Resolving polarization switching pathways of sliding ferroelectricity in trilayer 3R-MoS2
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Metabolic rewiring controlled by HIF-1α tunes IgA-producing B-cell differentiation and intestinal inflammation
Germinal centers where B cells undergo clonal expansion and antibody affinity maturation are hypoxic microenvironments. However, the function of hypoxia-inducible factor (HIF)-1α in immunoglobulin production remains incompletely characterized. Here, we demonstrated that B cells lacking HIF-1α exhibited significantly lower glycolytic metabolism and impaired IgA production. Loss of HIF-1α in B cells affects IgA-producing B-cell differentiation and exacerbates dextran sodium sulfate (DSS)-induced colitis. Conversely, promoting HIF-1α stabilization via a PHD inhibitor roxadustat enhances IgA class switching and alleviates intestinal inflammation. Mechanistically, HIF-1α facilitates IgA class switching through acetyl-coenzyme A (acetyl-CoA) accumulation, which is essential for histone H3K27 acetylation at the Sα region. Consequently, supplementation with acetyl-CoA improved defective IgA production in Hif1a-deficient B cells and limited experimental colitis. Collectively, these findings highlight the critical importance of HIF-1α in IgA class switching and the potential for targeting the HIF-1α-dependent metabolic‒epigenetic axis to treat inflammatory bowel diseases and other inflammatory disorders.
Targeting macrophage polarization by inhibiting Pim2 alleviates inflammatory arthritis via metabolic reprogramming
Macrophage polarization and energy metabolic reprogramming play pivotal roles in the onset and progression of inflammatory arthritis. Moreover, although previous studies have reported that the proviral integration of Moloney virus 2 (Pim2) kinase is involved in various cancers through the mediation of aerobic glycolysis in cancer cells, its role in inflammatory arthritis remains unclear. In this study, we demonstrated that multiple metabolic enzymes are activated upon Pim2 upregulation during M1 macrophage polarization. Specifically, Pim2 directly phosphorylates PGK1-S203, PDHA1-S300, and PFKFB2-S466, thereby promoting glycolytic reprogramming. Pim2 expression was elevated in macrophages from patients with inflammatory arthritis and collagen-induced arthritis (CIA) model mice. Conditional knockout of Pim2 in macrophages or administration of the Pim2 inhibitor HJ-PI01 attenuated arthritis development by inhibiting M1 macrophage polarization. Through molecular docking and dynamic simulation, bexarotene was identified as an inhibitor of Pim2 that inhibits glycolysis and downstream M1 macrophage polarization, thereby mitigating the progression of inflammatory arthritis. For targeted treatment, neutrophil membrane-coated bexarotene (Bex)-loaded PLGA-based nanoparticles (NM@NP-Bex) were developed to slow the progression of inflammatory arthritis by suppressing the polarization of M1 macrophages, and these nanoparticles (NPs) exhibited superior therapeutic effects with fewer side effects. Taken together, the results of our study demonstrated that targeting Pim2 inhibition could effectively alleviate inflammatory arthritis via glycolysis inhibition and reversal of the M1/M2 macrophage imbalance. NM@NPs loaded with bexarotene could represent a promising targeted strategy for the treatment of inflammatory arthritis.
Observationally derived magnetic field strength and 3D components in the HD 142527 disk
The magnetic fields in protoplanetary disks around young stars play an important role in disk evolution and planet formation. Measuring the polarized thermal emission from magnetically aligned grains is a reliable method for tracing magnetic fields. However, it has been difficult to observe magnetic fields from dust polarization in protoplanetary disks because other polarization mechanisms involving grown dust grains become efficient. Here we report multi-wavelength (0.87, 1.3, 2.1 and 2.7 mm) observations of polarized thermal emission in the protoplanetary disk around HD 142527, which shows a lopsided dust distribution. We revealed that smaller dust particles still exhibit magnetic alignment in the southern part of the disk. Furthermore, angular offsets between the observed magnetic field and the disk azimuthal direction were discovered. These offsets can be used to measure the relative strengths of each component of a three-dimensional magnetic field (radial (Br), azimuthal (Bϕ) and vertical (Bz)). Applying this method, we derived the magnetic field around a 200 au radius from the protostar as ∣Br∣:∣Bϕ∣:∣Bz∣ ≈ 0.26:1:0.23 with a strength of ~0.3 mG. Our observations provide some key parameters of magnetic activities, including the plasma beta, which has had to be assumed in theoretical studies. In addition, the radial and vertical angular momentum transfers were found to be comparable, which poses a challenge to theoretical studies of protoplanetary disks.
Full polarization control of photons with evanescent wave coupling in the ultra subwavelength gap of photonic molecules
Polarization of photons plays a key role in quantum optics and light-matter interactions, however, it is difficult to control in nanosystems since the eigenstate of a nanophotonic cavity is usually fixed and linearly polarized. Here, we reveal the polarization control of photons using photonic molecules (PMs) that host supermodes of two coupled nanobeam cavities. In contrast to conventional PMs in a 2D photonic crystal slab, for the two 1D photonic crystal nanobeam cavities the shift and gap between them can be tuned continuously. With an ultra subwavelength gap, the coupling between the two cavities is dominated by the evanescent wave coupling in the surrounding environment, rather not the emission wave coupling for conventional PMs. As such, the non-Hermiticity of the system becomes pronounced, and the supermodes consist of a non-trivial phase difference between bare eigenstates that supports elliptical polarization. We observe that both the polarization degree and polarization angle of the antisymmetric mode strongly depend on the shift and gap between the two cavities, exhibiting polarization states from linear to circular. This full polarization control indicates the great potential of PMs in quantum optical devices and spin-resolved cavity quantum electrodynamics.
Advancements in ultrafast photonics: confluence of nonlinear optics and intelligent strategies
Automatic mode-locking techniques, the integration of intelligent technologies with nonlinear optics offers the promise of on-demand intelligent control, potentially overcoming the inherent limitations of traditional ultrafast pulse generation that have predominantly suffered from the instability and suboptimality of open-loop manual tuning. The advancements in intelligent algorithm-driven automatic mode-locking techniques primarily are explored in this review, which also revisits the fundamental principles of nonlinear optical absorption, and examines the evolution and categorization of conventional mode-locking techniques. The convergence of ultrafast pulse nonlinear interactions with intelligent technologies has intricately expanded the scope of ultrafast photonics, unveiling considerable potential for innovation and catalyzing new waves of research breakthroughs in ultrafast photonics and nonlinear optics characters.
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