A MXene-derived redox homeostasis regulator perturbs the Nrf2 antioxidant program for reinforced sonodynamic therapy

Ultrasound (US)-mediated sonodynamic therapy (SDT) has emerged as a spatiotemporally controllable therapeutic modality in combating cancer because of its high tissue-penetration depth and minimal invasiveness. However, the elevated nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant program in cancer cells can serve as a chief reactive oxygen species (ROS) detoxification system to alleviate oxidative injury and promote tumorigenesis, and thus greatly antagonize the therapeutic efficacy of ROS-mediated anticancer therapies. Herein, we report that vanadium carbide MXene-derived carbon dots (PMQDs) can act as high-efficacy sonosensitizers to efficiently generate ROS upon US irradiation and simultaneously hinder the Nrf2 antioxidant program for enhanced sonodynamic therapy of cancer. These PMQDs show superior US-triggered ROS generating ability because of their efficient migration/separation of electron–hole pairs and narrow bandgap. Importantly, these PMQDs can serve as efficient redox homeostasis regulators to perturb the Nrf2 antioxidant mechanism and thus reduce its effects on ROS neutralization for enhanced SDT efficacy. Overall, the present study will not only provide a new paradigm to augment SDT by perturbing the Nrf2 antioxidant program, but also give valuable insights into developing high-efficacy MXene-derived nanoagents for cancer therapy.

A redox homeostasis regulator has been developed as a high-efficacy sonosensitizer to efficiently generate reactive oxygen species upon ultrasound irradiation and simultaneously hinder the Nrf2 antioxidant program for enhanced sonodynamic therapy.     

Toxic Effect of Fullerene and Its Derivatives upon the Transmembrane β2-Adrenergic Receptors

Numerous experiments have revealed that fullerene (C₆₀) and its derivatives can bind to proteins and affect their biological functions. In this study, we explored the interaction between fullerine and the β₂-adrenergic receptor (β₂AR). The MD simulation results show that fullerene binds with the extracellular loop 2 (ECL2) and intracellular loop 2 (ICL2) of β₂AR through hydrophobic interactions and π–π stacking interactions. In the C₆₀_in1 trajectory, due to the π–π stacking interactions of fullerene molecules with PHE and PRO residues on ICL2, ICL2 completely flipped towards the fullerene direction and the fullerene moved slowly into the lipid membrane. When five fullerene molecules were placed on the extracellular side, they preferred to stack into a stable fullerene cluster (a deformed tetrahedral aggregate), and had almost no effect on the structure of β₂AR. The hydroxyl groups of fullerene derivatives (C₆₀(OH)_X, X represents the number of hydroxyl groups, X = 4, 8) can form strong hydrogen bonds with the ECL2, helix6, and helix7 of β₂AR. The hydroxyl groups firmly grasp the β₂AR receptor like several claws, blocking the binding entry of ligands. The simulation results show that fullerene and fullerene derivatives may have a significant effect on the local structure of β₂AR, especially the distortion of helix4, but bring about no great changes within the overall structure. It was found that C₆₀ did not compete with ligands for binding sites, but blocked the ligands’ entry into the pocket channel. All the above observations suggest that fullerene and its derivatives exhibit certain cytotoxicity.     

Sargassum fusiforme Polysaccharide-Based Hydrogel Microspheres Enhance Crystal Violet Dye Adsorption Properties

In this study, a polysaccharide-based hydrogel microsphere (SFP/SA) was prepared using S. fusiforme polysaccharide (SFP) and sodium alginate (SA). Fourier transform infrared spectroscopy (FT-IR) demonstrated that SFP was effectively loaded onto the hydrogel microsphere. Texture profile analysis (TPA) and differential scanning calorimetry (DSC) showed that, with the increase of SFP concentration, the hardness of SFP/SA decreased, while the springiness and cohesiveness of SFP/SA increased, and the thermal stability of SFP/SA improved. The equilibrium adsorption capacity of SFP/SA increased from 8.20 mg/g (without SFP) to 67.95 mg/g (SFP accounted 80%) without swelling, and from 35.05 mg/g (without SFP) to 81.98 mg/g (SFP accounted 80%) after 24 h swelling. The adsorption of crystal violet (CV) dye by SFP/SA followed pseudo-first order and pseudo-second order kinetics (both with R² > 0.99). The diffusion of intraparticle in CV dye was not the only influencing factor. Moreover, the adsorption of CV dye for SFP/SA (SFP accounted 60%) fit the Langmuir and Temkin isotherm models. SFP/SA exhibited good regenerative adsorption capacity. Its adsorption rate remained at > 97% at the 10th consecutive cycle while SFP accounted for 80%. The results showed that the addition of Sargassum fusiforme polysaccharide could increase the springiness, cohesiveness and thermal stability of the hydrogel microsphere, as well as improve the adsorption capacity of crystal violet dye.     

Correlation between Irradiation Treatment and Metabolite Changes in Bactrocera dorsalis (Diptera: Tephritidae) Larvae Using Solid-Phase Microextraction (SPME) Coupled with Gas Chromatography-Mass Spectrometry (GC-MS)

The metabolites produced by the larvae of Bactrocera dorsalis (Diptera: Tephritidae) exposed to different doses of irradiation were analyzed using solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS), and a metabonomic analysis method of irradiated insects based on GC-MS was established. The analysis revealed 67 peaks, of which 23 peaks were identified. The metabolites produced by larvae treated with different irradiation doses were compared by multivariate statistical analysis, and eight differential metabolites were selected. Irradiation seriously influenced the fatty acid metabolic pathway in larvae. Using the R platform combined with the method of multivariate statistical analysis, changes to metabolite production under four irradiation doses given to B. dorsalis larvae were described. Differential metabolites of B. dorsalis larvae carried chemical signatures that indicated irradiation dose, and this method is expected to provide a reference for the detection of irradiated insects.     

Single-Stage Extraction and Separation of Co2+ from Ni2+ Using Ionic Liquid of [C4H9NH3][Cyanex 272]

The purpose of this study was to optimize the extraction conditions for separating Co²⁺ from Ni²⁺ using N-butylamine phosphinate ionic liquid of [C₄H₉NH₃][Cyanex 272]. A Box–Behnken design of response surface methodology was used to analyze the effects of the initial pH, extraction time, and extraction temperature on the separation factor of Co²⁺ from sulfuric acid solution containing Ni²⁺. The concentrations of Co²⁺ and Ni²⁺ in an aqueous solution were determined using inductively coupled plasma-optical emission spectrometry. The optimized extraction conditions were as follows: an initial pH of 3.7, an extraction time of 55.8 min, and an extraction temperature of 330.4 K. The separation factor of Co²⁺ from Ni²⁺ under optimized extraction conditions was 66.1, which was very close to the predicted value of 67.2, and the error was 1.7%. The equation for single-stage extraction with high reliability can be used for optimizing the multi-stage extraction process of Co²⁺ from Ni²⁺. The stoichiometry of chemical reaction for ion-exchange extraction was also investigated using the slope method.     

Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis

Myocardial infarction (MI) is the leading cause of premature death among adults. Cardiomyocyte death and dysfunction of the remaining viable cardiomyocytes are the main pathological factors of heart failure after MI. Mitochondrial complexes are emerging as critical mediators for the regulation of cardiomyocyte function. However, the precise roles of mitochondrial complex subunits in heart failure after MI remain unclear. Here, we show that NADH:ubiquinone oxidoreductase core subunit S1 (Ndufs1) expression is decreased in the hearts of heart failure patients and mice with myocardial infarction. Furthermore, we found that cardiac-specific Ndufs1 overexpression alleviates cardiac dysfunction and myocardial fibrosis in the healing phase of MI. Our results demonstrated that Ndufs1 overexpression alleviates MI/hypoxia-induced ROS production and ROS-related apoptosis. Moreover, upregulation of Ndufs1 expression improved the reduced activity of complex I and impaired mitochondrial respiratory function caused by MI/hypoxia. Given that mitochondrial function and cardiomyocyte apoptosis are closely related to heart failure after MI, the results of this study suggest that targeting Ndufs1 may be a potential therapeutic strategy to improve cardiac function in patients with heart failure.Subject terms: Heart failure, Myocardial infarction, Myocardial infarction     

Entropy of higher-dimensional charged Gauss–Bonnet black hole in de Sitter space

The fundamental equation of the thermodynamic system gives the relation between the internal energy, entropy and volume of two adjacent equilibrium states. Taking a higher-dimensional charged Gauss–Bonnet black hole in de Sitter space as a thermodynamic system, the state parameters have to meet the fundamental equation of thermodynamics. We introduce the effective thermodynamic quantities to describe the black hole in de Sitter space. Considering that in the lukewarm case the temperature of the black hole horizon is equal to that of the cosmological horizon, we conjecture that the effective temperature has the same value. In this way, we can obtain the entropy formula of spacetime by solving the differential equation. We find that the total entropy contains an extra term besides the sum of the entropies of the two horizons. The corrected term of the entropy is a function of the ratio of the black hole horizon radius to the cosmological horizon radius, and is independent of the charge of the spacetime.     

Theoretical study of the reaction 2,5-dimethylfuran + H → products

The reaction of 2,5-dimethylfuran (DMF) with H-atoms was studied using a potential energy surface calculated at the CBS-QB3 level of theory and master equation/RRKM modeling. Hydrogen abstraction by H-atom and hydrogen additions on DMF were considered. As the decomposition pathways of the initial adducts were unknown, a large number of decomposition routes was explored for these adducts. An important number of interconnected product channels were found and preliminary master equation calculations were performed to select the crucial wells and exit channels. The ipso substitution DMF + H → methylfuran (MF) + CH₃ and the formation of 1,3-butadiene and acetyl radical (CH₃CO) were found to be the major product channels in the addition process. The total calculated rate constant was found in good agreement with experimental data and is nearly pressure-independent. A small sensitivity to pressure was found for the computed branching ratios. At 1 bar, the yields of the two product channels of the addition process are maximal at 1100 K with computed branching ratios of 39% (MF + CH₃) and 27% (1,3-C₄H₆ + CH₃CO). Above 1300 K, hydrogen abstraction by H-atom becomes dominant and reaches a branching ratio of 56% at 2000 K.     

Real-time phase-resolved functional optical coherence tomography by use of optical Hilbert transformation

We have developed a novel real-time phase-resolved functional optical coherence tomography system that uses optical Hilbert transformation. When we use a resonant scanner in the reference arm of the interferometer, with an axial scanning speed of 4 kHz, the frame rate of both structural and Doppler blood-flow imaging with a size of 100 by 100 pixels is 10 Hz. The system has high sensitivity and a larger dynamic range for measuring the Doppler frequency shift that is due to moving red blood cells. Real-time images of in vivo blood flow in human skin obtained with this interferometer are presented.