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Taurine is an amino acid that has been considered by animal husbandry as a feed additive due to its abundant biological functions. However, the effective dose of taurine added to feed is unknown. The aim of current study was to determine the optimal taurine supplementation level by investigating its effects on growth performance, diarrhea index, intestinal health and antioxidant capacity of weaned piglets. A total of 160 crossbred piglets (Landrace × Yorkshire, initially 8.39 ±0.11 kg) were assigned to 4 groups (10 pigs/pen and 4 replicates/group). Basal diets containing 0 (control, CON), 0.1%, 0.3%, and 0.5% taurine were respectively provided to the piglets for a duration of 28 days. Six piglets from each group were selected for euthanasia and subsequent sample collection on day 29. The results showed that dietary 0.3% or 0.5% taurine supplementation increased average daily gain (P < 0.05), feed to gain ratio (P < 0.01), and serum albumin (P < 0.05), and decreased diarrhea index (P < 0.01) and diamine oxidase (DAO) level in the serum (P < 0.05). The greater expression of tight junction-related genes, including ZO-1 (P < 0.05) and Claudin-1 (P < 0.01), were observed in the duodenum after supplementation with 0.5% taurine. The supplementation of 0.3% or 0.5% taurine resulted in a significant reduction of crypt depth (P < 0.01) and an increase of villus height-to-crypt depth ratio (P < 0.01) in the duodenum. A greater abundance of goblet cells was detected in the duodenum and jejunum of piglets fed 0.5% taurine (P < 0.05). In addition, serum superoxide dismutase (SOD) level, liver catalase (CAT) level and liver total antioxidant capacity level were all significantly (P < 0.05) increased with 0.1%, 0.3% or 0.5% dietary taurine supplementation. On the whole, dietary supplementation with 0.3% or 0.5% taurine has the potential to significantly enhance the growth performance of piglets by improving the integrity of the intestinal barrier and boosting their antioxidant capacity.
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BACKGROUND: Metabolic disorder, malnutrition and inflammation are involved and interplayed in the mechanisms of heart failure with preserved ejection fraction (HFpEF). We aimed to construct a Metabolism-malnutrition-inflammation score (MIS) to predict the risk of death in patients with HFpEF. METHODS: We included patients diagnosed with HFpEF and without infective or systemic disease. 20 biomarkers were filtered by the Least absolute shrinkage and selection operator (Lasso)-Cox regression. 1000 times bootstrapping datasets were generated to select biomarkers that appeared above 95% frequency in repetitions to construct the MIS. RESULTS: Among 1083 patients diagnosed with HFpEF, 342 patients (31.6%) died during a median follow-up period of 2.5 years. The MIS was finally constructed based on 6 biomarkers, they were albumin (ALB), red blood cell distribution width-standard deviation (RDW-SD), high-sensitivity C-reactive protein (hs-CRP), lymphocytes, triiodothyronine (T3) and uric acid (UA). Incorporating MIS into the basic predictive model significantly increased both discrimination (∆C-index = 0.034, 95% CI 0.013-0.050) and reclassification (IDI, 6.6%, 95% CI 4.0%-9.5%; NRI, 22.2% 95% CI 14.4%-30.2%) in predicting all-cause mortality. In the time-dependent receiver operating characteristic (ROC) analysis, the mean area under the curve (AUC) for the MIS was 0.778, 0.782 and 0.772 at 1, 3, and 5 years after discharge in the cross-validation sets. The MIS was independently associated with all-cause mortality (hazard ratio: 1.98, 95% CI [1.70-2.31], P < 0.001). CONCLUSIONS: A risk score derived from 6 commonly used inflammatory, nutritional, thyroid and uric acid metabolic biomarkers can effectively identify high-risk patients with HFpEF, providing potential individualized management strategies for patients with HFpEF.
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Mitochondrial adaptations dynamically reprogram cellular bioenergetics and metabolism and confer key properties for human cancers. However, the selective regulation of these mitochondrial responses remains largely elusive. Here, inspired by a genetic screening in acute myeloid leukemia (AML), we identify RAS effector RREB1 as a translational regulator and uncover a unique translation control system for nuclear-encoded mitochondrial proteins in human cancers. RREB1 deletion reduces mitochondrial activities and succinate metabolism, thereby damaging leukemia stem cell (LSC) function and AML development. Replenishing complex II subunit SDHD rectifies these deficiencies. Notably, inhibition of complex II re-sensitizes AML cells to venetoclax treatment. Mechanistically, a short RREB1 variant binds to a conserved motif in the 3' UTRs and cooperates with elongation factor eEF1A1 to enhance protein translation of nuclear-encoded mitochondrial mRNAs. Overall, our findings reveal a unique translation control mechanism for mitochondrial adaptations in AML pathogenesis and provide a potential strategy for targeting this vulnerability of LSCs.
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AIMS: Clinical practice guidelines are commonly written by professional societies in high-income countries (HIC) with limited anticipation of implementation obstacles in other environments. We used heart failure (HF) guidelines as a paradigm to examine this concern, by conducting a survey to understand clinicians' ability to implement HF guidelines and their perceptions of the current HF guideline applicability in low- and middle-income countries (LMIC). METHODS AND RESULTS: An online survey of physicians in the database of the Translational Medicine Academy who treat HF patients was offered by email from 5 October to 27 November 2023, inquiring of participants' demographic information, experience, and views of HF guidelines as related to their practice. Of 2622 participating clinicians, 1592 partially completed, and an additional 1030 fully completed the survey. Participants were from 138 countries; 668 practiced in HIC, and 1954 in LMIC. Those from LMIC regarded HF guidelines to be less applicable in their country than did those from HIC (p = 0.0002). Of all those responding, 75.3% indicated that it was somewhat or mostly true that the HF guidelines were mostly applicable to HIC. Those from LMIC, but not HIC indicated that the greatest implementation obstacle was that the guidelines were for HIC (51.3% vs. 43.1%; p = 0.0387). A significantly higher proportion of respondents from LMIC indicated that resources for caring for their patients were somewhat or mostly limiting in most cases, than did those in HIC (41.6% vs. 32.5%, p = 0.0068). CONCLUSION: This survey examined the widely-held thought that HF guidelines are broadly applicable to all regions of the world, concluding that such a perception is incorrect. Clinicians from LMIC view the absence of consideration of local resource limitations as the greatest obstacle for guideline implementation. The results regarding HF guidelines likely also have implications for other guidelines and resultant patient outcomes.
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BACKGROUND: The association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear. METHODS: A cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index). RESULTS: Among the 4,109 HF patients, FFA levels exceeding 0.4-0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11-1.58) for CV death & HHP, 1.45 (95% CI: 1.16-1.82) for CV death, and 1.39 (95% CI: 1.15-1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P < 0.01). CONCLUSION: Increased plasma FFA concentrations were independently associated with greater risks of CV death & HHP, CV death, and ACM among HF patients, irrespective of the ejection fraction. The combination of FFA and NT-pro BNP biomarkers significantly improved risk stratification in HF patients.
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Biomarcadores , Ácidos Grasos no Esterificados , Insuficiencia Cardíaca , Péptido Natriurético Encefálico , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/sangre , Masculino , Femenino , Ácidos Grasos no Esterificados/sangre , Anciano , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Biomarcadores/sangre , Hospitalización , Fragmentos de Péptidos/sangre , Modelos de Riesgos Proporcionales , Volumen Sistólico , Pronóstico , Factores de Riesgo , Estudios de CohortesRESUMEN
In this paper, we present a two-phase multimodal optimization model designed to efficiently and accurately identify multiple optima. The first phase employs a population-based search algorithm to locate potential optima, while the second phase introduces a novel peak identification (PI) procedure to filter out non-optimal solutions, ensuring that each identified solution represents a distinct optimum. This approach not only enhances the effectiveness of multimodal optimization but also addresses the issue of redundant solutions prevalent in existing algorithms. We propose two PI algorithms: HVPI, which uses a hill-valley approach to distinguish between optima, without requiring prior knowledge of niche radii; and HVPIC, which integrates HVPI with bisecting K-means clustering to reduce the number of fitness evaluations (FEs). The performance of these algorithms was evaluated using the F-measure, a comprehensive metric that accounts for both the accuracy and redundancy in the solution set. Extensive experiments on a suite of benchmark functions and engineering problems demonstrated that our proposed algorithms achieved a high precision and recall, significantly outperforming traditional methods.
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AIMS: Acute myocarditis (AM) has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) infection. This study was conducted to present the clinical characteristics, disease courses and short-term prognoses of Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced AM in China, which has been unavailable so far. METHODS AND RESULTS: Data from 28 patients diagnosed with definite COVID-19-associated AM from 6 hospitals in China between 1 December 2022 and 30 June 2023 were collected and analysed. The diagnosis of AM was based on increased troponin level plus typical findings of AM on cardiac magnetic resonance (CMR) imaging and/or endomyocardial biopsy. Among 28 patients with definite COVID-19-related AM, median age was 37 years (Q1-Q3: 22-52) and 53.6% were men. Twenty-three patients occurred within 2 weeks of the onset of COVID-19 infection, 10 patients underwent endomyocardial biopsy and CMR was performed in all patients. Seven (25.0%) patients developed fulminant myocarditis that required inotropic agents or temporary mechanical circulatory support. Of the nine patients (32.1%) with left ventricular ejection fraction (LVEF) below 50% on admission, five had fully recovered LVEF and two demonstrated improvement but to levels below normal at discharge. The comparison of CMR parameters between the baseline and first follow-up showed that ECV was decreased at the first follow-up [28.95 (25.38, 32.55)% vs. 33.65 (31.58, 37.55)%, P = 0.028), while other CMR parameters had no significant changes. Eighteen patients (64.3%) were prescribed with corticosteroids, and seven patients (25.0%) underwent temporary mechanical circulatory support. Only two patients died during hospitalization. CONCLUSIONS: The majority of COVID-19-associated AM occurred within 2 weeks of Omicron variant infection. Fulminant myocarditis complicated by hemodynamic instability requiring temporary mechanical circulatory support was not uncommon. However, short-term outcome was generally good and most AM patients fully recovered.
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The number of spent lithium iron phosphate (LiFePO4, LFP) batteries will increase sharply in the next few years, owing to their large market share and development potential. Therefore, recycling of spent LFP batteries is necessary and urgent from both resource utilization and environmental protection standpoints. In this review, the significance of pretreatment for LFP recycling is first underscored, and its technical challenges and recent advancements are presented. Following that, the current recycling methods for spent LFP cathodes are outlined in terms of the respective treating processes, advantages, and disadvantages. Additionally, the preparation methods of LFP cathode material are reviewed to guide the resynthesis of LFP that uses salts obtained from spent LFP, which are beneficial for closed-loop recycling of LFP batteries. Lastly, we explore the future development direction of spent LFP battery recycling, highlighting the importance of technological innovation to advance the sustainable growth of the LFP battery industry.
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AIMS: This study aims to develop explainable machine learning models and clinical tools for predicting mortality in patients in the intensive care unit (ICU) with heart failure (HF). METHODS: Patients diagnosed with HF who experienced their first ICU stay lasting between 24 h and 28 days were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was all-cause mortality within 28 days. Data analysis was performed using Python and R, with feature selection conducted via least absolute shrinkage and selection operator (LASSO) regression. Fifteen models were evaluated, and the most effective model was rendered explainable through the Shapley additive explanations (SHAP) approach. A nomogram was developed based on logistic regression to facilitate interpretation. For external validation, the eICU database was utilized. RESULTS: After selection, the study included 2343 records, with 1808 surviving and 535 deceased patients. The median age of the study population was 70.00, with ~3/5 males (60.31%). The median length of stay in the ICU was 6.00 days. The median age of the survival group was younger than the non-survival group (69.00 vs. 73.00), and non-survival patients spent longer time in the ICU. Seventy-five features were initially selected, including basic information, vital signs, laboratory tests, haemodynamics and oxygen status. LASSO regression determined the shrinkage parameter α = 0.020, and 44 features were chosen for model construction. The linear discriminant analysis (LDA) model showed the best performance, and the accuracy reached 0.8354 in the training cohort and 0.8563 in the testing cohort. It showed satisfying area under the curve (AUC), recall, precision, F1 score, Cohen's kappa score and Matthew's correlation coefficient. The concordance index (c-index) reached 0.7972 in the training cohort and 0.8125 in the testing cohort. In external validation, the LDA model achieved approximately 0.9 in accuracy, precision, recall and F1 score, with an AUC of 0.79. Univariable analysis was performed in the training cohort. Features that differed significantly between the survival and non-survival groups were subjected to multiple logistic regression. The nomogram built on multiple logistic regression included 14 features and demonstrated excellent performance. The AUC of the nomogram is 0.852 in the training cohort, 0.855 in the internal validation cohort and 0.770 in the external validation cohort. The calibration curve showed good consistency. CONCLUSIONS: The study developed an LDA and a nomogram model for predicting mortality in HF patients in the ICU. The SHAP approach was employed to elucidate the LDA model, enhancing its utility for clinicians. These models were made accessible online for clinical application.
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Surfactants are hailed as "industrial monosodium glutamate", and are widely used as emulsifiers, demulsifiers, water treatment agents, etc., in the petroleum industry. However, due to the unidirectivity of conventional surfactants, the difficulty in demulsifying petroleum emulsions generated after emulsification with such surfactants increases sharply. Therefore, it is of great significance and application value to design and develop a novel switchable surfactant for oil exploitation. In this study, a CO2-switchable Gemini surfactant of N,N'-dimethyl-N,N'-didodecyl butylene diamine (DMDBA) was synthesized from 1, 4-dibromobutane, dodecylamine, formic acid, and formaldehyde. Then, the synthesized surfactant was structurally characterized by infrared (IR) spectroscopy, hydrogen nuclear magnetic resonance (1H NMR) spectroscopy, and electrospray ionization mass spectrometry (ESI-MS); the changes in conductivity and Zeta potential of DMDBA before and after CO2/N2 injection were also studied. The results show that DMDBA had a good CO2 response and cycle reversibility. The critical micelle concentration (CMC) of cationic surfactant obtained from DMDBA by injecting CO2 was 1.45 × 10-4 mol/L, the surface tension at CMC was 33.4 mN·m-1, and the contact angle with paraffin was less than 90°, indicating that it had a good surface activity and wettability. In addition, the kinetic law of the process of producing surfactant by injecting CO2 was studied, and it was found that the process was a second-order reaction. The influence of temperature and gas velocity on the reaction dynamics was explored. The calculated values from the equation were in good agreement with the measured values, with a correlation coefficient greater than 0.9950. The activation energy measured during the formation of surfactant was Ea = 91.16 kJ/mol.
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In recent years, perovskite quantum dots (PQDs) have successfully attracted widespread attention due to their excellent optical properties. However, the instability and toxicity problems of perovskite quantum dots are the main obstacles limiting their applications. In this work, bismuth-based perovskite quantum dots were synthesized by a ligand-assisted reprecipitation method, based on which a novel boric acid-functionalized bismuth-based non-toxic perovskite quantum dots fluorescent sensor (Cs3Bi2Br9-APBA) that can be stabilized in the ethanol phase was prepared by a boron affinity technique. Based on the covalent binding interaction of Cs3Bi2Br9-APBA with oxytetracycline (OTC), a highly selective and sensitive method for the detection of OTC was developed, which effectively solved the problems of poor stability and toxicity in the application of perovskite quantum dots. Under the optimal conditions, the fluorescence intensity of the synthesized Cs3Bi2Br9-APBA was linear with the concentration range of 0.1 â¼ 18 µM OTC, and the detection limit could reach 0.0802 µM. The fluorescence detection mechanism was explored and analyzed by spectral overlap analysis, suppression efficiency study of observed and corrected fluorescence, and fluorescence lifetime decay curve fitting, the mechanism of OTC detection by Cs3Bi2Br9-APBA was identified as the inner filter effect (IFE). In addition, the sensor successfully realized the quantitative detection of trace OTC in the environment, and our study provides a new idea for the preparation of green perovskite materials with high stability and selectivity.
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INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.
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Enfermedades Cardiovasculares , Corteza Cerebral , Imagen por Resonancia Magnética , Análisis de la Aleatorización Mendeliana , Humanos , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/epidemiología , Masculino , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Femenino , Persona de Mediana Edad , Corazón/diagnóstico por imagenRESUMEN
AIMS: Heart failure (HF) with supranormal ejection fraction (HFsnEF) represents a distinct clinical entity characterized by limited treatment options and an unfavourable prognosis. Revealing its phenotypic diversity is crucial for understanding disease mechanism and optimizing patient management. We aim to identify phenotypic subgroups in HFsnEF using unsupervised clustering analysis. METHODS: Consecutive hospitalized patients with a diagnosis of HF and a left ventricular ejection fraction ≥65% at baseline echocardiographic evaluations were included for analysis. We conducted unsupervised hierarchical clustering analysis on principal components (HCPC) to identify HFsnEF phenogroups using mixed data variables including demographics, HF duration, vital signs, anthropometrics, smoking/drinking status, HF aetiology, comorbid diseases, laboratory tests and echocardiographic parameters. We then employed decision tree modelling to identify parameters capable of distinguishing distinct clusters. Clinical outcomes, including all-cause death, cardiovascular (CV) death and CV readmission for different clusters, were examined. RESULTS: Three mutually exclusive clusters were identified from the cohort of 221 HFsnEF patients. Cluster 1 (52.5%) predominantly consisted of patients with valvular heart disease, who had larger cardiac chambers and a higher prevalence of atrial fibrillation/atrial flutter. Cluster 2 (26.2%) primarily comprised older ischaemic patients with a higher prevalence of metabolic comorbidities. Cluster 3 (21.3%) were mainly hypertrophic cardiomyopathy patients. Two clinical variables were identified that could be used to group all HFsnEF patients into one of the clusters; they were HF aetiology and comorbid diabetes. During the median follow-up of 53.4 months, 46 (20.8%) all-cause deaths occurred, among them 39 of CV causes. Seventy (31.7%) patients experienced CV readmissions. Three clusters showed distinct differences in mortality outcomes, with Cluster 1 exhibiting the highest risk of all-cause mortality [Cluster 1 vs. Cluster 2: adjusted hazard ratio (aHR) = 3.32, P = 0.022; Cluster 1 vs. Cluster 3: aHR = 3.81, P = 0.036; Cluster 2 vs. Cluster 3: aHR = 1.15, P = 0.865] and CV mortality (Cluster 1 vs. Cluster 2: aHR = 3.73, P = 0.022; Cluster 1 vs. Cluster 3: aHR = 4.27, P = 0.020; Cluster 2 vs. Cluster 3: aHR = 1.15, P = 0.870). CV readmission risk was comparable among the three clusters (Cluster 1 vs. Cluster 2: aHR = 0.82, P = 0.590; Cluster 1 vs. Cluster 3: aHR = 1.04, P = 0.900; Cluster 2 vs. Cluster 3: aHR = 1.28, P = 0.580). CONCLUSIONS: In a heterogeneous HFsnEF cohort, three clusters were identified by unsupervised HCPC with distinct clinical characteristics and outcomes.
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There are numerous applications of terahertz (THz) imaging in many fields. However, current THz imaging is generally based on scanning technique due to the limited intensity of the THz sources. Thus, it takes a long time to obtain a frame image of the target and cannot meet the requirement of fast THz imaging. Here, we demonstrate a single-shot direct THz imaging strategy based on a broadband intense THz source with a frequency range of 0.1~23 THz and a THz camera with a frequency response range of 1~7 THz. This THz source was generated from the laser-plasma interaction, with its central frequency at ~12 THz. The frame rate of this imaging system was 8.5 frames per second. The imaging resolution reached 146.2 µm. With this imaging system, a single-shot THz image for a target object with a size of more than 7 cm was routinely obtained, showing a potential application for fast THz imaging. Furthermore, we proposed and tested an image enhancement algorithm based on an improved dark channel prior (DCP) theory and multi-scale retinex (MSR) theory to optimize the image brightness, contrast, entropy and peak signal-to-noise ratio (PSNR).
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In challenging reservoirs where thermal recovery falls short, cold or chemical oil recovery methods are crucial. Spontaneous emulsification (SE), triggered by gentle disturbance, significantly enhances oil recovery. In elucidating SE mechanisms and kinetics, SE processes via direct contact between oil and aqueous phases without stirring were conducted. The effects of temperature, emulsifier concentration, pH, NaCl concentration, and the oil-to-water ratio on SE were investigated through droplet size analysis and turbidity measurements. Furthermore, the emulsification mechanism and derived emulsification kinetics based on turbidity data were obtained. The results underscore the feasibility of SE for oil-water systems, reducing viscous and capillary resistances without agitation. The emulsified oil mass increased with the temperature, pH, and aqueous-to-oil phase volume ratio while decreasing with the NaCl concentration. In this study, for GD-2 crude oil, the optimal emulsified oil amount occurred at a betaine surfactant (BetS-2) emulsifier concentration of 0.45%. Microscopic photo analysis indicated narrow particle size distributions and small droplets, which remained stable over time under various experimental conditions. A combined SE mechanism involving ultralow interfacial tension, interfacial turbulence due to Marangoni effects, and "diffusion and stranding" due to in situ emulsifier hydrophilicity, was speculated. Additionally, an analogous second-order kinetic equation for SE was proposed, indicating exceptional correlation with calculated and experimentally measured values. This study offers theoretical insight for enhancing oil recovery in chemical and cold production of heavy oil in oilfields.
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Super-resolution fluorescence microscopy has emerged as a powerful tool for studying endoplasmic reticulum (ER) dynamics in living cells. However, the lack of high-brightness, high-photostability, and stable labeling probes makes long-term super-resolution imaging of the ER still challenging. Herein, we reported a surface-functionalized Halo-tag gold nanofluorescent probe (GNP-Atto565-fR8-CA) that exhibits excellent brightness, photostability, and biocompatibility. GNP-Atto565-fR8-CA can simultaneously load multiple Atto565 dye molecules, significantly improving its brightness. Modifying the cell-penetrating peptide fR8 enables GNP-Atto565-fR8-CA to be efficiently delivered into the cytoplasm, overcoming the challenge of their easy entrapment in vesicles. Fluorescent labeling of ER proteins via Halo tags enables high specificity and stable labeling of GNP-Atto565-fR8-CA to the ER. The SIM super-resolution imaging results showed that GNP-Atto565-fR8-CA can track and observe the long-term dynamic process of the ER, and can also be used for long-term super-resolution imaging of the dynamic interactions between the ER and other organelles. This work offers a practical tool to study live-cell ER ultrastructure and dynamics.
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Retículo Endoplásmico , Oro , Nanopartículas del Metal , Retículo Endoplásmico/metabolismo , Oro/química , Humanos , Células HeLa , Nanopartículas del Metal/química , Microscopía Fluorescente , Colorantes Fluorescentes/química , Propiedades de SuperficieRESUMEN
Effective osteointegration is of great importance for pedicle screws in spinal fusion surgeries. However, the lack of osteoinductive activity of current screws diminishes their feasibility for osteointegration and fixation, making screw loosening a common complication worldwide. In this study, Ti-6Al-4V pedicle screws with full through-hole design were fabricated via selective laser melting (SLM) 3D printing and then deposited with porous oxide coatings by microarc oxidation (MAO). The porous surface morphology of the oxide coating and the release of bioactive ions could effectively support cell adhesion, migration, vascularization, and osteogenesis in vitro. Furthermore, an in vivo goat model demonstrated the efficacy of modified screws in improving bone maturation and osseointegration, thus providing a promising method for feasible orthopedic internal fixation.
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Cerámica , Cabras , Oseointegración , Oxidación-Reducción , Tornillos Pediculares , Impresión Tridimensional , Titanio , Animales , Oseointegración/efectos de los fármacos , Titanio/química , Titanio/farmacología , Cerámica/química , Cerámica/farmacología , Aleaciones/química , Aleaciones/farmacología , Osteogénesis/efectos de los fármacos , Humanos , Porosidad , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Adhesión Celular/efectos de los fármacosRESUMEN
This study investigated the influences of ultrafine fly ash (UFA) and ultrafine slag powder (USL) on the compressive strengths, autogenous shrinkage, phase assemblage, and microstructure of magnesium potassium phosphate cement (MKPC). The findings indicate that the aluminosilicate fractions present in both ultrafine fly ash and ultrafine slag participate in the acid-base reaction of the MKPC system, resulting in a preferential formation of irregularly crystalline struvite-K incorporating Al and Si elements or amorphous aluminosilicate phosphate products. UFA addition mitigates early age autogenous shrinkage in MKPC-based materials, whereas USL exacerbates this shrinkage. In terms of the sustained mechanical strength development of the MKPC system, ultrafine fly ash is preferred over ultrafine slag powder. MKPC pastes with ultrafine fly ash show greater compressive strength compared to those with ultrafine slag powder at 180 days due to denser interfaces between the ultrafine fly ash particles and hydration products like struvite-K. The incorporation of 30 wt% ultrafine fly ash enhances compressive strengths across all testing ages.
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BACKGROUND: Potentially inappropriate medications (PIMs) are common among older adults with cancer, but their association with overall survival (OS) among non-small cell lung cancer (NSCLC) patients remains unclear. This study aimed to investigate the association between the use of PIMs and OS in patients with NSCLC. METHODS: In this cohort study, we included patients ≥ 65 years with newly diagnosed NSCLC from January 2014 to December 2020. Potentially inappropriate medication (PIM) is defined by the Beers criteria of 2019 at baseline and within six months following the initiation of systemic therapy. Multivariable Cox regression model was built to assess the association between PIMs and overall survival (OS). RESULTS: We finally included 338 patients with a median follow-up for OS of 1777 days. The prevalence of patients receiving at least one PIM was 39.9% (135/338) and 61.2% (71/116) at baseline and after systemic therapy, respectively. The most important factor associated with PIM use was the number of prescribed medications (P < 0.001). Baseline PIM use and PIM after systemic therapy were significantly associated with inferior OS (476 days vs. 844 days, P = 0.044; and 633 days vs. 1600 days, P = 0.007; respectively). In multivariable analysis, both baseline PIM use and PIM after systemic therapy were independent predictors of poor prognosis (adjusted HR, 1.33; 95% CI, 1.01-1.75; P = 0.041; and adjusted HR, 1.86; 95% CI, 1.11-3.14; P = 0.020; respectively). CONCLUSIONS: PIMs are prevalent among older patients with NSCLC and are independent predictors of NSCLC prognosis. There is an urgent need for clinicians to conduct medication reconciliation and appropriate deprescribing for this population, especially for patients with multiple PIMs.