Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 257
Filtrar
1.
Virol Sin ; 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39426602

RESUMO

Genital herpes (GH) is a common sexually transmitted disease, which is primarily caused by herpes simplex virus type 2 (HSV-2), and continues to be a global health concern. Although our understanding of the alterations in immune cell populations and immunomodulation in GH patients is still limited, it is evident that systemic intrinsic immunity, innate immunity, and adaptive immunity play crucial roles during HSV-2 infection and GH reactivation. To investigate the mechanisms underlying HSV-2 infection and recurrence, single-cell RNA sequencing (scRNA-seq) was performed on immune cells isolated from the peripheral blood of both healthy individuals and patients with recurrent GH. Furthermore, the systemic immune response in patients with recurrent GH showed activation of classical monocytes, CD4+ T cells, natural killer cells (NK cells), and plasmacytoid dendritic cells (pDCs), especially of genes associated with the Toll-like receptor signaling pathway and T cell activation. Circulating immune cells in GH patients show higher expression of genes associated with inflammation and antiviral responses both in the scRNA-Seq data set and in independent quantitative real-time polymerase chain reaction (qRT-PCR) analysis and ELISA experiments. This study demonstrated that localized genital herpes, resulting from HSV reactivation, may influence the functionality of circulating immune cells, suggesting a potential avenue for future research into the role of systemic immunity during HSV infection and recurrence.

2.
ACS Appl Mater Interfaces ; 16(42): 57603-57613, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39395020

RESUMO

Composite copper foil is considered to be the future-proof anode current collector solution for lithium-ion batteries (LIBs) with high energy density, for its light weight and low cost. Polypropylene (PP) film is widely used as the support layer of composite copper foil current collectors (CCs) due to its excellent mechanical properties and chemical stability. However, the interface adhesion between the PP layer and the copper layer is weak, due to the significant difference in surface energy. In this study, we prepared a hydrophilic PP film by air plasma treatment. After magnetron sputtering and electroplating, the composite copper foil (PP@Cu-1) with strong adhesion was then successfully prepared. In the T-peel test, for PP@Cu-1, the pull required to separate PP from the copper layer is approximately 7 times that of PP@Cu-0. The PP@Cu-1 composite copper foil exhibits excellent electrochemical properties when applied to LIBs. As an anode CC material, it could be a favorable competitor to conventional commercial Bare Cu and holds broad prospects for application in high-energy-density LIBs.

3.
J Affect Disord ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299588

RESUMO

BACKGROUND: Despite evidence regarding prevalence and correlates of cannabis use (CU) and cannabis use disorder (CUD) in major depressive disorder (MDD) and bipolar disorder (BD) in adults, little is known about this topic among adolescents. METHODS: Data is from the 2001-2004 National Comorbidity Survey-Adolescent Supplement, an in-person, cross-sectional epidemiologic survey of mental disorders. Participants included adolescents, ages 13-18 years, with MDD (n = 354 with CU, n = 70 with CUD, n = 688 with no CU), BD (n = 79 with CU, n = 32 with CUD, n = 184 with no CU), or adolescents without mood disorders (n = 1413 with CU, n = 333 with CUD, n = 6970 with no CU). Analyses examined prevalence and correlates of CU and CUD within MDD and BD groups. RESULTS: CU was most prevalent in adolescents with MDD followed by adolescents with BD then controls. CUD was most prevalent in adolescents with BD followed by adolescents with MDD then controls. In covariate-adjusted ordinal logistic regression models, within MDD and BD, CU and CUD groups had significantly higher odds of lifetime suicidal ideation/attempts, as well as other significant indicators of clinical severity. LIMITATIONS: Based on changes in cannabis acceptance, potency, and availability in the two decades since this study was conducted, present findings may underestimate adverse cannabis associations. CONCLUSION: CU and CUD are both associated with adverse clinical characteristics in a community-based sample of adolescents with MDD and BD. Evidence that risks of cannabis use extend across the spectrum of use is important for adolescents with MDD and BD, in whom cannabis-related consequences tend to be more severe.

4.
Nanoscale ; 16(37): 17527-17536, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39225108

RESUMO

Electroreduction of carbon dioxide (CO2) to multiple carbon products plays a significant role in carbon neutrality and the production of valuable chemicals. Herein, we developed a magnesium-modified copper oxide nanosheet catalyst (Mg-CuO) using a post-impregnation method. Comprehensive elemental analysis demonstrated the effective incorporation of magnesium into CuO nanosheets, resulting in a noticeable alteration of the electron density of Cu atoms. Consequently, the Mg-CuO nanosheets exhibited an increased efficiency for CO2 electroreduction in comparison with the unmodified CuO nanosheets. The optimized Mg-CuO catalyst exhibited faradaic efficiencies of 46.33% for ethylene production and 62.64% for C2+ production at -1.3 V vs. reversible hydrogen electrode (RHE). DFT proved that the introduction of Mg species could increase the charge density of Cu and decrease the adsorption energy of *CO, which promoted C-C coupling and enhanced the selectivity of C2+ products. This study presents an effective way to adjust the electronic structure of common copper-based electrocatalysts and the corresponding interaction with *CO, resulting in an improved faradaic efficiency of C2+ products.

5.
Chem Sci ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39345766

RESUMO

Li-O2 batteries (LOBs) boast an exceptionally high theoretical energy density; however, the slow kinetics of the oxygen electrode reaction have been a significant hurdle in their advancement and practical application. In this study, a composite of bismuth oxyhalide heterojunction incorporated with metal-organic frameworks (MOFs) was engineered on carbon cloth (Zr-MOF/BiOIBr/CC) as an efficient bifunctional catalyst to enhance the oxygen electrode reaction in photo-assisted LOBs. Compared to Zr-MOF/CC, Zr-MOF/BiOIBr/CC significantly expands the light absorption spectrum of the catalyst. Furthermore, the built-in electric field in the heterojunction aids in the separation and directional movement of photogenerated carriers, thereby expediting the reaction kinetics of LOBs. Consequently, the photo-assisted LOBs with Zr-MOF/BiOIBr/CC as the cathodes display a discharge potential of 3.05 V, a low charge potential of 3.20 V, and an energy efficiency of up to 95.3%, and can sustain an extended cycle life of over 255 cycles. This study underscores the potential application of MOFs/semiconductor heterostructural materials in photo-assisted LOBs and offers insights into the systematic design of photo-assisted air batteries and other advanced semiconductors.

6.
Small ; : e2403683, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39109560

RESUMO

Li-O2 batteries (LOBs) have sparked significant interest due to their fascinating high theoretical energy density. However, the large overpotential for the formation and oxidation of Li2O2 during charge and discharge process seriously hinders the further development and application of LOBs. In this work, metal-organic frameworks (MOFs) with different metal clusters (Fe, Ti, Zr) are successfully synthesized, and they are employed as the photoelectrodes for the photo-assisted LOBs. The special dual excitation pathways of Fe-MOF under illumination and the superior separation efficiency of photocarriers, which significantly enhance the activation of O2/Li2O2, improving the catalytic activity of oxygen reduction reaction and oxygen evolution reaction. Moreover, compared to traditional inorganic semiconductor crystals, Fe-MOF exhibits large specific surface area and excellent O2 adsorption ability. Therefore, the LOB with Fe-MOF as the cathode exhibits large specific capacity, ultralow charge/discharge overpotential of 0.22 V at 0.05 mA cm-2 and excellent stability of 195 cycles under illumination. This study provides an environmentally friendly and highly efficient photocatalyst for LOBs, and a new strategy for designing photoelectrodes.

7.
Nano Lett ; 24(34): 10510-10518, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39145617

RESUMO

Low-dimensional semiconductor-based field-effect transistor (FET) biosensors are promising for label-free detection of biotargets while facing challenges in mass fabrication of devices and reliable reading of small signals. Here, we construct a reliable technology for mass production of semiconducting carbon nanotube (CNT) film and FET biosensors. High-uniformity randomly oriented CNT films were prepared through an improved immersion coating technique, and then, CNT FETs were fabricated with coefficient of performance variations within 6% on 4-in. wafers (within 9% interwafer) based on an industrial standard-level process. The CNT FET-based ion sensors demonstrated threshold voltage standard deviations within 5.1 mV at each ion concentration, enabling direct reading of the concentration information based on the drain current. By integrating bioprobes, we achieved detection of biosignals as low as 100 aM through a plug-and-play portable detection system. The reliable technology will contribute to commercial applications of CNT FET biosensors, especially in point-of-care tests.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Transistores Eletrônicos , Nanotubos de Carbono/química , Técnicas Biossensoriais/instrumentação , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Nanotecnologia/instrumentação , Desenho de Equipamento
8.
Ther Adv Hematol ; 15: 20406207241270788, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39149575

RESUMO

This is a case of hemophagocytic intravascular large B-cell lymphoma (IVLBCL) with central nervous system (CNS) involvement. Although R-CHOP chemotherapy regimen has been shown significant improvement in survival rate. The prognosis and outcomes remain unsatisfactory, which is identified as outstanding challenges and need solutions. Gene and molecular profiling studies may provide new therapeutic strategies, especially the BCR/TLR/IL-1R/NF-κB signaling pathway in IVLBCL. Here, we treated the hemophagocytic IVLBCL CNS-involved patient with the Bruton tyrosine kinase inhibitor (BTKi) to block NF-κB pathway, and indicated that the second-generation BTKi zanubrutinib-based treatment was feasible and efficient.

9.
World J Clin Cases ; 12(21): 4590-4600, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39070818

RESUMO

BACKGROUND: Acute lower extremity deep venous thrombosis (LEDVT) is a common vascular emergency with significant morbidity risks, including post-thrombotic syndrome (PTS) and pulmonary embolism. Traditional treatments like catheter-directed thrombolysis (CDT) often result in variable success rates and complications. AIM: To investigate the therapeutic efficacy of percutaneous mechanical thrombus removal in acute LEDVT. METHODS: A retrospective analysis was performed to examine 58 hospitalised patients with acute LEDVT between August 2019 and August 2022. The patients were categorised into the percutaneous mechanical thrombectomy (PMT) group (n = 24) and CDT group (n = 32). The follow-up, safety and treatment outcomes were compared between the two groups. The main observational indexes were venous patency score, thrombus removal effect, complications, hospitalisation duration and PTS. RESULTS: The venous patency score was 9.04 ± 1.40 in the PMT group and 8.81 ± 1.60 in the CDT group, and the thrombus clearance rate was 100% in both groups. The complication rate was 8.33% in the PMT group and 34.84% in the CDT group, and the difference was statistically significant (P < 0.05). The average hospitalisation duration was 6.54 ± 2.48 days in the PMT group and 8.14 ± 3.56 days in the CDT group. The incidence of PTS was lower in the PMT group than in the CDT group; however, the difference was not statistically significant (P < 0.05). CONCLUSION: Compared with CDT, treatment of LEDVT via PMT was associated with a better thrombus clearance rate, clinical therapeutic effect and PTS prevention function, but the difference was not statistically significant. Moreover, PMT was associated with a reduced urokinase dosage, shortened hospitalisation duration and reduced incidence of complications, such as infections and small haemorrhages. These results indicate that PMT has substantial beneficial effects in the treatment of LEDVT.

10.
J Am Med Inform Assoc ; 31(9): 2030-2039, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38857454

RESUMO

OBJECTIVES: Precise literature recommendation and summarization are crucial for biomedical professionals. While the latest iteration of generative pretrained transformer (GPT) incorporates 2 distinct modes-real-time search and pretrained model utilization-it encounters challenges in dealing with these tasks. Specifically, the real-time search can pinpoint some relevant articles but occasionally provides fabricated papers, whereas the pretrained model excels in generating well-structured summaries but struggles to cite specific sources. In response, this study introduces RefAI, an innovative retrieval-augmented generative tool designed to synergize the strengths of large language models (LLMs) while overcoming their limitations. MATERIALS AND METHODS: RefAI utilized PubMed for systematic literature retrieval, employed a novel multivariable algorithm for article recommendation, and leveraged GPT-4 turbo for summarization. Ten queries under 2 prevalent topics ("cancer immunotherapy and target therapy" and "LLMs in medicine") were chosen as use cases and 3 established counterparts (ChatGPT-4, ScholarAI, and Gemini) as our baselines. The evaluation was conducted by 10 domain experts through standard statistical analyses for performance comparison. RESULTS: The overall performance of RefAI surpassed that of the baselines across 5 evaluated dimensions-relevance and quality for literature recommendation, accuracy, comprehensiveness, and reference integration for summarization, with the majority exhibiting statistically significant improvements (P-values <.05). DISCUSSION: RefAI demonstrated substantial improvements in literature recommendation and summarization over existing tools, addressing issues like fabricated papers, metadata inaccuracies, restricted recommendations, and poor reference integration. CONCLUSION: By augmenting LLM with external resources and a novel ranking algorithm, RefAI is uniquely capable of recommending high-quality literature and generating well-structured summaries, holding the potential to meet the critical needs of biomedical professionals in navigating and synthesizing vast amounts of scientific literature.


Assuntos
Algoritmos , Armazenamento e Recuperação da Informação , PubMed , Armazenamento e Recuperação da Informação/métodos , Processamento de Linguagem Natural
11.
Exp Ther Med ; 27(6): 267, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38756907

RESUMO

The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3 (MMP-3) rs3025058 locus gene polymorphisms may be associated with AIS susceptibility, which has been controversial and needs to be further confirmed by updated meta-analysis. The aim of the present study was to investigate the association of MMP-3 rs3025058 and IL-6 rs1800795 single nucleotide polymorphisms (SNPs) with susceptibility to AIS. All relevant articles that met the criteria were retrieved and included, and the publication dates were limited from January 2005 to December 2023. The allele frequencies and different genotype frequencies of IL-6 rs1800795 and MMP-3 rs3025058 loci in each study were extracted and statistically analyzed by ReviewManager 5.4 software, and the odds ratio (OR) and 95% confidence interval (95% CI) of different genetic models were calculated. The results of the meta-analysis showed that there was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS. The allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility (5A vs. 6A, OR=1.18; 95% CI, 1.04-1.33; 5A5A vs. 6A6A, OR=1.65; 95% CI, 1.23-2.21; and 5A5A vs. 5A6A + 6A6A, OR=1.54; 95% CI, 1.19-1.99). Results of subgroup analysis revealed that the allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility in the Caucasian population, and the susceptibility of AIS was associated with the genotype 5A5A of MMP-3 rs3025058 SNP in an Asian population. There was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS, while the allele 5A of MMP-3 rs3025058 locus was associated with the susceptibility to AIS, especially in the Caucasian population.

12.
Front Immunol ; 15: 1380628, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774866

RESUMO

Introduction: TAM receptor-mediated efferocytosis plays an important function in immune regulation and may contribute to antigen tolerance in the lungs, a site with continuous cellular turnover and generation of apoptotic cells. Some studies have identified failures in efferocytosis as a common driver of inflammation and tissue destruction in lung diseases. Our study is the first to characterize the in vivo function of the TAM receptors, Axl and MerTk, in the innate immune cell compartment, cytokine and chemokine production, as well as the alveolar macrophage (AM) phenotype in different settings in the airways and lung parenchyma. Methods: We employed MerTk and Axl defective mice to induce acute silicosis by a single exposure to crystalline silica particles (20 mg/50 µL). Although both mRNA levels of Axl and MerTk receptors were constitutively expressed by lung cells and isolated AMs, we found that MerTk was critical for maintaining lung homeostasis, whereas Axl played a role in the regulation of silica-induced inflammation. Our findings imply that MerTk and Axl differently modulated inflammatory tone via AM and neutrophil recruitment, phenotype and function by flow cytometry, and TGF-ß and CXCL1 protein levels, respectively. Finally, Axl expression was upregulated in both MerTk-/- and WT AMs, confirming its importance during inflammation. Conclusion: This study provides strong evidence that MerTk and Axl are specialized to orchestrate apoptotic cell clearance across different circumstances and may have important implications for the understanding of pulmonary inflammatory disorders as well as for the development of new approaches to therapy.


Assuntos
Receptor Tirosina Quinase Axl , Homeostase , Pulmão , Macrófagos Alveolares , Camundongos Knockout , Proteínas Proto-Oncogênicas , Receptores Proteína Tirosina Quinases , Silicose , c-Mer Tirosina Quinase , Animais , Camundongos , c-Mer Tirosina Quinase/metabolismo , c-Mer Tirosina Quinase/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/genética , Silicose/metabolismo , Silicose/imunologia , Silicose/patologia , Masculino
13.
Cancer Res ; 84(10): 1597-1612, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38588411

RESUMO

Resistance to immune checkpoint blockade (ICB) therapy represents a formidable clinical challenge limiting the efficacy of immunotherapy. In particular, prostate cancer poses a challenge for ICB therapy due to its immunosuppressive features. A ketogenic diet (KD) has been reported to enhance response to ICB therapy in some other cancer models. However, adverse effects associated with continuous KD were also observed, demanding better mechanistic understanding and optimized regimens for using KD as an immunotherapy sensitizer. In this study, we established a series of ICB-resistant prostate cancer cell lines and developed a highly effective strategy of combining anti-PD1 and anti-CTLA4 antibodies with histone deacetylase inhibitor (HDACi) vorinostat, a cyclic KD (CKD), or dietary supplementation of the ketone body ß-hydroxybutyrate (BHB), which is an endogenous HDACi. CKD and BHB supplementation each delayed prostate cancer tumor growth as monotherapy, and both BHB and adaptive immunity were required for the antitumor activity of CKD. Single-cell transcriptomic and proteomic profiling revealed that HDACi and ketogenesis enhanced ICB efficacy through both cancer cell-intrinsic mechanisms, including upregulation of MHC class I molecules, and -extrinsic mechanisms, such as CD8+ T-cell chemoattraction, M1/M2 macrophage rebalancing, monocyte differentiation toward antigen-presenting cells, and diminished neutrophil infiltration. Overall, these findings illuminate a potential clinical path of using HDACi and optimized KD regimens to enhance ICB therapy for prostate cancer. SIGNIFICANCE: Optimized cyclic ketogenic diet and 1,3-butanediol supplementation regimens enhance the efficacy of immune checkpoint blockade in prostate cancer through epigenetic and immune modulations, providing dietary interventions to sensitize tumors to immunotherapy.


Assuntos
Dieta Cetogênica , Resistencia a Medicamentos Antineoplásicos , Epigênese Genética , Inibidores de Checkpoint Imunológico , Neoplasias da Próstata , Masculino , Dieta Cetogênica/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/dietoterapia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Camundongos , Epigênese Genética/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Vorinostat/farmacologia , Vorinostat/uso terapêutico , Vorinostat/administração & dosagem , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Ácido 3-Hidroxibutírico , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores
14.
bioRxiv ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-38617233

RESUMO

Ferroptosis is a non-apoptotic form of cell death resulting from the iron-dependent accumulation of lipid peroxides. Colorectal cancer (CRC) cells accumulate high levels of intracellular iron and reactive oxygen species (ROS) and are thus particularly sensitive to ferroptosis. The compound (S)-RSL3 ([1S,3R]-RSL3) is a commonly used ferroptosis inducing compound that is currently characterized as a selective inhibitor of the selenocysteine containing enzyme (selenoprotein) Gluathione Peroxidase 4 (GPx4), an enzyme that utilizes glutathione to directly detoxify lipid peroxides. However, through chemical controls utilizing the (R) stereoisomer of RSL3 ([1R,3R]-RSL3) that does not bind GPx4, combined with inducible genetic knockdowns of GPx4 in CRC cell lines, we revealed that GPx4 dependency does not always align with (S)-RSL3 sensitivity, questioning the current characterization of GPx4 as the central regulator of ferroptosis. Utilizing affinity pull-down mass spectrometry with chemically modified (S)-RSL3 probes we discovered that the effects of (S)-RSL3 extend far beyond GPx4 inhibition, revealing that (S)-RSL3 is a broad and non-selective inhibitor of selenoproteins. To further investigate the therapeutic potential of broadly disrupting the selenoproteome as a therapeutic strategy in CRC, we employed additional chemical and genetic approaches. We found that the selenoprotein inhibitor auranofin, an FDA approved gold-salt, chemically induced oxidative cell death and ferroptosis in both in-vitro and in-vivo models of CRC. Consistent with these data, we found that AlkBH8, a tRNA-selenocysteine methyltransferase required for the translation of selenoproteins, is essential for the in-vitro growth and xenograft survival of CRC cell lines. In summary, these findings recharacterize the mechanism of action of the most commonly used ferroptosis inducing molecule, (S)-RSL3, and reveal that broad inhibition of selenoproteins is a promising novel therapeutic angle for the treatment of CRC.

15.
Immun Inflamm Dis ; 12(4): e1207, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38661103

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa, with a gradually increasing incidence. Therefore, it is necessary to actively seek targets for the treatment of UC. METHODS: Common differentially expressed genes (DEGs) were screened from two microarray data sets related to UC. Protein-protein interaction network was constructed to find the hub genes. The UC mouse model and cell model were induced by dextran sulfate sodium (DSS). The pathological changes of colon tissue were observed by hematoxylin-eosin staining. Immunohistochemistry and immunofluorescence were performed to detect the expressions of Ki67 and Claudin-1. The performance of mice was observed by disease activity index (DAI). The effect of TOP2A on proliferation, inflammation, oxidative stress, and interleukin-17 (IL-17) signaling pathway in UC model was measured by cell counting kit-8, enzyme-linked immunosorbent assay, and western blot. RESULTS: Through bioinformatics analysis, 295 common DEGs were screened, and the hub gene TOP2A was selected. In UC model, there was obvious inflammatory cell infiltration in the colon and less goblet cells, while si-TOP2A lessened it. More Ki67 positive cells and less Claudin-1 positive cells were observed in UC model mice. Furthermore, knockdown of TOP2A increased the body weight and colon length of UC mice, while the DAI was decreased. Through in vivo and in vitro experiments, knockdown of TOP2A also inhibited inflammation and IL-17 signaling pathway, and promoted proliferation in DSS-induced NCM460 cells. CONCLUSION: Knockdown of TOP2A alleviated the progression of UC by suppressing inflammation and inhibited IL-17 signaling pathway.


Assuntos
Colite Ulcerativa , DNA Topoisomerases Tipo II , Modelos Animais de Doenças , Progressão da Doença , Interleucina-17 , Proteínas de Ligação a Poli-ADP-Ribose , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Sulfato de Dextrana , DNA Topoisomerases Tipo II/metabolismo , DNA Topoisomerases Tipo II/genética , Técnicas de Silenciamento de Genes , Interleucina-17/metabolismo , Interleucina-17/genética , Mapas de Interação de Proteínas
16.
J Healthc Inform Res ; 8(2): 206-224, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38681754

RESUMO

Biomedical relation extraction (RE) is critical in constructing high-quality knowledge graphs and databases as well as supporting many downstream text mining applications. This paper explores prompt tuning on biomedical RE and its few-shot scenarios, aiming to propose a simple yet effective model for this specific task. Prompt tuning reformulates natural language processing (NLP) downstream tasks into masked language problems by embedding specific text prompts into the original input, facilitating the adaption of pre-trained language models (PLMs) to better address these tasks. This study presents a customized prompt tuning model designed explicitly for biomedical RE, including its applicability in few-shot learning contexts. The model's performance was rigorously assessed using the chemical-protein relation (CHEMPROT) dataset from BioCreative VI and the drug-drug interaction (DDI) dataset from SemEval-2013, showcasing its superior performance over conventional fine-tuned PLMs across both datasets, encompassing few-shot scenarios. This observation underscores the effectiveness of prompt tuning in enhancing the capabilities of conventional PLMs, though the extent of enhancement may vary by specific model. Additionally, the model demonstrated a harmonious balance between simplicity and efficiency, matching state-of-the-art performance without needing external knowledge or extra computational resources. The pivotal contribution of our study is the development of a suitably designed prompt tuning model, highlighting prompt tuning's effectiveness in biomedical RE. It offers a robust, efficient approach to the field's challenges and represents a significant advancement in extracting complex relations from biomedical texts. Supplementary Information: The online version contains supplementary material available at 10.1007/s41666-024-00162-9.

17.
J Am Med Inform Assoc ; 31(9): 1904-1911, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38520725

RESUMO

OBJECTIVES: The rapid expansion of biomedical literature necessitates automated techniques to discern relationships between biomedical concepts from extensive free text. Such techniques facilitate the development of detailed knowledge bases and highlight research deficiencies. The LitCoin Natural Language Processing (NLP) challenge, organized by the National Center for Advancing Translational Science, aims to evaluate such potential and provides a manually annotated corpus for methodology development and benchmarking. MATERIALS AND METHODS: For the named entity recognition (NER) task, we utilized ensemble learning to merge predictions from three domain-specific models, namely BioBERT, PubMedBERT, and BioM-ELECTRA, devised a rule-driven detection method for cell line and taxonomy names and annotated 70 more abstracts as additional corpus. We further finetuned the T0pp model, with 11 billion parameters, to boost the performance on relation extraction and leveraged entites' location information (eg, title, background) to enhance novelty prediction performance in relation extraction (RE). RESULTS: Our pioneering NLP system designed for this challenge secured first place in Phase I-NER and second place in Phase II-relation extraction and novelty prediction, outpacing over 200 teams. We tested OpenAI ChatGPT 3.5 and ChatGPT 4 in a Zero-Shot setting using the same test set, revealing that our finetuned model considerably surpasses these broad-spectrum large language models. DISCUSSION AND CONCLUSION: Our outcomes depict a robust NLP system excelling in NER and RE across various biomedical entities, emphasizing that task-specific models remain superior to generic large ones. Such insights are valuable for endeavors like knowledge graph development and hypothesis formulation in biomedical research.


Assuntos
Processamento de Linguagem Natural , Mineração de Dados/métodos , Aprendizado de Máquina , Humanos
18.
PLoS One ; 19(3): e0300919, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512919

RESUMO

Though Vaccines are instrumental in global health, mitigating infectious diseases and pandemic outbreaks, they can occasionally lead to adverse events (AEs). Recently, Large Language Models (LLMs) have shown promise in effectively identifying and cataloging AEs within clinical reports. Utilizing data from the Vaccine Adverse Event Reporting System (VAERS) from 1990 to 2016, this study particularly focuses on AEs to evaluate LLMs' capability for AE extraction. A variety of prevalent LLMs, including GPT-2, GPT-3 variants, GPT-4, and Llama2, were evaluated using Influenza vaccine as a use case. The fine-tuned GPT 3.5 model (AE-GPT) stood out with a 0.704 averaged micro F1 score for strict match and 0.816 for relaxed match. The encouraging performance of the AE-GPT underscores LLMs' potential in processing medical data, indicating a significant stride towards advanced AE detection, thus presumably generalizable to other AE extraction tasks.


Assuntos
Vacinas contra Influenza , Influenza Humana , Humanos , Vacinas contra Influenza/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , Influenza Humana/prevenção & controle , Alanina Transaminase , Surtos de Doenças
19.
Small ; 20(27): e2310915, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38267813

RESUMO

Lithium dendrites are easily generated for excessively-solved lithium ions (Li+) inside the lithium metal batteries, which will lead serious safety issues. In this experiment, carbon spheres (CS) are successfully anchored on TiO2 (CS@TiO2) in the hydrothermal polymerization, which is filtrated on the commercial PE separator (CS@TiO2@PE). The negative charge in CS can suppress random diffusion of anions through electrostatic interactions. Density functional theory (DFT) calculations show that CS contributes to the desolvation of Li+, thereby increasing the migration rate of Li+. Furthermore, TiO2 exhibits high affinity to liquid electrolytes and acts as a physical barrier to lithium dendrite formation. CS@TiO2 is a combination of the advantages of CS and TiO2. As results, the Li+ transference number of the CS@TiO2@PE separator can be promoted to 0.63. The Li||Li cell with the CS@TiO2@PE separator exhibits a stable cycle performance for more than 600 h and lower polarization voltage (17 mV) at 1 mA cm-2. The coulombic efficiency (CE) of the Li||Cu cells employe the CS@TiO2@PE separator is 81.63% over 130 cycles. The discharge capacity of LiFePO4||Li cells based on the CS@TiO2@PE separator is 1.73 mAh (capacity retention = 91.53% after 260 cycles). Thus, the CS@TiO2 layer inhibits lithium dendrite formation.

20.
Molecules ; 29(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38257285

RESUMO

In this work, a surface dispersed heterojunction of BiVO4-nanoparticle@WO3-nanoflake was successfully prepared by hydrothermal combined with solvothermal method. We optimized the morphology of the WO3 nanoflakes and BiVO4 nanoparticles by controlling the synthesis conditions to get the uniform BiVO4 loaded on the surface of WO3 arrays. The phase composition and morphology evolution with different reaction precursors were investigated in detail. When used as photoanodes, the WO3/BiVO4 composite exhibits superior activity with photocurrent at 3.53 mA cm-2 for photoelectrochemical (PEC) water oxidation, which is twice that of pure WO3 photoanode. The superior surface dispersion structure of the BiVO4-nanoparticle@WO3-nanoflake heterojunction ensures a large effective heterojunction area and relieves the interfacial hole accumulation at the same time, which contributes to the improved photocurrents together with the stability of the WO3/BiVO4 photoanodes.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA