The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment.

Regulatory T (Treg) cells play key roles in cancer immunity by suppressing a range of antitumor immune responses and contributing to resistance to programmed death (PD)-1 blockade therapy. Given their critical roles in self-tolerance, local control of immunosuppression by Treg cells, such as in the tumor microenvironment (TME), has been intensively studied. Inhibition of heat shock protein 90 (HSP90), a chaperone with vital roles in regulating proteostasis in cancer cells, impedes cancer progression by interrupting oncogenic signaling pathways and potentially modulating antitumor immunity, but we have very little mechanistic insight into these immune modulatory effects.

Metabolic diversity analysis and genome wide assessment of oxalate accumulation in the leaves of rice () cultivars.

Soluble oxalate accumulates in rice leaves, and it causes mineral deficiency and urinary syndrome in livestock that consume the leaves. In our previous study, we found that the oxalate content was higher in the leaves of Koshihikari ( type cultivar) than in those of Takanari ( type cultivar). This difference was seen even when the two cultivars were grown under a high CO concentration, which inhibits oxalate synthesis via photorespiration, suggesting that the difference resulted from genetic factors rather than environmental factors.

The Challenge Initiative: Lessons on Rapid Scale-Up of Family Planning and Adolescent and Youth Sexual and Reproductive Health Services.

The articles in this supplement showcase The Challenge Initiative’s strategies and insights for sustainably scaling evidence-based family planning and adolescent and youth sexual and reproductive health interventions and emphasize the need for multipronged interventions that address the complex web of factors influencing adolescents’ and youth’s access to contraceptive services.

Improving Contraceptive Service Quality and Accessibility for Adolescents and Youth Through Proprietary Patent Medicine Vendors in Four Nigerian States.

Introduction: In Nigeria, health care services and commodities have increasingly been accessed through private sector entities, including retail pharmacies and drug shops (also called proprietary patent medicine vendors [PPMVs]). However, PPMVs cannot provide long-acting or permanent methods, and concerns have been raised about their quality of services and their need to better comply with government regulations. This article describes how The Challenge Initiative's (TCI) family planning program supported 4 state governments in Nigeria to develop a model to strengthen public-private partnerships between PPMVs and primary health centers (PHCs) to leverage PPMVs to provide adolescents and youth with high-quality contraceptive information, services, and referrals to PHCs.