Tough supramolecular hydrogels of poly(N,N-dimethylacrylamide)-grafted poly(methacrylic acid) with cooperative hydrogen bonds as physical crosslinks.

Incorporating associative interactions as the energy dissipation units has been recognized as an effective strategy to develop tough hydrogels. For hydrogen-bond associations, however, it is highly challenging to stabilize them under aqueous conditions. Although affording cooperativity can enhance and stabilize the hydrogen bonds, it usually requires stepwise polymerization to form these cooperative associations between different polymers and networks. Here, we report a series of tough supramolecular hydrogels with robust hydrogen-bond associations between grafted polymers that are synthesized by polymerization of a macromonomer of poly(N,N-dimethylacrylamide) (PDMAA) and a small monomer of methacrylic acid. The grafted chains of PDMAA form cooperative hydrogen bonds with the main chain of poly(methacrylic acid) (PMAAc), forming supramolecular hydrogels with high toughness and good stability. The tough and stiff hydrogels are in a glassy state, exhibit forced elastic deformation at room temperature, and remain stable over a wide pH range. In contrast, hydrogels prepared by the copolymerization of DMAA and MAAc are swollen and weak in water due to the lack of successive hydrogen donor/acceptor units and the absence of cooperative hydrogen bonds. In addition, these tough hydrogels exhibit good recyclability and shape memory properties, owing to the supramolecular nature of the network and the temperature-dependent mechanical properties. The influence of polymer structure on the associative interactions and macroscopic properties of the hydrogels should be informative for the design of tough soft materials with versatile applications.

Synthesis of Tetrasubstituted Enamines Using Secondary Amines and In Situ-Generated Allenes from Nitrocyclopropanes.

A novel reaction of cyclic and acyclic secondary amines with in situ-generated allene intermediate species from nitro-substituted donor-acceptor cyclopropanes is reported. In the presence of a simple inorganic base, NaOH, tetrasubstituted enamine derivatives can be obtained in moderate to excellent yields. The reaction is operationally easy, features mild reaction conditions and simple inorganic bases, and is free of transition metals.

Development and application of a nomogram model for predicting the risk of central precocious puberty in obese girls.

Objective: The purpose of this study is to develop and assess a nomogram risk prediction model for central precocious puberty (CPP) in obese girls. Methods: We selected 154 cases of obese girls and 765 cases of non-obese girls with precocious puberty (PP) who underwent the gonadotropin-releasing hormone stimulation test at the Jiangxi Provincial Children's Hospital. Univariate analysis and multivariate analysis were conducted to identify predictors of progression to CPP in girls with PP. A predictive model was developed and its predictive ability was preliminarily evaluated. The nomogram was used to represent the risk prediction model for CPP in girls with obesity. The model was validated internally using the Bootstrap method, and its efficacy was assessed using calibration curves and clinical decision analysis curves. Results: In obese girls with PP, basal luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels, as well as uterine volume, were identified as independent risk factors for progression to CPP. In non-obese girls, the basal LH level, bone age, and uterine volume were identified as independent risk factors for progression to CPP. With an AUC of 0.896, the risk prediction model for obese girls, was found to be superior to that for non-obese girls, which had an AUC of 0.810. The model displayed strong predictive accuracy. Additionally, a nomogram was used to illustrate the CPP risk prediction model for obese girls. This model performs well in internal validation and is well calibrated, providing a substantial net benefit for clinical use. Conclusion: A medical nomogram model of CPP risk in obese girls comprised of basal LH value, basal FSH value, and uterine volume, which can be used to identify those at high risk for progression of CPP in obese girls and develop individualized prevention programs.

Organo-cation catalyzed enantioselective α-hydroxylation of pyridinone-fused lactones: asymmetric synthesis of SN-38 and irinotecan.

A catalytic asymmetric α-hydroxylation of pyridinone-fused lactones, containing the core structure of camptothecin, is described. Development of a novel spiropyrrolidine amide (SPA) derived triazolium bromide organo-cation catalyst is crucial for a highly enantioselective oxidation, which also accommodates a wide array of lactones with various substituents. The resulting tricyclic tertiary alcohol with an oxa-quaternary carbon center can be further applied in the synthesis of SN-38 and irinotecan, two anti-cancer drugs derived from camptothecin.

Redescription of two species of Neoperla Needham, 1905 (Plecoptera, Perlidae) and new distribution records of Neoperlamnong Stark, 1987 in China.

Background: Two species of Neoperla from Guizhou Province, China, N.bituberculata Du, 2000 and N.dashahena Du, 2005 were described with brief morphological descriptions available only in Chinese and original illustrations being somewhat blurry. Recently, we examined type material of these two species and re-described them with clear colour pictures for the first time. New information: In this paper, detailed English descriptions and colour pictures of Neoperlabituberculata and N.dashahena are provided for the first time. The type locality of N.mnong Stark is from Vietnam and its geographical distribution is also discussed. Additionally, we also recorded the distribution of N.mnong Stark, 1987 in Guizhou, Hunan and Jiangxi Provinces of China for the first time and provided a geographical distribution map of this species.

Portal Venous and Hepatic Arterial Coefficients Predict Post-Hepatectomy Overall and Recurrence-Free Survival in Patients with Hepatocellular Carcinoma: A Retrospective Study.

Background: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy. Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models. Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534-2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290-1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149-2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380-2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005-2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236-2.263), higher BCLC stage (HR 1.516, 95% CI 1.300-1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198-2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060-1.997). Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients.

Recent advance for animal-derived polysaccharides in nanomaterials.

Inspired by the structure characteristics of natural products, the size and morphology of particles are carefully controlled using a bottom-up approach to construct nanomaterials with specific spatial unit distribution. Animal polysaccharide nanomaterials, such as chitosan and chondroitin sulfate nanomaterials, exhibit excellent biocompatibility, degradability, customizable surface properties, and novel physical and chemical properties. These nanomaterials hold great potential for development in achieving a sustainable bio-economy. This paper provides a summary of the latest research results on the preparation of nanomaterials from animal polysaccharides. The mechanism for preparing nanomaterials through the bottom-up method from different sources of animal polysaccharides is introduced. Furthermore, this paper discusses the potential hazards posed by industrial applications to the environment and human health, as well as the challenges and future prospects associated with using animal polysaccharides in nanomaterials.

Synthesis of scaberol C amino acid ester derivatives with anti-cancer activity.

A series of amino acid ester trifluoroacetate derivatives was synthesized from scaberol C. They were screened for their inhibitory activity against Non-Small Cell Lung Cancer (NSCLC) cells. Among them, compound 2 l showed significant cytotoxicity against A549 and H460 cells (IC50), and was more active than cisplatin (DDP). The epidermal growth factor receptor (EGFR) was overexpressed in NSCLC, which was the target of multiple cancer therapies and a strong prognostic indicator. Our previous studies reported that the target of scaberol C derivatives against NSCLC cells was EGFR. And then molecular docking analysis and molecular dynamics (MD) simulations indicated that 2 l can stably and covalently bind to the EGFR target protein.

Vaccarin alleviates septic cardiomyopathy by potentiating NLRP3 palmitoylation and inactivation.

BACKGROUND: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1ß and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. PURPOSE: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. STUDY DESIGN: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. METHODS/RESULTS: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. CONCLUSION: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.

Pharmacology of Hydrogen Sulfide and Its Donors in Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H2S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of H2S in regulating proteins via persulfidation, a well known modification intricately associated with the pathogenesis of CMDs. This review seeks to investigate recent updates on the physiological actions of endogenous H2S and the pharmacological roles of various H2S donors in addressing diverse aspects of CMDs across cellular, animal, and clinical studies. Of note, advanced methodologies, including multiomics, intestinal microflora analysis, organoid, and single-cell sequencing techniques, are gaining traction due to their ability to offer comprehensive insights into biomedical research. These emerging approaches hold promise in characterizing the pharmacological roles of H2S in health and diseases. We will critically assess the current literature to clarify the roles of H2S in diseases while also delineating the opportunities and challenges they present in H2S-based pharmacotherapy for CMDs. SIGNIFICANCE STATEMENT: This comprehensive review covers recent developments in H2S biology and pharmacology in cardiometabolic diseases CMDs. Endogenous H2S and its donors show great promise for the management of CMDs by regulating numerous proteins and signaling pathways. The emergence of new technologies will considerably advance the pharmacological research and clinical translation of H2S.

Tip60-FOXO regulates JNK signaling mediated apoptosis in Drosophila.

The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers. This study utilized the model organism Drosophila and employed multidisciplinary approaches encompassing genetics, developmental biology, biochemistry, and molecular biology to investigate the interplay between Tip60 and the JNK signaling pathway, and elucidated its regulatory mechanisms. Our findings suggest that loss of Tip60 acetyltransferase activity results in JNK signaling pathway activation and subsequent induction of JNK-dependent apoptosis. Genetic epistasis analysis reveals that Tip60 acts downstream of JNK, paralleling with the transcription factor FOXO. The biochemical results confirm that Tip60 can bind to FOXO and acetylate it. Introduction of human Tip60 into Drosophila effectively mitigates apoptosis induced by JNK signaling activation, underscoring conserved regulatory role of Tip60 in the JNK signaling pathway from Drosophila to humans. This study further enhances our understanding of the regulatory network of the JNK signaling pathway. By revealing the role and mechanism of Tip60 in JNK-dependent apoptosis, it unveils new insights and potential therapeutic avenues for preventing and treating associated cancers.

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In this study, we explored the changes in plant community diversity and their relationship with soil factors under shrub encroachment pressure by selecting four marsh areas in Sanjiang Plain with different degrees of shrub cover (a, 0≤a≤100%), including marsh with no shrub encroachment (a=0), light shrub encroachment (0

Modulation of the rat intestinal microbiota in the course of Anisakis pegreffii infection.

Background: Anisakis are globally distributed, marine parasitic nematodes that can cause human health problems, including symptoms such as vomiting, acute diarrhea, and allergic reactions. As parasitic nematodes that primarily affect the patient's digestive tract, intestinal helminths can interact directly with the host microbiota through physical contact, chemicals, or nutrient competition. It is widely accepted that the host microbiota plays a crucial role in the regulation of immunity. Materials and methods: Nematodes collected from the abdominal cavity of marine fish were identified by molecular biology and live worms were artificially infected in rats. Infection was determined by indirect ELISA based on rat serum and worm extraction. Feces were collected for 16S rDNA-based analysis of microbiota diversity. Results: Molecular biology identification based on ITS sequences identified the collected nematodes as A. pegreffii. The success of the artificial infection was determined by indirect ELISA based on serum and worm extraction from artificially infected rats. Microbiota diversity analysis showed that a total of 773 ASVs were generated, and PCoA showed that the infected group was differentiated from the control group. The control group contained five characterized genera (Prevotellaceae NK3B31 group, Turicibacter, Clostridium sensu stricto 1, Candidatus Stoquefichus, Lachnospira) and the infected group contained nine characterized genera (Rodentibacter, Christensenella, Dubosiella, Streptococcus, Anaeroplasma, Lactococcus, Papillibacter, Desulfovibrio, Roseburia). Based on the Wilcoxon test, four processes were found to be significant: bacterial secretion system, bacterial invasion of epithelial cells, bacterial chemotaxis, and ABC transporters. Conclusion: This study is the first to analyze the diversity of the intestinal microbiota of rats infected with A. pegreffii and to determine the damage and regulation of metabolism and immunity caused by the infection in the rat gut. The findings provide a basis for further research on host-helminth-microbe correlationships.

Cryptic diversity and rampant hybridization in annual gentians on the Qinghai-Tibet Plateau revealed by population genomic analysis.

Understanding the evolutionary and ecological processes involved in population differentiation and speciation provides critical insights into biodiversity formation. In this study, we employed 29,865 single nucleotide polymorphisms (SNPs) and complete plastomes to examine genomic divergence and hybridization in Gentiana aristata, which is endemic to the Qinghai-Tibet Plateau (QTP) region. Genetic clustering revealed that G. aristata is characterized by geographic genetic structures with five clusters (West, East, Central, South and North). The West cluster has a specific morphological character (i.e., blue corolla) and higher values of FST compared to the remaining clusters, likely the result of the geological barrier formed by the Yangtze River. The West cluster diverged from the other clusters in the Early Pliocene; these remaining clusters diverged from one another in the Early Quaternary. Phylogenetic reconstructions based on SNPs and plastid data revealed substantial cyto-nuclear conflicts. Genetic clustering and D-statistics demonstrated rampant hybridization between the Central and North clusters, along the Bayankala Mountains, which form the geological barrier between the Central and North clusters. Species distribution modeling demonstrated the range of G. aristata expanded since the Last Interglacial period. Our findings provide genetic and morphological evidence of cryptic diversity in G. aristata, and identified rampant hybridization between genetic clusters along a geological barrier. These findings suggest that geological barriers and climatic fluctuations have an important role in triggering diversification as well as hybridization, indicating that cryptic diversity and hybridization are essential factors in biodiversity formation within the QTP region.

Potential clinical value of fibrinogen-like protein 1 as a serum biomarker for the identification of diabetic cardiomyopathy.

Diabetic individuals with diabetic cardiomyopathy (DbCM) present with abnormal myocardial structure and function. DbCM cannot be accurately diagnosed due to the lack of suitable diagnostic biomarkers. In this study, 171 eligible participants were divided into a healthy control (HC), type 2 diabetes mellitus (T2DM) patients without DbCM (T2DM), or DbCM group. Serum fibrinogen-like protein 1 (FGL-1) and other biochemical parameters were determined for all participants. Serum FGL-1 levels were significantly higher in patients with DbCM compared with those in the T2DM group and HCs. Serum FGL-1 levels were negatively correlated with left ventricular fractional shortening and left ventricular ejection fraction (LVEF) and positively correlated with left ventricular mass index in patients with DbCM after adjusting for age, sex and body mass index. Interaction of serum FGL-1 and triglyceride levels on LVEF was noted in patients with DbCM. A composite marker including serum FGL-1 and triglycerides could differentiate patients with DbCM from those with T2DM and HCs with an area under the curve of 0.773 and 0.789, respectively. Composite marker levels were negatively correlated with N-terminal B-type natriuretic peptide levels in patients with DbCM. Circulating FGL-1 may therefore be a valuable index reflecting cardiac functions in DbCM and to diagnose DbCM.

The predictive value of γ-glutamyl transferase to serum albumin ratio in hepatocellular carcinoma patients after liver transplantation.

Background: Elevated preoperative γ-glutamyl transferase (GGT) levels or reduced serum albumin levels have been established as negative prognostic factors for patients with hepatocellular carcinoma (HCC) and various other tumors. Nonetheless, the prognostic significance of the GGT to serum albumin ratio (GAR) in liver transplantation (LT) therapy for HCC is still not well-defined. Methods: A retrospective analysis was conducted on the clinical data of 141 HCC patients who underwent LT at Shulan (Hangzhou) Hospital from June 2017 to November 2020. Using the receiver operating characteristic (ROC) curve, the optimal GAR cutoff value to predict outcomes following LT was assessed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent risk factors associated with both overall survival (OS) and recurrence-free survival (RFS). Results: A GAR value of 2.04 was identified as the optimal cutoff for predicting both OS and RFS, with a sensitivity of 63.2% and a specificity of 74.8%. Among these patients, 80 (56.7%) and 90 (63.8%) met the Milan and the University of California San Francisco (UCSF) criteria, respectively. Univariate Cox regression analysis showed that microvascular invasion (MVI), maximum tumor size (>5 cm), total tumor size (>8 cm), liver cirrhosis, TNM stage (III), and GAR (≥2.04) were significantly associated with both postoperative OS and RFS in patients with HCC (all p < 0.05). Multivariate Cox regression analysis indicated that GAR (≥2.04) was independently linked with RFS and OS. Conclusion: Pre-transplant GAR ≥2.04 is an independent correlate of prognosis and survival outcomes after LT for HCC and can be used as a prognostic indicator for both mortality and tumor recurrence following LT.

Cichoric acid ameliorates sepsis-induced acute kidney injury by inhibiting M1 macrophage polarization.

Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI. The aim of this study is to investigated the protective effect and possible mechanisms of CA against LPS-induced septic AKI. Sepsis-induced AKI was induced in mice through intraperitoneal injection of lipopolysaccharide (LPS), and RAW264.7 macrophages were incubated with LPS. LPS exposure significantly increased the levels of M1 macrophage biomarkers while reducing the levels of M2 macrophage indicators. This was accompanied by the release of inflammatory factors, superoxide anion production, mitochondrial dysfunction, activation of succinate dehydrogenase (SDH), and subsequent succinate formation. Conversely, pretreatment with CA mitigated these abnormalities. CA attenuated hypoxia-inducible factor-1α (HIF-1α)-induced glycolysis by lifting the NAD+/NADH ratio in macrophages. Additionally, CA disrupted the K (lysine) acetyltransferase 2A (KAT2A)/α-tubulin complex, thereby reducing α-tubulin acetylation and subsequently inactivating the NLRP3 inflammasome. Importantly, administration of CA ameliorated LPS-induced renal pathological damage, apoptosis, inflammation, oxidative stress, and disturbances in mitochondrial function in mice. Overall, CA restrained HIF-1α-mediated glycolysis via inactivation of SDH, leading to NLRP3 inflammasome inactivation and the amelioration of sepsis-induced AKI.

Superoxide dismutases: marker in predicting reduced left ventricular ejection fraction in patients with type 2 diabetes and acute coronary syndrome.

AIM: To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). METHODS: The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. RESULTS: Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493-0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482-0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. CONCLUSIONS: Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice.

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.

The type-I, III nodal ring, type-I, III quadratic nodal point, and Dirac valley phonons in 2D kagome lattices M2C3(M = As, Bi, Cd, Hg, P, Sb, Zn).

Topological phases in kagome systems have garnered considerable interest since the introduction of the colloidal kagome lattice. Our study employs first-principle calculations and symmetry analysis to predict the existence of ideal type-I, III nodal rings (NRs), type-I, III quadratic nodal points (QNPs), and Dirac valley phonons (DVPs) in a collection of two-dimensional (2D) kagome lattices M2C3(M = As, Bi, Cd, Hg, P, Sb, Zn). Specifically, the Dirac valley points (DVPs) can be observed at two inequivalent valleys with Berry phases of +πand-π, connected by edge arcs along the zigzag and armchair directions. Additionally, the QNP is pinned at the Γ point, and two edge states emerge from its projections. Notably, these kagome lattices also exhibit ideal type-I and III nodal rings protected by time inversion and spatial inversion symmetries. Our work examines the various categories of nodal points and nodal ring phonons within the 2D kagome systems and presents a selection of ideal candidates for investigating topological phonons in bosonic systems.