Exploration (Beijing, China)最新文献

Jellyfish stings have become a common injury among fishermen and divers. Severe jellyfish stings could worsen cardiac function and even cause cardiac complications, ultimately leading to cardiac failure (CF). Currently, there are no effective drugs available. Single cell sequencing revealed alpha-1 acid glycoprotein (AAG), an energy regulatory protein targeting to glycogen, was highly expressed in jellyfish stings-induced CF patients. However, the mechanism remains elusive. It is postulated that AAG could increase glycogen metabolism, protecting against jellyfish stings-induced CF. AAG deletion exacerbated CF, while exogenous and endogenous AAG ameliorated CF. AAG also rescued the decline triggered by the AAG knockout (KO). Intriguingly, AAG improved cardiac function and metabolic adaptation by glycogen-driven ATP production, shifting mitochondrial/glycolytic ATP production towards glycolysis. Sorted by single-cell RNA sequencing and spatial transcription technology, CC-chemokine receptor 5 (CCR5) and Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) were differentially expressed. Mechanistically, CCR5 inhibitor MVC abolished AAG's protective effect and PGC-1α overexpression. Collectively, jellyfish stings-induced CF was ameliorated through AAG-mediated glycogen-driven ATP production, promoting glycolytic/mitochondrial metabolic switches to rely energetically primarily on glycolysis, which might serve as a therapeutic target of CF.

Sonodynamic therapy (SDT) has been explored for cancer therapy, especially for deep tumors due to its low tissue penetration restriction. The therapeutic efficacy of SDT is limited due to the complicated tumor microenvironment. This study reports the construction of oxygen-carrying semiconducting polymer nanoprodrugs (OSPN_pro) for deep tumor treatment via combining amplified SDT with pyroptosis. An oxygen carrier perfluorohexane, sonodynamic semiconducting polymer as the sonosensitizer, and reactive oxygen species (ROS)-responsive prodrug are co-loaded into a nanoparticle system, leading to the formation of these polymer nanoprodrugs. Such OSPN_pro show an effective accumulation in tumor tissues after systemic administration, in which they deliver oxygen to relieve tumor hypoxia microenvironment and thus mediate amplified SDT via producing ROS under ultrasound (US) irradiation, even when the tumors are covered with a 2-cm chicken breast tissue. In addition, the ROS-responsive prodrugs are activated by the generated ROS to trigger pyroptosis of tumor cells. Such a sono-pyroptosis induces a strong antitumor immunity with obviously higher level infiltrations of effector immune cells into tumors. Therefore, OSPN_pro-based combinational therapy can greatly inhibit the growth of 2-cm chicken breast tissue-covered deep tumors and suppress tumor metastasis. This study offers a prodrug nanoplatform for treatment of deep tumor via sono-pyroptosis strategy.

Thromboelastography (TEG) remains a convenient and effective viscoelastic coagulation testing device for guiding blood component transfusion and assessing the risk of thrombosis. This work presents a novel TEG that incorporates a miniaturized triboelectric coagulation sensor, enabling a comprehensive assessment of the coagulation system and advancing the miniaturization of traditional TEGs.

Advanced battery characterization techniques contribute to revealing and clarifying the chemical reaction processes and mechanisms inside the batteries. From atomic scale to nanoscale to long-range periodic scale, from single scale to multiscale structure detection, this review comprehensively overviews the recent advances in battery characterization using in-situ synchrotron XAFS, SAXS, XRD, and their combining techniques.

Devices that simulate sensory systems go beyond simple stimulus processing. They comprehensively interpret daily responses, indicating an expansion into new domains. Artificial sensory systems based on memristive devices simulate perception, cognition and interaction by emulating human sensory systems. This enables robots and AI to efficiently exhibit more human-like responses and behaviors in real-world situations.

In review number 20230092, Hui Gao and co-workers summarized strategies to combat F. nucleatum and F. nucleatum biofilms for improving CRC treatment, including natural extracts, inorganic chemicals, organic chemicals, polymers, inorganic organic hybrid materials, bacteriophages, probiotics, and vaccines. The review provides an outlook on the antimicrobial specificity, potential clinical implications, challenges, and future improvements of these antimicrobial approaches in CRC management.

Plasma etching is an effective strategy to synthesize the electrocatalysts, and modify its performance. In this work, the activity improvement mechanism of electrocatalysts by plasma etching is revealed. The highly active metal-nitrogen species introduced by nitrogen plasma etching treatment are recognized as the main contribution to the improved electrocatalytic activity, and simultaneously the defects induced by plasma etching also contribute to the high performance.

Tian et al. introduced a wearable AI enabled smart insole system that serves as a promising prototype for future foot healthcare applications. The foot healthcare system validated a range of foot healthcare applications, including daily statistics, prevention of sports injuries, and effective management of diabetic foot ulcers.

Cornea is the major barrier to drug delivery to the eye, which results in low bioavailability and poor efficacy of topical eye treatment. In this work, we first select cornea-binding aptamers using tissue-SELEX on pig cornea. The top two abundant aptamers, Cornea-S1 and Cornea-S2, could bind to pig cornea, and their K_d values to human corneal epithelial cells (HCECs) were 361 and 174 nм, respectively. Aptamer-functionalized liposomes loaded with cyclosporine A (CsA) were developed as a treatment for dry eye diseases. The K_d of Cornea-S1- or Cornea-S2-functionalized liposomes reduces to 1.2 and 15.1 nм, respectively, due to polyvalent binding. In HCECs, Cornea-S1 or Cornea-S2 enhanced liposome uptake within 15 min and extended retention to 24 h. Aptamer CsA liposomes achieved similar anti-inflammatory and tight junction modulation effects with ten times less CsA than a free drug. In a rabbit dry eye disease model, Cornea-S1 CsA liposomes demonstrated equivalence in sustaining corneal integrity and tear break-up time when compared to commercial CsA eye drops while utilizing a lower dosage of CsA. The aptamers obtained from cornea-SELEX can serve as a general ligand for ocular drug delivery, suggesting a promising avenue for the treatment of various eye diseases and even other diseases.

Prodrug-based self-assembled nanoparticles (PSNs) with tailored responses to tumor microenvironments show a significant promise for chemodynamic therapy (CDT) by generating highly toxic reactive oxygen species (ROS). However, the insufficient level of intracellular ROS and the limited drug accumulation remain major challenges for further clinical transformation. In this study, the PSNs for the delivery of artesunate (ARS) are demonstrated by designing the pH-responsive ARS-4-hydroxybenzoyl hydrazide (HBZ)-5-amino levulinic acid (ALA) nanoparticles (AHA NPs) with self-supplied ROS for excellent chemotherapy and CDT. The PSNs greatly improved the loading capacity of artesunate and the ROS generation from endoperoxide bridge using the electron withdrawing group attached directly to C10 site of artesunate. The ALA and ARS-HBZ could be released from AHA NPs under the cleavage of hydrazone bonds triggered by the acidic surroundings. Besides, the ALA increased the intracellular level of heme in mitochondria, further promoting the ROS generation and lipid peroxidation with ARS-HBZ for excellent anti-tumor effects. Our study improved the chemotherapy of ARS through the chemical modification, pointing out the potential applications in the clinical fields.