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Monoacylglycerol lipase (MAGL) is a 33 kDa serine protease primarily responsible for hydrolyzing 2-arachidonoylglycerol into the proinflammatory eicosanoid precursor arachidonic acid in the central nervous system. Inhibition of MAGL constitutes an attractive therapeutic concept for treating psychiatric disorders and neurodegenerative diseases. Herein, we present the design and synthesis of multiple reversible MAGL inhibitor candidates based on a piperazinyl azetidine scaffold. Compounds 10 and 15 were identified as the best-performing reversible MAGL inhibitors by pharmacological evaluations, thus channeling their radiolabeling with fluorine-18 in high radiochemical yields and favorable molar activity. Furthermore, evaluation of [18F]10 and [18F]15 ([18F]MAGL-2102) by autoradiography and positron emission tomography (PET) imaging in rodents and nonhuman primates demonstrated favorable brain uptakes, heterogeneous radioactivity distribution, good specific binding, and adequate brain kinetics, and [18F]15 demonstrated a better performance. In conclusion, [18F]15 was found to be a suitable PET radioligand for the visualization of MAGL, harboring potential for the successful translation into humans.

Aims Type 2 diabetes mellitus (T2DM) is now very prevalent in China. Due to the lower rate of controlled diabetes in China compared to that in developed countries, there is a higher incidence of serious cardiovascular complications, especially acute coronary syndrome (ACS). The aim of this study was to establish a potent risk predictive model in the economically disadvantaged northwest region of China, which could predict the probability of new-onset ACS in patients with T2DM. Methods Of 456 patients with T2DM admitted to the First Affiliated Hospital of Xi’an Jiaotong University from January 2018 to January 2019 and included in this study, 270 had no ACS, while 186 had newly diagnosed ACS. Overall, 32 demographic characteristics and serum biomarkers of the study patients were analysed. The least absolute shrinkage and selection operator regression was used to select variables, while the multivariate logistic regression was used to establish the predictive model that was presented using a nomogram. The area under the receiver operating characteristics curve (AUC) was used to evaluate the discriminatory capacity of the model. A calibration plot and Hosmer–Lemeshow test were used for the calibration of the predictive model, while the decision curve analysis (DCA) was used to evaluate its clinical validity. Results After random sampling, 319 and 137 T2DM patients were included in the training and validation sets, respectively. The predictive model included age, body mass index, diabetes duration, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol, serum uric acid, lipoprotein(a), hypertension history and alcohol drinking status as predictors. The AUC of the predictive model and that of the internal validation set was 0.830 [95% confidence interval (CI) 0.786–0.874] and 0.827 (95% CI 0.756–0.899), respectively. The predictive model showed very good fitting degree, and DCA demonstrated a clinically effective predictive model. Conclusions A potent risk predictive model was established, which is of great value for the secondary prevention of diabetes. Weight loss, lowering of SBP and blood uric acid levels and appropriate control for DBP may significantly reduce the risk of new-onset ACS in T2DM patients in Northwest China.

// Qingbin Zhao 1 , Huiyi Wei 1 , Dandan Liu 2 , Baolan Shi 3 , Lei Li 3 , Mengdan Yan 4 , Xiyang Zhang 5 , Fengjiao Wang 5 , Yongri Ouyang 4 1 Department of Geratology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, China 2 Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, China 3 Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010050, China 4 School of Life Science, Northwest University, Xi’an, Shaanxi, 710069, China 5 Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi 710075, China Correspondence to: Qingbin Zhao, email: zhaoqingbin8244693@163.com Keywords: coronary artery disease (CAD), single nucleotide polymorphism (SNP), PHACTR1, SLC22A3, case-control study Received: September 22, 2016 Accepted: November 12, 2016 Published: November 22, 2016 ABSTRACT Previous studies showed that PHACTR1 and SLC22A3 are involved in coronary vascular development and are key determinants of cardiovascular disease risk. We conducted a case-control study to examine the effect of SLC22A3 and PHACTR1 single nucleotide polymorphisms (SNPs) on CAD risk among 376 male CAD patients and 388 male healthy controls from China. Eleven SLC22A3 and PHACTR1 SNPs were selected and genotyped using Sequenom Mass-ARRAY technology. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age. The rs9381439 minor allele “A” (OR = 0.72; 95% CI = 0.54–0.96; p = 0.024) in an allelic model was associated with reduced CAD risk, as were the rs2048327 “C/C” (OR = 0.60; 95% CI: 0.37–0.97; p = 0.036) and rs1810126 “T/T” (OR = 0.58; 95% CI: 0.36–0.93; p = 0.024) genotypes. Likewise, the rs9349379 “A/G” genotype in a dominant model ( p = 0.041), the rs1810126 “T/C” genotype in additive ( p = 0.041) and recessive ( p = 0.012) models, and the rs2048327 “C/T” genotype in a recessive model were associated with decreased CAD risk ( p = 0.016). These results suggest several PHACTR1 and SLC22A3 polymorphisms are associated with decreased CAD risk in the male Chinese Han population.

// Qingbin Zhao 1 , Shudan Liao 2 , Huiyi Wei 1 , Dandan Liu 3 , Jingjie Li 4,5 , Xiyang Zhang 5 , Mengdan Yan 4,5 and Tianbo Jin 4,5 1 Department of Geratology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China 2 Department of Cardiology, Xi’an Center Hospital, Xi’an, Shaanxi, China 3 Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China 4 Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi’an, Shaanxi, China 5 Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi, China Correspondence to: Qingbin Zhao, email: // Keywords : coronary heart disease; single nucleotide polymorphisms; CDKN2BAS; case-control,Gerotarget Received : September 01, 2016 Accepted : October 05, 2016 Published : October 11, 2016 Abstract The goal of our study was to determine whether CDKN2BAS polymorphisms are associated with coronary heart disease (CHD) risk in a Han Chinese population. Eight SNPs were genotyped in 676 men and 465 women. We used χ 2 tests and genetic model analyses to evaluate associations between the SNPs and CHD risk. We found that rs10757274 was associated with an increased risk of CHD in both men (allele G: Odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.05-1.61, P = 0.018; codominant model: P = 0.042; recessive model: OR = 1.70, 95% CI: 1.10-2.62, P = 0.016; log-additive model: OR = 1.34, 95% CI: 1.05-1.71, P = 0.019) and women (dominant model: OR = 2.26, 95% CI: 1.28-3.99, P = 0.004). In addition, rs7865618 was associated with an 8.10-fold increased risk of CHD in women under a recessive model (OR = 8.10, 95% CI: 1.74-37.68, P = 0.006). Interestingly, the haplotype AA (rs10757274 and rs1333042) of CDKN2BAS was associated with decreased the risk of CHD in men (OR = 0.72, 95% CI: 0.55 - 0.95, P = 0.022).