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•The intestinal toxicity of MPs with different length on zebrafish was investigated through metabolomics.•MPs can be taken up by zebrafish at different developmental stages, ...especially in the early life stage.•MPs were observed in zebrafish gut, causing length-dependent intestinal damage and toxicities.•Long MPs induced more serious effects, such as the dramatically derease of the food intake, etc.•Microplastic fibers up-regulated glycerophospholipids metabolism and down-regulated fatty acyls metabolism.
To explore the intestinal toxicity of microplastic fibers, zebrafish larvae and adults were exposed to different length of microplastic fibers (50 ± 26 μm and 200 ± 90 μm). After exposure, microplastic fibers were observed in the gut of zebrafish even at the early life stage, causing length-dependent intestinal damage and toxicities manifested by histopathological changes and biomarker responses. Long microplastic fibers induced more serious effects. They significantly decreased the food intake of zebrafish by 54 %–67 % compared with short microplastic fibers. Metabolomics was conducted to further reveal the metabolic alterations induced by microplastic fibers in zebrafish. A total of 124 and 123 metabolites were significantly changed by short and long microplastic fibers. At the meanwhile, 41 significantly changed metabolites were shared between short and long fibers treatment groups and were further investigated to reveal the influence of fiber length on the toxicity. The results demonstrate that microplastic fibers can up-regulate glycerophospholipids metabolism which exacerbates oxidative damage and inflammation and down-regulate fatty acyls metabolism related to nutritional deficiency. These novel findings enhance our understanding of the intestinal toxicity of microplastic fibers and demonstrate that metabolomics is powerful to unravel the underlying mechanisms of microplastics (MPs) toxicity.
The macrophage, one of the several key immune cell types, is believed to be involved in tumorigenesis. However, the mechanism of macrophages promoting tumor progression is largely unknown.
The ...differentially secreted proteins of M1 and M2 macrophages were analyzed by mass spectrometry. We performed GST pull-down assay for the identification of cell-membrane receptors that interact with chitinase 3-like protein 1 (CHI3L1) protein. The mouse model was used to validate the function of CHI3L1 in cancer metastasis in vivo. Protein phosphorylation and gene expression were performed to study the signaling pathway activation of cancer cells after CHI3L1 treatment.
M2 macrophage-secreted CHI3L1 promoted the metastasis of gastric and breast cancer cells in vitro and in vivo. The CHI3L1 protein functioned by interacting with interleukin-13 receptor α2 chain (IL-13Rα2) molecules on the plasma membranes of cancer cells. Activation of IL-13Rα2 by CHI3L1 triggered the activation of the mitogen-activated protein kinase signaling pathway, leading to the upregulated expression of matrix metalloproteinase genes, which promoted tumor metastasis. The results of this study indicated that the level of CHI3L1 protein in the sera of patients with gastric or breast cancer was significantly elevated compared with those of healthy donors.
Our study revealed a novel aspect of macrophages with respect to cancer metastasis and showed that CHI3L1 could be a marker of metastatic gastric and breast cancer in patients.
T regulatory (Treg) cells are crucial to maintain immune tolerance and repress antitumor immunity, but the mechanisms governing their cellular redox homeostasis remain elusive. We report that ...glutathione peroxidase 4 (Gpx4) prevents Treg cells from lipid peroxidation and ferroptosis in regulating immune homeostasis and antitumor immunity. Treg-specific deletion of Gpx4 impairs immune homeostasis without substantially affecting survival of Treg cells at steady state. Loss of Gpx4 results in excessive accumulation of lipid peroxides and ferroptosis of Treg cells upon T cell receptor (TCR)/CD28 co-stimulation. Neutralization of lipid peroxides and blockade of iron availability rescue ferroptosis of Gpx4-deficient Treg cells. Moreover, Gpx4-deficient Treg cells elevate generation of mitochondrial superoxide and production of interleukin-1β (IL-1β) that facilitates T helper 17 (T
17) responses. Furthermore, Treg-specific ablation of Gpx4 represses tumor growth and concomitantly potentiates antitumor immunity. Our studies establish a crucial role for Gpx4 in protecting activated Treg cells from lipid peroxidation and ferroptosis and offer a potential therapeutic strategy to improve cancer treatment.
The tumor suppressor phosphatase and tensin homolog (PTEN) is a nonredundant phosphatase, counteracting one of the most critical cancer-promoting pathways: the phosphatidylinositol 3-kinase ...(PI3K)/Akt signaling pathway. In addition to the canonical function of dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate (PIP3), recent studies showed the intriguing roles of PTEN in regulating genomic instability, DNA repair, stem cell self-renewal, cellular senescence, and cell migration and/or metastasis. Clinically, PTEN mutations and deficiencies are prevalent in many types of human cancers. Severe PTEN deficiency is also associated with advanced tumor stage and therapeutic resistance, such as the resistance to trastuzumab, an anti-HER2 therapy. Currently, targeting the deregulated PI3K/PTEN-Akt signaling axis has emerged as one of the major tenets in anticancer drug development. In this review, we highlight our current knowledge of PTEN function and the recent discoveries in dissecting the PTEN signaling pathway. The deregulations of PTEN in cancers, clinical lessons, and new prospects of rationally designed PI3K/Akt-targeted therapy for effective cancer treatment are also discussed.
Conjugated side-chain-isolated D–A copolymers, based on the donor unit of benzodithiophene (BDT) with a thiophene-conjugated side chain, thiophene π bridge, and the acceptor unit of benzotriazole ...(BTA) with or without fluorine substitution (PBDT-FBTA and PBDT-HBTA), were designed and synthesized for elucidating their structure–property relationships. The copolymer films demonstrated well-defined absorption peaks with steep absorption edges, consistent with their rigid and ordered structures in the solid films. The substitution of a thiophene-conjugated side chain on the BDT unit in the copolymers aroused 15-nm red-shifted absorption in comparison with its polymer analogues with alkoxy side chains on the BDT unit. Compared to PBDT-HBTA, PBDT-FBTA with two-fluorine-atom substitution on the BTA unit demonstrated a lower highest occupied molecular orbital energy level, higher hole mobility, and significantly better photovoltaic performance. A polymer solar cell (PSC) based on PBDT-FBTA/PC70BM (1:2, w/w) with a 5% 1,8-diiodooctane additive displayed a power conversion efficiency (PCE) of 6.0% with a J sc of 11.9 mA cm–2, a V OC of 0.75 V, and a fill factor of 67.2%, under the illumination of AM1.5G, 100 mW cm–2. Even at a thicker active layer of 400 nm, the PSC still demonstrated a higher PCE of 4.74%. The results indicate that PBDT-FBTA is a promising polymer donor material for future application of large-area PSCs.
Many reduced common mode voltage (CMV) modulation methods have been proposed for three-level inverters. However, most of them suffer from large current distortion because only part of the available ...base vectors is utilized. The interleaved paralleling can reduce both CMV and the output current distortion, though the CMV reduction is limited and large zero-sequence circulating current (ZSCC) is inevitably caused by the phase-shifted carriers. To further reduce the CMV while maintaining smaller current distortion and ZSCC, a five-level reduced CMV (RCMV) modulation method is proposed in this article, which treats the parallel inverters as a whole. Theoretical analysis reveals that the integrated modulation provides additional base vectors that contribute to smaller total harmonic distortion (THD) of the current, and the selected vectors ensure the nearest-three-vector synthesis and half-reduced CMV. The switching sequences design and neutral point balancing strategy are also developed for dual-parallel three-level inverters, ensuring that the average circulating current is zero and the neutral point voltage is balanced, which are both critical to the proper operation of parallel inverters. Superior performance in terms of CMV, THD, and ZSCC provided by the proposed method in comparison with conventional modulation is verified by comprehensive simulation and experimental results.
While metal is the most common conducting constituent element in the fabrication of metamaterials, graphene provides another useful building block, that is, a truly two-dimensional conducting sheet ...whose conductivity can be controlled by doping. Here we report the experimental realization of a multilayer structure of alternating graphene and Al2O3 layers, a structure similar to the metal-dielectric multilayers commonly used in creating visible wavelength hyperbolic metamaterials. Chemical vapour deposited graphene rather than exfoliated or epitaxial graphene is used, because layer transfer methods are easily applied in fabrication. We employ a method of doping to increase the layer conductivity, and our analysis shows that the doped chemical vapour deposited graphene has good optical properties in the mid-infrared range. We therefore design the metamaterial for mid-infrared operation; our characterization with an infrared ellipsometer demonstrates that the metamaterial experiences an optical topological transition from elliptic to hyperbolic dispersion at a wavelength of 4.5 μm.
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We present the detailed computation of full-color three-loop three-point form factors of both the stress-tensor supermultiplet and a length-three BPS operator in 𝒩 = 4 SYM. The integrands ...are constructed based on the color-kinematics (CK) duality and generalized unitarity method. An interesting observation is that the CK-dual integrands contain a large number of free parameters. We discuss the origin of these free parameters in detail and check that they cancel in the simplified integrands. We further perform the numerical evaluation of the integrals at a special kinematics point using public packages FIESTA and pySecDec based on the sector-decomposition approach. We find that the numerical computation can be significantly simplified by expressing the integrals in terms of uniformly transcendental basis, although the final three-loop computations still require large computational resources. Having the full-color numerical results, we verify that the non-planar infrared divergences reproduce the non-dipole structures, which firstly appear at three loops. As for the finite remainder functions, we check that the numerical planar remainder for the stress-tensor supermultiplet is consistent with the known result of the bootstrap computation. We also obtain for the first time the numerical results of the three-loop non-planar remainder for the stress-tensor supermultiplet as well as the three-loop remainder for the length-three operator.
In this study, a new approach is proposed for the restoration of reflectance information on organ samples using a commercial camera. This novel approach is comprised of three stages. In the first ...stage, a color clustering method is utilized to extract the representative colors of the organ samples as well as their corresponding spectral reflectance. In the second stage, the spectral reflectance is decomposed into two separate parts, i.e., the fundamental stimulus spectrum and the metameric black following the matrix-R theory, and the latter is further utilized to form a look-up table (LUT) via a lattice regression model. Finally, the reflectance information can be easily retrieved by referring to the newly built LUT. The performance of the proposed method was investigated, along with that of six other commonly adopted methods, through a physical experiment using real, measured organ samples. The results demonstrate that the proposed method outperformed all the other methods in terms of both colorimetric and spectral metrics, indicating that it is a promising strategy for organ sample reflectance restoration.
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