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The mosquito evolves two types of prophenoloxidases with diversified functions.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Tropical Veterinary Medicine and Vector Biology, School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou, Hainan 570228, China.
Insect phenoloxidase, presented as an inactive precursor prophenoloxidase (PPO) in hemolymph, catalyzes melanin formation, which is involved in wound healing, pathogen killing, reversible oxygen collection during insect respiration, and cuticle and eggshell formation. Mosquitoes possess 9 to 16 PPO members across different genera, a number that is more than that found in other dipteran insects. However, the reasons for the redundancy of these PPOs and whether they have distinct biochemical properties and physiological functions remain unclear.
View Article and Find Full Text PDFSeverity of Impaired Oxygenation and Conservative Oxygenation Targets in Mechanically Ventilated Children: A Post Hoc Subgroup Analysis of the Oxy-PICU Trial of Conservative Oxygenation.
Pediatr Crit Care Med
January 2025
Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children NHS Foundation Trust and NIHR Biomedical Research Centre, London, United Kingdom.
Objectives: A conservative oxygenation strategy is recommended in adult and pediatric guidelines for the management of acute respiratory distress syndrome to reduce iatrogenic lung damage. In the recently reported Oxy-PICU trial, targeting peripheral oxygen saturations (Spo2) between 88% and 92% was associated with a shorter duration of organ support and greater survival, compared with Spo2 greater than 94%, in mechanically ventilated children following unplanned admission to PICU. We investigated whether this benefit was greater in those who had severely impaired oxygenation at randomization.
View Article and Find Full Text PDFNovel Therapeutics in Soft Tissue Sarcoma.
Cancers (Basel)
December 2024
Sarcoma Unit, The Royal Marsden Hospital and Institute of Cancer Research, London SW3 6JZ, UK.
There has been noteworthy progress in molecular characterisation and therapeutics in soft tissue sarcomas. Novel agents have gained regulatory approval by the FDA. Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the γ-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours with fusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma.
View Article and Find Full Text PDFImmunogenicity of a recombinant chimera composed of CROP domain segments from the hemorrhagic and lethal toxins of Paeniclostridium sordellii.
Anaerobe
January 2025
Centro de Desenvolvimento Tecnológico, Biotecnologia, Universidade Federal de Pelotas, Rio Grande do Sul, Brazil.
Paeniclostridium sordellii is responsible for severe infections in horses, cattle, and sheep, however, conventional vaccines exhibit limitations in production and immunogenicity. This study assessed the immunogenicity of a recombinant bacterin composed of a chimera (rQTcsHL) that combines segments from the lethal (TcsL) and hemorrhagic (TcsH) toxins in mice and sheep. Both immunized animal groups exhibited elevated levels of IgG, with the mice demonstrating moderate protection (<50 %) against lethal challenges, comparable to that of the conventional vaccine.
View Article and Find Full Text PDFMulti-TACs: Targeting Solid Tumors with Multiple Immune Cell Co-engagers.
ACS Chem Biol
January 2025
Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Multiple immune components in the complex and heterogeneous tumor-immune microenvironment (TIME) work cooperatively to promote or impede cancer immunotherapy. Synergistically co-managing multiple immune cells with single agents for advanced antitumor immunity remains desirable but challenging. This In Focus article introduces a triple orthogonal linker (T-Linker)-based multimodal targeting chimera (Multi-TAC) platform, enabling the single-agent-mediated tumor-targeted co-engagement of multiple immune cell types within TIME for potentiated immunotherapy.
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