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Summary: Given the high and growing prevalence of obesity among adults in the United States, obesity treatment and prevention are important topics in biomedical and public health research. Although researchers recognize the significance of this problem, much remains unknown about safe and effective prevention and treatment of obesity in adults. In response to the worsening obesity epidemic and the many unknowns regarding the disease, a group of key scientific and program staff members of the National Institutes of Health (NIH) and other federal and non‐government agencies gathered virtually in September 2021 to discuss the current state of obesity research, research gaps, and opportunities for future research in adult obesity prevention and treatment. The current article synthesizes presentations given by attendees and shares their organizations' current initiatives and identified gaps and opportunities. By integrating the information discussed in the meeting and current initiatives, we identify potential targets and overlapping priorities for future research, including health equity and disparities in obesity, the heterogeneity of obesity, and the use of technological and innovative approaches in interventions. [ABSTRACT FROM AUTHOR]

Although many prior efforts found that road networks significantly affect landscape fragmentation, the spatially heterogeneous effects of road networks on urban ecoenvironments remain poorly understood. A new remote-sensing-based ecological index (RSEI) is proposed to calculate the ecoenvironmental quality, and a local model (geographically weighted regression, GWR) was applied to explore the spatial variations in the relationship between kernel density of roads (KDR) and ecoenvironmental quality and understand the coupling mechanism of road networks and ecoenvironments. The average effect of KDR on the variables of normalized difference vegetation index (NDVI), land surface moisture (LSM), and RSEI was negative, while it was positively associated with the soil index (SI), normalized differential build-up and bare soil index (NDBSI), index-based built-up index (IBI), and land surface temperature (LST). This study shows that rivers and the landscape pattern along rivers exacerbate the impact of road networks on urban ecoenvironments. Moreover, spatial variation in the relationship between road network and ecoenvironment is mainly controlled by the relationship of the road network with vegetation and bare soil. This research can help in better understanding the diversified relationships between road networks and ecoenvironments and offers guidance for urban planners to avoid or mitigate the negative impacts of roads on urban ecoenvironments. [ABSTRACT FROM AUTHOR]

The invariant natural killer T cells (iNKT) cells have emerged as an important regulator of immunity to infection, cancer, and autoimmune diseases. They can be activated by glycolipids that bind to CD1d. The most effective iNKT ligand reported to date is alpha-galactosylceramide (alpha-GalCer), which stimulates iNKT cells to secrete both Th-1 and Th-2 cytokines. Indiscriminate induction of both types of cytokines could limit the therapeutic potential of iNKT ligands, as Th-1 and Th-2 cytokines play different roles under physiological and pathological conditions. Therefore, a ligand with a biased cytokine-release profile would be highly desirable. Here, we report the synthesis and biological activity of alpha-lactosylceramide (alpha-LacCer). Our data demonstrate that alpha-LacCer can stimulate iNKT cells to proliferate and release cytokines, both in vitro and in vivo. Interestingly, while alpha-LacCer is approximately 1000-times less efficient than alpha-GalCer in inducing Th-1 cytokines, it is as potent as alpha-GalCer in the induction of Th-2 cytokines; therefore, alpha-LacCer is a novel compound that induces a biased cytokine release. Processing by beta-glycosidase was critical for alpha-LacCer activity. Moreover, in vivo experiments suggest that alpha-LacCer is at least as potent as alpha-GalCer in the treatment of tumors and experimental autoimmune encephalomyelitis.

Costimulatory molecules play critical roles in the induction and effector function of T cells. More recent studies reveal that costimulatory molecules enhance clonal deletion of autoreactive T cells as well as generation and homeostasis of the CD25(+)CD4(+) regulatory T cells. However, it is unclear whether the costimulatory molecules play any role in the proliferation and differentiation of T cells before they acquire MHC-restricted TCR. In this study, we report that targeted mutations of B7-1 and B7-2 substantially reduce the proliferation and survival of CD4(-)CD8(-) (double-negative (DN)) T cells in the thymus. Perhaps as a result of reduced proliferation, the accumulation of RAG-2 protein in the DN thymocytes is increased in B7-deficient mice, which may explain the increased expression of TCR gene and accelerated transition of CD25(+)CD44(-) (DN3) to CD25(-)CD44(-) (DN4) stage. Qualitatively similar, but quantitatively less striking effects were observed in mice with a targeted mutation of CD28, but not CTLA4. Taken together, our results demonstrate that the development of DN in the thymus is subject to modulation by the B7-CD28 costimulatory pathway.