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Polarization of immune cells is commonly observed in host responses associated with microbial immunity, inflammation, tumorigenesis, and tissue repair and fibrosis. In this process, immune cells adopt distinct programs and perform specialized functions in response to specific signals. Accumulating evidence indicates that inhalation of micro- and nano-sized particulates activates barrier immune programs in the lung in a time- and context-dependent manner, including type 1 and type 2 inflammation, and T helper (Th) 17 cell, regulatory T cell (Treg), innate lymphoid cell (ILC), and myeloid-derived suppressor cell (MDSC) responses, which highlight the polarization of several major immune cell types. These responses facilitate the pulmonary clearance and repair under physiological conditions. When exposure persists and overwhelms the clearance capacity, they foster the chronic progression of inflammation and development of progressive disease conditions, such as fibrosis and cancer. The pulmonary response to insoluble particulates thus represents a distinctive disease process wherein non-infectious, persistent exposures stimulate the polarization of immune cells to orchestrate dynamic inflammatory and immune reactions, leading to pulmonary and pleural chronic inflammation, fibrosis, and malignancy. Despite large variations in particles and their associated disease outcomes, the early response to inhaled particles often follows a common path. The initial reactions entail a barrier immune response dominated by type 1 inflammation that features active phagocytosis by M1 macrophages and recruitment of neutrophils, both of which are fueled by Th1 and proinflammatory cytokines. Acute inflammation is immediately followed by resolution and tissue repair mediated through specialized pro-resolving mediators (SPMs) and type 2 cytokines and cells including M2 macrophages and Th2 lymphocytes. As many particles and fibers cannot be digested by phagocytes, resolution is often extended and incomplete, and type 2 inflammation becomes heightened, which promotes interstitial fibrosis, granuloma formation, and tumorigenesis. Recent studies also reveal the involvement of Th17-, Treg-, ILC-, and MDSC-mediated responses in the pathogenesis caused by inhaled particulates. This review synopsizes the progress in understanding the interplay between inhaled particles and the pulmonary immune functions in disease pathogenesis, with focus on particle-induced polarization of immune cells and its role in the development of chronic inflammation, fibrosis, and cancer in the lung.

We examine a method to detect the light speed variation from gamma ray burst data observed by the Fermi Gamma-ray Space Telescope (FGST). We suggest new criteria to determine the characteristic time for low energy photons by the energy curve and the average energy curve respectively, and obtain similar results compared with those from the light curve. We offer a new criterion with both the light curve and the average energy curve to determine the characteristic time for low energy photons. We then apply the new criteria to the GBM NaI data, the GBM BGO data, and the LAT LLE data, and obtain consistent results for three different sets of low energy photons from different FERMI detectors.

Background We investigated the potential regulatory role of miR-219-5p in esophageal squamous cell carcinoma (ESCC) and looked at the underlying mechanisms in ESCC. Methods Real-time PCR was used to determine the levels of miR-219-5p in ESCC tissues and cell lines. The effects of miR-219-5p and cyclin A2 (CCNA2) on cell proliferation and cell cycle progression were evaluated using MTT, colony formation and flow cytometry assays with ESCC cell lines EC9706 and TE-9. Bioinformatics techniques and the luciferase reporter assay were applied to validate CCNA2 as the miR-219-5p target in ESCC cells. The mRNA and protein levels of CCNA2 were measured using real-time PCR and western blotting. Results MiR-219-5p expression was significantly lower in ESCC tissues and cells than in healthy tissues. Upregulation of miR-219-5p repressed cell proliferation and induced cell cycle arrest at the G2/M phase. CCNA2 was identified and confirmed as a direct downstream target of miR-219-5p and its expression negatively correlated with miR-219-5p profiles in ESCC tissues. Knockdown of CCNA2 potentiated the effects of miR-219-5p on cell proliferation and cell cycle distribution. Conclusions Our results demonstrate that miR-219-5p might function as a tumor suppressor by directly targeting CCNA2 expression. It could serve as a new therapeutic target for ESCC.

Tea plant (Camellia sinensis) is an economically important beverage crop. Drought stress (DS) seriously limits the growth and development of tea plant, thus affecting crop yield and quality. To elucidate the molecular mechanisms of tea plant responding to DS, we performed transcriptomic analysis of tea plant during the three stages [control (CK) and during DS, and recovery (RC) after DS] using RNA sequencing (RNA-Seq). Totally 378.08 million high-quality trimmed reads were obtained and assembled into 59,674 unigenes, which were extensively annotated. There were 5,955 differentially expressed genes (DEGs) among the three stages. Among them, 3,948 and 1,673 DEGs were up-regulated under DS and RC, respectively. RNA-Seq data were further confirmed by qRT-PCR analysis. Genes involved in abscisic acid (ABA), ethylene, and jasmonic acid biosynthesis and signaling were generally up-regulated under DS and down-regulated during RC. Tea plant potentially used an exchange pathway for biosynthesis of indole-3-acetic acid (IAA) and salicylic acid under DS. IAA signaling was possibly decreased under DS but increased after RC. Genes encoding enzymes involved in cytokinin synthesis were up-regulated under DS, but down-regulated during RC. It seemed probable that cytokinin signaling was slightly enhanced under DS. In total, 762 and 950 protein kinases belonging to 26 families were differentially expressed during DS and RC, respectively. Overall, 547 and 604 transcription factor (TF) genes belonging to 58 families were induced in the DS vs. CK and RC vs. DS libraries, respectively. Most members of the 12 TF families were up-regulated under DS. Under DS, genes related to starch synthesis were down-regulated, while those related to starch decomposition were up-regulated. Mannitol, trehalose and sucrose synthesis-related genes were up-regulated under DS. Proline was probably mainly biosynthesized from glutamate under DS and RC. The mechanism by which ABA regulated stomatal movement under DS and RC was partly clarified. These results document the global and novel responses of tea plant during DS and RC. These data will serve as a valuable resource for drought-tolerance research and will be useful for breeding drought-resistant tea cultivars.

Control over the protein corona of nanomaterials allows them to function better. Here, by taking graphene/gold as examples, we comprehensively assessed the association of surface properties with the protein corona. As revealed by in vitro measurements and computations, the interaction between graphene/gold and HSA/IgE was inversely correlated with the hydroxyl group availability, whereas the interaction between that and ApoE was comparatively less relevant. Molecular simulations revealed that the number and the distribution of surface hydroxyl groups could regulate the manner in which nanomaterials interact with proteins. Moreover, we validated that ApoE pre-adsorption before injection enhances the blood circulation of nanomaterials relative to their pristine and IgE-coated counterparts. This benefit can be attributed to the invulnerability of the complementary system provided by ApoE, whose encasement does not increase cytotoxicity. Overall, this study offers a robust yet simple way to create protein corona enriched in dysopsonins to realize better delivery efficacy. The interaction between proteins and nanomaterials is complex and of interest for controlling nanoparticle fate. Here, using experimental and computational methods, the authors report on the effect of hydroxyl groups on protein interaction and how they can be used to enhance circulation times.

Background Baicalin, which is isolated from Radix Scutellariae , possesses strong biological activities including an anti-inflammation property. Recent studies have shown that the anti-inflammatory effect of baicalin is linked to toll-like receptor 4 (TLR4), which participates in pathological changes of central nervous system diseases such as depression. In this study, we explored whether baicalin could produce antidepressant effects via regulation of TLR4 signaling in mice and attempted to elucidate the underlying mechanisms. Methods A chronic unpredictable mild stress (CUMS) mice model was performed to explore whether baicalin could produce antidepressant effects via the inhibition of neuroinflammation. To clarify the role of TLR4 in the anti-neuroinflammatory efficacy of baicalin, a lipopolysaccharide (LPS) was employed in mice to specially activate TLR4 and the behavioral changes were determined. Furthermore, we used LY294002 to examine the molecular mechanisms of baicalin in regulating the expression of TLR4 in vivo and in vitro using western blot, ELISA kits, and immunostaining. In the in vitro tests, the BV2 microglia cell lines and primary microglia cultures were pretreated with baicalin and LY292002 for 1 h and then stimulated 24 h with LPS. The primary microglial cells were transfected with the forkhead transcription factor forkhead box protein O 1 (FoxO1)-specific siRNA for 5 h and then co-stimulated with baicalin and LPS to investigate whether FoxO1 participated in the effect of baicalin on TLR4 expression. Results The administration of baicalin (especially 60 mg/kg) dramatically ameliorated CUMS-induced depressive-like symptoms; substantially decreased the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the hippocampus; and significantly decreased the expression of TLR4. The activation of TLR4 by the LPS triggered neuroinflammation and evoked depressive-like behaviors in mice, which were also alleviated by the treatment with baicalin (60 mg/kg). Furthermore, the application of baicalin significantly increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and FoxO1. The application of baicalin also promoted FoxO1 nuclear exclusion and contributed to the inhibition of the FoxO1 transactivation potential, which led to the downregulation of the expression of TLR4 in CUMS mice or LPS-treated BV2 cells and primary microglia cells. However, prophylactic treatment of LY294002 abolished the above effects of baicalin. In addition, we found that FoxO1 played a vital role in baicalin by regulating the TLR4 and TLR4-mediating neuroinflammation triggered by the LPS via knocking down the expression of FoxO1 in the primary microglia. Conclusion Collectively, these results demonstrate that baicalin ameliorated neuroinflammation-induced depressive-like behaviors through the inhibition of TLR4 expression via the PI3K/AKT/FoxO1 pathway.

As a basic symmetry of space-time, Lorentz symmetry has played important roles in various fields of physics, and it is a glamorous question whether Lorentz symmetry breaks. Since Einstein proposed special relativity, Lorentz symmetry has withstood very strict tests, but there are still motivations for Lorentz symmetry violation (LV) research from both theoretical consideration and experimental feasibility, that attract physicists to work on LV theories, phenomena and experimental tests with enthusiasm. There are many theoretical models including LV effects, and different theoretical models predict different LV phenomena, from which we can verify or constrain LV effects. Here, we introduce three types of LV theories: quantum gravity theory, space-time structure theory and effective field theory with extra-terms. Limited by the energy of particles, the experimental tests of LV are very difficult; however, due to the high energy and long propagation distance, high-energy particles from astronomical sources can be used for LV phenomenological researches. Especially with cosmic photons, various astronomical observations provide rich data from which one can obtain various constraints for LV researches. Here, we review four common astronomical phenomena which are ideal for LV studies, together with current constraints on LV effects of photons.

Leggett–Garg inequality (LGI) is a time analogue of Bell’s inequality that concerns measurements performed on a system at different times. Violation to LGI indicates quantum coherence. We present a Leggett–Garg-type inequality compatible with more general neutrino oscillation frameworks, allowing the effects of decoherence to be taken into consideration. The inequality is applied to test coherence for data from Daya Bay, MINOS, and KamLAND experiments, and their results are compared to theoretical predictions to investigate decoherence. Both Daya Bay and MINOS data exhibit clear violations of over 10σ, and of over 90% of theoretical predictions, while the KamLAND data exhibit violation of 1.9σ, being of 58% of the theoretical prediction. The present work is the first to have considered the energy uncertainties in neutrino coherence tests.

Lorentz invariance violation (LIV) can change the threshold behavior predicted by special relativity and cause threshold anomalies which affect the propagation of cosmic photons. In this work, we focus on the threshold anomaly effect on cosmic photon attenuations by extragalactic background light (EBL) and discuss how to identify LIV from observations of very high energy (VHE) photons propagated from long distance in the universe. We point out that the Large High Altitude Air Shower Observatory (LHAASO), one of the most sensitive gamma-ray detector arrays currently operating at TeV and PeV energies, is an ideal facility for performing such LIV searching. We apply the proposed strategy to discuss the newly observed gamma-ray burst GRB 221009A to demonstrate the predictive ability of our suggestions.

A bstract Previous studies on high-energy gamma-ray burst neutrinos from IceCube suggest a neutrino speed variation at the Lorentz violation (LV) scale of ~6 . 4 × 10 17 GeV, with opposite velocity variances between neutrinos and antineutrinos. Within a spacetime foam model, inspired by string theory, we develop an approach to describe the suggested neutrino/antineutrino propagation properties with both Lorentz invariance and CPT symmetry breaking. A threshold analysis on the bremsstrahlung of electron-positron pair ( ν → νee + ) for the superluminal (anti)neutrino is performed. We find that, due to the energy violation caused by the quantum foam, such reaction may be restricted to occur at sufficient high energies and could even be kinematically forbidden. Constraints on neutrino LV from vacuum ee + pair emission are naturally avoided. Future experiments are appealed to test further the CPT violation of cosmic neutrinos and/or neutrino superluminality.