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Hypothermic preservation (HP) is highly desired for the maintenance of the viability of living cell specimens, e.g. rare cells in whole-blood samples or therapeutic cells, in an unfrozen state. However, the extension of the viable preservation time is a challenge because of the multiple injuries suffered by hypothermically preserved cells. Here, based on a dynamic bond crosslinked zwitterionic hydrogel, we established a sensing preservation system that could monitor the levels of reactive oxygen species (ROS) via real-time electronic signals and intelligent control of antioxidant addition, to completely prevent an excess of ROS in the whole-cell specimen. Furthermore, the hydrogel-based system can counter the extracellular-matrix-loss-induced anoikis of living cells. Based on the design aimed at affording protection against two primary HP injuries (i.e. ROS overproduction and anoikis) to cells, this system extended the preservation time of cell specimens under refrigerated conditions to 24 days. After preservation, the use of a mild cell retrieval process guaranteed the activity of the preserved living cells. This work not only possesses the potential to facilitate intelligent cell-based clinical applications, but also paves the way for the preparation of living materials that can host programmed cells with long-term survival. STATEMENT OF SIGNIFICANCE: An intelligent system based on a zwitterionic sensing hydrogel is established, which can afford ultra-long hypothermic cell-preservation times of up to 24 days. The system enables the real-time monitoring of ROS overproduction and intelligent antioxidant addition, because of the merging of the smart hydrogel with a computer intelligent detection and control system. Furthermore, the automatic addition of an antioxidant according to the ROS-signal changes produced by the ZBA hydrogel effectively prevented HP lesions, including ROS over-production and ECM loss, in the preserved living cells. Subsequently, the system could also be gently dissociated, to retrieve the preserved cells. This work provides a solution for the real-time monitoring and long-term HP of living specimens, which holds the promise of benefiting cell-based medicine and the development of genetically programmed cell-based living materials.
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AIMS: This study aims to investigate the pharmacological effects and the underlying mechanism of cannabidiol (CBD) on methamphetamine (METH)-induced relapse and behavioral sensitization in male mice. METHODS: The conditioned place preference (CPP) test with a biased paradigm and open-field test were used to assess the effects of CBD on METH-induced relapse and behavioral sensitization in male mice. RNA sequencing and bioinformatics analysis was employed to identify differential expressed (DE) circRNAs, miRNAs, and mRNAs in the nucleus accumbens (NAc) of mice, and the interaction among them was predicted using competing endogenous RNAs (ceRNAs) network analysis. RESULTS: Chronic administration of CBD (40 mg/kg) during the METH withdrawal phase alleviated METH (2 mg/kg)-induced CPP reinstatement and behavioral sensitization in mice, as well as mood and cognitive impairments following behavioral sensitization. Furthermore, 42 DEcircRNAs, 11 DEmiRNAs, and 40 DEmRNAs were identified in the NAc of mice. The circMeis2-miR-183-5p-Kcnj5 network in the NAc of mice is involved in the effects of CBD on METH-induced CPP reinstatement and behavioral sensitization. CONCLUSIONS: This study constructed the ceRNAs network for the first time, revealing the potential mechanism of CBD in treating METH-induced CPP reinstatement and behavioral sensitization, thus advancing the application of CBD in METH use disorders.
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Cannabidiol , Metanfetamina , Ratones Endogámicos C57BL , MicroARNs , ARN Circular , ARN Mensajero , Animales , Cannabidiol/farmacología , Masculino , Metanfetamina/farmacología , MicroARNs/genética , MicroARNs/metabolismo , Ratones , ARN Circular/genética , ARN Mensajero/metabolismo , Recurrencia , Estimulantes del Sistema Nervioso Central/farmacología , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Redes Reguladoras de Genes/efectos de los fármacosRESUMEN
The immediate processing of whole blood specimen is required in circulating tumor cell-based liquid biopsy. Reliable blood specimen stabilization towards preserving circulating tumor cells can enable more extensive geographic sharing for precise rare-cell technology, but remains challenging due to the fragility and rarity of circulating tumor cells. Herein, we establish a zwitterionic magnetic microgel platform to stabilize whole blood specimen for long-term hypothermic preservation of model circulating tumor cells. We show in a cohort study of 20 cancer patients that blood samples can be preserved for up to 7 days without compromising circulating tumor cell viability and RNA integrity, thereby doubling the viable preservation duration. We demonstrate that the 7-day microgel-preserved blood specimen is able to reliably detect cancer-specific transcripts, similar to fresh blood specimens, while there are up/down expression regulation of 1243 genes in model circulating tumor cells that are preserved by commercial protectant. Mechanistically, we find that the zwitterionic microgel assembly counters the cold-induced excessive reactive oxygen species and platelet activation, as well as extracellular matrix loss-induced cell anoikis, to prevent circulating tumor cell loss in the whole blood sample. The present work could prove useful for the development of blood-based noninvasive diagnostics.
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Microgeles , Células Neoplásicas Circulantes , Humanos , Estudios de Cohortes , Anoicis , Matriz ExtracelularRESUMEN
Anti-icing coatings on outdoor infrastructures inevitably suffer from mechanical injuries in numerous icing scenarios such as hailstorms, sandstorms, impacts of foreign objects, and icing-deicing cycles. Herein, the mechanisms of surface-defect-induced icing are clarified. At the defects, water molecules exhibit stronger adsorption and the heat transfer rate increases, accelerating the condensation of water vapor as well as ice nucleation and propagation. Moreover, the ice-defect interlocking structure increases the ice adhesion strength. Thus, a self-healing (at -20 °C) antifreeze-protein (AFP)-inspired anti-icing coating is developed. The coating is based on a design that mimics the ice-binding and non-ice-binding sites in AFPs. It enables the coating to markedly inhibit ice nucleation (nucleation temperature < -29.4 °C), prevent ice propagation (propagation rate < 0.00048 cm2/s), and reduce ice adhesion on the surface (adhesion strength < 38.9 kPa). More importantly, the coating can also autonomously self-heal at -20 °C, as a result of multiple dynamic bonds in its structure, to inhibit defect-induced icing processes. The healed coating sustains high anti-icing and deicing performance even under various extreme conditions. This work reveals the in-depth mechanism of defect-induced ice formation as well as adhesion, and proposes a self-healing anti-icing coating for outdoor infrastructures.
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Anti-icing coatings on outdoor infrastructures and transportations inevitably suffer from surface injuries, especially in extreme weather events (e.g., freezing weather or acid rain). The coating surface damage can result in anti-icing performance loss or even icing promotion. The development of anti-icing coatings that enables self-healing in extreme conditions is highly desired but still challenging. Herein, an extreme-environment-resistant self-healing anti-icing coating is developed by integrating fluorinated graphene (FG) into a supramolecular polymeric matrix. The coating exhibits both anti-icing and deicing performance (ice nucleation temperature is ≈-30.3 °C; ice shear strength is ≈48.7 kPa), mainly attributable to the hydrophobic FG and silicone-based supramolecular material. Notably, owing to the crosslinking polymeric network with various dynamic bonds, this coating can sustain anti-icing/deicing performance after autonomous self-healing under harsh conditions including low temperature (-20 °C), strong acid (pH = 0), and strong alkali (pH = 14) environments. This coating paves the way to meet the anti-icing demand in open air, especially for the infrastructures in polar regions or acid/alkali environments.
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Wound infection can induce inflammation and impede wound healing, being a major challenge in wound care management. A household device that can monitor infection in real time, prevent bacterial, and promote wound healing is highly desired but still rarely investigated. In this work, a novel zwitterionic cellulose-based hydrogel that enables continuously real-time monitoring and pro-healing of infected wound is designed. It is based on interpenetrating polymeric networks, including zwitterionic covalent bond network and physical bond network of carboxymethyl cellulose (CMC) with Ag+via metal-coordination interactions. When used as a sensing dressing, it is developed to exhibit pH-responsive and temperature-responsive properties for assessment of wound infection. Moreover, Ag+ can be released from carboxyl groups of CMC in response to the decrease of pH, killing bacteria and promoting wound healing. This zwitterionic carboxymethyl cellulose-based hydrogel sensor opens new avenues for domestic real-time monitoring and pro-healing of infected wound.
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Celulosa , Infección de Heridas , Antibacterianos/química , Antibacterianos/farmacología , Bacterias , Vendajes , Carboximetilcelulosa de Sodio/química , Carboximetilcelulosa de Sodio/farmacología , Celulosa/química , Celulosa/farmacología , Humanos , Hidrogeles/química , Hidrogeles/farmacologíaRESUMEN
This article mainly discusses the evaluation and optimization of the green space utilization value of comprehensive parks used by people in dense urban areas based on the desire for green and healthy living in the postepidemic era. As a qualitative study of urban parks, this study builds an evaluation system based on the American landscape performance series and combines it with comprehensive indicators of China's urban parks, including environmental performance (such as park planning, infrastructure, trails, and vegetation), health performance (such as cultural education, park activities, and transportation accessibility) economic performance (such as tourist consumption and stimulating the development of surrounding construction) and three other aspects: conducting a site evaluation; evaluating observed behavior, interviews and questionnaires; and performing the analytic hierarchy process-coefficient of variation weight comprehensive evaluation analysis. Additionally, the park comprehensive index, land use index, traffic convenience, park vitality index and other dynamic changes are analyzed over time. The purpose is to explore the foundation of urban parks after the epidemic. The role of the urban park environment in sustainable ecological development is verified, and appropriate optimization and improvement actions are determined.
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Cell-based medicine has made great advances in clinical diagnosis and therapy for various refractory diseases, inducing a growing demand for cell preservation as support technology. However, the bottleneck problems in cell preservation include low efficiency and poor biocompatibility of traditional protectants. In this review, cell preservation technologies are categorized according to storage conditions: hypothermic preservation at 1 °C~35 °C to maintain short-term cell viability that is useful in cell diagnosis and transport, while cryopreservation at -196 °C~-80 °C to maintain long-term cell viability that provides opportunities for therapeutic cell product storage. Firstly, the background and developmental history of the protectants used in the two preservation technologies are briefly introduced. Secondly, the progress in different cellular protection mechanisms for advanced biomaterials are discussed in two preservation technologies. In hypothermic preservation, the hypothermia-induced and extracellular matrix-loss injuries to cells are comprehensively summarized, as well as the recent biomaterials dependent on regulation of cellular ATP level, stabilization of cellular membrane, balance of antioxidant defense system, and supply of mimetic ECM to prolong cell longevity are provided. In cryopreservation, cellular injuries and advanced biomaterials that can protect cells from osmotic or ice injury, and alleviate oxidative stress to allow cell survival are concluded. Last, an insight into the perspectives and challenges of this technology is provided. We envision advanced biocompatible materials for highly efficient cell preservation as critical in future developments and trends to support cell-based medicine. STATEMENT OF SIGNIFICANCE: Cell preservation technologies present a critical role in cell-based applications, and more efficient biocompatible protectants are highly required. This review categorizes cell preservation technologies into hypothermic preservation and cryopreservation according to their storage conditions, and comprehensively reviews the recently advanced biomaterials related. The background, development, and cellular protective mechanisms of these two preservation technologies are respectively introduced and summarized. Moreover, the differences, connections, individual demands of these two technologies are also provided and discussed.
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Materiales Biocompatibles , Hipotermia , Materiales Biocompatibles/farmacología , Supervivencia Celular , Criopreservación , Humanos , Estrés OxidativoRESUMEN
BACKGROUND: A better understanding the mechanisms of cerebral ischemia is important both for diagnosis and treatment. OBJECTIVE: The study aimed to quantify several characteristics of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to indicate the brain tissue changes at different stage of cerebral ischemia in rats. METHODS: In the present study, a rat model of cerebral ischemia was established by middle cerebral artery occlusion (MCAO) in the left hemisphere. MRI and MRS were performed on 15 Sprague Dawley rats 4 H, 24 H, and 1 W after MCAO. Apparent diffusion coefficient (ADC), relative ADC including FNR, PNR, PNF, and metabolite ratio NCC were proposed to reflect the changes of water diffusion and metabolism in brain tissue. RESULTS: ADCs of focal zone and penumbra zone from 1 W group were significantly larger than those from 4H group, respectively (both p < 0.05). PNR and PNF of 24H and 1 W groups were significantly less than 4H group (all p < 0.01). NCCs of focal zone and penumbra zone were significantly less than the normal zone within 4H, 24H, and 1 W groups, respectively (both p < 0.01). While NCCs of penumbra zone from 24H and 1 W groups were significantly larger than 4H group (both p < 0.01). CONCLUSION: We conclude that combination of MRI and MRS characteristics can provide significant indicators for ischemic damage at different stage of cerebral ischemia in a rat model.
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Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Modelos Animales de Enfermedad , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Análisis de Varianza , Animales , Mapeo Encefálico , Progresión de la Enfermedad , Procesamiento de Imagen Asistido por Computador , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate the effect of force level and fatigue on brain activity during handgrip tasks. METHODS: Electroencephalography (EEG) signals were recorded from eleven healthy male subjects when they performed 25%, 50% and 75% maximal voluntary contraction (MVC), and were in fatigue state. EEG powers in different handgrip tasks were analyzed in the frequency domain and time domain respectively. RESULTS: The EEG power at 25%MVC was significantly lower than that at 75%MVC in gamma band (p< 0.05) for electrode C3, C4, Cz, Pz and Fz. EEG power at 25%MVC was also significantly lower than that at 75%MVC in beta band (p< 0.05) for electrode C3. However, the handgrip force level and fatigue did not affect the EEG powers for the other frequencies and electrodes (p> 0.05). CONCLUSION: The results suggest that handgrip force level may modulate the brain activity in certain frequency bands and cortical regions. EEG power is a useful tool to characterize the motor state.