RESUMEN
OBJECTIVES: The combined impact of sleep quality and diet habits on ischemic stroke remains unclear, particularly in rural populations. Therefore, this study aimed to estimate the individual and joint associations of sleep quality and diet habits with nonfatal ischemic stroke among rural adults. METHODS: A total of 22â536 participants free of stroke were enrolled from the Henan Rural Cohort. Sleep quality and diet habits were evaluated with the Pittsburgh Sleep Quality Index and food frequency questionnaire, respectively. The ischemic stroke incidence was analyzed using Kaplan-Meier curves. Cox regression and restricted cubic spline were employed to estimate the correlation of sleep quality or diet habits with ischemic stroke. RESULTS: During an average 3.92 y of follow-up, 665 ischemic stroke patients were identified. The adjusted hazard ratio (95% confidence interval) of ischemic stroke risk compared with good sleep quality was 1.276 (1.057-1.542). The hazard ratio (95% confidence interval) of nonfatal ischemic stroke compared with unhealthy diet habits was 0.693 (0.589-0.814). The restricted cubic spline indicated that the risk of ischemic stroke increased with the increase of the Pittsburgh Sleep Quality Index. And the higher the diet quality score, the lower the risk of ischemic stroke. (Ptrend < 0.05). Further analysis indicated that the association of poor sleep quality with ischemic stroke was alleviated by healthy diet habits (P < 0.05). Additionally, a robust correlation remained after excluding individuals with ischemic stroke in the first year. CONCLUSIONS: Poor sleep quality was positively associated with nonfatal ischemic stroke among rural adults, and healthy diet habits attenuated this relationship. Developing healthy diet and sleep habits may have potential health implications for preventing ischemic stroke. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (registration no. ChiCTR-OOC-15006699). Date of registration: July 6, 2015.
RESUMEN
Fibrosis refers to the progressive tissue lesion process characterized by excessive secretion and deposition of extracellular matrix (ECM). Abnormal fibrous tissue deposition distorts tissue architecture and leads to the progressive loss of organ function. Notably, fibrosis is one of the primary pathological appearances of many end stage illnesses, and is considered as a lethal threat to human health, especially in the elderly with ageing-related diseases. CX3C ligand 1 (CX3CL1) is the only member of chemokine CX3C and binds specifically to CX3C receptor 1 (CX3CR1). Different from other chemokines, CX3CL1 possesses both chemotactic and adhesive activity. CX3CL1/CX3CR1 axis involves in various physiological and pathological processes, and exerts a critical role in cells from the immune system, vascular system, and nervous system etc. Notably, increasing evidence has demonstrated that CX3CL1/CX3CR1 signaling pathway is closely related to the pathological process of fibrosis in multiple tissue and organs. We reviewed the crucial role of CX3CL1/CX3CR1 axis in fibrosis and ageing and systematically summarized the underlying mechanism, which offers prospective strategies of targeting CX3C for the therapy of fibrosis and ageing-related diseases.
RESUMEN
DUX4 has been widely reported in facioscapulohumeral muscular dystrophy, but its role in Duchenne muscular dystrophy (DMD) is unclear. Dux is the mouse paralog of DUX4. In Dux-/- mdx mice, forelimb grip strength test and treadmill test were performed, and extensor digitorum longus (EDL) contraction properties were measured to assess skeletal muscle function. Pathological changes in mice were determined by serum CK and LDH levels and muscle Masson staining. Inflammatory factors, oxidative stress, and mitochondrial function indicators were detected using kits. Primary muscle satellite cells were isolated, and the antioxidant molecule Nrf2 was detected. MTT assay and Edu assay were used to evaluate proliferation and TUNEL assay for cell death. The results show that the deletion of Dux enhanced forelimb grip strength and EDL contractility, prolonged running time and distance in mdx mice. Deleting Dux also attenuated muscle fibrosis, inflammation, oxidative stress, and mitochondrial dysfunction in mdx mice. Furthermore, Dux deficiency promoted proliferation and survival of muscle satellite cells by increasing Nrf2 levels in mdx mice.
Asunto(s)
Proteínas de Homeodominio , Distrofia Muscular de Duchenne , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Animales , Masculino , Ratones , Eliminación de Gen , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Ratones Endogámicos C57BL , Ratones Endogámicos mdx , Ratones Noqueados , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patología , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Células Satélite del Músculo Esquelético/metabolismoRESUMEN
Introduction: The treatment of skip-level cervical degenerative disease (CDD) with no degenerative changes observed in the intervening segment (IS) is complicated. This research aims to provide a reference basis for selecting treatment approaches for noncontiguous CDD. Methods: To establish accurate finite element models (FEMs), this study included computed tomography (CT) data from 21 patients with CDD (10 males and 11 females) for modeling. The study primarily discusses four cross-segment surgical approaches: upper (C3/4) anterior cervical discectomy and fusion (ACDF) and lower (C5/6) cervical disc arthroplasty (CDA), FA model; upper CDA (C3/4) and lower ACDF (C5/6), AF model; upper ACDF (C3/4) and lower ACDF (C5/6), FF model; upper CDA (C3/4) and lower CDA (C5/6), AA model. An initial axial load of 73.6 N was applied at the motion center using the follower load technique. A moment of 1.0 Nm was applied at the center of the C2 vertebra to simulate the overall motion of the model. The statistical analysis was conducted using STATA version 14.0. Statistical significance was defined as a p value less than 0.05. Results: The AA group had significantly greater ROM in flexion and axial rotation in other segments compared to the FA group (p < 0.05). The FA group consistently exhibited higher average intervertebral disc pressure in C2/3 during all motions compared to the AF group (p < 0.001); however, the FA group displayed lower average intervertebral disc pressure in C6/7 during all motions (p < 0.05). The AA group had lower facet joint contact stresses during extension in all segments compared to the AF group (p < 0.05). The FA group exhibited significantly higher facet joint contact stresses during extension in C2/3 (p < 0.001) and C6/7 (p < 0.001) compared to the AF group. Discussion: The use of skip-level CDA is recommended for the treatment of non-contiguous CDD. The FA construct shows superior biomechanical performance compared to the AF construct.
RESUMEN
Healthy alveolar bone is the cornerstone of oral function and oral treatment. Alveolar bone is highly dynamic during the entire lifespan and is affected by both systemic and local factors. Importantly, alveolar bone is subjected to unique occlusal force in daily life, and mechanical force is a powerful trigger of bone remodeling, but the effect of occlusal force in maintaining alveolar bone mass remains ambiguous. In this study, the Piezo1 channel is identified as an occlusal force sensor. Activation of Piezo1 rescues alveolar bone loss caused by a loss of occlusal force. Moreover, we identify Piezo1 as the mediator of occlusal force in osteoblasts, maintaining alveolar bone homeostasis by directly promoting osteogenesis and by sequentially regulating catabolic metabolism through Fas ligand (FasL)-induced osteoclastic apoptosis. Interestingly, Piezo1 activation also exhibits remarkable efficacy in the treatment of alveolar bone osteoporosis caused by estrogen deficiency, which is highly prevalent among middle-aged and elderly women. Promisingly, Piezo1 may serve not only as a treatment target for occlusal force loss-induced alveolar bone loss but also as a potential target for metabolic bone loss, especially in older patients.
Daily occlusal force and estrogen synergistically maintain alveolar bone homeostasis. PIEZO1 in osteoblasts plays a critical role in sensing occlusal force and maintaining bone mass. PIEZO1 may promote osteoclastic apoptosis through osteoblast-secreted FasL through a PIEZO1-STAT3/ESR1-FasL pathway. Restoration of occlusal force with dental therapies as early as possible to prevent alveolar bone loss is the major priority in oral health care. PIEZO1 may serve as a potential target for bone metabolism disorders.
Asunto(s)
Homeostasis , Canales Iónicos , Animales , Femenino , Canales Iónicos/metabolismo , Ratones , Fuerza de la Mordida , Osteogénesis , Humanos , Osteoblastos/metabolismo , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/patología , Apoptosis , Osteoclastos/metabolismoRESUMEN
Spinal fusions are performed to treat congenital skeletal malformations, spondylosis, degenerative disk diseases, and other pathologies of the vertebrae that can be resolved by reducing motion between neighboring vertebrae. Unfortunately, up to 100,000 fusion procedures fail per year in the United States, suggesting that efforts to develop new approaches to improve spinal fusions are justified. We have explored whether the use of an osteotropic oligopeptide to target an attached bone anabolic agent to the fusion site might be exploited to both accelerate the mineralization process and improve the overall success rate of spinal fusions. The data presented below demonstrate that subcutaneous administration of a modified abaloparatide conjugated to 20 mer of D-glutamic acid not only localizes at the spinal fusion site but also outperforms the standard of care (topically applied BMP2) in both speed of mineralization (p < 0.05) and overall fusion success rate (p < 0.05) in a posterior lateral spinal fusion model in male and female rats, with no accompanying ectopic mineralization. Because the bone-localizing conjugate can be administered ad libitum post-surgery, and since the procedure appears to improve on standard of care, we conclude that administration of a bone-homing anabolic agent for improvement of spinal fusion surgeries warrants further exploration.
RESUMEN
OBJECTIVES: To develop a radiomics model based on diffusion-weighted imaging (DWI) utilizing automated machine learning method to differentiate cerebral cystic metastases from brain abscesses. MATERIALS AND METHODS: A total of 186 patients with cerebral cystic metastases (n = 98) and brain abscesses (n = 88) from two clinical institutions were retrospectively included. The datasets (129 from institution A) were randomly portioned into separate 75% training and 25% internal testing sets. Radiomics features were extracted from DWI images using two subregions of the lesion (cystic core and solid wall). A thorough image preprocessing method was applied to DWI images to ensure the robustness of radiomics features before feature extraction. Then the Tree-based Pipeline Optimization Tool (TPOT) was utilized to search for the best optimized machine learning pipeline, using a fivefold cross-validation in the training set. The external test set (57 from institution B) was used to evaluate the model's performance. RESULTS: Seven distinct TPOT models were optimized to distinguish between cerebral cystic metastases and abscesses either based on different features combination or using wavelet transform. The optimal model demonstrated an AUC of 1.00, an accuracy of 0.97, sensitivity of 1.00, and specificity of 0.93 in the internal test set, based on the combination of cystic core and solid wall radiomics signature using wavelet transform. In the external test set, this model reached 1.00 AUC, 0.96 accuracy, 1.00 sensitivity, and 0.93 specificity. CONCLUSION: The DWI-based radiomics model established by TPOT exhibits a promising predictive capacity in distinguishing cerebral cystic metastases from abscesses.
Asunto(s)
Absceso Encefálico , Neoplasias Supratentoriales , Humanos , Radiómica , Estudios Retrospectivos , Absceso Encefálico/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Aprendizaje AutomáticoRESUMEN
INTRODUCTION: The biosynthesis of tumor-associated sialoglycans involves Sialyltransferases expressed in cancer cells differentially. The current review aspires to bridge the existing knowledge gaps by consolidating evidence regarding the role of Sialyltransferases in gynecological malignant tumors (ovarian, cervix, endometrial, and breast). METHODS: In this systematic review, we searched databases, including PubMed, Embase, Web of Science, Scopus and Cochrane Library. Twenty-two high-quality articles were selected out of 559 researched studies using radiomics quality score (RQS) tools. RESULTS: Our findings indicated that 7 articles were related to Sialyltransferases in ovarian cancer, in which 6 studies was examined only ST6Gal-I and one study examined the ST3Gal-I, ST3Gal-II, ST3Gal-III, ST3Gal-IV, ST3Gal-VI, and ST3Gal-6. In addition, 5 articles were related to Sialyltransferases in cervix cancer (ST6Gal-I), 3 articles to endometrial cancer (ST6Gal-I, ST3Gal-III, ST3Gal-IV, and ST3Gal-6), and 7 articles to breast cancer (ST6Gal-I gene in 5 studies, ST6GAL-II gene in one study, and ST8SIA1 and ST3GAL-V genes in one study). CONCLUSION: ST6Gal-I gene expression occurs at a high speed in ovarian, cervix, endometrial, and breast cancers, leading to metastasis to distant cells, cell destruction, cell invasion, and reduced patient survival.
Asunto(s)
Neoplasias de la Mama , Neoplasias de los Genitales Femeninos , Neoplasias Ováricas , Neoplasias del Cuello Uterino , Femenino , Humanos , Sialiltransferasas/genética , Sialiltransferasas/metabolismo , Neoplasias del Cuello Uterino/patología , Cuello del Útero/patologíaRESUMEN
Aging negatively affects B cell production, resulting in a decrease in B-1 and B-2 cells and impaired antibody responses. Age-related B cell subsets contribute to inflammation. Investigating age-related alterations in the B-cell pool and developing targeted therapies are crucial for combating autoimmune diseases in the elderly. Additionally, optimal nutrition, including carbohydrates, amino acids, vitamins, and especially lipids, play a vital role in supporting immune function and mitigating the age-related decline in B cell activity. Research on the influence of lipids on B cells shows promise for improving autoimmune diseases. Understanding the aging B-cell pool and considering nutritional interventions can inform strategies for promoting healthy aging and reducing the age-related disease burden.
Asunto(s)
Envejecimiento , Enfermedades Autoinmunes , Humanos , Anciano , Linfocitos B , Vitaminas , LípidosRESUMEN
BACKGROUND: The selective recognition of drugs and its metabolism or decomposition products is significant to drug development and drug resistance research. Fluorescence-based techniques provide satisfying sensitivity by target-triggered chemical reaction. However, the interference from the matrix or additives usually restricts the specific detection. It is highly desirable to explore specific chemical reactions for achieving selective perception of these species. RESULTS: We report a specific m-aminophenol (MAP)-dopamine (DA) reaction, which generates highly fluorescent azamonardine-like products. Based on this reaction, fluorometric and indirect detection of p-aminosalicylic acid (typical antituberculosis drug, PAS) can be realized using the DA-based probe with high sensitivity. The acid induces the decarboxylation of PAS and produces MAP, which reacts with DA and generates fluorescent azamonardine-like products. The practical application of the proposed method is validated by the accurate PAS analysis in urine samples and Pasinazid tablets. Interestingly, none of additives in the Pasinazid tablets contribute comparable fluorescence variation. SIGNIFICANCE: This work discovers a new MAP-DA reaction for the first time, it not only explores sensitive PAS drug detection probe, but also demonstrates the feasibility of the development of novel drug analysis platform by recognizing decomposition product with specific reaction. Thus, new avenues for the exploration of simple and rapid spectrophotometric probes toward various drug analytes with high specify and sensitivity based on this tactic might be possible in analytical and drug-related fields.
Asunto(s)
Ácido Aminosalicílico , Dopamina , Espectrofotometría , Fluorometría , Bioensayo , ColorantesRESUMEN
An electrocatalyst of single-atomic Mn sites with MnP nanoparticles (NPs) on N, P co-doped carbon substrate was constructed to enhance the catalytic activity of oxygen reduction reaction (ORR) through one-pot in situ doping-phosphatization strategy. The optimized MnSA-MnP-980â catalyst exhibits an excellent ORR activity in KOH electrolyte with a half-wave potential (E1/2) of 0.88 V (vs. RHE), and the ORR current density of MnSA-MnP-980â maintained 97.9 % for over 25000 s chronoamperometric i-t measurement. When using as the cathode, the MnSA-MnP-980â displays a peak power density of 51 mW cm-2 in Zinc-Air batteries, which observably outperformed commercial Pt/C (20 wt%). The X-ray photoelectron spectroscopy reveal that the doped P atoms with a strong electron-donating effectively enhances electron cloud density of Mn SAs sites, facilitating the adsorption of O2 molecules. Meanwhile, the introduction of MnP NPs can regulate the electronic structure of Mn SAs sites, making Mn SAs active sites exist in a low oxidation state and are less positively charged, which can supply electrons for ORR process to narrow the adsorption energy barrier of ORR intermediates. This work constructs novel active sites with excellent ORR properties and provides valuable reference for the development of practical application.
RESUMEN
RNA ac4C modification is a novel and rare chemical modification observed in mRNA. Traditional biochemical studies had primarily associated ac4C modification with tRNA and rRNA until in 2018, Arango D et al. first reported the presence of ac4C modification on mRNA and demonstrated its critical role in mRNA stability and translation regulation. Furthermore, they established that the ac4C modification on mRNA is mediated by the classical N-acetyltransferase NAT10. Subsequent studies have underscored the essential implications of NAT10 and mRNA ac4C modification across both physiological and pathological regulatory processes. In this review, we aimed to explore the discovery history of RNA ac4C modification, its detection methods, and its regulatory mechanisms in disease and physiological development. We offer a forward-looking examination and discourse concerning the employment of RNA ac4C modification as a prospective therapeutic strategy across diverse diseases. Furthermore, we comprehensively summarize the functions and mechanisms of NAT10 in gene expression regulation and pathogenesis independent of RNA ac4C modification.
Asunto(s)
Mamíferos , Acetiltransferasas N-Terminal , Animales , Humanos , ARN Mensajero , Mamíferos/genéticaRESUMEN
Overactivated inflammatory reactions hinder the bone regeneration process. Timely transformation of microenvironment from pro-inflammatory to anti-inflammatory after acute immune response is favorable for osteogenesis. Macrophages play an important role in the immune response to inflammation. Therefore, this study adopts TIM3 high expression extracellular vesicles (EVs) with immunosuppressive function to reshape the early immune microenvironment of bone injury, mainly by targeting macrophages. These EVs can be phagocytosed by macrophages, thereby increasing the infiltration of TIM3-positive macrophages (TIM3+ macrophages) and M2 subtypes. The TIM3+ macrophage group has some characteristics of M2 macrophages and secretes cytokines, such as IL-10 and TGF-ß1 to regulate inflammation. TIM3, which is highly expressed in the engineered EVs, mediates the release of anti-inflammatory cytokines by inhibiting the p38/MAPK pathway and promotes osseointegration by activating the Bmp2 promoter to enhance macrophage BMP2 secretion. After evenly loading the engineered EVs into the hydrogel, the continuous and slow release of EVsTIM3OE recruits more anti-inflammatory macrophages during the early stages of bone defect repair, regulating the immune microenvironment and eliminating the adverse effects of excessive inflammation. In summary, this study provides a new strategy for the treatment of refractory wounds through early inflammation control.
RESUMEN
Three-dimensional (3D) printing is an advanced pharmaceutical manufacturing technology, and concerted efforts are underway to establish its applicability to various industries. However, for any technology to achieve widespread adoption, robustness and reliability are critical factors. Machine vision (MV), a subset of artificial intelligence (AI), has emerged as a powerful tool to replace human inspection with unprecedented speed and accuracy. Previous studies have demonstrated the potential of MV in pharmaceutical processes. However, training models using real images proves to be both costly and time consuming. In this study, we present an alternative approach, where synthetic images were used to train models to classify the quality of dosage forms. We generated 200 photorealistic virtual images that replicated 3D-printed dosage forms, where seven machine learning techniques (MLTs) were used to perform image classification. By exploring various MV pipelines, including image resizing and transformation, we achieved remarkable classification accuracies of 80.8%, 74.3%, and 75.5% for capsules, tablets, and films, respectively, for classifying stereolithography (SLA)-printed dosage forms. Additionally, we subjected the MLTs to rigorous stress tests, evaluating their scalability to classify over 3000 images and their ability to handle irrelevant images, where accuracies of 66.5% (capsules), 72.0% (tablets), and 70.9% (films) were obtained. Moreover, model confidence was also measured, and Brier scores ranged from 0.20 to 0.40. Our results demonstrate promising proof of concept that virtual images exhibit great potential for image classification of SLA-printed dosage forms. By using photorealistic virtual images, which are faster and cheaper to generate, we pave the way for accelerated, reliable, and sustainable AI model development to enhance the quality control of 3D-printed medicines.
RESUMEN
Cellular activities are carried out vastly by protein complexes but large repertoire of protein complexes remains functionally uncharacterized which necessitate new strategies to delineate their roles in various cellular processes and diseases. Thermal proximity co-aggregation (TPCA) is readily deployable to characterize protein complex dynamics in situ and at scale. We develop a version termed Slim-TPCA that uses fewer temperatures increasing throughputs by over 3X, with new scoring metrics and statistical evaluation that result in minimal compromise in coverage and detect more relevant complexes. Less samples are needed, batch effects are minimized while statistical evaluation cost is reduced by two orders of magnitude. We applied Slim-TPCA to profile K562 cells under different duration of glucose deprivation. More protein complexes are found dissociated, in accordance with the expected downregulation of most cellular activities, that include 55S ribosome and respiratory complexes in mitochondria revealing the utility of TPCA to study protein complexes in organelles. Protein complexes in protein transport and degradation are found increasingly assembled unveiling their involvement in metabolic reprogramming during glucose deprivation. In summary, Slim-TPCA is an efficient strategy for characterization of protein complexes at scale across cellular conditions, and is available as Python package at https://pypi.org/project/Slim-TPCA/ .
Asunto(s)
Glucosa , RibosomasRESUMEN
Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes, neural cells, myocytes, cardiomyocytes, adipocytes, endothelial cells, melanocytes, and hepatocytes. Odontoblastic differentiation of DMSCs is pivotal in dentinogenesis, a delicate and dynamic process regulated at the molecular level by signaling pathways, transcription factors, and posttranscriptional and epigenetic regulation. Mutations or dysregulation of related genes may contribute to genetic diseases with dentin defects caused by impaired odontoblastic differentiation, including tricho-dento-osseous (TDO) syndrome, X-linked hypophosphatemic rickets (XLH), Raine syndrome (RS), hypophosphatasia (HPP), Schimke immuno-osseous dysplasia (SIOD), and Elsahy-Waters syndrome (EWS). Herein, recent progress in the molecular regulation of the odontoblastic differentiation of DMSCs is summarized. In addition, genetic syndromes associated with disorders of odontoblastic differentiation of DMSCs are discussed. An improved understanding of the molecular regulation and related genetic syndromes may help clinicians better understand the etiology and pathogenesis of dentin lesions in systematic diseases and identify novel treatment targets.
RESUMEN
The alveolar bone, with a high turnover rate, is the most actively-remodeling bone in the body. Orthodontic tooth movement (OTM) is a common artificial process of alveolar bone remodeling in response to mechanical force, but the underlying mechanism remains elusive. Previous studies have been unable to reveal the precise mechanism of bone remodeling in any time and space due to animal model-related restrictions. The signal transducer and activator of transcription 3 (STAT3) is important in bone metabolism, but its role in osteoblasts during OTM is unclear. To provide in vivo evidence that STAT3 participates in OTM at specific time points and in particular cells during OTM, we generated a tamoxifen-inducible osteoblast lineage-specific Stat3 knockout mouse model, applied orthodontic force, and analyzed the alveolar bone phenotype. Micro-computed tomography (Micro-CT) and stereo microscopy were used to access OTM distance. Histological analysis selected the area located within three roots of the first molar (M1) in the cross-section of the maxillary bone as the region of interest (ROI) to evaluate the metabolic activity of osteoblasts and osteoclasts, indicating the effect of orthodontic force on alveolar bone. In short, we provide a protocol for using inducible osteoblast lineage-specific Stat3 knockout mice to study bone remodeling under orthodontic force and describe methods for analyzing alveolar bone remodeling during OTM, thus shedding new light on skeletal mechanical biology.
Asunto(s)
Factor de Transcripción STAT3 , Técnicas de Movimiento Dental , Ratones , Animales , Ratones Noqueados , Factor de Transcripción STAT3/genética , Microtomografía por Rayos X , Remodelación Ósea , Modelos Animales de EnfermedadRESUMEN
Macrophage pyroptosis and related inflammatory responses play an important role in periodontitis. Kynurenic acid (KA) is hypothesized to have antiinflammatory potential, but whether KA can inhibit macrophage pyroptosis and the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) was used to induce pyroptosis in THP1derived macrophages. KA or ML385 was used to pretreat macrophages, after which, cell viability, NODlike receptor protein 3 (NLRP3) inflammasomerelated protein expression, oxidative stress levels and nuclear factor erythroid 2related factor 2 (NRF2) expression were measured. The results showed that KA improved the LPSinduced decrease in macrophage viability and lactate dehydrogenase release. KA prevented THP1 macrophage pyroptosis induced by LPS by reducing the expression of NLRP3, GasderminD, and Caspase1, and decreased the expression of inflammatory factors. KA suppressed NLRP3 inflammasome activation by inhibiting ROS overproduction and increasing Heme Oxygenase 1 and glutathione levels. Moreover, KA promoted NRF2 translocation from the cytoplasm to the nucleus. In addition, the antipyroptotic and antioxidant effects of KA were reversed by ML385 inhibition of NRF2. In the present study, it was found that KA significantly suppressed macrophage pyroptosis induced by LPS. It was further demonstrated that the antipyroptotic effects of KA were mediated by activation of the NRF2 pathway.
Asunto(s)
Inflamasomas , Ácido Quinurénico , Proteína con Dominio Pirina 3 de la Familia NLR , Inflamasomas/metabolismo , Ácido Quinurénico/farmacología , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
The problem of corrosion-induced discoloration and embrittlement in silverware is a significant concern for the long-term preservation of excavated archeological silver artifacts, even after thermal restoration. The key to addressing this issue lies in the meticulous selection and evaluation of corrosion inhibitors that possess targeted corrosion inhibition capabilities. This study focuses on the evaluation of corrosion inhibitors for archeological silver artifacts using scanning electrochemical cell microscopy (SECCM) and X-ray photoelectron spectroscopy (XPS). The researchers aimed to compare the inhibition effects of four corrosion inhibitors [1,2,3-benzotriazole (BTA), 2-mercaptobenzimidazole (MBI), 2-mercaptobenzothiazole (MBT), and 2-mercaptobenzoxazole (MBO)] on a simulated Ag-Cu alloy sample and understand their mechanisms. The results showed that MBT exhibited better corrosion inhibition for microstructural regions with higher silver content due to its ability to form stable chelation structures with Ag(I). MBO exhibited better corrosion inhibition for microstructural regions with higher copper content due to its strong affinity with Cu(I). The targeted corrosion inhibition ability for the ß-phase was ranked as MBO > BTA ≈ MBI > MBT, while for the α-phase the ranking was MBT > MBO > MBI > BTA. The study demonstrated the feasibility and capabilities of SECCM in the targeted screening of corrosion inhibitors for different compositions and microstructural regions in archeological metal artifacts. This study highlights the potential of SECCM in corrosion inhibitor research for archeological metal artifacts and wider applications in metal material corrosion protection.
RESUMEN
Background: Multi-center research has demonstrated that adopting Silva's pattern-based classification system (SPBC) enhances the clinical prognosis and facilitates hierarchical management of patients with endocervical adenocarcinomas (EAC). However, inconsistencies in SPBC can arise due to variations in pathologists' experience levels. Thus, the implementation of standardized decision-making tools becomes crucial to enhance the practicality of SPBC in clinical diagnosis and treatment. Methods: We enrolled a total of 90 patients with EAC in this study, of which 63 were assigned to the training group, and the remaining 27 were allocated to the validation group. To create and validate the prediction models for SPBC, we utilized a deep learning system (DLS) and calculated the area under the receiver operating characteristic curve (AUC). Results: In Silva pattern classification, ResNet50 achieved an average accuracy of 74.36% (63.64% for pattern A, 55.56% for pattern B, and 89.47% for pattern C respectively). Moreover, in test set, ResNet50 achieved an AUC of 0.69 for pattern A, 0.58 for pattern B, and 0.91 for pattern C. Conclusions: We successfully established a DLS for SPBC, which holds the potential to aid pathologists in accurately classifying patients with EAC.