RESUMEN
BACKGROUND: In the repair of massive tissue defects using expanded large skin flaps, the incidence of complications increases with the size of the expanded area. Currently, stem cell therapy has limitations to solve this problem. We hypothesized that conditioned medium of adipose-derived stem cells (ADSC-CM) collected following mechanical pretreatment can assist skin expansion. METHODS: Rat aortic endothelial cells and fibroblasts were cultured with ADSC-CM collected under 0%, 10%, 12%, and 15% stretching force. Ten-milliliter cylindrical soft tissue expanders were subcutaneously implanted into the backs of 36 Sprague-Dawley rats. The 0% and 10% stretch groups were injected with ADSC-CM collected under 0% and 10% stretching force, respectively, while the control group was not injected. After 3, 7, 14, and 30 days of expansion, expanded skin tissue was harvested for staining and qPCR analyses. RESULTS: Endothelial cells had the best lumen formation and highest migration rate, and fibroblasts secreted the most collagen upon culture with ADSC-CM collected under 10% stretching force. The skin expansion rate was significantly increased in the 10% stretch group. After 7 days of expansion, the number of blood vessels in the expanded area, expression of the angiogenesis-associated proteins vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, and collagen deposition were significantly increased in the 10% stretch group. CONCLUSIONS: The optimal mechanical force upregulates specific paracrine proteins in ADSCs to increase angiogenesis and collagen secretion, and thereby promote skin regeneration and expansion. This study provides a new auxiliary method to expand large skin flaps.
Asunto(s)
Tejido Adiposo , Comunicación Paracrina , Ratas Sprague-Dawley , Piel , Animales , Ratas , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Piel/metabolismo , Fibroblastos/metabolismo , Fibroblastos/citología , Células Endoteliales/metabolismo , Células Endoteliales/citología , Medios de Cultivo Condicionados/farmacología , Expansión de Tejido/métodos , Masculino , Células Madre/metabolismo , Células Madre/citología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Células Cultivadas , Neovascularización Fisiológica , Estrés MecánicoRESUMEN
BACKGROUND: Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration. METHODS: Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system. RESULTS: Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration. CONCLUSIONS: Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.
Asunto(s)
Tejido Adiposo , Quimiocina CXCL12 , Receptores CXCR4 , Regeneración , Células Madre , Proteína de Unión al GTP rhoA , Quimiocina CXCL12/metabolismo , Animales , Receptores CXCR4/metabolismo , Ratones , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Células Madre/metabolismo , Células Madre/citología , Ratones Endogámicos C57BL , Retroalimentación Fisiológica , Movimiento Celular , Células Cultivadas , Masculino , Transducción de SeñalRESUMEN
Background: Global patterns of immune cell communications in the immune microenvironment of skin cutaneous melanoma (SKCM) haven't been well understood. Here we recognized signaling roles of immune cell populations and main contributive signals. We explored how multiple immune cells and signal paths coordinate with each other and established a prognosis signature based on the key specific biomarkers with cellular communication. Methods: The single-cell RNA sequencing (scRNA-seq) dataset was downloaded from the Gene Expression Omnibus (GEO) database, in which various immune cells were extracted and re-annotated according to cell markers defined in the original study to identify their specific signs. We computed immune-cell communication networks by calculating the linking number or summarizing the communication probability to visualize the cross-talk tendency in different immune cells. Combining abundant analyses of communication networks and identifications of communication modes, all networks were quantitatively characterized and compared. Based on the bulk RNA sequencing data, we trained specific markers of hub communication cells through integration programs of machine learning to develop new immune-related prognostic combinations. Results: An eight-gene monocyte-related signature (MRS) has been built, confirmed as an independent risk factor for disease-specific survival (DSS). MRS has great predictive values in progression free survival (PFS) and possesses better accuracy than traditional clinical variables and molecular features. The low-risk group has better immune functions, infiltrated with more lymphocytes and M1 macrophages, with higher expressions of HLA, immune checkpoints, chemokines and costimulatory molecules. The pathway analysis based on seven databases confirms the biological uniqueness of the two risk groups. Additionally, the regulon activity profiles of 18 transcription factors highlight possible differential regulatory patterns between the two risk groups, suggesting epigenetic event-driven transcriptional networks may be an important distinction. MRS has been identified as a powerful tool to benefit SKCM patients. Moreover, the IFITM3 gene has been identified as the key gene, validated to express highly at the protein level via the immunohistochemical assay in SKCM. Conclusion: MRS is accurate and specific in evaluating SKCM patients' clinical outcomes. IFITM3 is a potential biomarker. Moreover, they are promising to improve the prognosis of SKCM patients.
Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Monocitos , Macrófagos , Microambiente Tumoral , Proteínas de la Membrana , Proteínas de Unión al ARN , Melanoma Cutáneo MalignoRESUMEN
Skin cutaneous melanoma (SKCM) is the most malignant skin tumor for it is enormously easy to develop invasion and metastasis. Autophagy is a process by which cellular material is degraded by lysosomes or vacuoles and recycled. Autophagy-related long non-coding RNAs (lncRNAs) have been thought to correlate with SKCM. This study aims to explore the prognostic significance of autophagy-related lncRNAs and establish a prognostic model of autophagy-related lncRNA pairs in SKCM. Firstly, the RNA-seq data and related clinical information were downloaded from the TCGA database. 446 qualified samples were enrolled. 222 autophagy-related genes were obtained from the HADb database. Pearson correlation analysis was conducted to identify autophagy-related lncRNAs (ARLs). After that, we obtained prognosis-related ARLs and autophagy-related lncRNA pairs (ARLPs). Using Lasso-Cox regression analysis, an autophagy-related lncRNA-pair prognostic signature was established. The accuracy of the signature were confirmed through a series of validations in terms of mutation profiles, immunity infiltration, and cellular pathways. And we used the random forest method to find USP30-AS1 as a key mediating factor in SKCM.
Asunto(s)
Melanoma , ARN Largo no Codificante , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , ARN Largo no Codificante/genética , Autofagia/genética , Algoritmos , Pronóstico , Melanoma Cutáneo MalignoRESUMEN
Stem cells have attracted much attention in the field of regeneration due to their unique ability to promote regeneration. Among the many approaches used to regulate directed proliferation and differentiation of stem cells, application of mechanical forces is safe, simple, and easy to implement, all of which are advantageous to practical applications. In this review, the mechanisms of mechanical regulation of stem cell proliferation and differentiation are summarized with emphasis on force transduction pathways from the extracellular matrix to the nucleus. Prospects for future clinical applications are also discussed. In conclusion, through specific signaling pathways, mechanical signals ultimately affect gene expression and thus guide cell fate. Mechanical factors can regulate proliferation and differentiation of stem cells through signaling pathways, a greater understanding of which will contribute to future research and applications of cell regeneration therapy. Impact statement Mechanical mechanics is vital for the regulation of cell fate; especially in the field of regenerative medicine, mechanical control has characteristics that are simple and comparable. Mechanically regulated pathways exist widely in cells and are distributed at various structural levels of cells. In this review, we categorized the mechanical regulatory pathways through the clue of the mechanical transmission. We tried to include some newly researched pathways, such as Piezo-related pathways, to show the recent vigorous development in this field.
Asunto(s)
Transducción de Señal , Células Madre , Humanos , Diferenciación Celular , Proliferación Celular , Estrés MecánicoRESUMEN
As an important component carrying the core function and service life of switching appliances, the selection and improvement of electrical contact materials is of great significance. AgSnO2, which is non-toxic, environmentally friendly and has excellent performance, has become the most promising contact material to replace AgCdO. However, it has deficiencies in machinability and electrical conductivity. The property of AgSnO2 contact material was improved by doping element Cr. The relationship between the mechanical and electrical properties of AgSnO2 contact materials and doping concentrations were investigated and analyzed by simulation and experiment. Based on the first principle, the elastic constants of supercell models Sn1-xCrxO2 (x = 0, 0.083, 0.125, 0.167, 0.25) were calculated. The results show that the material with a doping ratio of 25% is least prone to warp and crack, and the material with a doping ratio of 12.5% has the best toughness and ductility and the lowest hardness, which leads to molding and is subsequently easier to process. The Cr-doped AgSnO2 contacts with different doping proportions were prepared by the sol-gel and powder metallurgy method. Additionally, their physical performance and electrical contact properties were measured in experiments. The results show that the doped SnO2 powders prepared by the sol-gel method realize integration doping, which is consistent with the crystal model constructed in the simulation calculation. Sn0.875Cr0.125O2 has lower hardness, which is beneficial to process and form. Doping helps to stabilize the arc root, inhibit the ablation of contact by arc, reduces arc duration and arc energy, improves the resistance to arc erosion of AgSnO2 contact material, and makes electrical contact performance more stable. The contact material with a doping concentration of 16.7% has the best arc erosion resistance.
RESUMEN
Skin cutaneous melanoma (SKCM) attracts attention worldwide for its extremely high malignancy. A novel term cytolytic activity (CYT) has been introduced as a potential immunotherapy biomarker associated with counter-regulatory immune responses and enhanced prognosis in tumors. In this study, we extracted all datasets of SKCM patients, namely, RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database, conducted differential expression analysis to yield 864 differentially expressed genes (DEGs) characteristic of CYT and used non-negative matrix factorization (NMF) method to classify molecular subtypes of SKCM patients. Among all genes, 14 hub genes closely related to prognosis for SKCM were finally screen out. Based on these genes, we constructed a 14-gene prognostic risk model and its robustness and strong predictive performance were further validated. Subsequently, the underlying mechanisms in tumor pathogenesis and prognosis have been defined from a number of perspectives, namely, tumor mutation burden (TMB), copy number variation (CNV), tumor microenvironment (TME), infiltrating immune cells, gene set enrichment analysis (GSEA) and immune checkpoint inhibitors (ICIs). Furthermore, combined with GTEx database and HPA database, the expression of genes in the model was verified at the transcriptional level and protein level, and the relative importance of genes in the model was described by random forest algorithm. In addition, the model was used to predict the difference in sensitivity of SKCM patients to chemotherapy and immunotherapy. Finally, a nomogram was constructed to better aid clinical diagnosis.
RESUMEN
Vacuum flat panel detectors (VFPDs) using cold cathode have important applications in large-area photoelectric detection. Based on the electron-bombardment-induced photoconductivity (EBIPC) mechanism, the photoconductor-type VFPDs achieved high detection sensitivity. However, pixelated imaging devices have not yet been developed. In this paper, we fabricate a 4 × 7 pixel vacuum flat panel detector array made of ZnS photoconductor and ZnO nanowires cold cathode for an imaging application. The responsivity of the device and the pixel current uniformity are studied, and imaging of the patterned objects is achieved. Our results verify the feasibility of VFPDs for imaging.
RESUMEN
Semiconductors with broadband photoelectric response have important practical needs in many aspects such as solar energy conversion, photocatalysis, and photodetection. We synthesized the first photochromic semiconductive hydrogen-bonded organic framework (HOF), [H2(bpyb)](H2PO4)2·2H2O (1), using the polycyclic viologen cation [H2(bpyb)] (bpyb = 1,4-bis(tetrapyridyl)benzene). After 1 s of xenon lamp irradiation, compound 1 showed a visible color change from the initial yellowish to dark purple after continuous irradiation. The photoinduced radical product has an absorption band covering 200-1700 nm, which is wider than the absorption ranges of silicon and perovskites. It produced photocurrent when irradiated with a xenon lamp or a laser (355, 532, or 808 nm). The on/off ratio of the current (Iirr/Idark) can be as high as 300 times under the irradiation of the 808 nm laser with a power of 1.9 W cm-2. In addition, under the 808 nm light source, the on/off ratio of 1B is 35 times that of 1A.
RESUMEN
Diabetes mellitus is the most common metabolic disease associated with impaired wound healing. Recently, Schwann cells (SCs), the glia of the peripheral nervous system, have been suggested to accelerate normal skin wound healing. However, the roles of SCs in diabetic wound healing are not fully understood. In this study, Full-thickness wounds were made in the dorsal skin of C57/B6 mice and db/db (diabetic) mice. Tissue samples were collected at different time points, and immunohistochemical and immunofluorescence analyses were performed to detect markers of de-differentiated SCs, including myelin basic protein, Sox 10, p75, c-Jun, and Ki67. In addition, in vitro experiments were performed using rat SC (RSC96) and murine fibroblast (L929) cell lines to examine the effects of high glucose conditions (50 mM) on the de-differentiation of SCs and the paracrine effects of SCs on myofibroblast formation. Here, we found that, compared with that in normal mice, wound healing was delayed and SCs failed to rapidly activate a repair program after skin wound injury in diabetic mice. Furthermore, we found that SCs from diabetic mice displayed functional impairments in cell de-differentiation, cell-cycle re-entry, and cell migration. In vitro, hyperglycemia impaired RSC 96 cell de-differentiation, cell-cycle re-entry, and cell migration, as well as their paracrine effects on myofibroblast formation, including the secretion of TGF-ß and Timp1. These results suggest that delayed wound healing in diabetes is due in part to a diminished SC repair response and attenuated paracrine effects on myofibroblast formation.
RESUMEN
PURPOSE: A high-precision rotated elliptical beam profiling method based on pixel ion chamber is proposed in this paper. This method aims to improve the accuracy by modeling the transverse profile of rotated beam as an ellipse with additional correlation coefficient and eliminating the fitting error due to the volume averaging effect of pixel ion chamber. METHODS: In pencil beam scanning (PBS) proton therapy systems, the transverse beam profile model is generally represented as a standard Gaussian distribution. Considering the elliptical spots, two-dimensional (2D) joint Gaussian distribution characterized with the correlation coefficient ρ is adopted in this study. Gaussian-type particle distribution with white noise was generated and processed in MATLAB to simulate the secondary particle collection in the pixel ion chamber. The simulated pixel ion chamber is a commercially available ion chamber which consists of 12 × 12 small square pixels (3.75 × 3.75 mm2 ) with a 0.05 mm interval. The simulated signals were preprocessed by filtering with the noise threshold and extracting the maximum simply connected domain (MSCD) of the signal. Then, five geometric parameters that identify the transverse beam profiles were fitted under different signal-to-noise ratio (SNR) conditions: the center of the beam (x0 , y0 ), the spot size (σmajor , σminor ), and the rotation angle θ formed between the major axes of elliptical spot and the x axes of the ion chamber. First, the simulated signals were preprocessed by filtering with the noise threshold and extracting the MSCD of the signal. Second, a rectification curve of systematic error in fitted spot size versus the prescribed spot size was used to predict the systematic error due to the volume averaging effect. Finally, the effects of fitting errors on therapeutic dose were evaluated in terms of gamma index and relative dose difference. RESULTS: When the SNR is not less than 20 dB, the relative fitting error of spot size and the absolute fitting error of angle θ are less than 1% and 6.1°, respectively. The fitting error of beam center increases with spot size and will not exceed 0.22 mm when spot size reaches up to 12 mm. At a SNR equal to 20 dB, neither cold nor hot spots were presented in dose distribution calculated with the fitted spot parameters. CONCLUSION: The improved Gaussian fitting algorithm performs well when SNR is not less than 20 dB. This method can effectively distinguish the nominal beam and rotated elliptical beam. An ideal systematic error curve can be predicted and used to correct the fitted spot size, thus eliminating the systematic error due to the volume averaging effect of the pixel ion chamber. The fitting error of spot size cannot be fully corrected, but it is negligible and shows little effect on the overall therapeutic dose.
Asunto(s)
Terapia de Protones , Algoritmos , Distribución Normal , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Relación Señal-RuidoRESUMEN
In this paper, we propose a deep-learning-based method using a convolutional neural network (CNN) to predict the volume flow rates of individual phases in the oil-gas-water three-phase intermittent flow simultaneously by analyzing the measurement data from multiple sensors, including a temperature sensor, a pressure sensor, a Venturi tube and a microwave sensor. To build datasets, a series of experiments for the oil-gas-water three-phase intermittent flow in a horizontal pipe, in which gas volume fraction and water-in-liquid ratio ranges are 23.77-94.45% and 14.95-86.97%, respectively, and gas flow superficial velocity and liquid flow superficial velocity ranges are 0.66-5.23 and 0.27-2.14 m/s, respectively, have been carried out on a test loop pipeline. The preliminary results indicate that the model can provide relative prediction errors on the testing-1 dataset for the volume flow rates of oil-phase, gas-phase and water-phase within ±10% with 94.49%, 92.56% and 95.71% confidence levels, respectively. Additionally, the prediction results on the testing-2 dataset also demonstrate the generalization ability of the model. The consuming time of a prediction with one sample is 0.43 s on an Intel Xeon CPU E5-2678 v3, and 0.01 s on an NVIDIA GeForce GTX 1080 Ti GPU. Hence, the proposed CNN-based prediction model, which can fulfill the real-time application requirements in the petroleum industry, reveals the potential of using deep learning to obtain accurate results in the multiphase flow measurement field.
RESUMEN
The mechanism underlying burn injury-induced enhanced vascular endothelial permeability and consequent body fluid extravasation is unclear. Here, the rat aortic endothelial cells (RAECs) were treated with the serum derived from rats with burn injury to elucidate the mechanism. Sprague-Dawley (SD) rats were grouped as follows (10 rats/group): control, 2, 4, 8, 12, and 24 hours postburn groups. The heart, liver, kidney, lung, jejunum, and ileum of rats injected with 2% Evans blue (EB) through the tail vein were excised to detect the EB level in each organ. The serum levels of hypoxia-inducible factor-1α (HIF-1α) and endothelin-1 (ET-1) were examined using enzyme-linked immunosorbent assay (ELISA). The effect of serum from 12-hour postburn group on the membrane permeability of RAEC monolayer, as well as on the mRNA and protein levels of ET-1, endothelin receptor A (ETA), ETB, and zonula occludens (ZO-1), was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The membrane permeability of GV230/HIF-1α-transfected or shRNA-HIF-1α-transfected RAECs, as well as the expression levels of HIF-1α, ET-1, ETA, ETB, vascular endothelial (VE)-cadherin, and claudin-5, was analyzed using qRT-PCR and western blotting, whereas the localization of VE-cadherin and claudin-5 was examined using immunofluorescence. The serum HIF-1α and ET-1 levels in the burn groups, which peaked at 12 hours postburn, were significantly upregulated (P < .01) when compared with those in the control group. Additionally, the serum HIF-1α levels were positively correlated with vascular permeability. Compared with the shRNA-negative control-transfected RAECs, the shRNA-II/HIF-1α-transfected RAECs exhibited downregulated expression of HIF-1α, ET-1, ETA, and ETB (P < .01), and upregulated expression of ZO-1, claudin-5, and VE-cadherin (P < .05). Compared with the GV230-transfected RAECs, the GV230/HIF-1α-transfected RAECs exhibited upregulated expression of HIF-1α, ET-1, ETA, and ETB (P < .01), and downregulated expression of ZO-1, claudin-5, and VE-cadherin (P < .05). The GV230/HIF-1α-transfected RAECs exhibited degradation and translocation of VE-cadherin and claudin-5. In addition to degradation of VE-cadherin and claudin-5, HIF-1α mediated enhanced endothelial cell permeability through upregulation of ET-1, ETA, and ETB, and downregulation of ZO-1 and VE-cadherin in rats with burn injury.
Asunto(s)
Quemaduras/metabolismo , Cadherinas/metabolismo , Claudina-5/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Permeabilidad Capilar , Femenino , Masculino , Permeabilidad , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Local tissue damage caused by electrical burns is often deep and severe. High-voltage electrical burns are common in the head, neck and torso areas. These are mostly caused by direct contact with the power supply and are often accompanied by deep injuries of the nerve, blood vessel, muscle, tendon, and bone. We must pay great attention to the clinical treatment of these parts injured by electrical burn. CASE PRESENTATION: The first case involved a migrant worker who touched a 6-kV high-tension wire when welding steel; this electric shock caused burns in many places. Deep electrical burn wounds were mainly located on the left shoulder and back, characterized by widespread skin and soft tissue defect and bone necrosis. We utilized a lower trapezius myocutaneous flap to repair these wounds in the neck and back caused by deep electrical burns. The flap survived completely and the wound was effectively repaired. The function and shape of the shoulder and back after the restoration were satisfactory. The second case involved a 29-year-old who accidentally touched a high-voltage wire while working and was burned by a 30,000-V electric shock. His wounds were mainly located on the left head, neck, back and left upper limbs. We designed a 30 cm × 12 cm right trapezius myocutaneous flap which completely covered the wound surface; the electrical burn wounds on the neck and back were effectively repaired. After the electrical burn wound was repaired, the neck function returned to normal with a satisfactory shape. CONCLUSION: The authors report two cases of patients who were burned by high voltage. We used lower trapezius myocutaneous flaps to repair their wounds, which achieved satisfactory clinical results. This study has provided a reliable surgical method for the clinical treatment of deep electrical burn wounds in the neck, shoulders and back.
Asunto(s)
Quemaduras por Electricidad/cirugía , Colgajo Miocutáneo/cirugía , Procedimientos de Cirugía Plástica/métodos , Traumatismos de los Tejidos Blandos/cirugía , Músculos Superficiales de la Espalda/cirugía , Adulto , Humanos , Masculino , Cicatrización de HeridasRESUMEN
OBJECTIVE: To investigate the effect of calmodulin (CaM) and its mutants on binding to voltage-gated Na channel isoleucine-glutamine domain (NaV1.2 IQ). METHODS: The cDNA of NaV1.2 IQ was constructed by PCR technique, CaM mutants CaM12, CaM34 and CaM1234 were constructed with QuickchangeTM site-directed mutagenesis kit (QIAGEN). The binding of NaV1.2 IQ to CaM and CaM mutants under calcium and calcium free conditions were detected by pull-down assay. RESULTS: NaV1.2 IQ and CaM were bound to each other at different calcium concentrations, while GST alone did not bind to CaM. The binding affinity of CaM and NaV1.2 IQ at [Ca2+]-free was greater than that at 100 nmol/L [Ca2+] (P < 0.05). In the absence of calcium, the binding amount of CaM wild-type to NaV1.2 IQ was greater than that of its mutant, and the binding affinity of CaM1234 to NaV1.2 IQ was the weakest among the three mutants (P < 0.05). CONCLUSIONS: The binding ability of CaM and CaM mutants to NaV1.2 IQ is Ca2+-dependent. This study has revealed a new mechanism of NaV1.2 regulated by CaM, which would be useful for the study of ion channel related diseases.
Asunto(s)
Calmodulina , Canal de Sodio Activado por Voltaje NAV1.2 , Calcio/metabolismo , Calmodulina/genética , Calmodulina/metabolismo , Mutación , Canal de Sodio Activado por Voltaje NAV1.2/metabolismo , Unión Proteica/genéticaRESUMEN
The solution of how to accurately and timely predict the flowrate of gas-liquid mixtures is the key to help petroleum and other related industries to reduce costs, improve efficiency, and optimize management. Although numerous studies have been carried out over the past decades, the problem is still significantly challenging due to the complexity of multiphase flows. This paper attempts to seek new possibilities for multiphase flow measurement and novel application scenarios for state-of-the-art machine learning (ML) techniques. Convolutional neural networks (CNNs) are applied to predict the flowrate of multiphase flows for the first time and can achieve promising performance. In addition, considering the difference between data distributions of training and testing samples and its negative impact on prediction accuracy of the CNN models on testing samples, we propose flow adversarial networks (FANs) that can distill both domain-invariant and flowrate-discriminative features from the raw input. The method is evaluated on dynamic experimental data of different multiphase flows on different flow conditions and operating environments. The experimental results demonstrate that FANs can effectively prevent the accuracy degradation caused by the gap between training and testing samples and have better performance than state-of-the-art approaches in the flowrate prediction field.
RESUMEN
OBJECTIVE: To examine the aberrant expression of endothelial permeability associated proteins including MLCK, p-MLC and ZO-1 in presence of different levels of hypoxia-inducible factor 1 alpha (HIF-1α). METHODS: We established monolayer vascular endothelial cell model with the primary rat endothelial cells. Over-expressed or under-expressed HIF-1α cell lines were made by endothelial cells transfected with plasmid vector constructed with HIF-1α gene or HIF-1α-specific short hairpin RNA (shRNA). Levels of mRNA and protein of MLCK, p-MLC and ZO-1 were determined using Real-Time PCR and Western blot. All data were analyzed using by One-Way ANOVA method and LSD. RESULTS: We successfully cultured the rat endothelial primary cells for four days. The mRNA and protein levels of MLCK and p-MLC were significantly increased in the HIF-1α over-expression group than that in the blank control group and the empty plasmid GV230 group (Pï¼0.05). ZO-1 was significantly lower in the HIF-1α over-expression group than that in the blank control group and the GV230 group. On the contrary, the mRNA and protein levels of MLCK and p-MLC were significantly lower in the HIF-1α under-expression group than that in the blank control group and the shRNA-NC group (Pï¼0.05). ZO-1 was significantly higher in the HIF-1α low-expression group than that in the blank control group and the shRNA-NC group. CONCLUSION: HIF-1α positively regulates the expression of MLCK and p-MLC and negatively regulates the expression of ZO-1 in rat monolayer endothelial cells.
Asunto(s)
Células Endoteliales/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Cadenas Ligeras de Miosina/metabolismo , Quinasa de Cadena Ligera de Miosina/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Cadenas Ligeras de Miosina/genética , Quinasa de Cadena Ligera de Miosina/genética , Fosforilación , Ratas , Ratas Sprague-Dawley , Proteína de la Zonula Occludens-1/genéticaRESUMEN
INTRODUCTION: Electrical burns are caused by the conversion of electrical energy flowing through the body into heat energy, which can cause coagulative necrosis of the skin and deep tissues. Deep tissue damage is often more serious than skin damage. Electrical burns have the characteristics of destructive and progressive damage and present the common symptoms of severe local tissue damage accompanied by a wide range of deep tissue necrosis, resulting in injury of nerves, blood vessels, bones, and internal organs. Autologous skin grafting alone cannot effectively cover deep tissues or repair electrical burn wounds. CASE REPORT: This article describes 2 patients with deep electrical burns in the lower abdomen that showed extensive skin and soft tissue damage, partial necrosis of abdominal muscle tissue, and weak abdominal wall. As a single tissue flap was too small to effectively cover the defect wound, ilioinguinal flap and tensor fascia lata muscle flap were utilized in both cases with good outcomes. These flaps survived completely, and the wounds were effectively repaired. After repair, the shape was satisfactory, and the function of the lower abdomen was normal. CONCLUSIONS: Transfer of flaps from a site near the wound for repairing electrical burns is convenient for transfer with minimal surgical trauma and a simpler operating procedure than the free flap.
Asunto(s)
Quemaduras por Electricidad/cirugía , Fascia/trasplante , Procedimientos de Cirugía Plástica/métodos , Trasplante de Piel/métodos , Traumatismos de los Tejidos Blandos/cirugía , Cicatrización de Heridas/fisiología , Autoinjertos , Quemaduras por Electricidad/diagnóstico , Niño , Desbridamiento/métodos , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Traumatismos de los Tejidos Blandos/diagnósticoRESUMEN
Controlling the formation of MnS inclusions during solidification influences the mechanical properties and machinability of the resulfurized steel. A coupled segregation-nucleation-growth model was developed by the finite-difference method involving solute redistribution, heterogeneous nucleation and growth kinetics. Laboratory solidification experiments were performed under various cooling rates in resulphurised 49MnVS steel. In this work, the influence of cooling rate on solute redistribution and growth size of MnS inclusions were simulated using the current coupled model, and the calculated results can provide a valuable reference for MnS formation. Increasing of the cooling rate led to early precipitation and refinement of formed MnS inclusions. Based on the simulation results and experimental data, mathematical relationships between the growing size of MnS with the cooling rate in the low ductility temperature region and in the whole solidification were obtained.
RESUMEN
OBJECTIVE: To explore the mechanism of hypertonic salt solution (HS) alleviates lung injury of rats at the early stage of severe scald. METHODS: Thirty-two female Sprague-Dawley (SD) rats were randomly assigned to sham group, lactated Ringer solution (LR) group, HS200 group (200 mmol/L HS group, 1 L 200 mmol/L HS contained 955 mL LR and 45 mL 10% NaCl) and HS400 group (400 mmol/L HS group, 1 L 400 mmol/L HS contained 846 mL LR and 154 mL 10% NaCl), with 8 rats in each group. A 30% total body surface area (TBSA) III degree scalded model was reproduced by scalded on the back with 98 centigrade boiling water for 12 seconds, whereas those in the sham group were exposed to 37 centigrade water without liquid resuscitation. Rats in the three drug intervention groups were resuscitated with LR, 200 mmol/L HS and 400 mmol/L HS by caudal vein according to the Parkland formula, respectively. All rats were sacrificed at 8 hours after scald injury to harvest abdominal aorta blood and lung tissues. Interleukins (IL-6, IL-10 and IL-17) in serum were determined by enzyme-linked immunosorbent assay (ELISA). Samples from the lung tissue were used to measure malondialdehyde (MDA) and superoxide dismutase (SOD) levels by ultraviolet spectrophotometer. Expressions of p38 mitogen-activated protein kinase (p38MAPK) and extracellular regulated protein kinase 1/2 (ERK1/2) in the lung were determined by Western Blot. The lung tissue was stained with hematoxylin and eosin (HE), and the pathological changes were observed with a light microscope. RESULTS: Compared with the sham group, the lung tissues in the LR group were damage obviously, which accompanied with more inflammatory cell infiltration, cell edema and pulmonary septum thickening, and the levels of IL-6, IL-10, IL-17 in serum and MDA content, the phosphorylation of p38MAPK and ERK1/2 in lung tissues were increased whereas the activity of SOD was decreased. Compared with the LR group, the lung injury was significantly alleviated, the levels of IL-6, IL-17 in serum and MDA content and the phosphorylation of p38MAPK and ERK1/2 were decreased, and the levels of IL-10 and SOD were increased in both HS groups with a dose-dependent manner. There were significant difference in above parameters between HS400 group and LR group [serum IL-6 (ng/L): 3.76±0.12 vs. 6.72±0.90, serum IL-10 (ng/L): 33.76±3.71 vs. 16.77±3.19, serum IL-17 (ng/L): 103.52±2.78 vs. 124.96±4.96, lung MDA (nmol/mg): 5.59±0.24 vs. 7.09±0.39, lung SOD (U/mg): 226.7±3.9 vs. 172.7±3.4, lung phosphorylation of p38MAPK (p-p38MAPK)/p38MAPK: 0.15±0.09 vs. 0.35±0.19, lung phosphorylation of ERK1/2 (p-ERK1/2)/ERK1/2: 0.27±0.01 vs. 0.70±0.01, all P < 0.01]. CONCLUSIONS: HS protected against lung injury induced by severe burns in rats with a dose-dependent manner, and it was better than LR, and its possible mechanism was related with reducing the expression of p38MAPK and ERK1/2 pathway in lung tissue, increasing the level of anti-inflammatory cytokines and decreasing the release of pro-inflammatory cytokines, thus inhibiting excessive inflammation and oxidative stress injury in lung.