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1.
Materials (Basel) ; 17(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38730922

RESUMEN

Hybrid bonded-bolted composite material interference connections significantly enhance the collaborative load-bearing capabilities of the adhesive layer and bolts, thus improving structural load-carrying capacity and fatigue life. So, these connections offer significant developmental potential and application prospects in aircraft structural assembly. However, interference causes damage to the adhesive layer and composite laminate around the holes, leading to issues with interface damage. In this study, we employed experimental and finite element methods. Initially, different interference-fit sizes were selected for bolt insertion to analyze the damage mechanism of the adhesive layer during interference-fit bolt installation. Subsequently, a finite element tensile model considering damage to the adhesive layer and composite laminate around the holes post-insertion was established. This study aimed to investigate damage in composite bonded-bolted hybrid joints, explore load-carrying rules and failure modes, and reveal the mechanisms of interference effects on structural damage and failure. The research results indicate that the finite element prediction model considering initial damage around the holes is more effective. As the interference-fit size increases, damage to the adhesive layer transitions from surface debonding to local cracking, while damage to the composite matrix shifts from slight compression failure to severe delamination and fiber-bending fracturing. The structural strength shows a trend of initially increasing and then decreasing, with the maximum strength observed at an interference-fit size of 1.1%.

2.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167215, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38714267

RESUMEN

Osteoarthritis (OA) is a prevalent joint degenerative disease, resulting in a significant societal burden. However, there is currently a lack of effective treatment option available. Previous studies have suggested that Botulinum toxin A (BONT/A), a macromolecular protein extracted from Clostridium Botulinum, may improve the pain and joint function in OA patients, but the mechanism remains elusive. This study was to investigate the impact and potential mechanism of BONT/A on OA in vivo and in vitro experiment. LPS increased the levels of ROS, Fe2+and Fe3+, as well as decreased GSH levels, the ratio of GSH / GSSH and mitochondrial membrane potential. It also enhanced the degeneration of extracellular matrix (ECM) and altered the ferroptosis-related protein expression in chondrocytes. BONT/A rescued LPS-induced decrease in collagen type II (Collagen II) expression and increase in matrix metalloproteinase 13 (MMP13), mitigated LPS-induced cytotoxicity in chondrocytes, abolished the accumulation of ROS and iron, upregulated GSH and the ratio of GSH/ GSSH, improved mitochondrial function, and promoted SLC7A11/GPX4 anti-ferroptosis system activation. Additionally, intra-articular injection of BONT/A inhibited the degradation of cartilage in OA model rats. This chondroprotective effect of BONT/A was reversed by erastin (a classical ferroptosis agonist) and enhanced by liproxstatin-1 (a classic ferroptosis inhibitor). Our research confirms that BONT/A alleviates the OA development by inhibiting the ferroptosis of chondrocytes, which revealed to be a potential therapeutic mechanism for BONT/A treating the OA.


Asunto(s)
Toxinas Botulínicas Tipo A , Condrocitos , Ferroptosis , Osteoartritis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Ferroptosis/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/patología , Animales , Toxinas Botulínicas Tipo A/farmacología , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Osteoartritis/patología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Ratas , Masculino , Lipopolisacáridos/farmacología , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Humanos
3.
Pharmacol Res ; 204: 107209, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38740147

RESUMEN

Considerable progress has recently been made in cancer immunotherapy, including immune checkpoint blockade, cancer vaccine, and adoptive T cell methods. The lack of effective targets is a major cause of the low immunotherapy response rate in colorectal cancer (CRC). Here, we used a proteogenomic strategy comprising immunopeptidomics, whole exome sequencing, and 16 S ribosomal DNA sequencing analyses of 8 patients with CRC to identify neoantigens and bacterial peptides that can serve as antitumor targets. This study directly identified several personalized neoantigens and bacterial immunopeptides. Immunoassays showed that all neoantigens and 5 of 8 bacterial immunopeptides could be recognized by autologous T cells. Additionally, T cell receptor (TCR) αß sequencing revealed the TCR repertoire of epitope-reactive CD8+ T cells. Functional studies showed that T cell receptor-T (TCR-T) could be activated by epitope pulsed lymphoblastoid cells. Overall, this study comprehensively profiled the CRC immunopeptidome, revealing several neoantigens and bacterial peptides with potential to serve as immunotherapy targets in CRC.

4.
Mol Cell Proteomics ; : 100784, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38735538

RESUMEN

Colorectal cancer (CRC) is characterized by high morbidity, high mortality, and limited response to immunotherapies. The peripheral immune system is an important component of tumor immunity, and enhancements of peripheral immunity help to suppress tumor progression. However, the functional alterations of the peripheral immune system in CRC are unclear. Here, we used mass spectrometry-based quantitative proteomics to establish a protein expression atlas for the peripheral immune system in CRC, including plasma and five types of immune cells (CD4+ T cells, CD8+ T cells, monocytes, natural killer cells, and B cells). Synthesizing the results of the multidimensional analysis, we observed an enhanced inflammatory phenotype in CRC, including elevated expression of plasma inflammatory proteins, activation of the inflammatory pathway in monocytes, and increased inflammation-related ligand-receptor interactions. Notably, we observed tumor effects on peripheral T cells, including altered cell subpopulation ratios and suppression of cell function. Suppression of CD4+ T cell function is mainly mediated by high expression levels of protein tyrosine phosphatases. Among them, the expression of protein tyrosine phosphatase receptor type J (PTPRJ) gradually increased with CRC progression; knockdown of PTPRJ in vitro could promote T cell activation, thereby enhancing peripheral immunity. We also found that the combination of leucine-rich α-2 glycoprotein 1 (LRG1) and apolipoprotein A4 (APOA4) had the best predictive ability for colorectal cancer and has the potential to be a biomarker. Overall, this study provides a comprehensive understanding of the peripheral immune system in CRC. It also offers insights regarding the potential clinical utilities of these peripheral immune characteristics as diagnostic indicators and therapeutic targets.

5.
Int J Mol Sci ; 25(7)2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38612472

RESUMEN

Birinapant, an antagonist of the inhibitor of apoptosis proteins, upregulates MHCs in tumor cells and displays a better tumoricidal effect when used in combination with immune checkpoint inhibitors, indicating that Birinapant may affect the antigen presentation pathway; however, the mechanism remains elusive. Based on high-resolution mass spectrometry and in vitro and in vivo models, we adopted integrated genomics, proteomics, and immunopeptidomics strategies to study the mechanism underlying the regulation of tumor immunity by Birinapant from the perspective of antigen presentation. Firstly, in HT29 and MCF7 cells, Birinapant increased the number and abundance of immunopeptides and source proteins. Secondly, a greater number of cancer/testis antigen peptides with increased abundance and more neoantigens were identified following Birinapant treatment. Moreover, we demonstrate the existence and immunogenicity of a neoantigen derived from insertion/deletion mutation. Thirdly, in HT29 cell-derived xenograft models, Birinapant administration also reshaped the immunopeptidome, and the tumor exhibited better immunogenicity. These data suggest that Birinapant can reshape the tumor immunopeptidome with respect to quality and quantity, which improves the presentation of CTA peptides and neoantigens, thus enhancing the immunogenicity of tumor cells. Such changes may be vital to the effectiveness of combination therapy, which can be further transferred to the clinic or aid in the development of new immunotherapeutic strategies to improve the anti-tumor immune response.


Asunto(s)
Presentación de Antígeno , Dipéptidos , Indoles , Masculino , Animales , Humanos , Terapia Combinada , Modelos Animales de Enfermedad
6.
Comput Biol Med ; 175: 108502, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38678943

RESUMEN

OBJECTIVES: Musculoskeletal (MSK) tumors, given their high mortality rate and heterogeneity, necessitate precise examination and diagnosis to guide clinical treatment effectively. Magnetic resonance imaging (MRI) is pivotal in detecting MSK tumors, as it offers exceptional image contrast between bone and soft tissue. This study aims to enhance the speed of detection and the diagnostic accuracy of MSK tumors through automated segmentation and grading utilizing MRI. MATERIALS AND METHODS: The research included 170 patients (mean age, 58 years ±12 (standard deviation), 84 men) with MSK lesions, who underwent MRI scans from April 2021 to May 2023. We proposed a deep learning (DL) segmentation model MSAPN based on multi-scale attention and pixel-level reconstruction, and compared it with existing algorithms. Using MSAPN-segmented lesions to extract their radiomic features for the benign and malignant classification of tumors. RESULTS: Compared to the most advanced segmentation algorithms, MSAPN demonstrates better performance. The Dice similarity coefficients (DSC) are 0.871 and 0.815 in the testing set and independent validation set, respectively. The radiomics model for classifying benign and malignant lesions achieves an accuracy of 0.890. Moreover, there is no statistically significant difference between the radiomics model based on manual segmentation and MSAPN segmentation. CONCLUSION: This research contributes to the advancement of MSK tumor diagnosis through automated segmentation and predictive classification. The integration of DL algorithms and radiomics shows promising results, and the visualization analysis of feature maps enhances clinical interpretability.


Asunto(s)
Neoplasias Óseas , Aprendizaje Profundo , Imagen por Resonancia Magnética , Humanos , Masculino , Persona de Mediana Edad , Femenino , Imagen por Resonancia Magnética/métodos , Anciano , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/clasificación , Algoritmos , Adulto , Interpretación de Imagen Asistida por Computador/métodos , Neoplasias de los Músculos/diagnóstico por imagen , Radiómica
7.
Nat Commun ; 15(1): 2033, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448427

RESUMEN

Constraining the electrochemical reactivity of free solvent molecules is pivotal for developing high-voltage lithium metal batteries, especially for ether solvents with high Li metal compatibility but low oxidation stability ( <4.0 V vs Li+/Li). The typical high concentration electrolyte approach relies on nearly saturated Li+ coordination to ether molecules, which is confronted with severe side reactions under high voltages ( >4.4 V) and extensive exothermic reactions between Li metal and reactive anions. Herein, we propose a molecular anchoring approach to restrict the interfacial reactivity of free ether solvents in diluted electrolytes. The hydrogen-bonding interactions from the anchoring solvent effectively suppress excessive ether side reactions and enhances the stability of nickel rich cathodes at 4.7 V, despite the extremely low Li+/ether molar ratio (1:9) and the absence of typical anion-derived interphase. Furthermore, the exothermic processes under thermal abuse conditions are mitigated due to the reduced reactivity of anions, which effectively postpones the battery thermal runaway.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38498765

RESUMEN

COVID-19, caused by the highly contagious SARS-CoV-2 virus, is distinguished by its positive-sense, single-stranded RNA genome. A thorough understanding of SARS-CoV-2 pathogenesis is crucial for halting its proliferation. Notably, the 3C- like protease of the coronavirus (denoted as 3CLpro) is instrumental in the viral replication process. Precise delineation of 3CLpro cleavage sites is imperative for elucidating the transmission dynamics of SARS-CoV-2. While machine learning tools have been deployed to identify potential 3CLpro cleavage sites, these existing methods often fall short in terms of accuracy. To improve the performances of these predictions, we propose a novel analytical framework, the Transformer and Deep Forest Fusion Model (TDFFM). Within TDFFM, we utilize the AAindex and the BLOSUM62 matrix to encode protein sequences. These encoded features are subsequently input into two distinct components: a Deep Forest, which is an effective decision tree ensemble methodology, and a Transformer equipped with a Multi-Level Attention Model (TMLAM). The integration of the attention mechanism allows our model to more accurately identify positive samples, thus enhancing the overall predictive performance. Evaluation on a test set demonstrates that our TDFFM achieves an accuracy of 0.955, an AUC of 0.980, and an F1-score of 0.367, substantiating the model's superior prediction capabilities.

9.
J Am Chem Soc ; 146(7): 4557-4569, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38345667

RESUMEN

Intelligent utilization of the anionic redox reaction (ARR) in Li-rich cathodes is an advanced strategy for the practical implementation of next-generation high-energy-density rechargeable batteries. However, due to the intrinsic complexity of ARR (e.g., nucleophilic attacks), the instability of the cathode-electrolyte interphase (CEI) on a Li-rich cathode presents more challenges than typical high-voltage cathodes. Here, we manipulate CEI interfacial engineering by introducing an all-fluorinated electrolyte and exploiting its interaction with the nucleophilic attack to construct a gradient CEI containing a pair of fluorinated layers on a Li-rich cathode, delivering enhanced interfacial stability. Negative/detrimental nucleophilic electrolyte decomposition has been efficiently evolved to further reinforce CEI fabrication, resulting in the construction of LiF-based indurated outer shield and fluorinated polymer-based flexible inner sheaths. Gradient interphase engineering dramatically improved the capacity retention of the Li-rich cathode from 43 to 71% after 800 cycles and achieved superior cycling stability in anode-free and pouch-type full cells (98.8% capacity retention, 220 cycles), respectively.

10.
Mol Cell Proteomics ; 23(1): 100691, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38072118

RESUMEN

T cells play the most pivotal roles in antitumor immunity; the T-cell proteome and the differentially expressed proteins in the tumor immune microenvironment have rarely been identified directly from the clinical samples, especially for tumors that lack effective immunotherapy targets, such as colorectal cancer (CRC). In this study, we analyzed the protein expression pattern of the infiltrating T cells isolated from CRC patients using quantitative proteomics. CD4+ and CD8+ T cells were isolated from clinical samples and labeled by tandem mass tag reagents, and the differentially expressed proteins were quantified by mass spectrometry. The T-cell proteome profiling revealed dysfunctions in these tumor-infiltrating T cells. Specifically, antitumor immunity was suppressed because of differentially expressed metal ion transporters and immunity regulators. For the first time, lipocalin-2 (LCN2) was shown to be significantly upregulated in CD4+ T cells. Quantitative proteomic analysis of LCN2-overexpressed Jurkat cells showed that LCN2 damaged T cells by changes in iron transport. LCN2 induced T-cell apoptosis by reducing cellular iron concentration; moreover, the iron that was transported to the tumor microenvironment aided tumor cell proliferation, promoting tumor development. Meanwhile, LCN2 also influenced tumor progression through immune cytokines and cholesterol metabolism. Our results demonstrated that LCN2 has immunosuppressive functions that can promote tumor development; therefore, it is a potential immunotherapy target for CRC.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias , Humanos , Apoptosis , Linfocitos T CD8-positivos/metabolismo , Proliferación Celular , Hierro/metabolismo , Lipocalina 2/metabolismo , Proteoma/metabolismo , Proteómica , Microambiente Tumoral
11.
Integr Environ Assess Manag ; 20(3): 875-887, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37849019

RESUMEN

Coordinated and stable development of economy-energy-environment (3E) systems represents a long-term strategy for the sustainable development of humankind. Following the research idea of "indicator system construction-3E system evaluation-obstacles identification-optimization management," this article innovatively constructs a multiangle and comparable methodology system for evaluation and optimized management of the 3E system and considers the core cities of three economic circles in China as cases for empirical research. The results show that all the coordination degree levels were of good or high quality, which was at the highest level in the country. The sustainability degree of the three cities showed an upward trend; of these, Beijing had the highest sustainability degree, followed by Guangzhou and Shanghai. Obstacle degree analysis shows that technology investment and energy factors were common factors hindering sustainable development of the 3E systems of the three cities, and each city also had its own unique factors that acted as obstacles. On this basis, this article formulates region-specific policy recommendations in order to provide a useful reference for top-level design for the government. Integr Environ Assess Manag 2024;20:875-887. © 2023 SETAC.

12.
Angew Chem Int Ed Engl ; 63(6): e202316790, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38116869

RESUMEN

Electrolyte engineering is a fascinating choice to improve the performance of Li-rich layered oxide cathodes (LRLO) for high-energy lithium-ion batteries. However, many existing electrolyte designs and adjustment principles tend to overlook the unique challenges posed by LRLO, particularly the nucleophilic attack. Here, we introduce an electrolyte modification by locally replacing carbonate solvents in traditional electrolytes with a fluoro-ether. By benefit of the decomposition of fluoro-ether under nucleophilic O-related attacks, which delivers an excellent passivation layer with LiF and polymers, possessing rigidity and flexibility on the LRLO surface. More importantly, the fluoro-ether acts as "sutures", ensuring the integrity and stability of both interfacial and bulk structures, which contributed to suppressing severe polarization and enhancing the cycling capacity retention from 39 % to 78 % after 300 cycles for the 4.8 V-class LRLO. This key electrolyte strategy with comprehensive analysis, provides new insights into addressing nucleophilic challenge for high-energy anionic redox related cathode systems.

13.
ACS Appl Mater Interfaces ; 15(48): 55570-55586, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38058105

RESUMEN

Recently, aqueous zinc-ion batteries (ZIBs) have become increasingly attractive as grid-scale energy storage solutions due to their safety, low cost, and environmental friendliness. However, severe dendrite growth, self-corrosion, hydrogen evolution, and irreversible side reactions occurring at Zn anodes often cause poor cyclability of ZIBs. This work develops a synergistic strategy to stabilize the Zn anode by introducing a molybdenum dioxide coating layer on Zn (MoO2@Zn) and Tween 80 as an electrolyte additive. Due to the redox capability and high electrical conductivity of MoO2, the coating layer can not only homogenize the surface electric field but also accommodate the Zn2+ concentration field in the vicinity of the Zn anode, thereby regulating Zn2+ ion distribution and inhibiting side reactions. MoO2 coating can also significantly enhance surface hydrophilicity to improve the wetting of electrolyte on the Zn electrode. Meanwhile, Tween 80, a surfactant additive, acts as a corrosion inhibitor, preventing Zn corrosion and regulating Zn2+ ion migration. Their combination can synergistically work to reduce the desolvation energy of hydrated Zn ions and stabilize the Zn anodes. Therefore, the symmetric cells of MoO2@Zn∥MoO2@Zn with optimal 1 mM Tween 80 additive in 1 M ZnSO4 achieve exceptional cyclability over 6000 h at 1 mA cm-2 and stability (>700 h) even at a high current density (5 mA cm-2). When coupling with the VO2 cathode, the full cell of MoO2@Zn∥VO2 shows a higher capacity retention (82.4%) compared to Zn∥VO2 (57.3%) after 1000 cycles at 5 A g-1. This study suggests a synergistic strategy of combining surface modification and electrolyte engineering to design high-performance ZIBs.

14.
Mol Neurobiol ; 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38038880

RESUMEN

Cerebral ischemia, also known as ischemic stroke, accounts for nearly 85% of all strokes and is the leading cause of disability worldwide. Due to disrupted blood supply to the brain, cerebral ischemic injury is trigged by a series of complex pathophysiological events including excitotoxicity, oxidative stress, inflammation, and cell death. Currently, there are few treatments for cerebral ischemia owing to an incomplete understanding of the molecular and cellular mechanisms. Accumulated evidence indicates that various types of programmed cell death contribute to cerebral ischemic injury, including apoptosis, ferroptosis, pyroptosis and necroptosis. Among these, necroptosis is morphologically similar to necrosis and is mediated by receptor-interacting serine/threonine protein kinase-1 and -3 and mixed lineage kinase domain-like protein. Necroptosis inhibitors have been shown to exert inhibitory effects on cerebral ischemic injury and neuroinflammation. In this review, we will discuss the current research progress regarding necroptosis in cerebral ischemia as well as the application of necroptosis inhibitors for potential therapeutic intervention in ischemic stroke.

15.
Int J Mol Sci ; 24(21)2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37958984

RESUMEN

Metastasis leads to a high mortality rate in colorectal cancer (CRC). Increased neutrophil extracellular traps (NETs) formation is one of the main causes of metastasis. However, the mechanism of NETs-mediated metastasis remains unclear and effective treatments are lacking. In this study, we found neutrophils from CRC patients have enhanced NETs formation capacity and increased NETs positively correlate with CRC progression. By quantitative proteomic analysis of clinical samples and cell lines, we found that decreased secreted protein acidic and rich in cysteine (SPARC) results in massive NETs formation and integrin α5ß1 is the hub protein of NETs-tumor cell interaction. Mechanistically, SPARC regulates the activation of the nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) pathway by interacting with the receptor for activated C kinase 1 (RACK1). Over-activated NADPH oxidase generates more reactive oxygen species (ROS), leading to the release of NETs. Then, NETs upregulate the expression of integrin α5ß1 in tumor cells, which enhances adhesion and activates the downstream signaling pathways to promote proliferation and migration. The combination of NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) and integrin α5ß1 inhibitor ATN-161 (Ac-PHSCN-NH2) effectively suppresses tumor progression in vivo. Our work reveals the mechanistic link between NETs and tumor progression and suggests a combination therapy against NETs-mediated metastasis for CRC.


Asunto(s)
Neoplasias Colorrectales , Trampas Extracelulares , Humanos , Trampas Extracelulares/metabolismo , NADPH Oxidasas/metabolismo , Integrina alfa5beta1/metabolismo , Osteonectina/metabolismo , Proteómica , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Colorrectales/patología
16.
Mol Cell Biochem ; 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37943469

RESUMEN

Survival of olfactory mucosal mesenchymal stem cells (OM-MSCs) remains the low level in the cerebral microenvironment during intracerebral hemorrhage (ICH). This article aims to reveal the differential expression profile of ICH-stimulated OM-MSCs based on whole transcriptome sequence analysis. OM-MSCs were isolated from 6-week C57BL/6 mice. Morphology and surface markers of OM-MSCs were investigated by light microscope and flow cytometry, respectively. OM-MSCs were incubated with 20 U/mL thrombin for 24 h to mimic ICH-induced injury in vitro. Total RNA was extracted for whole transcriptome sequencing and qPCR. OM-MSCs were characterized by negative for CD45 and CD34, and positive for CD44, CD90 and CD29. Thrombin led to decrease in cell viability and increase in senescence and apoptosis in OM-MSCs. In total, 736 lncRNAs (upregulated: 393; downregulated: 343), 21 miRNAs (upregulated: 7; downregulated: 14) and 807 mRNAs (upregulated: 422; downregulated: 385) were identified. GO and KEGG pathways were enriched in protein heterodimerization activity, trans-synaptic signaling, membrane pathway, alcohol metabolic process, organic hydroxy compound biosynthesis process, secondary alcohol metabolic process, alcoholism, neutrophil extracellular trap formation, systemic lupus erythematosus, metabolic process, steroid biosynthesis and drug metabolism-cytochrome P450. 200 lncRNA-miRNA-mRNA were predicted in thrombin-induced OM-MSCs. Based on qPCR, we validated COMMD1B, MOAP1, lncRNA CAPN15, lncRNA ALDH1L2, miR-3473b and miR-1964-3p were upregulated in thrombin-stimulated OM-MSCs, and GM20431, lncRNA GAPDH and miR-122b-3p were downregulated. Our findings provide novel understanding for thrombin-induced injury in OM-MSCs. Differently-expressed RNAs can be the targets of improving therapeutic application of OM-MSCs.

17.
Cell Mol Biol (Noisy-le-grand) ; 69(9): 234-238, 2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37807306

RESUMEN

To uncover the potential effect of Perindopril on cardiac fibrosis caused by pressure overload and the underlying mechanism. Cardiac fibrosis model in mice was established by TAC method. Mice were assigned into sham group, TAC group, 2 mg/kg Perindopril group (Per (2 mg/kg)) and 8 mg/kg Perindopril group (Per (8 mg/kg)). Cardiac structure changes were assessed by measuring HW/BW, HW/TBL, LW/BW and LW/TBL in each group. Echocardiography was performed to assess mouse cardiac function by recording EF, LVIDd, IVSd and LVPWd. Relative levels of fibrosis markers were determined. AngII content was examined by ELISA. Besides, mRNA levels of key genes in the AngII/AT1R pathway were finally detected. TAC induced cardiac insufficiency, left ventricular dilatation, cardiac hypertrophy and myocardial collagen deposition in mice. In addition, fibrosis markers were upregulated in mice of TAC group. Perindopril markedly reversed TAC-induced pathological changes in cardiac structure and function of mice. Meanwhile, Perindopril dose-dependently reversed the upregulated genes in the AngII/AT1R pathway. Perindopril improves cardiac fibrosis induced by pressure overload through activating the AngII/AT1R pathway.


Asunto(s)
Cardiomiopatías , Perindopril , Ratones , Animales , Perindopril/farmacología , Perindopril/uso terapéutico , Corazón , Cardiomegalia/patología , Cardiomiopatías/metabolismo , Miocardio/metabolismo , Fibrosis , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
18.
Phys Med Biol ; 68(20)2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37757848

RESUMEN

Objective. There has been a considerable amount of computer-aided diagnosis (CAD) methods highlighted in the field of ultrasonic examination (USE) of thyroid nodules. However, few researches focused on the automatic risk classification, which was the basis for determining whether fine needle aspiration (FNA) was needed. The aim of this work was to implement automatic risk level assessment of thyroid nodules.Approach. Firstly, 1862 cases of thyroid nodules with the results of USE and FNA were collected as the dataset. Then, an improved U-Net++ model was utilized for segmenting thyroid nodules in ultrasound images automatically. Finally, the segmentation result was imported into a multi-task convolutional neural network (MT-CNN), the design of which was based on the clinical guideline called KWAK TI-RADS. Apart from the category of benign and malignant, the MT-CNN also exported the classification result of four malignant features, solid component (SC), hypoechogenicity or marked hypoechogenicity (HMH), microlobulated or irregular margin (MIM), microcalcification (MC), which were used for counting the risk level in KWAK TI-RADS.Main results. The performance of the improved U-Net++ was evaluated on our test set, including 302 cases. The Dice coefficient and intersection over union reached 0.899, 0.816, respectively. The classification accuracy rates of SC, HMH, MIM, MC, were 94.5%, 92.8%, 86.1%, 88.9%, while the false positive (FP) rate was 6.0%, 5.6%, 10.6%, 12.9% respectively. As for the category of benign and malignant, the precision and recall rates were 93.7% and 94.4%.Significance. The proposed CAD method showed favourable performance in the diagnosis of thyroid nodules. Compared with other methods, it could provide reports closer to clinical practice for doctors.

19.
Hellenic J Cardiol ; 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37717695

RESUMEN

BACKGROUND: Left atrial appendage (LAA) closure (LAAC) procedures are conventionally performed using empirical fluoroscopic viewing angles. However, because the LAA is a highly variable anatomical structure, these angles cannot depict the LAA in the optimal position. The present study aimed to assess the efficiency of using a novel optimal fluoroscopic projection angle (OPA) for LAAC and to validate its feasibility. METHODS: The OPAs of the derivation cohort were acquired using cardiac computed tomography angiography (CCTA) to assess its superiority for depicting LAA depth versus traditional working angles (TAs) of RAO 30°, CAU 20°. The practicability of OPA-guided LAAC was demonstrated by comparison between clinical data from the validation cohort and those from a propensity-score matched (PSM) control group, as well as randomized controlled studies investigating LAAC. RESULTS: Of 705 patients in the derivation cohort, the median OPA was RAO 46°, CAU 31°. Compared with TA, the OPA depicted a longer mean (±SD) LAA depth (5.1 ± 4.4) mm and a larger orifice diameter (1.1 ± 1.1 mm), (P < 0.0001 for both). All 38 OPA-guided LAACs were successful, with a shorter mean procedure duration (42.9 ± 12.3 min versus [vs.] 107.2 ± 41.5 min; P < 0.0001) and reduced device consumption (1.08 vs. 1.5 per case), compared with the PSM control group. At the 3-month follow-up, the incidence of peri-device leak was 52.6% (20/38) detected by CCTA, with a mean leakage of 1.6 ± 0.8 mm. CONCLUSION: By unfolding the LAA depth and orifice diameter for a better view, OPA demonstrated the potential to optimize LAAC procedural efficiency, although further larger-scale studies are required to confirm this.

20.
Sci Total Environ ; 904: 166382, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37595916

RESUMEN

Solar heating is generally regarded as a clean and low-carbon heating method, while its high initial investment hinders its promotion in economically underdeveloped areas. With the implementation of the clean heating policy and the proposal of the carbon neutralization target, rural bulk coal heating in northern China is restricted. The Chinese government proposes to widely adopt solar heating to meet the heating demands of rural residents. In this research, the application of solar assisted heat pump systems in Beijing, Tianjin, Hebei and its surrounding areas in China is numerically simulated. A new evaluation method under the same initial investment constraint is proposed to verify its benefits throughout the entire life cycle. The results indicate that although solar thermal heating has the lowest environmental impact and carbon emissions among various heating methods, it is not the best solution to rural clean heating. The reason is that equal investment in other projects can bring much more benefits, such as roof solar photovoltaic. In contrast to the air source heat pump and photovoltaic panel scheme with the same initial investment, solar heating has obvious negative environmental impact, 53.3 % higher economic cost, 35.9 tons more carbon emissions, and 105.9 % higher roof area occupation. The sensitivity analysis of solar fraction, geographical coordinates, and energy price also supports the above findings. The recommendation is proposed to promote air source heat pumps or solar photovoltaic, rather than solar thermal collectors, so as to reduce the cost of rural clean heating and carbon emission reduction.

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