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ABSTRACT Existing methods to determine oxyresveratrol, a trans-polyphenolic stilbene, lack selectivity, require large plasma sample volumes or have time-consuming sample preparation and chromatographic isolation. Here an improved highly sensitive liquid chromatography-tandem mass spectrometry method was developed to determine low oxyresveratrol concentrations in rat plasma. The plasma samples were prepared by liquid-liquid extraction with acetoacetate. The s were separated on Venusil hydrophilic interaction chromatography (HILIC) column (2.1 × 50 mm, 5.0 µm) guarded by a HILIC column (4 × 3.0 mm, 5.0 µm). The mobile phase consisted of acetonitrile-water (containing 1 mmol/L ammonium formate) at gradient elution mode with a flow rate of 0.3 mL/min. Resveratrol was used as the internal standard. An electrospray ionization source was applied and operated in the negative multiple reaction monitoring (MRM) mode. Oxyresveratrol and resveratrol were detected on MRM by the transitions from the precursor to the product ion ( m/ z 243.1 → 175.1 and 227.1 → 143.0). The total running time was 5 min and the retention times of oxyresveratrol and resveratrol were 1.97 and 1.82 min. Chromatograms showed no endogenous interfering peaks with blank samples. The linear calibration curve was obtained over the concentration range of 1-500 ng/mL. The injection volume was 10 μL and the limit of quantification was 1 ng/mL. The extraction recovery varied from 78.2 to 84.3% for low, medium and high quality control samples. At the same time, the intra- and inter-day relative standard deviations were <6.78 and <10.02%, respectively, while the corresponding intra- and inter-day accuracy relative error values fell in the range of 3.75-6.67%. The HPLC-MS/MS method was successfully applied to a pharmacokinetics study, in which the experimental rats received a single dose of oxyresveratrol (10 mg/kg, intragastric administration). The pharmacokinetic results are presented. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Pneumonia involves complex immunological and pathological processes leading to pulmonary dysfunction, which can be life-threatening yet lacks effective specialized medications. Natural enzymes can be used as biological agents for the treatment of oxidative stress-related diseases, but limiting to catalytic and environmental stability as well as high cost. Herein, an artificial enzyme, gold nanoclusters (Au NCs) with excellent stability, bioactivity, and renal clearance can be used as the next-generation biological agents for acute lung injury (ALI) and allergic lung disease (ALD). The Au 25 clusters can mimic catalase (CAT) and glutathione peroxidase (GPx), and the K m of Au 24 Er 1 with H 2 O 2 reaches 1.28 mM, about 22 times higher than natural CAT (≈28.8 mM). The clusters inhibit the oxidative stress in the mitochondria and promote the synthesis of adenosine triphosphate (ATP). The molecular mechanism shows that the TLR4/MyD88/NF-κB pathway and M1 macrophage-mediated inflammatory response are suppressed in ALI and the Th1/Th2 imbalance in ovalbumin (OVA)-induced ALD is rescued. Further, the clusters can notably improve lung function in both ALI and ALD models which paves the way for immunomodulation and intervention for lung injury and can be used as a substitute for natural enzymes and potential biopharmaceuticals in the treatment of various types of pneumonia., (© 2024 Wiley‐VCH GmbH.)

Artificial enzymes, especially nanozymes, have attracted wide attention due to their controlled catalytic activity, selectivity, and stability. The rising Cerium-based nanozymes exhibit unique SOD-like activity, and Vanadium-based nanozymes always hold excellent GPx-like activity. However, most inflammatory diseases involve polymerase biocatalytic processes that require multi-enzyme activities. The nanocomposite can fulfill multi-enzymatic activity simultaneously, but large nanoparticles (>10 nm) cannot be excreted rapidly, leading to biosafety challenges. Herein, atomically precise Ce 12 V 6 clusters with a size of 2.19 nm are constructed. The Ce 12 V 6 clusters show excellent glutathione peroxidase (GPx) -like activity with a significantly lower Michaelis-Menten constant (K m , 0.0125 mM versus 0.03 mM of natural counterpart) and good activities mimic superoxide dismutase (SOD) and peroxidase (POD). The Ce 12 V 6 clusters exhibit the ability to scavenge the ROS including O 2 ·- and H 2 O 2 via the cascade reactions of multi-enzymatic activities. Further, the Ce 12 V 6 clusters modulate the proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and consequently rescue the multi-organ failure in the lipopolysaccharide (LPS)-induced sepsis mouse model. With excellent biocompatibility, the Ce 12 V 6 clusters show promise in the treatment of sepsis., (© 2024 Wiley‐VCH GmbH.)

Ultrasmall Au 25 (MPA) 18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg -1 ) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg -1 . Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au 25 (MPA) 18 and Au 24 Zn 1 (MPA) 18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

Recent advances in the synthesis of multifunctional nanomaterials create new opportunities for the rational design of multimodal chemodynamic therapy (CDT) agents. Precisely tailoring the nanostructure and composition of CDT nanoagents for maximum efficacy remains a challenge. Herein, we report the successful synthesis of nanocarbon framework-supported ultrafine Mo 2 C@MoO x nanoclusters (C/Mo 2 C@MoO x ) via a pyrolysis of a Mo/ZIF-8 MOF precursor at 900 °C followed by mild surface oxidation. The developed C/Mo 2 C@MoO x composite demonstrated outstanding performance in photothermal-enhanced tumor-specific tandem catalysis therapy. Specifically, C/Mo 2 C@MoO x efficiently catalyzed the conversion of endogenous H 2 O 2 to cytotoxic 1 O 2 via a Russell mechanism, while also converting the O 2 byproduct to cytotoxic ·O 2 - via an oxidase-like mechanism. A high dispersion of active Mo 5+ sites in the exposed MoO x shell enhanced the reactive oxygen species (ROS)-generating efficiency of C/Mo 2 C@MoO x . Moreover, the Mo 2 C core in the ultrafine Mo 2 C@MoO x nanoclusters allowed NIR-II (1064 nm)-driven photothermal heating, which significantly boosted the CDT process through photothermal effects. Additionally, the CDT process relied on a redox cycle involving Mo 5+ /Mo 6+ species, which could be sustained by glutathione (GSH) consumption. Given these advantages, C/Mo 2 C@MoO x demonstrated remarkable synergistic therapeutic efficacy for cancer treatment (both in vitro and in vivo ) through tumor microenvironment-stimulated generation of multiple ROS and NIR-II photothermal activity.

To explore the contribution of functional coding variants to psoriasis, we analyzed nonsynonymous single-nucleotide variants (SNVs) across the genome by exome sequencing in 781 psoriasis cases and 676 controls and through follow-up validation in 1,326 candidate genes by targeted sequencing in 9,946 psoriasis cases and 9,906 controls from the Chinese population. We discovered two independent missense SNVs in IL23R and GJB2 of low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. Rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association. Single-variant and gene-based association analyses of nonsynonymous SNVs did not identify newly associated genes for psoriasis in the regions subjected to targeted resequencing. This suggests that coding variants in the 1,326 targeted genes contribute only a limited fraction of the overall genetic risk for psoriasis.