Author: Li, Qianyong ; Zhang, Dezhi ; Guo, Xin ; Wei, Zhengkai ; Qian, Yuxiao ; Huang, Jing ; Jiang, Yuqian ; Jiang, Xi ; Huang, Wenlong ; Huang, Rongsheng ; Yang, Zhengtao ; Wang, Jiaxuan ; He, Kaifeng ; Liu, Quan

Bovine neosporosis, a protozoal disease caused by Neospora caninum ( N. caninum), poses a significant threat to the global cattle industry, resulting in substantial economic losses that are difficult to quantify. The current lack of effective commercial vaccines and specific treatments highlights the urgent need for the development of potent drugs against N. caninum. In this study, we investigate the efficacy of aurintricarboxylic acid (ATA), a derivative of polyaromatic carboxylic acid, against N. caninum both in vitro and in vivo. Cell cytotoxicity is evaluated using CCK-8 kits. N. caninum proliferation within cells is assessed by qPCR analysis. Transmission electron microscopy (TEM) is employed to examine the ultrastructures of N. caninum tachyzoites. The efficacy of ATA against N. caninum infection is validated in a mouse model. Our findings indicate that ATA not only inhibits N. caninum proliferation but also reduces parasite loads within individual cells. Furthermore, ATA (20 and 40 μM) has immunomodulatory effects by downregulating the mRNA expressions of N . caninum-induced cytokines, including tumor necrosis factor-α (TNF-α), interferon (IFN-α, -β, and -γ), and β-defensin 5 (BNBD5). ATA treatment directly targets and eliminates N. caninum by disrupting its ultrastructure. The in vivo study confirms the potential of ATA to increase body weight, decrease parasite loads in the lungs and duodenum, and ameliorate the pathological effects induced by N . caninum infection in mice. In conclusion, this study represents the first evidence of the anti- N. caninum ability of ATA and provides compelling data to support its potential as a candidate for developing anti- N. caninum drugs.

11 Feb 2025·Analytical Chemistry

Construction of a Multiple Cyclic Ligation-Promoted Exponential Recombinase Polymerase Amplification Platform for Sensitive and Simultaneous Monitoring of Cancer Biomarkers Fpg and FEN1

Article

Author: Zhou, Bao-mei ; Liu, Meng ; Zhang, Chun-yang ; Zhao, Ning-ning ; Guo, Fang-yu

Formamidopyrimidine DNA glycosylase (Fpg) and flap endonuclease 1 (FEN1) are essential to sustaining genomic stability and integrity, while the abnormal activities of Fpg and FEN1 may lead to various diseases and cancers. The development of simple methods for simultaneously monitoring Fpg and FEN1 is highly desirable. Herein, we construct a multiple cyclic ligation-promoted exponential recombinase polymerase amplification (RPA) platform for sensitive and simultaneous monitoring of Fpg and FEN1 in cells and clinical tissues. We designed two programmable substrate probes with 8-oxo-7,8-dihydroguanine (8-oxoG) damage sites and 5' flaps that can be identified/cleaved by Fpg and FEN1 to produce nicking sites. The juxtaposition of the cleavage sites is ligated by DNA ligase to form intact double-stranded DNA (dsDNA) templates that can be amplified via RPA to produce abundant dsDNA products labeled with Cy5 and Cy3 fluorophores and biotin, respectively. The resultant dsDNA can be captured by magnetic beads and subsequently disassembled into dispersed Cy3 and Cy5 molecules upon heat treatment, generating significant fluorescence signals. This assay exhibits a limit of detection of 1.12 × 10^-10 U μL^-1 for Fpg and 1.66 × 10^-9 U μL^-1 for FEN1, and it can be used for the analysis of enzymatic kinetic parameters, screening of inhibitors, and simultaneous monitoring of Fpg and FEN1 in a single cell and in clinic tissue samples. Moreover, the proposed strategy can be applied to monitor other DNA repair proteins by merely changing the recognition sites of dsDNA substrate probes, providing a promising platform for clinical diagnosis, biomedical research, and drug discovery.

01 Feb 2025·Advanced Materials

Piezoelectric‐Enhanced Nanocatalysts Trigger Neutrophil N1 Polarization against Bacterial Biofilm by Disrupting Redox Homeostasis

Article

Author: Ge, Min ; Yang, Chuang ; Shi, Jianlin ; Lin, Han ; Mei, Jiawei ; Hu, Tingting ; Zhu, Wanbo

AbstractStrategies of manipulating redox signaling molecules to inhibit or activate immune signals have revolutionized therapeutics involving reactive oxygen species (ROS). However, certain diseases with dual resistance barriers to the attacks by both ROS and immune cells, such as bacterial biofilm infections of medical implants, are difficult to eradicate by a single exogenous oxidative stimulus due to the diversity and complexity of the redox species involved. Here, this work demonstrates that metal‐organic framework (MOF) nanoparticles capable of disrupting the bacterial ROS‐defense system can dismantle bacterial redox resistance and induce potent antimicrobial immune responses in a mouse model of surgical implant infection by simultaneously modulating redox homeostasis and initiating neutrophil N1 polarization in the infection microenvironment. Mechanistically, the piezoelectrically enhanced MOF triggers ROS production by tilting the band structure and acts synergistically with the aurintricarboxylic acid loaded within the MOF, which inhibits the activity of the cystathionine γ‐cleaving enzyme. This leads to biofilm structure disruption and antigen exposure through homeostatic imbalance and synergistic activation of neutrophil N1 polarization signals. Thus, this study provides an alternative but promising strategy for the treatment of antibiotic‐resistant biofilm infections.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypotension	Preclinical	China	Shanghai Jiao Tong University	14 Feb 2019

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