Taurocholic acid ameliorates hypertension through the activation of TGR5 in the hypothalamic paraventricular nucleus.

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.

Can three-dimensional nitrate structure be reconstructed from surface information with artificial intelligence? - A proof-of-concept study.

Nitrate is one of the essential variables in the ocean that is a primary control of the upper ocean pelagic ecosystem. Its three-dimensional (3D) structure is vital for understanding the dynamic and ecosystem. Although several gridded nitrate products exist, the possibility of reconstructing the 3D structure of nitrate from surface data has never been exploited. In this study, we employed two advanced artificial intelligence (AI) networks, U-net and Earthformer, to reconstruct nitrate concentration in the Indian Ocean from surface data. Simulation from an ecosystem model was utilized as the labeling data to train and test the AI networks, with wind vectors, wind stress, sea surface temperature, sea surface chlorophyll-a, solar radiation, and precipitation as the input. We compared the performance of two networks and different pre-processing methods. With the input features decomposed into climatology and anomaly components, the Earthformer achieved optimal reconstruction results with a lower normalized mean square error (NRMSE = 0.1591), spatially and temporally, outperforming U-net (NRMSE = 0.2007) and the climatology prediction (NRMSE = 0.2089). Furthermore, Earthformer was more capable of identifying interannual nitrate anomalies. With a network interpretation technique, we quantified the spatio-temporal importance of every input feature in the best case (Earthformer with decomposed inputs). The influence of different input features on nitrate concentration in the adjacent Java Sea exhibited seasonal variation, stronger than the interannual one. The feature importance highlighted the role of dynamic factors, particularly the wind, matching our understanding of the dynamic controls of the ecosystem. Our reconstruction and network interpretation technique can be extended to other ecosystem variables, providing new possibilities in studies of marine environment and ecology from an AI perspective.

Corrosion Resistance and Thermal Conductivity Enhancement of Reduced Graphene Oxide-BaSO4-Epoxy Composites.

The results of studies on the corrosion protectiveness and thermal conductivity of reduced graphene oxide-BaSO4 epoxy composites are reported here. A commercial epoxy resin and reduced graphene oxide (rGO) were blended with a hardening reagent and then mixed with prepared BaSO4-epoxy resin (B-epoxy). The reduced graphene oxide-BaSO4-epoxy composite (rGO-B-epoxy) paste was used to coat the surfaces of Al 7205 alloy and the corrosion and thermal properties were investigated. A corrosion test in a 3.5 wt% synthetic sea water solution showed that the composite coating containing BaSO4 had the best corrosion resistance. Moreover, the rGO-B-epoxy composite showed better protection against corrosion than the epoxy alone. The rGO-B-epoxy composite with 5 wt% BaSO4 had an in-plane coefficient of thermal conductivity of approximately 165.0 W/m K, and the in-plane thermal diffusivity was 71.38 mm2/s. In standard thermal conductivity tests, all three samples had values below 40 W/m K. The rGO-B-epoxy composites showed good surface corrosion protection and in-plane thermal conductivity.

Oxidation Behavior Characterization of Zircaloy-4 Cladding with Different Hydrogen Concentrations at 500-800 °C in an Ambient Atmosphere.

This study simulated the after-burned zirconium cladding oxidation in air at temperatures between 500 and 800 °C. The weight changes of Zircaloy-4 cladding with hydrogen contents of 100-1000 ppm continuously measured through thermogravimetric analysis (TGA) during oxidation tests at different temperatures in an air atmosphere. The TGA results indicate a transition of oxidation kinetics from a parabolic rate law to a linear rate law for as-received and hydrided Zircaloy-4 cladding. The hydrogen concentration of Zircaloy-4 had a marked effect on its pre-transition oxidation in air between 500 and 800 °C. For all samples, the linear oxidation (post transition stage) at 650 °C, which is the critical oxidation temperature, displays a similar trend. In addition, scanning electron microscopy and transmission electron micros-copy examinations indicated the presence of a few and numerous discontinuous micro-cracks in the oxide layer in the pre-transition and post-transition stages, respectively.

Increasing fragmentation and squeezing of coastal wetlands: Status, drivers, and sustainable protection from the perspective of remote sensing.

Coastal wetlands are of great ecological and economic value but face significant degradation and losses because of human activities. Nevertheless, the changes in spatiotemporal landscape patterns, which have occurred as a result of coastal wetland losses, have not been well documented under the rapid urbanization in coastal zones. In this study, an algorithm based on periodic tidal inundations and full time-series indices was developed to map the detailed status and trends in the coastal wetlands in Fujian Province from 1994 to 2018 by using more than archived 5000 Landsat images. The results showed that in 2018, there were 1136.56 km2 of coastal wetlands along the coast of Fujian with an overall accuracy of 95.63%, which were mainly distributed in estuaries and bays. These coastal wetlands consisted of tidal flats, low marshes, and high marshes with proportions of 84.91%, 13.05%, and 2.04%, respectively. An unprecedented loss of coastal wetlands has occurred in Fujian Province, with an annual rate of 15.44 km2/a from 1994 to 2018. Many coastal wetlands were reclaimed, dredged, and converted into inland areas for aquaculture ponds, ports, and built-up areas in different urbanization periods, which has led to a great loss of coastal spaces with an area of 476.87 km2. The interplay between the loss of coastal wetlands and seaward urbanization will lead to severe fragmentation and squeezing effects in the coastal zone and will weaken the coastal protection from marine disasters that is provided by coastal wetlands. Therefore, we conceived two conceptional frameworks for sustainable coastal protection based on the current situations of the coastal communities to provide a trade-off between economic development and the protection of coastal developing countries in the world.

A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants.

In this study, a series of salicylic acid derivatives were designed and synthesized as novel non-saccharide α-glucosidase inhibitors. Biological evaluation indicated that when compared to acarbose, compounds T9, T10, and T32 exhibited a higher potency of α-glucosidase inhibitory activity with IC50 values of 0.15 ± 0.01, 0.086 ± 0.01 and 0.32 ± 0.02 mM, respectively. Evaluation of the inhibition kinetics indicated that T9, T10, T32, and acarbose interacted with α-glucosidase in a mixed non-competitive inhibitory manner. Moreover, T9, T10, and T32 statically quenched the fluorescence of α-glucosidase by formation of an inhibitor-α-glucosidase complex. The docking results showed that hydrogen bonds were generated between the test compounds and α-glucosidase. The antioxidant study revealed that compound T10 exhibited a higher antioxidant activity via scavenging 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), thereby inhibiting lipid peroxidation and the total reduction capacity. In brief, the salicylic acid derivatives identified in this study were promising candidates for development as novel non-saccharide α-glucosidase inhibitors.

A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects.

Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p < 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.

Hydroxytyrosol nicotinate, a new multifunctional hypolipidemic and hypoglycemic agent.

Hydroxytyrosol (HT) is a natural polyphenol antioxidant that exists in olive oil. In the study of multifunctional hypolipidemic of nicotinic derivatives, we found that hydroxytyrosol nicotinate (HT-N) incorporation of niacin with HT displayed ?-glucosidase inhibitory activities in vitro, such as yeast ?-glucosidase (IC50?=?117.72??M) and rat intestinal ?-glucosidases maltase (IC50?=?31.86??M) and sucrase (IC50?=?22.99??M), and had a good control of postprandial blood glucose (PBG). HT-N shown significantly hypoglycemic action by 16.9% and protection of pancreatic tissue in type 2 diabetic mellitus (T2DM) mouse model. HT-N also shown a potent antioxidant activity and property of anti-glycation in vitro, which were benefit for ameliorating diabetic complications. Moreover, HT-N exhibited much significant hypolipidemia, lowering plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 34.6%, 45.8% and 32.1% respectively, in hyperlipidemic mice induced by Triton WR 1339. The results indicated that HT-N has hypolipidemic, hypoglycemic and antioxidant actions. All these properties could be conducive to amelioration of oxidative stress, hyperlipidemia, and diabetes that HT-N may serve as a multifunctional potential therapeutic strategy in diabetic patients with hyperlipidemia.

A new multifunctional hydroxytyrosol-fenofibrate with antidiabetic, antihyperlipidemic, antioxidant and antiinflammatory action.

Dyslipidemia, oxidative stress and inflammation are major risky factors involved in the pathophysiology of type 2 diabetes mellitus and atherosclerosis. Multifunctional intervene is more meaningful. The aim of this study was to evaluate the multifunctional effects of two new compounds, combination of fenofibric acid (FA) with tyrosol (T) or hydroxytyrosol (HT). Compared with fenofibrate (FF), FF-HT exhibited excellent antioxidant capacities in vitro and much improved hypolipidemia, reducing plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 76%, 54%, and 28%, while FF-T decreased the plasma parameters by 16%, 10%, and 20% in hyperlipidemic mice induced by Triton WR 1339. Furthermore, compound FF-HT exhibited significant antihyperglycemic, antihyperlipidemic, antioxidant and anti-inflammatory activities as well as attenuating hepatotoxicity in a type 2 diabetes experimental mouse model. The histological findings showed that FF-HT suppressed the development of hepatic lipid accumulation and ameliorated the damage in hepatic and pancreatic tissues compared to model mice. This study indicates for the first time that reasonable optimized drug design produce a compound entity which is conducive to the prevention of type 2 diabetes mellitus and its complications.

Phenylsulfonylfuroxan NO-donor phenols: Synthesis and multifunctional activities evaluation.

Phenylsulfonyfuroxan nitric oxide (NO)-donor phenols were designed, synthesized and evaluated. The compounds were designed through a symbiotic approach using selected phenols and phenylsulfonylfuroxan NO-donor. The antioxidant activities of the hybrid compounds T2-T6 showed to be good in vivo. Compounds T4 and T6 revealed excellent yeast α-glucosidase inhibitory activity and anti-glycosylation activity. All of the compounds exhibited strong NO releasing activity and significant anti-platelet aggregation activity. The inhibition of platelet aggregation was more than 50% at low concentration (1.5µM) and 95% at higher concentration (15µM and 150µM). The vasodilatation experiment demonstrated that the six compounds under test exhibited definite vasodilation activity (pIC50 ranged from 5.698 to 6.383), especially compound T6 (pIC50 was 6.383) which was similar to sodium nitroprusside (pIC50 was 6.786). Both anticoagulant and vasodilatation effects were correlated with their NO releasing activities. These hybrid phenylsulfonyfuroxan-based NO-donor phenols offer a multifunctional prodrug design concept for the development of therapeutic or preventive agents for metabolic syndrome.

The coastal ocean response to the global warming acceleration and hiatus.

Coastlines are fundamental to humans for habitation, commerce, and natural resources. Many coastal ecosystem disasters, caused by extreme sea surface temperature (SST), were reported when the global climate shifted from global warming to global surface warming hiatus after 1998. The task of understanding the coastal SST variations within the global context is an urgent matter. Our study on the global coastal SST from 1982 to 2013 revealed a significant cooling trend in the low and mid latitudes (31.4% of the global coastlines) after 1998, while 17.9% of the global coastlines changed from a cooling trend to a warming trend concurrently. The trend reversals in the Northern Pacific and Atlantic coincided with the phase shift of Pacific Decadal Oscillation and North Atlantic Oscillation, respectively. These coastal SST changes are larger than the changes of the global mean and open ocean, resulting in a fast increase of extremely hot/cold days, and thus extremely hot/cold events. Meanwhile, a continuous increase of SST was detected for a considerable portion of coastlines (46.7%) with a strengthened warming along the coastlines in the high northern latitudes. This suggests the warming still continued and strengthened in some regions after 1998, but with a weaker pattern in the low and mid latitudes.