It has been reported that the biological functions of enzymes could be altered when they are encapsulated in metal–organic frameworks (MOFs) due to the interactions between them. Herein, we probed ...the interactions of catalase in solid and hollow ZIF-8 microcrystals. The solid sample with confined catalase is prepared through a reported method, and the hollow sample is generated by hollowing the MOF crystals, sealing freestanding enzymes in the central cavities of hollow ZIF-8. During the hollowing process, the samples were monitored by small-angle X-ray scattering (SAXS) spectroscopy, electron microscopy, powder X-ray diffraction (PXRD), and nitrogen sorption. The interfacial interactions of the two samples were studied by infrared (IR) and fluorescence spectroscopy. IR study shows that freestanding catalase has less chemical interaction with ZIF-8 than confined catalase, and a fluorescence study indicates that the freestanding catalase has lower structural confinement. We have then carried out the hydrogen peroxide degradation activities of catalase at different stages and revealed that the freestanding catalase in hollow ZIF-8 has higher activity.
Abstract
Fatty acids (FAs) are essential nutrients, but how they are transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn ...delivers FAs into adipocytes. During the process, binding of FAs to CD36 activates its downstream kinase LYN, which phosphorylates DHHC5, the palmitoyl acyltransferase of CD36, at Tyr91 and inactivates it. CD36 then gets depalmitoylated by APT1 and recruits another tyrosine kinase SYK to phosphorylate JNK and VAVs to initiate endocytic uptake of FAs. Blocking CD36 internalization by inhibiting APT1, LYN or SYK abolishes CD36-dependent FA uptake. Restricting CD36 at either palmitoylated or depalmitoylated state eliminates its FA uptake activity, indicating an essential role of dynamic palmitoylation of CD36. Furthermore, blocking endocytosis by targeting LYN or SYK inhibits CD36-dependent lipid droplet growth in adipocytes and high-fat-diet induced weight gain in mice. Our study has uncovered a dynamic palmitoylation-regulated endocytic pathway to take up FAs.
Aseptic loosening caused by wear particles is a common complication after total hip arthroplasty. We investigated the effect of the quercetin on wear particle‐mediated macrophage polarization, ...inflammatory response and osteolysis. In vitro, we verified that Ti particles promoted the differentiation of RAW264.7 cells into M1 macrophages through p‐38α/β signalling pathway by using flow cytometry, immunofluorescence assay and small interfering p‐38α/β RNA. We used enzyme‐linked immunosorbent assays to confirm that the protein expression of M1 macrophages increased in the presence of Ti particles and that these pro‐inflammatory factors further regulated the imbalance of OPG/RANKL and promoted the differentiation of osteoclasts. However, this could be suppressed, and the protein expression of M2 macrophages was increased by the presence of the quercetin. In vivo, we revealed similar results in the mouse skull by μ‐CT, H&E staining, immunohistochemistry and immunofluorescence assay. We obtained samples from patients with osteolytic tissue. Immunofluorescence analysis indicated that most of the macrophages surrounding the wear particles were M1 macrophages and that pro‐inflammatory factors were released. Titanium particle‐mediated M1 macrophage polarization, which caused the release of pro‐inflammatory factors through the p‐38α/β signalling pathway, regulated OPG/RANKL balance. Macrophage polarization is expected to become a new clinical drug therapeutic target.
A key challenge in environmental remediation is the design of adsorbents bearing an abundance of accessible chelating sites with high affinity, to achieve both rapid uptake and high capacity for the ...contaminants. Herein, we demonstrate how two-dimensional covalent organic frameworks (COFs) with well-defined mesopore structures display the right combination of properties to serve as a scaffold for decorating coordination sites to create ideal adsorbents. The proof-of-concept design is illustrated by modifying sulfur derivatives on a newly designed vinyl-functionalized mesoporous COF (COF-V) via thiol–ene “click” reaction. Representatively, the material (COF-S-SH) synthesized by treating COF-V with 1,2-ethanedithiol exhibits high efficiency in removing mercury from aqueous solutions and the air, affording Hg2+ and Hg0 capacities of 1350 and 863 mg g–1, respectively, surpassing all those of thiol and thioether functionalized materials reported thus far. More significantly, COF-S-SH demonstrates an ultrahigh distribution coefficient value (K d) of 2.3 × 109 mL g–1, which allows it to rapidly reduce the Hg2+ concentration from 5 ppm to less than 0.1 ppb, well below the acceptable limit in drinking water (2 ppb). We attribute the impressive performance to the synergistic effects arising from densely populated chelating groups with a strong binding ability within ordered mesopores that allow rapid diffusion of mercury species throughout the material. X-ray absorption fine structure (XAFS) spectroscopic studies revealed that each Hg is bound exclusively by two S via intramolecular cooperativity in COF-S-SH, further interpreting its excellent affinity. The results presented here thus reveal the exceptional potential of COFs for high-performance environmental remediation.
Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and ...urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low‐salt diet (3.0 g) for 7 days, and a high‐salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt‐Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high‐salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high‐salt diet than on a low‐salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high‐salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low‐salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.
We report the discovery of an infrared (IR)-bright dust-obscured galaxy (DOG) that shows a strong ionized-gas outflow but no significant molecular gas outflow. Based on detailed analysis of their ...optical spectra, we found some peculiar IR-bright DOGs that show strong ionized-gas outflow (O iii λ5007) from the central active galactic nucleus (AGN). For one of these DOGs (WISE J102905.90+050132.4) at zspec = 0.493, we performed follow-up observations using ALMA to investigate their CO molecular gas properties. As a result, we successfully detected 12CO(J = 2-1) and 12CO(J = 4-3) lines and the continuum of this DOG. The intensity-weighted velocity map of both lines shows a gradient, and the line profile of those CO lines is well-fitted by a single narrow Gaussian, meaning that this DOG has no sign of strong molecular gas outflow. The IR luminosity of this object is log (LIR/L☉) = 12.40, which is classified as an ultraluminous IR galaxy (ULIRG). We found that (i) the stellar mass and star formation rate relation and (ii) the CO luminosity and far-IR luminosity relation are consistent with those of typical ULIRGs at similar redshifts. These results indicate that the molecular gas properties of this DOG are normal despite the fact that its optical spectrum shows a powerful AGN outflow. We conclude that a powerful ionized-gas outflow caused by the AGN does not necessarily affect the cold interstellar medium in the host galaxy, at least for this DOG.
The design of low-price and flexible hydrogen evolution reaction (HER) electrode has attracted much attention on efficient utilization of sustainable hydrogen energy. Herein, we reported a facile ...fabrication of flexible HER electrode by anchoring CoP electrocatalyst on polyester (PET) textiles. Conductive nickel cloth (NC-PET) substrate was firstly obtained by sequentially electroless plating and electroplating of metallic Ni on textile fibers. The amorphous CoP catalyst was then assembled on the NC-PET substrate by controlled electrodeposition to obtain flexible HER electrode (CoP-NC/PET). The flexible CoP-NC/PET showed a low overpotential of 63 mV at 10 mA cm−2 for HER, with a Tafel slope of 48.09 mV dec−1 in 1 M KOH solution. The faradaic efficiency of CoP-NC/PET measured at 100 mA cm−2 current density was estimated to be nearly 100%. No significant loss of HER catalytic activity was observed after 2000 cycles and 1000 times folding operations, demonstrating the high flexibility and stability of the present CoP-NC/PET electrode.
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•HER electrode was facilely fabricated by anchoring CoP on textiles.•Amorphous CoP electrocatalyst was obtained by electrodeposition.•Exhibited excellent HER activity and flexibility.
Fatty acid uptake is the first step in fatty acid utilization, but it remains unclear how the process is regulated. Protein palmitoylation is a fatty acyl modification that plays a key regulatory ...role in protein targeting and trafficking; however, its function in regulating fatty acid metabolism is unknown. Here, we show that two of the Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC4 and DHHC5, regulate fatty acid uptake. DHHC4 and DHHC5 function at different subcellular localizations to control the palmitoylation, plasma membrane localization, and fatty acid uptake activity of the scavenger receptor CD36. Depletion of either DHHC4 or DHHC5 in cells disrupts CD36-dependent fatty acid uptake. Furthermore, both Dhhc4−/− and adipose-specific Dhhc5 knockout mice show decreased fatty acid uptake activity in adipose tissues and develop severe hypothermia upon acute cold exposure. These findings demonstrate a critical role of DHHC4 and DHHC5 in regulating fatty acid uptake.
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•CD36 is a physiological substrate of palmitoyl acyltransferases DHHC4/5•Palmitoylation of CD36 targets it to the plasma membrane•DHHC4/5 are required for the cellular fatty acid uptake activity of CD36•DHHC4/5 regulate fatty acid uptake activity in adipose tissues
Regulation of fatty acid uptake remains unclear. Wang et al. show that palmitoylation of CD36 by DHHC4 and DHHC5 is required for its plasma membrane localization and fatty acid uptake activity. Deficiency in DHHC4 or DHHC5 leads to decreased fatty acid uptake and increased susceptibility to cold.
This study has developed a method to prepare diastereo‐ and regio‐selective indoline‐fused 2,5‐diketopiperazine scaffolds. The synthetic process involved an Ugi four‐component reaction in which ...readily available starting materials were used and a metal‐free intramolecular post‐Ugi tandem consecutive 5‐exo‐trig/6‐exo‐dig cyclization under basic conditions. The plausible mechanism and substrate structures were elucidated by single‐crystal X‐ray diffraction analysis and supported by density functional theory calculations.
We present the ionized gas properties of infrared (IR)-bright dust-obscured galaxies (DOGs) that show an extreme optical/IR color, , selected with the Sloan Digital Sky Survey (SDSS) and Wide-field ...Infrared Survey Explorer (WISE). For 36 IR-bright DOGs that show O iiiλ5007 emission in the SDSS spectra, we performed a detailed spectral analysis to investigate their ionized gas properties. In particular, we measured the velocity offset (the velocity with respect to the systemic velocity measured from the stellar absorption lines) and the velocity dispersion of the O iii line. We found that the derived velocity offset and dispersion of most IR-bright DOGs are larger than those of Seyfert 2 galaxies (Sy2s) at , meaning that the IR-bright DOGs show relatively strong outflows compared to Sy2s. This can be explained by the difference in IR luminosity contributed from active galactic nuclei, (AGN), because we found that (i) (AGN) correlates with the velocity offset and dispersion of O iii and (ii) our IR-bright DOG sample has larger (AGN) than Sy2s. Nevertheless, the fact that about 75% IR-bright DOGs have a large (>300 km s−1) velocity dispersion, which is a larger fraction compared to other AGN populations, suggests that IR-bright DOGs are good laboratories to investigate AGN feedback. The velocity offset and dispersion of O iii and Ne iiiλ3869 are larger than those of O iiλ3727, which indicates that the highly ionized gas tends to show stronger outflows.
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