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The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery but is now facing the challenge of resistance due to point mutations. Herein, we have discovered a type II FLT3 inhibitor, SILA-123. This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC50 = 2.1 nM) and FLT3-ITD (IC50 = 1.0 nM), tumor cells with the FLT3-ITD mutant such as MOLM-13 (IC50 = 0.98 nM) and MV4-11 (IC50 = 0.19 nM), as well as BaF3 cells associated with the FLT3-ITD mutant and point mutations like BaF3-FLT3-ITD-G697R (IC50 = 3.0 nM). Moreover, SILA-123 exhibited promising kinome selectivity against 310 kinases (S score (10) = 0.06). In in vivo studies, SILA-123 significantly suppressed the tumor growth in MV4-11 (50 mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated allograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3-ITD-positive AML.

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The recent interest in developing low-cost, biocompatible, and lightweight bioelectronic devices has focused on organic electrochemical transistors (OECTs), which have the potential to fulfill these requirements. In this study, three types of poly(3-hexylthiophene) (P3HT)-based block copolymers (BCPs) incorporating different insulating blocks (poly(nbutyl acrylate) (PBA), polystyrene, and poly(ethylene oxide) (PEO)) were synthesized for application in OECTs. The morphological, crystallographic, and electrochemical properties of these BCPs are systematically investigated. Accordingly, P3HT-b-PBA demonstrates superior performance in the KCl-based aqueous electrolyte, with a higher product of mobility and capacitance (µC*) at 170 F s-1 cm-1 V-1 than that of the P3HT homopolymer at 58 F s-1 cm-1 V-1. P3HT-b-PBA exhibits better stability over 50 ON/OFF switching cycles than do other BCPs and P3HT homopolymers. With regard to the performance in the KPF6-based aqueous electrolyte, P3HT-b-PBA outperforms with a higher µC* of 9.2 F s-1 cm-1 V-1 than that of 8.6 F s-1 cm-1 V-1 observed from P3HT. Notably, both polymers exhibited almost no decay in device performance over 110 ON/OFF switching cycles. The strongly different performance of polymers in these two electrolytes is due to the side chain's hydrophobicity and interdigitated lamellar structures, thereby retarding the doping kinetics of the highly hydrated Cl- ions compared with the slightly hydrated PF6- ions. Concerning the improved performance of P3HT-b-PBA, this is attributed to its soft and hydrophobic backbone. Our morphological and crystallographic analyses reveal that P3HT-b-PBA experiences minimal structural disorder when swelled by the electrolyte, maintaining its original structure better than the P3HT homopolymer and the hydrophilic BCP of P3HT-b-PEO. The hydrophobic nature of P3HT-b-PBA contributes to the stability of its backbone structure, ensuring enhanced capacitance during the operation of the OECT operation. These findings provide reassurance about the stability and performance of P3HT-b-PBA in the field of OECT applications. In summary, this study represents the first exploration of P3HT-based BCPs for OECT applications and investigates their structure-performance relationships in mixed ionic-electronic conductors.

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Purpose: Primary surgery failure of macular holes causes poor visual acuity outcomes. Several studies indicate that small-medium idiopathic full-thickness macular holes (iFTMH) have consistent and high anatomical closure rates after vitrectomy and internal limiting membrane (ILM) peeling, regardless of iFTMH diameters. However, there is no systematic analysis examining the relationship between iFTMH diameters and anatomical closure rates. Methods: In this systematic review and meta-regression, we searched PubMed, Embase, and Web of Science databases on October 24th, 2022. We included studies regarding iFTMH, with ILM peeling/inverted flap technique, long-lasting gas tamponade, and face-down position after surgery. Univariable meta-regression with a restricted cubic spline model and component-plus-residual plot after covariables adjustment were used to explore non-linear association. Results: A total of 7257 participants from 19 randomized controlled trials and 49 observational studies were included in this meta-analysis. In ILM peeling group, every 100-µm increment in diameter was associated with a 3.8 % (95 % confidence interval [CI], 1.8%-5.7 %, P < 0.001) relatively lower anatomical closure rate. Yet, among studies using the inverted flap technique, baseline iFTMH diameter was not associated with a lower anatomical closure rate (0.2 %, 95%CI, -4.2 %-4.5 %, P > 0.9). The restricted cubic spline model and component-plus-residual plot controlling for age, sex, and symptom duration prior to surgery showed no evident non-linearity in both surgical techniques. Conclusions: The iFTMH diameter is linear and inversely associated with the anatomical closure rate after the ILM peeling technique, but not with the inverted flap technique. The present study supports the use of advanced techniques, e.g., inverted flap technique, in small-medium iFTMH to improve anatomical closure rates.

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Addressing environmental concerns and producing sustainable and environmentally friendly electronic devices with low power consumption poses a significant challenge. This study introduces phototransistor devices employing morphologically controlled block copolymers based on maltotriose, maltoheptaose, and ß-cyclodextrin as polymer electrets. Ordered self-assembled morphologies can be achieved by utilizing microwave radiation for rapid annealing (within 5 s) with optimized annealing conditions. Herein, face-centered cubic (FCC), vertical, and mixed cylindrical nanostructures are reported. The resulting well-defined morphologies play a pivotal role in enhancing the electron-trapping capability of the block copolymers and facilitating charge carrier transport between the electret and semiconducting layers. Consequently, the phototransistor memory manifests exceptional performance, featuring stability and endurance. Intriguingly, the cavity of ß-cyclodextrin provides a stable environment for the trapped charges, leading to a larger memory window than other block copolymers. On the other hand, a device consisting of MT-b-PS exhibited superior current contrast exceeding 106 even under a low drain voltage of -1 V, attributed to sub-10 nm FCC nanostructures. Furthermore, this phototransistor device successfully emulated the synaptic functions of sensing, learning, and short- and long-term memory in the human brain, along with a low energy consumption of 0.312 fJ. Hence, this report opens the pathways for developing promising bio-based electronic devices.

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INTRODUCTION: Pleural effusion is common in clinical practice, and its differential diagnosis remains challenging for clinicians. This study investigates the diagnostic value of apolipoprotein E (apoE) in patients with undetermined pleural effusion. METHODS: This prospective, double-blind study enrolled 152 patients with undiagnosed pleural effusion. Their pleural fluid apoE levels were measured, and a receiver operating characteristics (ROC) curve was used to evaluate the diagnostic accuracy of apoE. Decision curve analysis (DCA) was used to assess apoE's net benefit. Subgroup analyses were performed to investigate the effect of age on the diagnostic accuracy of apoE. RESULTS: Among the included participants, 23 had heart failure (HF). HF patients had the lowest apoE level among pleural effusion patients. The area under the curve (AUC) of apoE for HF was 0.79 (95% CI: 0.69-0.89). At the threshold of 40 mg/L, the sensitivity and specificity of apoE were 0.96 (95% CI: 0.87-1.00) and 0.33 (95% CI: 0.25-0.42), respectively. The decision curve for apoE was above reference lines. The AUC of apoE decreased in older patients. CONCLUSION: Pleural fluid apoE has moderate diagnostic value for HF and has net benefits in patients with undiagnosed pleural effusion. The diagnostic accuracy of apoE decreases with age.

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BACKGROUND: Bariatric surgery is one of the most effective ways to treat morbid obesity, and postoperative nausea and vomiting (PONV) is one of the common complications after bariatric surgery. At present, the mechanism of the high incidence of PONV after weight-loss surgery has not been clearly explained, and this study aims to investigate the effect of surgical position on PONV in patients undergoing bariatric surgery. AIM: To explore the effect of the operative position during bariatric surgery on PONV. METHODS: Data from obese patients, who underwent laparoscopic sleeve gastrectomy (LSG) in the authors' hospital between June 2020 and February 2022 were divided into 2 groups and retrospectively analyzed. Multivariable logistic regression analysis and the t-test were used to study the influence of operative position on PONV. RESULTS: There were 15 cases of PONV in the supine split-leg group (incidence rate, 50%) and 11 in the supine group (incidence rate, 36.7%) (P = 0.297). The mean operative duration in the supine split-leg group was 168.23 ± 46.24 minutes and 140.60 ± 32.256 minutes in the supine group (P < 0.05). Multivariate analysis revealed that operative position was not an independent risk factor for PONV (odds ratio = 1.192, 95% confidence interval: 0.376-3.778, P = 0.766). CONCLUSION: Operative position during LSG may affect PONV; however, the difference in the incidence of PONV was not statistically significant. Operative position should be carefully considered for obese patients before surgery.

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BACKGROUND: Klebsiella pneumoniae is the most commonly encountered pathogen in clinical practice. Widespread use of broad-spectrum antibiotics has led to the current global dissemination of carbapenem-resistant K. pneumoniae, which poses a significant threat to antibacterial treatment efficacy and public health. Outer membrane vesicles (OMVs) have been identified as carriers capable of facilitating the transfer of virulence and resistance genes. However, the role of OMVs in carbapenem-resistant K. pneumoniae under external pressures such as antibiotic and phage treatments remains unclear. METHODS: To isolate and purify OMVs under the pressure of phages and tigecycline, we subjected K. pneumoniae 0692 harboring plasmid-mediated blaNDM-1 and blaKPC-2 genes to density gradient separation. The double-layer plate method was used to isolate MJ1, which efficiently lysed K. pneumoniae 0692 cells. Transmission electron microscopy (TEM) was used to characterize the isolated phages and extract OMV groups for relevant morphological identification. Determination of protein content of each OMV group was conducted through bicinchoninic acid assay (BCA) and proteomic analysis. RESULTS: K. pneumoniae 0692 released OMVs in response to different environmental stimuli, which were characterized through TEM as having the typical structure and particle size of OMVs. Phage or tigecycline treatment alone resulted in a slight increase in the mean protein concentration of OMVs secreted by K. pneumoniae 0692 compared to that in the untreated group. However, when phage treatment was combined with tigecycline, there was a significant reduction in the average protein concentration of OMVs compared to tigecycline treatment alone. Proteomics showed that OMVs encapsulated numerous functional proteins and that under different external stresses of phages and tigecycline, the proteins carried by K. pneumoniae 0692-derived OMVs were significantly upregulated or downregulated compared with those in the untreated group. CONCLUSIONS: This study confirmed the ability of OMVs to carry abundant proteins and highlighted the important role of OMV-associated proteins in bacterial responses to phages and tigecycline, representing an important advancement in microbial resistance research.

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Antibacterianos , Bacteriófagos , Carbapenémicos , Klebsiella pneumoniae , Proteómica , Tigeciclina , Tigeciclina/farmacología , Klebsiella pneumoniae/virología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Bacteriófagos/genética , Bacteriófagos/fisiología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Infecciones por Klebsiella/microbiología , Humanos , Vesículas Extracelulares/metabolismo , Membrana Externa Bacteriana/metabolismo , Membrana Externa Bacteriana/efectos de los fármacos , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Plásmidos/genética , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo

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PURPOSE: To evaluate the diagnostic performance of radiomics models derived from multi-phase spleen CT for high-risk esophageal varices (HREV) in cirrhotic patients. METHODS: We retrospectively selected cirrhotic patients with esophageal varices from two hospitals from September 2019 to September 2023. Patients underwent non-contrast and contrast-enhanced CT scans and were categorized into HREV and non-HREV groups based on endoscopic evaluations. Radiomics features were extracted from spleen CT images in non-contrast, arterial, and portal venous phases, with feature selection via lasso regression and Pearson's correlation. Ten machine learning models were developed to diagnose HREV, evaluated by area under the curve (AUC). The AUC values of the three groups of models were statistically compared by the Kruskal-Wallis H test and Bonferroni-corrected Mann-Whitney U test. A p-value less than 0.05 was considered statistically significant. RESULTS: Among 233 patients, 11, 6, and 11 features were selected from non-contrast, arterial, and portal venous phases, respectively. Significant differences in AUC values were observed across phases (p < 0.05), and the arterial phase models showed the highest AUC values. The best model in arterial phase was the logical regression model, whose AUC value was 0.85, sensitivity was 83.3%, specificity was 80% and F1 score was 0.81. CONCLUSION: Radiomics models based on spleen CT, especially the arterial phase models, demonstrate high diagnostic accuracy for HREV, offering the potential for early detection and intervention.

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The photosynaptic transistor stands as a promising contender for overcoming the von Neumann bottleneck in the realm of photo-communication. In this context, photonic synaptic transistors is developed through a straightforward solution process, employing an organic semiconducting polymer with pendant-naphthalene-containing side chains (PDPPNA) in combination with ligand-density-engineered CsPbBr3 perovskite quantum dots (PQDs). This fabrication approach allows the devices to emulate fundamental synaptic behaviors, encompassing excitatory postsynaptic current, paired-pulse facilitation, the transition from short-to-long-term memory, and the concept of "learning experience." Notably, the phototransistor, incorporating the blend of the PDPPNA and CsPbBr3 PQDs washed with ethyl acetate, achieved an exceptional memory ratio of 104. Simultaneously, the same device exhibited an impressive paired-pulse facilitation ratio of 223% at a moderate operating voltage of -4 V and an extraordinarily low energy consumption of 0.215 aJ at an ultralow operating voltage of -0.1 mV. Consequently, these low-voltage synaptic devices, constructed with a pendant side-chain engineering of organic semiconductors and a ligand density engineering of PQDs through a simple fabrication process, exhibit substantial potential for replicating the visual memory capabilities of the human brain.

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Polymer-wrapped single-walled carbon nanotubes (SWNTs) are a potential method for obtaining high-purity semiconducting (sc) SWNT solutions. Conjugated polymers (CPs) can selectively sort sc-SWNTs with different chiralities, and the structure of the polymer side chains influences this sorting capability. While extensive research has been conducted on modifying the physical, optical, and electrical properties of CPs through side-chain modifications, the impact of these modifications on the sorting efficiency of sc-SWNTs remains underexplored. This study investigates the introduction of various conjugated side chains into naphthalene diimide-based CPs to create a biaxially extended conjugation pattern. The CP with a branched conjugated side chain (P3) exhibits reduced aggregation, resulting in improved wrapping ability and the formation of larger bundles of high-purity sc-SWNTs. Grazing incidence X-ray diffraction analysis confirms that the potential interaction between sc-SWNTs and CPs occurs through π-π stacking. The field-effect transistor device fabricated with P3/sc-SWNTs demonstrates exceptional performance, with a significantly enhanced hole mobility of 4.72 cm2 V-1 s-1 and high endurance/bias stability. These findings suggest that biaxially extended side-chain modification is a promising strategy for improving the sorting efficiency and performance of sc-SWNTs by using CPs. This achievement can facilitate the development of more efficient and stable electronic devices.

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Protein-based subunit vaccines like RBD-Fc are promising tools to fight COVID-19. RBD-Fc fuses the receptor-binding domain (RBD) of the SARS-CoV-2 virus spike protein with the Fc region of human IgG1, making it more immunogenic than RBD alone. Earlier work showed that combining RBD-Fc with iNKT cell agonists as adjuvants improved neutralizing antibodies but did not sufficiently enhance T cell responses, a limitation RBD-Fc vaccines share with common adjuvants. Here we demonstrate that aluminum hydroxide combined with α-C-GC, a C-glycoside iNKT cell agonist, significantly improved the RBD-Fc vaccine's induction of RBD-specific T-cell responses. Additionally, aluminum hydroxide with α-GC-CPOEt, a phosphonate diester derivative, synergistically elicited more robust neutralizing antibodies. Remarkably, modifying αGC with phosphate (OPO3H2) or phosphonate (CPO3H2) to potentially enhance aluminum hydroxide interaction did not improve efficacy over unmodified αGC with aluminum hydroxide. These findings underscore the straightforward yet potent potential of this approach in advancing COVID-19 vaccine development and provide insights for iNKT cell-based immunotherapy.

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Adyuvantes Inmunológicos , Hidróxido de Aluminio , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunas de Subunidad , Vacunas contra la COVID-19/inmunología , Hidróxido de Aluminio/inmunología , Hidróxido de Aluminio/farmacología , Hidróxido de Aluminio/química , Anticuerpos Neutralizantes/inmunología , Vacunas de Subunidad/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Animales , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Ratones , Inmunogenicidad Vacunal , Humanos , Células T Asesinas Naturales/inmunología , Glucolípidos/inmunología , Glucolípidos/química , Femenino , Adyuvantes de Vacunas , Ratones Endogámicos BALB C

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The open reduction of mandibular condyle neck fractures is difficult due to the limited surgical field and complex facial nerve structures. The most effective fixation method for narrow fractured segments is debated as standard double four-hole plate fixation is often not feasible. This research compared bone stability and force resistance between single-long-plate and double-short-plate fixations using clinical outcomes, a Sawbones mandible model, and finite element analysis. In patients with condyle neck fractures, nine were fixed with single-long-plate and twelve with double-short-plate fixations, with no significant differences in malocclusion and facial palsy rates. In compression tests with a Sawbones model, displacements in the posterior part were similar in both fixation groups. In contrast, the anterior part had significantly higher displacements in the single-long-plate group. Finite element analysis showed higher displacements in both anterior and posterior parts in the single-plate group compared to the double-short-plate group. Maximum stresses were at the second screw hole in single-long-plate fixation and the turning point of the upper plate at the condyle neck in double-short-plate fixation. Double-short-plate fixations demonstrated better stability and force resistance than single-long-plate fixations.

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Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC50 values of 3.3, 3.2 and 5.8 µM. Further cell assays showed IC50 values of 0.2, 1.2 and 0.6 µM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible.

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Overexposure of sewage workers to bioaerosol released from wastewater treatment plants (WWTPs) can cause serious infections, but practical method for controlling their health risk is lacking. In this study, reverse quantitative microbial risk assessment was used to estimate the daily critical exposure time (CET) of sewage workers exposing to Staphylococcus aureus bioaerosol emitted by three emission sources facilities in a WWTP based on either U.S. EPA or WHO benchmark, and sensitivity analysis was conducted to analyze the influence of various parameters on the outcomes of CET. The results showed that the CET of females was always 1.12-1.29 times that of males. In addition, the CET after wearing face masks was 28.28-52.37 times as long as before. The working time can be determined based on the CET results of male workers wearing face masks exposed to the inverted-umbrella aeration tank (14.73-550.98 min for U.S. EPA benchmark and 55.07-1972.24 min for WHO benchmark). In each scenario, the variable parameter exposure concentration (ec) always showed the most influence on the CET results. After wearing the face masks, the removal fraction by employing face masks also had a significant effect on the results, only second to ec. Therefore, the wearing of face mask is the most convenient and effective measure to prolong the CET. Furthermore, practical methods to reducing bioaerosol concentration in WWTPs exposure are also necessary to extend CET and safeguard worker health. This study enriches the application range of reverse quantitative microbial risk assessment framework and provides theoretical support for stakeholders to establish reasonable working time threshold guidelines, and practical method and novel perspective to protect the on-site health risks of sewage workers exposing to various facilities.

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Aerosoles , Exposición Profesional , Aguas Residuales , Aerosoles/análisis , Aguas Residuales/química , Exposición Profesional/análisis , Humanos , Medición de Riesgo , Staphylococcus aureus , Eliminación de Residuos Líquidos/métodos , Monitoreo del Ambiente , Microbiología del Aire , Femenino , Masculino , Contaminantes Ocupacionales del Aire/análisis

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The bioaccumulation and trophic transfer of organophosphate flame retardants (OPFRs) in marine ecosystems have attracted great attention in recent research, but our understanding of the trophic transfer mechanisms involved is limited. In this study, we investigated the trophodynamics of OPFRs and their metabolites in a subtropical coastal food web collected from the northern Beibu Gulf, China, and characterized their trophodynamics using fugacity- and biotransformation-based approaches. Eleven OPFRs and all seven metabolites were simultaneously quantified in the shellfish, crustacean, pelagic fish, and benthic fish samples, with total concentrations ranging from 164 to 4.11 × 104 and 4.56-4.28 × 103 ng/g lipid weight, respectively. Significant biomagnification was observed only for tris (phenyl) phosphate (TPHP) and tris (2-ethylhexyl) phosphate (TEHP), while other compounds except for tris(2-chloroethyl) phosphate (TCEP) displayed biomagnification trends based on Monte Carlo simulations. Using a fugacity-based approach to normalize the accumulation of OPFRs in biota to their relative biological phase composition, storage lipid is the predominant biological phase for the mass distribution of 2-ethylhexyl diphenyl phosphate (EHDPHP) and TPHP. The water content and structure protein are equally important for TCEP, whereas lipid and structure protein are the two most important phases for other OPFRs. The mass distribution of these OPFRs along with TLs can explain their trophodynamics in the food web. The organophosphate diesters (as OPFR metabolites) also displayed biomagnification trends based on bootstrapped estimation. The correlation analysis and Korganism-water results jointly suggested the metabolites accumulation in high-TL organisms was related to biotransformation processes. The metabolite-backtracked trophic magnification factors for tri-n­butyl phosphate (TNBP) and TPHP were both greater than the values that accounted for only the parent compounds. This study highlights the incorporation of fugacity and biotransformation analysis to characterize the trophodynamic processes of OPFRs and other emerging pollutants in food webs.

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Biotransformación , Retardadores de Llama , Cadena Alimentaria , Organofosfatos , Contaminantes Químicos del Agua , Retardadores de Llama/metabolismo , Organofosfatos/metabolismo , Animales , China , Contaminantes Químicos del Agua/metabolismo , Peces/metabolismo , Monitoreo del Ambiente

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RATIONALE AND OBJECTIVES: To explore the value of splenic hemodynamic parameters from low-dose one-stop dual-energy and perfusion CT (LD-DE&PCT) in non-invasively predicting high-risk esophageal varices (HREV) in cirrhotic patients. METHODS: We retrospectively analyzed cirrhotic patients diagnosed with esophageal varices (EV) through clinical, laboratory, imaging, and endoscopic examinations from September 2021 to December 2023 in our hospital. All patients underwent LD-DE&PCT to acquire splenic iodine concentration and perfusion parameters. Radiation dose was recorded. Patients were classified into non-HREV and HREV groups based on endoscopy. Univariate and multivariate logistic regression analysis were performed, and the prediction model for HREV was constructed. P < 0.05 was considered statistically significant. RESULTS: Univariate analysis revealed that significant differences were found in portal iodine concentration (PIC), blood flow (BF), permeability surface (PS), spleen volume (V-S), total iodine concentration (TIC), and total blood volume of the spleen (BV-S) between groups. TIC demonstrated the highest predictive value with an area under the curve (AUC) value of 0.87. Multivariate analysis showed that PIC, PS, and BV-S were independent risk factors for HREV. The logistic regression model for predicting HREV had an AUC of 0.93. The total radiation dose was 20.66 ± 4.07 mSv. CONCLUSION: Splenic hemodynamic parameters obtained from LD-DE&PCT can non-invasively and accurately assess the hemodynamic status of the spleen in cirrhotic patients with EV and predict the occurrence of HREV. Despite the retrospective study design and limited sample size of this study, these findings deserve further validation through prospective studies with larger cohorts.

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Rechargeable aqueous Zn-ion batteries have been deemed a promising energy storage device. However, the dendrite growth and side reactions have hindered their practical application. Herein, inspired by the ultrafluidic and K+ ion-sieving flux through enzyme-gated potassium channels (KcsA) in biological plasma membranes, a metal-organic-framework (MOF-5) grafted with -ClO4 groups (MOF-ClO4) as functional enzymes is fabricated to mimic the ultrafluidic lipid-bilayer structure for gating Zn2+ 'on' and anions 'off' states. The MOF-ClO4 achieved perfect Zn2+/SO4 2- selectivity (∼10), enhanced Zn2+ transfer number ([Formula: see text]) and the ultrafluidic Zn2+ flux (1.9 × 10-3 vs. 1.67 mmol m-2 s-1 for KcsA). The symmetric cells based on MOF-ClO4 achieve a lifespan of over 5400 h at 10 mA cm-2/20 mAh cm-2. Specifically, the performance of the PMCl-Zn//V2O5 pouch cell keeps 81% capacity after 2000 cycles at 1 A g-1. The regulated ion transport, by learning from a biological plasma membrane, opens a new avenue towards ultralong lifespan aqueous batteries.

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Background: The associations between platelet-to-lymphocyte ratio (PLR) and non-alcoholic fatty liver disease (NAFLD) and cirrhosis are unclear, and there are still no effective means for diagnosing or monitoring disease progression. Methods: Data from the National Health and Nutrition Examination Surveys were collected for analysis. Logistic regression and restricted cubic splines were used to evaluate the associations between PLR and NAFLD and cirrhosis in different populations. The Area Under Curve Receiver Operating Characteristic (AUCROC) was used to distinguish the models. Threshold analysis was performed by constructing a two-piecewise linear regression. Correlation analysis was performed separately on either side of the inflection point. Results: A total of 5724 adults were included. Logistic regression analysis revealed that the PLR was associated with NAFLD and cirrhosis (AUCROC of NAFLD: 0.803; AUCROC of cirrhosis: 0.851). The AUCROC of the PLR for predicting NAFLD incidence was 0.762 in the diabetic population and 0.804 in the nondiabetic population. High PLR predicted cirrhosis in the diabetic population, with an AUCROC of 0.824, whereas a high PLR was not associated with cirrhosis in the nondiabetic population. The restricted cubic spline revealed a negative linear correlation between the PLR and NAFLD incidence. The inflection point of the PLR for NAFLD was 180.74. A PLR ≤180.74 was statistically significant (odds ratio=0.997, 95% confidence interval=0.995-0.999). In the NAFLD population, the PLR was negatively correlated with cirrhosis at a PLR ≤130.5 (odds ratio=0.987, 95% confidence interval=0.977-0.996) and positively correlated with cirrhosis at a PLR > 130.5 (odds ratio=1.006, 95% confidence interval=1.001-1.012). Conclusions: The PLR and NAFLD were negatively correlated in the U.S. population. The PLR had a U-shaped relationship with cirrhosis in the NAFLD population. The PLR has potential value in monitoring NAFLD patient progression to cirrhosis.

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Plaquetas , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Masculino , Femenino , Cirrosis Hepática/sangre , Cirrosis Hepática/epidemiología , Persona de Mediana Edad , Estudios Transversales , Adulto , Plaquetas/patología , Linfocitos , Recuento de Plaquetas , Recuento de Linfocitos , Encuestas Nutricionales , Factores de Riesgo , Anciano , Valor Predictivo de las Pruebas

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Background: Epicardial adipose tissue (EAT) is unique type of visceral adipose tissue, sharing the same microcirculation with myocardium. This study aimed to assess the imaging features of EAT in patients with acute myocarditis (AM) and explore the relationships with clinical characteristics. Methods: For this retrospective case-control study, totally 38 AM patients and 52 controls were screened retrospectively from January 2019 to December 2022, and the EAT volume was measured from coronary computed tomography (CT) angiography imaging. Histogram analysis was performed to calculate parameters like the mean, standard deviation, interquartile range and percentiles of EAT attenuation. Whether EAT features change was assessed when clinical characteristics including symptoms, T wave abnormalities, pericardial effusion (PE), impairment of systolic function, and the need for intensive care presented. Results: The EAT volume (75.2±22.8 mL) and mean EAT attenuation [-75.8±4.4 Hounsfield units (HU)] of the AM group was significantly larger than the control group (64.7±26.0 mL, P=0.049; -77.9±5.0 HU, P=0.044). Among the clinical characteristics, only the presence of PE was associated with changes in EAT features. Patients with PE showed significantly changes in EAT attenuation including mean attenuation [analysis of variance (ANOVA) P=0.001] and quantitative histogram parameters. The mean attenuation of patients with PE (-71.9±4.0 HU) was significantly larger than controls (-77.9±5.0 HU, Bonferroni corrected P<0.001) and patients without PE (-77.4±3.5 HU, Bonferroni corrected P=0.003). Observed in histogram, the overall increase in EAT attenuation could lead to decrease in EAT volume, which resulted in no statistically significant difference in EAT volume between the AM patients with PE and controls (64.7±26.0 vs. 72.2±28.3 mL, Bonferroni corrected P>0.99). Conclusions: Compared to controls, EAT volume was significantly larger in AM, and EAT attenuation increased notably in the presence of PE. We recommend evaluating EAT volume and attenuation simultaneously when quantifying EAT using CT attenuation thresholds.

RESUMEN

BACKGROUND: The aim of this study was to investigate the complex heterozygous mutations of ANK1 and SPTA1 in the same individual and improve our understanding of hereditary spherocytosis (HS) in children. We also hope to promote the application of gene detection technology in children with HS, with the goals of identifying more related gene mutations, supporting the acquisition of improved molecular genetic information to further reveal the pathogenesis of HS in children, and providing important guidance for the diagnosis, treatment, and prevention of HS in children. CASE SUMMARY: A 1-year and 5-month-old patient presented jaundice during the neonatal period, mild anemia 8 months later, splenic enlargement at 1 year and 5 months, and brittle red blood cell permeability. Genetic testing was performed on the patient, their parents, and sister. Swiss Model software was used to predict the protein structure of complex heterozygous mutations in ANK1 and SPTA1. Genetic testing revealed that the patient harbored a new mutation in the ANK1 gene from the father and a mutation in the SPTA1 gene from the mother. Combined with the clinical symptoms of the children, it is suggested that the newly discovered complex heterozygous mutations of ANK1 and SPTA1 may be the cause, providing important guidance for revealing the pathogenesis, diagnosis, treatment, and promotion of gene detection technology in children with HS. CONCLUSION: This case involves an unreported complex heterozygous mutation of ANK1 and SPTA1, which provides a reference for exploring HS.