Integrating a Biomineralized Nanocluster for H₂S‑Sensitized ROS Bomb against Breast Cancer

Nanomaterial-assisted chemodynamic therapy (CDT) has received considerable attention in recent years. It outperforms other modalities by its distinctive reactive oxygen species (ROS) generation through a nonexogenous stimulant. However, CDT is limited by the insufficient content of endogenous hydrogen peroxide (H2O2). Herein, a biodegradable MnS@HA-DOX nanocluster (MnS@HA-DOX NC) was constructed by in situ biomineralization from hyaluronic acid, to enlarge the ROS cascade and boost Mn2+-based CDT. The acid-responsive NCs could quickly degrade after internalization into endo/lysosomes, releasing Mn2+, H2S gas, and anticancer drug doxorubicin (DOX). The Fenton-like reaction catalyzed by Mn2+ was amplified by both H2S and DOX, producing a mass of cytotoxic ·OH radicals. Through the combined action of gas therapy (GT), CDT, and chemotherapy, oxidative stress would be synergistically enhanced, inducing irreversible DNA damage and cell cycle arrest, eventually resulting in cancer cell apoptosis

Formula development of sizing for basalt fiber. Part I: Role of film former

Sizing is a multi-element liquid system consisting of film former, coupling agent and other functional additives. In this article, Taguchi method with orthogonal array design was used to get an optimal formula of sizing for basalt fiber, and the role of film former in sizing was studied. The results showed film former promoted the sizing to spread on fiber surface, which increased the interaction area between the fiber and sizing. With the assistance of film former in sizing, a uniform layer was formed on fiber surface, which repaired the surface defect on basalt fiber with reduced stress concentration. The sizing with an appropriate concentration of film former had the capability to increase the tensile strength of a single filament with the best effect of forming a film on fiber surface.</p

Carboxymethylated Dextran-Modified <i>N</i>‑Heterocyclic Carbene Self-Assembled Monolayers on Gold for Use in Surface Plasmon Resonance Biosensing

Surface chemistry is a key enabler for various biosensing applications. Biosensors based on surface plasmon resonance routinely employ thiol-based chemistry for the linker layer between gold-coated support surfaces and functional biosensor surfaces. However, there is a growing awareness that such sensor surfaces are prone to oxidation/degradation problems in the presence of oxygen, and previous efforts to improve the stability have shown limited advancements. As an alternative, recent studies employing <i>N</i>-heterocyclic carbene (NHC) self-assembled monolayers (SAMs) deposited on gold have shown significant promise in this area. Here, we describe a sensor surface employing an NHC SAM to couple a modified carboxymethylated dextran onto a gold surface. Such a dextran matrix is also used for affinity chromatography, and it is the most commonly employed matrix for commercial biosensor surfaces today. The performance reliability of the dextran-modified NHC chip to act as an alternative biosensing platform is compared with that of a thiol-based commercial chip in the proof-of-concept tests. The resultant NHC sensor surface shows a higher thermal stability compared to thiol analogues. Moreover, the plasma protein/drug and antibody/antigen interactions were validated on the NHC-based dextran chip and showed similar performance as compared to the thiol-based commercial chip. Ultimately, this study shows the strong potential applicability of chemical modifications to gold surfaces using NHC ligands for biosensing applications

Orientin Promotes Antioxidant Capacity, Mitochondrial Biogenesis, and Fiber Transformation in Skeletal Muscles through the AMPK Pathway

The sleep-breathing condition obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, which can exacerbate oxidative stress and free radical generation, thereby detrimentally impacting both motor and sensory nerve function and inducing muscular damage. OSA development is promoted by increasing proportions of fast-twitch muscle fibers in the genioglossus. Orientin, a water-soluble dietary C-glycosyl flavonoid with antioxidant properties, increased the expression of slow myosin heavy chain (MyHC) and signaling factors associated with AMP-activated protein kinase (AMPK) activation both in vivo and in vitro. Inhibiting AMPK signaling diminished the effects of orientin on slow MyHC, fast MyHC, and Sirt1 expression. Overall, orientin enhanced type I muscle fibers in the genioglossus, enhanced antioxidant capacity, increased mitochondrial biogenesis through AMPK signaling, and ultimately improved fatigue resistance in C2C12 myotubes and mouse genioglossus. These findings suggest that orientin may contribute to upper airway stability in patients with OSA, potentially preventing airway collapse

Itu generates DNA damage.

<p>A. Representative pictures of the karyotypes of HCT116 in the absence or presence of Itu. B. Detection of Itu derivative in genomic DNA in replicating cells. HPLC-MS analysis of Itu metabolites in the genomic DNA of Itu-treated cells. Genomic DNA was isolated from Itu-treated cells and digested into nucleosides, which were analyzed with HPLC (left panel), which was directly linked to mass spectrometer. MS analysis of the molecule with the size of dTU was shown at the right panel. C. The intracellular dATP and dGTP pools were not affected by Itu treatment. A and A1 are derivatives of dATP and G, G1 and G2 are derivatives of dGTP.</p

Itu induced cell death in p53-dependent and independent manners.

<p>A. HCT116 cells (p53+/+ and p53−/−) were treated with various concentrations of Itu for 48 hours and the number of cells were measured by Wst-1 assay. *p<0.05 when p53−/− cells were compared to p53+/+ cells. B. Atm+/+ and Atm−/− MEFs were treated with various concentrations of Itu for 48 hours and the number of cells were measured by Wst-1 assay. *p<0.05 when Atm−/− cells were compared to Atm+/+ cells. C. Wild type and p53−/− HCT116 cells were treated with Itu for 24 hours and the number of cells was measured by Wst-1 assay. Itu did not induce cell death when cells were cultured in 0.1% serum or confluent in wild type HCT116 cells. *p<0.05 when compared to untreated cells.</p

Itu showed anti-tumor activity.

<p>A. High dose of Itu resulted in tumor shrinkage in nude mice. p53+/+ and p53−/− HCT116 was injected into nude mice. Two weeks later, Itu was ip injected every day and the tumor size was measured. (n = 5) The tumor volumes at various days were normalized to that of day 1, which was set at 100%. *, p<0.05 when comparing Itu treatment with solvent injection. B. Low dose of Itu resulted in tumor shrinkage in nude mice. p53+/+ and p53−/− HCT116 was injected into nude mice. Two weeks later, Itu was ip injected every day and the tumor size was measured. (n = 5) The tumor volumes at various days were normalized to that of day 1, which was set at 100%. *, p<0.05 when comparing Itu treatment with solvent injection.</p

Itu treatment activates Atm and Chk2 and leads to p53 S15 phosphorylation.

<p>A. HCT116 cells were treated with 1 µM Itu for different periods of time and activation of Atm, Chk2, and p53 was assessed with western blot using specific phospho-antibodies. B. MEFs cells were treated with 1 µM Itu for different periods of time and activation of Atm, Chk2, and p53 was assessed with western blot using specific phospho-antibodies.</p

Itu treatment results in an increase in S and G2/M phase cells.

<p>A. HCT116 (p53+/+ and p53−/−) were treated with different concentrations of Itu for 24 hrs. The cells were fixed, stained with PI, and analyzed with FACS. Percentage of cells in different phases was shown. B. Representative cell cycle profiles of p53+/+ and p53−/− HCT116 in the presence of 2.5 µM of Itu for 24 hrs. C. HCT116 (p53+/+ and p53−/−) were treated with different concentrations of Itu for 48 hrs. The cells were fixed, stained with PI, and analyzed with FACS. Percentage of cells in different phases was shown. D. Representative cell cycle profiles of p53+/+ and p53−/− HCT116 in the presence of 1.0 µM of Itu for 48 hrs.</p

Identification of Itu as a p53 activator.

<p>A. The structures of Itu, adenosine, and Fludarabine. B. Western blot shows that Itu up-regulates p53 in MEFs in a dose-dependent manner. Cells were treated with various concentrations of Itu for 8 hrs and the levels of p53 were analyzed by western blot. C. Western blot shows that Itu up-regulates p53 in HCT116 cells in a dose-dependent manner. Cells were treated with various concentrations of Itu for 8 hrs and the levels of p53 were analyzed by western blot. A longer-exposed film was also shown to indicate that p53 was expressed in HCT116 cells at the basal level. D. Knock-down of ADK did not activate p53. Left panel: the decrease of ADK mRNA in the presence of ADK siRNA; Right panel: the protein levels of p53 in the presence of control and ADK siRNA in HCT116 cells.</p