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Group 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and type 1 innate lymphoid cells (ILC1s). The main functions of liver cNK cells and ILC1s not only include directly killing target cells but also regulating local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of liver cNK cells and ILC1s, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role of Prdm1 in shaping the composition and maturation of cNK cells. Although Prdm1 did not affect the killing function of cNK cells in an in vivo cytotoxicity model, a significant increase in cancer metastasis was observed in Prdm1 knockout mice. Interferon-gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly in Prdm1-deficient cNK cells and liver ILC1s. Single-cell RNA sequencing (scRNA-seq) data also provided evidences that Prdm1 maintains functional subsets of cNK cells and liver ILC1s and facilitates communications between cNK cells, liver ILC1s, and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in cNK cells and liver ILC1s, showing promising potential for developing innovative immune therapy strategies against liver cancer.
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Neoplasias Hepáticas , Ratones Noqueados , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Animales , Ratones , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/genética , Células Asesinas Naturales/inmunología , Interferón gamma/metabolismo , Inmunidad Innata , Linfocitos/inmunología , Vigilancia Inmunológica , Granzimas/metabolismo , Granzimas/genética , Receptor 1 Gatillante de la Citotoxidad Natural/metabolismo , Receptor 1 Gatillante de la Citotoxidad Natural/genética , Perforina/metabolismo , Perforina/genética , Hígado/inmunología , Hígado/metabolismo , Ratones Endogámicos C57BL , Microambiente Tumoral/inmunología , Antígenos LyRESUMEN
Electrofluorochromic (EFC) materials and devices with controllable fluorescence properties show great application potential in advanced anticounterfeiting, information storage and display. However, the low color purity caused by the broad emission spectra and underperforming switching time of the existing EFC materials limit their application. Through biomimetic exploration and the study of reversible electrochemical responsive coordination reactions, boron-nitrogen embedded polyaromatics (B,N-PAHs) with narrow-band emission and high color purity have been successfully integrated into EFC systems, which also help to better understand the role of boron in biological activity. The EFC device achieve good performance containing quenching efficiency greater than 90% within short switching time (ton: 0.6 s, toff: 2.4 s), and nearly no performance change after 200 cycles test. Three primary color (red, green, and blue) EFC devices are successfully prepared. In addition, new phenomena are obtained and discussed in this biomimetic exploration of related boron reactions. The success and harvest of this exploration are expected to provide new ideas for optimizing properties and broadening applications of EFC materials. Moreover, it may provide ideas and reference significance for further exploring and understanding the function of boron compounds in biological systems.
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Reconstructing the visible spectra of real objects is critical to the spectral camouflage from emerging spectral imaging. Electrochromic materials exhibit unique superiority for this goal due to their subtractive color-mixing model and structural diversity. Herein, a simulation model is proposed and a method is developed to fabricate electrochromic devices for dynamically reproducing the visible spectrum of the natural leaf. Over 20 kinds of pH-dependent leuco dyes have been synthesized/prepared through molecular engineering and offered available spectra/bands to reconstruct the spectrum of the natural leaf. More importantly, the spectral variance between the device and leaf is optimized from an initial 98.9 to an ideal 10.3 through the simulation model, which means, the similarity increased nearly nine-fold. As a promising spectrum reconstruction approach, it will promote the development of smart photoelectric materials in adaptive camouflage, spectral display, high-end encryption, and anti-counterfeiting.
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Boron-doped polycyclic aromatic hydrocarbons exhibit excellent optical properties, and regulating their photophysical processes is a powerful strategy to understand the luminescence mechanism and develop new materials and applications. Herein, an electrochemically responsive B-O dynamic coordination bond is proposed, and used to regulate the photophysical processes of boron-nitrogen-doped polyaromatic hydrocarbons. The formation of the B-O coordination bond under a suitable voltage is confirmed by experiments and theoretical calculations, and B-O coordination bond can be broken back to the initial state under opposite voltage. The whole process is accompanied by reversible changes in photophysical properties. Further, electrofluorochromic devices are successfully prepared based on the above electrochemically responsive coordination bond. The success and harvest of this exploration are beneficial to understand the luminescence mechanism of boron-nitrogen-doped polyaromatic hydrocarbons, and provide ideas for design of dynamic covalent bonds and broaden material types and applications.
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Pulmonary fibrosis (PF) is a chronic lung disease characterized by excess extracellular matrix deposition and prolonged inflammation that fails to resolve and is druggable. Using resolvins and their precursors for inflammation resolution, we demonstrate a nano-enabled approach for accomplishing robust antifibrotic effects in bleomycin- or engineered nanomaterial-induced mouse and rat PF models. Targeting the lipid peroxidation-triggered NLRP3 inflammasome and NF-κB pathway in macrophages and the ROS-mediated TGF-ß/Smad and S1P signaling in epithelial cells results in these potent protective effects at the ng/mL dosimetry. We further develop an inhalable biocompatible nanoparticle that encapsulates fish oil, a chosen resolvin precursor, with phosphatidylcholine and polyethylene glycol to enhance drug permeability and facilitate crossing the mucosal barrier, forming "fish-oilsome" (FOS). Oropharyngeal aspiration and inhalation of FOS improved the anti-inflammatory status, histological characteristics, and pulmonary function in fibrotic lungs, which was mechanistically supported by transcriptomic and proteomic analyses. Further, scale-up engineered FOS samples with the desired physicochemical properties, anti-PF efficacy, and in vivo biocompatibility were validated in different batch sizes (up to 0.2 L/batch). This study provides a practical and translatable approach to promoting inflammation resolution and PF treatment.
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Fibrosis Pulmonar , Ratas , Ratones , Animales , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Proteómica , Pulmón/metabolismo , Inflamación/patología , Modelos Animales , Modelos Animales de EnfermedadRESUMEN
The adsorption-catalysis synergy for accelerated conversion of polysulfides is critical toward the electrochemical stability of lithium-sulfur battery (LSB). Herein, a non-metallic polymer network with anion receptor units, trifluoromethanesulfonyl (CF3SO2-) substituted aza-ether, was in-situ integrated on PE separator, working as an efficient host for anchoring lithium thiophosphates (LPS) as redox mediators and polysulfides through Lewis acid-base interaction. The anchored LPS on the modified PE separator displayed a robust chemical adsorption ability towards polysulfides through the formation of SS bond. Meanwhile, LPS decreased the energy barrier of Li2S nucleation and promoted redox reaction kinetics. The battery with LPS decorated separator revealed a long cycling lifespan with a per cycle decay of 0.056 % after 600 cycles, and a competitive initial capacity of 889.1 mAh/g when the of sulfur cathode increased to 3 mg cm-2. This work developed a new design strategy to promote the utilization of lithium phosphorus sulfide compounds in LSB.
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We have developed tailor-designed mesoporous silica nanoparticles (MSNPs) specifically for delivering mRNA. Our unique assembly protocol involves premixing mRNA with a cationic polymer and then electrostatically binding it to the MSNP surface. Since the key physicochemical parameters of MSNPs could influence the biological outcome, we also investigated the roles of size, porosity, surface topology, and aspect ratio on the mRNA delivery. These efforts allow us to identify the best-performing carrier, which was able to achieve efficient cellular uptake and intracellular escape while delivering a luciferase mRNA in mice. The optimized carrier remained stable and active for at least 7 days after being stored at 4 °C and was able to enable tissue-specific mRNA expression, particularly in the pancreas and mesentery after intraperitoneal injection. The optimized carrier was further manufactured in a larger batch size and found to be equally efficient in delivering mRNA in mice and rats, without any obvious toxicity.
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Nanopartículas , Dióxido de Silicio , Animales , Ratones , Ratas , PorosidadRESUMEN
With the rapid development of optoelectronic fields, electrochromic (EC) materials and devices have received remarkable attention and have shown attractive potential for use in emerging wearable and portable electronics, electronic papers/billboards, see-through displays, and other new-generation displays, due to the advantages of low power consumption, easy viewing, flexibility, stretchability, etc. Despite continuous progress in related fields, determining how to make electrochromics truly meet the requirements of mature displays (e.g., ideal overall performance) has been a long-term problem. Therefore, the commercialization of relevant high-quality products is still in its infancy. In this review, we will focus on the progress in emerging EC materials and devices for potential displays, including two mainstream EC display prototypes (segmented displays and pixel displays) and their commercial applications. Among these topics, the related materials/devices, EC performance, construction approaches, and processing techniques are comprehensively disscussed and reviewed. We also outline the current barriers with possible solutions and discuss the future of this field.
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Dispositivos Electrónicos Vestibles , ElectrónicaRESUMEN
Flexible circularly polarized luminescence (CPL) switching devices have been long-awaited due to their promising potential application in wearable optoelectronic devices. However, on account of the few materials and complicated design of manufacturing systems, how to fabricate a flexible electric-field-driven CPL-switching device is still a serious challenge. Herein, a flexible device with multiple optical switching properties (CPL, circular dichroism (CD), fluorescence, color) is designed and prepared efficiently based on proton-coupled electron transfer (PCET) mechanism by optimizing the chiral structure of switching molecule. More importantly, this device can maintain the switching performance even after 300 bending-unbending cycles. It has a remarkable comprehensive performance containing bistable property, low open voltage, and good cycling stability. Then, prototype devices with designed patterns have been fabricated, which opens a new application pattern of CPL-switching materials.
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Luminiscencia , Protones , Dicroismo Circular , Transporte de Electrón , ElectronesRESUMEN
Bistable electrochromic materials are a promising alternative solution to reduce energy consumption in displays. Limited by the mechanism and lack of a design strategy, only a few electrochromic materials have truly been able achieve bistability. Herein, a novel strategy is proposed to design bistable electrochromic materials based on polymer-assisted dynamic metal-ligand coordination. The mechanism and materials of such unconventional electrochromic systems are proved by sufficient characterization. Synergistic stabilization of polymerized switchable dyes and the ionic ligand polymer are attracted to each other by supramolecular forces. The color states of the dye molecules are controlled and stabilized by valence changes of the metal ions. Meanwhile, through the polymerization of the electrochromic material and the nearby metal-ligand material, the metal ions of the electroinduced valence change are tightly fixed, and the related diffusion problem of the active EC component is also almost completely suppressed. This strategy successfully enables preparation of the corresponding transparent electrochromic displays with good performances, such as, the display information is clearly visible for more than 1.5 h without consuming energy. Furthermore, the new way of dynamic coordination or dissociation bistable displays could likely prosper the development of the electrochromic area and inspire other fields.
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Light-responsive color-switching materials (LCMs) are long-lasting hot fields. However, non-ideal comprehensive performance (such as color contrast and retention time cannot be combined, unsatisfactory repeatability, and non-automated coloring mode) significantly hinder their development toward high-end products. Herein, the development of LCMs that exhibit long retention time, good color contrast, repeatability, and the property of automatic coloring is reported. The realization of this goal stems from the adoption of a bio-inspired multi-component collaborative step-by-step coloring strategy. Under this strategy, a conventional one-step photochromic process is divided into a "light+heat" controlled multi-step process for the fabrication of the desired LCMs. The obtained LCMs can effectively resist the long-troubled ambient-light interference and avoid its inherent yellow background, thereby achieving the longest retention time and good repeatability. Multiple colors are generated and ultra-fast imaging compatible with the laser-printing technology is also realized. The application potential of the materials in short-term reusable identity cards, absorptive readers, billboards, and shelf labels is demonstrated. The results reported herein can potentially help in developing and designing various high-performance, switchable materials that can be used for the production of high-end products.
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OBJECTIVE: To study the effects of five tuina manipulations in rats with deep vein thrombosis (DVT) and to explore how to safely perform tuina in the treatment of thrombotic diseases. METHODS: Seventy-two male Sprague-Dawley (SD) rats were randomly divided into the model, pointing manipulation, plucking manipulation, kneading manipulation, pushing manipulation, and pulling manipulation groups (n = 12). DVT model was established by incomplete ligation. The tuina intervention was started on the next day after modeling and applied once a day 10 times by the manipulation simulators. On the 3rd and 10th days after intervention, respectively, the effects of tuina on thrombosis were evaluated based on thrombus elasticity, blood coagulation, fibrinolytic function and blood rheology with the ultrasound elastography, four coagulation tests, enzyme linked immunosorbent assay (ELISA), and hemorheology tests. RESULTS: In the pointing manipulation group, the strain rate ratio, 6-ketoprostaglandin F1α (6-Keto-PGF1α), and high shear rate were decreased, and the thromboxane B2 (TXB2) content was increased (P < 0.05). In the plucking manipulation group, the D-dimer and 6-Keto-PGF1α contents were increased, prothrombin time (PT) was shortened, and activated partial thromboplastin time (APTT) was activated, and the high shear rate and plasma viscosity were decreased (P < 0.05). In the kneading manipulation group, APTT was shortened, and 6-Keto-PGF1α, high shear rate, and plasma viscosity were decreased (P < 0.05). In the pushing manipulation group, the strain rate ratio, low shear rate, and high shear rate were all decreased (P < 0.05). In the pulling manipulation group, both the strain rate ratio and the low shear rate were decreased (P < 0.05). The 6-Keto-PGF1α changes on the 3rd and 10th days after intervention were opposite in the pushing manipulation group and the pulling manipulation group (P < 0.05). CONCLUSION: The pointing, pushing, and pulling manipulations seem to be safe in the early period of thrombosis, but the risk is likely to be elevated as the treatment course of intervention increases. The plucking and kneading manipulations potentially have certain risks in the treatment of DVT in rats.
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ConspectusStimuli-responsive materials have a great potential in various novel photoelectric devices, such as self-adaptive adjustment devices, intelligent detection, molecular computers with information storage capability, camouflage and anticounterfeiting display, various energy-saving displays, and others. However, progress in related areas has been relatively slow because of the lack of high-performance smart materials and the limitations of available reaction mechanisms currently. To address these problems fundamentally, new mechanisms need to be designed and developed, and learning from nature is an effective and intelligent method to achieve this long-awaited target, such as mimicking of proton transfer processes in nature at the molecular/supramolecular level. The stimuli-induced reversible proton transfer system is composed of materials that release or capture protons in response to stimuli and switch molecules that control color and/or fluorescence modulation by protons, and it is applied in stimuli-responsive materials and devices, including bistable electronic/electrochromic devices, electrofluorochromic devices, water-jet rewritable paper, visible-light-responsive rewritable paper, and mechanochromic materials.To help researchers gain deep insight into stimuli-induced reversible proton transfer, we attempted to summarize its reaction mechanism and design principle, and discuss strategies to design and prepare various related stimuli-responsive materials and devices. This Account discusses the different systems in which a color/fluorescence change is induced by the proton transfer process under various stimuli, including electric field, water, light, heat, and stress. Relative very promising applications as well as their performance especially for energy-saving and environmentally friendly devices are then summarized, such as energy-saving bistable electrochromic devices, water-jet rewritable paper, and visible-light-responsive rewritable paper. Meanwhile, we focus on the key influence factors and useful additives for improving the device's performance. At last, challenges and bottlenecks faced by stimuli-responsive materials and devices based on the mechanism of reversible proton transfer are proposed. Moreover, we put forward some suggestions on solving these limitations.These exciting results reveal that smart materials based on the mechanism of proton transfer are extremely attractive and possess great potential in the next generation of energy and resource saving and environmental protection display. We hope that this Account further prospers the field of intelligent stimuli-responsive discoloration materials and next-generation green displays.
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The technological revolution of long-awaited energy-saving and vision-friendly displays represented by bistable display technology is coming. Here we discuss methods, challenges, and opportunities for implementing bistable displays in terms of molecular design, device structure, further expansion, and required criteria, hopefully benefiting the light-related community.
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A new and simple strategy towards electric-field-driven multiple chirality switching device has been designed and fabricated by combining a newly synthesized base-responsive chiroptical polymer switch (R-FLMA) and p-benzoquinone (p-BQ) via proton-coupled electron transfer (PCET) mechanism. Clear and stable triple chirality states (silence, positive, negative) of this device in visible band can be regulated reversibly (>1000 cycles) by adjusting voltage programs. Furthermore, such chiral switching phenomena are also accompanied by apparent changes of color and fluorescence. More importantly, the potential application of this device for a spatial light modulator has also been demonstrated.
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Electrochromic devices (ECDs) have been regarded as promising candidates for energy-saving smart windows, next-generation displays and wearable electronics due to their significant benefits of simple and adjustable structures, low power consumption, flexible and stretchable features, and eye-friendly modes for displays. However, there are many existing issues waiting to be solved such as durability, reversibility and inadequate switching performances. These insurmountable technical bottlenecks significantly slow down the commercialization of next-generation ECDs. Nanomaterials with superior active reaction surface area have played indispensable roles in optimizing heterogeneous electron transfer and homogeneous ion transfer for ECDs and other optoelectronic devices. In recent years, with the joint efforts of various outstanding research teams, new kinds and methods for nanomaterials to fabricate ECDs with excellent performances have been rapidly developing. This review highlights the latest exciting results regarding the design and application of new and unique nanomaterials for each layer of ECDs. Meanwhile, the structures, mechanisms, features and preparation of the reported nanomaterials to improve the electrochromic properties have been discussed in detail. In addition, the remaining challenges and corresponding strategies of this field are also proposed. Hopefully, this review can inspire more and more researchers to enrich the nanomaterials for ECDs and other related fields to overcome faced technical barriers by innovative means and promote industrialization of ECDs and other optoelectronic technologies.
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With the rapid development of human society, consumer electronics have brought marvelous changes to human daily life, but they are accompanied by the much higher demand of display quality and visual experience. Therefore, ideal conversion among the three primary colors-red (R), green (G), and blue (B)-in a single pixel has been a better way to avoid the insurmountable technical barrier of subpixel technology of modern displays. Electrofluorochromic (EFC) materials capable of a novel luminescent switching, open a powerful way to design optoelectronic devices for displays and information storage etc. Colorful EFC devices, especially emitting the ideal three primary colors without subpixel technology, have been a challenge for years. Herein, a long-awaited single-pixel device with RGB color is fabricated successfully based on proton-coupled electron transfer. The RGB EFC device exhibits outstanding EFC properties, such as low turn-on voltage (+1.0 and -1.0 V), large color gamut, and good stability (500 cycles for each color). Prototypes of colorful alphanumeric displays are well demonstrated in a facile way. The success of this new exploration of single-pixel RGB EFC device not only provides the possibility of full-color emission in EFC devices, but also will widely broaden the EFC system and their applications.
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OBJECTIVE: To explore the effect of tuina on the gene expression at the point of nerve injury in rats with sciatic nerve injury (SNI) and to elucidate the repair mechanism of tuina promoting the functional recovery of peripheral nerve injury. METHODS: In the Sham group, the right sciatic nerve was exposed without clamping. The SNI model was established using the sciatic nerve clamp method on the right leg and then randomly divided into the SNI group and the Tuina group. Seven days after modeling, the Tuina group was treated daily with a "massage and tuina manipulation simulator" (Patent No. ZL 2007 0187403.1), which was used daily to stimulate Yinmen (BL37), Yanglingquan (GB34), and Chengshan (BL57) with point-pressing method, plucking method, and kneading method. The stimulating force was 4N, and the stimulating frequency was 60 times per minute; each method and each point were used for 1 minute, totaling 9 minutes (1 min/acupoint/method × 3 methods × 3 acupoints). Treatment was administered for 21 days, followed by a 1-day rest after the 10th treatment, for a total of 20 times of intervention. The sciatic function index (SFI) was used to evaluate the fine movements of the hind limbs of rats in each group. The ultrastructural changes at the point of nerve injury were observed by transmission electron microscopy, and the gene changes at the point of nerve injury were detected using RNA-sequencing (RNA-seq) technology. RESULTS: Compared with the baseline, the SFI of the SNI group and the Tuina group decreased significantly at the 0th intervention (7 days after molding); compared with the SNI group, the SFI of the Tuina group increased at the 10th intervention (P < 0.05) and increased significantly at the 15th and 20th intervention (P < 0.01). Compared with the Sham group, the myelin sheath integrity of the sciatic nerve in the SNI group was destroyed and the myelin sheath collapsed seriously, even forming myelin sheath ball, accompanied with severe axonal atrophy and mitochondrial degeneration. The tuina intervention could significantly improve the ultrastructure of the nerve injury point, and the nerve fiber myelin sheath in the Tuina group remained intact, without obvious axonal swelling or atrophy. Atrophic thread granules could be seen in the axon, but there were no vacuolated mitochondria. RNA-seq results showed that there were differences at 221 genes at the point of nerve injury between the Tuina group and the SNI group and the differentially expressed genes (DEGs) are enriched in the biological processes related to the regulation of myocyte. Regulations include the regulation of striated muscle cell differentiation, myoblast differentiation, and myotube differentiation. CONCLUSION: Tuina can improve the fine motor recovery and protect the myelin integrity in rats with peripheral nerve injury, and this is achieved by changing the gene sequence at the injured point.
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Objective: To study the effects of the three methods and three-acupoint technique on DRG gene expression in SNI model rats and to elucidate the molecular mechanism of the three methods and three-acupoint technique on promoting recovery in peripheral nerve injury. Methods: 27 male SD rats were randomly divided into three groups: a Sham group, the SNI group, and the Tuina group. The Tuina group was treated with a tuina manipulation simulator to simulate massage on points, controlling for both quality and quantity. Point-pressing, plucking, and kneading methods were administered quantitatively at Yinmen (BL37), Chengshan (BL57), and Yanglingquan (GB34) points on the affected side once a day, beginning 7 days after modeling. Intervention was applied once a day for 10 days, then 1 day of rest, followed by 10 more days of intervention, totally equaling 20 times of intervention. The effect of the three methods and three-point technique on the recovery of injured rats was evaluated using behavior analysis. RNA sequencing (RNA-Seq) analysis of differentially expressed genes in DRGs of the three groups of rats was also performed. GO and KEGG enrichment was analyzed and verified using real-time PCR. Results: RNA-Seq combined with database information showed that the number of differentially expressed genes in DRG was the largest in the Tuina group compared with the SNI group, totaling 226. GO function is enriched in the positive regulation of cell processes, ion binding, protein binding, neuron, response to pressure, response to metal ions, neuron projection, and other biological processes. GO function is also enriched in the Wnt, IL-17, and MAPK signaling pathways in the KEGG database. PCR results were consistent with those of RNA sequencing, suggesting that the results of transcriptome sequencing were reliable. Conclusion: The three methods and three-acupoint technique can promote the recovery of SNI model rats by altering the gene sequence in DRGs.