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Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune, allergic and inflammatory diseases. Recent evidence indicates that obesity and metabolic disease can also influence the immune system1-7, although the mechanisms and effects on immunotherapy outcomes remain largely unknown. Here, using two models of atopic dermatitis, we show that lean and obese mice mount markedly different immune responses. Obesity converted the classical type 2 T helper (TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 inflammation. We also observed divergent responses to biologic therapies targeting TH2 cytokines, which robustly protected lean mice but exacerbated disease in obese mice. Single-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells from obese mice relative to lean mice. Conditional ablation of PPARγ in T cells revealed that PPARγ is required to focus the in vivo TH response towards a TH2-predominant state and prevent aberrant non-TH2 inflammation. Treatment of obese mice with a small-molecule PPARγ agonist limited development of TH17 pathology and unlocked therapeutic responsiveness to targeted anti-TH2 biologic therapies. These studies reveal the effects of obesity on immunological disease and suggest a precision medicine approach to target the immune dysregulation caused by obesity.

The M13 bacteriophage, a nature-inspired environmentally friendly biomaterial, is used as a perovskite crystal growth template and a grain boundary passivator in perovskite solar cells. The amino groups and carboxyl groups of amino acids on the M13 bacteriophage surface function as Lewis bases, interacting with the perovskite materials. The M13 bacteriophage-added perovskite films show a larger grain size and reduced trap-sites compared with the reference perovskite films. In addition, the existence of the M13 bacteriophage induces light scattering effect, which enhances the light absorption particularly in the long-wavelength region around 825 nm. Both the passivation effect of the M13 bacteriophage coordinating to the perovskite defect sites and the light scattering effect intensify when the M13 virus-added perovskite precursor solution is heated at 90 °C prior to the film formation. Heating the solution denatures the M13 bacteriophage by breaking their inter- and intra-molecular bondings. The denatured M13 bacteriophage-added perovskite solar cells exhibit an efficiency of 20.1% while the reference devices give an efficiency of 17.8%. The great improvement in efficiency comes from all of the three photovoltaic parameters, namely short-circuit current, open-circuit voltage, and fill factor, which correspond to the perovskite grain size, trap-site passivation, and charge transport, respectively.

This study compared the anti-pseudomonal effects between nephrite-impregnated contact lenses (CLs) and conventional and cosmetic CLs. After inoculation with Pseudomonas aeruginosa (P.aeruginosa), we counted the number of bacteria on the CL surface and observed each surface using atomic force microscopy (AFM) and scanning electron microscopy (SEM). To estimate potential harm of nephrite-impregnated CLs, we conducted a safety test using a rabbit model, treated with all CL types. Both conventional and cosmetic CLs (n = 258 ± 2.9 × 104, 368 ± 2.2 × 104) showed significantly decreased number of attached bacteria when compared with those without nephrite impregnation (n = 134 ± 0.8 × 104, 238 ± 2.5 × 104, p < 0.0001, respectively). AFM and SEM revealed that P. aeruginosa was less attached to the nephrite-impregnated CLs than to the conventional and cosmetic CLs, although those with nephrite impregnation had rougher surface. In the safety test, there were no significant differences in the findings between four groups, and the clarity and stability of all corneas were preserved. Nephrite may be used as a next-generation substance to reduce infectious keratitis caused by P. aeruginosa when added to CLs. [ABSTRACT FROM AUTHOR]

Recently, there has been a growing interest in sustainable agricultural methods aimed at reducing energy consumption and mitigating environmental impacts. Among these methods, the integration of rooftop greenhouses into buildings has emerged as a promising solution for urban agriculture, offering various advantages such as energy-saving effects on both the host building and the rooftop greenhouse, improved resource use efficiency, enhanced food security, and reduced environmental impacts. However, there has been limited research on the energy-saving impact of rooftop greenhouses under different conditions and detailed heat transfer analysis based on actual buildings and rooftop greenhouses. The objective of this study is to investigate the energy benefits of building-integrated rooftop greenhouses by evaluating various operating scenarios for both the building and the greenhouse. A container and upper rooftop greenhouse structure were constructed, and building energy simulation models for the target system were developed. Four different operating scenarios for the greenhouse and three different operating scenarios for the building were compared. Depending on the operating scenarios, the total energy loads of the container and RTG were reduced by 18.4% to 24.7% and 0.7% to 6.3%, respectively. The findings of this study can be utilized for the development of optimized greenhouse control strategies. [ABSTRACT FROM AUTHOR]

Sepsis, a condition characterized by life-threatening organ dysfunction due to a dysregulated host response to infection, significantly impacts global health, with mortality rates varying widely across regions. Traditional therapeutic strategies that target hyperinflammation and immunosuppression have largely failed to improve outcomes, underscoring the need for innovative approaches. This review examines the development of therapeutic agents for sepsis, with a focus on clinical trials addressing hyperinflammation and immunosuppression. It highlights the frequent failures of these trials, explores the underlying reasons, and outlines current research efforts aimed at bridging the gap between theoretical advancements and clinical applications. Although personalized medicine and phenotypic categorization present promising directions, this review emphasizes the importance of understanding the complex pathogenesis of sepsis and developing targeted, effective therapies to enhance patient outcomes. By addressing the multifaceted nature of sepsis, future research can pave the way for more precise and individualized treatment strategies, ultimately improving the management and prognosis of sepsis patients. [ABSTRACT FROM AUTHOR]

An abnormally high number of macrophages are present in human brain arteriovenous malformations (bAVM) with or without evidence of prior hemorrhage, causing unresolved inflammation that may enhance abnormal vascular remodeling and exacerbate the bAVM phenotype. The reasons for macrophage accumulation at the bAVM sites are not known. We tested the hypothesis that persistent infiltration and pro-inflammatory differentiation of monocytes in angiogenic tissues increase the macrophage burden in bAVM using two mouse models and human monocytes. Mouse bAVM was induced through deletion of AVM causative genes, Endoglin (Eng) globally or Alk1 focally, plus brain focal angiogenic stimulation. An endothelial cell and vascular smooth muscle cell co-culture system was used to analyze monocyte differentiation in the angiogenic niche. After angiogenic stimulation, the Eng-deleted mice had fewer CD68(+) cells at 2 weeks (P = 0.02), similar numbers at 4 weeks (P = 0.97), and more at 8 weeks (P = 0.01) in the brain angiogenic region compared with wild-type (WT) mice. Alk1-deficient mice also had a trend toward more macrophages/microglia 8 weeks (P = 0.064) after angiogenic stimulation and more RFP(+) bone marrow-derived macrophages than WT mice (P = 0.01). More CD34(+) cells isolated from peripheral blood of patients with ENG or ALK1 gene mutation differentiated into macrophages than those from healthy controls (P