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Intralesional injection of CpG ODNs complexed with glatiramer acetate mitigates systemic cytokine toxicities and synergistically advances checkpoint blockade efficacy.
Drug Deliv Transl Res
January 2025
Kinimmune, Inc. St. Louis, 63141, Missouri, USA.
PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.
View Article and Find Full Text PDFFunctionally active modulators targeting the LRRK2 WD40 repeat domain identified by FRASE-bot in CACHE Challenge #1.
Chem Sci
January 2025
University of Missouri - Columbia, Department of Chemistry USA
Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenges emerged as real-life stress tests for computational hit-finding strategies. In CACHE Challenge #1, 23 participants contributed their original workflows to identify small-molecule ligands for the WD40 repeat (WDR) of LRRK2, a promising Parkinson's target. We applied the FRASE-based hit-finding robot (FRASE-bot), a platform for interaction-based screening allowing a drastic reduction of the explorable chemical space and a concurrent detection of putative ligand-binding sites.
View Article and Find Full Text PDFEssential and risk elements in horses affect haematology, serum biochemistry and oxidative status parameters.
Sci Rep
January 2025
Institute of Applied Biology, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76, Nitra, Slovakia.
The abundance of chemical elements in the blood of horses can indicate the physiological balance, health of animal as well as can be taken as an indicator of environmental pollution. The aim of this work was to analyse haematological, biochemical parameters, TOS, FRAP, SOD, Gpx, TAS and their correlations with concentrations of essential and risk elements in blood of horses stabled in two different locations: The National Stud Farm Topoľčianky (n = 11; 11 stallions, consisting of the breeds 6 Lipizzan, 3 Slovak warmblood, 2 Holsteiner) and Experimental Centre at Institute of Animal Husbandry, SUA in Nitra (n = 10; 4 stallions, 5 geldings, 1 mare, 4 stallions, 5 geldings and 1 mare, consisting of the breeds 3 Slovak warmblood, 4 Czech warmblood, 3 Holsteiner). Blood samples were obtained from horses (n = 21) from two localities in the Slovak Republic during May.
View Article and Find Full Text PDFA novel susceptibility locus to () identified by genetic mapping of automated microscopy computer vision data in grapevines.
Plant Dis
January 2025
State Fruit Experiment Station, Missouri State University, Mountain Grove, Missouri, United States;
Powdery mildew, caused by the fungus , is one of the primary causes of grape yield loss across the globe. While numerous resistance loci have been identified in various grapevine species, the genetic determinants of susceptibility to remain largely unexplored. Understanding the genetics of susceptibility for pathogenesis is equally important for developing durable resistance grapevines against this pathogen.
View Article and Find Full Text PDFSulfate Promotes Compact CaCO Formation and Protects Portland Cement from Supercritical CO Attack.
Environ Sci Technol
January 2025
Department of Energy, Environmental & Chemical Engineering, Washington University in St. Louis, St. Louis, Missouri 63130, United States.
Supercritical (sc) CO in geologic carbon sequestration (GCS) can chemically and mechanically deteriorate wellbore cement, raising concerns for long-term operations. In contrast to the conventional view of "sulfate attack" on cement, we found that adding 0.15 M sulfate to the acidic brine can significantly reduce the impact of scCO attack on Portland cement, resulting in stronger cement than that found in a sulfate-free system.
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