mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence-known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen-presenting cells (APCs) can synthesize mutant neo-antigens and multi-antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T-cell receptor (TCR), CD134, and immune-modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large-scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA-based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA-based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and thedevelopment of delivery systems, especially the lipidnanoparticleplatforms. In this review, the latest strategies for overcoming the limitations of mRNA-based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA-based cancer immunotherapy are also discussed.
Owing to the emergenceof energy storage and electric vehicles, the desire for safe high-energy-density energy storage devices has increased research interest in anode-free lithium metal batteries (AFLMBs). Unlike general lithium metal batteries (LMBs), in which excess Li exists to compensate for the irreversible loss of Li, only the current collector is employed as an anode and paired with a lithiated cathode in the fabrication of AFLMBs. Owing to their unique cell configuration, AFLMBs have attractive characteristics, including the highest energy density, safety, and cost-effectiveness. However, developing AFLMBs with extended cyclability remains an issue for practical applications because the high reactivity of Li with limited inventory causes severely low Coulombic efficiency (CE), poor cyclability, and dendrite growth. To address these issues, tremendous effort has been devoted to stabilizing Li metal anodes for AFLMBs. In this review, the importance and challenges of AFLMBs are highlighted. Then, diverse strategies, such as current collectorsmodification, advanced electrolytes, cathode engineering, and operation protocols are thoroughly reviewed. Finally, a future perspective on the strategy is provided for insight into the basis of future research. It is hoped that this review provides a comprehensive understanding by reviewing previous research and arousing more interest in this field.
Artificial nanofluidic networks are emerging systems for blue energy conversion that leverages surface charge-derived permselectivity to induce voltage from diffusive ion transport under salinity difference. Here the pivotal significance of electrostatic interchannel couplings inmulti-nanoporemembranes,which impose constraints on porosity and subsequently influence the generation of large osmotic power outputs, is illustrated. Constructive interference is observed between two 20 nm nanopores of 30 nm spacing that renders enhanced permselectivity to osmotic power output via the recovered electroneutrality. On contrary, the interference is revealed as destructive in two-dimensional arrays causing significant deteriorations of the ion selectivity even for the nanopores sparsely distributed at an order of magnitude larger spacing than the Dukhin length. Most importantly, a scaling law is provided for deducing the maximal membrane area and porosity to avoid the selectivity loss via the inter-pore electrostatic coupling. As the electric crosstalk is inevitable in any fluidic network, the present findings can be a useful guide to design nanoporous membranes for scalable osmotic power generations.
The progress of brain synaptic devices has witnessed an era of rapid and explosive growth. Because of their integrated storage, excellent plasticity and parallel computing, and system information processing abilities, various field effect transistors have been used to replicate the synapses of a human brain. Organic semiconductors are characterized by simplicity of processing, mechanical flexibility, low cost, biocompatibility, and flexibility, making them the most promising materials for implanted brain synaptic bioelectronics. Despite being used in numerous intelligent integrated circuits and implantable neural linkages with multiple terminals, organic synaptic transistors still facemanyobstacles thatmust be overcome toadvance their development. A comprehensive review would be an excellent tool in this respect. Therefore, the latest advancements in implantable neural links based on organic synaptic transistors are outlined. First, the distinction between conventional and synaptic transistors are highlighted. Next, the existing implanted organic synaptic transistors and their applicability to the brain as a neural link are summarized. Finally, the potential research directions are discussed.
The glymphatic system plays a key role in the clearance of waste from the parenchyma, and its dysfunction has been associated with the pathogenesis of Alzheimer’s disease (AD). However, questions remain regarding its complete mechanisms. Here, we report that efflux of cerebrospinal fluid (CSF)/interstitial fluid (ISF) solutes occurs through a triphasic process that cannot be explained by the current model, but rather hints at the possibility of other, previously undiscovered routes from paravenous spaces to the blood. Using real-time, in vivo observation of efflux, a novel drainage pathway was discovered, in which CSF molecules enter the bloodstream directly through dynamically assembled, trumpet-shaped pores (basolateral ϕ<8 µm; apical ϕ< 2 µm) on the walls of brain venules. As Zn2+ could facilitate the brain clearance of macromolecular ISF solutes, Zn2+-induced reconstruction of the tight junctions (TJs) in vascular endothelial cells may participate in pore formation. Thus, an updated model for glymphatic clearance of brain metabolites and potential regulation is postulated. In addition, deficient clearance of Aβ through these asymmetric venule pores was observed inADmodelmice, supporting the notion that impaired brain drainage function contributes to Aβ accumulation and pathogenic dilation of the perivascular space in AD.
The current generation of wearable sensors often experiences signal interference and external corrosion, leading to device degradation and failure. To address these challenges, the biomimetic superhydrophobic approach has been developed, which offers self-cleaning, low adhesion, corrosion resistance, anti-interference, and other properties. Such surfaces possess hierarchical nanostructures and low surface energy, resulting in a smaller contact area with the skin or external environment. Liquid droplets can even become suspended outside the flexible electronics, reducing the risk of pollution and signal interference,whichcontributes tothe long-termstabilityof thedevice incomplex environments.Additionally, the coupling of superhydrophobic surfaces and flexible electronics can potentially enhance the device performance due to their large specific surface area and low surface energy. However, the fragility of layered textures in various scenarios and the lack of standardized evaluation and testing methods limit the industrial production of superhydrophobic wearable sensors. This review provides an overview of recent research on superhydrophobic flexible wearable sensors, including the fabrication methodology, evaluation, and specific application targets. The processing, performance, and characteristics of superhydrophobic surfaces are discussed, as well as the working mechanisms and potential challenges of superhydrophobic flexible electronics. Moreover, evaluation strategies for application-oriented superhydrophobic surfaces are presented.
Traditional tumour-dynamic therapystill inevitably faces the critical challengeof limited reactive oxygen species (ROS)-generating efficiency due to tumour hypoxia, extreme pH condition for Fenton reaction, and unsustainable mono-catalytic reaction. To fight against these issues, we skilfully develop a tumour-microenvironment-driven yolk-shell nanoreactor to realize the high-efficiency persistent dynamic therapy via cascaderesponsive dual cycling amplification of •SO4−/•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the Na2S2O8 nanocrystals into hollow tetra-sulphide-introduced mesoporous silica (HTSMS) and afterward enclosed by epigallocatechin gallate (EG)-Fe(II) cross-linking. Within the tumour microenvironment, the intracellular glutathione (GSH) can trigger the tetrasulphide cleavage of nanoreactors to explosively release Na+/S2O82−/Fe2+ and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO4− (Fe2+-catalyzed S2O82− oxidation), proton (•SO4--catalyzed H2O decomposition), and •OH (proton-intensified Fenton oxidation). Synchronously, the oxidation-generated Fe3+ will be in turn recovered into Fe2+ by excessive EG to circularly amplify •SO4−/•OH radicals. The nanoreactors can also disrupt the intracellular osmolarity homeostasis by Na+ overload andweaken the ROS-scavenging systems byGSHexhaustion to further amplify oxidative stress. Our yolk–shell nanoreactors can efficiently eradicate tumours via multiple oxidative stress amplification, which will provide a perspective to explore dynamic therapy.
3D graphene porous materials (3GPM), which have low density, large porosity, excellent compressibility, high conductivity, hold huge promise for a wide range of applications. Nevertheless, most 3GPM have brittle and weak network structures, which limits their widespread use. Therefore, the preparation of a robust and elastic graphene porous network is critical for the functionalization of 3GPM. Herein, the recent research of 3GPM with excellent mechanical properties are summarized and the focus is on the effect factors that affect themechanical properties of 3GPM.Moreover, the applications of elastic 3GPM in various fields, such as adsorption, energy storage, solar steam generation, sensors, flexible electronics, and electromagnetic wave shielding are comprehensively reviewed. At last, the new challenges and perspective for fabrication and functionalization of robust and elastic 3GPM are outlined. It is expected that the perspective will inspire more new ideas in preparation and functionalization of 3GPM.
The emergence of drug-resistant bacteria poses a significant threat to people’s lives and health as bacterial infections continue to persist. Currently, antibiotic therapy remains the primary approach for tackling bacterial infections. However, the escalating rates of drug resistance coupled with the lag in the development of novel drugs have led to diminishing effectiveness of conventional treatments. Therefore, the development of nonantibiotic-dependent therapeutic strategies has become imperative to impede the rise of bacterial resistance. The emergence of chemodynamic therapy (CDT) has opened up a new possibility due to the CDT can convert H2O2 into •OH via Fenton/Fenton-like reaction for drug-resistant bacterial treatment. However, the efficacy of CDT is limited by a variety of practical factors. To overcome this limitation, the sterilization efficiency of CDT can be enhanced by introducing the therapeutics with inherent antimicrobial capability. In addition, researchers have explored CDT-based combined therapies to augment its antimicrobial effects andmitigate its potential toxic side effects toward normal tissues. This review examines the research progress of CDT in the antimicrobial field, explores various strategies to enhance CDT efficacy and presents the synergistic effects of CDT in combination with other modalities. And last, the current challenges faced by CDT and the future research directions are discussed.
The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment.Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an “all-in-one” red blood cell (RBC)- derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are “immolated” under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.
Multi-scale simulation is an important basis for constructing digital batteries to improve battery design and application. LiF-rich solid electrolyte interphase (SEI) is experimentally proven to be crucial for the electrochemical performance of lithiummetal batteries. However, the LiF-rich SEI is sensitive to various electrolyte formulas and the fundamental mechanism is still unclear. Herein, the structure and formation mechanism of LiF-rich SEI in different electrolyte formulas have been reviewed. On this basis, it further discussed the possible filming mechanism of LiF-rich SEI determined by the initial adsorption of the electrolyte-derived species on the lithiummetal anode (LMA). It proposed that individual LiF species follow the Volmer–Weber mode of film growth due to its poor wettability on LMA. Whereas, the synergistic adsorption of additive-derived species with LiF promotes the Frank-Vander Merwe mode of film growth, resulting in uniform LiF deposition on the LMA surface. This perspective provides new insight into the correlation between high LiF content, wettability of LiF, and highperformance of uniform LiF-rich SEI. It disclosed the importance of additive assistant synergistic adsorption on the uniform growth of LiF-rich SEI, contributing to the reasonable design of electrolyte formulas and high-performance LMA, and enlightening the way for multi-scale simulation of SEI.