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OBJECTIVES: The COVID-19 pandemic poses ongoing challenges to global public health systems, emphasizing the critical necessity for efficient diagnostic and prognostic markers. This study evaluates the MAGLUMI® SARS-CoV-2 Ag N protein chemiluminescent immunoassay (MAG-CLIA) for its analytical performance and its role in predicting disease severity and prognosis among severe COVID-19 patients with comorbidities. METHODS: Analytical validation of plasma MAG-CLIA SARS-CoV-2 Ag N protein encompassed precision, interference, LoQ and linearity. Plasma N protein concentrations and other biomarkers were measured within 48â¯h of admission, tracked until discharge or death. The Mann-Whitney U test explored the association between plasma N protein and COVID-19 severity or prognosis. Longitudinal monitoring of plasma N protein dynamics was conducted in representative patients. RESULTS: MAG-CLIA demonstrated precise quantification of plasma N protein with a CV below 10â¯% and minimal interference. The LoQ was 0.88â¯ng/L, with a broad linear range. Plasma N protein showed high diagnostic accuracy for COVID-19, achieving 95.42â¯% specificity and 78.32â¯% sensitivity at 2.388â¯ng/L. Plasma N protein emerged as a valuable prognostic indicator, correlating with mechanical ventilation need and patient survival. Plasma N protein concentrationsâ¯≥â¯424.3â¯ng/L (AUC 0.8102, sensitivity 78.38â¯%, specificity 85.48â¯%) were associated with poor prognosis in severe COVID-19 patients with comorbidities. CONCLUSIONS: MAG-CLIA's SARS-CoV-2â¯N protein detection in plasma demonstrates both analytical reliability and clinical relevance in our inaugural evaluation. As a promising prognostic biomarker for severe COVID-19 patients, it offers crucial insights into disease severity and progression, emphasizing the significance of early monitoring and intervention, especially for patients with comorbidities.
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Leukemia stem cells (LSCs) are recognized as the root cause of leukemia initiation, relapse, and drug resistance. Lipid species are highly abundant and essential component of human cells, which often changed in tumor microenvironment. LSCs remodel lipid metabolism to sustain the stemness. However, there is no useful lipid related biomarker has been approved for clinical practice in AML prediction and treatment. Here, we constructed and verified fatty acid metabolism-related risk score (LFMRS) model based on TCGA database via a series of bioinformatics analysis, univariate COX regression analysis, and multivariate COX regression analysis, and found that the LFMRS model could be an independent risk factor and predict the survival time of AML patients combined with age. Moreover, we revealed that Galectin-1 (LGALS1, the key gene of LFMRS) was highly expressed in LSCs and associated with poor prognosis of AML patients, and LGALS1 repression inhibited AML cell and LSC proliferation, enhanced cell apoptosis, and decreased lipid accumulation in vitro. LGALS1 repression curbed AML progression, lipid accumulation, and CD8+ T and NK cell counts in vivo. Our study sheds light on the roles of LFMRS (especially LGALS1) model in AML, and provides information that may help clinicians improve patient prognosis and develop personalized treatment regimens for AML.
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Ácidos Grasos , Galectina 1 , Leucemia Mieloide Aguda , Células Madre Neoplásicas , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/genética , Galectina 1/metabolismo , Galectina 1/genética , Ácidos Grasos/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Masculino , Animales , Femenino , Ratones , Factores de Riesgo , Microambiente Tumoral , Línea Celular Tumoral , Apoptosis , Proliferación Celular , Pronóstico , Persona de Mediana EdadRESUMEN
BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare malignant lymphoproliferative tumor. Our study aimed to investigate the mutational profile of VRL distinguishing from uveitis using next-generation sequencing (NGS) analysis on small amounts of vitreous fluid. METHODS: Vitreous samples from twenty-six eyes of twenty VRL patients and six eyes of five uveitis patients were enrolled. All vitreous samples underwent cytology, immunocytochemistry for B-cell markers, cytokines analysis of IL-10 and IL-6, and flow cytometry. NGS was performed in vitreous specimens from the 25 patients using 82 DLBCL-targeted mutation panels. Vitreous fluids from 8 cases were performed paired NGS-based mutation analysis on both cell-free DNA (cfDNA) and genomic DNA. RESULTS: The sensitivity and accuracy rates for vitreous cytology were 70 % and 76 %, and for cytokine analysis (IL-10/IL-6 > 1) were 65 % and 72 %, respectively. Overall, the common mutations in VRL were PIM1 (88.5 %), IGLL5 (88.5 %), KMT2C (73 %), MYD88 (77 %), CD79B (50 %) and TBL1XR1 (46.2 %). In addition, the genetic mutation in cfDNA was consistent with that in genomic DNA in eight VRL cases. CONCLUSIONS: The mutation analysis of 82 DLBCL-targeted spectrum mutation panels by NGS on the vitreous samples is a sensitive and specific tool for distinguishing VRL from uveitis. Utilizing cfDNA for NGS analysis may serve as a liquid biopsy to aid in the diagnosis of VRL, particularly when using small-volume aspirate.
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Pueblos del Este de Asia , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Neoplasias de la Retina , Cuerpo Vítreo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , China , Pueblos del Este de Asia/genética , Linfoma/genética , Linfoma/diagnóstico , Neoplasias de la Retina/genética , Neoplasias de la Retina/diagnóstico , Cuerpo Vítreo/patología , Cuerpo Vítreo/metabolismoRESUMEN
The visible light communication channel has time-varying characteristics and is difficult to predict. This paper proposes an equalization algorithm based on the structure of a convolutional neural network (CNN), combining time series feature length and long short-term memory (LSTM), and adding a residual structure. It can be seen that the equalization coefficient vector of the optical channel is a time series, which can reflect the noise characteristics of the channel and has storage characteristics. The equalizer algorithm can accurately learn the complex channel characteristics and calculate the compensation coefficient according to the channel characteristics. It can also restore the original transmission signal. At the same time, this paper also examines the compensation method of the receiver in the mobile state. The long-term memory parameters of LSTM are used to represent the sequence causality in the memory channel, and CNN and residual structure are used to refine the results and improve the accuracy of the reconstruction. The simulation results show that the algorithm can effectively eliminate the influence of the fading characteristics of the visible optical channel, improve the bit error rate performance of system transmission, solve the overall problem of channel corruption, and precisely restore the original transmission signal with fast convergence speed. In addition, this method can achieve a better balance between performance and complexity compared to the traditional contention balancing method, which proves the potential and effectiveness of the proposed channel balancing method.
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Skin-slip provides crucial cues about the interaction state and surface properties. Currently, most skin-slip devices focus on two-dimensional tactile slip display and have limitations when displaying surface properties like bumps and contours. In this paper, a wearable fingertip device with a simple, effective, and low-cost design for three-dimensional skin-slip display is proposed. Continuous multi-directional skin-slip and normal indentation are combined to convey the sensation of three-dimensional geometric properties in virtual reality during active finger exploration. The device has a tactile belt, a five-bar mechanism, and four motors. Cooperating with the angle-mapping strategy, two micro DC motors are used to transmit continuous multi-directional skin-slip. Two servo motors are used to drive the five-bar mechanism to provide normal indentation. The characteristics of the device were obtained through the bench tests. Three experiments were designed and sequentially conducted to evaluate the performance of the device in three-dimensional surface exploration. The experimental results suggested that this device could effectively transmit continuous multi-directional skin-slip sensations, convey different bumps, and display surface contours.
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Vehicular visible light communications (VVLC) is promising intelligent transportation systems technology with the utilization of light-emitting diodes. The main degrading factor for the performance of VVLC systems is noise. Traditional VVLC systems noise modeling is based on the additive white Gaussian noise assumption in the form of shot and thermal noise. In this paper, to investigate both time correlated and white noise components of the VVLC channel noise, we propose a noise analysis based on Allan variance, which provides a time-series analysis method to identify noise from the data. The results show that white noise and random walk are observed in the VVLC systems. We also propose a motion detection algorithm based on the adaptive Gaussian mixture (GM) model to generate a double Gaussian model of VVLC channel noise. We further present a study on the error performance of a VVLC system considering channel noise to be a mixture of Gaussian components. We derive the analytical expressions of probability of error for binary phase-shift keying and quadrature phase-shift keying constellations. It has been observed that, in the presence of GM noise, the system performance degrades significantly from the usual one expected in a Gaussian noise environment and becomes a function of the mixing coefficients of the GM distribution.
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Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an essential regulatory target of antioxidants, but the lack of Nrf2 active site information has hindered discovery of new Nrf2 agonists from food-derived compounds by large-scale virtual screening. Two deep-learning models were separately trained to screen for Nrf2-agonists and safety. The trained models screened potentially active chemicals from approximately 70,000 dietary compounds within 5 min. Of the 169 potential Nrf2 agonists identified via deep-learning screening, 137 had not been reported before. Six compounds selected from the new Nrf2 agonists significantly increased (p < 0.05) the activity of Nrf2 on carbon tetrachloride (CCl4)-intoxicated HepG2 cells (nicotiflorin (99.44 ± 18.5%), artemetin (97.91 ± 8.22%), daidzin (87.73 ± 3.77%), linonin (74.27 ± 5.73%), sinensetin (72.74 ± 10.41%), and tectoridin (77.78 ± 4.80%)), and their safety were demonstrated by an MTT assay. The safety and Nrf2 agonistic activity of nicotiflorin, artemetin, and daidzin were also reconfirm by a single-dose acute oral toxicity study and CCl4-intoxicated rat assay.
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Aprendizaje Profundo , Factor 2 Relacionado con NF-E2 , Ratas , Animales , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Antioxidantes/química , Dieta , Tetracloruro de Carbono/metabolismo , Estrés Oxidativo , Hígado/metabolismoRESUMEN
An integrated assessment of water environmental health risk through drinking water ingestion in Lhasa River has been implemented. The health risks caused by different pollutants in different age groups (children, juvenile and adult groups) are in the order of 10-8 ~ 10-7, 10-7 ~ 10-5 and 10-13 ~ 10-8 a-1, respectively. The total health risks for all age groups are lower than the International Commission on Radiation Protection recommended value and the U.S. Environmental Protection Agency recommended value at all points except LS4, LS12 and LS13. The total health risk levels in different age groups at most points are class III or II, which means that there are low or negligible negative effect in these points and age groups. It is more important to monitor the arsenic concentration. The water environment quality protecting in Lhasa River Basin must be consistent with the clear water and blue sky protecting in Tibet Autonomous Region and the national ecological security barrier construction on the Tibetan Plateau.
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Agua Potable , Contaminantes Químicos del Agua , Adulto , Niño , Humanos , Agua Potable/análisis , Monitoreo del Ambiente , Ríos , Contaminantes Químicos del Agua/análisis , Medición de Riesgo , Salud Ambiental , Ingestión de Alimentos , ChinaRESUMEN
Acute myeloid leukemia (AML) is a heterogeneous disorder with high morbidity and mortality under the existing treatment strategy. Here, we found that lysosome-associated protein transmembrane 4 beta (LAPTM4B) was frequently upregulated in AML, and high LAPTM4B was associated with poor outcome. Moreover, LAPTM4B promoted leukemia progression in vitro and in vivo. Mechanically, LAPTM4B interacted with RPS9, and positively regulated RPS9 protein stability, which enhanced leukemia cell progression via activating STAT3. Our findings indicate for the first time that LAPTM4B contributes to leukemia progression in a RPS9/STAT3-dependent manner, suggesting that LAPTM4B may serve as a promising target for treatment of AML.
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Leucemia Mieloide Aguda , Proteínas Oncogénicas , Humanos , Proteínas Oncogénicas/metabolismo , Proteínas de la Membrana/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
BACKGROUND: The Ferula genus encompasses 180-185 species and is one of the largest genera in Apiaceae, with many of Ferula species possessing important medical value. The previous studies provided more information for Ferula, but its infrageneric relationships are still confusing. In addition, its genetic basis of its adaptive evolution remains poorly understood. Plastid genomes with more variable sites have the potential to reconstruct robust phylogeny in plants and investigate the adaptive evolution of plants. Although chloroplast genomes have been reported within the Ferula genus, few studies have been conducted using chloroplast genomes, especially for endemic species in China. RESULTS: Comprehensively comparative analyses of 22 newly sequenced and assembled plastomes indicated that these plastomes had highly conserved genome structure, gene number, codon usage, and repeats type and distribution, but varied in plastomes size, GC content, and the SC/IR boundaries. Thirteen mutation hotspot regions were detected and they would serve as the promising DNA barcodes candidates for species identification in Ferula and related genera. Phylogenomic analyses with high supports and resolutions showed that Talassia transiliensis and Soranthus meyeri were nested in the Ferula genus, and thus they should be transferred into the Ferula genus. Our phylogenies also indicated the monophyly of subgenera Sinoferula and subgenera Narthex in Ferula genus. Twelve genes with significant posterior probabilities for codon sites were identified in the positively selective analysis, and their function may relate to the photosystem II, ATP subunit, and NADH dehydrogenase. Most of them might play an important role to help Ferula species adapt to high-temperatures, strong-light, and drought habitats. CONCLUSION: Plastome data is powerful and efficient to improve the support and resolution of the complicated Ferula phylogeny. Twelve genes with significant posterior probabilities for codon sites were helpful for Ferula to adapt to the harsh environment. Overall, our study supplies a new perspective for comprehending the phylogeny and evolution of Ferula.
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Ferula , Genoma del Cloroplasto , Genoma de Plastidios , Filogenia , Evolución Molecular , Genoma del Cloroplasto/genética , Codón/genéticaRESUMEN
OBJECTIVES: Various comorbidities associated with COVID-19 add up in severity of the disease and obviously prolonged the time for viral clearance. This study investigated a novel ultrasensitive MAGLUMI® SARS-CoV-2 Ag chemiluminescent immunoassay assay (MAG-CLIA) for diagnosis and monitoring the infectivity of COVID-19 patients with comorbid conditions during the pandemic of 2022 Shanghai. METHODS: Analytical performances of the MAG-CLIA were evaluated, including precision, limit of quantitation, linearity and specificity. Nasopharyngeal specimens from 232 hospitalized patients who were SARS-CoV-2 RT-qPCR positive and from 477 healthy donors were included. The longitudinal studies were performed by monitoring antigen concentrations alongside with RT-qPCR results in 14 COVID-19 comorbid participants for up to 22 days. The critical antigen concentration in determining virus infectivity was evaluated at the reference cycle threshold (Ct) of 35. RESULTS: COVID-19 patients were well-identified using an optimal threshold of 0.64 ng/L antigen concentration, with sensitivity and specificity of 95.7% (95% CI: 92.2-97.9%) and 98.3% (95% CI: 96.7-99.3%), respectively, while the Wondfo LFT exhibited those of 34.9% (95% CI: 28.8-41.4%) and 100% (95% CI: 99.23-100%), respectively. The sensitivity of MAG-CLIA remained 91.46% (95% CI: 83.14-95.8%) for the samples with Ct values between 35 and 40. Close dynamic consistence was observed between MAG-CLIA and viral load time series in the longitudinal studies. The critical value of 8.82 ng/L antigen showed adequate sensitivity and specificity in evaluating the infectivity of hospitalized convalescent patients with comorbidities. CONCLUSIONS: The MAG-CLIA SARS-CoV-2 Ag detection is an effective and alternative approach for rapid diagnosis and enables us to evaluate the infectivity of hospitalized convalescent patients with comorbidities.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Centros de Atención Terciaria , Prueba de COVID-19 , China , Nasofaringe , Pandemias , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The genus Seseli L., which consists of 125-140 species distributed in the Old World from western Europe and northwestern Africa to China and Japan, is one of the largest and most taxonomically difficult genera of Apiaceae Lindl. Although several previous studies have been conducted on Seseli based on limited morphological characteristics and molecular fragments, a robust and comprehensive phylogeny of Seseli remains elusive. Plastomes provide abundant genetic information and have been widely used in studying plant phylogeny and evolution. Consequently, we newly generated the complete plastomes of eleven Seseli taxa. We combined plastome data and morphological characteristics to investigate the phylogeny of Seseli. RESULTS: In our study, we observed that the genome length, gene numbers, IR/SC borders, and repeat composition of the eleven Seseli plastomes were variable. Several appropriate mutation hotspot regions may be developed as candidate DNA barcodes for evolution, phylogeny, and species identification of Seseli. The phylogenetic results identified that Seseli was not a monophyletic group. Moreover, the eleven newly sequenced Seseli taxa did not cluster with S. tortuosum (the type species of Seseli, belonging to the tribe Selineae), where S. delavayi clustered with Eriocycla belonging to the tribe Echinophoreae and the other ten belonged to Selineae. The comparative plastome and morphological characteristics analyses confirmed the reliability of the phylogenetic analyses and implied the complex evolution of Seseli. CONCLUSION: Combining molecular and morphological data is efficient and useful for studying the phylogeny of Seseli. We suggest that "a narrow sense" of Seseli will be meaningful for further study and the current taxonomic system of Seseli needs to be revised. In summary, our study can provide new insights into the phylogenetic relationships and taxonomic framework of Seseli.
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Apiaceae , Filogenia , Apiaceae/genética , Evolución Molecular , Reproducibilidad de los Resultados , Secuencia de BasesRESUMEN
Centrifugal modelling, both physical and numerical, has been used for studying groundwater flow and transport processes in the past. However, there was disagreement in previous studies whether numerical models can be used in simulating centrifugal systems under unsaturated flow condition. In the present study, a numerical model based on Richards' equation was developed to predict one-dimensional unsaturated flow in centrifugal systems. The validity of the model was tested using data from physical models in four published benchmark problems. The ability of the numerical model to close mass balance was also tested. It was shown that the newly developed numerical model was able to recreate the four benchmark problems quite successfully, indicating that using such a model under unsaturated flow condition is feasible. The mass conservation result shows that the model is more sensitive to spatial grid resolution than to specified temporal step. Therefore, fine spatial discretization is suggested to ensure the simulation quality. Additionally, adaptive temporal time stepping method can be used to improve the computational efficiency. It was found that the dimensionless factors used for scaling physical dimensions by 1/N, seepage velocity by N, and temporal dimension by 1/N2 were useful parameters for scaling centrifugal systems.
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Agua Subterránea , Movimientos del Agua , Modelos Teóricos , Suelo , AguaRESUMEN
Wearable devices with bimanual force feedback enable natural and cooperative manipulations within an unrestricted space. Weight and cost have a great influence on the potential applications of a haptic device. This paper presents a wearable robotic interface with bimanual force feedback that has considerably reduced weight and cost. To make the reaction force less perceivable than the interaction force, a waist-worn scheme is adopted. The interface mainly consists of a belt, a fastening tape, two serial robotic arms, and two electronics units and batteries. The robotic arms located on both sides of the belt are capable of 3-DoF position tracking and force feedback for each hand. The whole interface is lightweight (only 2.4 kg) and accessible. Furthermore, it is also easy to wear and the operator can wear it only by putting the belt on the waist and fastening the tape, reducing his/her dependency on additional assistance. The interface is optimized to obtain desirable force output and a dexterous workspace without singularity. To evaluate its performance in bimanual cooperative manipulations, an experiment in the virtual environment was conducted. The experimental results showed the subjects had more efficient and stable cooperative manipulations with bimanual force feedback than without force feedback.
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Procedimientos Quirúrgicos Robotizados , Robótica , Dispositivos Electrónicos Vestibles , Retroalimentación , Femenino , Mano , Humanos , Masculino , Interfaz Usuario-ComputadorRESUMEN
Pueraria lobata is utilized as a food source in China. The aim of this study is to combine virtual screening and molecular dynamics predictive model to screen out the potential synaptic plasticity-maintaining components from the root of P. lobate and to verify it by employing the amyloid ß-injected rats' model. Eighteen compounds were identified by HPLC-MS/MS; puerarin manifested the most potential to form a stable complex with calcium/calmodulin kinase IIα (CaMK IIα), which is the key protein in synaptic plasticity by the in silico study. The further in vivo assay showed that puerarin could elevate the synaptic thickness, density, and length, relieve calcium overload, regulate the expression of CaMK IIα, and other p38MAPK-CREB signaling pathway-related biochemical criteria. The behavioral test also verified the results. Results have confirmed that the root of P. lobate can work anti-AD by maintaining the synaptic plasticity and proved the reliability of using the in silico predictive model to determine active ingredients from the natural product.
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Enfermedad de Alzheimer/metabolismo , Productos Biológicos/farmacología , Simulación del Acoplamiento Molecular , Plasticidad Neuronal/efectos de los fármacos , Raíces de Plantas/química , Pueraria/química , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Productos Biológicos/química , Calcio/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Hipocampo/citología , Hipocampo/efectos de los fármacos , Humanos , Isoflavonas/química , Isoflavonas/farmacología , Neuronas/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Proteínas/genética , Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Tribe Lilieae, encompassing Lilium, Notholirion, Cardiocrinum, and Fritillaria, includes economically important crops with a horticultural and medicinal value. It is considered to be a core lineage of Liliaceae, but phylogenetic relationships within it, and the timing of the origin of individual clades, remain incompletely resolved. To address these issues, we reconstructed the evolutionary history of the tribe. We sequenced 45 Liliaceae plastomes and combined them with publicly available data (for a total of 139 plastomes) to explore the systematics, origin, divergence, and evolution of Lilieae. Our taxon sampling covers all ten sections of Lilium, all Cardiocrinum species, three Notholirion species, and major phylogenetic clades of Fritillaria. Our phylogenetic analysis confirms the monophyly of major sections/subgenera of Lilium and Fritillaria with strong support. We dated the origin of Lilieae to the Eocene, with genera and species radiations inferred to have occurred in the Miocene. The reconstruction of the ancestral area implies that Lilieae may have originated from the Qinghai-Tibet Plateau (QTP): the Himalayas and Hengduan Mountains and uplifting of the QTP likely promoted divergence within the tribe. Ancestral-state reconstructions of the bulb component number (including bulblets and scales) show a strong correlation with the genus-level phylogenetic diversity in Lilieae. They also predict that the most recent common ancestor of Lilieae had bulbs with numerous bulblets. Based on these observations, we predicted that climatic oscillations associated with the QTP uplift played an important role in the evolution of the Lilieae bulb. Our findings provide a well-supported picture of evolutionary relationships and a useful framework for understanding the pathway of bulb evolution within Lilieae, contributing to a better understanding of the evolutionary history of lilies.
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Haptic devices with multi-finger input are highly desirable in providing realistic and natural feelings when interacting with the remote or virtual environment. Compared with the conventional actuators, MR (Magneto-rheological) actuators are preferable options in haptics because of larger passive torque and torque-volume ratios. Among the existing haptic MR actuators, most of them are still bulky and heavy. If they were smaller and lighter, they would become more suitable for haptics. In this paper, a small-scale yet powerful MR actuator was designed to build a multi-finger interface for the 6 DOF haptic device. The compact structure was achieved by adopting the multi-disc configuration. Based on this configuration, the MR actuator can generate the maximum torque of 480 N.mm with dimensions of only 36 mm diameter and 18 mm height. Performance evaluation showed that it can exhibit a relatively high dynamic range and good response characteristics when compared with some other haptic MR actuators. The multi-finger interface is equipped with three MR actuators and can provide up to 8 N passive force to the thumb, index and middle fingers, respectively. An application example was used to demonstrate the effectiveness and potential of this new MR actuator based interface.
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Sistemas Hombre-Máquina , Tacto , Interfaz Usuario-Computador , Dispositivos Electrónicos Vestibles , Fenómenos Biomecánicos , Diseño de Equipo , Dedos , Análisis de Elementos Finitos , Humanos , Estimulación Física , TorqueRESUMEN
Effectively stimulating angiogenesis is great challenge in wound care management. It's necessary to develop a new wound dressing with angiogenic capacity. Therefore, strontium loaded SF/SA blend films were prepared as a potential wound dressing material, and their physicochemical and bioactive properties were evaluated. The strontium loaded SF/SA blend films (especially the strontium loaded SF/SA blend films prepared by treating with 5mg/ml Sir solution) could meet the needs of a wound dressing such as water absorption, water vapor transmission rate, mechanical properties and fibroblasts-cytocompatibility. What's more, these films had a potential to induce angiogenesis by improving vascular VEGF and bFGF protein secretion, which was important for wound dressings. Based on the previous studies, we could infer this novel wound dressing possesses the antibacterial activity. The present study suggests that the strontium loaded SF/SA blend film prepared by treating with 5mg/ml Sr solution are a promising biomaterial for wound dressing application.
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Alginatos/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Fibroínas/química , Neovascularización Fisiológica/efectos de los fármacos , Estroncio/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Vendajes , Línea Celular , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Ensayo de Materiales , Fenómenos Mecánicos , Ratones , Vapor , Factor A de Crecimiento Endotelial Vascular/metabolismo , HumectabilidadRESUMEN
Von Willebrand disease (VWD), the most common inherited bleeding disorder, is characterised by a variable bleeding tendency, heterogeneous laboratory phenotype and race specific distribution of mutations. The present study aimed to determine the correlation of genotype and phenotype in 200 Chinese individuals from 90 unrelated families with VWD. Next generation sequencing (NGS) of the whole coding VWF, copy number analysis of VWF by CNVplex® technique as well as a comprehensive phenotypic assessment were carried out in all index patients (IPs). We identified putative mutations in all IPs except five mild type 1 (85/90, 94.4 %). In total, 98 different mutations were detected, 62 (63.3 %) of which were reported for the first time (23 missense mutations, 1 regulatory mutation, 12 splice site mutations and 26 null mutations). Mutations p.Ser1506Leu and p.Arg1374His/Cys/Ser were the most frequent mutations in 2A (33 % of cases) and 2M VWD (67 % of cases), respectively. In addition, mutation p.Arg816Trp was detected repeatedly in type 2N patients, while mutation p.Arg854Gln, extremely common in Caucasians, was not found in our cohort. Thirty-three patients had two or more putative mutations. Unlike most cases of type 1 and type 2 VWD, which were transmitted dominantly, we presented seven severe type 1, two type 2A and one type 2M with autosomal recessive inheritance. Here the phenotypic data of patients with novel mutations will certainly contribute to the better understanding of the molecular genetics of VWF-related phenotypes.
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Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN/métodos , Dosificación de Gen , Hemostasis/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Reacción en Cadena de la Polimerasa Multiplex/métodos , Mutación , Enfermedades de von Willebrand/genética , Factor de von Willebrand/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Biomarcadores/sangre , Niño , Preescolar , China , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Lactante , Patrón de Herencia , Masculino , Persona de Mediana Edad , Tasa de Mutación , Fenotipo , Valor Predictivo de las Pruebas , Adulto Joven , Enfermedades de von Willebrand/sangre , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/etnologíaRESUMEN
Li-doped hydroxyapatite (LiHA) which is prepared through introducing low dose of Li into hydroxyapatite (HA) has been increasingly studied as a bone tissue-engineered scaffold. The degradation properties play a crucial role in the success of long-term implantation of a bone tissue-engineered construct. Herein, the in vitro degradation behaviors of LiHA scaffolds via two approaches were investigated in this study: solution-mediated degradation and osteoblast-mediated degradation. In solution-mediated degradation, after being immersed in simulated body fluid (SBF) for some time, some characteristics of these scaffolds (such as release of ionized lithium and phosphate, pH change, mechanical properties, cytocompatibility and SEM surface characterization) were systematically tested. A similar procedure was also employed to research the degradation behaviors of LiHA scaffolds in osteoblast-mediated degradation. The results suggested that the degradation in SBF and degradation in culture medium with cell existed distinguishing mechanisms. LiHA scaffolds were degraded via a hydrolytic mechanism when they were soaked in SBF. Upon degradation, an apatite precipitation (layer) was formed on the surfaces of scaffolds. While a biological mechanism was presented for the degradation of scaffolds in cell-mediated degradation. Compared with pure HA, LiHA scaffolds had a better effect on the growth of osteoblast cells, meanwhile, the release amount of PO4(3-) in a degradation medium indicated that osteoblasts could accelerate the degradation of LiHA due to the more physiological activities of osteoblast. According to the results from compressive strength test, doping Li into HA could enhance the strength of HA. Moreover, the results from MTT assay and SEM observation showed that the degradation products of LiHA scaffolds were beneficial to the proliferation of osteoblasts. The results of this research can provide the theoretical basis for the clinical application of LiHA scaffolds.