PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway.

While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests that PD-L1 has cell-intrinsic functions in immune and cancer cells. In line with these studies, here we show that engagement of PD-L1 via cellular ligands or agonistic antibodies, including those used in the clinic, potently inhibits the type I interferon pathway in cancer cells. Hampered type I interferon responses in PD-L1-expressing cancer cells resulted in enhanced efficacy of oncolytic viruses in vitro and in vivo.

Toward Sustaining Web-Based Senior Center Programming Accessibility With and for Older Adult Immigrants: Community-Based Participatory Research Cross-Sectional Study.

Background: During the COVID-19 pandemic, many community-based organizations serving Asian Americans pivoted to provide web-based care and social services. Asian American community leaders in the United States Pacific Northwest, including Asian Health & Service Center expressed that there are older immigrant adults who experienced backlash from discrimination, fear, and anxiety owing in part to anti-Asian hate and isolation, including from infection precautions. Pivoting supported staying safe from COVID-19 transmission and anti-Asian hate crimes.

Pharmacokinetic properties of a new sustained-release pregabalin tablet in subjects with reduced renal function.

Unlabelled: A new sustained-release (SR) pregabalin tablet, YHD1119, was formulated for once-daily dosing. In the current study, we aimed to evaluate the pharmacokinetics of YHD1119 tablets in patients with reduced renal function. Subjects were grouped by creatinine clearance: > 60 mL/min/1.

An experience on the model-based evaluation of pharmacokinetic drug-drug interaction for a long half-life drug.

Fixed-dose combinations development requires pharmacokinetic drugdrug interaction (DDI) studies between active ingredients. For some drugs, pharmacokinetic properties such as long half-life or delayed distribution, make it difficult to conduct such clinical trials and to estimate the exact magnitude of DDI. In this study, the conventional (non-compartmental analysis and bioequivalence [BE]) and modelbased analyses were compared for their performance to evaluate DDI using amlodipine as an example.

Leaf Carbon Export and Nonstructural Carbohydrates in Relation to Diurnal Water Dynamics in Mature Oak Trees.

Trees typically experience large diurnal depressions in water potential, which may impede carbon export from leaves during the day because the xylem is the source of water for the phloem. As water potential becomes more negative, higher phloem osmotic concentrations are needed to draw water in from the xylem. Generating this high concentration of sugar in the phloem is particularly an issue for the ∼50% of trees that exhibit passive loading.

Killers 2.0: NK cell therapies at the forefront of cancer control.

Natural killer (NK) cells are innate cytotoxic lymphocytes involved in the surveillance and elimination of cancer. As we have learned more and more about the mechanisms NK cells employ to recognize and eliminate tumor cells, and how, in turn, cancer evades NK cell responses, we have gained a clear appreciation that NK cells can be harnessed in cancer immunotherapy. Here, we review the evidence for NK cells' critical role in combating transformed and malignant cells, and how cancer immunotherapies potentiate NK cell responses for therapeutic purposes.