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JOURNAL/nrgr/04.03/01300535-202508000-00030/figure1/v/2024-09-30T120553Z/r/image-tiff Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death. However, there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation. Adeno-associated virus (AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa. The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function. To do this, we injected retinal degeneration 10 (rd10) mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark- and light-adapted electroretinogram, optical coherence tomography, and immunofluorescence. Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment, and the results from this analysis were verified by real-time polymerase chain reaction and western blotting. AAV2-PDE6B injection significantly upregulated PDE6ß expression, preserved electroretinogram responses, and preserved outer nuclear layer thickness in rd10 mice. Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception, and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice. Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways. Furthermore, the phototransduction-related proteins Pde6α, Rom1, Rho, Aldh1a1, and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment. Finally, Bax/Bcl-2, p-ERK/ERK, and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment. Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
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The efficient delivery of RNA-based drugs to solid tumors remains a formidable obstacle. We aim to develop a safe and efficient oral drug delivery system compatible with RNA-based drugs that is urgently needed to overcome challenges such as enzymatic degradation and gastrointestinal barriers to facilitate effective treatment for treating colorectal cancer (CRC). To address these challenges, we utilized engineered modified Saccharomyces cerevisiae to evaluate the delivery efficacy of miR21-antagomir for treating CRC in preclinical mouse models, including adenomatosis polyposis coli mutant transgenic mice ApcMin/+ and in situ tumor-bearing mice. An orally deliverable gene delivery system, YS@NPs21, was designed. This gene delivery system demonstrated effectively suppressed tumor growth in both ApcMin/+ and in situ tumor-bearing mice models. This system exhibited tumor-targeting capability, effective inhibition of tumor growth, and low toxicity toward nontumor cells. Successful implementation of this innovative oral drug delivery system could offer a straightforward, safe, and RNA drug-compatible approach to CRC treatment, ultimately improving patient outcomes and reducing medical costs.
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Neoplasias Colorrectales , Saccharomyces cerevisiae , Animales , Saccharomyces cerevisiae/genética , Ratones , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Administración Oral , Humanos , Técnicas de Transferencia de Gen , Ratones Transgénicos , MicroARNs/genética , MicroARNs/metabolismo , Antagomirs/farmacología , Antagomirs/química , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Ratones Endogámicos C57BL , Proliferación Celular/efectos de los fármacosRESUMEN
BACKGROUND: Estrogen receptor-positive breast cancer accounts for around 70% of all cases. Tamoxifen, an anti-estrogenic inhibitor, is the primary drug used for this type of breast cancer treatment. However, tamoxifen resistance is a major challenge in clinics. Metabolic reprogramming, an emerging hallmark of cancer, plays a key role in cancer initiation, progression, and therapy resistance. The metabolism of non-essential amino acids such as serine, proline, and glutamine is involved in tumor metabolism reprogramming. Although the association of glutamine metabolism with tamoxifen resistance has been well established, the role of proline metabolism and its critical enzyme PRODH is unknown. OBJECTIVE: The aim of this study is to explore the role and mechanism of PRODH in tamoxifen resistance in breast cancer cells. METHODS: PRODH and GPX4 expressions in tamoxifen-resistant cells were detected using real-time PCR and Western blot analysis. The breast cells' response to tamoxifen was measured using MTT assays. Trans-well assays were used to detect cell migration and invasion. A Xenograft tumor assay was used to detect the role of PRODH in tumor growth. Reactive oxygen species were measured using flow cytometry. RESULTS: PRODH expression is reduced in tamoxifen-resistant cells, and its overexpression enhances tamoxifen response in vitro and in vivo. Conversely, PRODH knockdown confers tamoxifen resistance in tamoxifen-sensitive cells. Mechanistic studies show that ferroptosis is inhibited in tamoxifen-resistant cells and overexpression of PRODH restores the ferroptosis in tamoxifen-resistant cells. Moreover, Ferrostatin-1 (Fer-1), the ferroptosis inhibitor, reversed the effect of PRODH on tamoxifen resistance. CONCLUSIONS: These findings suggest that PRODH regulates tamoxifen resistance by regulating ferroptosis in tamoxifen-resistant cells.
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Neoplasias de la Mama , Resistencia a Antineoplásicos , Ferroptosis , Tamoxifeno , Tamoxifeno/farmacología , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos/genética , Femenino , Animales , Ratones , Línea Celular Tumoral , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Prolina Oxidasa/genética , Prolina Oxidasa/metabolismo , Antineoplásicos Hormonales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Células MCF-7 , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Movimiento Celular/efectos de los fármacosRESUMEN
A large amount of antibiotics enters the soil environment and accumulates therein as individuals and mixtures, threatening the soil safety. However, there is little information regarding the influence of single and mixed antibiotics on key soil proteins at molecular level. In this study, setting sulfadiazine (SD) and tetracycline hydrochloride (TC) as the representative antibiotics, the interactions between these agents and α-amylase (an important hydrolase in soil carbon cycle) were investigated through multi-spectroscopic approaches, X-ray photoelectron spectrometry, and molecular modeling. It was found that both SD and TC spontaneously bound to α-amylase with 1:1 stoichiometry mainly via forming stable chemical bonds. The interactions altered the polarity of aromatic amino acids, protein backbone, secondary structure, hydrophobicity and activity of α-amylase. The SD-TC mixtures were designed based on the direct equipartition ray to comprehensively characterize the possible concentration distribution, and interactive effects indicated that the mixtures antagonistically impacted α-amylase. These findings reveal the binding characteristics between α-amylase and typical antibiotics, which probably influence the ecological functions of α-amylase in soil. This study clarifies the potential harm of antibiotics on soil functional enzyme, which is significant for the environmental risk assessment of antibiotics and their mixtures.
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Soil arthropods are a diverse group of invertebrates that play pivotal roles in nutrient cycling, decomposition, soil structure formation, and regulation of soil biodiversity. Understanding the ecological significance of soil arthropods and their interactions with other soil organisms is crucial. This review paper examines the potential of arthropods in improving soil health and quality, with a specific focus on their relevance in acidic, saline/alkaline, and contaminated soils. The paper investigates the interactions between arthropods and their associated microbiomes, their contributions to soil physical and chemical properties, their influence on nutrient cycling and organic matter mineralization, as well as their role as indicators of soil health due to their sensitivity to environmental changes. Furthermore, the review explores how arthropods enhance the activities of microorganisms, such as bacteria, fungi, and yeast, which employ molecular mechanisms to remediate heavy metal contamination in soils. Lastly, the paper addresses key challenges and future directions for utilizing soil arthropods in the restoration of environmentally friendly soils.
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To determine the characteristics of posterior precortical vitreous pockets (PPVPs) and to observe vitreous changes in myopic eyes by swept-source optical coherence tomography (SS-OCT) and en face imaging in a cohort of the Chinese Han population. This was a cross-sectional study. Volunteers (235 participants, 374 eyes) received an SS-OCT examination. The heights and widths of the PPVPs were measured by SS-OCT. The area of the PPVPs was measured on en face images. The relationships between PPVP size and sex, age, axial length (AL) and spherical equivalent (SE) were evaluated. The mean width and height were 6711.64 ± 1241.87 µm and 662.47 ± 326.39 µm, respectively. The area of the PPVPs was 30.296 ± 9.114 mm2. Boat-shaped, oval, and hook-shaped PPVPs were observed in 73.26%, 21.12%, and 5.62% of all eyes, respectively; 73.53% of all PPVPs had channels communicating with Cloquet's tubes. There was a significant difference in the PPVP width among the participates over and under 50 years old (t = -2.508, P = 0.031). Age had a positive correlation with the PPVP width (r = 0.53, P = 0.001). The PPVP height showed significant differences among the different myopia groups (F = 3.618, P = 0.013). SE had a negative correlation with the PPVP height (r = -0.176, P = 0.001). However, there were no correlations between the AL and the width, height or area of the PPVPs (P = 0.117; P = 0.334; P = 0.057, respectively). Age and myopia affect the size of PPVPs. SS-OCT greatly facilitates visualization of the complex structure of the vitreous.
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Miopía , Tomografía de Coherencia Óptica , Cuerpo Vítreo , Humanos , Tomografía de Coherencia Óptica/métodos , Masculino , Femenino , Cuerpo Vítreo/diagnóstico por imagen , Cuerpo Vítreo/patología , Persona de Mediana Edad , Adulto , Estudios Transversales , Miopía/diagnóstico por imagen , Miopía/patología , Anciano , Adulto Joven , AdolescenteRESUMEN
Home information profoundly influences behavioral states in both humans and animals. However, how "home" is represented in the brain and its role in driving diverse related behaviors remain elusive. Here, we demonstrate that home bedding contains sufficient home information to modulate affective behaviors, including aversion responses, defensive aggression, and mating behaviors. These varied responses to home information are mediated by gama-aminobutyric acid (GABA)ergic neurons in the lateral hypothalamus (LHGABA). Inhibiting LHGABA abolishes, while activating mimics, the effects of home bedding on these behaviors across different contexts. Specifically, projections from LHGABA to the ventral tegmental area (VTA) mediate the relaxation of aversive emotion, while projections to the periaqueductal gray (PAG) initiate defensive concerns. Thus, our data suggest that home information in different contexts converges to activate distinct subgroups of the LHGABA, which, in turn, elicit appropriate affective behaviors in relieving aversion, fighting intruders, or enhancing mating through involving distinct downstream projections.
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Wound management remains a critical challenge worldwide and imposes a huge financial burden on every nation. Hydrogels are promising for biomedical applications because of their extracellular matrix (ECM) like structure, good biocompatibility and multifunctional bioactivity. However, the poor mechanical properties and inconvenient operation of traditional hydrogels make it difficult to meet the complex and multifaceted needs of clinical practice. In recent years, the multifunctional nanocomposites hydrogel with especially sprayable feature have shown enhanced mechanical properties and facile operation, which enable their huge clinical applications value. A unique and powerful nanocomposite hydrogels (NCH) platform is developed by combining the many advantages of nanomaterials and hydrogels, which can achieve efficient trauma repair. This work reviews important advances on the preparation, functions and applications of sprayable NCH platforms. The challenges and future trends in the field with the aim of providing researchers with clarity on the past, present, and future of the emerging field of sprayable NCH are also proposed in detail.
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Developing bioactive materials with multifunctional properties is crucial for enhancing their biomedical applications in regenerative medicine. Bioactive glass nanoparticle (BGN) is a new generation of biomaterials that demonstrate high biocompatibility and tissue-inducing capacity. However, the hard nanoparticle surface and single surface property limited their wide biomedical applications. In recent years, the surface functional strategy has been employed to decorate the BGN and improve its biomedical applications in bone tissue repair, bioimaging, tumor therapy and wound repair. This review summarizes the progress of surface-interface design strategy, customized multifunctional properties and biomedical applications in detail. We also discussed the current challenges and further development of multifunctional BGN to meet the requirements of various biomedical applications.
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Increased or altered mitochondrial ROS production in the retinal ganglion cells is regarded as the chief culprit of the disease-causing Leber's hereditary optic neuropathy (LHON). SkQ1 is a rechargeable mitochondria-targeted antioxidant with high specificity and efficiency. SkQ1 has already been used to treat LHON patients, and a phase 2a randomized clinical trial of SkQ1 has demonstrated improvements in eyesight. However, the underlying mechanism of SkQ1 in LHON remains unclear. This study aimed to assess the effects and molecular mechanism of SkQ1 in the preservation of mitochondrial function using skin fibroblasts derived from LHON patients. Our study found that SkQ1 could reduce ROS production and stabilize the mitochondrial membrane. Mechanistically, through network pharmacology and molecular docking, we identified the key targets of SkQ1 as SOD2 and PINK1, which play crucial roles in redox and mitophagy. SkQ1 interacted with PINK1 and downregulated its expression to balance mitochondrial homeostasis. Collectively, the findings of our study reveal that by regulating PINK1/PRKN-mediated mitophagy, SkQ1 preserves mitochondrial function in LHON fibroblasts. The data indicate that SkQ1 may be a novel therapeutic intervention to prevent the progression of LHON.
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Retinitis pigmentosa (RP) is a progressive and degenerative retinal disease resulting in severe vision loss. RP have been extensively studied for pathogenetic mechanisms and treatments. Yet there is little information about alterations of RP associated proteins in phosphodiesterase 6 beta (Pde6b) mutated model. To explore the roles of RP causing proteins, we performed a label free quantitative mass spectrometry based proteomic analysis in rd10 mouse retinas. 3737 proteins were identified at the degenerative time points in rd10 mice. 222 and 289 differentially expressed proteins (DEPs) (fold change, FC > 2, p < 0.05) were detected at 5 and 8 weeks. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, visual perception and phototransduction were severely affected. The downregulated DEPs were significantly enriched in cilium assembly and protein localization. 25 decreased DEPs causing autosomal recessive/dominant retinitis pigmentosa were visualized by heatmaps. Protein-protein interaction network represented 13 DEPs interacted directly with Pde6b protein. 25 DEPs causing RP were involved in phototransduction, visual perception, response to stimulus, protein localization and cilium assembly pathways. The significantly reduced expressions of DEPs were further validated by quantitative reverse transcription polymerase chain reaction (qPCR), Western blots (WB) and immunohistochemistry (IHC). This study revealed the molecular mechanisms underlying early and late stage of RP, as well as changes of RP-causing proteins.
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Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6 , Modelos Animales de Enfermedad , Mutación , Proteómica , Retinitis Pigmentosa , Animales , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6/genética , Retinitis Pigmentosa/metabolismo , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/patología , Proteómica/métodos , Ratones , Proteínas del Ojo/metabolismo , Proteínas del Ojo/genética , Degeneración Retiniana/metabolismo , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Retina/metabolismo , Retina/patología , Mapas de Interacción de Proteínas , Proteoma/metabolismoRESUMEN
INTRODUCTION AND IMPORTANCE: Graft-versus-host disease (GvHD) is a rare but severe complication following liver transplantation (LT), occurring in 1-2 % of cases with a mortality rate exceeding 80 %. Immune checkpoint inhibitors (ICIs) used pretransplant are associated with increased allograft rejection risk, but their impact on GvHD in LT remains unclear. Dominant one-way donor-recipient human leukocyte antigen (HLA) matching is a known risk factor for GvHD. This report presents a rare case of fatal GvHD in a hepatocellular carcinoma (HCC) patient treated with PD-1 inhibitors before LT and transplanted with a liver graft from a deceased donor with donor-dominant one-way HLA matching. CASE PRESENTATION: A 59-year-old male with a 30-year history of hepatitis B and unresectable HCC underwent LT after receiving the last dose of PD-1 inhibitors 7 days prior to the transplant. On post-operative day (POD) 12, the patient developed a skin rash, fever, and vomiting, and was diagnosed with GvHD. Despite aggressive treatment, including high-dose corticosteroids and extracorporeal membrane oxygenation (ECMO), the patient succumbed to gastrointestinal bleeding and multi-organ failure on POD 30. HLA genotyping revealed typical donor-dominant one-way HLA matching. CLINICAL DISCUSSION: This case highlights a potential link between pretransplant exposure to ICIs and GvHD, particularly with donor-dominant one-way HLA matching. Residual anti-PD-1 antibodies may activate graft-resident immune cells, precipitating GvHD. Further research with larger cohorts and animal models is required to clarify this relationship and understand the underlying mechanisms. CONCLUSION: Besides allograft rejection, caution should also be exercised regarding GvHD in patients with prior exposure to ICIs before LT.
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The integration of visual simulation and biorehabilitation devices promises great applications for sustainable electronics, on-demand integration and neuroscience. However, achieving a multifunctional synergistic biomimetic system with tunable optoelectronic properties at the individual device level remains a challenge. Here, an electro-optically configurable transistor employing conjugated-polymer as semiconductor layer and an insulating polymer (poly(1,8-octanediol-co-citrate) (POC)) with clusterization-triggered photoactive properties as dielectric layer is shown. These devices realize adeptly transition from electrical to optical synapses, featuring multiwavelength and multilevel optical synaptic memory properties exceeding 3 bits. Utilizing enhanced optical memory, the images learning and memory function for visual simulation are achieved. Benefiting from rapid electrical response akin to biological muscle activation, increased actuation occurs under increased stimulus frequency of gate voltage. Additionally, the transistor on POC substrate can be effectively degraded in NaOH solution due to degradation of POC. Pioneeringly, the electro-optically configurability stems from light absorption and photoluminescence of the aggregation cluster in POC layer after 200 °C annealing. The enhancement of optical synaptic plasticity and integration of motion-activation functions within a single device opens new avenues at the intersection of optoelectronics, synaptic computing, and bioengineering.
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Currently, more and more lakes around the world are experiencing outbreaks of cyanobacterial blooms, and high-precision and rapid monitoring of the spatial distribution of algae in water bodies is an important task. Remote sensing technology is one of the effective means for monitoring algae in water bodies. Studies have shown that the Floating Algae Index (FAI) is superior to methods such as the Standardized Differential Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) in monitoring cyanobacterial blooms. However, compared to the NDVI method, the FAI method has difficulty in determining the threshold, and how to choose the threshold with the highest classification accuracy is challenging. In this study, FAI linear fitting model (FAI-L) is selected to solve the problem that FAI threshold is difficult to determine. Innovatively combine FAI index and NDVI index, and use NDVI index to find the threshold of FAI index. In order to analyze the applicability of FAI-L to extract cyanobacterial blooms, this paper selected multi-temporal Landsat8, HJ-1B, and Sentinel-2 remote sensing images as data sources, and took Chaohu Lake and Taihu Lake in China as research areas to extract cyanobacterial blooms. The results show that (1) the accuracy of extracting cyanobacterial bloom by FAI-L method is generally higher than that by NDVI and FAI. Under different data sources and different research areas, the average accuracy of extracting cyanobacterial blooms by FAI-L method is 95.13%, which is 6.98% and 18.43% higher than that by NDVI and FAI respectively. (2) The average accuracy of FAI-L method for extracting cyanobacterial blooms varies from 84.09 to 99.03%, with a standard deviation of 4.04, which is highly stable and applicable. (3) For simultaneous multi-source image data, the FAI-L method has the highest average accuracy in extracting cyanobacterial blooms, at 95.93%, which is 6.77% and 13.26% higher than NDVI and FAI methods, respectively. In this paper, it is found that FAI-L method shows high accuracy and stability in extracting cyanobacterial blooms, and it can extract the spatial distribution of cyanobacterial blooms well, which can provide a new method for monitoring cyanobacterial blooms.
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Cianobacterias , Monitoreo del Ambiente , Eutrofización , Lagos , Tecnología de Sensores Remotos , Cianobacterias/crecimiento & desarrollo , Monitoreo del Ambiente/métodos , Lagos/microbiología , China , Modelos LinealesRESUMEN
Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and Methicillin-resistant staphylococcus aureus (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the NF-κB signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior in vivo. The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF-κB. This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system.
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Liver transplantation (LT) is an ideal therapeutic option for selected patients with hepatocellular carcinoma (HCC). The selection criteria of HCC for LT have evolved in recent decades. Downstaging therapy is a promising strategy for patients with tumor burden beyond transplant criteria to increase the chance of receiving LT and improve posttransplant survival. Downstaging therapy is also a selection tool that refines the conventional selection criteria based on tumor morphology. Recently, the success of systemic treatment, including immune checkpoint inhibitors, antiangiogenic tyrosine kinase inhibitors, and VEGF inhibitors, in advanced HCC has prompted the discussion regarding the role of systemic therapies for HCC downstaging before transplantation. In this review, we aimed to summarize the current advances in selection criteria and therapeutic options of downstaging therapy for HCC before LT.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Selección de Paciente , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/terapia , Estadificación de NeoplasiasRESUMEN
Background: With the increasing application of large language models like ChatGPT in various industries, its potential in the medical domain, especially in standardized examinations, has become a focal point of research. Objective: The aim of this study is to assess the clinical performance of ChatGPT, focusing on its accuracy and reliability in the Chinese National Medical Licensing Examination (CNMLE). Methods: The CNMLE 2022 question set, consisting of 500 single-answer multiple choices questions, were reclassified into 15 medical subspecialties. Each question was tested 8 to 12 times in Chinese on the OpenAI platform from April 24 to May 15, 2023. Three key factors were considered: the version of GPT-3.5 and 4.0, the prompt's designation of system roles tailored to medical subspecialties, and repetition for coherence. A passing accuracy threshold was established as 60%. The χ2 tests and κ values were employed to evaluate the model's accuracy and consistency. Results: GPT-4.0 achieved a passing accuracy of 72.7%, which was significantly higher than that of GPT-3.5 (54%; P<.001). The variability rate of repeated responses from GPT-4.0 was lower than that of GPT-3.5 (9% vs 19.5%; P<.001). However, both models showed relatively good response coherence, with κ values of 0.778 and 0.610, respectively. System roles numerically increased accuracy for both GPT-4.0 (0.3%-3.7%) and GPT-3.5 (1.3%-4.5%), and reduced variability by 1.7% and 1.8%, respectively (P>.05). In subgroup analysis, ChatGPT achieved comparable accuracy among different question types (P>.05). GPT-4.0 surpassed the accuracy threshold in 14 of 15 subspecialties, while GPT-3.5 did so in 7 of 15 on the first response. Conclusions: GPT-4.0 passed the CNMLE and outperformed GPT-3.5 in key areas such as accuracy, consistency, and medical subspecialty expertise. Adding a system role insignificantly enhanced the model's reliability and answer coherence. GPT-4.0 showed promising potential in medical education and clinical practice, meriting further study.
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Evaluación Educacional , Licencia Médica , Humanos , China , Evaluación Educacional/métodos , Evaluación Educacional/normas , Reproducibilidad de los Resultados , Competencia Clínica/normasRESUMEN
OBJECTIVE: Complications or serious adverse events (SAEs) are common in the treatment of patients with large vessel occlusion stroke. There has been limited study of the impact of SAEs for patients after endovascular thrombectomy (EVT). The goal of this study was to characterize the rates and clinical impact of SAEs following EVT. METHODS: A post hoc analysis was performed using pooled databases of the "DEVT" and "RESCUE BT" trials. SAEs were designated as symptomatic intracranial hemorrhage, brain herniation or craniectomy, respiratory failure, circulatory failure, pneumonia, deep venous thrombosis, and systemic bleeding. The primary endpoint was functional independence (modified Rankin scale score 0-2 within 90 days). Logistic regression analysis was used to determine the predictors and associations between SAEs and outcomes. RESULTS: Of 1,182 enrolled patients, 402 (34%) had a procedural complication and 745 (63%) had 1,404 SAE occurrences with 4.65% in-hospital mortality. The three most frequent SAEs were pneumonia (620, 52.5%), systemic bleeding (174, 14.7%), and respiratory failure (173, 14.6%). Pneumonia, systemic bleeding, or deep venous thrombosis was less life-threatening. Patients with advanced age (adjusted odds ratio, 1.28 [95% confidence interval, 1.14-1.43]), higher NIHSS (1.09 [1.06-1.11]), occlusion site (middle cerebral artery-M1 vs. internal carotid artery [ICA]: 0.75 [0.53-1.04]; M2 vs. ICA: 1.30 [0.80-2.12]), longer procedure time (1.01 [1.00-1.01]), and unsuccessful vessel recanalization (1.79 [1.06-2.94]) were more likely to experience SAEs. Compared with no SAE, patients with SAEs had lower odds of functional independence (0.46 [0.40-0.54]). CONCLUSIONS: Overall, SAEs diagnosed following thrombectomy in patients with stroke were common (more than 60%) and associated with functional dependence. Patients with advanced age, higher NIHSS, longer procedure time, and failed recanalization were more likely to experience SAEs. There was no statistical difference in the risk of SAEs among patients with M1 and M2 occluded compared with those ICA occluded. An understanding of the prevalence and predictors of SAEs could alert clinicians to the estimated risk of an SAE for a patient after EVT.
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Aspartic proteases (APs) constitute a large family in plants and are widely involved in diverse biological processes, like chloroplast metabolism, biotic and abiotic stress responses, and reproductive development. In this study, we focused on overall analysis of the APs genes in tobacco. Our analysis included the phylogeny and cis-elements in the cell wall-associated promoters of these genes. To characterize the expression patterns of APs genes in stem vascular development. The tissue expression analysis showed that NtAED3-like was preferentially expressed in the differentiating xylem and phloem cells of the vascular system. Based on histochemical staining analysis showed that the NtAED3-like gene was specifically expressed in stem vascular tissue, root vascular tissue, and petiole vascular tissue. The TdT-mediated dUTP nick-end labeling (TUNEL) assay illustrated a delayed progression of programmed cell death (PCD) within the xylem of the ko-ntaed3a-like mutant, relative to the wild type. The mutant ko-ntaed3a-like exhibited a phenotype of thinning stem circumference and changed in xylem structure and lignin content. In addition, the two-dimension heteronuclear single quantum coherent nuclear magnetic resonance (2D-HSQC) analysis of three milled wood lignins (MWLs) showed that the content of ß-O-4 connection in ko-ntaed3a-like decreased slightly compared with wild type. In conclusion, this study provides our understanding of the regulation of vascular tissue development by the NtAED3-like gene in tobacco and provides a better basis for determining the molecular mechanism of the aspartic protease in secondary cell wall (SCW) development.