Exploration (Beijing, China)最新文献

Type 2 diabetes (T2D) is a prevalent metabolic disease inducing alterations of multiple organ systems with currently no cure. Extracellular vesicles (EVs) have been increasingly noticed as one critical paracrine communicator inducing insulin resistance and metabolic disorders in T2D, but clinically available pharmaceuticals for controlling pathological EV release is lacking. Here, we discover that the natural monosaccharide D-mannose exists with an altered level in the db/db mouse T2D model. Intriguingly, oral administration of D-mannose with the drinking water safely ameliorates diabetic symptoms in db/db mice. D-mannose administration does not critically regulate the gut microbiome and circulatory T lymphocytes in treating T2D, while administrated D-mannose rapidly accumulates in the liver, alleviates hepatic steatosis and rescues insulin resistance. Regarding the mechanism, the T2D pathological EVs released by macrophages are targeted and reduced by D-mannose, which metabolically inhibits CD36 expression and restores function of hepatocytes. Importantly, by regulating macrophage EV release, D-mannose administration reveals extra-hepatic benefits and retards diabetic bone loss. Taken together, our findings unveil D-mannose as a candidate T2D therapeutic and highlight sugars governing intercellular EV crosstalk, paving an avenue for pharmaceutical T2D approaches with amelioration of multi-organ deteriorations.

Cyclic dinucleotides, which act as agonists for the stimulator of interferon genes (STING), are pivotal in stimulating both adaptive and innate immune reactions for advancing cancer immunotherapy. However, their therapeutic potential is hampered by inherent limitations, including susceptible degradation and inefficient delivery. Herein, we design genetically engineered bacteria (2'3'-cGAMP@E.coli) capable of producing 2'3'-cGAMP in the cytoplasm and then fabricate personalized nanovaccines (nECTs) by assembling 2'3'-cGAMP@E.coli with autologous tumor antigens instead of complicated chemical synthesis. Our in vitro analysis confirms that nECTs are capable of potently stimulating dendritic cell activity and amplifying the cross-presentation of antigens by leveraging the STING signaling route, underscoring their potential to bolster immune response priming. Translating these findings into in vivo models, vaccination with nECTs leads to a pronounced infiltration of effector T cells into tumor sites, concurrent with an IFN-β-mediated remodeling of the suppressive tumor microenvironment by innate immune cells. Notably, the therapeutic efficacy of nECTs is further augmented when coupled with a fasting-mimicking diet regimen, highlighting the synergistic potential of this combinatory strategy. Collectively, this dual modality represents a significant stride towards enhancing the precision and effectiveness of immunotherapeutic interventions in oncology.

Irregular dendrite growth and complex side reactions pose critical challenges that significantly impede the further industrialization of aqueous zinc-ion batteries (AZIBs). The “competitive co-solvents” strategy could introduce hydrogen bond (H-bond) accepting sites to effectively alleviate the free water molecules. however, it suffers from low conductivity, high cost, and safety risks. Herein, we selected N, N'-methylenebisacrylamide (MBA) as a trace additive with amide groups to decrease the activity of water by disrupting the H-bond. The MBA additive, which incorporates both hydrogen bond donor and acceptor functionalities, successfully restricts H₂O molecules within a double-site anchoring configuration. This configuration enhances hydrogen-bonding interactions and breaks part of the original hydrogen bond network among H₂O molecules, thereby significantly restraining parasitic side reactions due to the decomposition of active water. Additionally, MBA molecules adsorbed on the surface of the Zn anode could regulate the desolvation and nucleation processes of zinc ions, achieving dense and flat zinc deposition. A high Zn reversibility with Coulombic efficiency (CE) of 99.74% and ultra-long lifespan of 2800 cycles at 1 and 0.5 mAh cm⁻² was demonstrated. Besides, a highly reversible Zn electrode significantly boosted the overall performance of Zn//Zn symmetric cells of 1500 h at 5 mA cm⁻² and Zn//V₂O₅ full cell of 2000 cycles at 5 A g⁻¹.

The inhibition of joint synovial inflammation, caused by poor oxygen (O₂) supply and excessive reactive oxygen species (ROS) generation, is an important treatment strategy for rheumatoid arthritis (RA). Herein, we formulated a targeted ruthenium-based anti-inflammatory nanosystem consisting of ruthenium clusters-loaded F127-organosilica micelles with folic acid (FA) modification (RuFOMs-FA) for RA treatment through a two-stage macrophage regulatory mechanism. At the first stage, RuFOMs-FA exhibited excellent photothermal capability with a high photothermal conversion efficiency of 55.3% upon external-field 808 nm NIR irradiation, which further induced the death of M1 macrophages through the folic acid-mediated active targeting pathway. Further, the resultant nanoagent mimicked enzymes displayed catalase-like and superoxide dismutase-like activities for endogenously scavenging ROS and producing O₂ to induce the polarization of pro-inflammatory M1 to anti-inflammatory M2 macrophages in the RA physiological environment. More importantly, RuFOMs-FA effectively alleviated hypoxia, inflammation, and cartilage destruction in the synovial joints in a rat RA model by the two-stage macrophage regulatory mechanism. Consequently, it is highly expected that the developed RuFOMs-FA could be applied as a new noble metal-based anti-inflammatory candidate nanosystem for efficient and safe RA treatment.

Solid waste remains a global crisis in which massive amount of solid waste is disposed of in landfills and the environment yearly, leading to detrimental environmental pollution and loss of resources. However, the current downcycling technologies, such as pyrolysis and gasification, usually require extensive energy input and harsh operating conditions, posing a high possibility of causing secondary pollution. In pursuit of a sustainable future, artificial photosynthesis arises as one of the promising but arduous approaches to reform solid waste into fuels and commodity chemicals under benign conditions. Under this backdrop, this review aims to present a thorough overview of the recent advancement in solid waste transformation through photocatalysis. To begin with, the principles of solar-driven conversion pathways for solid waste are discussed under different reaction conditions. Then this review also highlights the merits of artificial photosynthesis and diverse state-of-the-art photocatalysts for solid waste valorization. Special emphasis is placed on elucidating the application of external-field-assisted photocatalysis (e.g. photothermocatalysis, photoelectrocatalysis, photobiocatalysis, and piezo-photocatalysis) for solid waste upcycling to explore the synergistic effects on performance improvement. Finally, insights on the challenges and prospects in photocatalytic solid waste conversion are presented to bridge a new exemplification towards a sustainable circular economy in the future.

Messenger RNA (mRNA) therapeutics and vaccines have recently gained particular prominence following the COVID-19 epidemic. However, clinical translation of mRNAs is critically dependent on efficient and safe delivery in vivo. Currently, a plethora of mRNA delivery technology platforms (such as lipid nanoparticles) have been developed and have achieved stunning success. Nevertheless, many challenges remain to be overcome, including immunogenicity and toxicities, excessive liver accumulation, limited endosomal escape ability, low tissue bioavailability, poor mucosal immunity, and the need for cold chain storage. In recent years, extracellular vesicles (EVs) have emerged as an attractive mRNA delivery platform due to their favorable properties, such as low immunogenicity, natural capability to deliver RNAs, intrinsic targeting capacity, and the ability to negotiate with physiological barriers. In this review, we discuss the latest efforts to harness EVs for mRNA delivery and elaborate the behind mechanisms, aiming to offering insights into the rational design of effective and safe EV-based mRNA therapeutics and vaccines for biomedical applications. Additionally, we provide an overview of EV biogenesis, composition, cellular internalization, and their superiorities and challenges for mRNA delivery, with special emphasis on the state-of-the-art methodologies for packaging EVs with mRNAs.

The design of green and low-cost Z-scheme heterojunctions with the interfacial electric field (IEF) is of prime importance to their photocatalytic hydrogenation performance and practical application. In this work, we construct a novel Z-scheme heterojunction photocatalyst comprised of Zn-Ni₂P/g-C₃N₄ nanosheets for hydrogen evolution reaction (HER). Experimental results and density functional theory calculations demonstrate that the construction of Z-scheme Zn-Ni₂P/g-C₃N₄ heterostructure not only promotes the generation of IEF directing from Zn-Ni₂P to g-C₃N₄, along with work function, accelerating the photogenerated charge separation in Zn-Ni₂P/g-C₃N₄, but also leads to the upshift of the p-band state density in Zn-Ni₂P/g-C₃N₄, favorable for the H* adsorption toward HER. The Zn-Ni₂P/g-C₃N₄ photocatalyst demonstrated excellent photocatalytic HER activity, with a hydrogen production rate of up to 1077 µmol g⁻¹ h⁻¹ and a stability of 49 h. Our findings provide a new method to enhance the separation of photogenerated charges. This improvement boosts the photocatalytic properties of solar-driven materials and devices.

Multidrug-resistant Klebsiella pneumoniae constitutes a significant threat as a nosocomial pathogen, and no licensed vaccines are currently available. Generalized modules for membrane antigens (GMMA) have recently been recognized as a promising platform for developing outer membrane vesicle (OMV) vaccines against numerous infectious diseases. The study was carried out in use of the W3110 ΔwbbH-L ΔlpxM::lpxE in which E. coli was treated in order to eliminate the endogenous polysaccharide and use two new ones (polysaccharides from Klebsiella). The exogenous polysaccharides were accurately displayed on the surface of spontaneously released OMVs. The immune responses evoked by subcutaneous administration of these vaccines were evaluated, and the protective effects were assessed using a mouse intraperitoneal challenge model. Interference in the biosynthesis of endogenous polysaccharides (such as deleting related gene clusters) is a viable approach to increasing the yield of glycoengineered GMMA vaccines (geGMMA). The geGMMA platform, which is conducive to safer large-scale production, lays the foundations for the development of GMMA vaccines decorated with exogenous glycan antigens derived from pathogenic bacteria.

X. Li, W. Wang, Q. Gao, et al., “Intelligent Bacteria-Targeting ZIF-8 Composite for Fluorescence Imaging-Guided Photodynamic Therapy of Drug-Resistant Superbug Infections and Burn Wound Healing,” Exploration (Beijing, China) 4, no. 6 (2024): 20230113. https://doi.org/10.1002/EXP.20230113.

The images in Figure 4G (skin photographs) and Figure 5C (bacterial plate—NPs group) were erroneously utilized. The authors identified these inaccuracies and have provided the corrected versions of Figures 4G and 5C below:

We apologize for this error.

Flexible ionic conductive electrodes, as a fundamental component for electrical signal transmission, play a crucial role in skin-surface electronic devices. Developing a skin-seamlessly electrode that can effectively capture long-term, artifact-free, and high-quality electrophysiological signals remains a challenge. Herein, we report an ultra-thin and dry electrode consisting of deep eutectic solvent (DES) and zwitterions (CEAB), which exhibit significantly lower reactance and noise in both static and dynamic monitoring compared to standard Ag/AgCl gel electrodes. Our electrodes have skin-like mechanical properties (strain-rigidity relationship and flexibility), outstanding adhesion, and high electrical conductivity. Consequently, they excel in consistently capturing high-quality epidermal biopotential signals, such as the electrocardiogram (ECG), electromyogram (EMG), and electroencephalogram (EEG) signals. Furthermore, we demonstrate the promising potential of the electrodes in clinical applications by effectively distinguishing aberrant EEG signals associated with depressive patients. Meanwhile, through the integration of CEAB electrodes with digital processing and advanced algorithms, valid gesture control of artificial limbs based on EMG signals is achieved, highlighting its capacity to significantly enhance human-machine interaction.