RESUMEN
Patrinia punctiflora is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the isolation of six iridoids, which were previously unreported compounds, patriscabioins PU (1-6). Their structures were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Among them, compound 5 was screened to evaluate its insulin resistance activity on an IR-HepG-2 cell model. Compound 5 had no cytotoxicity compared with the control group and could promote glucose uptake in IR-HepG-2 cells. Through further mechanism studies, the undescribed compound 5 could increase the expression levels of PI-3 K, p-AKT, GLUT4 and p-GSK3ß proteins. Moreover, the expression of PEPCK and G6Pase proteins, which are key gluconeogenic enzymes, was also inhibited. Thus, compound 5 promotes the transfer of GLUT4 to the plasma membrane by activating the PI-3 K/AKT signaling pathway, at the same time, promotes glycogen synthesis and inhibits the onset of gluconeogenesis, which in turn ameliorates insulin resistance.
RESUMEN
Incorporating passive heating structures into personal thermal management technologies could effectively mitigate the escalating energy crisis. However, current passive heating materials struggle to balance thickness and insulating capability, resulting in compromised comfort, space efficiency, and limited thermoregulatory performance. Here, a dual air-gelation strategy, is developed to directly synthesize ultrathin and self-sustainable heating metafabric with 3D dual-network structure during electrospinning. Controlling the interactions among polymer, solvent, and water enables the microphase separation of charged jets, while adjusting the distribution of carbon black nanoparticles within charged fluids to form fibrous networks composed of interlaced aerogel micro/nanofibers with heat storage capabilities. With a low thickness of 0.18 mm, the integrated metafabric exhibits exceptional thermal insulation performance (15.8 mW m-1K-1), superhydrophobicity, enhanced mechanical properties, and high breathability while maintaining self-sustainable radiative heating ability (long-lasting warming of 8.8 °C). This strategy provides rich possibilities to develop advanced fibrous materials for smart textiles and thermal management.
RESUMEN
Angiogenesis plays a crucial role in bone regeneration. Hypoxia is a driving force of angiogenesis at the initial stage of tissue repair. The hypoxic microenvironment could activate the hypoxia-inducible factor (HIF)-1α signaling pathway in cells, thereby enhancing the proliferation, migration and pro-angiogenic functions of stem cells. However, long-term chronic hypoxia could inhibit osteogenic differentiation and even lead to apoptosis. Therefore, shutdown of the HIF-1α signaling pathway and providing oxygen at later stage probably facilitate osteogenic differentiation and bone regeneration. Herein, an oxygen tension regulating hydrogel that sequentially activate and deactivate the HIF-1α signaling pathway were prepared in this study. Its effect and mechanism on stem cell differentiation were investigated both in vitro and in vivo. We proposed a gelatin-based hydrogel capable of sequentially delivering a hypoxic inducer (copper ions) and oxygen generator (calcium peroxide). The copper ions released from the hydrogels significantly enhanced cell viability and VEGF secretion of BMSCs via upregulating HIF-1α expression and facilitating its translocation into the nucleus. Additionally, calcium peroxide promoted alkaline phosphatase activity, osteopontin secretion, and calcium deposition through the activation of ERK1/2. Both Cu2+ and calcium peroxide demonstrated osteogenic promotion individually, while their synergistic effect within the hydrogels led to a superior osteogenic effect by potentially activating the HIF-1α and ERK1/2 signaling pathways.
Asunto(s)
Regeneración Ósea , Hidrogeles , Subunidad alfa del Factor 1 Inducible por Hipoxia , Sistema de Señalización de MAP Quinasas , Células Madre Mesenquimatosas , Neovascularización Fisiológica , Osteogénesis , Oxígeno , Hidrogeles/farmacología , Hidrogeles/química , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Regeneración Ósea/efectos de los fármacos , Animales , Neovascularización Fisiológica/efectos de los fármacos , Neovascularización Fisiológica/fisiología , Oxígeno/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Gelatina , Supervivencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , PeróxidosRESUMEN
The acoustic tomography (AT) velocity field reconstruction technique has become a research hotspot in recent years due to its noninvasive nature, high accuracy, and real-time measurement advantages. However, most of the existing studies are limited to the reconstruction of the velocity field in a rectangular area, and there are very few studies on a circular area, mainly because the layout of acoustic transducers, selection of acoustic paths, and division of measured regions are more difficult in a circular area than in a rectangular area. Therefore, based on AT and using the reconstruction algorithm of the Markov function and singular value decomposition (MK-SVD), this paper proposes a measured regional division optimization algorithm for velocity field reconstruction in a circular area. First, an acoustic path distribution based on the multipath effect is designed to solve the problem of the limited emission angle of the acoustic transducer. On this basis, this paper proposes an adaptive optimization algorithm for measurement area division based on multiple sub-objectives. The steps are as follows: first, two optimization objectives, the condition number of coefficient matrix and the uniformity of acoustic path distribution, were designed. Then, the weights of each sub-objective are calculated using the coefficient of variation (CV). Finally, the measured regional division is optimized based on particle swarm optimization (PSO). The reconstruction effect of the algorithm and the anti-interference ability are verified through the reconstruction experiments of the model velocity field and the simulated velocity field.
RESUMEN
BACKGROUND: ChatGPT is a large language model (LLM) based on artificial intelligence (AI) capable of responding in multiple languages and generating nuanced and highly complex responses. While ChatGPT holds promising applications in medical education, its limitations and potential risks cannot be ignored. METHODS: A scoping review was conducted for English articles discussing ChatGPT in the context of medical education published after 2022. A literature search was performed using PubMed/MEDLINE, Embase, and Web of Science databases, and information was extracted from the relevant studies that were ultimately included. RESULTS: ChatGPT exhibits various potential applications in medical education, such as providing personalized learning plans and materials, creating clinical practice simulation scenarios, and assisting in writing articles. However, challenges associated with academic integrity, data accuracy, and potential harm to learning were also highlighted in the literature. The paper emphasizes certain recommendations for using ChatGPT, including the establishment of guidelines. Based on the review, 3 key research areas were proposed: cultivating the ability of medical students to use ChatGPT correctly, integrating ChatGPT into teaching activities and processes, and proposing standards for the use of AI by medical students. CONCLUSION: ChatGPT has the potential to transform medical education, but careful consideration is required for its full integration. To harness the full potential of ChatGPT in medical education, attention should not only be given to the capabilities of AI but also to its impact on students and teachers.
Asunto(s)
Inteligencia Artificial , Educación Médica , Simulación por Computador , Lenguaje , AprendizajeRESUMEN
Amygdalus species have considerable ecological and economic value, however, the phylogenetic relationships among Amygdalus remain controversy. In this study, we sequenced and assembled the chloroplast (cp) genomes of five Amygdalus species: Prunus communis, P. mongolica, P. pedunculata, P. triloba, and P. mira. We then conducted comparative genomic analyses and constructed their phylogenetic relationships. The genome length ranged from 157,870 to 158,451 bp, and 131 genes were annotated (86 protein-coding genes, 37 tRNAs, and 8 rRNAs). Additionally, 49-57 simple sequence repeats were detected, with most in the large single-copy region and with AT base preferences. Comparative genomic analyses revealed high similarities in structure, order, and gene content. However, we identified four highly divergent sequences: trnR-UCU-atpA, nbdhC-trnV-UAC, ycf4-cemA, and rpl32-trnL-UAG. The phylogenomic relationship analysis suggested that the Amygdalus species were grouped together, in which P. pedunculata, P. triloba, and Prunus tangutica were categorized into a branch, P. mongolica and Prunus davidiana were clustered a branch. This study provides an improved understanding of the genetic relationships among the Amygdalus and provides a basis for the development and utilization of Amygdalus resources.
RESUMEN
The dual-band polarization-independent all-optical logic gate by coherent absorption effect in an amorphous silicon (a-Si) graphene metasurface is investigated theoretically and numerically. Taking the substrate effect into consideration, the coherent perfect absorption condition of the a-Si graphene metasurface is derived on the basis of the Cartesian multipole method. The coherent nearly perfect absorption of the a-Si graphene metasurface is realized by the interference of multipole moments and the interband transition of monolayer graphene, achieving peak values of 91% and 92% at 894.5 nm and 991.5 nm, respectively. The polarization independence of the coherent absorption is revealed due to the center symmetry of the structure of the a-Si graphene metasurface. The dual-band polarization-independent all-optical XOR and OR logic gates are implemented at 894.5 nm and 991.5 nm by the a-Si graphene metasurface based on the coherent nearly perfect absorption, which has the opportunity to be utilized in all-optical computing, all-optical data processing, and future all-optical networks.
RESUMEN
This study demonstrates the effect and DNA methylation-related mechanisms of a high-salt diet and salt memory-induced hypertension and vasculopathy. Thirty Sprague Dawley rats were randomly divided into a control (CON) group (n = 6) and a modeling group (n = 24). A 12% NaCl solution (1 mL/100 g) was intragastrically administered for 60 consecutive days for modeling. An increase in blood pressure up to 140 mmHg was considered successful modeling. Twelve of fifteen successfully modeled rats were randomly selected and divided into a High Salt Diet (HSD) group and a High Salt Memory (HSM) group (n = 6). Rats in HSD group were intragastrically administered a 12% NaCl solution, while rats in HSM group were administered a 3% NaCl solution twice a day for 30 days. At the end of the intervention, blood pressure and the serum levels of ET-1, NO, TNF-α and IL-1ß were measured. RRBS-heavy sulfite sequencing technology was selected for DNA methylation analysis. The systolic blood pressure of rats in the HSD group and HSM group was significantly higher than that in the CON group. Compared with those in the CON group, the serum levels of ET-1 in the HSM group and the serum levels of NO in the HSD group and HSM group were significantly increased. The methylation level of the CON group was lower than that of the HSD group and the HSM group, and there was no significant difference between the HSD group and the HSM group. The methylation level of Myoz3 was downregulated in the HSD group and HSM group. The methylation level of Fgd3 were upregulated in HSD group and downregulated in the HSM group. The methylation levels of AC095693.1, Adamts3, PDGFA and PDGFRα were downregulated in the HSD group and upregulated in the HSM group. According to the GO database, the differentially methylated genes were significantly enriched in the coordination of cell function, genetic development, and RNA transcription. There were three main metabolic pathways that were enriched in the differentially expressed genes between the groups: the PI3K-Akt signaling pathway, MAPK signaling pathway, and Hippo signaling pathway. Excessive salt intake may cause hypertension and vascular damage, and this damage may continue after the reduction of salt intake. Therefore, salt memory phenomenon exists, and this memory effect may be correlated with the levels of DNA methylation.
Asunto(s)
Hipertensión , Cloruro de Sodio , Animales , Ratas , Ratas Sprague-Dawley , Cloruro de Sodio Dietético/efectos adversos , Metilación de ADN , Fosfatidilinositol 3-Quinasas , Hipertensión/genéticaRESUMEN
BACKGROUND: Exercising at different times of the day is a widely employed strategy for treating essential hypertension, aimed at enhancing the circadian rhythm of blood pressure. This study aimed to investigate the effects of Liuzijue exercise in the morning and afternoon on the circadian rhythm of blood pressure in patients with essential hypertension. METHODS: This clinical randomized trial recruited 36 patients. They were randomly divided into 3 groups: morning exercise, afternoon exercise, and waiting treatment group. Randomization was performed at a ratio of 1:1:1, ensuring an equal distribution of participants among the 3 groups. Based on maintaining routine work and rest and continuing the original drug treatment, the exercise performed Liuzijue exercise for 12 weeks. The exercise time was 9:00 to 10:00 in the morning exercise group and 14:00 to 15:00 in the afternoon exercise group. The waiting treatment group did not perform any form of fitness exercise. The subjects in the 3 groups were monitored by 24-hour ambulatory blood pressure on the day before and after the first day. RESULTS: After the 12-week Liuzijue exercise intervention, mean systolic blood pressure during the night significantly decreased in the morning exercise group (Pâ <â .01). In contrast, the waiting group experienced substantial increases in 24-hour mean systolic blood pressure (24hSBP), 24-hour mean diastolic blood pressure (24hDBP), mean systolic blood pressure during the daytime (dSBP), and mean diastolic blood pressure during the daytime (dDBP) (Pâ <â .01). Further analysis showed that the morning exercise group had significantly lower 24hSBP, 24hDBP, dSBP, dDBP, and mean systolic blood pressure during the night than the waiting group (Pâ <â .05). Additionally, the morning exercise group had lower 24hSBP and dSBP levels than the afternoon exercise group (Pâ <â .05). In contrast, the afternoon exercise group had lower 24hDBP and dDBP than the waiting treatment group (Pâ <â .05). CONCLUSIONS: The 12-week Liuzijue exercise in the morning regimen demonstrated superior efficacy in reducing 24-hour ambulatory blood pressure levels among patients with essential hypertension. Moreover, it facilitates the transition of non-dipper blood pressure patterns to dippers, thereby rectifying aberrant circadian rhythms.
Asunto(s)
Hipertensión , Humanos , Presión Sanguínea , Hipertensión/tratamiento farmacológico , Monitoreo Ambulatorio de la Presión Arterial , Hipertensión Esencial/terapia , Ritmo Circadiano/fisiologíaRESUMEN
INTRODUCTION: Refractory cough, a chronic cough with an unclear diagnosis or poor treatment response. The symptoms are often stubborn and persistent, causing serious complications and lowering the patient's quality of life. Cough hypersensitivity syndrome (CHS) is proposed as a potential cause, and reducing sensory nerve hyperresponsiveness is suggested as an effective treatment. However, current drugs have low efficacy and benefit rates and numerous side effects. This trail proposes using duloxetine, a selective 5-HT and norepinephrine reuptake inhibitor, as a potential treatment for refractory cough, which has shown promise in treating pain and depression. Duloxetine may inhibit pain conduction and oxidative stress in peripheral nerves by inhibiting the activity of TRPV1 channels, which play an important role in the peripheral afferent pathway of refractory cough. Meanwhile, the antidepressant effects of duloxetine may also play a role in the treatment of refractory cough. METHODS AND ANALYSIS: This is a single-center, prospective, randomized, double-blind, and controlled trial. A total of 98 individuals will be randomized in a 1:1 ratio to duloxetine group and placebo control group (starting with 20 mg QD, increasing 20 mg daily until 20 mg TID). After a screening period, the second stage runs from baseline to the 42nd (last) day of treatment, with follow-up visits on the 3rd, 7th, 14th, 21st, 28th, 35th, 42nd and 49th days. The main end-stage observation indicators include objective cough frequency, cough visual analog scale (VAS), cough symptom score, Leicester Cough Questionnaire (LCQ), and cough evaluation test (CET); the secondary end-stage observation indicators include capsaicin cough sensitivity, Patient Health Questionnaire-9 (PHQ-9), Major Depression Inventory (MDI), the Generalized Anxiety Disorder-7 scale (GAD-7), Life Events Scale (LES-32), induced sputum supernatant. The safety measures will be AEs/SAEs, vital signs, liver and kidney function, fecal occult blood test. DISCUSSION: This study is the first randomized, double-blind, and controlled clinical trial investigating the use of duloxetine in the treatment of refractory coughs. The study aims to provide a high-quality basis for evaluating the efficacy and safety of duloxetine for this condition. TRIAL REGISTRATION: Our study was registered in the Chinese Clinical Trials Register ( www.chictr.org.cn/ ) (ChiCTR2000037429) in 28/08/2020.
Asunto(s)
Tos , Calidad de Vida , Humanos , Clorhidrato de Duloxetina/uso terapéutico , Clorhidrato de Duloxetina/efectos adversos , Tos/tratamiento farmacológico , Tos/inducido químicamente , Comprimidos Recubiertos , Estudios Prospectivos , Dolor , Método Doble Ciego , Resultado del TratamientoRESUMEN
DeePMD-kit is a powerful open-source software package that facilitates molecular dynamics simulations using machine learning potentials known as Deep Potential (DP) models. This package, which was released in 2017, has been widely used in the fields of physics, chemistry, biology, and material science for studying atomistic systems. The current version of DeePMD-kit offers numerous advanced features, such as DeepPot-SE, attention-based and hybrid descriptors, the ability to fit tensile properties, type embedding, model deviation, DP-range correction, DP long range, graphics processing unit support for customized operators, model compression, non-von Neumann molecular dynamics, and improved usability, including documentation, compiled binary packages, graphical user interfaces, and application programming interfaces. This article presents an overview of the current major version of the DeePMD-kit package, highlighting its features and technical details. Additionally, this article presents a comprehensive procedure for conducting molecular dynamics as a representative application, benchmarks the accuracy and efficiency of different models, and discusses ongoing developments.
RESUMEN
Osteosarcoma is an aggressive malignant neoplasm, and it is of great significance to the fabrication and investigation of the anti-tumor mechanism of nanomedicine in the treatment of osteosarcoma. Herein, a cinnamaldehyde polymeric prodrug micelle with pH-sensitive charge-conversion ability (mPEG-b-P(C7-co-CA)) was fabricated, and the anti-osteosarcoma mechanism of mPEG-b-P(C7-co-CA) micelle was investigated. mPEG-b-P(C7-co-CA) micelles were prepared by self-assembly method, and their diameter was 227 nm. mPEG-b-P(C7-co-CA) micelles could regulate the cell cycle and inhibit the proliferation of 143B cells, which was demonstrated by flow cytometry analysis, CCK-8 assay and 5-Ethynyl-2'-deoxyuridine (EdU) staining. The wound-healing assay and transwell assay showed that mPEG-b-P(C7-co-CA) micelles effectively inhibited the migration and invasion of 143B cells. It was proven that mPEG-b-P(C7-co-CA) micelles downregulated the levels of proliferation and apoptosis-related proteins and affected osteosarcoma migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT). In addition, mPEG-b-P(C7-co-CA) micelles can also inhibit the transcriptional activity of the PI3K/Akt signaling pathway. Therefore, these findings provide new evidence for the pharmacological effects of mPEG-b-P(C7-co-CA) micelles.
RESUMEN
Somatic symptom disorder (SSD) is a new diagnosis introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is expected to solve the diagnostic difficulties of patients with medically unexplained symptoms. Based on the previous work, this review aims to comprehensively synthesise updated evidence related to SSD from recent years in English publications and, more extensively, from data published in Chinese language journals. The scoping review update was based on an earlier scoping review and included Chinese language publication data from China National Knowledge Internet (CNKI), WANFANG and WEIPU between January 2013 and May 2022 and data from PubMed, PsycINFO, and Cochrane Library between June 2020 and May 2022. Initially, 2 984 articles were identified, of which 63 full texts were included for analysis. In China, SSD is mainly applied in scientific research, but it also shows good predictive validity and clinical application potential. The mean frequency of SSD was 4.5% in the general population, 25.2% in the primary care population and 33.5% in diverse specialised care settings. Biological factors, such as brain region changes and heart rate variability, are associated with the onset of SSD. Psychological impairment related to somatic symptoms is the best predictor of prognosis. While adolescent SSD was significantly associated with family function, SSD overall is associated with an increased dysfunction of cognition and emotion, decreased quality of life, and high comorbidity with anxiety and depressive disorders. Further research is needed on suicide risk and cultural and gender-related issues. Updating the data of Chinese language studies, our research enriches the evidence-based findings related to the topics addressed in the text sections of the SSD chapter of DSM-5. However, research gaps remain about SSD reliability, population-based prevalence, suicide risk, and cultural and gender-related issues.
RESUMEN
[This corrects the article DOI: 10.1016/j.jot.2022.10.015.].
RESUMEN
Extracellular vesicles (EVs) have been widely used in liquid biopsy to diagnose and monitor cancers. However, since samples containing EVs are usually body fluids with complex components, the cumbersome separation steps for EVs during detection limit the clinical application and promotion of EV detection methods. In this study, a dyad lateral flow immunoassay (LFIA) strip for EV detection, containing CD9-CD81 and EpCAM-CD81, was developed to detect universal EVs and tumor-derived EVs, respectively. The dyad LFIA strip can directly detect trace plasma samples and effectively distinguish the cancerous sample from healthy plasma. The limit of detection for detecting universal EVs was 2.4 × 105 mL-1. The whole immunoassay can be performed in 15 min and only consumes 0.2 µL of plasma for one test. To improve the suitability of a dyad LFIA strip in complex scenarios, a smartphone-based photographic method was developed, which provided a consistency of 96.07% to a specialized fluorescence LFIA strip analyzer. In further clinical testing, EV-LFIA discriminated lung cancer patient groups (n = 25) from healthy controls (n = 22) with 100% sensitivity and 94.74% specificity at the best cutoff. The detection of EpCAM-CD81 tumor EVs (TEVs) in lung cancer plasma revealed the differences in TEVs in individuals, which reflected the different treatment effects. TEV-LFIA results were compared with CT scan findings (n = 30). The vast majority of patients with increased TEV-LFIA detection intensity had lung masses that enlarged or remained unchanged in size, which reported no response to treatment. In other words, patients who reported no response (n = 22) had a high TEV level compared with patients who reported a response to treatment (n = 8). Taken together, the developed dyad LFIA strip provides a simple and rapid platform to characterize EVs to monitor lung cancer therapy outcomes.
Asunto(s)
Adenocarcinoma del Pulmón , Vesículas Extracelulares , Neoplasias Pulmonares , Humanos , Molécula de Adhesión Celular Epitelial , Inmunoensayo/métodos , Adenocarcinoma del Pulmón/diagnóstico , Neoplasias Pulmonares/diagnósticoRESUMEN
Osteogenesis imperfecta (OI) is a hereditary skeletal dysplasia with an incidence of approximately 1:15,000 to 20,000. OI is usually caused by the mutation of COL1A1 and COL1A2, which would encode the α-chain of type I collagen. OI is clinically characterized by decreased bone mass, increased risk of bone fragility, blue sclerae, and dentinogenesis. Case presentation: A 29-year-old male patient was diagnosed with right tibial plateau fracture caused by slight violence. Physical examination revealed the following: height, 140 cm; weight, 70 kg; body mass index (BMI), 35.71 kg/m2; blue sclera and barrel chest were observed. X-ray examination showed left convex deformity of the thoracic vertebrae with reduced thoracic volume. Laboratory examinations revealed a decrease in both vitamin D and blood calcium levels. Bone mineral density (BMD) was lower than the normal range. After the preoperative preparation was completed, the open reduction and internal fixation of the right tibial plateau fracture were performed. Meanwhile, whole blood samples of this OI patient and the normal control were collected for RNA transcriptome sequencing. The RNA sequence analysis revealed that there were 513 differentially expressed genes (DEGs) between this OI patient and the normal control. KEGG-enriched signaling pathways were significantly enriched in extracellular matrix (ECM)-receptor interactions. Conclusion: In this case, DEGs between this OI patient and the normal control were identified by RNA transcriptome sequencing. Moreover, the possible pathogenesis of OI was also explored, which may provide new evidence for the treatment of OI.
Asunto(s)
Fracturas Óseas , Osteogénesis Imperfecta , Fracturas de la Meseta Tibial , Masculino , Humanos , Adulto , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/epidemiología , Mutación , Fracturas Óseas/epidemiologíaRESUMEN
In this study, biomimetic porous magnesium alloy scaffolds were prepared to repair femoral bone defects in ovariectomized osteoporotic rats. The purpose of the study was to investigate the effect of biomimetic porous magnesium alloy scaffolds on repairing osteoporotic bone defects and possible mechanisms. The animal model of osteoporosis was established in female SD rats. Three months later, a bone defect of 3 mm in diameter and 3 mm in depth was created in the lateral condyle of the right femur. The rats were then randomly divided into two groups: an experimental group and a control group. Four weeks after surgery, gross specimens were observed and micro-CT scans were performed. The repair of osteoporotic femoral defects in rats was studied histologically using HE staining, Masson staining, and Goldner staining. The expression of Wnt5a, ß-catenin, and BMP-2 was measured between groups by immunohistochemical staining. The bone defect was repaired better after the application of biomimetic porous magnesium alloy scaffolds. Immunohistochemical results showed significantly higher expression of Wnt5a, ß-catenin, and BMP-2. To conclude, the biomimetic porous magnesium alloy scaffolds proposed in this paper might promote the repair of osteoporotic femoral bone defects in rats possibly through activating the Wnt/ß-catenin signaling pathway.
Asunto(s)
Magnesio , Osteoporosis , Vía de Señalización Wnt , Animales , Femenino , Ratas , Aleaciones , beta Catenina/metabolismo , Biomimética , Porosidad , Ratas Sprague-Dawley , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
The plastic deformation of crystalline materials can be understood by considering their structural defects such as disclinations and dislocations. Although also glasses are solids, their structure resembles closely the one of a liquid and hence the concept of structural defects becomes ill-defined. As a consequence it is very challenging to rationalize on a microscopic level the mechanical properties of glasses close to the yielding point and to relate plastic events to structural properties. Here we investigate the topological characteristics of the eigenvector field of the vibrational excitations of a two-dimensional glass model, notably the geometric arrangement of the topological defects as a function of vibrational frequency. We find that if the system is subjected to a quasistatic shear, the location of the resulting plastic events correlate strongly with the topological defects that have a negative charge. Our results provide thus a direct link between the structure of glasses prior their deformation and the plastic events during deformation.
RESUMEN
Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1-34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1-34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1ß-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.
Asunto(s)
Hidrogeles , Osteoartritis , Ratones , Animales , Hidrogeles/uso terapéutico , Liposomas/uso terapéutico , Gelatina , Teriparatido/uso terapéutico , Fosfatidilinositol 3-Quinasas , Osteoartritis/tratamiento farmacológico , Inyecciones IntraarticularesRESUMEN
We propose a quantum Monte Carlo approach to solve the many-body Schrödinger equation for the electronic ground state. The method combines optimization from variational Monte Carlo and propagation from auxiliary field quantum Monte Carlo in a way that significantly alleviates the sign problem. In application to molecular systems, we obtain highly accurate results for configurations dominated by either dynamic or static electronic correlation.