The pathogenesis of bronchopulmonary dysplasia (BPD), involves inflammatory, mechanisms that are not fully characterized. Here we report that overexpression of C-C chemokine receptor 5 (CCR5) and its ligands is associated with BPD development. Lipopolysaccharide-induced BPD rats have increased CCR5 and interleukin-1β (IL-1β) levels, and decreased alveolarization, while CCR5 or IL-1β receptor antagonist treatments decreased inflammation and increased alveolarization. CCR5 enhances macrophage migration, macrophage infiltration in the lungs, IL-1β levels, lysyl oxidase activity, and alveolar development arrest. CCR5 expression on monocytes, and its ligands in blood samples from BPD infants, are elevated. Furthermore, batyl alcohol supplementation reduced CCR5 expression and IL-1β production in lipopolysaccharide-exposed rat lungs. Moreover, receptor-interacting kinase 3 (RIP3) upstream regulator of CCR5-cultured RIP3-/- macrophages exhibited partly blocked lipopolysaccharide-induced CCR5 expression. We conclude that increased CCR5 expression is a key mechanism in BPD development and represents a novel therapeutic target for treatment.Throughout the history of science, physics-based modeling has relied on judiciously approximating observed dynamics as a balance between a few dominant processes. However, this traditional approach is mathematically cumbersome and only applies in asymptotic regimes where there is a strict separation of scales in the physics. Here, we automate and generalize this approach to non-asymptotic regimes by introducing the idea of an equation space, in which different local balances appear as distinct subspace clusters. Unsupervised learning can then automatically identify regions where groups of terms may be neglected. We show that our data-driven balance models successfully delineate dominant balance physics in a much richer class of systems. In particular, this approach uncovers key mechanistic models in turbulence, combustion, nonlinear optics, geophysical fluids, and neuroscience.Memory formation is a hallmark of T cell-mediated immunity, but how differentiation into either short-lived effector cells (SLECs, CD127-KLRG1+) or memory precursors cells (MPECs, CD127+KLRG1-) and subsequent regulation of long-term memory is adjusted is incompletely understood. Here, we show that loss of the nuclear orphan receptor NR2F6 in germ-line Nr2f6-deficient mice enhances antigen-specific CD8+ memory formation up to 70 days after bacterial infection with Listeria monocytogenes (LmOVA) and boosts inflammatory IFN-γ, TNFα, and IL-2 cytokine recall responses. Tacrolimus Adoptive transfer experiments using Nr2f6-/- OT-I T-cells showed that the augmented memory formation is CD8+ T-cell intrinsic. Although the relative difference between the Nr2f6+/+ and Nr2f6-/- OT-I memory compartment declines over time, Nr2f6-deficient OT-I memory T cells mount significantly enhanced IFN-γ responses upon reinfection with increased clonal expansion and improved host antigen-specific CD8+ T-cell responses. Following a secondary adoptive transfer into naïve congenic mice, Nr2f6-deficient OT-I memory T cells are superior in clearing LmOVA infection. Finally, we show that the commitment to enhanced memory within Nr2f6-deficient OT-I T cells is established in the early phases of the antibacterial immune response and is IFN-γ mediated. IFN-γ blocking normalized MPEC formation of Nr2f6-deficient OT-I T cells. Thus, deletion or pharmacological inhibition of NR2F6 in antigen-specific CD8+ T cells may have therapeutic potential for enhancing early IFN-γ production and consequently the functionality of memory CD8+ T cells in vivo.Microgravity is well-known to induce Osteopenia. However, the combined effects of microgravity and radiation that commonly exist in space have not been broadly elucidated. This research investigates the combined effects on MC3T3-E1 cells and rat femurs. In MC3T3-E1 cells, simulated microgravity and X-ray radiation, alone or combination, show decreased cell activity, increased apoptosis rates by flow cytometric analysis, and decreased Runx2 and increased Caspase-3 mRNA and protein expressions. In rat femurs, simulated microgravity and X-ray radiation, alone or combination, show increased bone loss by micro-CT test and Masson staining, decreased serum BALP levels and Runx2 mRNA expressions, and increased serum CTX-1 levels and Caspase-3 mRNA expressions. The strongest effect is observed in the combined group in MC3T3-E1 cells and rat femurs. These findings suggest that the combination of microgravity and radiation exacerbates the effects of either treatment alone on MC3T3-E1 cells and rat femurs.Stochastic asynchronous replication timing (AS-RT) is a phenomenon in which the time of replication of each allele is different, and the identity of the early allele varies between cells. By taking advantage of stable clonal pre-B cell populations derived from C57BL6/Castaneous mice, we have mapped the genome-wide AS-RT loci, independently of genetic differences. These regions are characterized by differential chromatin accessibility, mono-allelic expression and include new gene families involved in specifying cell identity. By combining population level mapping with single cell FISH, our data reveal the existence of a novel regulatory program that coordinates a fixed relationship between AS-RT regions on any given chromosome, with some loci set to replicate in a parallel and others set in the anti-parallel orientation. Our results show that AS-RT is a highly regulated epigenetic mark established during early embryogenesis that may be used for facilitating the programming of mono-allelic choice throughout development.Recent studies have reported a variety of health consequences of climate change. However, the vulnerability of individuals and cities to climate change remains to be evaluated. We project the excess cause-, age-, region-, and education-specific mortality attributable to future high temperatures in 161 Chinese districts/counties using 28 global climate models (GCMs) under two representative concentration pathways (RCPs). To assess the influence of population ageing on the projection of future heat-related mortality, we further project the age-specific effect estimates under five shared socioeconomic pathways (SSPs). Heat-related excess mortality is projected to increase from 1.9% (95% eCI 0.2-3.3%) in the 2010s to 2.4% (0.4-4.1%) in the 2030 s and 5.5% (0.5-9.9%) in the 2090 s under RCP8.5, with corresponding relative changes of 0.5% (0.0-1.2%) and 3.6% (-0.5-7.5%). The projected slopes are steeper in southern, eastern, central and northern China. People with cardiorespiratory diseases, females, the elderly and those with low educational attainment could be more affected.Tacrolimus