分类: 物理学 >> 基本粒子与场物理学 提交时间: 2016-05-15
摘要: We propose a realistic flipped SU(5) model derived from a five-dimensional orbifold SO(10) model. The Standard Model (SM) fermion masses and mixings are explained by combining the traditional Froggatt-Nielsen mechanism with the five-dimensional wave function profiles of the SM fermions. Employing tree-level spontaneous R-symmetry breaking in the hidden sector and extra( ordinary) gauge mediation, we obtain realistic supersymmetry breaking soft mass terms with non-vanishing gaugino masses. Including the messenger fields at the intermediate scale and Kaluza-Klein states at the compactification scale, we study gauge coupling unification. We show that the SO(10) unified gauge coupling is very strong and the unification scale can be much higher than the compactification scale. We briefly discuss proton decay as well.
分类: 物理学 >> 基本粒子与场物理学 提交时间: 2016-05-15
摘要: We embed the minimal left-right model SU(2) L x SU(2) R x U(1)B-L into an SU(4) W gauge group, and break the unified group via five-dimensional S-1/(Z(2) x Z2) orbifolding. Leptons are fitted into SU(4)(W) multiplets and located on a symmetry preserving O brane, while quarks are placed onto an O' brane where the symmetry is broken. This approach predicts sin(2) theta(W) = 0.25 for the weak mixing angle at tree level and leads to a rather low weakly ( strongly) coupled unification scale of order 3 x 10(2) TeV (several TeV) with supersymmetry, or as low as several TeV in the non-supersymmetric case. Another symmetry breaking chain with the low-energy gauge group SU(2)(L) x U(1)(3R) x U(1)(B-L) can also give rise to a weak mixing angle sin 2. W = 0.25 at tree level after gauge symmetry breaking by orbifolding. Such theories with low-scale unification have interesting phenomenological consequences.
分类: 药物科学 >> 其他 分类: 医学、药学 >> 药学 提交时间: 2024-05-10
摘要: The progression of simple steatosis to non-alcoholic steatohepatitis (NASH) has emerged as a significant health concern. The activation of FXR shows promise in countering this transition and its detrimental consequences. However, the specific alterations within the NASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse NASH samples, we identified central perturbations within the NASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis, thus shedding light on the complex molecular mechanisms underlying NASH progression. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and publicly available human datasets, we determined that hepatic FXR activation effectively ameliorated NASH by reversing the dysregulated metabolic and inflammatory networks implicated in NASH pathogenesis. This mitigation encompassed resolving fibrosis, reducing immune infiltration, and creating an immune microenvironment that mirrors the positive trends observed in clinical disease progression. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of NASH at a transcriptional level and highlights the complex interplay between FXR activation and both NASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.
分类: 生物学 >> 生物物理学 >> 免疫学 提交时间: 2016-05-11
摘要: Microbiota-mediated effects on the host immune response facilitate colonization resistance against pathogens. However, it is unclear whether and how the host immune response can regulate the microbiota to mediate colonization resistance. ID2, an essential transcriptional regulator for the development of innate lymphoid cell (ILC) progenitors, remains highly expressed in differentiated ILCs with unknown function. Using conditionally deficient mice in which ID2 is deleted from differentiated ILC3s, we observed that these mutant mice exhibited greatly impaired gut colonization resistance against Citrobacter rodentium. Utilizing gnotobiotic hosts, we showed that the ID2-dependent early colonization resistance was mediated by interleukin-22 (IL-22) regulation of the microbiota. In addition to regulating development, ID2 maintained homeostasis of ILC3s and controlled IL-22 production through an aryl hydrocarbon receptor (AhR) and IL-23 receptor pathway. Thus, ILC3s can mediate immune surveillance, which constantly maintains a proper microbiota, to facilitate early colonization resistance through an ID2-dependent regulation of IL-22.
分类: 物理学 分类: 物理学 >> 基本粒子与场物理学 提交时间: 2016-12-28
摘要: We propose the SUSY SU(7) unification of the SU(3)_C* SU(4)_W* U(1)_{B-L} model. Such unification scenario has rich symmetry breaking chains in a five-dimensional orbifold. We study in detail the SUSY SU(7) symmetry breaking into SU(3)_C* SU(4)_W* U(1)_{B