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1.
bioRxiv ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39091823

RESUMEN

There is a growing interest in using diffusion MRI to study the white matter tracts and structural connectivity of the fetal brain. Recent progress in data acquisition and processing suggests that this imaging modality has a unique role in elucidating the normal and abnormal patterns of neurodevelopment in utero. However, there have been no efforts to quantify the prevalence of crossing tracts and bottleneck regions, important issues that have been extensively researched for adult brains. In this work, we determined the brain regions with crossing tracts and bottlenecks between 23 and 36 gestational weeks. We performed probabilistic tractography on 59 fetal brain scans and extracted a set of 51 distinct white tracts, which we grouped into 10 major tract bundle groups. We analyzed the results to determine the patterns of tract crossings and bottlenecks. Our results showed that 20-25% of the white matter voxels included two or three crossing tracts. Bottlenecks were more prevalent. Between 75-80% of the voxels were characterized as bottlenecks, with more than 40% of the voxels involving four or more tracts. The results of this study highlight the challenge of fetal brain tractography and structural connectivity assessment and call for innovative image acquisition and analysis methods to mitigate these problems.

2.
J Med Virol ; 96(8): e29842, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39115036

RESUMEN

To explore the impacts of cytomegalovirus (CMV) infection and antiviral treatment (AVT) on native liver survival (NLS) in biliary atresia (BA) infants. This retrospective cohort study included infants diagnosed as BA between January 2015 and December 2021 at Hunan Children's Hospital. CMV infection was defined by DNA polymerase chain reaction alone (DNA data set) and combination of DNA and immunoglobulin M (CMV data set). In the DNA data set of 330 patients, 234 patients (70.9%) survived with their native liver in 2 years, with 113 (73.9%) in the DNA- cohort, 70 (65.4%) in the DNA+ and AVT- cohort and 51 (72.9%) in the DNA+ and AVT+ cohort, without significant differences by log-rank tests. In patients administrated between 2015 and March 2019, there were 206 evaluable patients in the DNA data set, with rates of 5-year NLS of 68.3% in the DNA- cohort, similar to that in the DNA+ and AVT+ cohort (62.2%, p = 0.546), but significantly higher than that in the DNA+ and AVT- cohort (51.4%, p = 0.031). Similar trends were also observed in the CMV data set, although statistically insignificant. CMV infection before or on the day of HPE can reduce the rate of 5-year NLS and AVT was recommended for CMV-infected BA infants.


Asunto(s)
Antivirales , Atresia Biliar , Infecciones por Citomegalovirus , Citomegalovirus , Humanos , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/virología , Estudios Retrospectivos , Atresia Biliar/tratamiento farmacológico , Antivirales/uso terapéutico , Femenino , Masculino , Lactante , Citomegalovirus/genética , Citomegalovirus/efectos de los fármacos , Pronóstico , ADN Viral , Recién Nacido
3.
Chem Commun (Camb) ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39104313

RESUMEN

The electrochemical carbon dioxide reduction reaction (eCO2RR) represents an effective means of achieving renewable energy storage and a supply of carbon-based raw materials. However, there are still great challenges in selectively producing specific hydrocarbon compounds. The unique ability of the copper (Cu) catalyst to promote proton-coupled electron transfer processes offers clear advantages in generating value-added products. This review presents molecular enhancement strategies for Cu-based catalysts for CO2 electroreduction. We also elucidate the principles of each strategy for enhancing eCO2RR performance, discuss the structure-activity relationships, and propose some promising molecular enhancement strategies. This review will provide guidance for the development of organic-inorganic hybrid Cu-based catalysts as high-performance CO2 electroreduction catalysts.

4.
Sci Total Environ ; 950: 175053, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39097008

RESUMEN

Mining activities disrupt the natural oxidative balance underground, increasing the oxidation of metal sulfides like pyrite. This process leads to the formation of highly acidic mine drainage (AMD) with elevated concentrations of iron (Fe) and sulfate (SO42-). However, generic plugging and backfilling methods, when applied without considering the specific post-mining oxidative environments of different metal mines, often yields minimal results. To clarify the distribution of the underground redox environment after mining of a metal mine in Dexing, China, fifteen water samples from flood and dry periods, as well as fifteen borehole samples, were collected for hydrogeological and chemical analysis. For the first time, the study proposed that the redox zone could be identified and delineated through vertical analysis of water storage media, mineral composition, and hydrochemical characteristics. A hydrogeochemical cause model was constructed, revealing that AMD formation primarily occurs in oxidative and transition zones. Based on the redox zone characteristics of the study area, actual engineering sealing was performed on the oxidation and transition zones of cavity No. 23. As a result, the pH increased from 2.5 before remediation to 4.5, indicating a reduction in acidity. The concentrations of SO42- and Fe significantly decreased, reducing from 1360.0 mg/L and 147.0 mg/L before treatment to 726.0 mg/L and 23.6 mg/L after treatment; the total decrease amounting to 46.6 % and 84.0 %, respectively. The concentrations of Mn and Cu similarly, decreased by 10.7 % and 15.6 %, respectively. This study provides a novel approach and valuable reference for the refined identification and classification of redox zones after metal mine exploitation, as well as for the targeted plugging and treatment of cavities that produce AMD.

5.
Technol Cancer Res Treat ; 23: 15330338241273160, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099463

RESUMEN

Introduction: The independent diagnostic value of inflammatory markers neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the diagnostic efficacy of NLR, derived neutrophil to lymphocyte ratio (dNLR), PLR, and lymphocyte-to-monocyte ratio (LMR) in glioma cases remain unclear. We investigated the correlation of preoperative peripheral blood inflammatory markers with pathological grade, Ki-67 Proliferation Index, and IDH-1 gene phenotype in patients with glioma, focusing on tumor grade and prognosis. Methods: We retrospectively analyzed the clinical, pathological, and laboratory data of 334 patients with glioma with varying grades and 345 with World Health Organization (WHO I) meningioma who underwent initial surgery at the Affiliated Hospital of Jining Medical University from December 2019 to December 2021. The diagnostic value of peripheral blood inflammatory markers for glioma was investigated. Results: The proportion of men smoking and drinking was significantly higher in the glioma group than in the meningioma group (P < .05); in contrast, the age and body mass index (Kg/m2) were significantly lower in the glioma group (P = .01). Significant differences were noted in the pathological grade (WHO II, III, and IV), Ki-67 Proliferation Index, and peripheral blood inflammatory markers such as lymphocyte median, NLR, dNLR, and PLR between the groups (P < .05). No significant correlation existed between peripheral blood inflammatory factors and IDH-1 gene mutation status or tumor location in patients with glioma (P > .05). LMR, NLR, dNLR, and PLR, varied significantly among different glioma types (P < .05). White blood cell (WBC) count, neutrophil, NLR, and dNLR correlated positively with glioma risk. Further, WBC, neutrophil, NLR, dNLR, and LMR had a high diagnostic efficiency. Conclusion: Peripheral blood inflammatory markers, serving as noninvasive biomarkers, offer high sensitivity and specificity for diagnosing glioma, differentiating it from meningioma, diagnosing GBM, and distinguishing GBM from low-grade glioma. These markers may be implemented as routine screening tools.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Encefálicas , Glioma , Clasificación del Tumor , Neutrófilos , Humanos , Glioma/patología , Glioma/sangre , Glioma/cirugía , Glioma/diagnóstico , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Neutrófilos/patología , Adulto , Estudios Retrospectivos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico , Anciano , Linfocitos/patología , Periodo Preoperatorio , Inflamación/patología , Inflamación/sangre , Plaquetas/patología , Curva ROC
6.
BMC Public Health ; 24(1): 2109, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103831

RESUMEN

BACKGROUND: Loneliness and social isolation have been found to be associated with various health-related outcomes. Our study aimed to evaluate the association of loneliness and social isolation with the risk of glaucoma. METHODS: A total of 373,330 participants from the UK Biobank without glaucoma at recruitment were included in this study. Self-reported questionnaires were used to define loneliness and social isolation. Incident glaucoma events were identified by hospital inpatient admissions and self-reported data. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During a median follow-up of 13.1 (interquartile range: 12.3-13.9) years, 6,489 participants developed glaucoma. After adjusting for confounding factors, loneliness (yes vs. no: adjusted HR: 1.16; 95% CI: 1.04-1.30; P = 0.009) and social isolation (yes vs. no: adjusted HR: 1.08; 95% CI: 1.01-1.16; P = 0.033) were associated with an increased risk of glaucoma. CONCLUSIONS: In this population-based prospective cohort study, loneliness and social isolation were associated with a higher risk of glaucoma.


Asunto(s)
Glaucoma , Soledad , Aislamiento Social , Humanos , Soledad/psicología , Reino Unido/epidemiología , Aislamiento Social/psicología , Masculino , Femenino , Persona de Mediana Edad , Glaucoma/psicología , Glaucoma/epidemiología , Estudios Prospectivos , Factores de Riesgo , Anciano , Adulto , Bancos de Muestras Biológicas , Modelos de Riesgos Proporcionales , Encuestas y Cuestionarios , Autoinforme , Biobanco del Reino Unido
7.
Drug Dev Res ; 85(5): e22241, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39104176

RESUMEN

The role of KRAS mutation in non-small cell lung cancer (NSCLC) initiation and progression is well-established. However, "undruggable" KRAS protein poses the research of small molecule inhibitors a significant challenge. Addressing this, proteolysis-targeting chimeras (PROTACs) have become a cutting-edge treatment method, emphasizing protein degradation. A modified ethanol injection method was employed in this study to formulate liposomes encapsulating PROTAC drug LC-2 (LC-2 LPs). Precise surface modifications using cell-penetrating peptide R8 yielded R8-LC-2 liposomes (R8-LC-2 LPs). Comprehensive cellular uptake and cytotoxicity studies unveiled that R8-LC-2 LPs depended on concentration and time, showcasing the superior performance of R8-LC-2 LPs compared to normal liposomes. In vivo pharmacokinetic profiles demonstrated the capacity of DSPE-PEG2000 to prolong the circulation time of LC-2, leading to higher plasma concentrations compared to free LC-2. In vivo antitumor efficacy research underscored the remarkable ability of R8-LC-2 LPs to effectively suppress tumor growth. This study contributed to the exploration of enhanced therapeutic strategies for NSCLC, specifically focusing on the development of liposomal PROTACs targeting the "undruggable" KRAS protein. The findings provide valuable insights into the potential of this innovative approach, offering prospects for improved drug delivery and heightened antitumor efficacy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Liposomas , Neoplasias Pulmonares , Proteolisis , Proteínas Proto-Oncogénicas p21(ras) , Animales , Humanos , Ratones , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Línea Celular Tumoral , Péptidos de Penetración Celular , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Fosfatidiletanolaminas/química , Polietilenglicoles/química , Proteolisis/efectos de los fármacos , Quimera Dirigida a la Proteólisis/administración & dosificación , Quimera Dirigida a la Proteólisis/farmacocinética , Quimera Dirigida a la Proteólisis/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genética , Ratas
8.
Crit Care Res Pract ; 2024: 9562200, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104663

RESUMEN

Background: Elevated red blood cell distribution width (RDW) levels are strongly associated with an increased risk of mortality in patients with congestive heart failure (CHF). Additionally, heart failure has been closely linked to diabetes. Nevertheless, the relationship between RDW and in-hospital mortality in the intensive care unit (ICU) among patients with both congestive heart failure (CHF) and diabetes mellitus (DM) remains uncertain. Methods: This retrospective study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, a comprehensive critical care repository. RDW was assessed as both continuous and categorical variables. The primary outcome of the study was in-hospital mortality at the time of hospital discharge. We examined the association between RDW on ICU admission and in-hospital mortality using multivariable logistic regression models, restricted cubic spline analysis, and subgroup analysis. Results: The cohort consisted of 7,063 patients with both DM and CHF (3,135 females and 3,928 males). After adjusting for potential confounders, we found an association between a 9% increase in mortality rate and a 1 g/L increase in RDW level (OR = 1.09; 95% CI, 1.05∼1.13), which was associated with 11 and 58% increases in mortality rates in Q2 (OR = 1.11, 95% CI: 0.87∼1.43) and Q3 (OR = 1.58, 95% CI: 1.22∼2.04), respectively, compared with that in Q1. Moreover, we observed a significant linear association between RDW and in-hospital mortality, along with strong stratified analyses to support the findings. Conclusions: Our findings establish a positive association between RDW and in-hospital mortality in patients with DM and CHF.

9.
Front Pharmacol ; 15: 1368776, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114359

RESUMEN

Background: The fibrous root of ginseng (GFR) is the dried thin branch root or whisker root of Ginseng (Panax ginseng C. A. Mey). It is known for its properties such as tonifying qi, producing body fluid, and quenching thirst. Clinically, it is used to treat conditions such as cough, hemoptysis, thirst, stomach deficiency, and vomiting. While GFR and Ginseng share similar metabolites, they differ in their metabolites ratios and efficacy. Furthermore, the specific role of GFR in protecting the body remains unclear. Methods: We employed ultra-high performance liquid chromatography-triple quadrupole mass spectrometry to examine alterations in brain neurotransmitters and elucidate the impact of GFR on the central nervous system. Additionally, we analyzed the serum and brain metabolic profiles of rats using ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry to discern the effect and underlying mechanism of GFR in delaying aging in naturally aged rats. Results: The findings of the serum biochemical indicators indicate that the intervention of GFR can enhance cardiovascular, oxidative stress, and energy metabolism related indicators in naturally aging rats. Research on brain neurotransmitters suggests that GFR can augment physiological functions such as learning and memory, while also inhibiting central nervous system excitation to a certain degree by maintaining the equilibrium of central neurotransmitters in aged individuals. Twenty-four abnormal metabolites in serum and seventeen abnormal metabolites in brain could be used as potential biomarkers and were involved in multiple metabolic pathways. Among them, in the brain metabolic pathways, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, histidine metabolism, and tyrosine metabolism were closely related to central neurotransmitters. Butanoate metabolism improves energy supply for life activities in the aging body. Cysteine and methionine metabolism contributes to the production of glutathione and taurine and played an antioxidant role. In serum, the regulation of glycerophospholipid metabolism pathway and proline metabolism demonstrated the antioxidant capacity of GFR decoction. Conclution: In summary, GFR plays a role in delaying aging by regulating central neurotransmitters, cardiovascular function, oxidative stress, energy metabolism, and other aspects of the aging body, which lays a foundation for the application of GFR.

10.
Am J Transl Res ; 16(7): 3148-3156, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114731

RESUMEN

OBJECTIVE: This study aimed to investigate the impact of lower limb alignment abnormalities, specifically physiological knee valgus, on the functional recovery outcomes of athletes with meniscal injuries. It also examined the factors influencing these abnormalities to provide scientific evidence for treatment and rehabilitation of related sports injuries. METHODS: We conducted a retrospective study of 118 athletes from Guizhou Normal University, who were divided into two groups based on the presence or absence of lower limb alignment abnormalities. The Simple group comprised athletes with isolated meniscal injuries, while the Combined group included athletes with meniscal injuries and concurrent lower limb alignment abnormalities. We assessed the functional status of both groups and analyzed factors influencing lower limb alignment abnormalities. RESULTS: Of the 118 athletes, 46 (38.98%) exhibited lower limb alignment abnormalities, and 72 (61.02%) did not. No significant differences in general characteristics were found between the groups (all P > 0.05). The Combined group displayed higher Visual Analog Scale (VAS) scores and Functional Performance Test (FPT) results (coordinated contraction, shuttle run, CarioCa) compared to the Simple group (P < 0.05). Conversely, joint range of motion (ROM), knee muscle strength (flexors), and International Knee Documentation Committee (IKDC) scores were lower in the Combined group (all P < 0.05). Multivariate logistic regression analysis identified active ROM < 105.32°, passive ROM < 101.66°, and knee muscle strength (flexors) < 84.41 N as risk factors for lower limb alignment abnormalities (P < 0.05), while FPT acted as a protective factor (P < 0.05). The combined testing model demonstrated higher predictive efficacy (AUC = 0.903, 95% CI: 0.852-0.955, P < 0.001). CONCLUSION: Lower limb alignment abnormalities significantly affect the functional recovery outcomes of athletes with meniscal injuries. Factors such as ROM, knee muscle strength, and IKDC score may pose risks for these abnormalities, whereas FPT can provide protective benefits. Timely detection and correction of lower limb alignment abnormalities during the rehabilitation process from meniscal injuries are crucial to enhance recovery and improve prognosis.

11.
J Hazard Mater ; 478: 135407, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39116745

RESUMEN

The accurate spatial mapping of heavy metal levels in agricultural soils is crucial for environmental management and food security. However, the inherent limitations of traditional interpolation methods and emerging machine-learning techniques restrict their spatial prediction accuracy. This study aimed to refine the spatial prediction of heavy metal distributions in Guangxi, China, by integrating machine learning models and spatial regionalization indices (SRIs). The results demonstrated that random forest (RF) models incorporating SRIs outperformed artificial neural network and support vector regression models, achieving R2 values exceeding 0.96 for eight heavy metals on the test data. Hierarchical clustering for feature selection further improved the model performance. The optimized RF models accurately predicted the heavy metal distributions in agricultural soils across the province, revealing higher levels in the central-western regions and lower levels in the north and south. Notably, the models identified that 25.78 % of agricultural soils constitute hotspots with multiple co-occurring heavy metals, and over 6.41 million people are exposed to excessive soil heavy metal levels. Our findings provide valuable insights for the development of targeted strategies for soil pollution control and agricultural soil management to safeguard food security and public health.

12.
Front Plant Sci ; 15: 1396929, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135649

RESUMEN

The uneven spatial and temporal distribution of light resources and water scarcity during the grain-filling stage pose significant challenges for sustainable crop production, particularly in the arid areas of the Loess Plateau in Northwest China. This study aims to investigate the combined effects of drought and shading stress on winter wheat growth and its physio-biochemical and antioxidative responses. Wheat plants were subjected to different drought levels- full irrigation (I100), 75% of full irrigation (I75), 50% of full irrigation (I50), and 25% of full irrigation (I25), and shading treatments - 12, 9, 6, 3 and 0 days (SD12, SD9, SD6, SD3, and CK, respectively) during the grain-filling stage. The effects of drought and shading treatments reduced yield in descending order, with the most significant reductions observed in the SD12 and I25 treatments. These treatments decreased grain yield, spikes per plant, 1000-grain weight, and spikelets per spike by 160.67%, 248.13%, 28.22%, and 179.55%, respectively, compared to the CK. Furthermore, MDA content and antioxidant enzyme activities exhibited an ascending trend with reduced irrigation and longer shading durations. The highest values were recorded in the I75 and SD12 treatments, which increased MDA, SOD, POD, and CAT activities by 65.22, 66.79, 65.07 and 58.38%, respectively, compared to the CK. The Pn, E, Gs, and iCO2 exhibited a decreasing trend (318.14, 521.09, 908.77, and 90.85%) with increasing shading duration and decreasing irrigation amount. Drought and shading treatments damage leaf chlorophyll fluorescence, decreasing yield and related physiological and biochemical attributes.

13.
Nanotechnology ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39137792

RESUMEN

Low-cost, highly efficient thermoelectric thin-film materials are becoming increasingly popular as miniaturization progresses. Mg3Sb2 has great potential due to its low cost and high performance. However, the fabrication of Mg3Sb2 thin films with high power factors poses a certain challenge. In this work, we propose a general approach to prepare Mg3Sb2 thin films with excellent thermoelectric properties. Using a two-step thermal evaporation and rapid annealing process, (001)-oriented Mg3Sb2 thin films are fabricated on c-plane-oriented Al2O3 substrates. The structure of the film orientation is optimized by controlling the film thickness, which modulates the thermoelectric performance. The power factor of the Mg3Sb2 at 500 nm (14 µW·m-1·K-2) would increase to 169 µW·m-1·K-2 with Ag doping (Mg3Ag0.02Sb2) at room temperature. This work provides a new strategy for developing high-performance thermoelectric thin films at room temperature.

14.
Neuroimage ; 298: 120779, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39122059

RESUMEN

[18F]-Florbetazine ([18F]-92) is a selective PET tracer for ß-amyloid (Aß) depositions with a novel diaryl-azine scaffold to reduce lipophilicity and to achieve higher gray-to-white matter contrast. We aimed to assess its diagnostic value in Alzheimer's disease (AD) and pharmacokinetics characteristics in human subjects. METHODS: Six healthy controls (HCs) and nine AD patients underwent dynamic PET examination with [18F]-Florbetazine and a structural MRI scan. The time-activity-curves (TACs) for volumes of interest (VOIs) in cerebral cortex, cerebellar cortex and cerebral white matter was depicted and their standardized uptake value ratios (SUVRs) with cerebellar cortex as reference were compared between HCs and AD patients. The cerebral gray-to-white matter SUV ratio (GWR) was also calculated. RESULTS: In HCs, radioactivities in the cerebral cortex VOIs were homogeneously low and at the same level as in cerebellar cortex, while in AD patients, cortical VOIs expected to contain Aß exhibited high radioactivity. Cerebral cortex SUVRs remain relatively low in HCs while keep increasing along with time in AD patients. After 15 min, the cerebral cortex SUVRs became significant higher in AD patients compared to HCs with 100 % discrimination accuracy. In AD patients, GWR remained over 1.3 for all time intervals and visual inspection showed lower uptake in cerebral white matter compared to cerebral cortex. CONCLUSION: [18F]-Florbetazine PET showed high uptake on Aß plaques and high gray-to-white contrast in AD patients that are favorable in visual read. [18F]-Florbetazine can be potentially used for detection and quantification of Aß depositions in the living human brain.

15.
Int J Mol Sci ; 25(15)2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39125808

RESUMEN

Multifactorial diseases demand therapeutics that can modulate multiple targets for enhanced safety and efficacy, yet the clinical approval of multitarget drugs remains rare. The integration of machine learning (ML) and deep learning (DL) in drug discovery has revolutionized virtual screening. This study investigates the synergy between ML/DL methodologies, molecular representations, and data augmentation strategies. Notably, we found that SVM can match or even surpass the performance of state-of-the-art DL methods. However, conventional data augmentation often involves a trade-off between the true positive rate and false positive rate. To address this, we introduce Negative-Augmented PU-bagging (NAPU-bagging) SVM, a novel semi-supervised learning framework. By leveraging ensemble SVM classifiers trained on resampled bags containing positive, negative, and unlabeled data, our approach is capable of managing false positive rates while maintaining high recall rates. We applied this method to the identification of multitarget-directed ligands (MTDLs), where high recall rates are critical for compiling a list of interaction candidate compounds. Case studies demonstrate that NAPU-bagging SVM can identify structurally novel MTDL hits for ALK-EGFR with favorable docking scores and binding modes, as well as pan-agonists for dopamine receptors. The NAPU-bagging SVM methodology should serve as a promising avenue to virtual screening, especially for the discovery of MTDLs.


Asunto(s)
Descubrimiento de Drogas , Descubrimiento de Drogas/métodos , Humanos , Simulación del Acoplamiento Molecular , Ligandos , Máquina de Vectores de Soporte , Aprendizaje Profundo , Aprendizaje Automático Supervisado , Aprendizaje Automático
16.
Adv Sci (Weinh) ; : e2404792, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39119825

RESUMEN

Fluorogens with aggregation-induced emission (AIEgens) are promising agents for two-photon fluorescence (TPF) imaging. However, AIEgens' photophysical properties are fixed and unoptimizable once synthesized. Therefore, it is urgent and meaningful to explore an efficient post-regulation strategy to optimize AIEgens' photophysical properties. Herein, a general and efficient post-regulation strategy is reported. By simply tuning the ratio of inert AIEgens within binary nanoparticles (BNPs), the fluorescence quantum yield and two-photon absorption cross-section of functional AIEgens are enhanced by 8.7 and 5.4 times respectively, which are not achievable by conventional strategies, and the notorious phototoxicity is almost eliminated. The experimental results, theoretical simulation, and mechanism analysis demonstrated its feasibility and generality. The BNPs enabled deep cerebrovascular network imaging with ≈1.10 mm depth and metastatic cancer cell detection with single-cell resolution. Furthermore, the TPF imaging quality is improved by the self-supervised denoising algorithm. The proposed binary molecular post-regulation strategy opened a new avenue to efficiently boost the AIEgens' photophysical properties and consequently TPF imaging quality.

17.
Adv Sci (Weinh) ; : e2405643, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39119878

RESUMEN

The construction of near-infrared (NIR) light-activated hydrogen-producing materials that enable the controlled generation and high-concentration release of hydrogen molecules in deep tumor tissues and enhance the effects of hydrogen therapy holds significant scientific importance. To address the key technical challenge of low-efficiency oxidation-reduction reactions for narrow-bandgap photocatalytic materials, this work proposes an innovative approach for the controllable fabrication of multiphoton photocatalytic materials to overcome the limitations imposed by traditional near-infrared photocatalysts with "narrow-bandgap" constraints. Herein, an NIR-responsive multiphoton photocatalyst, ZrTc-Co, is developed by utilizing a post-synthetic coordination modification strategy to introduce hydrogenation active site CoII into a multiphoton responsive MOF (ZrTc). The results reveal that with the introduction of the CoII site, electron-hole recombination can be efficiently suppressed, thus promoting the efficiency of hydrogen evolution reaction. In addition, the integration of CoII can effectively enhance charge transfer and improve static hyperpolarizability, which endows ZrTc-Co with excellent multiphoton absorption. Moreover, hyaluronic acid modification endows ZrTc-Co with cancer cell-specific targeting characteristics, laying the foundation for tumor-specific elimination. Collectively, the proposed findings present a strategy for constructing NIR-II light-mediated hydrogen therapeutic agents for deep tumor elimination.

19.
Nanomaterials (Basel) ; 14(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39120385

RESUMEN

Carbon Capture, Utilization, and Storage (CCUS) stands as one of the effective means to reduce carbon emissions and serves as a crucial technical pillar for achieving experimental carbon neutrality. CO2-enhanced oil recovery (CO2-EOR) represents the foremost method for CO2 utilization. CO2-EOR represents a favorable technical means of efficiently developing extra-low-permeability reservoirs. Nevertheless, the process known as the direct injection of CO2 is highly susceptible to gas scrambling, which reduces the exposure time and contact area between CO2 and the extra-low-permeability oil matrix, making it challenging to utilize CO2 molecular diffusion effectively. In this paper, a comprehensive study involving the application of a CO2 nanobubble system in extra-low-permeability reservoirs is presented. A modified nano-SiO2 particle with pro-CO2 properties was designed using the Pickering emulsion template method and employed as a CO2 nanobubble stabilizer. The suitability of the CO2 nanobubbles for use in extra-low-permeability reservoirs was evaluated in terms of their temperature resistance, oil resistance, dimensional stability, interfacial properties, and wetting-reversal properties. The enhanced oil recovery (EOR) effect of the CO2 nanobubble system was evaluated through core experiments. The results indicate that the CO2 nanobubble system can suppress the phenomena of channeling and gravity overlap in the formation. Additionally, the system can alter the wettability, thereby improving interfacial activity. Furthermore, the system can reduce the interfacial tension, thus expanding the wave efficiency of the repellent phase fluids. The system can also improve the ability of CO2 to displace the crude oil or water in the pore space. The CO2 nanobubble system can take advantage of its size and high mass transfer efficiency, among other advantages. Injection of the gas into the extra-low-permeability reservoir can be used to block high-gas-capacity channels. The injected gas is forced to enter the low-permeability layer or matrix, with the results of core simulation experiments indicating a recovery rate of 66.28%. Nanobubble technology, the subject of this paper, has significant practical implications for enhancing the efficiency of CO2-EOR and geologic sequestration, as well as providing an environmentally friendly method as part of larger CCUS-EOR.

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