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1.
PeerJ Comput Sci ; 10: e2146, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38983210

RESUMEN

In recent years, the growing importance of accurate semantic segmentation in ultrasound images has led to numerous advances in deep learning-based techniques. In this article, we introduce a novel hybrid network that synergistically combines convolutional neural networks (CNN) and Vision Transformers (ViT) for ultrasound image semantic segmentation. Our primary contribution is the incorporation of multi-scale CNN in both the encoder and decoder stages, enhancing feature learning capabilities across multiple scales. Further, the bottleneck of the network leverages the ViT to capture long-range high-dimension spatial dependencies, a critical factor often overlooked in conventional CNN-based approaches. We conducted extensive experiments using a public benchmark ultrasound nerve segmentation dataset. Our proposed method was benchmarked against 17 existing baseline methods, and the results underscored its superiority, as it outperformed all competing methods including a 4.6% improvement of Dice compared against TransUNet, 13.0% improvement of Dice against Attention UNet, 10.5% improvement of precision compared against UNet. This research offers significant potential for real-world applications in medical imaging, demonstrating the power of blending CNN and ViT in a unified framework.

2.
Sensors (Basel) ; 24(13)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39001147

RESUMEN

With the development of data mining technology, the analysis of event-related potential (ERP) data has evolved from statistical analysis of time-domain features to data-driven techniques based on supervised and unsupervised learning. However, there are still many challenges in understanding the relationship between ERP components and the representation of familiar and unfamiliar faces. To address this, this paper proposes a model based on Dynamic Multi-Scale Convolution for group recognition of familiar and unfamiliar faces. This approach uses generated weight masks for cross-subject familiar/unfamiliar face recognition using a multi-scale model. The model employs a variable-length filter generator to dynamically determine the optimal filter length for time-series samples, thereby capturing features at different time scales. Comparative experiments are conducted to evaluate the model's performance against SOTA models. The results demonstrate that our model achieves impressive outcomes, with a balanced accuracy rate of 93.20% and an F1 score of 88.54%, outperforming the methods used for comparison. The ERP data extracted from different time regions in the model can also provide data-driven technical support for research based on the representation of different ERP components.


Asunto(s)
Potenciales Evocados , Reconocimiento Facial , Humanos , Potenciales Evocados/fisiología , Reconocimiento Facial/fisiología , Electroencefalografía/métodos , Algoritmos , Cara/fisiología
3.
Angew Chem Int Ed Engl ; : e202411724, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38973233

RESUMEN

Covalent organic frameworks (COFs), at the forefront of porous materials, hold tremendous potential in membrane separation; however, achieving high continuity in COF membranes remains crucial for efficient gas separation. Here, we present a unique approach termed assembly-dissociation-reconstruction for fabricating COF membranes tailored for CO2/N2 separation. A parent COF is designed from two-node aldehyde and three-node amine monomers and dissociated to high-aspect-ratio nanosheets. Subsequently, COF nanosheets are orderly reconstructed into a crack-free membrane by surface reaction under water evaporation. The membrane exhibits high crystallinity, open pores and a strong affinity for CO2 adsorption over N2, resulting in CO2 permeance exceeding 1060 GPU and CO2/N2 selectivity surpassing 30.6. The efficacy of this strategy offers valuable guidance for the precise fabrication of gas-separation membranes.

4.
Front Public Health ; 12: 1367818, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966706

RESUMEN

Background: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019. Methods: Data on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0-4, 5-9, 10-14 and 15-19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC. Results: The global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0-4, 5-9, 10-14 and 15-19 years were also associated with the incidences, particularly for the exposures at ages 15-19 years. Conclusion: The global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.


Asunto(s)
Neoplasias Colorrectales , Salud Global , Humanos , Incidencia , Neoplasias Colorrectales/epidemiología , Adolescente , Niño , Lactante , Preescolar , Adulto Joven , Salud Global/estadística & datos numéricos , Factores de Riesgo , Recién Nacido , Femenino , Masculino , Carga Global de Enfermedades/tendencias , Edad de Inicio , Adulto
5.
Eur J Pharm Sci ; 200: 106838, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960205

RESUMEN

Physiologically based pharmacokinetic (PBPK) models which can leverage preclinical data to predict the pharmacokinetic properties of drugs rapidly became an essential tool to improve the efficiency and quality of novel drug development. In this review, by searching the Application Review Files in Drugs@FDA, we analyzed the current application of PBPK models in novel drugs approved by the U.S. Food and Drug Administration (FDA) in the past five years. According to the results, 243 novel drugs were approved by the FDA from 2019 to 2023. During this period, 74 Application Review Files of novel drugs approved by the FDA that used PBPK models. PBPK models were used in various areas, including drug-drug interactions (DDI), organ impairment (OI) patients, pediatrics, drug-gene interaction (DGI), disease impact, and food effects. DDI was the most widely used area of PBPK models for novel drugs, accounting for 74.2 % of the total. Software platforms with graphical user interfaces (GUI) have reduced the difficulty of PBPK modeling, and Simcyp was the most popular software platform among applicants, with a usage rate of 80.5 %. Despite its challenges, PBPK has demonstrated its potential in novel drug development, and a growing number of successful cases provide experience learned for researchers in the industry.

6.
Int Ophthalmol ; 44(1): 237, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902457

RESUMEN

PURPOSE: Calculating the intraocular lens (IOL) in patients after corneal refractive surgery presents a challenge. Because an overestimation of corneal power in cases undergone this surgery leading to a subsequent under-correction of IOL power. However, recent advancements in technology have eliable measurement of total corneal power. The aim of this research was to assess the agreement in simulated keratometry (SimK) and total keratometry (TK) values between IOLMaster 700 and Pentacam AXL. METHODS: The study involved 99 patients (99 eyes) undergone small incision lenticule extraction (SMILE) surgery. Each patient underwent scans using IOL Master 700 and Pentacam AXL. The following parameters were recorded: SimK1, SimK2, Total K1 (TK1), and Total K2 (TK2) for IOLMaster 700; and SimK1, SimK2, True Net Power (TNP) K1, TNPK2, Total Corneal Refractive Power (TCRP) K1, and TCRP K2 for Pentacam AXL. Agreement between the two devices was evaluated using Bland-Altman plot, while paired t-test was utilized to compare any differences in the same parameter by both instruments. RESULTS: The results revealed a strong correlation between the two devices.Noticeable comparability was identified for all SimK variables. However, there were noticeable differences in TK measurements as well as TK1-TNPK1, TK2-TNP K2, TK1-TCRP K1, and TK2-TCRP K2 parameters when comparing the two devices. The IOLMaster 700 consistently measured steeper values than the Pentacam AXL, with significant and clinically relevant differences of 1.34, 1.37, 0.87, and 0.95 diopters, respectively. CONCLUSION: While there was a noticeable correlation between the IOLMaster 700 and Pentacam AXL in SimK measurements, a marked difference was noted in TK values. The two devices cannot be used interchangeably when quantifying TK values.


Asunto(s)
Córnea , Topografía de la Córnea , Miopía , Refracción Ocular , Humanos , Masculino , Femenino , Adulto , Córnea/cirugía , Córnea/diagnóstico por imagen , Córnea/patología , Refracción Ocular/fisiología , Topografía de la Córnea/métodos , Miopía/cirugía , Miopía/diagnóstico , Persona de Mediana Edad , Adulto Joven , Lentes Intraoculares , Biometría/métodos , Biometría/instrumentación , Estudios Prospectivos , Reproducibilidad de los Resultados , Agudeza Visual , Cirugía Laser de Córnea/métodos
7.
Nat Commun ; 15(1): 5162, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890313

RESUMEN

Two-dimensional (2D) ferroelectric materials have emerged as significant platforms for multi-functional three-dimensional (3D) integrated electronic devices. Among 2D ferroelectric materials, ferro-ionic CuInP2S6 has the potential to achieve the versatile advances in neuromorphic computing systems due to its phase tunability and ferro-ionic characteristics. As CuInP2S6 exhibits a ferroelectric phase with insulating properties at room temperature, the external temperature and electrical field should be required to activate the ferro-ionic conduction. Nevertheless, such external conditions inevitably facilitate stochastic ionic conduction, which completely limits the practical applications of 2D ferro-ionic materials. Herein, free-standing 2D ferroelectric heterostructure is mechanically manipulated for nano-confined conductive filaments growth in free-standing 2D ferro-ionic memristor. The ultra-high mechanical bending is selectively facilitated at the free-standing area to spatially activate the ferro-ionic conduction, which allows the deterministic local positioning of Cu+ ion transport. According to the local flexoelectric engineering, 5.76×102-fold increased maximum current is observed within vertical shear strain 720 nN, which is theoretically supported by the 3D flexoelectric simulation. In conclusion, we envision that our universal free-standing platform can provide the extendable geometric solution for ultra-efficient self-powered system and reliable neuromorphic device.

8.
Cell Rep ; 43(6): 114356, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38865246

RESUMEN

In addition to its role in vision, light also serves non-image-forming visual functions. Despite clinical evidence suggesting the antipruritic effects of bright light treatment, the circuit mechanisms underlying the effects of light on itch-related behaviors remain poorly understood. In this study, we demonstrate that bright light treatment reduces itch-related behaviors in mice through a visual circuit related to the lateral parabrachial nucleus (LPBN). Specifically, a subset of retinal ganglion cells (RGCs) innervates GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which subsequently inhibit CaMKIIα+ neurons in the LPBN. Activation of both the vLGN/IGL-projecting RGCs and the vLGN/IGL-to-LPBN projections is sufficient to reduce itch-related behaviors induced by various pruritogens. Importantly, we demonstrate that the antipruritic effects of bright light treatment rely on the activation of the retina-vLGN/IGL-LPBN pathway. Collectively, our findings elucidate a visual circuit related to the LPBN that underlies the antipruritic effects of bright light treatment.


Asunto(s)
Núcleos Parabraquiales , Prurito , Animales , Ratones , Núcleos Parabraquiales/fisiología , Prurito/patología , Luz , Células Ganglionares de la Retina/efectos de la radiación , Vías Visuales/efectos de la radiación , Ratones Endogámicos C57BL , Masculino , Antipruriginosos/farmacología , Antipruriginosos/uso terapéutico , Neuronas GABAérgicas/metabolismo , Neuronas GABAérgicas/efectos de la radiación , Conducta Animal/efectos de la radiación , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo
9.
Nanotechnology ; 35(38)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38906124

RESUMEN

A variety of strategies have been developed to enhance the cycling stability of Si-based anodes in lithium-ion batteries. Although significant progress has been made in enhancing the cycling stability of Si-based anodes, the low initial Coulombic efficiency (ICE) remains a significant challenge to their commercial application. Herein, pitch-based carbon (C) coated Si nanoparticles (NPs) were wrapped by graphene (G) to obtain Si@C/G composite with a small specific surface area of 11.3 m2g-1, resulting in a high ICE of 91.2% at 500 mA g-1. Moreover, the integrated utilization of graphene and soft carbon derived from the low-cost petroleum pitch strongly promotes the electrical conductivity, structure stability, and reaction kinetics of Si NPs. Consequently, the synthesized Si@C/G with a Si loading of 54.7% delivers large reversible capacity (1191 mAh g-1at 500 mA g-1), long cycle life over 200 cycles (a capacity retention of 87.1%), and superior rate capability (952 mAh g-1at 1500 mA g-1). When coupled with a homemade LiNi0.8Co0.1Mn0.1O2(NCM811) cathode in a full cell, it exhibits a promising cycling stability for 200 cycles. This work presents an innovative approach for the manufacture of Si-based anode materials with commercial application.

10.
Nanoscale ; 16(25): 11879-11913, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38845582

RESUMEN

Brain disorders, including neurodegenerative diseases (NDs) and traumatic brain injury (TBI), present significant challenges in early diagnosis and intervention. Conventional imaging modalities, while valuable, lack the molecular specificity necessary for precise disease characterization. Compared to the study of conventional brain tissues, liquid biopsy, which focuses on blood, tear, saliva, and cerebrospinal fluid (CSF), also unveils a myriad of underlying molecular processes, providing abundant predictive clinical information. In addition, liquid biopsy is minimally- to non-invasive, and highly repeatable, offering the potential for continuous monitoring. Raman spectroscopy (RS), with its ability to provide rich molecular information and cost-effectiveness, holds great potential for transformative advancements in early detection and understanding the biochemical changes associated with NDs and TBI. Recent developments in Raman enhancement technologies and advanced data analysis methods have enhanced the applicability of RS in probing the intricate molecular signatures within biological fluids, offering new insights into disease pathology. This review explores the growing role of RS as a promising and emerging tool for disease diagnosis in brain disorders, particularly through the analysis of liquid biopsy. It discusses the current landscape and future prospects of RS in the diagnosis of brain disorders, highlighting its potential as a non-invasive and molecularly specific diagnostic tool.


Asunto(s)
Espectrometría Raman , Espectrometría Raman/métodos , Humanos , Biopsia Líquida/métodos , Encefalopatías/diagnóstico , Encefalopatías/patología , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/metabolismo , Encéfalo/patología , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen
11.
Sci Rep ; 14(1): 14113, 2024 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898266

RESUMEN

Skin cutaneous melanoma (SKCM) is a highly malignant form of skin cancer, known for its unfavorable prognosis and elevated mortality rate. RARRES1, a gene responsive to retinoic acid receptors, displays varied functions in various cancer types. However, the specific role and underlying mechanisms of RARRES1 in SKCM are still unclear. GSE15605 was utilized to analyze the expression of RARRES1 in SKCM. Subsequently, the TCGA and GEO databases were employed to investigate the relationships between RARRES1 and clinicopathological parameters, as well as the prognostic implications and diagnostic efficacy of RARRES1 in SKCM. GO, KEGG, and GSEA analyses were conducted to explore the potential functions of RARRES1. Furthermore, the associations between RARRES1 and immune infiltration were examined. Genomic alterations and promoter methylation levels of RARRES1 in SKCM were assessed using cBioPortal, UALCAN, and the GEO database. Finally, RARRES1 expression in SKCM was validated through immunohistochemistry, and its functional role in SKCM progression was elucidated via in vivo and in vitro experiments. We found that RARRES1 was downregulated in SKCM compared with normal tissues, and this low expression was associated with worse clinicopathological features and poor prognosis of SKCM. The diagnostic efficacy of RARRES1, as determined by ROC analysis, was 0.732. Through GO, KEGG, and GSEA enrichment analysis, we identified 30 correlated genes and pathways that were mainly enriched in the tumor immune microenvironment, proliferation, apoptosis, and autophagy. Additionally, RARRES1 expression was found to be positively related to the infiltration of various immune cells in SKCM, particularly macrophages and T helper cells, among others. Analysis of genomic alterations and promoter methylation revealed that shallow deletion and hypermethylation of the RARRES1 promoter could lead to reduced RARRES1 expression. IHC validation confirmed the downregulation of RARRES1 in SKCM. Moreover, overexpression of RARRES1 inhibited the proliferation and migration of A375 cells, promoted apoptosis, and inhibited autophagic flux. In the mouse xenograft model, RARRES1 overexpression also suppressed SKCM tumor growth. Collectively, these findings suggest that RARRES1 may function as a suppressor and could potentially serve as a prognostic biomarker and therapeutic target for SKCM.


Asunto(s)
Biomarcadores de Tumor , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Melanoma Cutáneo Maligno , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Biología Computacional/métodos , Animales , Línea Celular Tumoral , Ratones , Pronóstico , Metilación de ADN , Femenino , Proliferación Celular , Masculino , Microambiente Tumoral/genética , Regiones Promotoras Genéticas , Persona de Mediana Edad , Apoptosis/genética , Proteínas de la Membrana
12.
Biosci Trends ; 18(3): 263-276, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853000

RESUMEN

This study aims to determine the predictive role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) derived radiomic model in tumor immune profiling and immunotherapy for cholangiocarcinoma. To perform radiomic analysis, immune related subgroup clustering was first performed by single sample gene set enrichment analysis (ssGSEA). Second, a total of 806 radiomic features for each phase of DCE-MRI were extracted by utilizing the Python package Pyradiomics. Then, a predictive radiomic signature model was constructed after a three-step features reduction and selection, and receiver operating characteristic (ROC) curve was employed to evaluate the performance of this model. In the end, an independent testing cohort involving cholangiocarcinoma patients with anti-PD-1 Sintilimab treatment after surgery was used to verify the potential application of the established radiomic model in immunotherapy for cholangiocarcinoma. Two distinct immune related subgroups were classified using ssGSEA based on transcriptome sequencing. For radiomic analysis, a total of 10 predictive radiomic features were finally identified to establish a radiomic signature model for immune landscape classification. Regarding to the predictive performance, the mean AUC of ROC curves was 0.80 in the training/validation cohort. For the independent testing cohort, the individual predictive probability by radiomic model and the corresponding immune score derived from ssGSEA was significantly correlated. In conclusion, radiomic signature model based on DCE-MRI was capable of predicting the immune landscape of chalangiocarcinoma. Consequently, a potentially clinical application of this developed radiomic model to guide immunotherapy for cholangiocarcinoma was suggested.


Asunto(s)
Colangiocarcinoma , Inmunoterapia , Imagen por Resonancia Magnética , Humanos , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/inmunología , Colangiocarcinoma/terapia , Colangiocarcinoma/genética , Imagen por Resonancia Magnética/métodos , Inmunoterapia/métodos , Masculino , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/inmunología , Neoplasias de los Conductos Biliares/terapia , Femenino , Persona de Mediana Edad , Medios de Contraste , Curva ROC , Anciano , Transcriptoma
13.
ACS Appl Mater Interfaces ; 16(27): 35505-35515, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38935928

RESUMEN

The commercialization of 3D heterogeneous integration through hybrid bonding has accelerated, and accordingly, Cu-polymer bonding has gained significant attention as a means of overcoming the limitations of conventional Cu-SiO2 hybrid bonding, offering high compatibility with other fabrication processes. Polymers offer robust bonding strength and a low dielectric constant, enabling high-speed signal transmission with high reliability, but suffer from low thermomechanical stability. Thermomechanical stability of polymers was not achieved previously because of thermal degradation and unstable anchoring. To overcome these limitations, wafer-scale Cu-polymer bonding via N-heterocyclic carbene (NHC) nanolayers was presented for 3D heterogeneous integration, affording ultrastable packing density, crystallinity, and thermal properties. NHC nanolayers were deposited on copper electrodes via electrochemical deposition, and wafer-scale 3D heterogeneous integration was achieved by adhesive bonding at 170 °C for 1 min. Ultrastable conductivity and thermomechanical properties were observed by the spatial mapping of conductivity, work function, and force-distance curves. With regard to the characterization of NHC nanolayers, low-temperature bonding, robust corrosion inhibition, enhanced electrical conductivity, back-end-of-line process compatibility, and fabrication process reduction, NHC Cu/polymer bonding provides versatile advances in 3D heterogeneous integration, indicating that NHC Cu/polymer bonding can be utilized as a platform for future 3D vertical chip architectures.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38916485

RESUMEN

BACKGROUND: The therapeutic impact of the Wenyang Huoxue (WYXH) formula on coronary atherosclerotic heart disease (CHD) is well established, yet the precise mechanisms are currently not fully understood. This study provides preliminary insights into the potential mechanisms underlying the therapeutic effects of the formula on CHD by utilizing network pharmacology and molecular docking technology. MATERIALS AND METHODS: The primary active constituents and their corresponding action targets for the formula were retrieved from the TCMSP database. Utilizing Cytoscape 3.9.1 software, a network linking the components of the formula to their respective targets was constructed. Information was collected from Genecards, OMIM, TTD, and DrugBank databases to identify targets related to CHD. The common targets shared by the formula and CHD were then imported into the STRING database to create a protein-protein interaction (PPI) network. Following this, enrichment analyses were performed on the shared targets using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, molecular docking was conducted on the primary active compounds and the core targets. RESULTS: The network encompassing the components and targets of the formula comprises a total of 311 nodes and 895 edges. Compounds exhibiting higher degree centrality consist of quercetin, ß-sitosterol, and kaempferol. In the PPI network, proteins with elevated degree centrality are protein kinase B (AKT1), epidermal growth factor receptor (EGFR), and mitogen-activated protein kinase 3 (MAPK3). The results of GO and KEGG enrichment analyses reveal that the biological processes associated with the efficacy of the formula in treating CHD primarily involve positive regulation of gene expression, hypoxia response, and lipopolysaccharide response, among others. The signaling pathways primarily involved include phosphatidylinositol 3-kinase and protein kinase B (PI3K-AKT), MAPK3, tumor necrosis factor (TNF), and so on. Molecular docking results demonstrate a strong affinity between quercetin, ß-sitosterol, and kaempferol with AKT1, EGFR, and MAPK3. CONCLUSION: We showed for the first time that AKT1, EGFR, and MAPK3 are potential targets influenced by the WYHX formula in CHD treatment. The therapeutic effects could possibly involve signaling pathways such as the PI3K-AKT, MAPK, TNF, and AGE-RAGE pathways.

15.
Angew Chem Int Ed Engl ; 63(29): e202400143, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38698663

RESUMEN

The chemistry of quinone methides formed in situ has been flourishing in recent years. In sharp contrast, the development and utilization of biphenyl quinone methides are rare. In this study, we achieved a remote stereocontrolled 1,12-conjugate addition of biphenyl quinone methides formed in situ for the first time. In the presence of a suitable chiral phosphoric acid, alkynyl biphenyl quinone methides were generated from α-[4-(4-hydroxyphenyl)phenyl]propargyl alcohols, followed by enantioselective 1,12-conjugate addition with indole-2-carboxylates. The strategy enabled the alcohols to serve as efficient allenylation reagents, providing practical access to a broad range of axially chiral allenes bearing a (1,1'-biphenyl)-4-ol unit, which were previously less accessible. Combined with control experiments, density functional theory calculations shed light on the reaction mechanism, indicating that enantioselectivity originates from the nucleophilic addition of alkynyl biphenyl quinone methides. Notably, not only the presence of biphenyl quinone methides as versatile intermediates was confirmed but also organocatalytic enantioselective 1,12-addition was established.

16.
J Med Chem ; 67(8): 6726-6737, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38570733

RESUMEN

Cyclin-dependent kinase 19 (CDK19) is overexpressed in prostate cancer, making it an attractive target for both imaging and therapy. Since little is known about the optimized approach for radioligands of nuclear proteins, linker optimization strategies were used to improve pharmacokinetics and tumor absorption, including the adjustment of the length, flexibility/rigidity, and hydrophilicity/lipophilicity of linkers. Molecular docking was conducted for virtual screening and followed by IC50 determination. Both BALB/c mice and P-16 xenografts were used for tissue distribution and PET/CT imaging. The ligand 68Ga-10c demonstrated high absorption in tumor 5 min after injection and sustains long-term imaging within 3 h. Furthermore, 68Ga-10c exhibited slow clearance within the tumor and was predominantly metabolized in both the liver and kidneys, showing the potential to alleviate metabolic pressure and enhance tissue safety. Therefore, the linker optimization strategy is well suited for CDK19 and provides a reference for the radioactive ligands of other nuclear targets.


Asunto(s)
Quinasas Ciclina-Dependientes , Ratones Endogámicos BALB C , Animales , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/metabolismo , Humanos , Ratones , Masculino , Simulación del Acoplamiento Molecular , Diseño de Fármacos , Distribución Tisular , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Radiofármacos/química , Radiofármacos/farmacocinética , Línea Celular Tumoral
17.
Biomimetics (Basel) ; 9(4)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38667237

RESUMEN

In this paper, we proposed a miniature quadrupedal piezoelectric robot with a mass of 1.8 g and a body length of 4.6 cm. The robot adopts a novel spatial parallel mechanism as its transmission. Each leg of the robot has two degrees of freedom (DOFs): swing and lift. The trajectory necessary for walking is achieved by the appropriate phasing of these two DOFs. A new manufacturing method for piezoelectric actuators was developed. During the stacking process, discrete patterned PZT pieces are used to avoid dielectric failure caused by laser cutting. Copper-clad FR-4 is used as the solder pad instead of copper foil, making the connection between the pad and the actuator more reliable. The lift powertrain of the robot was modeled and the link length of the powertrain was optimized based on the model. The maximum output force of each leg can reach 26 mN under optimized design parameters, which is 1.38 times the required force for successful walking. The frequency response of the powertrain was measured and fitted to the second-order system, which enabled increased leg amplitudes near the powertrain resonance of approximately 70 Hz with adjusted drive signals. The maximum speed of the robot without load reached 48.66 cm/s (10.58 body lengths per second) and the payload capacity can reach 5.5 g (3.05 times its mass) near the powertrain resonance.

18.
J Environ Manage ; 357: 120783, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38579475

RESUMEN

The rapid development of the economy and society is causing an increase in the amount of municipal solid waste (MSW) produced by people's daily lives. With the strong support of the Chinese government, incineration power generation has steadily become the primary method of treating MSW, accounting for 79.86%. However, burning produces a significant amount of municipal solid waste incineration fly ash (MSWI-FA), which contains heavy metals, soluble chlorine salts, and dioxins. China's MSWI-FA yield increased by 8.23% annually to 7.80 million tons in 2022. Besides, the eastern region, especially the southeastern coastal region, has the highest yield of MSWI-FA. There are certain similarities in the chemical characteristics of MSWI-FA samples from Northeast, North, East, and South China. Zn and CaO have the largest amounts of metals and oxides, respectively. The Cl content is about 20 wt%. This study provides an overview of the techniques used in the thermal treatment method, solidification and stabilization, and separation and extraction of MSWI-FA and compares their benefits and drawbacks. In addition, the industrial applications and standard requirements of landfill treatment and resource utilization of MSWI-FA in China are analyzed. It is discovered that China's resource utilization of MSWI-FA is insufficient through the study on the fly ash disposal procedures at a few MSW incineration facilities located in the economically developed Guangdong Province and the traditional industrial city of Tianjin. Finally, the prospects for the disposal of MSWI-FA were discussed.


Asunto(s)
Metales Pesados , Eliminación de Residuos , Humanos , Ceniza del Carbón/química , Residuos Sólidos/análisis , Material Particulado/análisis , Carbono/análisis , Incineración , Metales Pesados/análisis , China
20.
J Microencapsul ; 41(3): 190-203, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38602138

RESUMEN

AIMS: To develop Antarctic krill oil emulsions with casein and whey protein concentrate (WPC) and study their physicochemical properties and storage stability. METHODS: Emulsions were prepared by homogenisation and ultrasonication. The properties of the emulsions were investigated via ultraviolet ray spectroscopy, dynamic light scattering, confocal laser scanning microscope, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, Fourier transform infra-red spectrometer, and fluorescence spectrum. Shelf life was predicted by the Arrhenius model. RESULTS: Casein- and WPC-krill oil emulsions were well formed; the mean particle diameters were less than 128.19 ± 0.64 nm and 158 ± 1.56 nm, the polymer dispersity indices were less than 0.26 ± 0.01 and 0.27 ± 0.01, and the zeta potential were around -46.88 ± 5.02 mV and -33.51 ± 2.68 mV, respectively. Shelf life was predicted to be 32.67 ± 1.55 days and 29.62 ± 0.65 days (40 °C), 27.69 ± 1.15 days and 23.58 ± 0.14 days (50 °C), 24.02 ± 0.15 days and 20.1 ± 0.08 days (60 °C). CONCLUSION: The prepared krill oil emulsions have great potential to become a new krill oil supplement.


Asunto(s)
Caseínas , Euphausiacea , Animales , Emulsiones/química , Proteína de Suero de Leche/química , Aceites
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