Manipulation of neuronal activity in behaving experimental animals is crucial for elucidating neuronal networks underlying brain function. Both optogenetic¹ and chemogenetic² approaches continue to be highly valuable for identifying the contributions of genetically defined neuron populations to circuit and behavioral outputs. Both methods offer distinct advantages, with optogenetic control of the activity of subsets of neurons at precise temporal scales and slower chemogenetic control of the activity of entire populations of neurons across the brain. Previous work has developed a toolset that integrates opto- and chemogenetic approaches by fusing a light-emitting luciferase to an optogenetic light-responsive element, resulting in a luminescent opsin, or luminopsin (LMO)^{3 – 5} [Fig. 1(a)]. Bioluminescence produced by oxidation of a diffusible luciferin substrate by the luciferase enzyme activates a tethered, nearby opsin. Depending on the biophysical properties of the opsin, the light generated by the luciferase can either excite or inhibit target neurons expressing the LMO. Such integration of opto- and chemogenetic approaches allows manipulation of neural activity over a range of spatial and temporal scales of the same neurons in the same experimental animal. For example, the contribution to behavioral components of the activation of an entire population of neurons can be compared to those of a subset of the same neurons, activating the opsin chemogenetically through bioluminescence or optogenetically through light fibers.⁶

Interleukin-11 (IL-11) is a cytokine involved in inflammatory processes and a previous study showed that blocking or knocking down IL11 in mice prolongs a healthy lifespan. This study investigates DNA methylation (DNAm) changes in the IL11 and IL-11 receptor subunit alpha (IL-11RA) gene across ages to explore age-related epigenetic patterns that may influence IL-11 production and pathway sensitivity. A genome-wide DNAm database focusing on Cytosine-phosphate-Guanine (CpG) sites within the IL11 and IL11RA was analyzed. Hierarchical regression analyses examined the relationship between DNAm, age, and the squared age term for quadratic associations. The database comprised 10,297 samples (5156 males and 5141 females) with a mean age of 53.9 years (SD = 14.1 years). The majority of IL11 and IL11RA CpG sites in the TSS1500 and 3′UTR regions exhibited significant inverse U-shaped associations with age. DNAm levels were low during youth, increased in middle age (40s-50s), and decreased again in older age. The observed inverse U-shaped DNAm patterns in the IL11 and IL11RA suggest non-linear age-related regulation that may influence IL-11 expression and sensitivity. These findings indicate that IL-11 may have different roles across life stages and suggest that therapeutic interventions targeting IL-11 should consider age-specific effects.

Epigenetic studies of psychiatric and neurological disorders rely largely on peripheral tissues, yet where peripheral DNA methylation (DNAm) reflects the brain remains unclear. We generated a paired brain and peripheral DNAm dataset from 148 donors in three cohorts and combined it with five published cohorts for consensus brain–peripheral correlations. By cross-validation across cohorts, we defined brain epigenome shared sites (BrESS), more than 100,000 CpGs per tissue at which peripheral DNAm reproducibly predicts brain DNAm. BrESS lay at promoters active in both brain and periphery and in housekeeping genes, and most were not explained by genetic effects. BrESS did not contribute to the heritability of seven disorders, and CpGs from epigenome-wide association studies of these disorders were not enriched at BrESS. Peripheral DNAm reflects the brain mainly in a regulatory compartment shared across tissues, outside which disease signals largely lie, and BrESS separate peripheral signals attributable to the brain from others.

Although the gap between research and implementation is frequently emphasized, examples from United States (US) cancer care demonstrate that health services research can be translated into meaningful policy and practice. This Health Policy piece examines four US oncology cases spanning state legislation, federal payment reform, patient advocacy, and clinical measurement, which are the Delaware Cancer Consortium, the Oncology Care Model and Enhancing Oncology Model, COLONTOWN, and the COST financial toxicity measure. We assess how evidence moved into routine care through top-down policy and bottom-up community pathways. Across these cases, implementation has depended on sustained political and financial commitment, durable delivery mechanisms, data-driven evaluation, and collaboration among clinicians, policymakers, researchers, and patient advocates. These cases also illustrate limitations, which include administrative burden, financial toxicity, and uneven evidence of cost, quality, and equity outcomes. Some lessons of these cases include protected funding, navigation infrastructure, incentives centered around equity, patient and community engagement, and measurement that is linked to actionable interventions. Together, these examples show how health services research can influence cancer care when evidence is paired with appropriate policy mechanisms, financing structures, and implementation capacity.