Site-specific engineering of S-Te-S bridged nano-prodrug: A dual equilibrium strategy for enhanced antitumor efficacy and safety of paclitaxel.

Homodimeric prodrug nanoassemblies (HPNs) have emerged as an effective strategy to enhance the therapeutic efficacy and safety of chemotherapeutic drugs. However, achieving both stable assembly and rapid drug release in tumor remains a critical challenge. Herein, we designed S-Te-S linkages with varying linkage lengths (α-, β-, and γ-) to develop three paclitaxel (PTX) homodimeric prodrug nanoassemblies (PHPNs).

Lycium barbarum glycopeptide attenuates intracerebral hemorrhage-induced inflammation and oxidative stress via activation of the Sirt3 signaling pathway.

Background: Intracerebral hemorrhage (ICH) is a severe neurological condition characterized by high morbidity and mortality rates, with no effective treatment currently available. Lycium barbarum glycopeptide (LbGP), derived from the further purification of Lycium barbarum polysaccharides (LBP), has demonstrated anti-inflammatory effects, suggesting its potential as a therapeutic agent for ICH. However, the role and mechanisms of LbGP in ICH remain unclear.

Long-Term Exposure to Tire-Derived 6-PPD Quinone Causes Neurotoxicity and Neuroinflammation via Inhibition of HTR2A in C57BL/6 Mice.

-(1,3-dimethylbutyl)-'-phenyl--phenylenediamine quinone (6-PPDQ), a novel contaminant derived from tire wear, has raised concerns due to its potential neurotoxicity, yet its long-term effects on mammalian neurological health remain poorly understood. This study investigates the neurotoxic and neuroinflammatory impacts of prolonged 6-PPDQ exposure using male C57BL/6 mice. Behavioral assessments revealed significant cognitive deficits, while biochemical analyses demonstrated increased levels of reactive oxygen species, apoptosis, and blood-brain barrier (BBB) disruption.

Apelin-13-Loaded Macrophage Membrane-Encapsulated Nanoparticles for Targeted Ischemic Stroke Therapy via Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis.

Purpose: Ischemic stroke is a refractory disease wherein the reperfusion injury caused by sudden restoration of blood supply is the main cause of increased mortality and disability. However, current therapeutic strategies for the inflammatory response induced by cerebral ischemia-reperfusion (I/R) injury are unsatisfactory. This study aimed to develop a functional nanoparticle (MM/ANPs) comprising apelin-13 (APNs) encapsulated in macrophage membranes (MM) modified with distearoyl phosphatidylethanolamine-polyethylene glycol-RVG29 (DSPE-PEG-RVG29) to achieve targeted therapy against ischemic stroke.

Ultralow Energy Consumption and Fast Neuromorphic Computing Based on LaBiFeO Ferroelectric Tunnel Junctions.

Low-power and fast artificial neural network devices represent the direction in developing analogue neural networks. Here, an ultralow power consumption (0.8 fJ) and rapid (100 ns) LaBiFeO/LaSrMnO ferroelectric tunnel junction artificial synapse has been developed to emulate the biological neural networks.

Carbon-Spaced Tandem-Disulfide Bond Bridge Design Addresses Limitations of Homodimer Prodrug Nanoassemblies: Enhancing Both Stability and Activatability.

Redox-responsive homodimer prodrug nanoassemblies (RHPNs) have emerged as a significant technology for overcoming chemotherapeutical limitations due to their high drug-loading capacity, low excipient-associated toxicity, and straightforward preparation method. Previous studies indicated that α-position disulfide bond bridged RHPNs exhibited rapid drug release rates but unsatisfactory assembly stability. In contrast, γ-disulfide bond bridged RHPNs showed better assembly stability but low drug release rates.

Deletion of Tmem268 in mice suppresses anti-infectious immune responses by downregulating CD11b signaling.

Transmembrane protein 268 (TMEM268) is a novel, tumor growth-related protein first reported by our laboratory. It interacts with the integrin subunit β4 (ITGB4) and plays a positive role in the regulation of the ITGB4/PLEC signaling pathway. Here, we investigated the effects and mechanism of TMEM268 in anti-infectious immune response in mice.

Emergent Chirality and Hyperuniformity in an Active Mixture with Nonreciprocal Interactions.

We investigate collective dynamics in a binary mixture of programmable robots in experiments and simulations. While robots of the same species align their motion direction, interaction between species is distinctly nonreciprocal: species A aligns with B and species B antialigns with A. This nonreciprocal interaction gives rise to the emergence of collective chiral motion that can be stabilized by limiting the robot angular speed to be below a threshold.

RNF115/BCA2 deficiency alleviated acute liver injury in mice by promoting autophagy and inhibiting inflammatory response.

The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has been linked with the growth of some cancers and immune regulation, which is negatively correlated with prognosis. Here, it is demonstrated that the RNF115 deletion can protect mice from acute liver injury (ALI) induced by the treatment of lipopolysaccharide (LPS)/D-galactosamine (D-GalN), as evidenced by decreased levels of alanine aminotransaminase, aspartate transaminase, inflammatory cytokines (e.g.

Exploring the criticality hypothesis using programmable swarm robots with Vicsek-like interactions.

A widely mentioned but not experimentally confirmed view (known as the 'criticality hypothesis') argues that biological swarm systems gain optimal responsiveness to perturbations and information processing capabilities by operating near the critical state where an ordered-to-disordered state transition occurs. However, various factors can induce the ordered-disordered transition, and the explicit relationship between these factors and the criticality is still unclear. Here, we present an experimental validation for the criticality hypothesis by employing real programmable swarm-robotic systems (up to 50 robots) governed by Vicsek-like interactions, subject to time-varying stimulus-response and hazard avoidance.

A Minimalist Self-Localization Approach for Swarm Robots Based on Active Beacon in Indoor Environments.

When performing indoor tasks, miniature swarm robots are suffered from their small size, poor on-board computing power, and electromagnetic shielding of buildings, which means that some traditional localization methods, such as global positioning system (GPS), simultaneous localization and mapping (SLAM), and ultra-wideband (UWB), cannot be employed. In this paper, a minimalist indoor self-localization approach for swarm robots is proposed based on active optical beacons. A robotic navigator is introduced into a swarm of robots to provide locally localization services by actively projecting a customized optical beacon on the indoor ceiling, which contains the origin and the reference direction of localization coordinates.

AIM2 and NLRC4-driven inflammasome activation in adult-onset Still's disease and the preliminary therapeutic effect exploration of carboxyamidotriazole.

Objectives: This study aimed to explore the changes of four major inflammasomes in adult-onset Still's disease (AOSD) and preliminarily evaluate the therapeutic effect of carboxyamidotriazole (CAI), which has previously been reported to have the significant anti-inflammatory activity.

Method: The mRNA expressions of proinflammatory cytokines and inflammasome components in peripheral blood mononuclear cells (PBMCs) from AOSD patients and healthy controls (HC) were determined by reverse transcription-quantitative PCR. Poly(dA:dT)-induced AIM2 inflammasome and flagellin-induced NLRC4 inflammasome activation models were established in bone marrow-derived macrophages (BMDMs).

Novel assays for quality evaluation of XueBiJing: Quality variability of a Chinese herbal injection for sepsis management.

XueBiJing is an intravenous five-herb injection used to treat sepsis in China. The study aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS)- or liquid chromatography-ultraviolet (LC-UV)-based assay for quality evaluation of XueBiJing. Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in parallel.

TMEM189 negatively regulates the stability of ULK1 protein and cell autophagy.

ULK1 is crucial for initiating autophagosome formation and its activity is tightly regulated by post-translational modifications and protein-protein interactions. In the present study, we demonstrate that TMEM189 (Transmembrane protein 189), also known as plasmanylethanolamine desaturase 1 (PEDS1), negatively regulates the proteostasis of ULK1 and autophagy activity. In TMEM189-overexpressed cells, the formation of autophagesome is impaired, while TMEM189 knockdown increases cell autophagy.

Carboxyamidotriazole exerts anti-inflammatory activity in lipopolysaccharide-induced RAW264.7 macrophages by inhibiting NF-κB and MAPKs pathways.

Carboxyamidotriazole (CAI), originally developed as a non-cytotoxic anti-cancer drug, was shown to have anti-inflammatory activity according to recent studies in a number of animal models of inflammation. However, its mechanism of action has not been characterized. Therefore, the present study was performed to identify the anti-inflammatory action of CAI in lipopolysaccharide (LPS)-induced RAW 264.

Urate transport capacity of glucose transporter 9 and urate transporter 1 in cartilage chondrocytes.

Chronic gouty arthritis, caused by a persistent increase in, and the deposition of, soluble uric acid (sUA), can induce pathological chondrocyte destruction; however, the effects of urate transport and intracellular sUA on chondrocyte functionality and viability are yet to be fully determined. Thus, the aim of the present study was to investigate the presence and functionality of a urate transport system in chondrocytes. The expression profiles of two primary urate reabsorptive transporters, glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), in human articular cartilage and chondrocyte cell lines were examined via western blotting, reverse transcription‑quantitative PCR, immunohistochemistry and immunofluorescence.