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1.
Eur Radiol ; 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39412667

RESUMEN

OBJECTIVES: To evaluate the value of a magnetic resonance imaging (MRI)-based deep learning radiomic nomogram (DLRN) for distinguishing intracranial solitary fibrous tumors (ISFTs) from angiomatous meningioma (AMs) and predicting overall survival (OS) for ISFT patients. METHODS: In total, 1090 patients from Beijing Tiantan Hospital, Capital Medical University, and 131 from Lanzhou University Second Hospital were categorized as primary cohort (PC) and external validation cohort (EVC), respectively. An MRI-based DLRN was developed in PC to distinguish ISFTs from AMs. We validated the DLRN and compared it with a clinical model (CM) in EVC. In total, 149 ISFT patients were followed up. We carried out Cox regression analysis on DLRN score, clinical characteristics, and histological stratification. Besides, we evaluated the association between independent risk factors and OS in the follow-up patients using Kaplan-Meier curves. RESULTS: The DLRN outperformed CM in distinguishing ISFTs from AMs (area under the curve [95% confidence interval (CI)]: 0.86 [0.84-0.88] for DLRN and 0.70 [0.67-0.72] for CM, p < 0.001) in EVC. Patients with high DLRN score [per 1 increase; hazard ratio (HR) 1.079, 95% CI: 1.009-1.147, p = 0.019] and subtotal resection (STR) [per 1 increase; HR 2.573, 95% CI: 1.337-4.932, p = 0.004] were associated with a shorter OS. A statistically significant difference in OS existed between the high and low DLRN score groups with a cutoff value of 12.19 (p < 0.001). There is also a difference in OS between total excision (GTR) and STR groups (p < 0.001). CONCLUSION: The proposed DLRN outperforms the CM in distinguishing ISFTs from AMs and can predict OS for ISFT patients. CLINICAL RELEVANCE STATEMENT: The proposed MRI-based deep learning radiomic nomogram outperforms the clinical model in distinguishing ISFTs from AMs and can predict OS of ISFT patients, which could guide the surgical strategy and predict prognosis for patients. KEY POINTS: Distinguishing ISFTs from AMs based on conventional radiological signs is challenging. The DLRN outperformed the CM in our study. The DLRN can predict OS for ISFT patients.

2.
Bioinformatics ; 40(10)2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39383521

RESUMEN

MOTIVATION: Drug-drug interactions (DDIs) can cause unexpected adverse drug reactions, affecting treatment efficacy and patient safety. The need for computational methods to predict DDIs has been growing due to the necessity of identifying potential risks associated with drug combinations in advance. Although several deep learning methods have been recently proposed to predict DDIs, many overlook feature learning based on interactions between the substructures of drug pairs. RESULTS: In this work, we introduce a molecular Substructure-based Dual Attention Feature Learning framework (MSDAFL), designed to fully utilize the information between substructures of drug pairs to enhance the performance of DDI prediction. We employ a self-attention module to obtain a set number of self-attention vectors, which are associated with various substructural patterns of the drug molecule itself, while also extracting interaction vectors representing inter-substructure interactions between drugs through an interactive attention module. Subsequently, an interaction module based on cosine similarity is used to further capture the interactive characteristics between the self-attention vectors of drug pairs. We also perform normalization after the interaction feature extraction to mitigate overfitting. After applying three-fold cross-validation, the MSDAFL model achieved average precision scores of 0.9707, 0.9991, and 0.9987, and area under the receiver operating characteristic curve scores of 0.9874, 0.9934, and 0.9974 on three datasets, respectively. In addition, the experiment results of five-fold cross-validation and cross-datum study also indicate that MSDAFL performs well in predicting DDIs. AVAILABILITY AND IMPLEMENTATION: Data and source codes are available at https://github.com/27167199/MSDAFL.


Asunto(s)
Interacciones Farmacológicas , Biología Computacional/métodos , Aprendizaje Profundo , Algoritmos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos
3.
Huan Jing Ke Xue ; 45(10): 6086-6095, 2024 Oct 08.
Artículo en Chino | MEDLINE | ID: mdl-39455152

RESUMEN

The nitrogen cycle is of great importance for material circulation and energy flow in lake ecosystems. It is driven by microorganisms in lake sediments and can contribute to balancing lake ecosystems. In this study, physical and chemical properties of the sediments sampled from Hongfeng Lake in Guizhou Province were assayed and analyzed using metagenomics to reveal relevant microorganisms, functional genes, metabolic pathways, and their relationships throughout nitrogen metabolism. The results showed that bacteria were dominant, and the top three relative abundant genera were Thiobacillus (16.64%), Rubrivivax(9.43%), and Nitrospira (7.09%). Only six pathways, including nitrogen fixation, nitrification, denitrification, assimilatory nitrate reduction, dissimilatory nitrate reduction, and complete nitrification, were detected in total, of which denitrification and dissimilatory nitrate reduction were the primary processes, but anaerobic ammonia oxidation was not detected. Bacteria and archaea participated in these six pathways, while eukaryotes only functioned in dissimilatory nitrate reduction, denitrification, and complete nitrification. Ammonia nitrogen, nitrate nitrogen, and total phosphorus, as main environmental factors affecting the distribution of functional genes for nitrogen metabolism, differentiated with each other in their respective real-world conditions. A positive correlation (95.04%) was observed between the functional genes and microorganisms, and narG, narZ, and nxrA possessed the highest abundance and the highest host genes. On this basis, these findings are expected to further elucidate the nitrogen cycle of typical karst lakes in Guizhou Province.


Asunto(s)
Archaea , Bacterias , Sedimentos Geológicos , Lagos , Nitrógeno , Lagos/microbiología , Sedimentos Geológicos/microbiología , China , Nitrógeno/metabolismo , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genética , Archaea/genética , Archaea/metabolismo , Archaea/clasificación , Redes y Vías Metabólicas , Desnitrificación , Nitrificación , Thiobacillus/metabolismo , Thiobacillus/genética , Ciclo del Nitrógeno , Fijación del Nitrógeno
4.
Abdom Radiol (NY) ; 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39320496

RESUMEN

PURPOSE: To investigate the magnetic resonance imaging (MRI) and clinicopathological features of primary hepatic angiosarcoma (PHA) and enhance preoperative diagnosis. METHODS: MRI and clinicopathological information of 12 cases proved PHA were reviewed. Summarize the MRI characteristics of PHA combined with literature reviews. RESULTS: Among 12 cases (6 males and 6 females; age range, 23-70 years; mean, 53.3 years), one presented as a large mass, two as a diffuse infiltrating tumor, and nine as a mixed pattern of large masses with multiple nodules, all involving both lobes of the liver and ranging from 0.1 cm to 11 cm in diameter. A total of 63 lesions were analyzed, including 21 masses and 42 nodules. 13 masses (61.9%) demonstrated intratumoral hemorrhage. 18 masses (85.7%) demonstrated heterogeneous patchy, ring-shaped, septate, or irregular shaped enhancing foci on late arterial phase (LAP). On dynamic contrast-enhanced MRI (DCE-MRI), 14 masses (66.7%) showed a centripetal or centrifugal pattern of incomplete progressive enhancement. 6 nodules (14.3%) appeared intratumoral hemorrhage. 31 nodules (73.8%) showed no enhancing foci on LAP images and 27 nodules (64.3%) showed enhancement pattern of complete filling, either centripetal or centrifugal pattern. Moreover, 12 cases (100%) exhibited prominent vessels within or adjacent to at least one lesion. CONCLUSION: PHA exhibits diverse appearances on MRI. Typical MRI signs include multifoci with intratumoral hemorrhage, prominent vessels within or adjacent to the foci, as well as varied degrees of progressive enhancement with incomplete filling in dominant masses of PHA.

5.
ACS Appl Mater Interfaces ; 16(39): 52753-52765, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39287510

RESUMEN

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.

6.
Carbohydr Polym ; 344: 122476, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39218535

RESUMEN

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.

7.
Stem Cell Res ; 81: 103550, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39307104

RESUMEN

ADNP syndrome is a neurodevelopmental disorder characterized by autism, intellectual disability, and other physical and behavioral health manifestations. Mutations in ADNP gene is responsible for ADNP syndrome. A human iPSC line with a de novo heterozygous ADNP mutation (ADNP c. 2059 T>C) was generated from peripheral blood mononuclear cells of a patient with ADNP syndrome. This iPSC line showed typical human embryonic stem cell-like morphology, normal karyotype, pluripotency, and ability to differentiate into three germ layers. This iPSC line provides a useful resource to study the pathogenesis and drug screening of ADNP syndrome.

8.
J Med Chem ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258312

RESUMEN

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.

9.
Heliyon ; 10(17): e36588, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39263185

RESUMEN

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.

10.
Expert Rev Respir Med ; 18(9): 735-741, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39136379

RESUMEN

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.


Asunto(s)
Apolipoproteínas E , Derrame Pleural , Humanos , Derrame Pleural/diagnóstico , Derrame Pleural/metabolismo , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Método Doble Ciego , Apolipoproteínas E/genética , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/metabolismo , Biomarcadores/metabolismo , Biomarcadores/análisis , Diagnóstico Diferencial , Factores de Edad , Sensibilidad y Especificidad , Adulto , Curva ROC , Anciano de 80 o más Años , Valor Predictivo de las Pruebas
11.
ACS Appl Mater Interfaces ; 16(34): 45275-45288, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39137092

RESUMEN

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.

12.
Abdom Radiol (NY) ; 49(12): 4373-4382, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39096392

RESUMEN

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.


Asunto(s)
Várices Esofágicas y Gástricas , Bazo , Tomografía Computarizada por Rayos X , Humanos , Várices Esofágicas y Gástricas/diagnóstico por imagen , Masculino , Femenino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Bazo/diagnóstico por imagen , Medios de Contraste , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/complicaciones , Anciano , Aprendizaje Automático , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Radiómica
13.
World J Gastrointest Surg ; 16(7): 2088-2095, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39087131

RESUMEN

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.

14.
Small ; : e2402567, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39132749

RESUMEN

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.

15.
Ann Clin Microbiol Antimicrob ; 23(1): 73, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164718

RESUMEN

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.


Asunto(s)
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
16.
Mol Inform ; 43(9): e202300336, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39031899

RESUMEN

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.


Asunto(s)
Reposicionamiento de Medicamentos , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Humanos , Reposicionamiento de Medicamentos/métodos
17.
Environ Pollut ; 360: 124611, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39053806

RESUMEN

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.


Asunto(s)
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
18.
Vaccine ; 42(21): 126145, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39034218

RESUMEN

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.


Asunto(s)
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
19.
Quant Imaging Med Surg ; 14(7): 5072-5083, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39022264

RESUMEN

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.

20.
Acad Radiol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38997882

RESUMEN

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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