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Calcific aortic valve disease (CAVD) is prevalent in developed nations and has emerged as a pressing global public health concern due to population aging. The precise etiology of this disease remains uncertain, and recent research has primarily focused on examining the role of valvular interstitial cells (VICs) in the development of CAVD. The predominant treatment options currently available involve open surgery and minimally invasive interventional surgery, with no efficacious pharmacological treatment. This article seeks to provide a comprehensive understanding of valvular endothelial cells (VECs) from the aspects of valvular endothelium-derived nitric oxide (NO), valvular endothelial mechanotransduction, valvular endothelial injury, valvular endothelial-mesenchymal transition (EndMT), and valvular neovascularization, which have received less attention, and aims to establish their role and interaction with VICs in CAVD. The ultimate goal is to provide new perspectives for the investigation of non-invasive treatment options for this disease.
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Estenosis de la Válvula Aórtica , Válvula Aórtica , Calcinosis , Células Endoteliales , Humanos , Calcinosis/patología , Válvula Aórtica/patología , Válvula Aórtica/metabolismo , Células Endoteliales/patología , Células Endoteliales/metabolismo , Animales , Estenosis de la Válvula Aórtica/patología , Óxido Nítrico/metabolismo , Mecanotransducción Celular , Enfermedad de la Válvula Aórtica/metabolismo , Enfermedad de la Válvula Aórtica/patología , Transición Epitelial-MesenquimalRESUMEN
In recent years, organoids have become a crucial model for studying the physiopathological processes in tissues and organs. The emergence of organoids has promoted the research on the mechanisms of the occurrence and clinical translation of diseases. Among these organoid models, colorectal organoid models are increasingly mature. Colorectal cancer is a common gastrointestinal malignant tumor worldwide, posing a serious threat to human health. Colorectal organoids provide a new model for studying the pathophysiology, drug sensitivity, and precision medicine of colorectal cancer. The conventional culture systems of colorectal organoids focus more on the role of biochemical factors, neglecting the fact that the gut is also influenced by biophysical signals in vivo. Therefore, in this review, we discuss the theories related to colorectal organoids and biomechanics and expound the effects of biomechanics on colorectal organoid culture.
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Neoplasias Colorrectales , Organoides , Organoides/citología , Humanos , Fenómenos Biomecánicos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Colon/citología , Técnicas de Cultivo de Célula/métodos , Recto/citología , Técnicas de Cultivo de Tejidos/métodosRESUMEN
Background: The crucial role of inflammation in aortic aneurysm (AA) is gaining prominence, while there is still a lack of key cytokines or targets for effective clinical translation. Methods: Mendelian randomization (MR) analysis was performed to identify the causal relationship between 91 circulating inflammatory proteins and AA and between 731 immune traits and AA. Bulk RNA sequencing data was utilized to demonstrate the expression profile of the paired ligand-receptor. Gene enrichment analysis, Immune infiltration, and correlation analysis were employed to deduce the potential role of CX3CR1. We used single-cell RNA sequencing data to pinpoint the localization of CX3CL1 and CX3CR1, which was further validated by multiplex immunofluorescence staining. Cellchat analysis was utilized to infer the CX3C signaling pathway. Trajectory analysis and the Cytosig database were exploited to determine the downstream effect of CX3CL1-CX3CR1. Results: We identified 4 candidates (FGF5, CX3CL1, IL20RA, and SCF) in multiple two-sample MR analyses. Subsequent analysis of the expression profile of the paired receptor revealed the significant upregulation of CX3CR1 in AA and its positive correlation with pro-inflammatory macrophages. Two sample MR between immune cell traits and AA demonstrated the potential causality between intermediate monocytes and AA. We finally deciphered in single-cell sequencing data that CX3CL1 sent by endothelial cells (ECs) acted on CX3CR1 of intermediated monocytes, leading to its recruitment and pro-inflammatory responses. Conclusion: Our study presented a genetic insight into the pathogenetic role of CX3CL1-CX3CR1 in AA, and further deciphered the CX3C signaling pathway between ECs and intermediate monocytes.
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Aneurisma de la Aorta , Receptor 1 de Quimiocinas CX3C , Quimiocina CX3CL1 , Análisis de la Aleatorización Mendeliana , Receptor 1 de Quimiocinas CX3C/genética , Receptor 1 de Quimiocinas CX3C/metabolismo , Humanos , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Aneurisma de la Aorta/genética , Aneurisma de la Aorta/metabolismo , Perfilación de la Expresión Génica , Transcriptoma , Transducción de Señal , Predisposición Genética a la EnfermedadRESUMEN
The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise mechanisms underlying the senescence of VICs remain unclear, demanding the identification of a novel target to mitigate this process. Previous studies have highlighted the anti-aging potential of morusin. Thus, this study aimed to explore the therapeutic potential of morusin in CAVD. Cellular experiments reveal that morusin effectively suppresses cellular senescence and cause a shift toward osteogenic differentiation of VICs in vitro. Mechanistically, morusin activate the Nrf2-mediated antiaging signaling pathway by downregulating CCND1 expression and aiding Keap1 degradation through Trim 25. This activation lead to the upregulated expression of antioxidant genes, thus reducing reactive oxygen species production and thereby preventing VIC osteogenic differentiation. In vivo experiments in ApoE-/- mice on a high-fat Western diet demonstrate the positive effect of morusin in mitigating aortic valve calcification. These findings emphasize the antiaging properties of morusin and its potential as a therapeutic agent for CAVD.
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Estenosis de la Válvula Aórtica , Calcinosis , Senescencia Celular , Flavonoides , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/genética , Estenosis de la Válvula Aórtica/patología , Calcinosis/metabolismo , Calcinosis/genética , Senescencia Celular/efectos de los fármacos , Ciclina D1/metabolismo , Ciclina D1/genética , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Osteogénesis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Flavonoides/administración & dosificaciónRESUMEN
Valvular endothelial cells (VECs) derived from human induced pluripotent stem cells (hiPSCs) provide an unlimited cell source for tissue engineering heart valves (TEHVs); however, they are limited by their low differentiation efficiency and immature function. In our study, we applied unidirectional shear stress to promote hiPSCs differentiation into valvular endothelial-like cells (VELs). Compared to the static group, shear stress efficiently promoted the differentiation and functional maturation of hiPSC-VELs, as demonstrated by the efficiency of endothelial differentiation reaching 98.3% in the high shear stress group (45 dyn/cm2). Furthermore, we found that Piezo1 served as a crucial mechanosensor for the differentiation and maturation of VELs. Mechanistically, the activation of Piezo1 by shear stress resulted in the influx of calcium ions, which in turn initiated the Akt signaling pathway and promoted the differentiation of hiPSCs into mature VELs. Moreover, VELs cultured on decellularized heart valves (DHVs) exhibited a notable propensity for proliferation, robust adhesion properties, and antithrombotic characteristics, which were dependent on the activation of the Piezo1 channel. Overall, our study demonstrated that proper shear stress activated the Piezo1 channel to facilitate the differentiation and maturation of hiPSC-VELs via the Akt pathway, providing a potential cell source for regenerative medicine, drug screening, pathogenesis, and disease modeling. STATEMENT OF SIGNIFICANCE: This is the first research that systematically analyzes the effect of shear stress on valvular endothelial-like cells (VELs) derived from human induced pluripotent stem cells (hiPSCs). Mechanistically, unidirectional shear stress activates Piezo1, resulting in an elevation of calcium levels, which triggers the Akt signaling pathway and then facilitates the differentiation of functional maturation VELs. After exposure to shear stress, the VELs exhibited enhanced proliferation, robust adhesion capabilities, and antithrombotic characteristics while being cultured on decellularized heart valves. Thus, it is of interest to develop hiPSCs-VELs using shear stress and the Piezo1 channel provides insights into the functional maturation of valvular endothelial cells, thereby serving as a catalyst for potential applications in the development of therapeutic and tissue-engineered heart valves in the future.
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Células Madre Pluripotentes Inducidas , Humanos , Células Endoteliales , Calcio/metabolismo , Fibrinolíticos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Diferenciación Celular/fisiología , EndotelioRESUMEN
Background: The purpose of this study was to investigate the prognostic significance of serum albumin to creatinine ratio (ACR) in patients receiving heart transplantation of end-stage heart failure. Methods: From January 2015 to December 2020, a total of 460 patients who underwent heart transplantation were included in this retrospective analysis. According to the maximum Youden index, the optimal cut-off value was identified. Kaplan-Meier methods were used to describe survival rates, and multivariable analyses were conducted with Cox proportional hazard models. Meanwhile, logistic regression analysis was applied to evaluate predictors for postoperative complications. The accuracy of risk prediction was evaluated by using the concordance index (C-index) and calibration plots. Results: The optimal cut-off value was 37.54 for ACR. Univariable analysis indicated that recipient age, IABP, RAAS, BB, Hb, urea nitrogen, D-dimer, troponin, TG, and ACR were significant prognostic factors of overall survival (OS). Multivariate analysis showed that preoperative ACR (HR: 0.504, 95% = 0.352-0.722, P < 0.001) was still an independent prognostic factor of OS. The nomogram for predicting 1-year and 5-year OS in patients who underwent heart transplantation without ACR (C-index = 0.631) and with ACR (C-index = 0.671). Besides, preoperative ACR level was a significant independent predictor of postoperative respiratory complications, renal complications, liver injury, infection and in-hospital death. Moreover, the calibration plot showed good consistency between the predictions by the nomogram for OS and the actual outcomes. Conclusion: Our research showed that ACR is a favorable prognostic indicator in patients of heart transplantation.
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Video behavior recognition often needs to focus on object motion processes. In this work, a self-organizing computational system oriented toward behavioral clustering recognition is proposed, which achieves the extraction of motion change patterns through binary encoding and completes motion pattern summarization using a similarity comparison algorithm. Furthermore, in the face of unknown behavioral video data, a self-organizing structure with layer-by-layer accuracy progression is used to achieve motion law summarization using a multi-layer agent design approach. Finally, the real-time feasibility is verified in the prototype system using real scenes to provide a new feasible solution for unsupervised behavior recognition and space-time scenes.
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Algoritmos , Análisis por ConglomeradosRESUMEN
(1) Background: To expand the donor pool, greater donor hearts tended to be used in heart transplantation. However, the data about the feasibility of expanding the donor and recipient weight ratios (DRWRs. All donor and recipient weight ratio (DRWR) in this study or cited from other articles were converted to the DRWR calculated by ((donor weight-recipient weight)/recipient weight) × 100%.) to >30% was still scant in China's pediatric heart transplantation (HTx). The potential risk increased along with the further expansion of the appropriate range of DRWR to >30% and its upper limit was still in debate. (2) Methods: Seventy-eight pediatric patients (age < 18 years) undergoing HTx between 2015 and 2020 at our center were divided into two groups based on the DRWR (>30% and ≤30%). Variables were summarized and analyzed via univariate analyses and multivariate analyses. A Kaplan-Meier methodology was used to calculate survival and conditional survival. (3) Results: No significant difference was found in one-year, three-year or five-year survival between the two groups. (4) Conclusions: The expansion of DRWR to >30% was acceptable for China's pediatric HTx. Notably, continuously liberalizing of the upper DRWR boundary to more than 200% could be used as a stop-loss option but should be applied with caution.
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Mercury pollution from coal-fired power plants has always been an environmental concern, and adsorption technology is an effective method for Hg0 removal. In this study, copper-iron binary metal sulfide modified activated carbon ([Formula: see text]) adsorbent was synthesized. The performance and mechanism of mercury removal were tested by adsorption experiments and characterization methods. The results showed that the mercury removal efficiency of [Formula: see text] under simulated flue gas (SFG) conditions at 150 °C could reach 91%, which was higher than [Formula: see text] and [Formula: see text]. Compared with [Formula: see text], the introduction of Fe increased the proportion of [Formula: see text], which was usually linked to [Formula: see text], resulting in the generation of more [Formula: see text](CuISI) species. Meanwhile, the generation of active sulfur sites such as [Formula: see text] was generated, which had a facilitative effect on the oxidation of Hg0. Stable [Formula: see text] was the predominant product on the adsorbent surface. The 2% sulfur loadings had significantly improved the sulfur resistance of conventional AC.
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Contaminantes Atmosféricos , Mercurio , Adsorción , Contaminantes Atmosféricos/análisis , Carbón Mineral , Mercurio/análisis , Metales , Centrales Eléctricas , AzufreRESUMEN
Urea formaldehyde was used as wall material and waterborne coatings as a core material to prepare microcapsules. So as to explore the influence of mass ratio of core to shell, reaction temperature and standing time on the performance of microcapsules, the orthogonal test of three factors and two levels was put into effect. The orthogonal experimental results showed the mass ratio of core to shell was the most important factor. With the increase of the mass ratio of core to shell, the output and clad ratio of microcapsules increased first and then decreased. The microcapsule with the mass ratio of core to shell of 0.67:1 had better appearance, output, and encapsulation performance. The optical properties of waterborne wood coating with the microcapsules of waterborne coating as core materials did not decrease significantly, while the hardness, impact resistance, and toughness were improved. At the same time, the microcapsules have a certain self-repairing effect on coating micro-cracks. Compared with the properties of waterborne coatings with other microcapsules, the coating with waterborne coating as core material has better comprehensive performance. The results provide a new research idea for the performance enhancement and self-healing of wood waterborne coating.
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Microcapsules were prepared by in situ polymerization with urea formaldehyde resin as the wall material and Dulux waterborne acrylic acid as the core material. The effects of the core-wall ratio, water bath temperature and depositing time on the morphology, particle size, yield and encapsulation ratio of microcapsules were investigated by orthogonal experiment of three factors and two levels. The results showed that the core-wall ratio had the greatest influence on the performance of microcapsules. When the core-wall ratio was 0.58:1, the water bath temperature was 70 °C, and the depositing time was 5 d, the microcapsule performance was the best. With the increase in depositing time, the yield of microcapsule particles increased gradually, and the microcapsules appeared to show an adhesive phenomenon. However, the long-term depositing time did not lead to complete deposition and agglomeration of microcapsules. When 10.0% concentration of the waterborne acrylic microcapsules with 0.58:1 of core-wall ratio was added to the coatings, the mechanical and optical properties of the coatings did not decrease significantly, but the elongation at break increased significantly. Therefore, this study offers a new prospect for using waterborne acrylic microcapsules to improve the toughness of waterborne paint film which can be cured at room temperature on a wood surface.
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Using Cunninghamia lanceolata as a substrate, the thermochromic ink was added to the waterborne finish to test the optical properties and mechanical properties of the finish film. The results showed that the discoloration performance of the finish film with 15.0% and 30.0% of the thermochromic ink was better. The gloss of the finish film changes irregularly when the concentration increases. The finish film with a thermochromic ink concentration of 10.0% has the highest gloss, and with a concentration of 30.0% has the lowest gloss. When the thermochromic ink concentration exceeds 15.0%, the impact resistance of the finish film is slightly enhanced. The concentration is not related to the liquid resistance of the finish film. When the thermochromic ink concentration was 0-15.0%, the particle distribution uniform reunion was not much. The discoloration mechanism of discolored finish film can be considered to be as follows. After adding thermochromic ink, when the finish film temperature rises, it fades from red to colorless. When the temperature is lowered, the thermochromic ink changes to its original colour again, and the thermochromic effect is stable and sustainable. On the basis of the above results, when the thermochromic ink concentration is 15.0%, the general performance of the waterborne finish film on the Cunninghamia lanceolata surface is the best. This study provides new prospects in using thermochromic ink for waterborne finish film.
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In this study, the effect of glass fiber powder on the properties of waterborne coatings with thermochromic ink was investigated, using Chinese fir board as the base material and temperature-sensitive thermochromic waterborne coatings with thermochromic ink as the paint base. The concentration of glass fiber powder was determined when the microstructure, optical properties, mechanical properties, liquid resistance, and heat preservation effect were the best. The results showed that the paint film with glass fiber powder concentration of 1.0% to 7.0% had better discoloration performance. With an increase of the glass fiber powder concentration, the gloss of the paint film decreased gradually, and when the concentration of glass fiber powder was 0% to 5.0%, the gloss of the paint film was better. The concentration of glass fiber powder had no effect on the adhesion, impact resistance, and liquid resistance. In the first 2.5 min, the temperature value of the waterborne coating with 3.0% glass fiber powder was higher than that without glass fiber powder, which has a certain heat preservation effect. When the glass fiber powder content was 3.0%, the microstructure of paint film was the best. The composition of paint film with different glass fiber powder concentrations was not different and the discoloration performance of paint film with heat preservation effect was not affected by time. The analysis showed that the waterborne coating with 3.0% glass fiber powder had the best comprehensive performance. This work provides a technical reference for the industrialization of heat preservation and thermochromic coating on wood.
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In this study, Fraxinus mandshurica veneer was dyed with reactive brilliant red X-3B, black KN-B and blue K-3R dyes. The dye concentration, bath ratio and dyeing time were selected for an orthogonal experiment. Analysis of variance showed that the dye concentration had the greatest effect on the dye uptake of F. mandshurica veneer. In the independent experiments, dye uptake increased at first and then decreased with increasing dye concentration; the chromatic aberration increased with the dye concentration and then remained steady. The infrared spectra were used to examine the dyeing behaviors before and after dyeing and the binding form between reactive dyes and F. mandshurica veneer was analyzed. Based on the optimization of process parameters, the optimal dyeing condition was considered to be 75 °C, the dye concentration to be 0.5â»1.0%, the dyeing time to be 60 min and the bath ratio to be 20:1. The dye uptakes of reactive brilliant red X-3B, black KN-B and blue K-3R dyes were 75.0â»75.4%, 50.0â»64.6% and 32.0â»66.0%, respectively. The chromatic aberration of F. mandshurica veneer dyed with reactive brilliant red X-3B, black KN-B and blue K-3R dyes was 53.0â»59.0, which was a significant increase. After dyeing, the hardness and impact strength of the waterborne coating on the dyed F. mandshurica increased but adhesion was reduced. The coating films produced a matte glossiness.