrial integrity. In addition, mitochondrial biogenesis occurs during myogenic differentiation. Inhibition of the AMPK pathway inhibits mitochondrial biogenesis, decreases the level of PGC-1ß, and increases apoptosis. Resveratrol dimer can reverse the mitochondrial damage induced by AMPK pathway inhibition and decrease myoblast apoptosis. Our results provided a regulatory mechanism for hypoxic injury in genioglossus which may contribute to the pathogenesis and treatment of OSAHS.

General practitioner trainees' career perspectives after COVID-19: a qualitative study in China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been a worldwide public health emergency that has put great pressure on medical workers and the medical system. General Practitioners (GPs) played an important role in controlling the epidemic, and GP trainees also took an active part in this approach. This study was to explore Chinese GP trainees' career perspectives after COVID-19. METHODS: We conducted a qualitative research study which included 12 GP trainees from three teaching hospitals in China. Semi-structured telephone interviews were conducted. Grounded theory and thematic analysis were used to code the data and identify categories and factors. RESULTS: Eleven participants chose to continue a GP career after COVID-19, and nearly half of the participants strengthened their determination to dedicate themselves to this career. Only one participant decided to change the career choice because of interest in another specialty. Four main themes influencing GP trainees' perceptions of career development after COVID-19 emerged from the interviews: changes of GPs' work content in COVID-19, challenges of being a GP, psychological changes of the career, how to provide better primary care. Although some negative psychological changes existed, most of participants were inspired by role models and medical colleagues. They had more in-depth understanding of GPs' role and responsibility during COVID-19, and exhibited intensions for self-improvement in career development, especially in public health education and self-protection in preventing infectious diseases. In addition, the wide use of telemedicine provided a new work way for GP trainees. However, challenges, such as increased workloads, low income, lack of resources in primary medical institutions, and distrust of GPs are faced by trainees during the outbreak. CONCLUSIONS: Overall, no substantial changes were seen in the career choice of GP trainees after COVID-19 outbreak. However, they were inspired and had an in-depth understanding about the GP's work and responsibility during an epidemic. Owing to the challenges faced by the GPs, measures are needed to improve the GP education and work environment in the training phase.

IgG4-related fibrosing mediastinitis: clinical presentation, treatment efficacy and comparison with IgG4-RD without fibrosing mediastinitis.

OBJECTIVES: This study aimed to investigate the clinical characteristics and treatment efficacy of immunoglobulin G4 (IgG4)-related fibrosing mediastinitis (IgG4-RFM) and to compare IgG4-RFM patients with IgG4-related disease (IgG4-RD) patients without fibrosing mediastinitis (FM). METHODS: Twenty IgG4-RFM patients and 60 randomly matched IgG4-RD patients without FM from a prospective cohort at the Peking Union Medical College Hospital (PUMCH) were enrolled from 2011 to 2019. Patient demographic data, clinical characteristics, laboratory parameters and treatment efficacy were analysed. RESULTS: The prevalence of IgG4-RFM in our cohort was 2.8%. The average age was 51.7±14.8 years, and the patients were predominantly male (60.0%). Periaortic masses (75.0%) and paravertebral masses (35.0%) were the most common characteristic imaging findings of IgG4-RFM. Compared with male patients with IgG4-RFM, a lower percentage of female patients had abdominal aorta involvement (p=0.015). IgG4-RFM patients had a shorter disease duration; lower percentage of allergy history, submandibular gland involvement, and pancreas involvement; lower serum IgG4; higher erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hsCRP) levels; and a higher percentage of single organ involvement than patients without FM (p<0.001, p=0.008, p=0.033, p=0.001, p=0.027, p=0.007, p=0.004 and p=0.047, respectively). After treatment, 94.7% of patients achieved a mediastinal soft tissue reduction of >30%. CONCLUSIONS: IgG4-RFM is a distinct fibrotic subtype of IgG4-RD. Periaortic masses and paravertebral masses were the most common characteristic imaging findings of IgG4-RFM. Most IgG4-RFM patients respond well to glucocorticoid (GC) and immunosuppressant treatments.

Performance of China's new medical licensing examination for rural general practice.

BACKGROUND: To evaluate the performance of China's new medical licensing examination (MLE) for rural general practice, which determines the number of qualified doctors who can provide primary care for China's rural residents, and to identify associated factors. METHODS: Data came from all 547 examinees of the 2017 MLE for rural general practice in Hainan province, China. Overall pass rates of the MLE and pass rates of the MLE Step 1 practical skills examination and Step 2 written exam were examined. Chi-square tests and multivariable logistic regression were used to identify examinee characteristics associated with passing Step 1 and Step 2, respectively. RESULTS: Of the 547 examinees, 68% passed Step 1, while only 23% of Step 1 passers passed Step 2, yielding an 15% (82 of 547) overall pass rate of the whole examination. Junior college medical graduates were 2.236 (95% CI, 1.127-4.435) times more likely to pass Step 1 than secondary school medical graduates. Other characteristics, including age, gender, forms of study and years of graduation, were also significantly associated with passing Step 1. In contrast, examinees' vocational school major and Step 1 score were the only two significant predictors of passing Step 2. CONCLUSIONS: Our study reveals a low pass rate of China's new MLE for rural general practice in Hainan province, indicating a relatively weak competency of graduates from China's alternative medical education. An effective long-term solution might be to improve examinees' clinical competency through mandating residency training for graduates of China's alternative medical education.

The role of chlorine atom on the binding between 2-phenyl-1H-benzimidazole analogues and fat mass and obesity-associated protein.

In this work, nine 2-phenyl-1H-benzimidazole structural analogues were screened for potential inhibitor of the fat mass and obesity-associated protein (FTO) by isothermal titration calorimetry (ITC). The results show that the binding between 6-chloro-2-phenyl-1H-benzimidazole (1d) and FTO was dominated by entropy. Results of enzymatic activity assays provided an IC50 value of 24.65 µM for 1d. Our previous results and comparison of nine structural analogues indicated that the chlorine atom was crucial for the binding of small molecules with FTO. The identification of novel small molecules may provide information for the design of FTO inhibitors and the treatment of leukemia.

Identification of Clausine E as an inhibitor of fat mass and obesity-associated protein (FTO) demethylase activity.

The alkaloids containing a carbazole nucleus are an established class of natural products with wide range of biological activities. A combination of thermodynamic and enzymatic activity studies provides an insight into the recognition of Clausine E by the fat mass and obesity-associated protein (FTO). The binding of Clausine E to FTO was driven by positive entropy and negative enthalpy changes. Results also indicated that the hydroxyl group was crucial for the binding of small molecules with FTO. The structural and thermodynamic information provides the basis for the design of more effective inhibitors for FTO demethylase activity.