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Aqueous zinc-ion batteries have become a promising energy storage battery due to high theoretical specific capacity, abundant zinc resources and low cost. However, zinc dendrite growth and hydrogen evolution reaction limit their application. This study aims to improve the cycling performance and stability of aqueous zinc-ion batteries by improving the gel electrolyte. Polyacrylamide (PAM) is selected as the base material of the gel electrolyte, which has good stability and safety, but the water retention capacity, Zn2+ migration number, and ionic conductivity of PAM are low, which affects the long-term stability of the battery. In response to these problems, we optimized PAM by chemical cross-linking method, and formed an enhanced PAM gel by adding disodium citrate dihydrate (SC). Experimental results show that the introduction of an appropriate amount of SC in the enhanced PAM gel electrolyte can significantly improve its electrochemical performance. The zinc-ion symmetric battery achieved a stable cycle of more than 2100 hours at a current density of 0.5 mA cm-2, which is mainly attributed to the inhibitory effect of the enhanced PAM gel on zinc dendrite growth and hydrogen evolution reaction. This study provides a new direction for the development and application of flexible zinc-ion batteries.
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Single-cell sequencing is frequently affected by "omission" due to limitations in sequencing throughput, yet bulk RNA-seq may contain these ostensibly "omitted" cells. Here, we introduce the single cell trajectory blending from Bulk RNA-seq (BulkTrajBlend) algorithm, a component of the OmicVerse suite that leverages a Beta-Variational AutoEncoder for data deconvolution and graph neural networks for the discovery of overlapping communities. This approach effectively interpolates and restores the continuity of "omitted" cells within single-cell RNA sequencing datasets. Furthermore, OmicVerse provides an extensive toolkit for both bulk and single cell RNA-seq analysis, offering seamless access to diverse methodologies, streamlining computational processes, fostering exquisite data visualization, and facilitating the extraction of significant biological insights to advance scientific research.
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Algoritmos , Análise de Sequência de RNA , Análise de Célula Única , Análise de Célula Única/métodos , Humanos , Análise de Sequência de RNA/métodos , Biologia Computacional/métodos , RNA-Seq/métodos , Redes Neurais de Computação , Software , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
Thrombin is a crucial enzyme in the coagulation cascade, and inhibitors of thrombin have been extensively studied as potential antithrombotic agents. The objective of this study was to identify natural inhibitors of thrombin from Panax notoginseng and evaluate their biological activity in vitro and binding characteristics. A combined approach involving molecular docking, thrombin inhibition assays, surface plasmon resonance, and molecular dynamics simulation was utilized to identify natural thrombin inhibitors. The results demonstrated that panaxatriol directly inhibits thrombin, with an IC50 of 10.3 µM. Binding studies using surface plasmon resonance revealed that panaxatriol interacts with thrombin, with a KD value of 7.8 µM. Molecular dynamics analysis indicated that the thrombin-panaxatriol system reached equilibrium rapidly with minimal fluctuations, and the calculated binding free energy was - 23.8 kcal/mol. The interaction between panaxatriol and thrombin involves the amino acid residues Glu146, Glu192, Gly216, Gly219, Tyr60A, and Trp60D. This interaction provides a mechanistic basis for further optimizing panaxatriol as a thrombin inhibitor. Our study has shown that panaxatriol serves as a direct thrombin inhibitor, laying the groundwork for further research and development of novel thrombin inhibitors.
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Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Panax notoginseng , Trombina , Panax notoginseng/química , Trombina/antagonistas & inibidores , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Humanos , Antitrombinas/farmacologia , Antitrombinas/química , Ressonância de Plasmônio de SuperfícieRESUMO
Microplastics/nanoplastics (MNPs) inevitably coexist with other pollutants in the natural environment, making it crucial to study the interactions between MNPs and other pollutants as well as their combined toxic effects. In this study, we investigated neurotoxicity in marine medaka (Oryzias melastigma) exposed to polystyrene micro/nanoplastics (PS-MNPs), triphenyltin (TPT), and PS-MNPs + TPT from physiological, behavioral, biochemical, and genetic perspectives. The results showed that marine medaka exposed to 200 ng/L TPT or 200 µg/L PS-NPs alone exhibited some degree of neurodevelopmental deficit, albeit with no significant behavioral abnormalities observed. However, in the PS-MP single exposure group, the average acceleration of short-term behavioral indices was significantly increased by 78.81%, indicating a highly stress-responsive locomotor pattern exhibited by marine medaka. After exposure to PS-MNPs + TPT, the swimming ability of marine medaka significantly decreased. In addition, PS-MNPs + TPT exposure disrupted normal neural excitability as well as activated detoxification processes in marine medaka larvae. Notably, changes in neural-related genes suggested that combined exposure to PS-MNPs and TPT significantly increased the neurotoxic effects observed with exposure to PS-MNPs or TPT alone. Furthermore, compared to the PS-MPs + TPT group, PS-NPs + TPT significantly inhibited swimming behavior and thus exacerbated the neurotoxicity. Interestingly, the neurotoxicity of PS-MPs was more pronounced than that of PS-NPs in the exposure group alone. However, the addition of TPT significantly enhanced the neurotoxicity of PS-NPs compared to PS-MPs + TPT. Overall, the study underscores the combined neurotoxic effects of MNPs and TPT, providing in-depth insights into the ecotoxicological implications of MNPs coexisting with pollutants and furnishing comprehensive data.
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Microplásticos , Compostos Orgânicos de Estanho , Oryzias , Poluentes Químicos da Água , Animais , Oryzias/fisiologia , Poluentes Químicos da Água/toxicidade , Compostos Orgânicos de Estanho/toxicidade , Microplásticos/toxicidade , Comportamento Animal/efeitos dos fármacos , Nanopartículas/toxicidade , Larva/efeitos dos fármacosRESUMO
Esophageal squamous cell carcinoma (ESCC) is a common malignancy of the gastrointestinal tract with a single therapeutic option and a lack of effective clinical therapeutic biomarkers. Extracellular matrix (ECM) remodeling plays a pro-carcinogenic role in a variety of malignancies, but its role in esophageal squamous carcinoma remains to be elucidated. In this study, we examined the expression levels of ECM remodeling markers in 71 pairs of esophageal squamous carcinoma tissues and normal tissues adjacent to the carcinoma using immunohistochemical staining, and analyzed their relationship with clinicopathological features and prognosis. The results suggested that extracellular matrix remodeling markers (integrin αV, fibronectin, MMP9) were abnormally highly expressed in esophageal squamous carcinoma tissues. There was a statistically significant difference between the positive expression of ECM remodeling and the TNM stage of esophageal squamous carcinoma, and there was no statistically significant correlation with age, gender and carcinoembryonic antigen expression, differentiation degree, T stage, and lymph node metastasis. Overall survival rate and overall survival time were significantly lower in patients with positive ECM remodeling expression, which was an independent risk factor for poor prognosisof esophageal squamous carcinoma.
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Biomarcadores Tumorais , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Matriz Extracelular , Fibronectinas , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Masculino , Feminino , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Matriz Extracelular/metabolismo , Prognóstico , Pessoa de Meia-Idade , Fibronectinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Idoso , Metaloproteinase 9 da Matriz/metabolismo , Integrina alfaV/metabolismo , Integrina alfaV/genética , Estadiamento de Neoplasias , Regulação Neoplásica da Expressão Gênica , Metástase Linfática , AdultoRESUMO
Herein we report silyl radicals serve as isocyanide transfer agents for Giese-type reaction from aliphatic amines and electron-deficient olefins. α-Primary, α-secondary, and sterically encumbered α-tertiary primary amines could be easily converted into isocyanides for coupling with electron-deficient olefins by employing latent silyl radicals under visible light irradiation. Notably, the abstraction of silane-mediated isocyanide not only enables voltage-independent activation of strong C-N bonds but also represents a mechanistic alternative Giese-type reaction in which single electron reduction and protonation processes are replaced by direct hydrogen atom transfer. This transformation occurs under photoinduced catalyst-free conditions and exhibits excellent functional group compatibility and mild reaction conditions.
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The objective of this study was to identify multiple alkaloids in Coptis chinensis that demonstrate inhibitory activity against DPP-4 and systematically evaluate their activity and binding characteristics. A combined strategy that included molecular docking, a DPP-4 inhibition assay, surface plasmon resonance (SPR), and a molecular dynamics simulation technique was employed. The results showed that nine alkaloids in Coptis chinensis directly inhibited DPP-4, with IC50 values of 3.44-53.73 µM. SPR-based binding studies revealed that these alkaloids display rapid binding and dissociation characteristics when interacting with DPP-4, with KD values ranging from 8.11 to 29.97 µM. A molecular dynamics analysis revealed that equilibrium was rapidly reached by nine DPP-4-ligand systems with minimal fluctuations, while binding free energy calculations showed that the ∆Gbind values for the nine test compounds ranged from -31.84 to -16.06 kcal/mol. The most important forces for the binding of these alkaloids with DPP-4 are electrostatic interactions and van der Waals forces. Various important amino acid residues, such as Arg125, His126, Phe357, Arg358, and Tyr547, were involved in the inhibition of DPP-4 by the compounds, revealing a mechanistic basis for the further optimization of these alkaloids as DPP-4 inhibitors. This study confirmed nine alkaloids as direct inhibitors of DPP-4 and characterized their binding features, thereby providing a basis for further research and development on novel DPP-4 inhibitors.
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Alcaloides , Coptis , Inibidores da Dipeptidil Peptidase IV , Humanos , Alcaloides/química , Alcaloides/farmacologia , Sítios de Ligação , Coptis/química , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Descoberta de Drogas/métodos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Ressonância de Plasmônio de SuperfícieRESUMO
The rapid development of modern society has led to an increasing severity in the generation of new pollutants and the significant emission of old pollutants, exerting considerable pressure on the ecological environment and posing a serious threat to both biological survival and human health. The skeletal system, as a vital supportive structure and functional unit in organisms, is pivotal in maintaining body shape, safeguarding internal organs, storing minerals, and facilitating blood cell production. Although previous studies have uncovered the toxic effects of pollutants on vertebrate skeletal systems, there is a lack of comprehensive literature reviews in this field. Hence, this paper systematically summarizes the toxic effects and mechanisms of environmental pollutants on the skeletons of vertebrates based on the evolutionary context from fish to mammals. Our findings reveal that current research mainly focuses on fish and mammals, and the identified impact mechanisms mainly involve the regulation of bone signaling pathways, oxidative stress response, endocrine system disorders, and immune system dysfunction. This study aims to provide a comprehensive and systematic understanding of research on skeletal toxicity, while also promoting further research and development in related fields.
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Poluentes Ambientais , Peixes , Mamíferos , Animais , Poluentes Ambientais/toxicidade , Osso e Ossos/efeitos dos fármacos , Evolução Biológica , VertebradosRESUMO
This paper discusses regression analysis of interval-censored failure time data arising from semiparametric transformation models in the presence of missing covariates. Although some methods have been developed for the problem, they either apply only to limited situations or may have some computational issues. Corresponding to these, we propose a new and unified two-step inference procedure that can be easily implemented using the existing or standard software. The proposed method makes use of a set of working models to extract partial information from incomplete observations and yields a consistent estimator of regression parameters assuming missing at random. An extensive simulation study is conducted and indicates that it performs well in practical situations. Finally, we apply the proposed approach to an Alzheimer's Disease study that motivated this study.
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Doença de Alzheimer , Simulação por Computador , Modelos Estatísticos , Humanos , Análise de Regressão , Interpretação Estatística de DadosRESUMO
Objective. Electroencephalogram (EEG) analysis has always been an important tool in neural engineering, and the recognition and classification of human emotions are one of the important tasks in neural engineering. EEG data, obtained from electrodes placed on the scalp, represent a valuable resource of information for brain activity analysis and emotion recognition. Feature extraction methods have shown promising results, but recent trends have shifted toward end-to-end methods based on deep learning. However, these approaches often overlook channel representations, and their complex structures pose certain challenges to model fitting.Approach. To address these challenges, this paper proposes a hybrid approach named FetchEEG that combines feature extraction and temporal-channel joint attention. Leveraging the advantages of both traditional feature extraction and deep learning, the FetchEEG adopts a multi-head self-attention mechanism to extract representations between different time moments and channels simultaneously. The joint representations are then concatenated and classified using fully-connected layers for emotion recognition. The performance of the FetchEEG is verified by comparison experiments on a self-developed dataset and two public datasets.Main results. In both subject-dependent and subject-independent experiments, the FetchEEG demonstrates better performance and stronger generalization ability than the state-of-the-art methods on all datasets. Moreover, the performance of the FetchEEG is analyzed for different sliding window sizes and overlap rates in the feature extraction module. The sensitivity of emotion recognition is investigated for three- and five-frequency-band scenarios.Significance. FetchEEG is a novel hybrid method based on EEG for emotion classification, which combines EEG feature extraction with Transformer neural networks. It has achieved state-of-the-art performance on both self-developed datasets and multiple public datasets, with significantly higher training efficiency compared to end-to-end methods, demonstrating its effectiveness and feasibility.
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Eletroencefalografia , Emoções , Humanos , Eletroencefalografia/métodos , Emoções/fisiologia , Aprendizado Profundo , Atenção/fisiologia , Redes Neurais de Computação , Masculino , Feminino , AdultoRESUMO
Spleen tyrosine kinase (Syk) plays a crucial role as a target for allergy treatment due to its involvement in immunoreceptor signaling. The purpose of this study was to identify natural inhibitors of Syk and assess their effects on the IgE-mediated allergic response in mast cells and ICR mice. A list of eight compounds was selected based on pharmacophore and molecular docking, showing potential inhibitory effects through virtual screening. Among these compounds, sophoraflavanone G (SFG) was found to inhibit Syk activity in an enzymatic assay, with an IC50 value of 2.2 µM. To investigate the conformational dynamics of the SYK-SFG system, we performed molecular dynamics simulations. The stability of the binding between SFG and Syk was evaluated using root mean square deviation (RMSD) and root mean square fluctuation (RMSF). In RBL-2H3 cells, SFG demonstrated a dose-dependent suppression of IgE/BSA-induced mast cell degranulation, with no significant cytotoxicity observed at concentrations below 10.0 µM within 24 h. Furthermore, SFG reduced the production of TNF-α and IL-4 in RBL-2H3 cells. Mechanistic investigations revealed that SFG inhibited downstream signaling proteins, including phospholipase Cγ1 (PLCγ1), as well as mitogen-activated protein kinases (AKT, Erk1/2, p38, and JNK), in mast cells in a dose-dependent manner. Passive cutaneous anaphylaxis (PCA) experiments demonstrated that SFG could reduce ear swelling, mast cell degranulation, and the expression of COX-2 and IL-4. Overall, our findings identify naturally occurring SFG as a direct inhibitor of Syk that effectively suppresses mast cell degranulation both in vitro and in vivo.
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Interleucina-4 , Mastócitos , Camundongos , Animais , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Mastócitos/metabolismo , Anafilaxia Cutânea Passiva , Simulação de Acoplamento Molecular , Imunoglobulina E/metabolismo , Imunoglobulina E/farmacologia , Camundongos Endogâmicos ICR , Camundongos Endogâmicos BALB CRESUMO
Organic and mineral fertilization increase crop productivity, but their combined effects on soil quality index (SQI) and ecosystem multifunctionality (EMF, defined as the capacity of soils to simultaneously provide multiple functions and services) are not clear. We conducted a 13-year field trial in North China Plain to examine how five maize-derived organic fertilizers (straw, manure, compost, biogas residue, and biochar) at equal C input rate (3.2 t C ha-1), with or without nitrogen (N) fertilization influenced topsoil (0-15 cm) physico-chemical properties, activities of enzymes responsible for carbon (C), N, and phosphorus (P) cycling, as well as SQI and soil EMF. Organic fertilizers with or without N increased SQI by 51-187 % and EMF by 31-351 % through the enhancement of soil physical (mean weight diameter of soil aggregates) and chemical properties (C, N, and P contents) as well as C, N, and P acquisition enzyme activities, albeit the biochar effects were of minor importance. N application increased EMF compared to soil without N. Soil quality increased with EMF. Random forest analysis revealed that microbial biomass C and N, available P, permanganate oxidizable C, dissolved organic C and N, mean weight diameter of aggregates, hot water extractable C, and electrical conductivity were the main contributions to soil EMF. We conclude that application of maize-derived organic fertilizers, especially compost and straw, with optimal N fertilization is a plausible strategy to increase SQI and EMF under a wheat/maize system.
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Ecossistema , Fertilizantes , Nitrogênio , Solo , Solo/química , Nitrogênio/análise , China , Agricultura/métodos , Fósforo/análise , Zea mays , Carbono/análiseRESUMO
A radical initiator-free defunctionalization reaction of alkyl isocyanides with a hydrosilane has been established through C-N bond cleavage under catalyst-free visible light irradiation. Various alkyl isocyanides participated in the defunctionalization with tris(trimethylsilyl)silane under blue light irradiation at room temperature, delivering the reduced products in good yields with high chemoselectivity.
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Classical swine fever virus (CSFV) is a highly contagious pathogen causing significant economic losses in the swine industry. Conventional inactivated or attenuated live vaccines for classical swine fever (CSF) are effective but face biosafety concerns and cannot distinguish vaccinated animals from those infected with the field virus, complicating CSF eradication efforts. It is noteworthy that nanoparticle (NP)-based vaccines resemble natural viruses in size and antigen structure, and offer an alternative tool to circumvent these limitations. In this study, we developed an innovative vaccine delivery scaffold utilizing self-assembled mi3 NPs, which form stable structures carrying the CSFV E2 glycoprotein. The expressed yeast E2-fused protein (E2-mi3 NPs) exhibited robust thermostability (25 to 70 °C) and long-term storage stability at room temperature (25 °C). Interestingly, E2-mi3 NPs made with this technology elicited enhanced antigen uptake by RAW264.7 cells. In a rabbit model, the E2-mi3 NP vaccine against CSFV markedly increased CSFV-specific neutralizing antibody titers. Importantly, it conferred complete protection in rabbits challenged with the C-strain of CSFV. Furthermore, we also found that the E2-mi3 NP vaccines triggered stronger cellular (T-lymphocyte proliferation, CD8+ T-lymphocytes, IFN-γ, IL-2, and IL-12p70) and humoral (CSFV-specific neutralizing antibodies, CD4+ T-lymphocytes, and IL-4) immune responses in pigs than the E2 vaccines. To sum up, these structure-based, self-assembled mi3 NPs provide valuable insights for novel antiviral strategies against the constantly infectious agents.
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Vírus da Febre Suína Clássica , Peste Suína Clássica , Lagomorpha , Nanopartículas , Animais , Coelhos , Suínos , Nanovacinas , Peste Suína Clássica/prevenção & controle , Vacinas Atenuadas , Proteínas FúngicasRESUMO
Atherosclerosis ï¼ASï¼ is the primary reason behind cardiovascular diseases, leading to approximately one-third of global deaths. Developing a novel multi-model probe to detect AS is urgently required. Macrophages are the primary cells from which AS genesis occurs. Utilizing natural macrophage membranes coated on the surface of nanoparticles is an efficient delivery method to target plaque sites. Herein, Fe3 O4 -Cy7 nanoparticles (Fe3 O4 -Cy7 NPs), functionalized using an M2 macrophage membrane and a liposome extruder for Near-infrared fluorescence and Magnetic resonance imaging, are synthesized. These macrophage membrane-coated nanoparticles (Fe3 O4 @M2 NPs) enhance the recognition and uptake using active macrophages. Moreover, they inhibit uptake using inactive macrophages and human coronary artery endothelial cells. The macrophage membrane-coated nanoparticles (Fe3 O4 @M0 NPs, Fe3 O4 @M1 NPs, Fe3 O4 @M2 NPs) can target specific sites depending on the macrophage membrane type and are related to C-C chemofactor receptor type 2 protein content. Moreover, Fe3 O4 @M2 NPs demonstrate excellent biosafety in vivo after injection, showing a significantly higher Fe concentration in the blood than Fe3 O4 -Cy7 NPs. Therefore, Fe3 O4 @M2 NPs effectively retain the physicochemical properties of nanoparticles and depict reduced immunological response in blood circulation. These NPs mainly reveal enhanced targeting imaging capability for atherosclerotic plaque lesions.
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Aterosclerose , Nanopartículas , Humanos , Células Endoteliais , Nanopartículas/química , Imageamento por Ressonância Magnética/métodos , Aterosclerose/diagnóstico por imagemRESUMO
This study aims to investigate the impact of tralopyril, a newly developed marine antifouling agent, on the reproductive endocrine system and developmental toxicity of offspring in marine medaka. The results revealed that exposure to tralopyril (0, 1, 20 µg/L) for 42 days resulted in decreased reproductive capacity in marine medaka. Moreover, it disrupted the levels of sex hormones E2 and T, as well as the transcription levels of genes related to the HPG axis, such as cyp19b and star. Sex-dependent differences were observed, with females experiencing more pronounced effects. Furthermore, intergenerational toxicity was observed in F1 offspring, including increased heart rate, changes in retinal morphology and cartilage structure, decreased swimming activity, and downregulation of transcription levels of relevant genes (HPT axis, GH/IGF axis, cox, bmp4, bmp2, runx2, etc.). Notably, the disruption of the F1 endocrine system by tralopyril persisted into adulthood, indicating a transgenerational effect. Molecular docking analysis suggested that tralopyril's RA receptor activity might be one of the key factors contributing to the developmental toxicity observed in offspring. Overall, our study highlights the potential threat posed by tralopyril to the sustainability of fish populations, as it can disrupt the endocrine system and negatively impact aquatic organisms for multiple generations.
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Oryzias , Poluentes Químicos da Água , Animais , Feminino , Oryzias/fisiologia , Simulação de Acoplamento Molecular , Sistema Endócrino , Pirróis , Poluentes Químicos da Água/toxicidadeRESUMO
PROBLEM: Emergency triage faces multiple challenges, including limited medical resources and inadequate manual triage nurses, which cause incorrect triage, overcrowding in the emergency department (ED), and long patient waiting time. OBJECTIVE: This paper aims to propose and validate an accurate and efficient artificial intelligence-based method for effectively ED triage and alleviating the pressure on medical resources. METHODS: We propose two novel machine learning models, TransNet and TextRNN, for predicting patient severity levels and clinical departments using heterogeneous medical data in ED triage. Our models employ a parallel structure for feature extraction and incorporate an attention mechanism to extract essential information from the fused features, enabling accurate predictions. The models analyze the triage data (2020-2022) from the ED of Beijing University People's Hospital, incorporating variables (demographics, triage vital signs, and chief complaints) to identify patient severity levels and clinical departments. We performed data cleaning, categorization, and encoding first. Then, we divided the available data into a training set (56%), a validation set (24%), and a test set (20%) by random sampling. Finally, our models underwent 5-fold cross-validation and were compared with other state-of-the-art models. RESULTS: We comprehensively evaluated the proposed models against various Recurrent Neural Networks (RNN), Convolutional Neural Networks (CNN), Traditional Machine Learning (TML), and Transformer-based (TF) models, achieving excellent performance in predicting triage outcomes. Specifically, TextRNN achieved a prediction success rate of 86.23% [85.86-86.70] for severity levels and 94.30% [94.00-94.46] for clinical departments among 161,198 ED visits. Moreover, TransNet demonstrated higher sensitivities of 84.08% and 90.05% for severity levels and clinical departments, respectively, with specificities of 76.48% and 95.16%. The accuracy of our model is 0.87%, 0.18%, 4.29%, and 1.96%, higher than that of the above four family models on average. Furthermore, our method significantly reduced under-triage by 12.06% and over-triage by 17.92% compared to manual triage. CONCLUSIONS: Experimental results demonstrated that the proposed models fuse heterogeneous medical data in the triage process, successfully predicting patients' triage outcomes. Our models can improve triage efficiency, reduce the under/over-triage rate, and provide physicians with valuable decision-making support.
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Inteligência Artificial , Aprendizado de Máquina , Humanos , Serviço Hospitalar de Emergência , Triagem/métodos , Redes Neurais de Computação , Estudos RetrospectivosRESUMO
BACKGROUND: The optimal approach for perioperative pain management in laparoscopic gynecological surgery is unclear due to a lack of comprehensive analysis, which limits the development of evidence-based enhanced recovery after surgery protocols. This study aimed to conduct a systematic review and network meta-analysis to support clinical decision-making for optimal analgesia. MATERIALS AND METHODS: This study conducted a systematic literature search in PubMed, Embase, CENTRAL, Web of Science, and CINAHL from inception to 3 December 2021, and updated on 19 August 2022. Randomized controlled trials comparing the perioperative use of nonopioid analgesics and regional techniques in adults undergoing elective laparoscopic gynecological surgery under general anesthesia were included in the analysis, either alone or in combination. The co-analgesic interventions during the perioperative period for the intervention and control groups of each eligible study were also considered. We assessed the risk of bias using the Risk of Bias 2 tool and evaluated the certainty of evidence using the Confidence in Network Meta-Analysis (CINeMA) approach. A Bayesian network meta-analysis was used to estimate the efficacy of the analgesic strategies. The primary outcomes were pain score at rest and cumulative oral morphine milligram equivalents at 24 h postoperatively. RESULTS: Overall, 108 studies with 9582 participants and 35 different interventions were included. Compared with inert treatments, combinations of two or more interventions showed better efficacy and longer duration in reducing postoperative pain and opioid consumption within 24 h than monotherapies, and showed stepwise enhanced effects with increasing analgesic modes. In combination therapies, regional techniques that included peripheral nerve blocks and intraperitoneal local anesthetics, in combination with nonopioid systemic analgesics, or combining local anesthetics with adjuvant drugs, were found to be more effective. Monotherapies were found to be mostly ineffective. The most effective peripheral nerve blocks were found to be ultrasound-guided transversus abdominis plane block with adjuvant and ultrasound-guided quadratus lumborum block. CONCLUSIONS: These results provide robust evidence for the routine use of regional techniques in combination with nonopioid analgesics in perioperative pain management. However, further better quality and larger trials are needed, considering the low confidence levels for certain interventions.
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Analgésicos não Narcóticos , Laparoscopia , Adulto , Humanos , Feminino , Anestésicos Locais , Manejo da Dor/métodos , Analgésicos não Narcóticos/uso terapêutico , Metanálise em Rede , Teorema de Bayes , Analgésicos/uso terapêutico , Analgésicos Opioides , Dor Pós-Operatória/tratamento farmacológico , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversosRESUMO
BACKGROUND: Many types of cancer exhibit high nuclear factor erythroid 2-related factor 2 (NRF2), which is effective in resisting drugs and radiation. However, the role of NRF2 gene expression in predicting the prognosis of esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: The association between NRF2, heme oxygenase-1 (HO-1), baculovirus IAP repeat 5 (BIRC5), P53 gene expression levels and their relationship to immune-infiltrating cells were assessed using the Cancer Genome Atlas dataset, the Human Protein Atlas and the TISDB database. The expression of NRF2, HO-1, BIRC5, and TP53 in 118 ESCC patients was detected by immunohistochemistry, and the relationship between their expression level and clinicopathological parameters and prognosis was analyzed. RESULTS: In ESCC, NRF2 overexpression was significantly associated with Han ethnicity, lymph node metastasis, and distant metastasis. HO-1 overexpression was significantly associated with differentiation, advanced clinical staging, lymph node metastasis, nerve invasion, and distant metastasis. BIRC5 overexpression was significantly associated with Han ethnicity and lymph node metastasis. TP53 overexpression was significantly associated with Han ethnicity and T staging. The NRF2/HO-1 axis expression was positively correlated with BIRC5 and TP53. Kaplan-Meier and multivariate Cox regression analysis showed that NRF2, BIRC5, and TP53 genes co-expression was an independent prognostic risk factor. TISIDB dataset analysis showed that immune-infiltrating cells were significantly negatively correlated with NRF2 and BIRC5. CONCLUSION: NRF2, BIRC5, and TP53 axis gene expressions are predictors of poor prognosis for ESCC. The overexpression of the NRF2/HO-1/BIRC5 axis may not be related to immune-infiltrating cells.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas/patologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias Esofágicas/patologia , Metástase Linfática , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Baculoviridae/metabolismo , Prognóstico , Biomarcadores Tumorais/metabolismo , Proteína Supressora de Tumor p53/genética , Survivina/genética , Survivina/metabolismoRESUMO
Recently, photodynamic therapy (PDT) has been considered as a new strategy for atherosclerosis treatment. Targeted delivery of photosensitizer could significantly reduce its toxicity and enhance its phototherapeutic efficiency. CD68 is an antibody that can be conjugated to nano-drug delivery systems to actively target plaque sites, owing to its specific binding to CD68 receptors that are highly expressed on the surfaces of macrophage-derived foam cells. Liposomes are very popular nanocarriers due to their ability to encapsulate a wide range of therapeutic compounds including drugs, microRNAs and photosensitizers, and their ability to be surface-modified with targeting moieties leading to the development of nanocarriers with an improved targeted ability. Hence, we designed a Ce6-loaded liposomes using the film dispersion method, followed by the conjugation of CD68 antibody on the liposomal surface through a covalent crosslinking reaction, forming CD68-modified Ce6-loaded liposomes (CD68-Ce6-mediated liposomes). Flow cytometry results indicated that Ce6-containing liposomes were more effective in promoting intracellular uptake after laser irradiation. Furthermore, CD68-modified liposomes significantly strengthened the cellular recognization and thus internalization. Different cell lines have been incubated with the liposomes, and the results showed that CD68-Ce6-mediated liposomes had no significant cytotoxicity to coronary artery endothelial cells (HCAEC) under selected conditions. Interestingly, they promoted autophagy in foam cells through the increase in LC3-â , LC3-â ¡ expression and the decrease in p62 expression, and restrained the migration of mouse aortic vascular smooth muscle cells (MOVAS) in vitro. Moreover, the enhancement of atherosclerotic plaque stability and the reduction in the cholesterol content by CD68-Ce6-mediated liposomes were dependent on transient reactive oxygen species (ROS) generated under laser irradiation. In summary, we demonstrated that CD68-Ce6-mediated liposomes, as a photosensitizer nano-drug delivery system, have an inhibitory effect on MOVAS migration and a promotion of cholesterol efflux in foam cells, and thereby, represent promising nanocarriers for atherosclerosis photodynamic therapy.