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1.
Front Pharmacol ; 15: 1420602, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268468

RESUMEN

Background: Kawasaki disease (KD) is a self-limiting and acute systemic vasculitis of unknown etiology, mainly affecting children. Ferulic acid (FA), a natural phenolic substance, has multiple pharmacological properties, including anti-inflammatory, anti-apoptosis, and anti-fibrosis, and so on. So far, the protective effects of FA on KD have not been explored. Methods: In this study, we established Candida albicans water soluble fraction (CAWS)-induced mouse coronary artery vasculitis of KD model and the tumor necrosis factor α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury model to investigate the anti-inflammatory and anti-apoptosis effects of FA on KD, and try to elucidate the underlying mechanism. Results: Our in vivo results demonstrated that FA exerted anti-inflammatory effects on KD by inhibiting the infiltration of CD45-positive leukocytes and fibrosis around the coronary artery. Additionally, FA downregulated the levels of inflammatory and chemotactic cytokines, alleviated splenomegaly, and exhibited anti-apoptotic effects on KD by reducing TUNEL-positive cells, downregulating BAX expression, and upregulating BCL-2 expression. In addition, Our in vitro findings showed that FA could effectively inhibit TNF-α-induced HUVEC inflammation like NF-κB inhibitor QNZ by downregulating the expression of pro-inflammatory cytokines as well as attenuated TNF-α-induced HUVEC apoptosis by reducing apoptotic cell numbers and the BAX/BCL-2 ratio, which could be reversed by the AMPK inhibitor compound c (CC). The further mechanistic study demonstrated that FA could restrain vascular endothelial cell inflammation and apoptosis in KD through activating the AMPK/mTOR/NF-κB pathway. However, FA alone is hard to completely restore KD into normal condition. Conclusion: In conclusion, FA has potential protective effects on KD, suggesting its promising role as an adjuvant for KD therapy in the future.

2.
Phytomedicine ; 134: 155976, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39265445

RESUMEN

BACKGROUND: Pulmonary hypertension (PH) is a chronic lung disease characterized by the progressive pulmonary vascular remodeling with increased pulmonary arterial pressure and right ventricular failure. Pulmonary vascular remodeling involves the proliferation, migration, and resistance to apoptosis of pulmonary artery smooth cells (PASMCs). Parthenolide (PTN) is a bioactive compound derived from a traditional medical plant feverfew (Tanacetum parthenium), and it has been studied for treatment of pulmonary fibrosis, lung cancer, and other related ailments. However, the function of PTN in the treatment of PH has not been studied. PURPOSE: This study aimed to evaluate the anti-proliferation and pro-apoptosis effects of PTN on PH and investigate its potential mechanisms. METHODS: An in vivo hypoxia-induced pulmonary hypertension (HPH) model was established by maintaining male rats in a hypoxia chamber (10% O2) for 3 weeks, and PTN was intraperitoneally administered at the dose of 10 or 30 mg/kg. We assessed the impact of PTN on mean pulmonary arterial pressure (mPAP), pulmonary vascular remodeling, and right ventricular hypertrophy. In vitro, we evaluated hypoxia-induced cellular proliferation, migration, and apoptosis of rat PASMCs. Proteins related to the STAT3 signaling axis were analyzed by western blotting and immunofluorescence assays. Recovery experiments were performed using the STAT3 activator, colivelin TFA. RESULTS: PTN significantly alleviated the symptoms of HPH rats by attenuating pulmonary arterial remodeling. It also prevented the proliferation and migration of PASMCs. PTN also induced the apoptosis of PASMCs. PTN could directly interact with STAT3 and markedly inhibited STAT3 phosphorylation and nuclear translocation. In vitro, and in vivo experiments demonstrated that overexpression of STAT3 partially suppressed the effect of PTN. CONCLUSION: Our study indicated that PTN alleviated hypoxia-induced pulmonary hypertension in rats by suppressing STAT3 activity.

3.
Chem Commun (Camb) ; 60(74): 10156-10159, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39189692

RESUMEN

An efficient chalcogenative annulation strategy for constructing functionalized saturated N-heterocycles from unactivated alkenes with dichalcogenides under electrochemical conditions has been presented. This protocol is applicable to mono-, di- or tri-substituted alkenes, providing a straightforward pathway to aziridines, azetidines, pyrrolidines, and piperidines with high regioselectivity. Moreover, the strategy is qualified to realize the oxychalcogenation of alkenes as well.

4.
Heliyon ; 10(14): e34179, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39092257

RESUMEN

Purpose: Individuals with chronic kidney disease (CKD) face an elevated residual risk of cardiovascular events, but the relationship between this residual risk and 1,5-anhydroglucitol (1,5-AG) is uncertain. Our study aimed to examine the effect of 1,5-AG on major adverse cardiovascular events (MACEs) and all-cause mortality in acute coronary syndrome (ACS) individuals. Methods: 1253 ACS participants hospitalized were enrolled at Beijing Hospital between March 2017 and March 2020. All participants were classified into 2 groups based on their eGFR (60 ml/min/1.73 m2). The link between 1,5-AG and adverse outcome was investigated in non-CKD and CKD participants. Results: CKD patients had reduced concentrations of 1,5-AG than those without CKD. Throughout a median follow-up duration of 43 months, 1,5-AG was an autonomous hazard factor for MACEs and all-cause mortality. 1,5-AG<14 µg/ml participants had greater MACEs and all-cause mortality risk than those with 1,5-AG≥14 µg/ml, regardless of renal function. Furthermore, concomitant reduced concentrations of 1,5-AG and CKD portended a dismal prognosis in ACS patients. Conclusions: 1,5-AG was autonomously linked to MACEs and all-cause mortality in ACS participants with both non-CKD and CKD. Co-presence of reduced concentrations of 1,5-AG and CKD may portend adverse clinical outcomes.

5.
Front Endocrinol (Lausanne) ; 15: 1360861, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39092284

RESUMEN

Background: Gut microbiota has significant impact on the cardio-metabolism and inflammation, and is implicated in the pathogenesis and progression of atherosclerosis. However, the long-term prospective association between trimethylamine N-oxide (TMAO) level and major adverse clinical events (MACEs) in patients with coronary artery disease (CAD) with or without diabetes mellitus (DM) habitus remains to be investigated. Methods: This prospective, single-center cohort study enrolled 2090 hospitalized CAD patients confirmed by angiography at Beijing Hospital from 2017-2020. TMAO levels were performed using liquid chromatography-tandem mass spectrometry. The composite outcome of MACEs was identified by clinic visits or interviews annually. Multivariate Cox regression analysis, Kaplan-Meier analysis, and restricted cubic splines were mainly used to explore the relationship between TMAO levels and MACEs based on diabetes mellitus (DM) habitus. Results: During the median follow-up period of 54 (41, 68) months, 266 (12.7%) developed MACEs. Higher TMAO levels, using the tertile cut-off value of 318.28 ng/mL, were significantly found to be positive dose-independent for developing MACEs, especially in patients with DM (HR 1.744, 95%CI 1.084-2.808, p = 0.022). Conclusions: Higher levels of TMAO are significantly associated with long-term MACEs among CAD patients with DM. The combination of TMAO in patients with CAD and DM is beneficial for risk stratification and prognosis.


Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Metilaminas , Humanos , Metilaminas/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Diabetes Mellitus/epidemiología , Pronóstico , Biomarcadores/sangre , Estudios de Seguimiento , Factores de Riesgo , Estudios de Cohortes
6.
Atherosclerosis ; 395: 117552, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38954858

RESUMEN

BACKGROUND AND AIMS: The immuno-inflammatory response is a crucial early step in the development of acute coronary syndrome (ACS). In this study, we investigated whether immunoglobulin M (IgM) in the body's initial immune response can predict the prognosis of patients with ACS. METHODS: This prospective cohort study enrolled 1556 ACS patients at Beijing Hospital between March 2017 and October 2020. All patients underwent coronary angiography (CAG). The serum IgM concentration and biochemical indicators were evaluated prior to CAG. The primary endpoint was the composite endpoint of major adverse cardiovascular and cerebrovascular events (MACCEs). Multivariate Cox proportional hazards models was used to explore the association between IgM levels and the endpoint. RESULTS: The average serum IgM levels of the population was 61.3 (42.6-88.4) mg/dL. During the median follow-up period of 55 months, 150 MACCEs occurred. Kaplan-Meier analysis showed that low serum IgM levels were associated with occurrence of MACCEs (log-rank p = 0.009). Univariate Cox proportional hazards models showed that low serum IgM (≤78.05 mg/dL) was associated with MACCEs (hazard ratio (HR) 1.648, 95 % confidence interval (CI): 1.129-2.406, p = 0.010). In patients with IgM ≤78.05 mg/dL, the HR for partially adjusted MACCEs events was 1.576 (95 % CI: 1.075-2.310) and 1.930 (95 % CI: 1.080-3.449) after adjusting for multiple covariates. The subgroup analysis showed that for patients in ≤24 BMI, never smoking and non-dyslipidemia subgroup, the lower serum IgM levels was significantly associated with the risk of MACCEs (pinteraction < 0.001, pinteraction = 0.037, pinteraction = 0.024, respectively). CONCLUSIONS: Low serum IgM levels was independently associated with MACCEs in ACS patients, especially for patients without obesity, smoking and dyslipidemia.


Asunto(s)
Síndrome Coronario Agudo , Biomarcadores , Inmunoglobulina M , Humanos , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/inmunología , Síndrome Coronario Agudo/diagnóstico , Inmunoglobulina M/sangre , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pronóstico , Anciano , Biomarcadores/sangre , Factores de Riesgo , Medición de Riesgo , Angiografía Coronaria , Beijing/epidemiología
7.
Respir Res ; 25(1): 292, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080722

RESUMEN

BACKGROUND: Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. METHODS: A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. RESULTS: During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P < 0.001) identified these patient groups better than the GNRI. All three malnutrition tools were associated with well-validated variables that reflected IPAH severity, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide level. The CONUT score exhibited better predictive ability than both the GNRI (ΔAUC = 0.059, P < 0.001) and PNI (ΔAUC = 0.095, P < 0.001) for adverse outcomes and significantly improved reclassification and discrimination beyond the ESC risk score. Multivariable Cox regression analysis indicated that only the CONUT score (hazard ratio = 1.363, 95% confidence interval 1.147, 1.619 per 1.0-standard deviation increment, P < 0.001) independently predicted adverse outcomes. CONCLUSIONS: The malnutrition status was associated with disease severity in patients with IPAH. The CONUT score provided additional information regarding the risk of clinically worsening events, making it a meaningful risk stratification tool for these patients.


Asunto(s)
Desnutrición , Índice de Severidad de la Enfermedad , Humanos , Femenino , Masculino , Desnutrición/diagnóstico , Desnutrición/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Estado Nutricional , Adulto , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/fisiopatología , Hipertensión Pulmonar Primaria Familiar/mortalidad , Anciano , Evaluación Nutricional , Estudios de Cohortes , Estudios de Seguimiento , Medición de Riesgo/métodos , Pronóstico , Factores de Riesgo
8.
ACS Appl Mater Interfaces ; 16(30): 39784-39795, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39036892

RESUMEN

The utilization of hydrogels for DNA/cationic polymer polyplex nanoparticle (polyplex) delivery has significantly advanced gene therapy in tissue regeneration and cancer treatment. However, persistent challenges related to the efficacy and safety of encapsulated polyplexes, stemming from issues such as aggregation, degradation, or difficulties in controlled release during or postintegration with hydrogel scaffolds, necessitate further exploration. Here, we introduce an injectable gene therapy gel achieved by incorporating concentrated polyplexes onto densely packed hydrogel microparticles (HMPs). Polyplexes, when uniformly adhered to the gene therapy gel through reversible electrostatic interactions, can detach from the HMP surface in a controlled manner, contrasting with free polyplexes, and thereby reducing dose-dependent toxicity during transfection. Additionally, the integration of RGD cell adhesion peptides enhances the scaffolding characteristics of the gel, facilitating cell adhesion, migration, and further minimizing toxicity during gene drug administration. Notably, despite the overall transfection efficiency showing average performance, utilizing confocal microscopy to meticulously observe and analyze the cellular states infiltrating into various depths of the gene therapy gel resulted in the groundbreaking discovery of significantly enhanced local transfection efficiency, with primary cell transfection approaching 80%. This phenomenon could be potentially attributed to the granular hydrogel-mediated delivery of polyplex nanoparticles, which revolutionizes the spatial and temporal distribution and thus the "encounter" mode between polyplexes and cells. Moreover, the gene therapy gel's intrinsic injectability and self-healing properties offer ease of administration, making it a highly promising candidate as a novel gene transfection gel dressing with significant potential across various fields, including regenerative medicine and innovative living materials.


Asunto(s)
ADN , Terapia Genética , Hidrogeles , Nanopartículas , Nanopartículas/química , Nanopartículas/toxicidad , Humanos , Hidrogeles/química , Hidrogeles/farmacología , ADN/química , Transfección/métodos , Animales , Oligopéptidos/química , Técnicas de Transferencia de Gen
9.
Sci Total Environ ; 949: 175081, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39069182

RESUMEN

Lost soil organic carbon (SOC) in degraded grasslands can be restored via the 'grazing exclusion' practice, but it was unknown how long (# of years) the restoration process can take. A synthesis of four decades of studies revealed that grazing exclusion increased SOC stocks in the topsoil (0-0.30 m) by 14.8 % (±0.8 Std Err), on average, compared to moderate-to-heavy grazing (MtH); During which SOC stock increased steadily, peaked in Year 18.5, and then declined. At peak, SOC stock was 42.5 % greater under grazing exclusion than under MtH due to 100.4 ± 4.2 % increase in aboveground biomass and 80.3 ± 33.5 % increase in root biomass. Grazing exclusion also increased soil C:N ratio by 7.6 % while decreasing bulk density by 9.4 %. Grazing exclusion could be ceased 18.5 years after initiation of grazing exclusion as plant biomass input balances carbon decomposition and SOC equilibrium occurs then additional benefits start diminishing.

10.
Adv Mater ; 36(35): e2406837, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38923606

RESUMEN

Na metal batteries (NMBs) are attracting increasing attention because of their high energy density. However, the widespread application of NMBs is hindered by the growth of Na dendrites and interface instability. The design of artificial solid electrolyte interphase (SEI) with tuned chemical/electrochemical/mechanical properties is the key to achieving high-performance NMBs. This work develops a metal-doped nanoscale polymeric film with tunable composition, sodiophilic sites and improved stiffness. The incorporation of metal crosslinkers in the polymer chains results in exceptional electrochemical stability for Na metal anodes, leading to a significantly prolonged lifespan even at high current densities, which is at the top of the reported literature. The mechanical properties measurements and electro-chemo-mechanical phase-field model are performed to interpret the impact of the ionic transportation capability (decoupled mechanical) and mechanic property in the metal-doped polymer interface. In addition, this approach provides a promising strategy for the rational design of electrode interfaces, providing enhanced mechanical stability and improved sodiophilicity, which can open up opportunities for the fabrication of next-generation energy storage.

11.
Front Public Health ; 12: 1351849, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38864022

RESUMEN

Background: Healthcare resources are necessary for individuals to maintain their health. The Chinese government has implemented policies to optimize the allocation of healthcare resources and achieve the goal of equality in healthcare for the Chinese people since the implementation of the new medical reform in 2009. Given that no study has investigated regional differences from the perspective of healthcare resource agglomeration, this study aimed to investigate China's healthcare agglomeration from 2009 to 2017 in China and identify its determinants to provide theoretical evidence for the government to develop and implement scientific and rational healthcare policies. Methods: The study was conducted using 2009-2017 data to analyze health-resource agglomeration on institutions, beds, and workforce in China. An agglomeration index was applied to evaluate the degree of regional differences in healthcare resource allocation, and spatial econometric models were constructed to identify determinants of the spatial agglomeration of healthcare resources. Results: From 2009 to 2017, all the agglomeration indexes of healthcare exhibited a downward trend except for the number of institutions in China. Population density (PD), government health expenditures (GHE), urban resident's disposable income (URDI), geographical location (GL), and urbanization level (UL) all had positive significant effects on the agglomeration of beds, whereas both per capita health expenditures (PCHE), number of college students (NCS), and maternal mortality rate (MMR) had significant negative effects on the agglomeration of institutions, beds, and the workforce. In addition, population density (PD) and per capita gross domestic product (PCGDP) in one province had negative spatial spillover effects on the agglomeration of beds and the workforce in neighboring provinces. However, MMR had a positive spatial spillover effect on the agglomeration of beds and the workforce in those regions. Conclusion: The agglomeration of healthcare resources was observed to remain at an ideal level in China from 2009 to 2017. According to the significant determinants, some corresponding targeted measures for the Chinese government and other developing countries should be fully developed to balance regional disparities in the agglomeration of healthcare resources across administrative regions.


Asunto(s)
Recursos en Salud , China , Humanos , Estudios Longitudinales , Recursos en Salud/estadística & datos numéricos , Modelos Econométricos , Asignación de Recursos , Gastos en Salud/estadística & datos numéricos , Análisis Espacial
12.
Front Public Health ; 12: 1327844, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841657

RESUMEN

Objective: This study explored the impact of a family intervention on the relapse rate of Chinese patients with alcohol dependence. Methods: A total of 151 male patients with alcohol dependence who were discharged from the Substance Dependence Department of the Wenzhou Seventh People's Hospital from January to December 2020 were selected. They were divided into the control (n = 73) and experimental (n = 78) groups. Patients in both groups received routine alcohol cessation treatment. Moreover, patients in the experimental group were followed up by a professional psychiatrist to carry out individual family intervention. The Family Function Rating Scale (FAD), a Self-made general information questionnaire, and the Chinese version of the Family Intimacy and Adaptability Scale (FACESI-CV) were performed. Re-drinking rate and readmission rate were assessed. Results: Family intervention could reduce relapse rate (31, 39.74%) and rehospitalization (27, 34.62%) compared with the control group. After family training, FAD factor scores were improved in the experiment group in comparison with the control group. Family training improved communication (18.2 ± 3.7), role (20.8 ± 2.5), emotional response (10.8 ± 1.8), emotional involvement (13.7 ± 1.2), behavioral control (19.8 ± 1.2), and overall functionality (23.5 ± 2.1) in the experiment group in comparison with the control group. After family training, intimacy (70.5 ± 8.7) and adaptability (64.1 ± 6.9) in the experiment group was higher than in the control group. After family intervention, Michigan Alcohol Dependence Scale (MAST) (9.21 ± 0.68) and Short-Form 36 (SF-36) (80.32 ± 4.47) in the experiment group were higher than the control group. Conclusion: Family intervention for families of patients with alcohol dependence can improve their family function, increase their family intimacy and adaptability, and reduce the rate of relapse.


Asunto(s)
Alcoholismo , Recurrencia , Humanos , Masculino , Alcoholismo/psicología , Adulto , China , Persona de Mediana Edad , Encuestas y Cuestionarios , Terapia Familiar/métodos , Familia/psicología
13.
J Chem Theory Comput ; 20(13): 5396-5407, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38900275

RESUMEN

Self-assembly of platinum(II) complex foldamers is an essential approach to fabricate advanced luminescent materials. However, a comprehensive understanding of folding kinetics and their absorption spectra remains elusive. By constructing Markov state models (MSMs) from large-scale molecular dynamics simulations, we reveal that two largely similar dinuclear alknylplatinum(II) terpyridine foldamers, Pt-PEG and Pt-PE with slightly different bridges, exhibit distinctive folding kinetics. Particularly, Pt-PEG bears bridge-dominant, plane-dominant, and cooperative pathways, while Pt-PE only prefers the plane-dominant pathway. Such preference originates from their difference in intrabridge electrostatic interactions, leading to contrastive distributions of metastable states. We also found that the bridge-dominant pathway for Pt-PEG becomes more favorable when lowering the temperature. Interestingly, based on the comprehensive conformation ensembles from our MSMs, we reveal the conformation-dependent absorption spectra of Pt-PEG and Pt-PE. Our theoretical spectra not only align with experimental results but also reveal the contributions of diverse conformations to the overall absorption bands explicitly, facilitating the rational design of stimuli-responsive smart luminescent molecules.

14.
Cardiovasc Diabetol ; 23(1): 154, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702735

RESUMEN

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.


Asunto(s)
Biomarcadores , Glucemia , Resistencia a la Insulina , Índice de Severidad de la Enfermedad , Triglicéridos , Adulto , Femenino , Humanos , Masculino , Biomarcadores/sangre , Glucemia/metabolismo , China/epidemiología , HDL-Colesterol/sangre , Progresión de la Enfermedad , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/sangre , Hipertensión Pulmonar Primaria Familiar/fisiopatología , Hipertensión Pulmonar Primaria Familiar/mortalidad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Triglicéridos/sangre
15.
Phytomedicine ; 129: 155647, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38703660

RESUMEN

BACKGROUND: Oxaliplatin is the most common chemotherapeutic agent for patients with colorectal cancer. However, its anti-cancer efficacy is restricted by drug resistance occurring through several mechanisms, including autophagy. Liensinine exerts a considerable anti-tumor effect and can regulate autophagy. Inhibition of autophagy is a strategy to reverse resistance to oxaliplatin. The aim of this study was to check if liensinine can enhance the therapeutic efficacy of oxaliplatin in colorectal cancer and if so, elucidate its mechanism. METHODS: Two colorectal cancer cell lines, HCT116 and LoVo, and one normal intestinal epithelial cell, NCM-460 were used for in vitro experiments. Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays were used to evaluate the cytotoxicity of liensinine and oxaliplatin. Network pharmacology analysis and Human XL Oncology Array were used to screen targets of liensinine. Transfections and autophagy regulators were used to confirm these targets. The relationship between the target and clinical effect of oxaliplatin was analyzed. Patient-derived xenograft (PDX) models were used to validate the effects of liensinine and oxaliplatin. RESULTS: CCK-8 and colony formation assays both showed that the combination treatment of liensinine and oxaliplatin exerted synergistic effects. Results of the network pharmacology analysis and Human XL Oncology Array suggested that liensinine can inhibit autophagy by targeting HIF-1α/eNOS. HIF-1α was identified as the key factor modulated by liensinine in autophagy and induces resistance to oxaliplatin. HIF-1α levels in tumor cells and prognosis for FOLFOX were negatively correlated in clinical data. The results from three PDX models with different HIF-1α levels showed their association with intrinsic and acquired resistance to oxaliplatin in these models, which could be reversed by liensinine. CONCLUSIONS: Research on the relationship between HIF-1α levels and the clinical effect of oxaliplatin is lacking, and whether liensinine regulates HIF-1α is unknown. Our findings suggest that liensinine overcomes the resistance of colorectal cancer cells to oxaliplatin by suppressing HIF-1α levels to inhibit autophagy. Our findings can contribute to improving prognosis following colorectal cancer therapy.


Asunto(s)
Autofagia , Neoplasias Colorrectales , Resistencia a Antineoplásicos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Oxaliplatino , Humanos , Oxaliplatino/farmacología , Autofagia/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Animales , Resistencia a Antineoplásicos/efectos de los fármacos , Línea Celular Tumoral , Ratones , Ratones Desnudos , Células HCT116 , Ensayos Antitumor por Modelo de Xenoinjerto , Sinergismo Farmacológico , Isoquinolinas , Fenoles
16.
J Colloid Interface Sci ; 671: 653-663, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38820849

RESUMEN

The application of Li-S batteries on large scale is held back by the sluggish sulfur kinetics and low synthesis efficiency of sulfur host. In addition, the preparation of catalysts that promote polysulfide redox kinetics is complex and time-consuming, reducing the cost of raw materials in Li-S. Here, a universal synthetic strategy for rapid fabrication of sulfur cathode and metal compounds nanocatalysts is reported based on microwave heating of graphene. Heat-sensitive materials can achieve rapid heating due to graphene reaching 500 ℃ within 4 s via microwave irradiation. The MoP-MoS2/rGO catalyst demonstrated in this work was synthesized within 60 s. When used for catalysts for Li-S batteries whose graphene/sulfur cathodes were also synthesized by microwave heating, enhanced catalytic effect for sulfur redox reaction was verified via experimental and DFT theoretical results. Benefiting from fast redox reaction (MoP), smooth Li+ diffusion pathways (MoS2), and large conductive network (rGO), the assembled Li-S battery with MoP-MoS2/rGO-Add@CS displays a remarkable initial specific capacity, stable lithium anode and good cycle stability (in pouch cells) using this two-pronged strategy. The work provides a practical strategy for advanced Li-S batteries toward a wide range of applications.

17.
J Stomatol Oral Maxillofac Surg ; : 101925, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38815725

RESUMEN

Achieving robust soft tissue integration around dental implants is crucial for long-term clinical success, as it forms a protective biological seal against bacterial invasion. However, the soft tissue attachment to implants is relatively deficient compared to natural teeth, particularly in the connective tissue region lacking sufficient gingival fibroblasts and collagen fiber alignment. This study proposed an innovative strategy to enhance peri­implant soft tissue integration by modulating gingival fibroblast behavior via photothermal conversion. Zirconia surfaces were coated with polydopamine (PDA), a melanin-like polymer exhibiting near-infrared (NIR) absorption for photothermal conversion. Under NIR irradiation, the PDA coating enabled mild hyperthermia (42-43 °C) on the zirconia surface. Remarkably, this mild photothermal stimulation significantly promoted human gingival fibroblast proliferation, adhesion, and collagen production compared to unmodified zirconia in vitro. By utilizing the photothermal properties of PDA coatings to modulate cellular behaviors beneficial for connective tissue formation, this approach provides a promising avenue to achieve improved soft tissue integration and long-term stability of dental implants. The findings highlight the innovative potential of combining biomaterial surface engineering with photothermal therapy for applications in implant dentistry.

18.
Glob Chang Biol ; 30(4): e17291, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38647225

RESUMEN

Terrestrial ecosystem resilience is crucial for maintaining the structural and functional stability of ecosystems following disturbances. However, changes in resilience over the past few decades and the risk of future resilience loss under ongoing climate change are unclear. Here, we identified resilience trends using two remotely sensed vegetation indices, analyzed the relative importance of potential driving factors to resilience changes, and finally assessed the risk of future resilience loss based on the output data of eight models from CMIP6. The results revealed that more than 60% of the ecosystems experienced a conversion from an increased trend to a declined trend in resilience. Attribution analysis showed that the most important driving factors of declined resilience varied regionally. The declined trends in resilience were associated with increased precipitation variability in the tropics, decreased vegetation cover in arid region, increased temperature variability in temperate regions, and increased average temperature in cold regions. CMIP6 reveals that terrestrial ecosystems under SPP585 are expected to experience more intense declines in resilience than those under SSP126 and SSP245, particularly in cold regions. These results highlight the risk of continued degradation of ecosystem resilience in the future and the urgency of climate mitigation actions.


Asunto(s)
Cambio Climático , Ecosistema , Temperatura , Modelos Teóricos
19.
Sci Total Environ ; 931: 172745, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38677425

RESUMEN

The impact of global climate change on mountainous regions with significant elevational gaps is complex and often unpredictable. In particular, alpine grassland ecosystems, are experiencing changes in their spatial patterns along elevational gradients, which increases their vulnerability to degradation. Therefore, a more detailed understanding of spatiotemporal changes in alpine grassland productivity along elevational gradients and an elevation-dependent characterization of the effects of climatic variables on grassland productivity dynamics are essential. Thus, we conducted a study in the Tibetan Plateau, where we collected 2251 above-ground biomass (AGB) observations collected from 1986 to 2020. Mean annual temperature (TMP), annual precipitation (PRE), interannual precipitation variability (CVP), and snowmelt (SNMM) were chosen as influential variables. Using the Random Forest algorithm, we generated an AGB raster dataset covering the period 1989-2020 based on earth observation data at 30 m resolution to examine the dynamics of alpine grasslands and their response to climate change with respect to elevation. The results showed that the AGB of alpine grassland on the Tibetan Plateau was 49.17 g/m2. We observed an increasing trend in grassland AGB at high elevations, with a growth rate of about 0.28 g/m2 per year within the interval of 3100-4800 m. However, above the elevation of approximately 4400-4600 m, we observed a decoupling trend between grassland AGB and TMP. Moreover, at most elevations, the proportion of maximum partial correlation coefficients for CVP, PRE, and SNMM surpassed that of TMP. We found the dominant role of precipitation variability on grassland AGB dynamics, with 22.80 % and 18.86 % for CVP+ and CVP-, respectively. The proportion of CVP+ did not vary much at different elevations, whereas the proportion of CVP- increased with elevation, varying between 12.85 and 30.25 %. In the future, precipitation on the Tibetan plateau is expected to increase, potentially reversing its original positive impact.


Asunto(s)
Altitud , Biomasa , Cambio Climático , Pradera , Tibet , Lluvia , Monitoreo del Ambiente , Nieve
20.
Phys Rev Lett ; 132(11): 117401, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38563954

RESUMEN

When studying interacting systems, computing their statistical properties is a fundamental problem in various fields such as physics, applied mathematics, and machine learning. However, this task can be quite challenging due to the exponential growth of the state space as the system size increases. Many standard methods have significant weaknesses. For instance, message-passing algorithms can be inaccurate and even fail to converge due to short loops, while tensor network methods can have exponential computational complexity in large graphs due to long loops. In this Letter, we propose a new method called "tensor network message passing." This approach allows us to compute local observables like marginal probabilities and correlations by combining the strengths of tensor networks in contracting small subgraphs with many short loops and the strengths of message-passing methods in globally sparse graphs, thus addressing the crucial weaknesses of both approaches. Our algorithm is exact for systems that are globally treelike and locally dense-connected when the dense local graphs have a limited tree width. We have conducted numerical experiments on synthetic and real-world graphs to compute magnetizations of Ising models and spin glasses, and have demonstrated the superiority of our approach over standard belief propagation and the recently proposed loopy message-passing algorithm. In addition, we discuss the potential applications of our method in inference problems in networks, combinatorial optimization problems, and decoding problems in quantum error correction.

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