Antitumor Activity and Mechanism of Action of the Antimicrobial Peptide AMP-17 on Human Leukemia K562 Cells

Cancer is one of the most common malignant diseases in the world. Hence, there is an urgent need to search for novel drugs with antitumor activity against cancer cells. AMP-17, a natural antimicrobial peptide derived from Musca domestica, has antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and fungi. However, its antitumor activity and potential mechanism of action in cancer cells remain unclear. In this study, we focused on evaluating the in vitro antitumor activity and mechanism of AMP-17 on leukemic K562 cells. The results showed that AMP-17 exhibited anti-proliferative activity on K562 cells with an IC₅₀ value of 58.91 ± 3.57 μg/mL. The membrane integrity of K562 was disrupted and membrane permeability was increased after AMP-17 action. Further observation using SEM and TEM images showed that the cell structure of AMP-17-treated cells was disrupted, with depressions and pore-like breaks on the cell surface, and vacuolated vesicles in the cytoplasm. Furthermore, further mechanistic studies indicated that AMP-17 induced excessive production of reactive oxygen species and calcium ions release in K562 cells, which led to disturbance of mitochondrial membrane potential and blocked ATP synthesis, followed by activation of Caspase-3 to induce apoptosis. In conclusion, these results suggest that the antitumor activity of AMP-17 may be achieved by disrupting cell structure and inducing apoptosis. Therefore, AMP-17 is expected to be a novel potential agent candidate for leukemia treatment.     

Metabolites Identification and Mechanism Prediction of Neobavaisoflavone In Vitro and In Vivo of Rats through UHPLC-Q-Exactive Plus Orbitrap MS Integrated Network Pharmacology

Neobavaisoflavone is an important isoflavone component isolated from Psoraleae Fructus. It is used extensively worldwide because of its antibacterial, antioxidant, anti-inflammatory, anticancer, and anti-osteoporotic activities. However, there is no systematic and comprehensive research on the metabolism of neobavaisoflavone in vivo and in vitro. The study aimed to analyze the metabolic characteristics and mechanism of neobavaisoflavone for the first time. Firstly, biological samples were pretreated by the solid-phase extraction (SPE) method, methanol precipitation, and acetonitrile precipitation. Secondly, the samples were analyzed on UHPLC-Q-Exactive Plus Orbitrap MS. Thirdly, metabolites were tentatively identified based on retention time, parallel reaction monitoring strategy, diagnostic product ions, and neutral loss fragments. A total of 72 metabolites of neobavaisoflavone were tentatively identified, including 28 in plasma, 43 in urine, 18 in feces, six in the liver, and four in the liver microsome. The results suggested that neobavaisoflavone mainly underwent glucuronidation, sulfation, hydroxylation, methylation, cyclization, hydration, and their composite reactions in vivo and in vitro. In addition, nine active components with high bioavailability and 191 corresponding targets were predicted by the Swiss Drug Design database. The 1806 items of GO and 183 KEGG signaling pathways were enriched. These results showed that metabolites expanded the potential effects of neobavaisoflavone. The present study would provide the scientific basis for the further exploitation and application of neobavaisoflavone.     

Self-Assembled CuCo2S4 Nanoparticles for Efficient Chemo-Photothermal Therapy of Arterial Inflammation

Cardiovascular disease caused by atherosclerosis (AS) seriously affects human health. Photothermal therapy (PTT) brings hope to the diagnosis and treatment of AS, with the development of nanotechnology. To improve treatment efficiency, self-assembled CuCo₂S₄ nanocrystals (NCs) were developed as a drug-delivery nanocarrier, triggered by near-infrared (NIR) light for efficient chemophotothermal therapy of arterial inflammation. The as-prepared self-assembled CuCo₂S₄ NCs exhibited excellent biocompatibility and a very high chloroquine (CL)-loading content. In addition, the self-assembled CuCo₂S₄ NCs/CL nanocomposites showed good photothermal performance, due to strong absorption in the NIR region, and the release of CL from the NCs/CL nanocomposites was driven by NIR light. When illuminated by NIR light, both PTT from the NCs and chemotherapy from the CL were simultaneously triggered, resulting in killing macrophages with a synergistic effect. Moreover, chemo-photothermal therapy with CuCo₂S₄ NCs/CL nanocomposites showed an effective therapeutic effect for arterial inflammation, in vivo. Our work demonstrated that chemo-photothermal therapy could be a promising strategy for the treatment of arterial inflammation against atherosclerosis.     

In situ monitoring of functional activity of extracellular matrix stiffness-dependent multidrug resistance protein 1 using scanning electrochemical microscopy

Extracellular matrix (ECM) stiffness affects the drug resistance behavior of cancer cells, while multidrug resistance protein 1 (MRP1) on the cell membrane confers treatment resistance via actively transporting drugs out of cancer cells. However, the relationship between ECM stiffness and MRP1 functional activity in cancer cells remains elusive, mainly due to the technical challenge of in situ monitoring. Herein, we engineered in vitro cancer cell models using breast cancer cells (MCF-7 and MDA-MB-231 cells) as the reprehensive cells on polyacrylamide (PA) gels with three stiffness, mimicking different developmental stages of cancer. We in situ characterized the functional activity of MRP1 and investigated the effect of ECM stiffness on MRP1 of cancer cells before and after vincristine treatment using scanning electrochemical microscopy (SECM) with ferrocenecarboxylic acid (FcCOOH) as the redox mediator and endogenous glutathione (GSH) as the indicator. The SECM results show that the functional activity of MRP1 is enhanced with increasing ECM stiffness, and the MRP1-mediated vincristine efflux activity of MCF-7 cells is more affected by ECM stiffness than that of MDA-MB-231 cells. This work, for the first time, applied SECM to in situ and quantitatively monitor the functional activity of MRP1 in cancer cells in different tumor mechanical microenvironments, which could help to elucidate the mechanism of matrix stiffness-dependent drug resistance behavior in cancer cells.

SECM using FcCOOH as the redox mediator and endogenous GSH as the indicator was employed to investigate the effect of extracellular matrix stiffness on the functional activity of MRP1 in cancer cells in situ.     

A smelting–rolling strategy for ZnIn bulk phase alloy anodes

Reversibility and stability are considered as the key indicators for Zn metal anodes in aqueous Zn-ion batteries, yet they are severely hindered by uncontrolled Zn stripping/plating and side reactions. Herein, we fabricate a bulk phase ZnIn alloy anode containing trace indium by a typical smelting–rolling process. A uniformly dispersed bulk phase of the whole Zn anode is constructed rather than only a protective layer on the surface. The Zn deposition can be regarded as instantaneous nucleation due to the adsorption of the evenly dispersed indium, and formation of the exclusion zone for further nucleation can be prevented at the same time. Owing to the bulk phase structure of ZnIn alloy, the indium not only plays a crucial role in Zn deposition, but also improves the Zn stripping. Consequently, the as-designed ZnIn alloy anode can sustain stable Zn stripping/plating for over 2500 h at 4.4 mA cm⁻² with nearly 6 times smaller voltage hysteresis than that of pure Zn. Moreover, it enables a substantially stable ZnIn//NH₄V₄O₁₀ battery with 96.44% capacity retention after 1000 cycles at 5 A g⁻¹. This method of regulating the Zn nucleation by preparing a Zn-based alloy provides a potential solution to the critical problem of Zn dendrite growth and by-product generation fundamentally.

A ZnIn alloy anode with trace indium is obtained by smelting–rolling method. The Zn deposition could be regarded as instantaneous nucleation that can alleviate the effect of deposition layer for the diffusion zone and suppresses dendrite growth.     

Molecular Beam Epitaxy Growth and Electronic Structures of Monolayer GdTe_3

GdTe_3 is a layered antiferromagnetic(AFM) metal with charge density wave(CDW).We grew monolayer(ML)GdTe_3 on graphene/6H-SiC(0001) substrates by molecular beam epitaxy.The electronic and magnetic structures are studied by scanning tunneling microscopy/spectroscopy,quasi-particle interference(QPI) and first-principles calculations.Strong evidence of CDW persisting at the two-dimensional(2D) limit is found.Band dispersions and partially gapped energy bands near the Fermi surface are revealed by the QPI patterns.By density functional theory +U calculations,AFM order with stripe pattern is found to be the magnetic ground state for ML GdTe_(3).These results provide fundamental understanding and pave the way for further investigation of GdTe_3 at the 2D limit.     

CdS Nanocubes Adorned by Graphitic C3N4 Nanoparticles for Hydrogenating Nitroaromatics: A Route of Visible-Light-Induced Heterogeneous Hollow Structural Photocatalysis

Modulating the transport route of photogenerated carriers on hollow cadmium sulfide without changing its intrinsic structure remains fascinating and challenging. In this work, a series of well-defined heterogeneous hollow structural materials consisting of CdS hollow nanocubes (CdS NCs) and graphitic C₃N₄ nanoparticles (CN NPs) were strategically designed and fabricated according to an electrostatic interaction approach. It was found that such CN NPs/CdS NCs still retained the hollow structure after CN NP adorning and demonstrated versatile and remarkably boosted photoreduction performance. Specifically, under visible light irradiation (λ ≥ 420 nm), the hydrogenation ratio over 2CN NPs/CdS NCs (the mass ratio of CN NPs to CdS NCs is controlled to be 2%) toward nitrobenzene, p-nitroaniline, p-nitrotoluene, p-nitrophenol, and p-nitrochlorobenzene can be increased to 100%, 99.9%, 83.2%, 93.6%, and 98.2%, respectively. In addition, based on the results of photoelectrochemical performances, the 2CN NPs/CdS NCs reach a 0.46% applied bias photo-to-current efficiency, indicating that the combination with CN NPs can indeed improve the migration and motion behavior of photogenerated carriers, besides ameliorating the photocorrosion and prolonging the lifetime of CdS NCs.     

Extraction of Uranium in Nitric Media with Novel Asymmetric Tetra-Alkylcarbamide

The use of tetra-alkylcarbamides as novel ligands: N,N-butyl-N’,N’-hexylurea (L1: ABHU), and N,N-butyl-N’,N’-pentylurea (L2: ABPU), for the solvent extraction and complexation behaviors of uranium(VI) was synthesized and investigated in this study. The effects of HNO₃ and NO₃⁻ concentrations in the aqueous phase on the distribution ratio of U(VI) were examined. Under 5 mol/L HNO₃ concentration, D_U reached 5.02 and 4.94 respectively without third-phase formation. During the extraction, slope measurements and IR spectral analysis revealed that the U(VI) complexes are a form of UO₂(NO₃)₂·2L for both ligands. In addition, thermodynamic studies showed that the uranium extraction reaction was a spontaneous exothermic reaction. The deep structural analysis of the complexes was realized with DFT calculation. The bond length, bond properties, and topology of the complexes were discussed in detail to analyze the extraction behavior. This study enriches the coordination chemistry of U(VI) by tetra-alkylcarbamides, which may offer new clues for the design and synthesis of novel ligands for the separation, enrichment, and recovery of uranium in the nuclear fuel cycle.     

Sophorolipids—Bio-Based Antimicrobial Formulating Agents for Applications in Food and Health

Sophorolipids are well-known glycolipid biosurfactants, produced mainly by non-pathogenic yeast species such as Candida bombicola with high yield. Its unique environmental compatibility and high biodegradable properties have made them a focus in the present review for their promising applications in diverse areas. This study aims to examine current research trends of sophorolipids and evaluate their applications in food and health. A literature search was conducted using different research databases including PubMed, ScienceDirect, EBSCOhost, and Wiley Online Library to identify studies on the fundamental mechanisms of sophorolipids and their applications in food and health. Studies have shown that various structural forms of sophorolipids exhibit different biological and physicochemical properties. Sophorolipids represent one of the most attractive biosurfactants in the industry due to their antimicrobial action against both Gram-positive and Gram-negative microorganisms for applications in food and health sectors. In this review, we have provided an overview on the fundamental properties of sophorolipids and detailed analysis of their applications in diverse areas such as food, agriculture, pharmaceutical, cosmetic, anticancer, and antimicrobial activities.     

Nano-Based Co-Delivery System for Treatment of Rheumatoid Arthritis

A systemic autoimmune condition known as rheumatoid arthritis (RA) has a significant impact on patients’ quality of life. Given the complexity of RA’s biology, no single treatment can totally block the disease’s progression. The combined use of co-delivery regimens integrating various diverse mechanisms has been widely acknowledged as a way to make up for the drawbacks of single therapy. These days, co-delivery systems have been frequently utilized for co-treatment, getting over drug limitations, imaging of inflammatory areas, and inducing reactions. Various small molecules, nucleic acid drugs, and enzyme-like agents intended for co-delivery are frequently capable of producing the ability to require positive outcomes. In addition, the excellent response effect of phototherapeutic agents has led to their frequent use for delivery together with chemotherapeutics. In this review, we discuss different types of nano-based co-delivery systems and their advantages, limitations, and future directions. In addition, we review the prospects and predicted challenges for the combining of phototherapeutic agents with conventional drugs, hoping to provide some theoretical support for future in-depth studies of nano-based co-delivery systems and phototherapeutic agents.