Elastomers with excellent mechanical properties are in substantial demand for various applications, but there is always a tradeoff between their mechanical strength and stretchability. For example, partially replacing strong covalent crosslinking by weak sacrificial bonds can enhance the stretchability but also usually decreases the mechanical strength. To surmount this inherent tradeoff, a supramolecular strategy of introducing a zipper‐like sliding‐ring mechanism in a hydrogen‐bond‐crosslinked polyurethane network is proposed. A very small amount (0.5 mol%) of an external additive (pseudo[2]rotaxane crosslinker) can dramatically increase both the mechanical strength and elongation of this polyurethane network by nearly one order of magnitude. Based on the investigation of the relationship between molecular structure and mechanical properties, this enhancement is attributable to a unique molecular‐level zipper‐like ring‐sliding motion, which efficiently dissipates mechanical work in the solvent‐free network. This research not only provides a distinct and general strategy for the construction of high‐performance elastomers but also paves the way for the practical application of artificial molecular machines toward solvent‐free polyurethane networks.

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Many discharged COVID-19 patients affected by sequelae experience reduced quality of life leading to an increased burden on the healthcare system, their families and society at large. Possible pathophysiological mechanisms of long COVID include: persistent viral replication, chronic hypoxia and inflammation. Ongoing vascular endothelial damage promotes platelet adhesion and coagulation, resulting in the impairment of various organ functions. Meanwhile, thrombosis will further aggravate vasculitis contributing to further deterioration. Thus, long COVID is essentially a thrombotic sequela. Unfortunately, there is currently no effective treatment for long COVID. This article summarizes the evidence for coagulation abnormalities in long COVID, with a focus on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) released by various types of cells can carry SARS-CoV-2 through the circulation and attack distant tissues and organs. Furthermore, EVs express tissue factor and phosphatidylserine (PS) which aggravate thrombosis. Given the persistence of the virus, chronic inflammation and endothelial damage are inevitable. Pulmonary structural changes such as hypertension, embolism and fibrosis are common in long COVID. The resulting impaired lung function and chronic hypoxia again aggravates vascular inflammation and coagulation abnormalities. In this article, we also summarize recent research on antithrombotic therapy in COVID-19. There is increasing evidence that early anticoagulation can be effective in improving outcomes. In fact, persistent systemic vascular inflammation and dysfunction caused by thrombosis are key factors driving various complications of long COVID. Early prophylactic anticoagulation can prevent the release of or remove procoagulant substances, thereby protecting the vascular endothelium from damage, reducing thrombotic sequelae, and improving quality of life for long-COVID patients.

. Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway. Am J Physiol Endocrinol Metab 309: E925-E935, 2015. First published October 6, 2015; doi:10.1152/ajpendo.00294.2015.-Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPK␣2 Ϫ/Ϫ mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPKmTOR pathway. hydrogen sulfide; triglyceride; NAFLD; autophagy; AMPK HYPERTRIGLYCERIDEMIA (HTG) is the most common lipid metabolism disorder and is an important independent risk factor for cardiovascular and cerebrovascular diseases (2, 10, 29). The liver plays a cardinal role in lipid metabolism. Increased production and/or decreased clearance of triglyceride (TG) in the liver inevitably results in HTG (13, 30), while TG accumulation in the liver can lead to nonalcoholic fatty liver disease (NAFLD) (40). NAFLD is the most prevalent chronic liver disease in the developed world and is an important risk factor for the development of liver fibrosis and cirrhosis and predisposes to the development of hepatocellular carcinoma (1, 26).Recent research suggests that autophagy participates in the regulation of liver lipid metabolism (5, 33, 34). Autophagy modulates hepatocyte lipid metabolism through lipophagy, which involves sequestration of lipid drops in double-membrane autophagosomes, followed by fusion with lysosomes to form autolysosomes, and subsequent degradation of TG by lipases within the autolysosomes. Reduction of liver cell autophagic activity causes decreased lipolysis and provokes free fatty acid (FFA) ␤-oxidation, resulting in hepatic steatosis and often progresses to NAFLD and HTG (34).AMP-activated pro...

The mechanisms contributing to an increased risk of thrombosis in uremia are complex and require clarification. There is scant morphological evidence of membrane-dependent binding of factor Xa (FXa) and factor Va (FVa) on endothelial cells (EC) in vitro. Our objectives were to confirm that exposed phosphatidylserine (PS) on microparticle (MP), EC, and peripheral blood cell (PBC) has a prothrombotic role in uremic patients and to provide visible and morphological evidence of PS-dependent prothrombinase assembly in vitro. We found that uremic patients had more circulating MP (derived from PBC and EC) than controls. Additionally, patients had more exposed PS on their MPs and PBCs, especially in the hemodialysis group. In vitro, EC exposed more PS in uremic toxins or serum. Moreover, reconstitution experiments showed that at the early stages, PS exposure was partially reversible. Using confocal microscopy, we observed that PS-rich membranes of EC and MP provided binding sites for FVa and FXa. Further, exposure of PS in uremia resulted in increased generation of FXa, thrombin, and fibrin and significantly shortened coagulation time. Lactadherin, a protein that blocks PS, reduced 80% of procoagulant activity on PBC, EC, and MP. Our results suggest that PBC and EC in uremic milieu are easily injured or activated, which exposes PS and causes a release of MP, providing abundant procoagulant membrane surfaces and thus facilitating thrombus formation. Blocking PS binding sites could become a new therapeutic target for preventing thrombosis.

An elevated concentration of serum sST2 is found in CKD patients and correlates with disease severity. Serum sST2 may be also associated with parathyroid hormone disorder of CKD. The sST2 may have an important role in the development of CKD or as a marker of disease severity.

ObjectiveTo investigate whether microRNAs (miRs) can serve as novel biomarkers for in-stent restenosis (ISR).MethodsThis retrospective, observational single-centre study was conducted at the cardiovascular department of a tertiary hospital centre in the north of China. Follow-up coronary angiography at 6 to 12 months was performed in 181 consecutive patients implanted with drug-eluting stents. Fifty-two healthy volunteers served as the control group. The plasma miRs levels were analyzed by quantitative real-time PCR. Receiver-operating characteristic curve (ROC) analysis was performed to investigate the characters of these miRs as potential biomarkers of ISR.ResultsMiR-21 levels in ISR patients were significantly higher than those in non-ISR patients and healthy controls (P<0.05), while miR-100 (P<0.05), miR-143 (P<0.001) and miR-145 (P<0.0001) levels were significantly decreased in ISR patients. Further analysis showed that miR-21 levels were remarkably increased (P = 0.045), while miR-100 (P = 0.041), miR-143 (P = 0.029) and miR-145 (P<0.01) levels were dramatically decreased in patients with diffuse ISR compared to those with focal ISR. ROC analysis demonstrated that the area under curve of miR-145, miR-143, miR-100 and miR-21 were 0.880 (95% confidence interval; CI = 0.791–0.987, P<0.001), 0.818 (95% confidence interval; CI = 0.755–0.963, P<0.001), 0.608 (95% confidence interval; CI = 0.372–0.757, P<0.05) and 0.568 (95% confidence interval; CI = 0.372–0.757, P<0.05), with specificity of 83.1%, 80.1%, 68.9% and 68.6%, and sensitivity of 88.7%, 82.1%, 60.2% and 50.1%, respectively.ConclusionsCirculating miR-143 and miR-145 levels are associated with the occurrence of ISR and can serve as novel noninvasive biomarkers for ISR.

A series of quinoline oligoamide foldamers bearing a β-pinene-derived pyridyl group at the N-terminus or the C-terminus were synthesized, and the efficiencies of chiral inductions have been evaluated by H NMR and CD spectra. The chiral inductions were quantitative when chiral pyridyl acid was appended at the N-terminus, but were inferior when chiral pyridyl amine was appended at the C-terminus. Unexpectedly, N-oxidation on the pyridine ring at the C-terminus does not notably enhance the chiral induction efficiency in spite of the presence of three-center hydrogen bonds.