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Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.

• Kink bands (KBs) were introduced into an ultra-coarse-grained Fe-13.5Cr-4.5Al alloy through warm deformation. • KBs evolved from dislocation walls and formed with significant grain rotation. • KBs can strengthen the alloy by 150–225.3 MPa by their heterogeneity-refinement and HDI-strengthening. • KBs can induce a boundary-delamination effect to maintain ductility during tensile deformation. Fe-Cr-Al alloys, owing to their absence of allotropic transformation, require multiple cycles of rolling and recrystallization annealing processes to achieve substantial grain refinement, ultimately leading to the attainment of outstanding mechanical properties. However, the corresponding manufacturing costs will also increase greatly. In this work, we have proposed a new microstructural preparation process. Simply using warm rolling for an ultra-coarse-grained Fe-Cr-Al alloy to introduce lamellar kink bands (KBs) into the matrix, the mechanical properties can be significantly improved. By using electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM), and combined with Schmid factor (SF) calculation, the formation mechanism of KBs has been revealed. When the slip plane and direction are nearly perpendicular to the loading force direction (LFD) during the continuous grain rotation, the dislocation wall will evolve into the KBs boundaries. Simultaneously, a huge orientation separation between the matrix and KBs will be produced. As strain continues to rise, KBs undergo a transformation, transitioning from low-angle-grain boundaries (LAGBs) to high-angle-grain boundaries (HAGBs), occasionally adopting a configuration as coincident site lattice (CSL) boundaries with reduced interface energy. Results of the tensile test, cyclic loading-unloading-reloading tensile test, and the strengthening calculation show that KBs can pronouncedly enhance the strength by their heterogeneous refinement on the original grains and hetero-deformation induced (HDI) strengthening effect from the dislocation density discrepancy between the matrix and internal KBs, the grains containing KBs (KBGs) and the grains without KBs (or KBs-free-grains, KFGs). The theoretical calculation value of the strengthening contribution from KBs on yield strength can be up to 225.5 MPa, with a minimum value exceeding 153 MPa. On the other hand, the ductility can be retained to some extent through stimulating the KBs boundary delamination mechanism. The present study provides a low-cost and feasible processing method for fabricating Fe-Cr-Al alloy with high strength and good ductility. [Display omitted] [ABSTRACT FROM AUTHOR]

BackgroundThe diagnosis of cerebral thrombosis origin is challenging and remains unclear. This study aims to identify thrombosis due to cardioembolism (CE) and large artery atherosclerosis (LAA) from a new perspective of distinct metabolites.MethodsDistinct metabolites between 26 CE and 22 LAA origin thrombi, which were extracted after successful mechanical thrombectomy in patients with acute ischemic stroke in the anterior circulation, were analyzed with a ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) system. Enriched metabolic pathways related to the metabolites were identified. Least absolute shrinkage selection operator regression analyses and a filtering method were used to select potential predictors. Furthermore, four machine learning classifiers, including decision tree, logistic regression, random forest (RF), and k means unsupervised classification model, were used to evaluate the predictive ability of the selected metabolites.ResultsUPLC-QTOF-MS analysis revealed that levels of 88 and 55 metabolites were elevated in LAA and CE thrombi, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed a significant difference between the pathways enriched in the two types of thrombi. Six metabolites (diglyceride (DG, 18:3/24:0), DG (22:0/24:0), phytosphingosine, galabiosylceramide (18:1/24:1), triglyceride (15:0/16:1/o–18:0), and glucosylceramide (18:1/24:0)) were finally selected to build a predictive model. The predictive RF model was confirmed to be the best, with a satisfactory stability and prediction capacity (area under the curve=0.889).ConclusionsSix metabolites as potential predictors for distinguishing between cerebral thrombi of CE and LAA origin were identified. The results are useful for understanding the pathogenesis and for secondary stroke prevention.

Pericytes are present tight around the intervals of capillaries, play an essential role in stabilizing the blood–brain barrier, regulating blood flow and immunomodulation, and persistent contraction of pericytes eventually leads to impaired blood flow and poor clinical outcomes in ischemic stroke. We previously show that iptakalim, an ATP-sensitive potassium (K-ATP) channel opener, exerts protective effects in neurons, and glia against ischemia-induced injury. In this study we investigated the impacts of iptakalim on pericytes contraction in stroke. Mice were subjected to cerebral artery occlusion (MCAO), then administered iptakalim (10 mg/kg, ip). We showed that iptakalim administration significantly promoted recovery of cerebral blood flow after cerebral ischemia and reperfusion. Furthermore, we found that iptakalim significantly inhibited pericytes contraction, decreased the number of obstructed capillaries, and improved cerebral microcirculation. Using a collagen gel contraction assay, we demonstrated that cultured pericytes subjected to oxygen-glucose deprivation (OGD) consistently contracted from 3 h till 24 h during reoxygenation, whereas iptakalim treatment (10 μM) notably restrained pericyte contraction from 6 h during reoxygenation. We further showed that iptakalim treatment promoted K-ATP channel opening via suppressing SUR2/EPAC1 complex formation. Consequently, it reduced calcium influx and ET-1 release. Taken together, our results demonstrate that iptakalim, targeted K-ATP channels, can improve microvascular disturbance by inhibiting pericyte contraction after ischemic stroke. Our work reveals that iptakalim might be developed as a promising pericyte regulator for treatment of stroke.

The acetonitrile ligands in [(MeCN)4Co(C4F8)][PF6] were found to be labile toward ligand substitution reactions, allowing for the preparation of [(MeCN)(tpy)Co(C4F8)][PF6], [(tpy)CoBr(C4F8)], [(bpy)2Co(C4F8)][PF6], and [(cis-κ2-pym-PPh2)2Co(C4F8)][PF6] (tpy = 2,2′:6′,2″-terpyridine, bpy = 2,2′-bipyridine, and pym-PPh2= diphenyl(2-pyrimidyl)phosphine). All of the aforementioned complexes have been structurally characterized by X-ray diffraction. Additionally, an improved procedure for the preparation of [(MeCN)4Co(C4F8)][X] (X = PF6or BF4) is reported.

In this report, synthetic routes to [(MeCN)3Co(CF3)3], [Co(MeCN)6][PF6]2, [(MeCN)4Co(CF3)2][PF6], [(MeCN)2(py)Co(CF3)3], [(MeCN)(py)2Co(CF3)3], and [(MeCN)4Co(C4F8)][PF6] are described. The unusual [(py)2(CF3)2Co(μ-CH2CN)]2has also been identified as a decomposition product of [(py)2(MeCN)Co(CF3)3]. The aforementioned compounds, all of which have been characterized by X-ray crystallography, are expected to serve as useful precursors to cobalt trifluoromethyl- and C4F8-containing derivatives.

TS-2 microspheres, consisting of intergrown primary nanocrystals, was prepared by controlling the synthetic parameters. The effects of the amount of quaternary ammonium cations as structure-directing agent, H2O/Si ratio, the presence of alcohol and the temperature were carefully investigated on the crystallization process. The high alkalinity was proved to be highly important for the preservation of the microsphere morphology initially formed, due to the unique intergrown stacking style. An alkali treatment with the aqueous solution of structure-directing agent, organic amine and ammonium salt and subsequent Na+ion-exchange were performed to enhance the catalytic activity of TS-2 microsphere in the cyclohexanone ammoximation reactions, with both the conversion and selectivity higher than 99%. In the continuous reaction, the TS-2 microspheres exhibited to be durable catalyst with potential application in industrial ammoximation processes.

A facile and effective method to synthesize TS-1 zeolite aggregates has been presented. The crystallization of silanized seeds and nanocrystallites led to large and irregular TS-1 zeolite aggregates ranging from 5 to 40 μm in size, based on the special sol-gel chemistry of bridged organosilane. Epoxidation of 1-hexene and cyclohexene was used as a probe reaction to investigate the catalytic performance of the resulting materials. These TS-1 zeolite aggregates possessed both the conventional nanoparticle properties of TS-1 zeolites and variable surface hydrophilic/hydrophobic features, which enhanced the catalytic properties of hydroperoxides for alkene epoxidation. Moreover, the large aggregates effectively simplified the separation procedure during preparation and catalytic reactions.

Therapeutic hypothermia is a promising strategy for acute cerebral ischemia via physical or pharmacological methods. In this study, we pharmacologically induced hypothermia on Sprague Dawley rats by intraperitoneally injecting PD149163. We found that mild hypothermia was induced by PD149163 treatment without local cerebral blood flow (LCBF) alteration. To evaluate the neuroprotective effects of PD149163, TTC staining, HE staining and Nissl's staining were performed in our study. We found that PD149163 could prevent neuronal damage, and inhibit proliferation and activation of glial cells induced by ischemia. Simultaneously, we observed PD149163 ameliorated apoptosis characterized by down-regulated caspase-3 and Bax, but elevated Bcl-2. Moreover, PD149163 dramatically reduced JNK and AMPK/mTOR signaling pathway activation, and thereby inhibited autophagy by increased P62 expression, decreased the ratio of LC3-Ⅱ to LC3-Ⅰ and the expression of Beclin. Taken together, the present findings reveal the therapeutic effects of PD149163-induced hypothermia in brain ischemia, and provide a new strategy for stroke treatment.

Hierarchically porous ZSM-5 (SiO2/Al2O3≈ 120) containing phosphorus was prepared by a one-step post-synthesis treatment involving controlled desilication and phosphorous modification. The hierarchically porous ZSM-5 featured high thermal and hydrothermal stability. The obtained ZSM-5 zeolites were systematically characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, N2adsorption-desorption, NH3temperature-programmed desorption, and 27Al and 31P magic-angle spinning nuclear magnetic resonance spectroscopy. The prepared ZSM-5 displayed enhanced activity and prolonged lifetime toward hydrocarbon cracking. The high activity was attributed to improved coke tolerance owing to the presence of the highly stable mesoporous network of ZSM-5 and acid sites introduced upon phosphorus modification. Additionally a mechanism of the stabilization of the zeolites by phosphorus was proposed and discussed.

The hydrogenation activity of Pd nanoparticles Pd NPs supported on MIL-140 analogs consisting of different aromatic moieties have been explored and the results show that catalysts comprising Pd and a phenyl groups exhibit superior performance to those containing Pd and naphthalene or biphenyl groups.

Small-crystal TS-1 was synthesized via a seed-induced approach using ammonia as the alkali source and tetrapropylammonium bromide as an auxiliary structure-directing agent. The TS-1 samples were characterized using X-ray diffraction, N2adsorption-desorption, Fourier-transform infrared spectroscopy, inductively coupled plasma atomic emission spectroscopy, scanning electron microscopy, and ultraviolet-visible spectroscopy. The use of the colloidal seed reduced the crystal size, and an appropriate amount of silicalite-1 seed assisted Ti incorporation into the TS-1 framework. This method reduces the cost of TS-1 synthesis because a significantly smaller amount of tetrapropylammonium hydroxide is used. The catalytic performance of the synthesized small-crystal TS-1 samples in cyclohexanone ammoximation was better than that of bulk TS-1 as a result of improved diffusion and a larger number of active tetrahedral Ti centers.

The hydrogenation activity of 3 wt.% Pd nanoparticles supported on various mono-group (H, OCH3, NH2, Cl, and NO2) substituted Al–MIL-53 materials has been investigated. Substituents enhanced the dispersion of palladium nanoparticles on Al–MIL-53, leading to a narrow particle size distribution in the range of 2 to 4 nm. Pd nanoparticles on fresh catalysts were present as a mixture of Pd(ii) and Pd(0) with different ratios. These Pd species readily became metallic in a hydrogen flow even at room temperature. Their activities in hydrogenation of phenol and phenylacetylene are linked to the substituents on the aromatic ring of the framework. Catalysts with electron-donating groups (OCH3and NH2) show much higher activity than those containing electron-withdrawing groups (Cl and NO2). This behavior might be explained by the hydrogen dissociation abilities of metallic Pd nanoparticles affected by the organic linkers.

Well supported: Stable hemin–graphene conjugates (see picture) formed by immobilization of monomeric hemin on graphene, showed excellent catalytic activity, more than 10 times better than that of the recently developed hemin–hydrogel system and 100 times better than that of unsupported hemin. The catalysts also showed excellent binding affinities and catalytic efficiencies approaching that of natural enzymes.

Gut unterstützt: Hämin‐Graphen‐Konjugate (siehe Bild) zeigen eine katalytische Aktivität, die mehr als 10‐mal höher ist als die eines Hämin‐Hydrogel‐Systems und 100‐mal höher als die von Hämin ohne Trägermaterial. Die Katalysatoren zeichnen sich außerdem durch hervorragende Bindungsaffinitäten aus, und die Katalyseeffizienzen kommen denen natürlicher Enzyme nahe.

Following the structural concept of copper‐containing proteins in which dinuclear copper centers are connected by hydroxide bridging ligands, a bidentate copper(II) complex has been incorporated into nano‐confined MCM‐41 silica by a multistep sequential grafting technique. Characterization by a combination of EPR spectroscopy, X‐ray photoelectron spectroscopy (XPS), UV/Vis spectroscopy, IR spectroscopy , and solid‐state 13C and 29Si cross‐polarization magic‐angle spinning (CP‐MAS) NMR suggests that dinuclear Cu complexes are bridged by hydroxide and other counterions (chloride or perchlorate ions), similar to the situation for EPR‐undetectable [CuII⋅⋅⋅CuII] dimer analogues in biological systems. More importantly, a dynamic mononuclear–dinuclear equilibrium between different coordination modes of copper is observed, which strongly depends on the nature of the counterions (Cl−or ClO4−) in the copper precursor and the pore size of the silica matrix (the so‐called confinement effect). A proton‐transfer mechanism within the hydrogen‐bonding network is suggested to explain the dynamic nature of the dinuclear copper complex supported on the MCM‐41 silica.

We report herein a facile electrochemical approach to synthesizing various layered composite films of nanomaterials and conducting polymers, called nanoveneers. Layered structures of polypyrrole film with single-walled carbon nanotubes (SWNTs), graphene, and Au nanoparticles have been obtained by electropolymerization of pyrrole molecules on a heavily doped silicon wafer preloaded with target conductive nanomaterials. A free-standing, transparent, and highly conductive composite film was achieved after peeling off from a silicon wafer. Different from traditional homogeneous composite materials, such kinds of nanoveneers combined to the best extent the structural continuity and processability of conducting polymers with the high conductivity and functionality of discontinuous SWNTs, graphene, and other nanomaterials. The layered electrochemical deposition provides a great freedom for constructing various nanostructures with well-controlled geometry and thus physicochemical properties, as demonstrated by SWNT/polypyrrole nanoveneers. These nanoveneers are particularly attractive in areas of chemical sensors, labels, transparent electronics, and optoelectronics.

Photocatalyst mediated photoelectrochemical processes can make use of the photogenerated electrons and holes onsite for photocatalytic redox reactions, and enable the harness and conversion of solar energy into chemical energy, in analogy to natural photosynthesis. However, the photocatalysts available to date are limited by either poor efficiency in the visible light range or insufficient photoelectrochemical stability. Here, it is shown that a Pt/Si/Ag nanowire heterostructure can be rationally synthesized to integrate a nanoscale metal‐semiconductor Schottky diode encased in a protective insulating shell with two exposed metal catalysts. The synthesis of Pt/Si/Ag nanowire diodes involves a scalable process including the formation of silicon nanowire array through wet chemical etching, electrodeposition of platinum and photoreduction of silver. The Pt/Si/Ag diodes exhibit highly efficient photocatalytic activity for a wide range of applications including environmental remediation and solar fuel production in the visible range. In this article, photodegradation of indigo carmine and 4‐nitrophenol are used to evaluate the photoactivity of Pt/Si/Ag diodes. The Pt/Si/Ag diodes also show high activity for photoconversion of formic acid into carbon dioxide and hydrogen.

Summary Clinical resistance to adriamycin (ADR) develops readily, and cardiotoxicity is a major dose-limiting side effect. A range of anthracycline derivatives have been synthesized recently, and a number reported to exhibit significantly reduced cardiotoxicity in experimental animals. Using NIL 8 Syrian hamster overy cells and two continuous human tumour cell lines derived from colon carcinomas we have screened a series of 11 anthracycline analogues, determining their in vitro cytotoxic effects by colony-forming assays. Five agents proved significantly more cytotoxic than ADR: dihydroxyanthraquinone (DHAQ), mitoxantrone (DHAD), 4-demethoxydaunorubicin (4-DNR), 4′-0-tetrahydropyranyl-adriamycin (THP-ADR), and 4′-deoxyadriamycin (4-ADR). We have also established in vitro a subline of the L5178Y murine lymphoma resistant to ADR and have used this model to identify derivatives with potential value for overcoming ADR resistance. We have observed three patterns of response: (i) complete cross-resistance with 4′-epiadriamycin and daunorubicin; (ii) slight cross-resistance with 4-DNR, THP-ADR, 7-con-0-methyl-nogarol and aclacinomycin A; and (iii) complete absence of cross-resistance with 4-ADr, 4′-0-methyladriamycin, DHAQ, DHAD, and methylhydroxyellipticinium. These straightforward preclinical screens thus identify three drugs which may merit clinical evaluation, since they not only show an increased level of cytotoxicity in vitro to ADR at equivalent concentrations but also overcome resistance to ADR in this murine model system.

Stable hemin–graphene conjugatesformed by immobilization of monomeric hemin on graphene showed excellent catalytic activity approaching that of natural enzymes. The catalytic activity was more than 10 times better than that of the recently developed hemin–hydrogel system and 100 times better than that of unsupported hemin, as demonstrated Y. Huang, X. Duan, and co‐workers in their Communication on page 3822 ff.The picture shows the artistic illustration of the hemin–graphene conjugates.

Stabile Hämin‐Graphen‐Konjugate, hergestellt durch Immobilisieren von monomerem Hämin auf Graphen, zeigen eine hervorragende katalytische Aktivität, die der natürlicher Enzyme nahekommt. Die katalytische Aktivität ist über 10‐mal höher als in einem Hämin‐Hydrogel‐System und 100‐mal höher als in Hämin ohne Trägermaterial, wie Y. Huang, X. Duan et al. in der Zuschrift auf S. 3888 ff. berichten. Das Bild zeigt die Hämin‐Graphen‐Konjugate.

Photocatalyst mediated photoelectrochemical processes can make use of the photogenerated electrons and holes onsite for photocatalytic redox reactions, and enable the harness and conversion of solar energy into chemical energy, in analogy to natural photosynthesis. However, the photocatalysts available to date are limited by either poor efficiency in the visible light range or insufficient photoelectrochemical stability. Here, it is shown that a Pt/Si/Ag nanowire heterostructure can be rationally synthesized to integrate a nanoscale metal‐semiconductor Schottky diode encased in a protective insulating shell with two exposed metal catalysts. The synthesis of Pt/Si/Ag nanowire diodes involves a scalable process including the formation of silicon nanowire array through wet chemical etching, electrodeposition of platinum and photoreduction of silver. The Pt/Si/Ag diodes exhibit highly efficient photocatalytic activity for a wide range of applications including environmental remediation and solar fuel production in the visible range. In this article, photodegradation of indigo carmine and 4‐nitrophenol are used to evaluate the photoactivity of Pt/Si/Ag diodes. The Pt/Si/Ag diodes also show high activity for photoconversion of formic acid into carbon dioxide and hydrogen.