Spatial mapping of human hematopoiesis at single-cell resolution reveals aging-associated topographic remodeling.

The spatial anatomy of hematopoiesis in the bone marrow (BM) has been extensively studied in mice and other preclinical models, but technical challenges have precluded a commensurate exploration in humans. Institutional pathology archives contain thousands of paraffinized BM core biopsy tissue specimens, providing a rich resource for studying the intact human BM topography in a variety of physiologic states. Thus, we developed an end-to-end pipeline involving multiparameter whole tissue staining, in situ imaging at single-cell resolution, and artificial intelligence-based digital whole slide image analysis and then applied it to a cohort of disease-free samples to survey alterations in the hematopoietic topography associated with aging.

TIGIT is a key inhibitory checkpoint receptor in lymphoma.

Background: PD-1 checkpoint blockade therapy (CBT) has greatly benefited patients with select solid tumors and lymphomas but has limited efficacy against diffuse large B-cell lymphoma (DLBCL). Because numerous inhibitory checkpoint receptors have been implicated in driving tumor-specific T cell dysfunction, we hypothesized that combinatorial CBT would enhance the activity of anti-PD-1-based therapy in DLBCL. T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a coinhibitory receptor expressed on dysfunctional tumor-infiltrating T cells, and TIGIT blockade has demonstrated encouraging activity in combination with PD-1 blockade in murine tumor models and in clinical studies.

Pharmacokinetic profile, tissue residue depletion and anthelmintic efficacy of supramolecular fenbendazole.

A supramolecular complex of fenbendazole (SFBZ) with polyvinylpyrrolidone (PVP) was created by mechanochemical processing to increase its anthelmintic efficacy and to reduce the dose of applied drugs. The aim of our research was to study the pharmacokinetic profile and tissue residue depletion of fenbendazole (FBZ) and its metabolites: sulfoxide and sulfone in sheep after SFBZ treatment by high-performance liquid chromatography with tandem mass spectrometric detection and to evaluate its efficacy against gastrointestinal strongylatosis of sheep in field trials. The results revealed that FBZ and its metabolites were detected in blood serum in 2 h after SFBZ administration and in 4-6 h after the administration of the basic - FBZ.

Lack of intrafollicular memory CD4 + T cells is predictive of early clinical failure in newly diagnosed follicular lymphoma.

Despite a characteristic indolent course, a substantial subset of follicular lymphoma (FL) patients has an early relapse with a poor outcome. Cells in the microenvironment may be a key contributor to treatment failure. We used a discovery and validation study design to identify microenvironmental determinants of early failure and then integrated these results into the FLIPI.