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BACKGROUND: Previous meta-analyses have investigated the efficacy of lipid-lowering therapies for atherosclerotic cardiovascular disease; however, few have focused on patients with acute coronary syndrome (ACS). This meta-analysis aimed to compare the benefits of intensive lipid-lowering therapy with those of background statin therapy in patients with ACS. METHODS: Searches were performed on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for articles published until April 13, 2023. Randomized controlled trials that compared intensive lipid-lowering therapies and background statin therapies in patients with prior ACS and recorded the outcome of three-point major cardiovascular events (MACE) were included. The risk ratio (RR) with 95% confidence interval (CI) was used as a measure of primary and secondary outcomes. RESULTS: Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83-0.94; p < 0.001), recurrent ACS (RR, 0.82; 95% CI, 0.71-0.96; p = 0.013), nonfatal myocardial infarction (MI) (RR, 0.87; 95% CI, 0.81-0.93; p < 0.001), stroke (RR, 0.83; 95% CI, 0.73-0.94; p = 0.003), and unstable angina-related hospitalization (RR, 0.57; 95% CI, 0.33-0.99; p = 0.046), but not all-cause mortality (RR, 0.94; 95% CI, 0.82-1.07; p = 0.329), cardiovascular disease-related mortality (RR, 0.96; 95% CI, 0.88-1.06; p = 0.457) or coronary revascularization (RR, 0.89; 95% CI, 0.79-1.00; p = 0.057). CONCLUSIONS: Intensive lipid-lowering therapies may reduce the risk of three-point MACE, recurrent ACS, nonfatal MI, stroke, and hospitalization for unstable angina in patients with ACS undergoing background statin therapy. These results may assist in clinical decision-making for the secondary prevention of cardiovascular events to initiate intensive lipid-lowering therapies immediately after ACS.
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Síndrome Coronario Agudo , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/mortalidad , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Hipolipemiantes/uso terapéutico , Hipolipemiantes/administración & dosificación , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Resultado del Tratamiento , Hospitalización/estadística & datos numéricos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: GLP-1 receptor agonists are clinically utilized for type 2 diabetes and obesity. In vitro and in vivo preclinical studies were performed to assess the druggability of a novel small molecule GLP-1 receptor biased agonist SAL0112. EXPERIMENTAL APPROACH: The HTRF assay, FLIPR assay, TR-FRET assay, and PathHunter assay were utilized for in vitro studies. Liver transporter tests were conducted using the HEK293-OATP1B1 and HEK293-OATP1B3 cell lines. In vitro stability assessments of various species and in vivo PK studies in rodents were performed. A model of type 2 diabetes and obesity induced by a high-energy diet in transgenic C57BL/6 mice expressing the human GLP-1 receptor gene was conducted. PRINCIPAL RESULTS: SAL0112 demonstrated high potency and selectivity in activating the Gαs pathway of the GLP-1 receptor, with no observed desensitization. SAL0112 demonstrated greater stability in human and rat liver microsomes compared to Danuglipron. In vivo PK studies revealed higher absorption of SAL0112 in rats. SAL0112 displayed a significantly lower potential for DDI on liver transporters compared to Danuglipron. SAL0112 led to significant reductions in body weight (P<0.001), blood glucose levels in OGTT (P<0.001), HbA1c (P<0.05) and improved insulin resistance (P<0.01). Notably, it increased peripheral adipocyte density and resolved hepatic steatosis. The efficacy of SAL0112 was found to be comparable to that of Danuglipron and Liraglutide. CONCLUSION: SAL0112 demonstrated potent and selective GLP-1 receptor biased agonism, effectively alleviating signs of type 2 diabetes in a mouse model. These promising findings pave the way for the advancement of SAL0112 into clinical trials.
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Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Ratones Endogámicos C57BL , Animales , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Humanos , Masculino , Ratas , Células HEK293 , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangre , Ratones , Hipoglucemiantes/farmacología , Hipoglucemiantes/farmacocinética , Ratones Transgénicos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Microsomas Hepáticos/metabolismo , Ratas Sprague-Dawley , Glucemia/efectos de los fármacos , Glucemia/metabolismoRESUMEN
Objective: Population-based studies on chronic sinusitis have predominantly focused on Europe and the Americas, but research on chronic sinusitis within large Asian populations remains scarce. This study aims to explore the link between dietary factors and chronic sinusitis among ethnic Koreans in Asia. Design: A cross-sectional study. Setting: Data were collected from the Korean National Health and Nutrition Examination Survey (KNHANES) in 2012. Participants: Participants in the study were included based on a doctor's diagnosis of chronic sinusitis, as determined through the ear, nose, and throat examination questionnaires. Results: Adolescents [adjusted P value (aP) < .001, adjusted odds ratio (aOR) = 1.881, 95% confidence interval (CI) = 1.380-2.564] and individuals with college and higher education (aP = .042, aOR = 1.298, 95% CI = 1.009-1.669) were more likely to develop chronic rhinosinusitis. In addition, levels of dietary fat [P = .001, interquartile range (IQR) = 34.085] and energy intake (P = .004, IQR = 981.106) were associated with an increased risk of chronic sinusitis. Moreover, high dietary inflammatory index (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721), and high intake of fried pork chops (aP = .028, aOR = 1.335, 95% CI = 1.033-1.777), bread (aP = .024, aOR = 1.364, 95% CI = 1.042-1.786), and rice (aP = .021, aOR = 1.382, 95% CI = 1.051-1.818) were risk factors for chronic sinusitis, while cucumber consumption (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721) was a protective factor for chronic sinusitis. Conclusion: This study revealed a significant correlation between diet and development of chronic sinusitis. These findings suggest that promoting an anti-inflammatory dietary pattern and providing guidance on healthy eating habits could help reduce the incidence of chronic sinusitis and enhance its management.
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Purpose: Acute pancreatitis is a common gastrointestinal emergency. Approximately 20% of patients with acute pancreatitis develop organ failure, which is significantly associated with adverse outcomes. This study aimed to establish an early prediction model for persistent organ failure in acute pancreatitis patients using 24-hour admission indicators. Patients and Methods: Clinical data and 24-h laboratory indicators of patients diagnosed with acute pancreatitis from January 1, 2017 to January 1, 2022 in Shanxi Bethune Hospital were collected. Patients from 2017 to 2021 were used as the training cohort to establish the prediction model, and patients from 2021 to 2022 were used as the validation cohort. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve (AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group. Results: A total of 1166 patients with acute pancreatitis were included, a total of 145 patients suffered from persistent organ failure from 2017 to 2021. Data were initially selected for 100 variables, and after inclusion and exclusion, 46 variables were used for further analysis. Two prediction models were established and nomogram was drawn respectively. After comparison, the prediction values of the two models were similar (The univariate model AUC was 0.867, 95% CI (0.834-0.9). The LASSO model AUC was 0.864, 95% CI (0.828-0.895)), and the model established by LASSO regression was more parsimonious. A web calculator was developed using the model established by LASSO. Conclusion: Predictive model including 6 risk indicators can be used to predict the risk of persistent organ failure in patients with acute pancreatitis.
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Introduction: Angiotensin receptor-neprilysin inhibitor (ARNi), comprised of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has established itself as a safe and effective intervention for hypertension. S086 is a novel ARNi cocrystal developed by Salubris for the treatment of heart failure and hypertension. Methods: Dahl Salt Sensitive (DSS) hypertensive rat model and telemetry system were employed in this study to investigate the anti-hypertensive efficacy of S086 and compare it with the first ARNi-LCZ696. Results and discussion: The study showed that oral administration of S086 dose-dependently lowered blood pressure (P < 0.001). The middle dosage of S086 (23 mg/kg) exhibited efficacy comparable to LCZ696 (68 mg/kg), while also demonstrating superiority at specific time points (P < 0.05). Notably, water consumption slightly decreased post-treatment compared to the vehicle group. Furthermore, there were significant increases in natriuresis and diuresis observed on the first day of treatment with 23 mg/kg and 68 mg/kg S086 (P < 0.001). However, over the course of treatment, the effects in all treatment groups gradually diminished. This study demonstrates the anti-hypertensive efficacy of S086 in DSS hypertensive rat model, offering promising avenues for the clinical development of S086 as a hypertension treatment.
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Reducing CO2 emissions of the iron and steel industry, a typical heavy CO2-emitting sector, is the only way that must be passed to achieve the 'dual-carbon' goal, especially in China. In previous studies, however, it is still unknown what is the difference between blast furnace-basic oxygen furnace (BF-BOF), scrap-electric furnace (scrap-EF) and hydrogen metallurgy process. The quantitative research on the key factors affecting CO2 emissions is insufficient. There is also a lack of research on the prediction of CO2 emissions by adjusting industrial structure. Based on material flow analysis, this study establishes carbon flow diagrams of three processes, and then analyze the key factors affecting CO2 emissions. CO2 emissions of the iron and steel industry in the future is predicted by adjusting industrial structure. The results show that: (1) The CO2 emissions of BF-BOF, scrap-EF and hydrogen metallurgy process in a site are 1417.26, 542.93 and 1166.52 kg, respectively. (2) By increasing pellet ratio in blast furnace, scrap ratio in electric furnace, etc., can effectively reduce CO2 emissions. (3) Reducing the crude steel output is the most effective CO2 reduction measure. There is still 5.15 × 108-6.17 × 108 tons of CO2 that needs to be reduced by additional measures.
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Contaminantes Atmosféricos , Hierro , Contaminantes Atmosféricos/análisis , Dióxido de Carbono/análisis , Acero , Carbono , Metalurgia , HidrógenoRESUMEN
Aim: Investigate TKI sitravatinib plus anti-PD-1 antibody tislelizumab in patients with unresectable/advanced/metastatic melanoma with disease progression on/after prior first-line anti-PD-(L)1 monotherapy. Methods: Open-label, multicenter, multicohort study (NCT03666143). Patients in the melanoma cohort (N = 25) received sitravatinib once daily plus tislelizumab every 3 weeks. The primary end point was safety and tolerability. Results: Treatment-emergent adverse events (TEAEs) occurred in all patients, with ≥grade 3 TEAEs in 52.0%. Most TEAEs were mild-or-moderate in severity, none were fatal, and few patients discontinued treatment owing to TEAEs (12.0%). Objective response rate was 36.0% (95% CI: 18.0-57.5). Median progression-free survival was 6.7 months (95% CI: 4.1-not estimable). Conclusion: Sitravatinib plus tislelizumab had manageable safety/tolerability in patients with anti-PD-(L)1 refractory/resistant unresectable/advanced/metastatic melanoma, with promising antitumor activity. Clinical Trial Registration: NCT03666143 (ClinicalTrials.gov).
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Anilidas , Anticuerpos Monoclonales Humanizados , Crocus , Melanoma , Piridinas , Humanos , Melanoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Liver cancer is one of the most common malignant tumors in the world, and its incidence and mortality are increasing year by year. The prognosis of liver cancer depends on the stage of liver cancer, the treatment method, the liver function, and individual differences. The prognosis of liver cancer mainly worsens with the progression of the stage. The prediction and staging system of liver cancer prognosis plays a very important role in the outcome of liver cancer prognosis, providing some guidance for clinical practice and bringing benefits for patients. This article reports on the prediction models and staging systems that have been applied in the field of liver cancer in the past 5 years, objectively analyzes the advantages and disadvantages, applicable population of each model and staging system, and searches for other patient and clinical characteristics that need to be considered for successfully establishing a prediction model, aiming to improve the specificity, sensitivity, and accuracy of liver cancer prediction and increase the overall survival rate of liver cancer.
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Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , PronósticoRESUMEN
BACKGROUND: Hypertension is a clinical syndrome characterized by elevated systemic arterial blood pressure associated with injury to the heart, kidney, brain, and other organs. Angiotensin receptor neprilysin inhibitors (ARNi), including angiotensin receptor blockers (ARBs) and neprilysin inhibitors (NEPi), have been shown to be safe and effective at reducing blood pressure and alleviating development of target organ injury. This study was used to develop S086 as a novel ARNi and conducted preclinical studies in animal models to evaluate the protective effects of S086 on target organs. METHODS: This study used a 14-month-old spontaneously hypertensive rat (SHR) model to evaluate the protective effects of S086 on the cardiovascular system and organs such as heart and kidney by blood pressure monitoring, urine and blood examination, pathological examination, and immunological index detection. RESULTS: After administering S086 orally to the SHR, their blood pressure and levels of renal injury indicators such as serum creatinine and urinary microalbumin were reduced, and myocardial cell necrosis and cardiac fibrosis of the heart were significantly improved. In addition, there were also significantly improvements in the histological lesions of blood vessels and the kidneys. CONCLUSIONS: The findings showed that S086 effectively reduced the blood pressure of SHR and had effects on alleviating development of heart, blood vessels and kidney.
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Hipertensión , Neprilisina , Ratas , Animales , Ratas Endogámicas SHR , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Hipertensión/patología , Presión Sanguínea , Receptores de AngiotensinaRESUMEN
Designing flexible wearable sensors with a wide sensing range, high sensitivity, and high stability is a vulnerable research direction with a futuristic field to study. In this paper, Ti3C2Tx MXene/carbon nanotube (CNT)/thermoplastic polyurethane (TPU)/polysulfone (PSF) composite films with excellent sensor performance were obtained by self-assembly of conductive fillers in TPU/PSF porous films with an asymmetric structure through vacuum filtration, and the porous films were prepared by the phase inversion method. The composite films consist of the upper part with finger-like "cavities" filled by MXene/CNTs, which reduces the microcracks in the conductive network during the tensile process, and the lower part has smaller apertures of a relatively dense resin cortex assisting the recovery process. The exclusive layer structure of the MXene/CNTs/TPU/PSF film sensor, with a thickness of 46.95 µm, contains 0.0339 mg/cm2 single-walled carbon nanotubes (SWNTs) and 0.348 mg/cm2 MXene only, providing functional range (0-80.7%), high sensitivity (up to 1265.18), and excellent stability and durability (stable sensing under 2300 fatigue tests, viable to the initial resistance), endurably cycled under large strains with serious damage to the conductive network. Finally, the MXene/CNTs/TPU/PSF film sensor is usable for monitoring pulse, swallow, tiptoe, and various joint bends in real time and distributing effective electrical signals. This paper implies that the MXene/CNTs/TPU/PSF film sensor has broad prospects in pragmatic applications.
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Nanotubos de Carbono , Humanos , Poliuretanos , Corteza CerebralRESUMEN
Observational data, such as electronic clinical records and claims data, can prove invaluable for evaluating the Average Treatment Effect (ATE) and supporting decision-making, provided they are employed correctly. The Inverse Probability of Treatment Weighting (IPTW) method, based on propensity scores, has demonstrated remarkable efficacy in estimating ATE, assuming that the assumptions of exchangeability, consistency, and positivity are met. Directed Acyclic Graphs (DAGs) offer a practical approach to assess the exchangeability assumption, which asserts that treatment assignment and potential outcomes are independent given a set of confounding variables that block all backdoor paths from treatment assignment to potential outcomes. To ensure a consistent ATE estimator, one can adjust for a minimally sufficient adjustment set of confounding variables that block all backdoor paths from treatment assignment to the outcome. To enhance the efficiency of ATE estimators, our proposal involves incorporating both the minimally sufficient adjustment set of confounding variables and predictors into the propensity score model. Extensive simulations were conducted to evaluate the performance of propensity score-based IPTW methods in estimating ATE when different sets of covariates were included in the propensity score models. The simulation results underscored the significance of including the minimally sufficient adjustment set of confounding variables along with predictors in the propensity score models to obtain a consistent and efficient ATE estimator. We applied this proposed method to investigate whether tracheostomy was causally associated with in-hospital infant mortality, utilizing the 2016 Healthcare Cost and Utilization Project Kids' Inpatient Database. The estimated ATE was found to be approximately 2.30%-2.46% with p-value >0.05.
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Due to high material density, high energy consumption density and CO2 emission density, it is not only difficult but significant to clarify the relationship between energy consumption, the CO2 emission and the production cost in different conditions. However, the previous researches rarely refer how to balance the energy consumption, the CO2 emission and the production cost after the fluctuation of material, energy and carbon price as well as what will happen to them if production structure changes. Therefore, based on the conservation law of mass and energy, to study iron and steel manufacturing process (ISMP), this paper, taking carbon price into consideration, establishes a muti-optimization model of energy consumption, CO2 emission and cost. After optimization with different objectives, the production cost per tonne of crude steel is reduced by 192.03 CNY (7.71%), the CO2 emission per tonne of crude steel is reduced by 224.22 kg (13.37%), and the energy consumption per tonne of steel is reduced by 51.20 kgce (9.10%). Moreover, based on the optimization results under different objectives, it is ironmaking process (coal ratio and ore ratio) and steelmaking process (amount of scrap steel) that has more impact on three above as well as ore blending and coal blending have a great influence on production cost but little effect on energy consumption and CO2 emission.
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Dióxido de Carbono , Hierro , Acero/química , Carbón Mineral , CarbonoRESUMEN
Heterogeneous N-heterocyclic carbene materials have attracted increasing interest in the fields of materials science and catalysis due to their unique properties and potential applications. However, current heterogeneous systems primarily focus on a single class of carbene. In this work, we simultaneously introduce two classes of typical five-membered carbenes into a graphene lattice, forming a series of novel two-dimensional heterogeneous N-heterocyclic carbene nanomaterials (2D-NCMs) composed of multiple carbenes. First-principles calculations demonstrate the thermodynamic stability of the designed 2D-NCMs, as well as their diverse electronic properties ranging from metallic to semiconducting. The incorporation of carbenes in the 2D-NCMs enables them to adsorb both acidic BCl3 and basic CO molecules, thus exhibiting unique amphoteric properties. Furthermore, the 2D-NCMs exhibit remarkable adsorption capacities for ten transition metals, highlighting their promising potential for future catalytic applications. By adjusting the proportions of the two classes of carbenes, we can effectively regulate the electronic properties and adsorption capacities of small molecules and transition metals in the 2D-NCMs. This study presents a novel strategy for designing and regulating the properties of heterogeneous N-heterocyclic carbenes, offering significant implications in the fields of catalysis and materials science.
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Allisartan isoproxil (AI) is an angiotensin II type 1 receptor blocker and be converted into the active substance EXP3174 in vivo. We evaluated the drug-drug interactions of AI and an indapamide sustained-release (Ind SR) preparation, as well as the pharmacokinetic characteristics and safety of AI and Ind SR in healthy subjects. The trial was set up in 6 sequences and 3 cycles, and each cycle contained a 7-day washout period. Subjects received 3 different trial drugs (A, AI; B, Ind SR; C, AI + Ind SR) during 3 different cycles. Twenty-four subjects were enrolled in the clinical trial. Of these, 22 completed the study, 2 subjects dropped out due to adverse events (AEs). For subjects given AI alone or combined with Ind SR, the pharmacogenetic parameters Cmax and the geometric mean ratio of steady state (combined/single) of EXP3174 was 130%. The geometric mean ratio of area under the concentration-time curve over the dosing interval at steady state (combined/single use) was 144.5%. Therefore, the combination of Ind SR had an impact on the pharmacokinetics of AI. Then, the results indicated that the AI combination had no effect on the pharmacokinetics of Ind SR. Serious AEs did not occur. The AEs in this clinical trial were the same as those for AI and Ind SR. Combined administration resulted in 2 cases (2 subjects) of Grade 3 hypotension and 1 case of Grade 3 hypotension with AI alone. Considering that this trial included healthy volunteers, the risk of hypotension was expected to be manageable.
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Hipotensión , Indapamida , Humanos , Indapamida/efectos adversos , Indapamida/farmacocinética , Preparaciones de Acción Retardada , Interacciones Farmacológicas , Hipotensión/inducido químicamenteRESUMEN
The effect of time-restricted eating (TRE) has been summarized in previous studies, but its benefits in combination with calorie restriction (CR) still need to be determined. The present meta-analysis aimed to evaluate the efficacy of TRE with CR on weight loss and cardiometabolic risk. PubMed, Embase, Cochrane Library, and gray literature databases were searched from inception to October 18, 2022, for potential randomized controlled trial (RCT) studies based on predefined inclusion and exclusion criteria. Body weight and other cardiometabolic risk factors were described as weighted mean difference (WMD) with a 95% confidence interval (CI). Eight RCTs involving 579 participants were enrolled in the present analysis. The pooled results showed that TRE with CR reduced the body weight, fat mass, and waist circumference significantly (WMD: -1.40, 95% CI: -1.81 to -1.00, and I2: 0%; WMD: -0.73, 95% CI: -1.39 to -0.07, and I2: 0%; WMD: -1.87, 95% CI: -3.47 to -0.26, and I2: 67.25%, respectively). However, compared with CR alone, TRE plus CR exhibited no significant benefit on the blood pressure, glucose profile, and lipid profile. Subgroup analysis suggested that early TRE is more effective in weight loss (WMD: -1.42, 95% CI: -1.84 to -1.01, and I2: 0%) and improving fat mass (WMD: -1.06, 95% CI: -1.91 to -0.22, and I2: 0%) than delayed or broader TRE when combined with CR. Although the combination of TRE and CR can effectively decrease body weight, fat mass, and waist circumference, the long-term effects, particularly those on cardiometabolic risk in participants with chronic cardiovascular disease and diabetes, remain to be explored.
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Restricción Calórica , Enfermedades Cardiovasculares , Humanos , Peso Corporal , Pérdida de Peso , Enfermedades Cardiovasculares/prevención & control , Presión SanguíneaRESUMEN
Interleukin-33 (IL-33) is a member of the IL-1 family of cytokines. IL-33 is associated with the expression of tissue damage or necrosis after increasing and being released into the cell, it influences the suppression of tumorigenicity 2 (ST2) receptor expression of a variety of immune cells (including mast cells and type 2 congenital lymphocytes). Furthermore, during type 2 innate immune reactions and allergic inflammation IL-33 plays a central role in immune amplification and "alarming"; thus, regulating immune responeses. IL-33 is closely related to inflammation-related diseases such as allergic diseases, autoimmune diseases, infectious diseases, and tumors. It is essential in maintaining tissue homeostasis, eliminating inflammation, and repairing tissue damage. We searched the Web of Science Core Collection (WoSCC) database for relevant publications on IL-33 from 2005 to 2021 and screened them according to specific inclusion criteria. A total of 2626 articles were included in our analysis. Using Microsoft Excel 2019 (Redmond, WA), VOSviewer 1.6.11 (The Centre for Science and Technology Studies, CWTS), and Citespace5.8. R2 (Drexel University, Philadelphia, PA) were used for data processing and visualization. Countries/regions, journals, authors, co-cited references, and keywords were analyzed. We discovered that IL-33 plays an important role as a cytokine in numerous diseases, especially allergic diseases. Studying its mechanism of action is of great importance for developing novel drugs and therapeutics.
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Microcystis aeruginosa is the competitively dominant algal species in eutrophic waters and poses a serious threat to the aquatic ecological environment. To investigate the effects of eucalyptus tannins (TFL) and black water in eucalyptus plantations on M. aeruginosa, this study exposed M. aeruginosa to different concentrations (0 (control), 20, 50, 80, 110, and 140 mg L-1) of tannic acid (TA; hydrolyzed tannins, HT; reagent tannin), epigallocatechin gallate (EGCG; condensed tannins, CT; reagent tannin), eucalyptus tannins (TFL, complex tannin) and mixed TFL + Fe3+ solution (tannin: Fe3+ molar ratio = 1:10). The cell density, chlorophyll-a (Chl-a) content, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and soluble protein (SP) contents of algae under tannin stress were determined, and the algal cell density treated with under the combination of TFL and Fe3+ was determined. The results showed a reduction in the Chl-a content of algal cells, which inhibited photosynthesis; leading to membrane lipid peroxidation; and the complexation of soluble proteins resulting in blocked protein synthesis were the main mechanisms by which tannins inhibited the growth of M. aeruginosa. TFL achieved the same inhibition of algal cells as the tannin reagent at the same concentration. At 4 d, TFL at 80 mg L-1 and above could achieve more than 54.87 % algal density inhibition. The inhibition rate of 80 mg L-1 and above TFL + Fe3+ on algal density was more than 75 %, indicating that TFL + Fe3+ had a stronger inhibitory effect on algal density. The results may facilitate the resource utilization of eucalyptus harvesting residues, explorations of the potential application of eucalyptus tannins in the control of M. aeruginosa, and provide new ideas for ecological algal inhibition in eucalyptus plantations.
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Eucalyptus , Microcystis , Polifenoles , Taninos/metabolismo , Clorofila A/metabolismoRESUMEN
BACKGROUND: The assembly of metagenomes decomposes members of complex microbe communities and allows the characterization of these genomes without laborious cultivation or single-cell metagenomics. Metagenome assembly is a process that is memory intensive and time consuming. Multi-terabyte sequences can become too large to be assembled on a single computer node, and there is no reliable method to predict the memory requirement due to data-specific memory consumption pattern. Currently, out-of-memory (OOM) is one of the most prevalent factors that causes metagenome assembly failures. RESULTS: In this study, we explored the possibility of using Persistent Memory (PMem) as a less expensive substitute for dynamic random access memory (DRAM) to reduce OOM and increase the scalability of metagenome assemblers. We evaluated the execution time and memory usage of three popular metagenome assemblers (MetaSPAdes, MEGAHIT, and MetaHipMer2) in datasets up to one terabase. We found that PMem can enable metagenome assemblers on terabyte-sized datasets by partially or fully substituting DRAM. Depending on the configured DRAM/PMEM ratio, running metagenome assemblies with PMem can achieve a similar speed as DRAM, while in the worst case it showed a roughly two-fold slowdown. In addition, different assemblers displayed distinct memory/speed trade-offs in the same hardware/software environment. CONCLUSIONS: We demonstrated that PMem is capable of expanding the capacity of DRAM to allow larger metagenome assembly with a potential tradeoff in speed. Because PMem can be used directly without any application-specific code modification, these findings are likely to be generalized to other memory-intensive bioinformatics applications.
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Metagenoma , Microbiota , Metagenómica , Programas Informáticos , Biología ComputacionalRESUMEN
BACKGROUND: The cardiovascular toxicity of aromatase inhibitors (AIs) for women with estrogen receptor-positive breast cancer is controversial. We aimed to evaluate the association between AIs and the risk of myocardial infarction (MI) in women with estrogen receptor-positive breast cancer based on real-world studies. METHOD: PubMed, Embase, and Cochrane Library were searched to identify studies that estimated the association between MI risk and AIs. A random-effects model was used to evaluate the hazard ratio (HR) and 95% confidence intervals (CIs) of the predefined outcomes. RESULTS: A total of 134 476 patients from eight cohort studies were enrolled in our analysis. For MI incidence, no significant difference was found between the users of AIs and non-users (HR: .98, 95% CI: .83-1.17). The subgroup analysis of patients without a history of cardiovascular disease (CVD) suggested a reduced risk of MI (HR: .86, 95% CI: .77-.96). No significant difference was found for ischemic stroke (HR: .93, 95% CI: .82-1.07) and heart failure (HR: 1.24, 95% CI: .92-1.66) between the two groups. CONCLUSION: Based on real-world data, AIs may be a safe treatment route for patients with estrogen receptor-positive breast cancer and those with a history of CVD. AIs caused a major decrease in MI in patients without CVD history. However, more in-depth investigations are needed to explore the association between AI use and the incidence of MI in the treatment of estrogen receptor-positive breast cancer.