Tianjin Pharmaceutical Holdings Ltd.

Dual-atom nanozymes (DAzymes), a novel class of nanozymes featuring dual-metal atomic active centers, mimic the multi-metal synergistic mechanisms of natural enzymes to achieve superior catalytic activity compared to conventional single-atom nanozymes. Their unique dual-atom architecture not only effectively mitigates metal atom aggregation but also significantly enhances substrate adsorption capacity and catalytic efficiency through interatomic electronic coupling and spatial synergy. This structural innovation addresses critical limitations of single-atom nanozymes, including low metal loading and homogeneous active sites. This review systematically summarizes recent advancements in DAzymes: First, we elucidate their design principles and structural advantages, with a focus on precise synthesis strategies (e.g., spatial confinement, coordination stabilization) and atomic-level characterization techniques (e.g., synchrotron radiation-based X-ray absorption spectroscopy, spherical aberration-corrected electron microscopy). By unraveling structure-activity relationships, we clarify the multi-dimensional regulatory mechanisms of dual-atom systems-including coordination environments, electronic coupling, and spatial configurations-on redox enzyme-like activities such as peroxidase and superoxide dismutase mimics. Furthermore, we elaborate on their groundbreaking biomedical applications, including antibacterial and antitumor therapies via reactive oxygen species (ROS) regulation, antioxidant damage repair, and biosensing. This review aims to provide theoretical guidance for the rational design of high-performance DAzymes and to advance their translational applications in precision medicine and intelligent biomaterials.

Gout is a crystal-related arthropathy caused by monosodium urate (MSU) deposition, resulting from purine metabolism disorders and hyperuricemia (HUA). Gout belongs to the traditional medicine category of Bi syndrome. Biqi capsules (BQ) is a traditional Chinese medicine formula used to treat Bi syndrome. The BQ prescription is derived from the ancient prescription of Hua Tuo, a famous physician in the Han Dynasty.

To study the effect and mechanism of BQ in treating acute gouty arthritis (AGA) and HUA.

Analyzing BQ's signaling pathways for gout treatment via network pharmacology. The HUA model was induced orally with adenine and potassium oxonate. The rat AGA model was established by MSU injection. In vitro, MH7A and RAW 246.7 cells were treated with LPS and MSU. Serum uric acid, creatinine, and urea nitrogen levels were evaluated. Kidney and ankle joint pathology was observed via HE staining. Inflammatory signaling pathway proteins, epithelial-mesenchymal transition (EMT) pathway proteins, and uric acid metabolism-related proteins were detected by Western blot.

1780 potential targets for gout treatment were identified, and 1039 target proteins corresponding to BQ's active ingredients were obtained. Pathway enrichment analysis revealed BQ improved gout mainly through inflammatory pathways. Experimental results showed BQ could reduce serum uric acid level and increase uric acid clearance rate by regulating the expression of adenosine deaminase (ADA), and organic anion transporter 1 (OAT1) and glucose transporter 9 (GLUT9) in HUA mice. BQ could improve renal function and injury by inhibiting the NLRP3 pathway in HUA mice' kidneys. Additionally, BQ could alleviate ankle joint swelling and synovial injury, inhibit the TLR4/NLRP3 pathway, and reduce levels of inflammatory factors including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) in AGA rats. The main component of BQ, brucine, could inhibit the activation of NLRP3/NF-κB pathway induced by MSU and reduce the expression level of inflammatory factors (IL-6, IL-1β, and TNF-α) in macrophages. Brucine could inhibit the activation of the EMT pathway and reduce the expression level of inflammatory factors (IL-6, TNF-α) in human fibroblast-like synoviocytes (MH7A cells) induced by MSU.

BQ effectively reduced serum uric acid levels, improved kidney and joint damage, and ameliorated the inflammatory response caused by MSU. Its main component, brucine, effectively improved the inflammatory response and reduced the invasive ability of synoviocytes induced by MSU.

Chronic cerebral hypoperfusion (CCH) is a major risk factor for cognitive decline and degenerative processes. Shunaoxin dropping pill (SNX) has been clinically used to treat cerebrovascular diseases. However, the effect and mechanism of SNX in treating CCH-induced cognitive impairment remain unclear. In this study, CCH was induced in rats using permanent bilateral common carotid artery ligation (2-VO). CCH rats were characterized by impaired spatial learning and memory ability, as well as increased oxidative stress and inflammation in the hippocampus. Additionally, CCH rats had reduced richness and biodiversity of fecal microbiota, which showed a strong correlation with altered serum metabolites. SNX significantly improved the cognitive impairment and restored the dysbiosis of fecal microbiota and serum metabolites in CCH rats. Notably, SNX did not prevent cognitive impairment in antibiotics-treated CCH rats. Our findings suggest that the microbiota-gut-brain axis is a promising therapeutic target for the treatment of CCH-induced cognitive impairment.