Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo.

The serotonergic system plays important roles in both physiological and pathological processes, and is a therapeutic target for many psychiatric disorders. Although several genetically encoded GFP-based serotonin (5-HT) sensors were recently developed, their sensitivities and spectral profiles are relatively limited. To overcome these limitations, we optimized green fluorescent G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB5-HT) sensors and developed a red fluorescent GRAB5-HT sensor. These sensors exhibit excellent cell surface trafficking and high specificity, sensitivity and spatiotemporal resolution, making them suitable for monitoring 5-HT dynamics in vivo. Besides recording subcortical 5-HT release in freely moving mice, we observed both uniform and gradient 5-HT release in the mouse dorsal cortex with mesoscopic imaging. Finally, we performed dual-color imaging and observed seizure-induced waves of 5-HT release throughout the cortex following calcium and endocannabinoid waves. In summary, these 5-HT sensors can offer valuable insights regarding the serotonergic system in both health and disease.

Diversity-oriented synthesis of marine polybrominated diphenyl ethers as potential KCNQ potassium channel activators.

Natural polybrominated diphenyl ethers, often isolated from marine sponges, have been reported to possess various biological activities, such as antibacterial, antioxidant and antidiabetic effects. Via a high throughput screening of our marine natural product library, the polybrominated diphenyl ether 3 was found to display a KCNQ potassium channel activation effect. To obtain more compound 3 related natural products and their derivatives for further bioactivity study, a diversity-oriented synthesis was conducted, leading to the successful synthesis of five polybrominated diphenyl ether natural products (1-4, 6) and 30 new derivatives. Compound 3 was found to preferentially potentiate KCNQ1 potassium channel, whereas 17h relatively activated KCNQ2 potassium channel. The structure-activity relationship was analyzed assisted by molecular docking and 17h was further conducted for its agonistic mechanism study on KCNQ2 channel. This research work may give an insight for the discovery of marine polybrominated diphenyl ether derived new drug leads.

[Prevalence of central obesity among floating population employment in 5 surveillance sites of Xinjiang Uygur Autonomous Region in 2012].

OBJECTIVE: To investigate the prevalence of central obesity among different gender and age groups of floating population employment in 5 surveillance sites of Xinjiang Uygur Autonomous Region. METHODS: 1491 floating population aged > 18 years old were selected through multistage clustering sampling method, stratified by 6 major industries in5 sites of Xinjiang Uygur Autonomous Region( Xinhe County, Yining County, Tianshan District, Hetian County and Kashi City) in 2012. Unified questionnaire( including basic information, behavioral risk factors, etc. ), designed by China CDC, were used to collect information by face-to-face interviews. Height, weight and waist circumference were measured by unified equipment. RESULTS: The average age was( 35. 73 ± 11. 61) years old. Male and female accounted for 48. 02%( 716/1491) and 51. 98%( 775/1491)each. Han, Uygur and other ethnic group accounted for 75. 59%( 1127/1491), 18. 31%( 273/1491) and 6. 10%( 91/1491). The prevalence of central obesity was 25. 62%( 382/1491) of floating population in 5 surveillance sites of Xinjiang Uygur Autonomous Region, 50-59 years age group( 45. 63%) and the obese group( 86. 15%) in BMI were the highest prevalence of central obesity. There was statistical significance on prevalence of central obesity in different age groups floating population( χ~2= 77. 295, P <0. 001), and in different BMI groups floating population( χ~2= 648. 619, P < 0. 001). CONCLUSION: Floating population aged 50-59 years old and obese in BMI of Xinjiang Uygur Autonomous Region were key groups for prevention and control of central obesity.

An Analysis of Injury Trends and Disease Burden From Three Surveillance Hospitals in Urumqi From 2006 to 2018.

Objective: To investigate injury trends, injury distribution, and disease burden from three surveillance hospitals in Urumqi from 2006 to 2018. Method: Injury data from the National Injury Surveillance System (NISS) from three hospitals in Urumqi (2006 to 2018) were collected to analyze changes in the characteristics of outpatient injury cases. Years of potential life lost (YPLL) were calculated to determine the disease burden of the injury cases. Results: A total of 161,400 injury cases were recorded over 13 years, and the average age of the patient seeking medical attention was 32.4 years old. Male patients outnumbered female patients with a ratio of 1.6:1, but the proportion of female patients was greater after 45 years of age. The highest number of cases occurred in patients 15-29 years of age, accounting for 26.8% of all injury cases. Injury in females occurred most frequently in the home. A total of 41.4% of injury cases occurred while doing housework. The top three causes of injury were falls (49.7%), blunt force of an object, (13.7%), and motor vehicle accidents (MVA) (13.5%). Years of potential life lost from injury accounted for 7.39% of the total YPLL in the three hospitals. Conclusion: Males should be targeted for injury prevention and intervention in Urumqi. The prevention of falls, blunt force of objects, and MVA should be made a priority. Injury prevention strategies and targeted projects should be developed to reduce the disease burden of injury.