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The well known trade-off between hardness and toughness (resistance to fracture) makes simultaneous improvement of both properties challenging, especially in diamond. The hardness of diamond can be increased through nanostructuring strategies1,2, among which the formation of high-density nanoscale twins - crystalline regions related by symmetry - also toughens diamond2. In materials other than diamond, there are several other promising approaches to enhancing toughness in addition to nanotwinning3, such as bio-inspired laminated composite toughening4-7, transformation toughening8 and dual-phase toughening9, but there has been little research into such approaches in diamond. Here we report the structural characterization of a diamond composite hierarchically assembled with coherently interfaced diamond polytypes (different stacking sequences), interwoven nanotwins and interlocked nanograins. The architecture of the composite enhances toughness more than nanotwinning alone, without sacrificing hardness. Single-edge notched beam tests yield a toughness up to five times that of synthetic diamond10, even greater than that of magnesium alloys. When fracture occurs, a crack propagates through diamond nanotwins of the 3C (cubic) polytype along {111} planes, via a zigzag path. As the crack encounters regions of non-3C polytypes, its propagation is diffused into sinuous fractures, with local transformation into 3C diamond near the fracture surfaces. Both processes dissipate strain energy, thereby enhancing toughness. This work could prove useful in making superhard materials and engineering ceramics. By using structural architecture with synergetic effects of hardening and toughening, the trade-off between hardness and toughness may eventually be surmounted.
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The essence of wound healing is the accumulation of suberin at wounds, which is formed by suberin polyphenolic (SPP) and suberin polyaliphatic (SPA). The biosynthesis of SPP and SPA monomers is catalyzed by several enzyme classes related to phenylpropanoid metabolism and fatty acid metabolism, respectively. However, how suberin biosynthesis is regulated at the transcriptional level during potato (Solanum tuberosum) tuber wound healing remains largely unknown. Here, 6 target genes and 15 transcription factors related to suberin biosynthesis in tuber wound healing were identified by RNA-seq technology and qRT-PCR. Dual luciferase and yeast one-hybrid assays showed that StMYB168 activated the target genes StPAL, StOMT, and St4CL in phenylpropanoid metabolism. Meanwhile, StMYB24 and StMYB144 activated the target genes StLTP, StLACS, and StCYP in fatty acid metabolism, and StFHT involved in the assembly of SPP and SPA domains in both native and wound periderms. More importantly, virus-induced gene silencing in S. tuberosum and transient overexpression in Nicotiana benthamiana assays confirmed that StMYB168 regulates the biosynthesis of free phenolic acids, such as ferulic acid. Furthermore, StMYB24/144 regulated the accumulation of suberin monomers, such as ferulates, α, ω-diacids, and ω-hydroxy acids. In conclusion, StMYB24, StMYB144, and StMYB168 have an elaborate division of labor in regulating the synthesis of suberin during tuber wound healing.
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Regulación de la Expresión Génica de las Plantas , Lípidos , Proteínas de Plantas , Tubérculos de la Planta , Solanum tuberosum , Factores de Transcripción , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tubérculos de la Planta/genética , Tubérculos de la Planta/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Lípidos/biosíntesis , Nicotiana/genética , Nicotiana/metabolismo , Plantas Modificadas Genéticamente , Ácidos Cumáricos/metabolismoRESUMEN
In this study, gallium- and gelatin-modified strontium-doped hydroxyapatite (SrHA-Gel-Ga) bilayer coatings were prepared on titanium substrates by electrodeposition and spin-coating techniques. The results showed that gallium and gelatin were uniformly doped into the SrHA coatings, which exhibited good hydrophilicity and bioactivity. Furthermore, SrHA-Gel-Ga demonstrated good antimicrobial properties against E. coli and S. aureus, especially S. aureus. The co-doping of Sr and gelatin in the coatings was effective in mitigating the cytotoxicity of Ga. SrHA-Gel-Ga was better able to promote the adhesion, proliferation and early differentiation of MC3T3-E1 cells. This study provides a new strategy for the development of anti-infective bone repair coatings.
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Antiinfecciosos , Gelatina , Gelatina/farmacología , Escherichia coli , Staphylococcus aureus , Osteogénesis , Antiinfecciosos/farmacología , Materiales Biocompatibles Revestidos/farmacología , Titanio/farmacologíaRESUMEN
BACKGROUND: Quality of parent-child interaction in early childhood functions as a critical indicator of nurturing care and is strongly associated with short-term and long-term development (health, cognition, language, social emotion, well-being, etc.). NCAST PCI Teaching Scale (PCI-TS), a video-based assessment regarded as a gold standard to measure PCI, has been widely used worldwide. However, its psychometric soundness among the urban Chinese population is unclear. This study assesses the PCI-TS's reliability and validity and explores predictive factors among urban Chinese parent-child dyads. METHODS: PCI-TS was adopted to code mother-child interaction among urban Chinese dyads recruited during the children's regular health checks in local maternal and child health centres. Reliability was evaluated by internal consistency (Cronbach'α coefficient) and test-retest reliability (Pearson correlation) with an average interval of 18 days. Score distribution of each subscale and total scale were compared with NCAST Database and Canadian community sample by single sample t-test. Criteria-related validity was conducted by Infant-Toddler Home Observation Measurement of the Environment (Pearson correlation). Predictive factors was performed by multiple linear regression. RESULTS: Four hundred and twenty-nine eligible mother-child dyads were included for data analysis among the 466 recruited samples. Four qualified local paediatricians accomplished video coding with an average agreement of 86%. The PCI-TS has strong reliability among the Chinese population with the Cronbach'α coefficients of the Caregiver-Infant total score, Caregiver total and Infant total scores of 0.81, 0.81 and 0.74, respectively; an acceptable test-retest reliability (r = 0.73, p < 0.01); and moderate correlation with IT-HOME, ranging from 0.53 to 0.62. Child age, birth weight, maternal education, full-time housewife, living with grandparent(s) and living space were predictive factors on PCI-TS in the Chinese population. CONCLUSION: PCI-TS showed good psychometric properties for measuring mother-child interactions among urban Chinese dyads, offering clinicians and researchers a practical tool to evaluate PCI objectively. Child age, maternal education and living space were beneficial factors, while full-time mothers and living with grandparent(s) were risk factors.
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Intervención Coronaria Percutánea , Lactante , Femenino , Humanos , Preescolar , Psicometría , Reproducibilidad de los Resultados , Canadá , Relaciones Padres-Hijo , Lenguaje , China , Encuestas y CuestionariosRESUMEN
AIMS/HYPOTHESIS: An increasing body of evidence has shown that the catabolism of branched-chain amino acids (BCAAs; leucine, isoleucine and valine) is impaired in obese animals and humans, contributing to the development of insulin resistance and type 2 diabetes. Promoting BCAA catabolism benefits glycaemic control. It remains unclear whether BCAA catabolism plays a role in the therapeutic efficacy of currently used glucose-lowering drugs such as metformin. METHODS: Mice were treated with vehicle or metformin (250 mg/kg per day) for more than 4 weeks to investigate the effects of metformin in vivo. In vitro, primary mouse hepatocytes and HepG2 cells were treated with 2 mmol/l metformin. The therapeutic efficacy of metformin in the treatment of type 2 diabetes was assessed in genetically obese (ob/ob) mice and high-fat-diet-induced obese (DIO) mice. Enhancing BCAA catabolism was achieved with a pharmacological agent, 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2). The ob/ob mice were treated with a low-BCAA diet or intermittent protein restriction (IPR) to reduce BCAA nutritional intake. RESULTS: Metformin unexpectedly inhibited the catabolism of BCAAs in obese mice, resulting in an elevation of BCAA abundance. AMP-activated protein kinase (AMPK) mediated the impact of metformin on BCAA catabolism in hepatocytes. Importantly, enhancing BCAA catabolism via a pharmacological agent BT2 significantly potentiated the glucose-lowering effect of metformin while decreasing circulating BCAA levels in ob/ob and DIO mice. Similar outcomes were achieved by a nutritional approach of reducing BCAA intake. IPR also effectively reduced the circulating BCAA abundance and enhanced metformin's glucose-lowering effect in ob/ob mice. BT2 and IPR treatments reduced the expression of fructose-1,6-bisphosphatase 1, a rate-limiting enzyme in gluconeogenesis, in the kidney but not liver, indicating the involvement of renal gluconeogenesis. CONCLUSIONS/INTERPRETATION: Metformin self-limits its therapeutic efficacy in the treatment of type 2 diabetes by triggering the suppression of BCAA catabolism. Enhancing BCAA catabolism pharmacologically or reducing BCAA intake nutritionally potentiates the glucose-lowering effect of metformin. These data highlight the nutritional impact of protein on metformin's therapeutic efficacy and provide new strategies targeting BCAA metabolism to improve metformin's effects on the clinical outcome in diabetes.
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Ratones , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Aminoácidos de Cadena Ramificada/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Dieta Alta en Grasa , GlucosaRESUMEN
Layered black phosphorus (LBP) is drawing increasing attention because of its excellent potential in biomedical applications. Properties and bioeffects of LBP depend on its layer number (LN). However, the variation of LN during applications, especially in organisms, is largely unknown. Herein, LBP is found to be exfoliated by human serum albumin (HSA) after the formation of protein coronas. The sorption of HSA on LBP exhibits multiple intermediate equilibrium and size-dependent capacity and is distinguished from traditional multilayer sorption. The loss of LN for LBP increases with the increase of HSA concentrations, e.g., 2, 4, and 6 layers of LBP are exfoliated at 35, 135, and 550 mg/L HSA, respectively. The energy distribution shows that at low HSA concentrations, exfoliation is mainly driven by electrostatic and hydrogen bond interactions. With middle or high HSA concentrations, exfoliation is mainly driven by p-π or hydrophobic interactions, respectively. Layer exfoliation causes the continuous emergence of an unsaturated LBP surface available for adsorbing further HSA, breaking previous sorption saturations. The complete exfoliation of LBP weakens cytotoxicity and promotes internalization to the A-549 cell line compared with pristine or less exfoliated LBP. This finding unveils the exfoliation mechanism of proteins toward LBP and is of benefit to evaluating application performance and biosafety of LBP.
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Fósforo , Albúmina Sérica Humana , Humanos , Albúmina Sérica Humana/químicaRESUMEN
The production scalability and increasing demand for nano-black phosphorus materials (nano-BPs) inevitably lead to their environmental leakage, thereby raising the risk of human exposure through inhalation, ingestion, dermal, and even intravenous pathways. Consequently, a systematic evaluation of their potential impacts on human health is necessary. This Review outlines recent progress in the understanding of various biological responses to nano-BPs. Attention is particularly given to the inconsistent toxicological findings caused by a wide variation of nano-BPs' physicochemical properties, toxicological testing methods, and cell types examined in each study. Additionally, cellular uptake and intracellular trafficking, cell death modes, immunological effects, and other biologically relevant processes are discussed in detail, providing evidence for the potential health implications of nano-BPs. Finally, we address the remaining challenges related to the health risk evaluation of nano-BPs and propose a broader range of applications for these promising nanomaterials.
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Nanoestructuras , Fósforo , Humanos , Fósforo/química , Nanoestructuras/toxicidad , Transporte BiológicoRESUMEN
This study evaluated the effects of high concentrate diets (HCD) on the rumen fermentation and the digestibility of nutrients in different sites of the gastrointestinal tract (GIT) in goats. Four goats were used in a crossover design. The goats were fitted with a ruminal cannula and flexible T-cannulae proximal duodenum and terminal ileum. Treatments were as follows: low concentrate group (LCG) and high concentrate group (HCG). Duodenal flow and forestomach digestibility of starch were significantly higher in the HCG than those in the LCG (p < 0.05); There was no significant difference in ileum flow and digestibility of starch in the small intestine, large intestine and total GIT (p > 0.05). The digestibility of crude protein (CP) in the forestomach was significantly higher in the HCG than in the LCG (p < 0.05); the flow of the duodenum and ileum of CP, and the CP digestibility of the small intestine, large intestine and total GIT were not significantly different between groups (p > 0.05). The duodenal and ileal flow of neutral detergent fiber (NDF), the NDF digestibility of the different segments and total GIT were not significantly different between groups (p > 0.05). Compared to the LCG, the ruminal pH of the HCG was significantly lower (p < 0.05). The HCG concentrations of microbial crude protein, ammonia nitrogen and isovaleric acid were significantly higher (p < 0.05) than the LCG. The foam strength, foam production and viscosity of the rumen fluid in the HCG were higher than the LCG (p < 0.01). These results showed that when the goats were fed with HCD, the digestibility of nutrients was not significantly impaired, but the risk of frothy rumen bloat increased. ImplicationsDue to a serious shortage of high-quality roughage in China, producers commonly used a high-concentrate diet in ruminants, which can improve animal production performance.Gastrointestinal digestive function plays a vital role in the absorption of nutrients and the healthy growth of animals.Therefore, this research evaluated the digestibility of various nutrients in different segments of the gastrointestinal tract (GIT) under HCD feeding by using three-site cannula goats as experimental animals.The results indicated that the GIT of goats could fully digest nutrients such as starch and protein under HCD feeding conditions.
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Cabras , Rumen , Animales , Alimentación Animal/análisis , Dieta/veterinaria , Fermentación , Tracto Gastrointestinal/metabolismo , Cabras/metabolismo , Nutrientes , Rumen/metabolismo , Almidón/metabolismo , Estudios CruzadosRESUMEN
This article proposes a CBAM-ASPP-SqueezeNet model based on the attention mechanism and atrous spatial pyramid pooling (CBAM-ASPP) to solve the problem of robot multi-target grasping detection. Firstly, the paper establishes and expends a multi-target grasping dataset, as well as introduces and uses transfer learning to conduct network pre-training on the single-target dataset and slightly modify the model parameters using the multi-target dataset. Secondly, the SqueezeNet model is optimized and improved using the attention mechanism and atrous spatial pyramid pooling module. The paper introduces the attention mechanism network to weight the transmitted feature map in the channel and spatial dimensions. It uses a variety of parallel operations of atrous convolution with different atrous rates to increase the size of the receptive field and preserve features from different ranges. Finally, the CBAM-ASPP-SqueezeNet algorithm is verified using the self-constructed, multi-target capture dataset. When the paper introduces transfer learning, the various indicators converge after training 20 epochs. In the physical grabbing experiment conducted by Kinova and SIASUN Arm, a network grabbing success rate of 93% was achieved.
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Algoritmos , Aprendizaje , Tecnología , Aprendizaje AutomáticoRESUMEN
Constructed on the moiety of a lactam screw ring, a near-infrared fluorescent probe RCya for Pd2+ was designed under the PET mechanism and synthesized by incorporating 2,4-dihydroxybenzaldehyde as the recognition group. Dynamic detection of aqueous Pd2+ by the probe RCya could be accomplished through ion competition, linear response, fluorescence-pH/time stabilities, and other optical tests. Moreover, the high selectivity, low cytotoxicity, cell permeability, and lysosome accumulation properties of RCya enabled the imaging applications on solid-state RCya-PAN composite nanofibers and in living cells. The recognition mechanism of probe RCya toward Pd2+ was further studied through simulation calculation and MS analysis.
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Colorantes Fluorescentes , Nanofibras , Fluorescencia , Lisosomas , Tomografía de Emisión de Positrones , Imagen ÓpticaRESUMEN
High security and effectiveness are critical performance metrics in the data transmission process for satellite remote sensing images, medical images, and so on. Previously, the receiver could gain a high-quality cover image (lossy) after decryption in a separable manner to balance embedding capacity (EC) and security. Completely separable, reversible data hiding in encrypted image (SRDH-EI) algorithms are proposed to address this issue. In this study, the cover image was preprocessed at the sender's end. The pre-embedded pixels and most significant bits (MSB) were compressed via two coding methods to reserve space. Additionally, the header data were embedded for marking. Finally, auxiliary data and secret data were embedded in a forward "Z" and reverse "Z" shape before and after encryption, respectively. The receiver could extract secret data and decrypt the cover image separately using the keys and markers. The experimental results demonstrate that the algorithm reached a high EC for remote sensing images by utilizing pixel correlation at multiple positions within the groups. The cover image could maintain its entropy during the data embedding process, ensuring security. The decrypted image could be recovered without distortion, furthermore, the receiver could achieve complete separability, so it has good application prospects for remote sensing images.
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The remarkable progress of applied black phosphorus nanomaterials (BPNMs) is attributed to BP's outstanding properties. Due to its potential for applications, environmental release and subsequent human exposure are virtually inevitable. Therefore, how BPNMs impact biological systems and human health needs to be considered. In this comprehensive Minireview, the most recent advancements in understanding the mechanisms and regulation factors of BPNMs' endogenous toxicity to mammalian systems are presented. These achievements lay the groundwork for an understanding of its biological effects, aimed towards establishing regulatory principles to minimize the adverse health impacts.
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Nanoestructuras , Fósforo , Animales , Humanos , Nanoestructuras/toxicidad , MamíferosRESUMEN
In tumor metastasis, the margination and adhesion of tumor cells are two critical and closely related steps, which may determine the destination where the tumor cells extravasate to. We performed a direct three-dimensional simulation on the behaviors of the tumor cells in a real microvascular network, by a hybrid method of the smoothed dissipative particle dynamics and immersed boundary method (SDPD-IBM). The tumor cells are found to adhere at the microvascular bifurcations more frequently, and there is a positive correlation between the adhesion of the tumor cells and the wall-directed force from the surrounding red blood cells (RBCs). The larger the wall-directed force is, the closer the tumor cells are marginated towards the wall, and the higher the probability of adhesion behavior happen is. A relatively low or high hematocrit can help to prevent the adhesion of tumor cells, and similarly, increasing the shear rate of blood flow can serve the same purpose. These results suggest that the tumor cells may be more likely to extravasate at the microvascular bifurcations if the blood flow is slow and the hematocrit is moderate.
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Biología Computacional/métodos , Microcirculación , Modelos Cardiovasculares , Neoplasias/genética , Neoplasias/metabolismo , Animales , Adhesión Celular , Simulación por Computador , Elasticidad , Eritrocitos/citología , Hematócrito , Hemodinámica , Humanos , Metástasis de la Neoplasia , Ratas , Estrés MecánicoRESUMEN
Prodiginines are a large family of microbial secondary metabolites with a core structure of tripyrrole rings. They exhibit not only diverse chemical structures but also rich biological activities, such as anti-cancer, anti-microbial, anti-algae, anti-parasitic, pesticides, and UV radiation resistance. The preferred cytotoxicity to cancer cells rather than normal cells indicates a good biological selectivity and safety, which makes the prodiginines promising candidates for drug development and novel additives for food processing. Until now, 33 prodiginine natural products have been identified in various bacteria, including Serratia, Hahella, Pseudoalteromonas, Vibrio, Zooshikella, Streptomyces, and Actinomadura. However, most efforts are still focused on the star molecule prodigiosin, while little yet is known about other prodiginine members, which retards the research and application of prodiginine compounds. To gain insight into the prodiginine family, we reviewed the recent discoveries on their chemical structures, biosynthesis, biological activities, and mechanisms of action. We believe this article will provide a guideline for new research on prodiginines, such as the discovery of new congeners and drug development. KEY POINTS: ⢠The prodiginines are a large family of natural products with a core structure of tripyrrole rings and exhibit various bioactivities. ⢠The prodiginines have a widespread distribution among many environmental microbes and diverse biosynthetic pathways, indicating important ecological roles and a great potential for new congeners. ⢠The potent biological activities and good selectivity of action make prodiginines good lead compounds for drug development.
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Productos Biológicos , Streptomyces , Prodigiosina/metabolismo , Productos Biológicos/farmacología , Streptomyces/metabolismo , Serratia/metabolismoRESUMEN
BACKGROUND: To investigate and understand the determinants of decisions not to attempt resuscitation following out-of-hospital cardiac arrest, to contribute to establishing rules that are appropriate to China. METHODS: We recruited participants through directors of emergency medical services across China. A 28-question web survey was available between February 5 and March 6, 2021 that targeted demographic information and views on emergency work and cardiopulmonary resuscitation. Each question was assigned a value between 1 and 7 based on the level of importance from low to high. T-tests, one-way analysis of variance, and Kruskal-Wallis H-tests were used to compare continuous variables. Binary logistic regression analysis was used to identify factors influencing when people considered it suitable to initiate cardiopulmonary resuscitation. RESULTS: The study involved 4289 participants from 31 provinces, autonomous regions and municipalities in mainland China, of whom 52.8% were male. The top three reasons for not attempting cardiopulmonary resuscitation were decomposition/hypostasis/rigor mortis (6.39 ± 1.44 points), massive injury (4.57 ± 2.08 points) and family members' preference (4.35 ± 1.98 points). In total, 2761 (64.4%) thought emergency services should not attempt cardiopulmonary resuscitation when cardiac arrest had happened more than 30 min before, and there had been no bystander cardiopulmonary resuscitation. Gender (OR 1.233, p = 0.002), religion (OR 1.147, p = 0.046), level (OR 0.903, p = 0.028) or classification of city (OR 0.920, p = 0.049), years of work experience (OR 0.884, p = 0.004), and major (OR 1.032, p = 0.044) all influenced how long after cardiac arrest was considered suitable for initiating cardiopulmonary resuscitation. CONCLUSIONS: Chinese emergency physicians have different perceptions of when not to attempt resuscitation to those practicing elsewhere. The existing guidelines for resuscitation are not suitable for China, and China-specific guidelines need to be established.
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Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco Extrahospitalario , China , Femenino , Humanos , Masculino , Paro Cardíaco Extrahospitalario/terapia , Órdenes de ResucitaciónRESUMEN
By incorporating a rhodamine spirolactam structure as the recognition site for Cu2+, two novel probes were synthesized through a connection of rhodamine 6G acylhydrazine and 5-formyl-6-hydroxyl-4-methylcoumarin/2,4-dihydroxybenzaldehyde. In the recognition process of probes towards Cu2+, the spirolactam ring exhibited opening and closing, accompanying an instant and specific change in fluorescence and in color, which could also achieve a naked-eye and semiquantitative recognition of aqueous Cu2+ besides the fluorescent Cu2+ detection method. Fluorescent analyses and ECV304 cell imaging further revealed the probes' good optical stability, instant response, low toxicity, and membrane permeability, which offers future possibilities for the probes' instant detection and the real-time tracking of Cu2+ in biological systems.
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Cobre/análisis , Cobre/química , Colorantes Fluorescentes/química , Color , Permeabilidad , Rodaminas/química , Agua/químicaRESUMEN
Nanogels have been identified as outstanding nanocarrier candidates for drug delivery due to their desirable physiochemical properties and versatile applicability for diverse therapeutic molecules and imaging probes. One of the main challenges that hinder the clinical translation of nanogels is the low efficiency of drug delivery to the target sites because of the complex biological barriers during the inâ vivo journey. The purpose of this review is to examine and summarize the recent advances on the rational design and structural modulation of nanogels to overcome the barriers and challenges on the way to the site of action following various dosing modes. In particular, the functional moieties or domains have been incorporated in the nanogels, allowing them to spontaneously regulate their structure and physiochemical properties to cross one or more of the multifaceted barriers. In addition, the future perspectives are presented with regards to opportunities and challenges for the precise and efficient therapeutic use of nanogel formulations.
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Nanogeles/química , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Sistemas de Liberación de Medicamentos , Humanos , Nanogeles/administración & dosificaciónRESUMEN
Contraction stimulates skeletal muscle glucose uptake predominantly through activation of AMP-activated protein kinase (AMPK) and Rac1. However, the molecular details of how contraction activates these signaling proteins are not clear. Recently, Axin1 has been shown to form a complex with AMPK and liver kinase B1 during glucose starvation-dependent activation of AMPK. Here, we demonstrate that electrical pulse-stimulated (EPS) contraction of C2C12 myotubes or treadmill exercise of C57BL/6 mice enhanced reciprocal coimmunoprecipitation of Axin1 and AMPK from myotube lysates or gastrocnemius muscle tissue. Interestingly, EPS or exercise upregulated total cellular Axin1 levels in an AMPK-dependent manner in C2C12 myotubes and gastrocnemius mouse muscle, respectively. Also, direct activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide treatment of C2C12 myotubes or gastrocnemius muscle elevated Axin1 protein levels. On the other hand, siRNA-mediated Axin1 knockdown lessened activation of AMPK in contracted myotubes. Further, AMPK inhibition with compound C or siRNA-mediated knockdown of AMPK or Axin1 blocked contraction-induced GTP loading of Rac1, p21-activated kinase phosphorylation, and contraction-stimulated glucose uptake. In summary, our results suggest that an AMPK/Axin1-Rac1 signaling pathway mediates contraction-stimulated skeletal muscle glucose uptake.
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Proteínas Quinasas Activadas por AMP/fisiología , Proteína Axina/fisiología , Glucosa/metabolismo , Contracción Muscular/fisiología , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiología , Neuropéptidos/fisiología , Transducción de Señal/fisiología , Proteína de Unión al GTP rac1/fisiología , Proteínas Quinasas Activadas por AMP/genética , Animales , Proteína Axina/genética , Línea Celular , Estimulación Eléctrica , Técnicas de Silenciamiento del Gen , Masculino , Ratones , Ratones Endogámicos C57BL , Neuropéptidos/genética , ARN Interferente Pequeño/farmacología , Transducción de Señal/genética , Proteína de Unión al GTP rac1/genéticaRESUMEN
A method is described for cysteine (Cys) determination on paper-based analytical devices using aspartic acid modified gold nanoparticles (Asp-AuNPs). The Asp-AuNPs were characterized by their size, zeta potential, and UV-visible absorption spectrum. After the addition of Cys, it will interact with Asp-AuNPs selectively and leads to the aggregation of Asp-AuNPs. A color change from red to blue can be observed on the paper-based analytical devices. The results were recorded using a cell phone and subsequently analyzed using the Photoshop software. The ratiometric color intensity at red channel and blue channel (Red/Blue) increased linearly in the range 99.9-998.7 µM for Cys (R = 0.9984), and the limit of detection was 1.0 µM. The effects of assay conditions have been investigated and are discussed. The Cys concentration was determined as (0.27 ± 0.02 mM) in human plasma, and the recovery was from 99.2 to 101.1%. Graphical abstract Schematic representation of the paper-based assay system using aspartic acid modified gold nanoparticles (Asp-AuNPs). The ratiometric color intensity method was used for the cysteine (Cys) determination.
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Ácido Aspártico/química , Colorimetría/métodos , Cisteína/sangre , Nanopartículas del Metal/química , Papel , Secuencia de Carbohidratos , Teléfono Celular , Colorimetría/instrumentación , Oro/química , Humanos , Límite de Detección , Programas InformáticosRESUMEN
An open-tubular capillary electrochromatography method has been developed for the determination of binding constants between ß2 -adrenergic receptor (ß2 -AR) and seven drugs. ß2 -AR was oriented immobilized onto one part of inner surface of capillary via microwave-assisted technical synthesis. According to the linear relationship between coating length and the apparent mobility of analyte, the binding constant (Kb ) can be obtained by related theories and equations. The order of Kb values between drugs such as adrenaline hydrochloride, norepinephrine bitartrate, and propranolol hydrochloride with ß2 -AR is well consistent with that reported in the literature. By the method, Kb values between four extracts of Radix Paeoniae Rubra and ß2 -AR were also successfully obtained. Subsequently, computer models were applied to interpret the CEC experiments. And the results proved to be in good agreement with the method. The work, herein, demonstrates the potential of the method in drug-receptor affinity interactions evaluation and screening of lead compounds from natural sources.