Exploration (Beijing, China)最新文献

Molecular hydrogen (H₂) ortho-para conversion (O/P conversion) proceeds slowly at low temperatures accompanying a heat release. Thus, catalysts for accelerating this conversion rate are highly demanded in terms of the storage and utilization of liquid H₂. The catalysts for this purpose are experimentally screened by examining a broad range of materials covering magnetic, non-magnetic, metallic, and nonmetallic oxides. The primary conclusions obtained are summarized below. (1) active materials are required to be non-metallic and to bear the cations with ionic radii smaller than the bond length of H₂. (2) Metallic materials have almost no activity irrespective of with or without magnetism (3) The activity of materials belonging to (1) is largely enhanced when the constituting cation has a magnetic moment. In addition, there is a class of materials for which the activity is distinctly enhanced just upon substitution by the foreign ions.

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.

Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well-being. Currently, existing treatments for atherosclerosis lack sufficient efficiency, while the utilization of surface-modified nanoparticles holds the potential to deliver highly effective therapeutic outcomes. These nanoparticles can target and bind to specific receptors that are abnormally over-expressed in atherosclerotic conditions. This paper reviews recent research (2018–present) advances in various ligand-modified nanoparticle systems targeting atherosclerosis by specifically targeting signature molecules in the hope of precise treatment at the molecular level and concludes with a discussion of the challenges and prospects in this field. The intention of this review is to inspire novel concepts for the design and advancement of targeted nanomedicines tailored specifically for the treatment of atherosclerosis.

Previously, the effect of soil mineral N deficiency on nodule nitrogen fixation capacity (NFC) is unclear. In this study, we found that N deficiency would enhance sucrose allocation to nodules and PEP allocation to bacteroid to promote nodule NFC. Our findings provide new insights into the design of leguminous crops with improved adaptation to fluctuating N levels in the soil.

COVID-19 is currently pandemic and the detection of SARS-CoV-2 variants in wastewater is causing widespread concern. Herein, cold atmospheric plasma (CAP) is proposed as a novel wastewater disinfection technology that effectively inactivates SARS-CoV-2 transcription- and replication-competent virus-like particles, coronavirus GX_P2V, pseudotyped SARS-CoV-2 variants, and porcine epidemic diarrhoea virus in a large volume of water within 180 s (inhibition rate > 99%). Further, CAP disinfection did not adversely affect the viability of various human cell lines. It is identified that CAP produced peroxynitrite (ONOO⁻), ozone (O₃), superoxide anion radicals (O₂⁻), and hydrogen peroxide (H₂O₂) as the major active substances for coronavirus disinfection. Investigation of the mechanism showed that active substances not only reacted with the coronavirus spike protein and affected its infectivity, but also destroyed the nucleocapsid protein and genome, thus affecting virus replication. This method provides an efficient and environmentally friendly strategy for the elimination of SARS-CoV-2 and other coronaviruses from wastewater.

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 in AD model mice, supporting the notion that impaired brain drainage function contributes to Aβ accumulation and pathogenic dilation of the perivascular space in AD.

Protein-based drugs have shown unique advantages to treat various diseases in recent years. However, most protein therapeutics in clinical use are limited to extracellular targets with low delivery efficiency. To realize targeted protein delivery, a series of stimuli-triggered nanoparticle formulations have been developed to improve delivery efficiency and reduce off-target release. These smart nanoparticles are designed to release cargo proteins in response to either internal or external stimuli at pathological tissues. In this way, varieties of protein-based drugs including antibodies, enzymes, and pro-apoptotic proteins can be effectively delivered to desired sites for the treatment of cancer, inflammation, metabolic diseases, and so on with minimal side effects. In this review, recent advances in the design of stimuli-triggered nanomedicine for targeted protein delivery in different biomedical applications will be discussed. A deeper understanding of these emerging strategies helps develop more efficient protein delivery systems for clinical use in the future.

Thromboelastography (TEG) remains a convenient and effective viscoelastic blood coagulation testing device for guiding blood component transfusion and assessing the risk of thrombosis. Here, a TEG enabled by a non-contact triboelectric angle sensor (NTAS) with a small size (∼7 cm³) is developed for assessing the blood coagulation system. With the assistance of a superelastic torsion wire structure, the NTAS-TEG realizes the detection of blood viscoelasticity. Benefiting from a grating and convex design, the NTAS holds a collection of compelling features, including accurate detection of rotation angles from −2.5° to 2.5°, high linearity (R² = 0.999), and a resolution of 0.01°. Besides, the NTAS exhibits merits of low cost and simplified fabrication. Based on the NTAS-TEG, a viscoelastic blood coagulation detection and analysis system is successfully constructed, which can provide a graph and parameters associated with clot initiation, formation, and stability for clinicians by using 0.36 mL of whole blood. The system not only validates the feasibility of the triboelectric coagulation testing sensor, but also further expands the application of triboelectric sensors in healthcare.

The fibrillation of amyloid-β (Aβ) is the critical causal factor in Alzheimer's disease (AD), the dissolution and clearance of which are promising for AD therapy. Although many Aβ inhibitors are developed, their low Aβ-binding affinity results in unsatisfactory effect. To solve this challenge, the Aβ sequence-matching strategy is proposed to tail-design dissociable nanosystem (B6-PNi NPs). Herein, B6-PNi NPs aim to improve Aβ-binding affinity for effective dissolution of amyloid fibrils, as well as to interfere with the in vivo fate of amyloid for Aβ clearance. Results show that B6-PNi NPs decompose into small nanostructures and expose Aβ-binding sites in response to AD microenvironment, and then capture Aβ via multiple interactions, including covalent linkage formed by nucleophilic substitution reaction. Such high Aβ-binding affinity disassembles Aβ fibrils into Aβ monomers, and induces the reassembly of Aβ&nanostructure composite, thereby promoting microglial Aβ phogocytosis/clearance via Aβ receptor-mediated endocytosis. After B6-PNi NPs treatment, the Aβ burden, neuroinflammation and cognitive impairments are relieved in AD transgenic mice. This work provides the Aβ sequence-matching strategy for Aβ inhibitor design in AD treatment, showing meaningful insight in biomedicine.

Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI. Here, an “ion cocktail therapy” is proposed to simultaneously reverse cardiac structural and electrical remodeling post-MI in rats and minipigs by applying a unique combination of silicate, strontium (Sr) and copper (Cu) ions due to their specific regulatory effects on the behavior of the key cells involved in MI including angiogenesis of endothelial cells, M2 polarization of macrophages and apoptosis of cardiomyocyte. The results demonstrate that ion cocktail treatment attenuates structural remodeling post-MI by ameliorating infarct size, promoting angiogenesis in both peri-infarct and infarct areas. Meantime, to some extent, ion cocktail treatment reverses the deteriorative electrical remodeling by reducing the incidence rate of early/delayed afterdepolarizations and minimizing the heterogeneity of cardiac electrophysiology. This ion cocktail therapy reveals a new strategy to effectively treat MI with great clinical translation potential due to the high effectiveness and safety of the ion cocktail combination.