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We previously found that miR-664a-5p is specifically expressed in urinary exosomes of idiopathic membranous nephropathy (IMN) patients. Homeodomain-interacting protein kinase 2 (HIPK2), a nuclear serine/threonine kinase, plays an important role in nephropathy. But the function of these factors and their connection in MN are unclear. To investigate the function and mechanism of miR-664a-5p in MN, the miR-664a-5p expression in HK-2 cells, exosomes, podocytes and renal tissues were studied, as well as cell growth and apoptosis of these cells, the binding of miR-664a-5p to HIPK2 mRNA, the levels of relative proteins and autophagy. The MN progression in MN mice model was also studied. Albumin increased the miR-664a-5p content and apoptosis of HK-2 cells, which was blocked by miR-664a-5p antagomir. miR-664a-5p bound to the 3' UTR of HIPK2 mRNA, resulting in the up-regulation of Calpain1, GSα shear and the inhibition of autophagy level. Autophagy inhibitor CQ blocked the protective effect of miR-664a-5p antagomir, HIPK2 overexpression, Calpain inhibitor SJA6017 on albumin-mediated injury. MiR-664a-5p from albumin-treated HK-2 cells could be horizontally transported to podocytes through exosomes. Exosomes from albumin-treated HK-2 cells promoted progression of MN mice, AAV-Anti-miR-664-5p (mouse homology miRNA) could improve them. Albumin increases the miR-664a-5p level and causes changes of HIPK2/Calpain1/GSα pathway, which leads to autophagy inhibition and apoptosis up-regulation of renal tubular epithelial cells. miR-664a-5p can horizontally enter podocytes through exosomes resulting in podocytes injury. Targeted inhibition of miR-664a-5p can reduce the apoptosis of renal tubule cells and podocytes, and may improve the MN progression.
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Glomerulonefritis Membranosa , MicroARNs , Animales , Humanos , Ratones , Albúminas/metabolismo , Antagomirs , Apoptosis , Autofagia , Proteínas Portadoras , Glomerulonefritis Membranosa/genética , MicroARNs/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ARN MensajeroRESUMEN
Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.
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Glicósidos , Hiperuricemia , Proteína con Dominio Pirina 3 de la Familia NLR , Piranos , Ácido Úrico , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Ácido Úrico/sangre , Masculino , Glicósidos/farmacología , Glicósidos/uso terapéutico , Piranos/farmacología , Piranos/uso terapéutico , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , FN-kappa B/metabolismo , Ratones Endogámicos C57BLRESUMEN
With global warming, high temperature (HT) has become one of the most common abiotic stresses resulting in significant crop yield losses, especially for jujube (Ziziphus jujuba Mill.), an important temperate economic crop cultivated worldwide. This study aims to explore the coping mechanism of jujube to HT stress at the transcriptional and post-transcriptional levels, including identifying differentially expressed miRNAs and mRNAs as well as elucidating the critical pathways involved. High-throughput sequencing analyses of miRNA and mRNA were performed on jujube leaves, which were collected from "Fucumi" (heat-tolerant) and "Junzao" (heat-sensitive) cultivars subjected to HT stress (42 °C) for 0, 1, 3, 5, and 7 days, respectively. The results showed that 45 known miRNAs, 482 novel miRNAs, and 13,884 differentially expressed mRNAs (DEMs) were identified. Among them, integrated analysis of miRNA target genes prediction and mRNA-seq obtained 1306 differentially expressed miRNAs-mRNAs pairs, including 484, 769, and 865 DEMIs-DEMs pairs discovered in "Fucuimi", "Junzao" and two genotypes comparative groups, respectively. Furthermore, functional enrichment analysis of 1306 DEMs revealed that plant-pathogen interaction, starch and sucrose metabolism, spliceosome, and plant hormone signal transduction were crucial pathways in jujube leaves response to HT stress. The constructed miRNA-mRNA network, composed of 20 DEMIs and 33 DEMs, displayed significant differently expressions between these two genotypes. This study further proved the regulatory role of miRNAs in the response to HT stress in plants and will provide a theoretical foundation for the innovation and cultivation of heat-tolerant varieties.
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Genotipo , MicroARNs , ARN Mensajero , ARN de Planta , Ziziphus , Ziziphus/genética , Ziziphus/fisiología , MicroARNs/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN de Planta/genética , Regulación de la Expresión Génica de las Plantas , Calor , Hojas de la Planta/genética , Estrés Fisiológico/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Respuesta al Choque Térmico/genéticaRESUMEN
BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. METHODS AND RESULTS: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. CONCLUSION: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.
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Diabetes Mellitus Tipo 1 , Cardiomiopatías Diabéticas , Ferroptosis , Humanos , Animales , Ratones , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/prevención & control , Sirtuina 1 , Fibronectinas , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Proteína p53 Supresora de Tumor , Miocitos CardíacosRESUMEN
Two new compounds namely [Zn(L1)phen]31 and Ni(L1)phen(MeOH) 2 (L1 = 3, 5-dichlorosalicylaldehyde thiosemicarbazone) were synthesized by the slow evaporation method at room temperature. The structure of ligand L1 was determined using 1H NMR and 13C NMR spectra. X-ray single crystal diffraction analysis revealed that compounds 1-2 can form 3D supramolecular network structures through π···π stacking and hydrogen bonding interactions. The DFT calculation shows that the coordination of ligand and metal is in good agreement with the experimental results. Hirshfeld surface analysis revealed that H H and Cl H interactions were the predominant interactions in compounds 1-2. Energy framework analysis indicated that dispersion energy played a dominant role in the energy composition of compounds 1-2. The inhibitory effects of compounds 1-2 against Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA) were tested using the paper disk diffusion method (1: E. coli: 18 mm, MRSA: 17 mm, 2: E. coli: 15 mm, MRSA: 16 mm). Ion releasing experiments were conducted to assess the ion release capacity of compounds 1-2 (Zn2+, 4 days, 38.33 µg/mL; Ni2+, 4 days, 29.12 µg/mL). Molecular docking demonstrated the interaction modes of compounds 1-2 with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and dihydrofolate reductase (DHFR) in bacteria, involving hydrophobic, stacking, hydrogen bonding and halogen bonding interactions. The generation of reactive oxygen species (ROS) in bacteria under the presence of compounds 1-2 were evaluated using a fluorescent dye known as dichlorodihydrofluorescein diacetate (DCFH-DA). Potential antibacterial mechanisms of compounds 1-2 were proposed.
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Staphylococcus aureus Resistente a Meticilina , Antibacterianos/farmacología , Escherichia coli , Ligandos , Simulación del Acoplamiento Molecular , Zinc/farmacología , Zinc/química , Níquel/química , Complejos de Coordinación/química , Complejos de Coordinación/farmacologíaRESUMEN
Although great efforts have been made to elucidate the pathological mechanisms of renal diseases and potential prevention and treatment targets that would allow us to retard kidney disease progression, we still lack specific and effective management methods. Epigenetic mechanisms are able to alter gene expression without requiring DNA mutations. Accumulating evidence suggests the critical roles of epigenetic events and processes in a variety of renal diseases, involving functionally relevant alterations in DNA methylation, histone methylation, RNA methylation, and expression of various non-coding RNAs. In this review, we highlight recent advances in the impact of methylation events (especially RNA m6A methylation, DNA methylation, and histone methylation) on renal disease progression, and their impact on treatments of renal diseases. We believe that a better understanding of methylation modification changes in kidneys may contribute to the development of novel strategies for the prevention and management of renal diseases.
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Metilación de ADN , Enfermedades Renales , Metilación de ARN , Humanos , Progresión de la Enfermedad , Epigénesis Genética , Histonas/metabolismo , Enfermedades Renales/genética , Enfermedades Renales/metabolismoRESUMEN
Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.
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Lesión Renal Aguda , Ferroptosis , Ratones Endogámicos C57BL , Fenilendiaminas , Animales , Ferroptosis/efectos de los fármacos , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Ratones , Masculino , Fenilendiaminas/farmacología , Fenilendiaminas/uso terapéutico , Ciclohexilaminas/farmacología , Ciclohexilaminas/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismoRESUMEN
Background: Volume overload is a fatal complication for people undergoing hemodialysis. Therefore, regulating a patient's "dry weight" based on their fluid status is imperative. Clinical experiences are too subjective to accurately judge a patient's fluid status, but techniques have emerged for improved fluid control in the two decades. Specifically, lung ultrasonography (LUS) uses a unique aspect of ultrasound images, the B-lines, to evaluate extravascular lung water, which has increasingly attracted attention. However, the role of B-line quantification in predicting short-mid-term death and/or cardiovascular complications is unclear. Methods: Patients undergoing MHD at the hemodialysis center of Zhejiang Provincial People's Hospital from October 1, 2020, to February 28, 2021, were examined using LUS and a bioelectrical impedance analysis before and after dialysis, and related clinical data were collected. All patients were followed up for one year after the examination, and deaths and first cardiovascular events (e.g., stroke, myocardial infarction, and heart failure) during this period were recorded. Results: 98 patients were enrolled and divided into three groups in relation to their mild (<16 B-lines), moderate (16-30 B-lines), or severe (>30 B-lines) hypervolemia, defined by the number of B-lines. The long-term survival rate was significantly lower in the severe group than in the mild and moderate groups. LUS and bioelectrical impedance-related parameters (e.g., extracellular water-to-water ratio) were closely related to cardiac ultrasound parameters (left ventricular ejection fraction) (P < 0.001). The optimal B-line cutoff value on LUS for predicting fluid overload (defined clinically) in patients on hemodialysis was 11.5 lines (AUC = 0.840, 95% confidence interval 0.735-0.945, P < 0.001), and the diagnostic sensitivity and specificity were both 76.5%. During the one-year follow-up period, ten deaths and six cardiovascular events occurred. The survival rate was significantly lower in the severe group than in the mild group (log-rank test χ2 = 10.050, P=0.002) but did not differ between the severe and moderate groups (χ2 = 2.629, P=0.105). Conclusion: LUS is a cheap, noninvasive, simple, and repeatable volume-monitoring method that can assist with individualized fluid volume management in patients undergoing MHD. LUS results may also help to predict the short-mid-term survival rate of patients to a certain extent.
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Insuficiencia Cardíaca , Función Ventricular Izquierda , Humanos , Volumen Sistólico , Impedancia Eléctrica , Pulmón/diagnóstico por imagen , Ultrasonografía , Diálisis Renal/efectos adversosRESUMEN
Diabetic nephropathy (DN) is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Germacrone (Ger) possesses anti-inflammatory, antioxidant and anti-DN properties. However, it is unclear whether the improvement in kidney damage caused by Ger in DN mice is related to abnormal compositions and metabolites of the gut microbiota. This study generates a mouse model of DN to explore the potent therapeutic ability and mechanism of Ger in renal function by 16S rRNA sequencing and untargeted fecal metabolomics. Although there is no significant change in microbiota diversity, the structure of the gut microbiota in the DN group is quite different. Serratia_marcescens and Lactobacillus_iners are elevated in the model group but significantly decreased after Ger intervention ( P<0.05). Under the treatment of Ger, no significant differences in the diversity and richness of the gut microbiota are observed. An imbalance in the intestinal flora leads to the dysregulation of metabolites, and non-targeted metabolomics data indicate high expression of stearic acid in the DN group, and oleic acid could serve as a potential marker of the therapeutic role of Ger in the DN model. Overall, Ger improves kidney injury in diabetic mice, in part potentially by reducing the abundance of Serratia_marcescens and Lactobacillus_iners, as well as regulating the associated increase in metabolites such as oleic acid, lithocholic acid and the decrease in stearic acid. Our research expands the understanding of the relationship between the gut microbiota and metabolites in Ger-treated DN. This contributes to the usage of natural products as a therapeutic approach for the treatment of DN via microbiota regulation.
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Diabetes Mellitus Experimental , Nefropatías Diabéticas , Lactobacillus , Animales , Ratones , Nefropatías Diabéticas/genética , ARN Ribosómico 16S/genética , Diabetes Mellitus Experimental/genética , Sesquiterpenos de GermacranoRESUMEN
Paraquat (PQ) causes fatal poisoning that leads to systemic multiple organ fibrosis, and transforming growth factor (TGF)-ß1 plays a critical role in this process. In this study, we aimed to investigate the effects of AZ12601011 (a small molecular inhibitor of TGFßRI) on PQ-induced multiple organ fibrosis. We established a mouse model of PQ in vivo and used PQ-treated lung epithelial cell (A549) and renal tubular epithelial cells (TECs) in vitro. Haematoxylin-eosin and Masson staining revealed that AZ12601011 ameliorated pulmonary, hepatic, and renal fibrosis, consistent with the decrease in the levels of fibrotic indicators, alpha-smooth muscle actin (α-SMA) and collagen-1, in the lungs and kidneys of PQ-treated mice. In vitro data showed that AZ12601011 suppressed the induction of α-SMA and collagen-1 in PQ-treated A549 cells and TECs. In addition, AZ12601011 inhibited the release of inflammatory factors, interleukin (IL)-1ß, IL-6, and tumour necrosis factor-α. Mechanistically, TGF-ß and TGFßRI levels were significantly upregulated in the lungs and kidneys of PQ-treated mice. Cellular thermal shift assay and western blotting revealed that AZ12601011 directly bound with TGFßRI and blocked the activation of Smad3 downstream. In conclusion, our findings revealed that AZ12601011 attenuated PQ-induced multiple organ fibrosis by blocking the TGF-ß/Smad3 signalling pathway, suggesting its potential for PQ poisoning treatment.
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Lesión Pulmonar Aguda , Paraquat , Fibrosis Pulmonar , Ratones , Animales , Paraquat/toxicidad , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta , Factor de Crecimiento Transformador beta/toxicidad , Factor de Crecimiento Transformador beta1/toxicidad , Factor de Crecimiento Transformador beta1/metabolismo , Colágeno/toxicidad , Colágeno/metabolismo , Factores de Crecimiento Transformadores/toxicidadRESUMEN
BACKGROUND: In some resource-limited regions, the placement of tunneled dialysis catheters (TDC) is often preferred under ultrasound guidance rather than fluoroscopy. This study compared ultrasound-and digital subtraction angiography-guided (DSA)-guided TDC in renal replacement therapy. METHODS: This retrospective cohort study included all TDC placements performed at our hospital between January 2020 and October 2022. We utilized 1:1 propensity score matching (PSM) to balance the demographic and clinical characteristics of the DSA-guided and ultrasound-guided groups. Dialysis prescriptions and actual dialysis completion were assessed using intraclass correlation coefficients (ICC). Multivariable logistic regression analyses determined the risk factors for early termination of dialysis. The differences in adverse events, catheter function, and catheter tip position were evaluated between the two groups. RESULTS: The study included 261 patients (142 in the DSA-guided group and 119 in the ultrasound-guided group). After PSM, 91 patients were included in each group, with no significant baseline differences (p > .1). Both groups achieved adequate catheter blood flow and ultrafiltration volumes without deviations from dialysis prescriptions (ICC ≥ 0.75). The DSA-guided group had fewer early dialysis terminations than the ultrasound-guided group (3.3 vs. 12.0%, p = .026). The position of the catheter tip in the right atrium was more consistent in the DSA-guided group (100 vs. 74.2%, p < .001). CONCLUSION: Hemodialysis catheters inserted under DSA guidance exhibited superior performance compared to those inserted under ultrasound guidance, primarily due to more accurate catheter tip positioning. DSA guidance is recommended when ensuring optimal catheter tip placement.
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Angiografía de Substracción Digital , Estudios de Factibilidad , Puntaje de Propensión , Diálisis Renal , Ultrasonografía Intervencional , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Diálisis Renal/instrumentación , Diálisis Renal/métodos , Anciano , Cateterismo Venoso Central/métodos , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Adulto , Catéteres de PermanenciaRESUMEN
Cell adhesion is a dynamic process that plays a fundamental role in cell proliferation, maintenance, differentiation, and migration. Basal cell adhesion molecule (BCAM), also known as Lutheran (Lu), belongs to the immunoglobulin superfamily of cell adhesion molecules. Lu/BCAM, which is widely expressed in red blood cells, endothelial cells, smooth muscle cells and epithelial cells across various tissues, playing a crucial role in many cellular processes, including cell adhesion, cell motility and cell migration. Moreover, Lu/BCAM, dysregulated in many diseases, such as blood diseases and various types of cancer, may act as a biomarker and target for the treatment of these diseases. This review explores the significance of Lu/BCAM in cell adhesion and its potential as a novel target for treating hematological diseases and tumors.
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Enfermedades Hematológicas , Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Enfermedades Hematológicas/metabolismo , Sistema del Grupo Sanguíneo Lutheran/metabolismo , Adhesión Celular , Animales , Moléculas de Adhesión Celular/metabolismo , Movimiento CelularRESUMEN
Fleshy fruit ripening is a unique biological process that involves dramatic changes in a diverse array of cellular metabolisms. The regulation of these metabolisms is essentially mediated by cellular signal transduction of internal (e.g., hormones) and external cues (i.e., environmental stimuli). Mitogen-activated protein kinase (MAPK) signaling pathways play crucial roles in a diverse array of biological processes, such as plant growth, development and biotic/abiotic responses. Accumulating evidence suggests that MAPK signaling pathways are also implicated in fruit ripening and quality formation. However, while MAPK signaling has been extensively reviewed in Arabidopsis and some crop plants, the comprehensive picture of how MAPK signaling regulates fruit ripening and quality formation remains unclear. In this review, we summarize and discuss research in this area. We first summarize recent studies on the expression patterns of related kinase members in relation to fruit development and ripening and then summarize and discuss the crucial evidence of the involvement of MAPK signaling in fruit ripening and quality formation. Finally, we propose several perspectives, highlighting the research matters and questions that should be afforded particular attention in future studies.
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Frutas , Desarrollo de la Planta , Frutas/metabolismo , Transducción de Señal , Sistema de Señalización de MAP Quinasas , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genéticaRESUMEN
Numerous impediments beset contemporary art education, notably the unidimensional delivery of content and the absence of real-time interaction during instructional sessions. This study endeavors to surmount these challenges by devising a multimodal perception system entrenched in Internet of Things (IoT) technology. This system captures students' visual imagery, vocalizations, spatial orientation, movements, ambient luminosity, and contextual data by harnessing an array of interaction modalities encompassing visual, auditory, tactile, and olfactory sensors. The synthesis of this manifold information about learning scenarios entails strategically placing sensors within physical environments to facilitate intuitive and seamless interactions. Utilizing digital art flower cultivation as a quintessential illustration, this investigation formulates tasks imbued with multisensory channel interactions, pushing the boundaries of technological advancement. It pioneers advancements in critical domains such as visual feature extraction by utilizing DenseNet networks and voice feature extraction leveraging SoundNet convolutional neural networks. This innovative paradigm establishes a novel art pedagogical framework, accentuating the importance of visual stimuli while enlisting other senses as complementary contributors. Subsequent evaluation of the usability of the multimodal perceptual interaction system reveals a remarkable task recognition accuracy of 96.15% through the amalgamation of Mel-frequency cepstral coefficients (MFCC) speech features with a long-short-term memory (LSTM) classifier model, accompanied by an average response time of merely 6.453 seconds-significantly outperforming comparable models. The system notably enhances experiential fidelity, realism, interactivity, and content depth, ameliorating the limitations inherent in solitary sensory interactions. This augmentation markedly elevates the caliber of art pedagogy and augments learning efficacy, thereby effectuating an optimization of art education.
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Given the prevalent issues surrounding accuracy and efficiency in contemporary stereo-matching algorithms, this research introduces an innovative image segmentation-based approach. The proposed methodology integrates residual and Swim Transformer modules into the established 3D Unet framework, yielding the Res-Swim-UNet image segmentation model. The algorithm estimates the disparateness of segmented outputs by employing regression techniques, culminating in a comprehensive disparity map. Experimental findings underscore the superiority of the proposed algorithm across all evaluated metrics. Specifically, the proposed network demonstrates marked improvements, with IoU and mPA enhancements of 2.9% and 162%, respectively. Notably, the average matching error rate of the algorithm registers at 2.02%, underscoring its efficacy in achieving precise stereoscopic matching. Moreover, the model's enhanced generalization capability and robustness underscore its potential for widespread applicability.
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Introduction: Diabetic nephropathy (DN) is a leading cause of kidney failure. Lysozyme (LYZ) is an essential component of innate immunity and exhibits antibacterial properties. However, LYZ has been reported to induce nephropathy, implying a possible association between impaired renal function and lysozyme expression. Material and methods: Bioinformatics analysis was used to predict the hub gene associated with DN, and the differential expression of the hub gene was confirmed using a mouse model. A mouse model of streptozotocin (STZ)-induced diabetic nephropathy was established to investigate the correlation between DN and LYZ expression, and the functionality of LYZ was verified through knockdown and overexpression experiments conducted in vivo. Immunohistochemistry (IHC) was utilized to assess fibrosis-related markers and cytokines, while Masson staining was performed to assess renal fibrosis. Fibroblast proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The role of the JAK pathway was confirmed using the JAK inhibitor AG490, and Western blot was used to investigate the underlying mechanisms. Results: Mechanistically, 25 mM glucose promotes the expression of LYZ in fibroblastic cells, and LYZ may in turn promote the proliferation of renal interstitial fibroblasts. Western blot shows that glucose can activate STAT3 in an LYZ-dependent manner, and the JAK inhibitor AG490 can partially suppress LYZ-induced STAT3 activation. Furthermore, in vivo observations have revealed that overexpression of LYZ is associated with the senescent phenotype of renal tubular epithelial cells (RTECs). Conclusions: Lysozyme promotes kidney fibrosis via the JAK/STAT3 signaling pathway in diabetic nephropathy, and glucose may promote fibroblast proliferation by promoting LYZ auto-secretion.
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Colorectal cancer (CRC) is one of the most common non-cutaneous malignancies, causing significant mortality and a substantial burden. This study aims to explore the role of KIAA1429 (also known as vir-like m6A methyltransferase associated [VIRMA]) protein in the radioresistance of CRC. CRC cells and a radioresistant cell line were cultured, and KIAA1429 expression was detected. After the down-regulation of KIAA1429, its effect on the radioresistance and ferroptosis of cancer cells was analyzed. The role of ferroptosis in radioresistance was verified. The binding relationship among long non-coding RNA endogenous Bornavirus-like nucleoprotein 3, pseudogene (lncRNA EBLN3P), microRNA (miR)-153-3p, and KIAA1429 was analyzed. KIAA1429 and lncRNA EBLN3P were highly expressed in CRC, while miR-153-3p was poorly expressed. KIAA1429 and lncRNA EBLN3P were further increased/decreased in the radioresistant cells. KIAA1429 knockdown decreased the survival rate of the radioresistant cell line after X-ray irradiation and increased gamma H2A histone family member X (γ-H2AX), ferroptosis, and oxidative stress. A ferroptosis inhibitor alleviated the inhibitory effect of KIAA1429 knockdown on radioresistance. KIAA1429-mediated m6A modification up-regulated lncRNA EBLN3P, and lncRNA EBLN3P increased KIAA1429 by competitively binding to miR-153-3p. miR-153-3p silencing or lncRNA EBLN3P overexpression attenuated the promotion of ferroptosis and the inhibition of radioresistance induced by KIAA1429 knockdown. Overall, KIAA1429-mediated m6A modification up-regulated lncRNA EBLN3P expression, and lncRNA EBLN3P increased KIAA1429 expression by competitively binding to miR-153-3p, thus reducing ferroptosis and increasing the radioresistance of CRC.
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Background: With the rapid development of technology, artificial intelligence (AI) has been widely used in the diagnosis and prognosis prediction of a variety of diseases, including cardiovascular disease. Facts have proved that AI has broad application prospects in rapid and accurate diagnosis. Objective: This study mainly summarizes the research on the application of AI in the field of cardiovascular disease through bibliometric analysis and explores possible future research hotpots. Methods: The articles and reviews regarding application of AI in cardiovascular disease between 2000 and 2023 were selected from Web of Science Core Collection on 30 December 2023. Microsoft Excel 2019 was applied to analyze the targeted variables. VOSviewer (version 1.6.16), Citespace (version 6.2.R2), and a widely used online bibliometric platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references, and keywords in this field. Results: A total of 4,611 articles were selected in this study. AI-related research on cardiovascular disease increased exponentially in recent years, of which the USA was the most productive country with 1,360 publications, and had close cooperation with many countries. The most productive institutions and researchers were the Cedar sinai medical center and Acharya, Ur. However, the cooperation among most institutions or researchers was not close even if the high research outputs. Circulation is the journal with the largest number of publications in this field. The most important keywords are "classification", "diagnosis", and "risk". Meanwhile, the current research hotpots were "late gadolinium enhancement" and "carotid ultrasound". Conclusions: AI has broad application prospects in cardiovascular disease, and a growing number of scholars are devoted to AI-related research on cardiovascular disease. Cardiovascular imaging techniques and the selection of appropriate algorithms represent the most extensively studied areas, and a considerable boost in these areas is predicted in the coming years.