Zgg

Various adenosine receptor nucleoside-like ligands were found to modulate ATP hydrolysis by the multidrug transporter ABCG2. Both ribose-containing and rigidified (N)-methanocarba nucleosides (C2-, N6- and 5'-modified), as well as adenines (C2-, N6-, and deaza modified), were included. 57 compounds out of 63 tested either stimulated (50) or inhibited (7) basal ATPase activity. Structure-activity analysis showed a separation of adenosine receptor and ABCG2 activities. The 7-deaza modification had favorable effects in both (N)-methanocarba nucleosides and adenines. Adenine 37c (MRS7608) and (N)-methanocarba 7-deaza-5'-ethyl ester 60 (MRS7343) were found to be potent stimulators of ABCG2 ATPase activity with EC50 values of 13.2 ± 1.7 and 13.2 ± 2.2 nM, respectively. Both had affinity in the micromolar range for A3 adenosine receptor and lacked the 5'-amide agonist-enabling group (37c was reported as a weak A3 antagonist, Ki 6.82 μM). Compound 60 significantly inhibited ABCG2 substrate transport (IC50 0.44 μM). Docking simulations predicted the interaction of 60 with 21 residues in the drug-binding pocket of ABCG2.

Objective: The variety and use of technologies used in vestibular rehabilitation are very limited. The purpose of this study was to investigate the effects of a Web-based system on vestibular rehabilitation in patients with vestibular hypofunction. Design: A total of 20 patients with unilateral vestibular hypofunction were randomly assigned to two groups. Conventional vestibular rehabilitation was applied to the control group, whereas the study group received treatment with the Web-based system supporting the vestibulo-ocular reflex with oculomotor and optokinetic stimulus (Simulation of Vestibulo-Ocular Reflex Exercises). Vestibular and balance tests, oculomotor level, the Tampa Kinesiophobia Scale, and the Dizziness Handicap Inventory were used to evaluate the treatment's efficacy. Results: Vestibular symptoms and findings, balance tests, oculomotor functions, Tampa Kinesiophobia Scale, and Dizziness Handicap Inventory improved significantly in both groups after the interventions (P < 0.05). In the intergroup analysis, improvement was found in eyes closed Romberg, semitandem, and left one-foot position balance tests in favor of the study group (P < 0.05). Conclusion: The new vestibular technology, Simulation of Vestibulo-Ocular Reflex Exercises, was found to be effective in vestibular rehabilitation. Trial registration: ClinicalTrials.gov NCT04133025.

This research project was designed to study the residues of OCPs (organochlorine pesticides) in the sediments of the Meijiang River Basin. Samples from the Meijiang River Basin were analyzed by gas chromatography-mass spectrometry after being pretreated by Soxhlet extraction, and their compositions, distributions and sources were evaluated. The current study presents the distribution of OCPs in the soils and sediments of the Meijiang River Basin. The results demonstrate that OCPs contamination is an important environmental concern due to the excessive use of these compounds in the agricultural and industrial sectors. The ratios of α-HCH/γ-HCH, (DDE + DDD)/∑DDTs, p,p-DDT/o,p-DDT, and DDD/DDE were used as indices for identifying the possible pollution sources and assessing the decomposition of the parent compounds and the recent γ-HCH and DDT inputs. At the XY (Xiyang) and DSGYY (Dongshenggongyeyan) sites, the pollutants had industrial origins. At other sites (QTH (Qutianhu), LXC (Longxichun), ZJC (Zhenjiaochun), HKC (Hekouchun), GS (Guangshan) and RGQ (Raogongqiao)), the pollution was caused by dissolved organic matter. The SHB site was polluted by transportation and upstream pollutants. At the SXC (Shixichun), YZX (Youzhihe), DSH (Dongshihe) and ZGG (Zhegupai) sites, the metabolite was p,p'-DDD and was produced in an environment with anaerobic conditions. At the FJC (Fujiangkou), QTH (Qiutianhu), GS (Guangshang) and MX (Meixi) sites, the metabolite was DDE and was produced under aerobic conditions. In view of the health risks, the risk quotients for these contaminants were evaluated, and all risk quotients were less than 1 under the best-case scenario. This result suggests that the investigated pollutants may pose little hazard to the local ecosystem. The sediments containing toxic pesticides had a less than 55% ecological risk, indicating that the ecological risk of HCHs in the soils from the Meijiang River Basin is low.