The supramolecular polymer hydrogels feature self-healability, adjustable mechanical strength, and thermoplasticity, which are derived from the formation of supramolecular physical interactions in the hydrogel networks, such as H-bonding interactions, [6] host-guest interactions, [7] metal-ligand coordination interactions, [8] hydrophobic interactions, [9] multiple combined interactions. [10] Among them, H-bonds are generally weak noncovalent bonds, ubiquitous in biomolecules, but their synergistic interactions can reach a strength of the covalent bond; thus it is commonly utilized in designing supramolecular tough hydrogels. [11] Our previous study suggested that supramolecular polymer hydrogels based on single amide H-bonding interaction were unstable in water, [12] because the competitive solvation of H-bond donor and acceptor in polar solvents weakens its strengthening effect. [13] Inspired by the hydrogen-bonded clusters in the secondary structure of proteins, we constructed a supramolecular poly(N-acryloyl glycinamide) (PNAGA) hydrogel whose dual amide motifs in the side chain contributed to high strengths and outstanding antiswelling ability due to strong shielding of the hydrogen-bonded microdomains from water molecule attack. [12] By utilizing Type II photoinitiated self-condensing vinyl polymerization of N-acryloyl glycinamide (NAGA), the resultant hyperbranched PNAGA hydrogels demonstrated superior mechanical performances to those of linear PNAGA counterparts owing to the higher cross-linking density of H-bonds. [14] In addition, the H-bonding interactions of dual amide motifs could also be modulated by copolymerizing other monomers, [15][16][17][18] thus achieving the versatile hydrogels with mechanical properties spanning from high strength to soft injectability, which show promising applications as 3D printed osteochondral regeneration scaffold, [16] artificial vitreous body, [17] and postoperative antiadhesion barrier. [18] Our recent study revealed that only introducing one methyl group to the double bond of NAGA could lead to a considerable decrease in mechanical strengths and an increase in room temperature autonomous self-healability of the poly(N-methacryloyl glycinamide) hydrogels (MNAGA), which was resulted from the perturbation of one methyl substitution to H-bonds. [19] The intermolecular H-bonding density heavily influences the gelation and rheological behavior of hydrogen-bonded supramolecular polymer hydrogels, thus offering a delicate pathway to tailor their physicochemical properties for meeting a specific biomedical application. Herein, one methylene spacer between two amides in the side chain of N-acryloyl glycinamide (NAGA) is introduced to generate a variant monomer, N-acryloyl alaninamide (NAAA). Polymerization of NAAA in aqueous solution affords an unprecedented ultrasoft and highly swollen supramolecular polymer hydrogel due to weakened H-bonds caused by an extra methylene spacer, which is verified by variabletemperature Fourier transform infrared (FTIR) spectroscopy and s...

Administration of HAM-RS2 for eight weeks significantly reduced levels of inflammatory and oxidative markers in hemodialysis patients confirming the results observed in CKD animals. Long term trials are needed to explore the impact of HAM-RS2 supplementation on clinical outcomes in end stage renal disease population.

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Highlights The effect of LCZ696 (Sacubitril/valsartan) against cardiorenal syndrome is proposed. LCZ696 more improved CKD related heart failure than valsartan therapy alone. LCZ696 attenuated CKD related cardiac hypertrophy and fibrosis and aortic fibrosis. Effects of LCZ696 for heart are mediated by anti-inflammation and oxidative stress. LCZ696 also improved indicators of mitochondrial mass/function. AbstractBackground: Chronic kidney disease (CKD) is associated with cardiac hypertrophy, fibrosis and

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(±)-Praeruptorin A (PA) is the major component of Peucedani Radix. The present study investigated stereoselectivity in PA metabolism in liver microsomes of rats (RLMs) and humans (HLMs), for the first time. PA was enantioseparated by semi-preparative chiral HPLC. Metabolic profiles of the dextrorotatory (dPA) and the levorotatory (lPA) forms in HLMs and RLMs were determined using LC-MS/MS. (-)-cis-Khellactone (D1) prepared from basic hydrolysis of dPA, and (3'R, 4'R)-4'-angeloyl-khellactone (L8) and (3'R, 4'R)-3'-angeloyl-khellactone (L9) isolated from a scale-up incubation of lPA with rat plasma were unambiguously identified by LC-MS/MS and NMR analysis. Other metabolites were tentatively identified using LC-MS/MS. In the absence of NADPH-regenerating system, dPA remained intact, however, lPA yielded L8 and L9 via a carboxylesterase(s)-mediated process. In the presence of NADPH-regenerating system, lPA produced 9 (L1-9) metabolites in both species, while dPA generated 12 (D1-12) and 6 (D1-3, 6, 9 and 10) metabolites in RLMs and HLMs, respectively. Hydrolysis, oxidation and acyl migration were demonstrated to be the predominant pathways for both enantiomers. Both enantiomers were eliminated faster in RLMs than in HLMs, while lPA showed greater species difference. PA enantiomers exhibited stereoselective metabolism in RLMs and HLMs, implying chiral discrimination in their actions.