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PurposeTriple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has the highest propensity among breast cancer subtypes to develop leptomeningeal disease (LMD). LMD is a spread of cancer into leptomeningeal space that speeds up the disease progression and severely aggravates the prognosis. LMD has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD.MethodsA small-molecule screen involving TNBC cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used to evaluate cell migration capacity and the effect of MBZ. For in vivo testing, CNS metastasis was introduced into BALB/c athymic nude mice through internal carotid artery injections of brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth and spread was monitored by bioluminescence imaging and immunohistochemistry. MBZ was given orally at 50 and 100 mg/kg doses. MBZ bioavailability was assayed by mass spectrometry.ResultsBioinformatic analysis and migration assays revealed higher migratory capacity of TNBC compared to other breast cancer subtypes. MBZ effectively slowed down migration of TNBC cell line MDA-MB-231 and its brain tropic derivative MDA-MB-231-BR. In animal studies, MBZ reduced leptomeningeal spread, and extended survival in brain metastasis model produced by MDA-MB-231-BR cells. MBZ did not have an effect in the non-migratory MCF7-BR model.ConclusionsWe demonstrated that MBZ is a safe and effective oral agent in an animal model of TNBC CNS metastasis. Our findings are concordant with previous efforts involving MBZ and CNS pathology and support the drug's potential utility to slow down leptomeningeal spread.

Aluminum nitride (AlN) has high thermal conductivity, good insulation, low thermal expansion coefficient, non-magnetic, and other excellent properties used as a key material for high-end equipment in semiconductor, electric vacuum, and other fields. Especially in aerospace, rail transportation, new energy equipment, high-power LED, 5G communication, power transmission, industrial control, and other fields of power devices, AlN has an irreplaceable role. The high-grade powders are the basis for the preparation of high-performance ceramics. The properties of AlN powders directly affect the forming, sintering, microstructure, and performance of the AlN ceramics. Carbothermal reduction-nitridation method is a promising method to produce the AlN powders with high purity, fine particle size, and high sintering property. The evaluation indexes of the AlN powders and the research progress on the carbothermal reduction-nitridation of AlN powders were reviewed in this paper, and the direction and trend of future research and industrialization were proposed.

Silicon nitride (Si3N4) is considered to be the best ceramic material for the comprehensive properties. High thermal conductivity and the excellent mechanical properties make it widely used as the ceramic substrate in electric vehicles and hybrid electric vehicles (EV/HEV). Sintering additives have the great influence on the sintering activity, microstructure, and the second phase composition of silicon nitride, and then affect the thermal conductivity of ceramics. Selecting the suitable sintering additives is very important for the preparation of high thermal conductivity silicon nitride ceramics. The research status of sintering additives used for the preparation of high thermal conductivity silicon nitride ceramics was summarized in this paper, the influence of sintering additives on the thermal conductivity and mechanical properties of silicon nitride ceramics was analyzed, and the future research direction and development trend of sintering additives were put forward.

Traumatic spinal cord injury (SCI) initiates an intricate secondary injury cascade, characterized by persistent inflammatory responses with neurotoxic microglia and astrocyte activation. Inhibition of neuroinflammation would significantly benefit SCI treatment. Here, tetrandrine with anti-neuroinflammatory activity was delivered into the intrathecal space for SCI treatment. The tetrandrine was encapsulated in MPEG-PDLLA nanoparticles and further loaded into GelMA microgels via a fast 3D printing process based on digital light. After intrathecal injection, the drug-loaded microgels could sustain the release of tetrandrine in the intrathecal space, resulting in efficient repair of the injured spinal cord with recovery of function. Its mechanisms were associated with the modulation of neurotoxic microglia and astrocytes as well as their crosstalk. This work demonstrates a tetrandrine-loaded microgel with potential application in SCI treatment via sustained inhibition of neuroinflammation. [ABSTRACT FROM AUTHOR]

Background: Osteoclasts are integral to the advancement of osteoporosis (OP), and their generation under conditions of oxidative stress (OS) involves various pathways. However, the specific mechanism through which the natural antioxidant kaempferol (KAE) mitigates the influence of OS on osteoclasts remains somewhat uncertain. This study aims to evaluate the effect of KAE on osteoclast formation under OS and explore its possible mechanism. Methods: Zebrafish were used to observe the effects of KAE on OP and OS. OP and OS "double disease targets" network pharmacology were used to predict the action target and mechanism of KAE on OP under OS. The effects of KAE on osteoclast differentiation induced by OS were evaluated using RWA264.7 cells induced by LPS. To elucidate the potential mechanism, we detected the expression of related factors and target genes during induction. Results: The presence of KAE exhibited potential in improving the conditions of OP and OS in zebrafish. KAE can reduce the OS of RAW 264.7 cells stimulated by LPS, inhibit the formation of osteoclasts, and change the level of related factors of OS, and reduce the increase of TRAP. The utilization of network pharmacology and target gene expression assay revealed that KAE exerted a down‐regulatory effect on the expression of proto‐oncogene tyrosine protein kinase (SRC), nuclear factor kappa‐B (NF‐κB), Serine/Threonine Kinase‐1 (AKT1), Nitric Oxide Synthase 3 (NOS3) and Matrix Metallopeptidase‐2 (MMP2). Conclusion: Based on the results of this study, KAE may effectively mitigate OS and impede the formation of osteoclasts through the SRC/NF‐κB‐AKT/NOS3 axis. [ABSTRACT FROM AUTHOR]

Introduction: The industrial processing of corn (Zeamays L.) generates byproducts such as corn silk, straw peels, and straw core, which contribute to adverse environmental impacts. Our study aimed to investigate sustainable approaches for mitigating these effects by evaluating the hypoglycemic potential and mechanisms of ethyl acetate fractions derived from these corn derivatives. Methods: We employed glucose consumption assays, high glucose stress tests, UPLC-QE-Orbitrap-MS analysis, molecular docking, and simulations to assess their components and efficacy. Antioxidant capacities were evaluated using DPPH, FRAP, ABTS, and •OH scavenging assays. Results: Notably, the ethyl acetate fraction extracted from straw peels (SPE) exhibited a high concentration of flavonoids and phenolic compounds along with pronounced hypoglycemic activity and antioxidant capacity. SPE significantly enhanced glucose consumption in insulin-resistant HepG2 cells while protecting HUVECs against damage caused by high glucose levels. Molecular docking analyses confirmed the interaction between active compounds and α-glucosidase as well as α-amylase, while molecular dynamic simulations indicated stability at their binding sites. Discussion: In conclusion, the hypoglycemic and antioxidative properties observed in corn by-products such as straw peels, corn silk, and straw core can be attributed to the inhibition of α-glucosidase and α-amylase activities, coupled with their rich phenolic and flavonoid content. These findings highlight the potential of these by-products for applications in healthcare management and their sustainable utilization, demonstrating significant value in the use of agricultural residues. [ABSTRACT FROM AUTHOR]

In the quest to achieve "double carbon" goals, the urgency to develop an efficient Integrated Energy System (IES) is paramount. This study introduces a novel approach to IES by refining the conventional Power-to-Gas (P2G) system. The inability of current P2G systems to operate independently has led to the incorporation of hydrogen fuel cells and the detailed investigation of P2G's dual-phase operation, enhancing the integration of renewable energy sources. Additionally, this paper introduces a carbon trading mechanism with a refined penalty–reward scale and a detailed pricing tier for carbon emissions, compelling energy suppliers to reduce their carbon footprint, thereby accelerating the reduction in system-wide emissions. Furthermore, this research proposes a flexible adjustment mechanism for the heat-to-power ratio in cogeneration, significantly enhancing energy utilization efficiency and further promoting conservation and emission reductions. The proposed optimization model in this study focuses on minimizing the total costs, including those associated with carbon trading and renewable energy integration, within the combined P2G-Hydrogen Fuel Cell (HFC) cogeneration system. Employing a bacterial foraging optimization algorithm tailored to this model's characteristics, the study establishes six operational modes for comparative analysis and validation. The results demonstrate a 19.1% reduction in total operating costs and a 22.2% decrease in carbon emissions, confirming the system's efficacy, low carbon footprint, and economic viability. [ABSTRACT FROM AUTHOR]