One-Step Calcination to Gain Exfoliated g-C3N4/MoO2 Composites for High-Performance Photocatalytic Hydrogen Evolution

The difficulty of exposing active sites and easy recombination of photogenerated carriers have always been two critical problems restricting the photocatalytic activity of g-C₃N₄. Herein, a simple (NH₄)₂MoO₄-induced one-step calcination method was successfully introduced to transform bulk g-C₃N₄ into g-C₃N₄/MoO₂ composites with a large specific surface area. During the calcination, with the assistance of NH₃ and water vapor produced by ammonium molybdate, the pyrolytical oxidation and depolymerization of a g-C₃N₄ interlayer were accelerated, finally realizing the exfoliation of the g-C₃N₄. Furthermore, another pyrolytical product of ammonium molybdate was transformed into MoO₂ under an NH₃ atmosphere, which was in situ loaded on the surface of a g-C₃N₄ nanosheet. Additionally, the results of photocatalytic hydrogen evolution under visible light show that the optimal g-C₃N₄/MoO₂ composite has a high specific surface area and much improved performance, which is 4.1 times that of pure bulk g-C₃N₄. Such performance improvement can be attributed to the full exposure of active sites and the formation of abundant heterojunctions. However, with an increasing feed amount of ammonium molybdate, the oxidation degree of g-C₃N₄ was enhanced, which would widen the band gap of g-C₃N₄, leading to a weaker response ability to visible light. The present strategy will provide a new idea for the simple realization of exfoliation and constructing a heterojunction for g-C₃N₄ simultaneously.     

Protective Effect of Flavonoids against Methylglyoxal-Induced Oxidative Stress in PC-12 Neuroblastoma Cells and Its Structure–Activity Relationships

Methylglyoxal-induced oxidative stress and cytotoxicity are the main factors causing neuronal death-related, diabetically induced memory impairment. Antioxidant and anti-apoptotic therapy are potential intervention strategies. In this study, 25 flavonoids with different substructures were assayed for protecting PC-12 cells from methylglyoxal-induced damage. A structure–activity relationship (SAR) analysis indicated that the absence of the double bond at C-2 and C-3, substitutions of the gallate group at the 3 position, the pyrogallol group at the B-ring, and the R configuration of the 3 position enhanced the protection of flavan-3-ols, and a hydroxyl substitution at the 4′ and meta-positions were important for the protection of flavonol. These SARs were further confirmed by molecular docking using the active site of the Keap1–Nrf2 complex as the receptor. The mechanistic study demonstrated that EGCG with the lowest EC₅₀ protected the PC-12 cells from methylglyoxal-induced damage by reducing oxidative stress via the Nrf2/Keap1/HO-1 and Bcl-2/Bax signaling pathways. These results suggested that flavan-3-ols might be a potential dietary supplement for protection against diabetic encephalopathy.     

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.     

Antimicrobial Activity of Smilax china L. Root Extracts against the Acne-Causing Bacterium,Cutibacterium acnes,and Its Active Compounds

The root of Smilax china L. is used in traditional Korean medicine. We found that the Smilax china L. root extract has strong antimicrobial activity against two Cutibacterium acnes strains (KCTC 3314 and KCTC 3320). The aim of this study was to identify the beneficial properties of Smilax china L. extracts for their potential use as active ingredients in cosmetics for the treatment of human skin acne. The high-performance liquid chromatography (HPLC) and liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC/QTOF/MS) methods were used to obtain the profile of secondary metabolites from the ethyl acetate-soluble fraction of the crude extract. Agar diffusion and resazurin-based broth microdilution assays were used to evaluate antimicrobial activity and minimum inhibitory concentrations (MIC), respectively. Among the 24 metabolites, quercetin, resveratrol, and oxyresveratrol were the most potent compounds against Cutibacterium acnes. Minimum inhibitory concentrations of quercetin, resveratrol, and oxyresveratrol were 31.25, 125, and 250 μg/mL, respectively.     

Epigallocatechin Gallate Attenuates Gentamicin-Induced Nephrotoxicity by Suppressing Apoptosis and Ferroptosis

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.     

Snapshots of key intermediates unveiling the growth from silver ions to Ag70 nanoclusters

Nanoclusters (NCs) are considered as initial states of condensed matter, and unveiling their formation mechanism is of great importance for directional synthesis of nanomaterials. Here, we initiate the reaction of Ag(i) ions under weak reducing conditions. The prolonged reaction period provides a unique opportunity for revealing the five stages of the growth mechanism of 20-electron superatomic Ag₇₀ NCs by a time-dependent mass technique, that is, aggregate (I) → reduction (II) → decomposition and recombination (III) → fusion (IV) → surface recombination and motif enrichment (V), which is different from the formation process applicable to the gold clusters. More importantly, the key intermediates, Ag₁₄ without free electrons (0e) in the first (stage I) and Ag₂₄ (4e) in the second (stage II), were crystallized and structurally resolved, and the later transformation rate towards Ag₇₀ was further controlled by modulating solvents for easy identification of more intermediates. In a word, we establish a reasonable path of gradual expansion in size and electrons from Ag(i) ions to medium-sized 20e Ag₇₀. This work provides new insights into the formation and evolution of silver NCs, and unveils the corresponding optical properties along with the process.

The bottom-up synthesis of “medium-sized” Ag₇₀ (20e) was controlled and tracked, and then revealed. The crystallized key intermediates of Ag₁₄ (0e) and Ag₂₄ (4e) present the growth snapshots of silver nanoclusters.     

Surface differences of oxide nanocrystals determined by geometry and exogenously coordinated water molecules

Determining the different surfaces of oxide nanocrystals is key in developing structure–property relations. In many cases, only surface geometry is considered while ignoring the influence of surroundings, such as ubiquitous water on the surface. Here we apply ¹⁷O solid-state NMR spectroscopy to explore the facet differences of morphology-controlled ceria nanocrystals considering both geometry and water adsorption. Tri-coordinated oxygen ions at the 1^st layer of ceria (111), (110), and (100) facets exhibit distinct ¹⁷O NMR shifts at dry surfaces while these ¹⁷O NMR parameters vary in the presence of water, indicating its non-negligible effects on the oxide surface. Thus, the interaction between water and oxide surfaces and its impact on the chemical environment should be considered in future studies, and solid-state NMR spectroscopy is a sensitive approach for obtaining such information. The work provides new insights into elucidating the surface chemistry of oxide nanomaterials.

Both atomic geometry and the influence of surroundings (e.g., exogenously coordinated water) are key issues for determining the chemical environment of oxide surfaces, whereas the latter is usually ignored and should be considered in future studies.     

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.