Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 246
Filtrar
1.
JAMA Dermatol ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320907

RESUMO

Importance: China carries a heavy burden of postherpetic neuralgia, with an unmet need for novel drugs with greater efficacy and less prominent neurotoxic effects than existing calcium channel ligands. Objective: To investigate the efficacy and safety of crisugabalin, an oral calcium channel α2δ-1 subunit ligand, for postherpetic neuralgia. Design, Setting, and Participants: This randomized clinical trial, carried out between November 9, 2021, and January 5, 2023, at 48 tertiary care centers across China had 2 parts. Part 1 was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisting of a 2-week screening period, a 7-day run-in period, and a 12-week double-blind treatment period. Part 2 was a 14-week open-label extension study. Investigators, statisticians, trial clinicians, and patients were blinded to trial group assignments. Participants included adults with postherpetic neuralgia with an average daily pain score (ADPS) of at least 4 on the 11-point Numeric Pain Rating Scale over the preceding week, with the exclusion of patients with pain not controlled by prior therapy with pregabalin (≥300 mg/d) or gabapentin (≥1200 mg/d). Interventions: Patients were randomized 1:1:1 to receive crisugabalin, 20 mg twice daily (ie, 40 mg/d), and crisugabalin, 40 mg twice daily (ie, 80 mg/d), or placebo for 12 weeks. Eligible patients received crisugabalin, 40 mg, twice daily during extension. Main Outcome and Measure: The primary efficacy end point was the change from baseline in ADPS at week 12. Results: The study enrolled 366 patients (121 patients receiving crisugabalin, 40 mg/d; 121 patients receiving crisugabalin, 80 mg/d; 124 patients receiving placebo; median [IQR] age, 63.0 [56.0-69.0] years; 193 men [52.7%]). At week 12, the least squares mean (SD) change from baseline in ADPS was -2.2 (0.2) for crisugabalin, 40 mg/d, and -2.6 (0.2) for crisugabalin, 80 mg/d, vs -1.1 (0.2) for placebo, with a least squares mean difference of -1.1 (95% CI, -1.6 to -0.7; P < .001) and -1.5 (-95% CI, -2.0 to -1.0; P < .001) vs placebo, respectively. No new safety concerns emerged. Conclusions and Relevance: Crisugabalin, 40 mg/d, or crisugabalin, 80 mg/d, was well tolerated and demonstrated a statistically significant improvement in ADPS over placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT05140863.

2.
J Agric Food Chem ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316410

RESUMO

Reaction efficiency in glycation lacks sufficient attention, leading to the waste of process costs. Cyclic continuous glycation (CCG) is an effective approach to accelerate covalent binding between myofibrillar protein (MP) and glucose. This study elucidated that CCG promoted the exposure of reactive glycated sites in MP with full unfolding of secondary and tertiary structures. Notably, the glycation rate was significantly increased by 65.43%. Physicochemical properties indicated that MP-glucose conjugates with high graft degree exhibited favorable solubility, dispersibility, and thermal stability. Furthermore, proteomics was applied to reveal the glycated sites and products in glycoconjugates of MP. Glycation preferentially acted on the tails of the myosin heavy chain. The glucosylation modification on the head region was enhanced by CCG contributing to the inhibition of the head-head interaction. Overall, this study systematically clarifies the mechanism of CCG, providing a theoretical basis for the application of glycation in innovative meat products.

3.
Sci Rep ; 14(1): 20398, 2024 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223319

RESUMO

Hand, foot, and mouth disease (HFMD) is a prevalent acute infectious disease caused by enteroviruses, presenting substantial public health challenges in Shanghai, especially among children. The dynamic nature of HFMD's etiology necessitates an ongoing evaluation of its epidemiological and virological trends to inform effective control strategies. This study aims to investigate the epidemiological patterns and viral evolution of HFMD in Fengxian District, Shanghai, China, with a focus on shifts in predominant viral strains over a 14-year period. We conducted a retrospective analysis of HFMD cases reported to the National Notifiable Disease Reporting System in Fengxian District from January 1, 2009 to December 31, 2022. Epidemiological trends, strain prevalence, and demographic impacts were assessed. A total of 27,272 HFMD cases were documented during the study period, with incidence showing pronounced seasonal fluctuations-peaking in spring and summer and a lesser peak in autumn. The disease incidence demonstrated significant positive correlations with several meteorological variables: daily average temperature (r = 0.30, P < 0.05), relative humidity (r = 0.20, P < 0.05), wind speed (r = 0.17, P < 0.05), and precipitation (r = 0.17, P < 0.05). Geographically, Nanqiao Town, Fengcheng Town, and Xidu Subdistrict reported the highest incidence rates. The demographic analysis revealed a male-to-female ratio of 1.60:1, predominantly affecting children aged 1-3 years. Prior to 2017, Enterovirus 71 (EV71) and Coxsackievirus A16 (CoxA16) were the primary detected strains; post-2017, Coxsackievirus A6 (CoxA6) emerged as the dominant strain. Statistical analysis confirmed significant year-to-year variations in virus detection rates, with decreasing trends for EV71 and other enteroviruses and an increasing trend for CoxA6. The findings indicate a distinct seasonal incidence of HFMD in Fengxian District. This study underscores the need for targeted public health education, enhanced surveillance, and proactive measures in childcare facilities to mitigate disease spread during peak seasons. Moreover, the evolving viral landscape warrants accelerated efforts in vaccine development against new strains to reduce HFMD incidence.


Assuntos
Doença de Mão, Pé e Boca , Estações do Ano , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/virologia , Humanos , China/epidemiologia , Masculino , Feminino , Pré-Escolar , Lactente , Incidência , Estudos Retrospectivos , Criança , Análise Espaço-Temporal , Enterovirus/isolamento & purificação , Prevalência , Adolescente
4.
J Alzheimers Dis Rep ; 8(1): 999-1007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39114550

RESUMO

Background: Effect of stenosis of vertebrobasilar artery (VBA) on cognitive function is elusive. Objective: To investigate association of cerebral hypoperfusion and poor collaterals with vascular cognitive impairment (VCI) in severe VBA stenosis patients. Methods: We consecutively enrolled patients with severe VBA stenosis confirmed by digital subtraction angiography who underwent computed tomographic perfusion (CTP) and cognitive assessments. Patients were divided into poor or good collaterals groups according to the collateral circulation status, and were grouped into different perfusion groups according to CTP. Cognitive function was measured by Montreal Cognitive Assessment (MoCA), Clock Drawing Test, Stroop Color Word Test, Trail Making Test, Digital Span Test, Auditory Verbal Learning Test, and Boston Naming Test scales. The association of cerebral perfusion and collaterals with VCI were explored. Results: Among 88 eligible patients, VCI occurred in 51 (57.9%) patients experienced. Poor collateral was present in 73 (83.0%) patients, and hypoperfusion in 64 (72.7%). Compared with normal perfusion patients, the odds ratio with 95% confidence interval for VCI was 12.5 (3.7-42.4) for overall hypoperfusion, 31.0 (7.1-135.5) for multiple site hypoperfusion, 3.3 (1.0-10.5) for poor collaterals, and 0.1 (0-0.6) for presence of posterior communicating artery (PcoA) compensated for posterior cerebral artery (PCA) and basilar artery (BA). Additionally, decreased scores of cognitive function tests occurred in patients with decompensated perfusion or poor collaterals. Conclusions: Hypoperfusion and poor collaterals were positively associated with cognitive impairment in patients with severe VBA. However, PcoA compensated for the PCA and BA had a protective role in cognitive impairment development.

5.
Biomed Opt Express ; 15(7): 4345-4364, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39022540

RESUMO

Proximal rotary scanning is predominantly used in the clinical practice of endoscopic and intravascular OCT, mainly because of the much lower manufacturing cost of the probe compared to distal scanning. However, proximal scanning causes severe beam stability issues (also known as non-uniform rotational distortion, NURD), which hinders the extension of its applications to functional imaging, such as OCT elastography (OCE). In this work, we demonstrate the abilities of learning-based NURD correction methods to enable the imaging stability required for intensity-based OCE. Compared with the previous learning-based NURD correction methods that use pseudo distortion vectors for model training, we propose a method to extract real distortion vectors from a specific endoscopic OCT system, and validate its superiority in accuracy under both convolutional-neural-network- and transformer-based learning architectures. We further verify its effectiveness in elastography calculations (digital image correlation and optical flow) and the advantages of our method over other NURD correction methods. Using the air pressure of a balloon catheter as a mechanical stimulus, our proximal-scanning endoscopic OCE could effectively differentiate between areas of varying stiffness of atherosclerotic vascular phantoms. Compared with the existing endoscopic OCE methods that measure only in the radial direction, our method could achieve 2D displacement/strain distribution in both radial and circumferential directions.

6.
Small ; : e2405080, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39073300

RESUMO

The design of electrocatalysts for oxygen evolution reaction (OER) remains a limitation of industrial hydrogen production by electrolysis of water. Excellent and stable OER catalysts can be developed by activating lattice oxygen and changing the reaction path. Herein, S and FeOOH on the Co(OH)2 nanoneedle arrays are introduced to construct a heterostructure (S-FeOOH/Co(OH)2/NF) as a proof of concept. Theoretical calculations and experimental suggest that the Co-O-Fe motif formed at the heterogeneous interface with the introduction of FeOOH, inducing electron transfer from Co to Fe, enhancing Co─O covalency and reducing intramolecular charge transfer energy, thereby stimulating direct intramolecular lattice oxygen coupling. Doping of S in FeOOH further accelerates electron transfer, improves lattice oxygen activity, and prevents dissolution of FeOOH. Consequently, the overpotential of S-FeOOH/Co(OH)2/NF is only 199 mV at 10 mA cm-2, and coupled with the Pt/C electrode can be up to 1 A cm-2 under 1.79 V and remain stable for over 120 h in an anion exchange membrane water electrolyzer (AEMWE). This work proposes a strategy for the design of efficient and stable electrocatalysts for industrial water electrolysis and promotes the commercialization of AEMWE.

7.
iScience ; 27(7): 110021, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39055931

RESUMO

Existing automatic analysis of fundus fluorescein angiography (FFA) images faces limitations, including a predetermined set of possible image classifications and being confined to text-based question-answering (QA) approaches. This study aims to address these limitations by developing an end-to-end unified model that utilizes synthetic data to train a visual question-answering model for FFA images. To achieve this, we employed ChatGPT to generate 4,110,581 QA pairs for a large FFA dataset, which encompassed a total of 654,343 FFA images from 9,392 participants. We then fine-tuned the Bootstrapping Language-Image Pre-training (BLIP) framework to enable simultaneous handling of vision and language. The performance of the fine-tuned model (ChatFFA) was thoroughly evaluated through automated and manual assessments, as well as case studies based on an external validation set, demonstrating satisfactory results. In conclusion, our ChatFFA system paves the way for improved efficiency and feasibility in medical imaging analysis by leveraging generative large language models.

8.
Free Radic Biol Med ; 222: 424-436, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38960008

RESUMO

Abnormal polarization of adipose tissue macrophages (ATMs) results in low-grade systemic inflammation and insulin resistance (IR), potentially contributing to the development of diabetes. However, the underlying mechanisms that regulate the polarization of ATMs associated with gestational diabetes mellitus (GDM) remain unclear. Thus, we aimed to determine the effects of abnormal fatty acids on macrophage polarization and development of insulin resistance in GDM. Levels of fatty acids and inflammation were assessed in the serum samples and adipose tissues of patients with GDM. An in vitro cell model treated with palmitic acid was established, and the mechanisms of palmitic acid in regulating macrophage polarization was clarified. The effects of excessive palmitic acid on the regulation of histone methylations and IR were also explored in the high-fat diet induced GDM mice model. We found that pregnancies with GDM were associated with increased levels of serum fatty acids, and inflammation and IR in adipose tissues. Increased palmitic acid could induce mitochondrial dysfunction and excessive ROS levels in macrophages, leading to abnormal cytoplasmic and nuclear metabolism of succinate and α-ketoglutarate (αKG). Specifically, a decreased nuclear αKG/succinate ratio could attenuate the enrichment of H3K27me3 at the promoters of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, leading to cytokine secretion. Importantly, GDM mice treated with GSK-J4, an inhibitor of histone lysine demethylase, were protected from abnormal pro-inflammatory macrophage polarization and excessive production of pro-inflammatory cytokines. Our findings highlight the importance of the metabolism of αKG and succinate as transcriptional modulators in regulating the polarization of ATMs and the insulin sensitivity of adipose tissue, ensuring a normal pregnancy. This novel insight sheds new light on gestational fatty acid metabolism and epigenetic alterations associated with GDM.


Assuntos
Tecido Adiposo , Diabetes Gestacional , Resistência à Insulina , Ácidos Cetoglutáricos , Macrófagos , Ácido Palmítico , Ácido Succínico , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Gravidez , Ácido Palmítico/farmacologia , Animais , Feminino , Camundongos , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Humanos , Ácidos Cetoglutáricos/metabolismo , Ácido Succínico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Adulto , Camundongos Endogâmicos C57BL , Inflamação/metabolismo , Inflamação/patologia , Modelos Animais de Doenças
9.
J Colloid Interface Sci ; 675: 496-504, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38986323

RESUMO

The coordination environment of Cu (the coordination number and arrangement of surface atoms) plays an important role in CO2 hydrogenation to CH3OH. Compared with the extensive studies of the effects of coordination number, the comprehensive effects of coordination number and arrangement of surface atoms were seldom explored in literature. To unravel the effects of surface Cu coordination environment on CO2 hydrogenation to CH3OH, the adsorption and reaction behaviors of H2 and CO2 on Cu(111), (100), (110) and (211) with different coordination numbers and arrangement of surface Cu were systematically calculated by density functional theory (DFT) and kinetic Monte Carlo (kMC) simulation. It was found that the adsorption energies of intermediates in CO2 hydrogenation on Cu surfaces increase with the decrease of coordination number. When the Cu coordination numbers are similar, the charge density on the open surface derived from the different atom arrangement becomes larger and leads to stronger interaction with intermediates than that on the compact one. DFT calculation and kMC simulation indicate that methanol formation pathway follows CO2*→HCOO*→HCOOH*→H2COOH*→H2CO*→CH3O*→CH3OH* on four Cu facets; CO formation is via CO2 direct dissociation on Cu(111), (100) and (110) but COOH* dissociation on (211). The low-coordinated surface Cu with more openness on Cu(211) is the highly active site for CO2 hydrogenation to CH3OH with high turnover of frequency (3.71 × 10-4 s-1) and high selectivity (87.17 %) at 600 K, PCO2 = 7.5 atm and PH2 = 22.5 atm, which is much higher than those on Cu(111), (100) and (110). This work unravels the effects of coordination environment on CO2 hydrogenation at the molecular level and provides an important insight into the design and development of catalysts with high performance in CO2 hydrogenation to CH3OH.

10.
J Clin Anesth ; 97: 111545, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38971135

RESUMO

STUDY OBJECTIVE: The aim of this study was to evaluate the accuracy of lung recruitment maneuver induced stroke volume variation (ΔSVLRM) in predicting fluid responsiveness in mechanically ventilated adult patients by systematic review and meta-analysis. METHODS: A comprehensive electronic search of relevant literature was conducted in PubMed, Web of Science, Cochrane Library, Ovid Medline, Embase and Chinese databases (including China National Knowledge Infrastructure, Wanfang and VIP databases). Review Manager 5.4, Meta-DiSc 1.4 and STATA 16.0 were selected for data analysis, and QUADAS-2 tool was used for quality assessment. Data from selected studies were pooled to obtain sensitivity, specificity, diagnostic likelihood ratio (DLR) of positive and negative, diagnostic odds ratio (DOR), and summary receiver operating characteristic curve. RESULTS: A total of 6 studies with 256 patients were enrolled through March 2024. The risk of bias and applicability concerns for each included study were low, and there was no significant publication bias. There was moderate to substantial heterogeneity for the non-threshold effect, but not for the threshold effect. The combined sensitivity and specificity were 0.84 (95% CI, 0.77-0.90) and 0.79 (95% CI, 0.70-0.86), respectively. The DOR and the area under the curve (AUC) were 22.15 (95%CI, 7.62-64.34) and 0.90 (95% CI, 0.87-0.92), respectively. The positive and negative predictive values of DLR were 4.53 (95% CI, 2.50-8.18) and 0.19 (95% CI, 0.11-0.35), respectively. Fagan's nomogram showed that with a pre-test probability of 52%, the post-test probability reached 83% and 17% for the positive and negative tests, respectively. CONCLUSIONS: Based on the currently available evidence, ΔSVLRM has a good diagnostic value for predicting the fluid responsiveness in adult patients undergoing mechanical ventilation. Given the heterogeneity and limitations of the published data, further studies with large sample sizes and different clinical settings are needed to confirm the diagnostic value of ΔSVLRM in predicting fluid responsiveness. PROSPERO registration number: CRD42023490598.


Assuntos
Hidratação , Respiração Artificial , Volume Sistólico , Humanos , Respiração Artificial/métodos , Respiração Artificial/estatística & dados numéricos , Hidratação/métodos , Volume Sistólico/fisiologia , Sensibilidade e Especificidade
11.
Anal Chem ; 96(25): 10111-10115, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38869290

RESUMO

The Si window is the most widely used internal reflection element (IRE) for electrochemical attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), yet local chemical etching on Si by concentrated OH- anions bottlenecks the reliable application of this method in strong alkaline electrolytes. In this report, atomic layer deposition of a 25 nm nonconductive TiO2 barrier layer on the reflecting plane of a Si prism is demonstrated to address this challenge. In situ ATR-SEIRAS measurement on a Au film electrode with the Si/TiO2 composite IRE in 1 M NaOH reveals reversible global spectral features without spectral distortion at 1000-1300 cm-1, in stark contrast to those obtained with a bare Si window. By applying this structured ATR-SEIRAS, ethanol electrooxidation on a Pt/C catalyst in 1 and 5 M NaOH is explored, manifesting that such high pH values prevent the adsorption of as-formed acetate in the C2 pathway but not that of CO intermediate in the C1 pathway.

12.
Anat Sci Educ ; 17(6): 1251-1264, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38853404

RESUMO

Dental anatomy education for dental technology students should be developed in alignment with digital dental laboratory practices. We hypothesized that a virtually assisted sketching-based dental anatomy teaching module could improve students' acquisition of skills essential for digital restoration design. The second-year dental technology curriculum included a novel virtual technology-assisted sketching-based module for dental anatomy education. Pre- and post-course assessments evaluated students' skill sets and knowledge bases. Computer-aided design (CAD) scores were analyzed after one year to assess how the skills students developed through this module impacted their subsequent CAD performance. Participants who undertook the dental sketching-based teaching module demonstrated significantly improved theoretical knowledge of dental anatomy, dental aesthetic perception, and spatial reasoning skills. A partial least squares structural equation model indicated that the positive effects of this module on subsequent CAD performance were indirectly mediated by dental aesthetic perception, spatial reasoning, and practice time. A virtually assisted sketching-based dental anatomy teaching module significantly improved students' acquisition of skills and knowledge and positively mediated dental technology students' CAD performance.


Assuntos
Anatomia , Desenho Assistido por Computador , Instrução por Computador , Currículo , Educação em Odontologia , Avaliação Educacional , Humanos , Educação em Odontologia/métodos , Feminino , Anatomia/educação , Masculino , Avaliação Educacional/estatística & dados numéricos , Instrução por Computador/métodos , Estudantes de Odontologia , Aprendizagem , Adulto Jovem , Prótese Dentária , Planejamento de Prótese Dentária , Restauração Dentária Permanente/métodos , Adulto
13.
Food Res Int ; 187: 114413, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763665

RESUMO

In this study, the highly loaded myofibrillar protein (MP)-luteolin (Lut) complexes were noncovalently constructed by using green high-pressure homogenization technology (HPH) and high-pressure micro-fluidization technology (HPM), aiming to optimize the encapsulation efficiency of flavonoids in the protein-based vehicle without relying on the organic solvent (i.e. DMSO, ethanol, etc.). The loading efficiency of Lut into MPs could reach 100 % with a concentration of 120 µmol/g protein by using HPH (103 MPa, 2 passes) without ethanol adoption. The in vitro gastrointestinal digestion behavior and antioxidant activity of the complexes were then compared with those of ethanol-assisted groups. During gastrointestinal digestion, the MP digestibility of complexes, reaching more than 70.56 % after thermal treatment, was higher than that of sole protein. The release profile of Lut encapsulated in ethanol-containing and ethanol-free samples both well fitted with the Hixson-Crowell release kinetic model (R2 = 0.92 and 0.94, respectively), and the total phenol content decreased by ≥ 40.02 % and ≥ 62.62 %, respectively. The in vitro antioxidant activity (DPPH, ABTS, and Fe2+) of the digestive products was significantly improved by 23.89 %, 159.69 %, 351.12 % (ethanol groups) and 13.43 %, 125.48 %, 213.95 % (non-ethanol groups). The 3 mg/mL freeze-dried digesta significantly alleviated lipid accumulation and oxidative stress in HepG2 cells. The triglycerides and malondialdehyde contents decreased by at least 57.62 % and 67.74 % after digesta treatment. This study provides an easily approached and environment-friendly strategy to construct a highly loaded protein-flavonoid conjugate, which showed great potential in the formulation of healthier meat products.


Assuntos
Antioxidantes , Disponibilidade Biológica , Digestão , Humanos , Antioxidantes/química , Miofibrilas/química , Miofibrilas/metabolismo , Flavonoides/química , Flavonoides/farmacocinética , Trato Gastrointestinal/metabolismo , Animais
14.
NPJ Digit Med ; 7(1): 111, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702471

RESUMO

Fundus fluorescein angiography (FFA) is a crucial diagnostic tool for chorioretinal diseases, but its interpretation requires significant expertise and time. Prior studies have used Artificial Intelligence (AI)-based systems to assist FFA interpretation, but these systems lack user interaction and comprehensive evaluation by ophthalmologists. Here, we used large language models (LLMs) to develop an automated interpretation pipeline for both report generation and medical question-answering (QA) for FFA images. The pipeline comprises two parts: an image-text alignment module (Bootstrapping Language-Image Pre-training) for report generation and an LLM (Llama 2) for interactive QA. The model was developed using 654,343 FFA images with 9392 reports. It was evaluated both automatically, using language-based and classification-based metrics, and manually by three experienced ophthalmologists. The automatic evaluation of the generated reports demonstrated that the system can generate coherent and comprehensible free-text reports, achieving a BERTScore of 0.70 and F1 scores ranging from 0.64 to 0.82 for detecting top-5 retinal conditions. The manual evaluation revealed acceptable accuracy (68.3%, Kappa 0.746) and completeness (62.3%, Kappa 0.739) of the generated reports. The generated free-form answers were evaluated manually, with the majority meeting the ophthalmologists' criteria (error-free: 70.7%, complete: 84.0%, harmless: 93.7%, satisfied: 65.3%, Kappa: 0.762-0.834). This study introduces an innovative framework that combines multi-modal transformers and LLMs, enhancing ophthalmic image interpretation, and facilitating interactive communications during medical consultation.

15.
Eur J Med Chem ; 271: 116425, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38636129

RESUMO

Phosphatidylinositol 3-kinase (PI3K) is one of the most attractive therapeutic targets for cervical cancer treatment. In this study, we designed and synthesized a series of benzimidazole derivatives and evaluated their anti-cervical cancer activity. Compound 4r exhibited strong antiproliferative activity in different cervical cancer cell lines HeLa, SiHa and Ca Ski, and relative lower cytotoxicity to normal hepatic and renal cell lines LO2 and HEK-293t (IC50 values were at 21.08 µM and 23.96 µM respectively). Its IC50 value was at 3.38 µM to the SiHa cells. Further mechanistic studies revealed that 4r induced apoptosis, arrested cell cycle in G2/M phase, suppressed PI3K/Akt/mTOR pathway and inhibit the polymerization of tubulin. Molecular docking study suggested that 4r formed key H-bonds action with PI3Kα (PDB ID:8EXU) and tubulin (PDB ID:1SA0). Zebrafish acute toxicity experiments showed that high concentrations of 4r did not cause death or malformation of zebrafish embryos. All these results demonstrated that 4r would be a promising lead candidate for further development of novel PI3K and tubulin dual inhibitors in cervical cancer treatment.


Assuntos
Antineoplásicos , Benzimidazóis , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Moduladores de Tubulina , Tubulina (Proteína) , Neoplasias do Colo do Útero , Peixe-Zebra , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Benzimidazóis/farmacologia , Benzimidazóis/química , Benzimidazóis/síntese química , Tubulina (Proteína)/metabolismo , Proliferação de Células/efeitos dos fármacos , Animais , Relação Estrutura-Atividade , Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Estrutura Molecular , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos
16.
Artigo em Inglês | MEDLINE | ID: mdl-38581337

RESUMO

Objective: With the improvement of living standards, consumers are paying more and more attention to the quality of rice. Traditional rice quality detection relies on human sensory judgment, which is inaccurate and inefficient. With the continuous development of molecular imaging technology, more and more scholars at home and abroad have begun to pay attention to its application in the nondestructive testing of agricultural products. Molecular imaging technology combines the advantages of spectral technology and image technology, which can achieve rapid, nondestructive and accurate detection of rice quality. In this paper, taking rice as the research object, we carried out nondestructive detection research on rice varieties, moisture and starch content using molecular imaging technology. We proposed a rapid detection method based on molecular imaging technology for rice variety identification, moisture content and starch content. Molecular images of the rice samples from four origins were obtained using a molecular imaging system, the regions of interest of the rice were identified and, spectral data, textural features and morphological features of the rice were extracted. Spectral, textural and morphological features were selected by principal component analysis (PCA), and nine feature wavelengths were obtained and an optimal model was established with an accuracy of 91.67%, which demonstrated the feasibility of molecular imaging. By comparing the models, the BCC-LS-SVR model based on the RB function had the highest accuracy with R2 of 0.989, RMSEP of 0.767%, R2 of 0.985, and RMSEC of 0.591%. Moreover, starchy rice was detected using molecular imaging. The PCA-SVR model based on the RBF kernel function had the highest accuracy with R2 of 0.989, RMSEC of 0.445%, R2 of 0.991, and RMSEP of 0.669%. Our models demonstrated high accuracy in identifying rice varieties, as well as quantifying moisture and starch content, showcasing the feasibility of molecular imaging technology in rice quality assessment. This research offers a rapid, nondestructive, and accurate method for rice quality assessment, promising significant benefits for agricultural producers and consumers.

17.
BMJ Open ; 14(4): e080200, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670623

RESUMO

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) has become an important treatment in patients with aortic valve disease with the continuous advancement of technology and the improvement of outcomes. However, TAVR-related complications still increase patient morbidity and mortality. Remote ischaemic preconditioning (RIPC) is a simple procedure that provides perioperative protection for many vital organs. However, the efficiency of RIPC on TAVR remains unclear based on inconsistent conclusions from different clinical studies. Therefore, we will perform a protocol for a systematic review and meta-analysis to identify the efficiency of RIPC on TAVR. METHODS AND ANALYSIS: English databases (PubMed, Web of Science, Ovid Medline, Embase and Cochrane Library), Chinese electronic databases (Wanfang Database, VIP Database and China National Knowledge Infrastructure) and trial registry databases will be searched from inception to December 2023 to identify randomised controlled trials of RIPC on TAVR. We will calculate mean differences or standardised mean differences with 95% CIs for continuous data, and the risk ratio (RR) with 95% CIs for dichotomous data by Review Manager version 5.4. Fixed-effects model or random-effects model will be used according to the degree of statistical heterogeneity assessed by the I-square test. We will evaluate the risk of bias using the Cochrane risk-of-bias tool 2 and assess the evidence quality of each outcome by the Grading of Recommendations Assessment, Development and Evaluation. The robustness of outcomes will be evaluated by trial sequential analysis. In addition, we will evaluate the publication bias of outcomes by Funnel plots and Egger's regression test. ETHICS AND DISSEMINATION: Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023462926.


Assuntos
Precondicionamento Isquêmico , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/métodos , Precondicionamento Isquêmico/métodos , Projetos de Pesquisa , Estenose da Valva Aórtica/cirurgia
18.
Br J Ophthalmol ; 108(10): 1450-1456, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-38508675

RESUMO

BACKGROUND: Indocyanine green angiography (ICGA) is vital for diagnosing chorioretinal diseases, but its interpretation and patient communication require extensive expertise and time-consuming efforts. We aim to develop a bilingual ICGA report generation and question-answering (QA) system. METHODS: Our dataset comprised 213 129 ICGA images from 2919 participants. The system comprised two stages: image-text alignment for report generation by a multimodal transformer architecture, and large language model (LLM)-based QA with ICGA text reports and human-input questions. Performance was assessed using both qualitative metrics (including Bilingual Evaluation Understudy (BLEU), Consensus-based Image Description Evaluation (CIDEr), Recall-Oriented Understudy for Gisting Evaluation-Longest Common Subsequence (ROUGE-L), Semantic Propositional Image Caption Evaluation (SPICE), accuracy, sensitivity, specificity, precision and F1 score) and subjective evaluation by three experienced ophthalmologists using 5-point scales (5 refers to high quality). RESULTS: We produced 8757 ICGA reports covering 39 disease-related conditions after bilingual translation (66.7% English, 33.3% Chinese). The ICGA-GPT model's report generation performance was evaluated with BLEU scores (1-4) of 0.48, 0.44, 0.40 and 0.37; CIDEr of 0.82; ROUGE of 0.41 and SPICE of 0.18. For disease-based metrics, the average specificity, accuracy, precision, sensitivity and F1 score were 0.98, 0.94, 0.70, 0.68 and 0.64, respectively. Assessing the quality of 50 images (100 reports), three ophthalmologists achieved substantial agreement (kappa=0.723 for completeness, kappa=0.738 for accuracy), yielding scores from 3.20 to 3.55. In an interactive QA scenario involving 100 generated answers, the ophthalmologists provided scores of 4.24, 4.22 and 4.10, displaying good consistency (kappa=0.779). CONCLUSION: This pioneering study introduces the ICGA-GPT model for report generation and interactive QA for the first time, underscoring the potential of LLMs in assisting with automated ICGA image interpretation.


Assuntos
Corantes , Angiofluoresceinografia , Verde de Indocianina , Humanos , Verde de Indocianina/administração & dosagem , Angiofluoresceinografia/métodos , Corantes/administração & dosagem , Feminino , Masculino , Fundo de Olho , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/diagnóstico , Pessoa de Meia-Idade , Doenças da Coroide/diagnóstico por imagem , Doenças da Coroide/diagnóstico , Reprodutibilidade dos Testes , Idoso
20.
Heliyon ; 10(5): e25505, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434336

RESUMO

Shanghai as an international metropolis is representative of modern urban agriculture in China, so it is of great significance to analyse the pesticide residue in vegetables grown in Shanghai. This study investigated the residue of 68 commonly used pesticides (divided into insecticides, fungicides, herbicides and plant growth regulators) in 7028 vegetable samples in Shanghai from 2018 to 2021, and estimated the dietary intake risk of these pesticides. These samples were divided into 6 categories. A total of 29.21% of vegetable samples had pesticide residues, and 0.47% of samples exceeded the maximum residue limits (MRLs) set by the national food safety standard of China. Leafy vegetables had the highest detection rate of pesticide residues (32.9%), multiple detection rate (12.2%), pesticide residue concentration (35.7 mg/kg), and the number of samples exceeding the MRL (30). There were 36 out of 68 pesticides detected in vegetables, and the top 3 were dimethomorph, propamocarb and acetamiprid. The target hazard quotient (THQ) and hazard index (HI) of these noticeablepesticides were all less than 1, illustrating that there may be no obvious health hazard for residents exposed to the pesticide levels. This study can promote the green development of the pesticide industry and provide important reference data for the monitoring of pesticide residues and their hazards under modern urban agriculture.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA