Toxicological mechanism of cannabidiol (CBD) exposure on zebrafish embryonic development.

Cannabidiol (CBD) is the main component of plant Cannabis (Cannabis sativa), which exhibits strong antioxidant and anti-inflammatory activities. With the legalization of CBD in the United States, it is an inevitable tendency for its global legalization in the future. Therefore, it has become an urgent task to conduct the toxicological evaluation of CBD before clinical application. In this study, the developmental toxicities of CBD on zebrafish embryos were systematically evaluated, and the mechanisms were revealed. The results showed that the phenotype of liver degeneration was observed in 96 hpf zebrafish embryos after 0.1-5 µmol/L CBD exposure, further RT-qPCR experiments indicated that the above result may attributed by the the alterations of FABP10A, GCLC, and GSR. Besides, 1 and 5 µmol/L CBD contributed to the developmental toxicities of heart and eye in zebrafish embryos, characterizing by the decrease in heart rate, the phenotype of pericardial edema, and the reduce of eye area. Compared to other organs, the liver of zebrafish displayed the most sensitive characteristic to CBD exposure, as 0.1 µmol/L CBD already led to the phenotype of liver degeneration. In summary, this paper provided theoretical supports for CBD toxicology research, and laid the foundation for its future clinical application.

Co-Regulating Solvation Structure and Hydrogen Bond Network via Bio-Inspired Additive for Highly Reversible Zinc Anode.

The feasibility of aqueous zinc-ion batteries for large-scale energy storage is hindered by the inherent challenges of Zn anode. Drawing inspiration from cellular mechanisms governing metal ion and nutrient transport, erythritol is introduced, a zincophilic additive, into the ZnSO4 electrolyte. This innovation stabilizes the Zn anode via chelation interactions between polysaccharides and Zn2+. Experimental tests in conjunction with theoretical calculation results verified that the erythritol additive can simultaneously regulate the solvation structure of hydrated Zn2+ and reconstruct the hydrogen bond network within the solution environment. Additionally, erythritol molecules preferentially adsorb onto the Zn anode, forming a dynamic protective layer. These modifications significantly mitigate undesirable side reactions, thus enhancing the Zn2+ transport and deposition behavior. Consequently, there is a notable increase in cumulative capacity, reaching 6000 mA h cm⁻2 at a current density of 5 mA cm-2. Specifically, a high average coulombic efficiency of 99.72% and long cycling stability of >500 cycles are obtained at 2 mA cm-2 and 1 mA h cm-2. Furthermore, full batteries comprised of MnO2 cathode and Zn anode in an erythritol-containing electrolyte deliver superior capacity retention. This work provides a strategy to promote the performance of Zn anodes toward practical applications.

Ice-template-induced highly ionic conductive PVA/PEG-SiO2 gel polymer electrolyte for zinc-ion batteries.

In this work, a SiO2 doped polyvinyl alcohol/polyethylene glycol (PVA/PEG) gel polymer electrolyte (PVA/PEG-SiO2) was constructed via an ice-crystal template for zinc-ion batteries. The SiO2 and the three-dimensional porous skeleton make it have excellent ionic conductivity and mechanical strength, and inhibit the growth of dendrites. The assembled ZIBs exhibit excellent rate performance and cycle stability, making it a promising electrolyte membrane candidate for flexible wearable electronics.

Phase-Modified Strongly Coupled δ/ε-MnO2 Homojunction Cathode for Kinetics-Enhanced Zinc-Ion Batteries.

Rechargeable Zn-MnO2 batteries using mild water electrolytes have garnered significant interest owing to their impressive theoretical energy density and eco-friendly characteristics. However, MnO2 suffers from huge structural changes during the cycles, resulting in very poor stability at high charge-discharge depths. Briefly, the above problems are caused by slow kinetic processes and the dissolution of Mn atoms in the cycles. In this paper, a 2D homojunction electrode material (δ/ε-MnO2) based on δ-MnO2 and ε-MnO2 has been prepared by a two-step electrochemical deposition method. According to the DFT calculations, the charge transfer and bonding between interfaces result in the generation of electronic states near the Fermi surface, giving δ/ε-MnO2 a more continuous distribution of electron states and better conductivity, which is conducive to the rapid insertion/extraction of Zn2+ and H+. Moreover, the strongly coupled Mn-O-Mn interfacial bond can effectively impede dissolution of Mn atoms and thus maintain the structural integrity of δ/ε-MnO2 during the cycles. Accordingly, the δ/ε-MnO2 cathode exhibits high capacity (383 mAh g-1 at 0.1 A g-1), superior rate performance (150 mAh g-1 at 5 A g-1), and excellent cycling stability over 2000 cycles (91.3% at 3 A g-1). Profoundly, this unique homojunction provides a novel paradigm for reasonable selection of different components.

Reductive amination of ω-conotoxin MVIIA: synthesis, determination of modification sites, and self-assembly.

Peptide drugs have disadvantages such as low stability, short half-life and side effects, which limit their widespread use in clinical practice. Therefore, peptide drugs can be modified to improve these disadvantages. Numerous studies have shown that alkyl-modified peptide drugs can self-assemble to prolong the duration of efficacy and/or reduce side effects. However, the commonly used solid-phase synthesis method for alkyl-modified peptides is time-consuming. To overcome this, a simple reductive amination reaction was employed, which can directly graft the alkyl chain to the peptide sequence and effectively avoid stepwise synthesis from C- to N-terminal with amino acids. In this study, ω-conotoxin MVIIA was used as the peptide drug, while myristic aldehyde was used as the alkylating agent. To obtain the maximum productivity of modified peptides, the molar ratio of peptide MVIIA to myristic aldehyde in the reductive amination reaction was optimized. Furthermore, the peptide modification sites in this reaction were confirmed by secondary mass spectrometry analysis. Besides, alkyl-modified peptide MVIIA was able to form micelles by self-assembly and improved stability in serum, which was related to our previous work where myristoylated peptide MVIIA micelles can improve the drug stability. Finally, this study was intended to provide a methodological basis for modifying the alkyl chain of peptide drugs.

UTP23 Functions in Breast Cancer Progression and Predicts Poor Prognosis of Luminal a Breast Cancer.

BACKGROUND: Luminal A breast cancer is the most common molecular subtype of breast cancer. Exploring biomarkers to identify luminal A breast cancer patients at high risk of recurrence and metastasis has important clinical significance. UTP23 is a component of ribosomal small-subunit processome, which is involved in ribosome synthesis and RNA maturation. The role of UTP23 in breast cancer has not been reported. METHODS: TCGA-BRCA data, LinkedOmics, STRING, Metascape and ssGSEA were used to analyze UTP23 expression in breast cancer and evaluate prognosis. Quantitative real-time PCR, western blot and in vitro cell experiment were used to demonstrate the role of UTP23 in breast cancer. RESULTS: UTP23 showed abnormally high expression in multiple cancers and was associated with poor prognosis. UTP23 was associated with T stage, lymph node metastasis, race, histological type, molecular subtypes and survival status in breast cancer. Importantly, UTP23 was significantly associated with poor OS in luminal A or early breast cancer, not in non-luminal A or advanced breast cancer. UTP23 expression was significantly correlated with immune cells infiltration. Enrichment analysis suggested that UTP23 might regulate cell cycle and cell division. Bioinformatics analysis showed DCAF13 might be downstream factor of UTP23. UTP23 expression promoted MCF-7 cells proliferation, migration and invasion possibly through regulating DCAF13 expression. CONCLUSIONS: UTP23 may function in breast cancer progression. The elevated UTP23 may be a potential prognostic biomarker for luminal A or early breast cancer.

Nonivamide inhibits proliferation of human corneal epithelial cells by inducing cell cycle arrest and oxidative stress.

Nonivamide, an agonist of transient receptor potential vanilloid type 1 (TRPV1), is widely used as a riot control agent, police incapacitant spray and pesticide. Although generally considered non-fatal, eye discomfort and even ocular injuries caused by such products are common. Little research has been conducted on the effects of nonivamide on corneal epithelial cells. Cell viability, impedance, flow cytometry, western blotting, and real-time fluorescence analyses were performed to investigate the effects of nonivamide on human corneal epithelial cells (HCE-T cells). We found that nonivamide impaired proliferation at subtoxic doses (100 µM and 200 µM) in HCE-T cells. Next, we described the mechanisms of action of nonivamide. Nonivamide caused cell cycle arrest by increasing p21 and decreasing cyclin D1. TRPV1 was activated by nonivamide, leading to an influx of Ca2+. Enhanced Ca2+ influx partially contributed to oxidative stress. Mitochondrial membrane potential (MMP) also decreased. All combined stress resulted in the inhibition of cell proliferation in HCE-T cells. In summary, nonivamide inhibited the proliferation of HCE-T cells at sub-toxic doses by inducing cell cycle arrest and oxidative stress. Our data demonstrate the corneal toxicity of nonivamide and explain the mechanisms underlying nonivamide-induced corneal injury.

Different Size Formulations of Fluopyram: Preparation, Antifungal Activity, and Accumulation in the Fungal Pathogen Botrytis cinerea.

Nanotechnology is revolutionizing the efficient production and sustainable development of modern agriculture. Understanding the pesticide activity of both nano- and conventional methods is useful for developing new pesticide formulations. In this study, three solid fluopyram formulations with varying particle sizes were developed, and the mechanisms underlying the difference in the antifungal activity among these formulations were investigated. Wet media milling combined with freeze drying was used to prepare fluopyram nanoparticles (FLU-NS) and a micron-sized solid formulation (FLU-MS), and a jet grinding mill was employed to fabricate fluopyram wettable powder (FLU-WP). The mean particle sizes of FLU-NS, FLU-MS, and FLU-WP were 366.8 nm, 2.99 µm, and 10.16 µm, respectively. Notably, FLU-NS displayed a toxicity index against Botrytis cinerea (gray mold) that was approximately double those of FLU-MS and FLU-WP. Similar trends were noticed in the antifungal tests on Alternaria solani. The uptake of FLU-NS by B. cinerea was approximately twice that of FLU-MS and FLU-WP, indicating that fluopyram nanoparticles are more easily taken up by the pathogen (B. cinerea), and display better bioactivity than the larger fluopyram particles. Therefore, the nanosizing of pesticides appears to be a viable strategy to enhance efficiency without increasing the amount of pesticide used.

4-ATP-modified CNTs@NiO-Fe2O3-Ag SERS filter membrane for rapid in-situ detection of furfural in mineral oil.

Evaluating the transformer aging state and detecting multi-aging characteristics in transformer oil with high sensitivity and fast speed has become a key challenge. This study introduces a P-N heterojunction (CNTs@NiO-α-Fe2O3) fabricated through electroless nickel plating and a one-step hydrothermal method. Additionally, silver nanoparticles (AgNPs) with adjustable particle sizes are grown on the surface using a chemical reduction method. To obtain high sensitivity and rapid SERS signal, CNTs@NiO-α-Fe2O3-Ag gel is adsorbed on a disposable needle filter (220 nm) surface, and 4-aminothiophene (4-ATP) is grafted onto the surface of SERS substrate. The minimum detection limit was 0.025 mg/L (EF = 5.22 × 104), and the response time of SERS best signal could be shortened to 3 min. Density functional theory (DFT) calculations reveal that by constructing a P-N heterostructure of NiO-Fe2O3 and assessing the adsorption energies of furfural, acetone, and methanol on the surface of the P-N heterojunction. This SERS strategy has a huge application prospect in the aging diagnosis of oil-paper insulation systems in a transformer.

Self-Assembly Nanostructure of Myristoylated ω-Conotoxin MVIIA Increases the Duration of Efficacy and Reduces Side Effects.

Chronic pain is one of the most prevalent health problems worldwide. An alternative to suppress or alleviate chronic pain is the use of peptide drugs that block N-type Ca2+ channels (Cav2.2), such as ω-conotoxin MVIIA. Nevertheless, the narrow therapeutic window, severe neurological side effects and low stability associated with peptide MVIIA have restricted its widespread use. Fortunately, self-assembly endows the peptide with high stability and multiple functions, which can effectively control its release to prolong its duration of action. Inspired by this, MVIIA was modified with appropriate fatty acid chains to render it amphiphilic and easier to self-assemble. In this paper, an N-terminal myristoylated MVIIA (Myr-MVIIA, medium carbon chain length) was designed and prepared to undergo self-assembly. The present results indicated that Myr-MVIIA can self-assemble into micelles. Self-assembled micelles formed by Myr-MVIIA at higher concentrations than MVIIA can prolong the duration of the analgesic effect and significantly reduce or even eliminate the side effects of tremor and coordinated motor dysfunction in mice.

[Application of self-assembly in polypeptide drugs: a review].

Self-assembly refers to the spontaneous process where basic units such as molecules and nanostructured materials form a stable and compact structure. Peptides can self-assemble by non-covalent driving forces to form various morphologies such as nanofibers, nano layered structures, and micelles. Peptide self-assembly technology has become a hot research topic in recent years due to the advantages of definite amino acid sequences, easy synthesis and design of peptides. It has been shown that the self-assembly design of certain peptide drugs or the use of self-assembled peptide materials as carriers for drug delivery can solve the problems such as short half-life, poor water solubility and poor penetration due to physiological barrier. This review summarizes the formation mechanism of self-assembled peptides, self-assembly morphology, influencing factors, self-assembly design methods and major applications in biomedical field, providing a reference for the efficient use of peptides.

Turn-up Luminescent Sensing of Ultraviolet Radiation by Lanthanide Metal-Organic Frameworks.

Here, we report a series of two-dimensional lanthanide metal-organic frameworks Ln-DBTPA (where DBTPA = 2,5-dibromoterephthalic acid and Ln = Tb (1), Eu (2), or Gd (3)) showing a unique turn-up responsiveness toward ultraviolet (UV) radiation. The luminescence enhancement was derived from the accumulated radicals that can promote the intersystem crossing process. The compound 1 shows an ultralow detection limit of 9.1 × 10-9 J toward UV radiation, representing a new type of luminescent UV detectors.

Simulation Analysis and Experimental Study of Piezoelectric Power Generation Device Based on Shape Memory Alloy Drive.

In order to solve the problem of waste heat collection from energy consumption, a thermal energy generation device combining shape memory alloy and piezoelectric materials has been designed. The shape memory alloy is heated and deformed to drive the drive wheel continuously, and the impact wheel is deformed against the piezoelectric cantilever beam during the rotation of the drive wheel to generate electricity. In this paper, the impact force generated by the impact wheel and the output voltage of the piezoelectric cantilever beam during the rotation process are given. Finally, the experimental test shows that the larger the radius of the drive wheel, the lower the impact force of the wheel and the lower the output voltage of the piezoelectric cantilever beam; the larger the diameter of the shape memory alloy wire, the higher the impact force of the wheel and the higher the output voltage of the piezoelectric cantilever beam; the more teeth of the drive wheel, the higher the impact frequency of the piezoelectric cantilever beam and the higher the output voltage. The maximum output voltage of the thermoelectric converter is 14.2 V, when the drive wheel radius is 13 mm, the shape memory alloy wire diameter is 1 mm and the number of impact wheel teeth is 6. The new structural design provides a new structural model for waste heat recovery and thermal energy generation technology. The new structural design provides a new approach and idea for waste heat recovery and thermal energy generation technology.

Terahertz-Based Method for Accurate Characterization of Early Water Absorption Properties of Epoxy Resins and Rapid Detection of Water Absorption.

Moisture is detrimental to the performance of epoxy resin material for electrical equipment in long-term operation and insulation. Therefore, moisture absorption is one of the critical indicators for insulation of the material. However, some relevant test methods, e.g., the direct weighing method, are time-consuming, and it usually takes months to complete a test. For this, it is necessary to have some modification to save the test time. Firstly, the study analyzes the present prediction method (according to ISO 62:2008). Under the same accuracy, the time required is reduced from 104 days to 71 days. Subsequently, the Langmuir curve-fitting method for water absorption of epoxy resin is analyzed, and the initial values of diffusion coefficient, bonding coefficient, and de-bonding coefficient are determined based on the results of molecular simulation, relevant experiment, and literature review. With the optimized prediction model, it takes only 1.5 days (reduced by 98% as compared with the standard prediction method) to determine the moisture absorbability. Then, the factors influencing the prediction accuracy are discussed. The results have shown that the fluctuation of balance at the initial stage will affect the test precision significantly. Accordingly, this study proposes a quantitative characterization method for initial trace moisture based on the terahertz method, by which the trace moisture in epoxy resin is represented precisely through the established terahertz time-domain spectroscopy system. When this method is used to predict the moisture absorbability, the experimental time may be further shortened by 33% to 1 day. For the whole water absorption cycle curve, the error is less than 5%.

Effect of chelating agents on Reactive Green 19 decolorization through Fe0-activated persulfate oxidation process.

The effect of chelating agents on the decolorization of Reactive Green 19 (RG19) through Fe0 activated persulfate (PS/Fe0) process was investigated. Though other previous studies reported that chelating agent can enhance the degradation of organic contaminant in Fenton-like system, our finding showed that the presence of chelating agents would chelate free Fe2+ and minimize free Fe2+ concentration, which resulted in the retardation of RG19 decolorization. RG19 decolorization decreased to 7%, 21%, and 15% in the presence of sodium citrate, sodium EDTA, and sodium oxalate, compared with control test (without chelating agent, 99%) within 10 min. The degradation efficiencies decreased with increasing chelating agent concentrations because of complex formation with Fe2+. Higher PS concentration, Fe0 dosage, and temperature had an obvious enhancement for RG19 decolorization efficiency. Elucidation of RG19 containing sodium EDTA degradation pathways indicated that PS/Fe0 process could degrade RG19 to carboxylic acids and inorganic salts efficiently. The presence of sodium EDTA had no influence on by-products, and EDTA just played a chelating agent function for chelating Fe ions.