Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa

GluR5-containing kainate receptors (KARs) are known to be involved in nociceptive transmission. Our previous work has shown that the activation of presynaptic KARs regulates GABAergic and glycinergic synaptic transmission in cultured dorsal horn neurons. However, the role of GluR5-containing KARs in the modulation of inhibitory transmission in the spinal substantia gelatinosa (SG) in slices remains unknown. In the present study, pharmacological, electrophysiological and genetic methods were used to show that presynaptic GluR5 KARs are involved in the modulation of inhibitory transmission in the SG of spinal slices in vitro. The GluR5 selective agonist, ATPA, facilitated the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) in SG neurons. ATPA increased sIPSC frequency in all neurons with different firing patterns as delayed, tonic, initial and single spike patterns. The frequency of either GABAergic or glycinergic sIPSCs was significantly increased by ATPA. ATPA could also induce inward currents in all SG neurons recorded. The frequency, but not amplitude, of action potential-independent miniature IPSCs (mIPSCs) was also facilitated by ATPA in a concentration-dependent manner. However, the effect of ATPA on the frequency of either sIPSCs or mIPSCs was abolished in GluR5(-/- )mice. Deletion of the GluR5 subunit gene had no effect on the frequency or amplitude of mIPSCs in SG neurons. However, GluR5 antagonist LY293558 reversibly inhibited sIPSC and mIPSC frequencies in spinal SG neurons. Taken together, these results suggest that GluR5 KARs, which may be located at presynaptic terminals, contribute to the modulation of inhibitory transmission in the SG. GluR5-containing KARs are thus important for spinal sensory transmission/modulation in the spinal cord

Metabolomics analysis of stool in rats with type 2 diabetes mellitus after single-anastomosis duodenal–ileal bypass with sleeve gastrectomy

BackgroundSingle-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is one of the most effective bariatric procedures in the treatment of type 2 diabetes mellitus (T2DM). However, the mechanisms by which SADI-S improves T2DM are not well-known.ObjectiveTo explore the effects of SADI-S on metabolites in the stool of rats with T2DM.MethodsTwenty rats were fed on high-fat diet and administered with a low-dose (30mg/kg) of streptozotocin to establish T2DM models. The rats were then randomly assigned to the SADI-S group (n=10) and sham operation group (n=9). Stool samples were collected from all rats at 8 weeks after surgery and stored at -80 °C. Metabolomics analysis was performed to identify differential metabolites through ultra- performance liquid chromatography-mass spectrometry.ResultsAt 8-week after surgery, rats of the SADI-S group showed significantly decreased fasting blood glucose, glucose tolerance test 2-hour, glycated haemoglobin, and body weight compared with those of the sham group. A total of 245 differential metabolites were identified between the two groups, among which 8 metabolites were detectable under both the positive ion model and negative ion model. Therefore, a total of 237 differential metabolites were identified in our study which were mainly involved in tryptophan metabolism; cysteine and methionine metabolism; phenylalanine metabolism; phenylalanine; tyrosine and tryptophan biosynthesis; arginine biosynthesis; alanine, aspartate and glutamate metabolism; Arginine and proline metabolism; glyoxylate and dicarboxylate metabolism; alpha-Linolenic acid metabolism; Linoleic acid metabolism; riboflavin metabolism; nicotinate and nicotinamide metabolism; pyrimidine metabolism; porphyrin and chlorophyll metabolism.ConclusionSADI-S significantly improved the glucose metabolism in T2DM rats. In addition, SADI-S significantly changed the composition of metabolites in T2DM rats which were involved in tryptophan metabolism pathway, linoleic acid metabolism pathway and so on. This may be the mechanism by which SADI-S improved T2DM

Cumulative exposure to remnant cholesterol and the risk of fragility fractures: a longitudinal cohort study

ObjectiveTo investigate the association between cumulative remnant cholesterol (cumRC) and the risk of new-onset fragility fractures.MethodsThis study included individuals who participated in the 2006, 2008, and 2010 Kailuan health examinations. Baseline characteristics were compared between groups according to cumRC quartiles. The incidence density was calculated, and the log-rank test was used to compare the cumulative incidence. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI), and restricted cubic spline was used to examine the possibly non-linear relation between cumRC and the risk of fragility fractures. Additional analyses were performed with stratification by age (≥ or <65 years).ResultsA total of 43,839 individuals were included in this study. During the median follow-up period of 10.97 years, a total of 489 fragility fractures occurred. Multivariable Cox proportional hazards regression model 3 showed that the Q1 and Q4 groups versus the Q2 group were associated with a higher HR of fragility fracture (HR 1.61, 95% CI: 1.23–2.11; HR 1.38, 95% CI: 1.06–1.81), and restricted cubic spline regression analysis showed a non-linear relationship between cumRC level and the risk of fragility fractures (POverall association < 0.001, PNon-linear association = 0.001). The association was significant in the age group <65 years but not in the age group ≥65 years. The sensitivity analyses were consistent with the main results.ConclusionsBoth too high and too low cumRC levels were associated with a greater risk of fragility fractures, and this association was more significant in young and middle-aged people

Energy Sustainability of Rural Residential Buildings with Bio-Based Building Fabric in Northeast China

Due to the cold winters in northeast China, the energy consumption of the rural residential buildings is much higher in this region than in other regions. In this study, the energy sustainability of bio-based wall construction is examined through applications in rural residential buildings. Comparisons of the energy sustainability of the bio-based wall constructions and the conventional wall constructions are evaluated using IESVE-2019 computational simulation. The results show notable reductions in heating energy requirements and coal use, which is the major heating source for rural residential buildings in China. The results show that reductions of 45.82–204.07 kWh/m2/year in heating energy requirements and more than 40% in coal use are possible through application of bio-based wall constructions. The application of bio-based wall construction will result in lower seasonal air pollution and coal use through straw burning in northeast China

A rare earth metal catalyzed aerobic dehydrogenation of N-heterocycles

Rare earth metals exhibit high catalytic activity and selectivity in various organic reactions due to their unique electronic properties. Among them, praseodymium has shown high catalytic activity under mild reaction conditions compared with transitional metals. Here, we report a strategy of Pr-catalyzed aerobic dehydrogenative aromatization of saturated N-heterocycles to produce 7 classes of products with a broad substrate scope.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Nanyang Technological UniversitySubmitted/Accepted versionWe thank the financial support from the Start-up Grant of Nanjing Tech University (Nos. 38274017103, 38037037). T.-P.L. thanks the financial support from Distinguished University Professor grant (Nanyang Technological University), AcRF Tier 1 grants from the Ministry of Education of Singapore (RG 107/19, RG 11/20 and RT 14/20), and the Agency for Science, Technology and Research (A*STAR) under its MTC Individual Research Grants (M21K2c0114)