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Background And Objectives: Breast cancers (BCs) of patients with paraneoplastic neurologic syndromes and anti-Yo antibodies (Yo-PNS) overexpress human epidermal growth factor receptor 2 (HER2) and display genetic alterations and overexpression of the Yo-onconeural antigens. They are infiltrated by an unusual proportion of B cells. We investigated whether these features were also observed in patients with PNS and anti-Ri antibodies (Ri-PNS).

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Perfluorohexane Sulfonic Acid Disrupts the Immune Microenvironment for Spermatogenesis by Damaging the Structure of the Blood-Testis Barrier in Mice.

Adv Sci (Weinh)

January 2025

State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.

Perfluorohexane sulfonic acid (PFHxS) is extensively used in waterproof coatings and fire-fighting foams, and several studies have found it to be a potential health hazard, but there is still unknown about its effects on spermatogenesis. Our results showed that PFHxS-treated mice have significant reproductive toxicity, including a decrease in sperm count and motility, and the levels of sex hormones (P < 0.05).

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KSHV hijacks the antiviral kinase IKKε to initiate lytic replication.

PLoS Pathog

January 2025

Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45.

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Mast cells, immune sentinels that respond to various stimuli in barrier organs, provide defense by expressing pattern recognition receptors, such as Toll-like receptors (TLRs). They may affect inflammatory responses and wound healing. Here, we investigated the effect of TLR2/6-stimulated mast cells on wound healing in keratinocytes.

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Despite substantial advances in the antitumor effects of annonaceous acetogenins (ACGs), the absence of a defined biological action mechanism remains a major barrier to their clinical application. Here, it is found that squamocin effectively depletes both EZH2 and MYC in multiple cancer cell lines, including head and neck squamous cell carcinoma, and gastric and colorectal cancer, demonstrating potent efficacy in suppressing these in vivo tumor models. Through the combination of surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and cellular thermal shift assay (CETSA), heat shock protein 90α (HSP90α) is identified as the direct binding target of squamocin.

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