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Electrocatalytic upgrading of biomass represents a promising way for the green synthesis of value-added fine chemicals. Rational construction of highly active and low-cost electrocatalysts with superior durability is of great importance for promoting this electrochemical process. In this work, we reported a novel 3D hierarchical NixSey–NiFe layered double hydroxide (LDH) core–shell nanostructure in situ grown on Ni foam (NixSey–NiFe@NF) for efficient electrocatalytic oxidation of biomass-derived 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) and furfural (FUR) to furoic acid (FurAc), respectively. By virtue of the excellent electrical conductivity and good mechanical strength of the NixSey nanowire core, abundant exposed active sites of the NiFe LDH nanosheet shell, and the open structure of the hierarchical nanoarrays, the integrated core–shell NixSey–NiFe LDH@NF electrode exhibited outstanding catalytic performance for HMF and FUR oxidation by obtaining considerable yields of FDCA (99.3%) and FurAc (99.7%) with high faradaic efficiency (FE) for FDCA (98.9%) and FurAc (99.5%), as well as superior stability retaining 96.7% FE for FDCA and 97.1% FE for FurAc after six successive electrolysis cycles. This work offers an effective approach to engineer novel electrocatalysts towards efficient upgrading of biomass-derived platform chemicals.

Met tyrosine kinase, a receptor for a hepatocyte growth factor (HGF), plays a critical role in tumor growth, metastasis, and drug resistance. Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network. Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers. Here, using structured illumination microscopy (SIM) and high spatial and temporal resolution live cell imaging, we identified mitochondrial trafficking of receptor tyrosine kinase Met. The contacts between activated Met kinase and mitochondria formed dramatically, and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements. Mechanically, we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38 (Fis1 pY38). Fis1 pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) to mitochondria. Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma (HCC) cells both in vitro and in vivo. These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities, which may provide a therapeutic target for metastatic HCC.

A lack of efficient diagnostic tools for early and noninvasive diagnosis of breast cancer has restricted the clinical treatment effect. This problem might be addressed by the combination of aggregation-induced emission (AIE) fluorescence imaging and positron emission tomography (PET) with the dual advantages of high resolution and easy operation, and unlimited penetration and high sensitivity. Here, a mitochondria-targeted AIE luminogen (AIEgen) radiolabeled with 18 F was developed through a two-step radiochemical reaction by virtue of a prosthetic group. The obtained 18/19 F-Bz-CP imaging probe was examined by in vitro cell uptake and cell proliferation inhibition in two breast cancer cell lines, showing that the probe can efficiently target and locate in the mitochondria through the analysis of fluorescence imaging and PET simultaneously. Additionally, the probe can induce cancer cell apoptosis with the half maximal inhibitory concentration (IC50) of 4.8 μM for MCF-7 cells and 7.2 μM for T47D cells, indicating its potential application for breast cancer therapy.

We recently reported that intraperitoneal injection of 7,8-dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor-mimicking small compound, could attenuate alcohol-related behaviors in a two-bottle choice ethanol consumption procedure (IA2BC) in rats via tropomyosin receptor kinase B in the ventral tegmental area (VTA), which is closely related to alcohol use disorder. However, the detailed mechanisms underlying the regulation of 7,8-DHF on alcohol drinking behavior remain elusive. In this study, we determined the role of nitric oxide (NO), a pleiotropic signaling molecule, in the VTA in the action of 7,8-DHF upon alcohol drinking behavior. Intermittent alcohol exposure led to the overexpression of NO in the VTA, especially 72 h after withdrawal from four weeks of ethanol exposure in IA2BC rats. A higher amount of alcohol intake was also found at the same time point, consistent with the overexpression of NO in the VTA. Microinjection of NG-Nitro-l-Arginine Methyl Ester, (NO synthase inhibitor) or 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (NO scavenger) into the VTA inhibited alcohol intake, whereas application of S-Nitroso-N-acetyl-DL-penicillamine (SNAP, the NO donor) in the VTA further enhanced alcohol consumption in IA2BC rats. Interestingly, either 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (a sGC inhibitor) or KT5823 [a selective protein kinase G (PKG) inhibitor] blocked NO's enhancing effect on ethanol intake. Intraperitoneal injection of 7,8-DHF reduced the overexpression of NO; SNAP microinjected into the VTA reversed the inhibitory effects of 7,8-DHF on alcohol consumption. Our findings suggest that NO-cGMP-PKG might be involved in regulation of 7,8-DHF on alcohol consumption in IA2BC rats.

Sevoflurane (Sev) is a commonly used anesthetic in hospitals that can cause neurotoxicity. Postoperative cognitive dysfunction (POCD) is a common clinical problem induced by some anesthetics. However, the exact mechanism of neurotoxicity induced by Sev is unclear. Here we studied a new mechanism of POCD induced by Sev. We treated 15-month-old mice with 2% Sev for 6 hours, and we had found that Sev causes POCD. Using isobaric tags for relative and absolute quantitation (iTRAQ), we found that the transporter and the metabolism of carbohydrates and inorganic ions were involved in the cognitive impairment induced by Sev. Using synchrotron radiation micro-X-ray fluorescence (μ-XRF), we showed that Sev caused the iron overload in the brain of 15-month-old mice. Subsequently, excessive iron led to oxidative stress and impaired mitochondrial function that further led to glucose metabolism disorder and reduced ATP production by regulating the expression of key enzyme genes or proteins including G6Pase, Pck1, and Cs. Meanwhile, Sev also inhibited the oxygen consumption rate and glucose absorption by downregulating the expression of glucose transporter 1 in cerebral vascular endothelial cells. The cross-dysfunction of iron and glucose metabolism caused the apoptosis in the cortex and hippocampus through Bcl2/Bax pathway. In conclusion, the data here showed a new mechanism that Sev caused apoptosis by cross-dysregulation of iron and glucose metabolism and induced energy stress in mice. Maintaining iron and glucose metabolism homeostasis may play an important role in cognitive impairment induced by Sev.

Photoresponsive materials with high photoresponse sensitivity and photofatigue resistance are indispensable for applications, such as textiles and sensors fields. Herein, we synthesized photoresponsive polyamide 6 (PA6) with spiropyran (SP) as molecular component, by incorporating spiropyran-containing diisocyanate activator into anionic ring-opening polymerization of e-caprolactam. To improve photosensitivity and reduce response time, the corresponding nanofibrous membranes were obtained by electrospinning. The reversibility of the isomerization of SP resulted in colored nanofibrous membrane patterns, which can be written, erased, and rewritten, using UV light and visible light. It revealed that photosensitivity of nanofibrous membranes were further improved, when appropriate polyethylene glycol was covalently embedded into PA6 segments to increase the chain flexibility. Photoresponse reversibility and photofatigue resistance displayed that UV–vis absorbance intensity of SP-embedded PA6 nanofibrous membrane decreased just 13% after 10 cycles of UV light irradiation, while its absorbance intensity in UV–vis spectra after visible light irradiation has negligible decrease. For better understanding the structure, electronic characteristics and UV–vis absorbance peak of SP-embedded PA6, theoretical calculations were also carried out. Finally, UV absorption of transparent and flexible poly(dimethyl siloxane) (PDMS)/photoresponsive nanofibers composite film was assessed. The composite film was photochromic, and possessed excellent property for blocking ultraviolet radiation. This work explores a strategy for synthesizing photoresponsive SP-embedded polyamide 6 by incorporating spiropyran-containing activator into anionic ring-opening polymerization of e-caprolactam. SP-embedded PA6 nanofibrous membrane with excellent photosensitivity and photofatigue resistance was electrospun. The isomerization reversibility of spiropyran-merocyanine (SP-MC) resulted in colored patterns which can be written, erased, and rewritten using UV light and visible light. Transparent photochromic composite film for UV absorption and protection was also developed.

A series of hierarchical ZSM-5 zeolites were prepared by seed induction method and alkali-treated method. The crystal structural, textural and acidic properties were characterized by XRD, TEM, NH3-TPD, and N2-sorption. The effect of hierarchical ZSM-5 zeolites on the product distribution of low rank coal fast pyrolysis in a fluidized bed was investigated. The results showed that the specific surface area, mesoporous pore volume and average pore size of the zeolites increase to different degrees after alkali treatment. Hierarchical ZSM-5 zeolites could promote the cyclization of aliphatics and the dissociation of phenol pool of volatile from coal pyrolysis, increasing the content of light aromatics. The yield of light aromatics reaches the maximumwhen the zeolites used are treated with 0.3 mol NaOH, in which the content of mono-aromatics and naphthalene/methylnaphthalene increases by 2.7 times and 0.9 times, respectively, compared with microporous zeolites. The performance of catalysts decreases when treated with 0.4 mol NaOH due to the excessive desilication.

Title compound (E)-1-(4-(4-bromobenzyl)piperazin-1-yl)-3-(4-chlorophenyl)prop-2-en-1-one (5) (C20H20BrClN2O, Mr = 419.74) is designed, synthesized, and evaluated for its biological activity. Its structure is confirmed by FTIR, 1H and 13C NMR, HRMS, and X-ray single crystal diffraction. The structure is stabilized via inter- as well as intra- C–H…O interactions and intra hydrogen bonding C–H…N interactions. The Hirshfeld surface intermolecular interactions are studied using the crystal structure. The maximum surface area of the molecule is occupied by C–H…O interactions. In addition, the biological activity in vitro and in vivo of title compound 5 is also evaluated.

Background and purpose Acute kidney injury is a common clinical problem with no definitive or specific treatment. Therefore, the molecular mechanisms of acute kidney injury must be fully understood to develop novel treatments. Nuciferine, a major bioactive compound isolated from the lotus leaf, possesses extensive pharmacological activities. Its effect on folic acid-induced acute kidney injury, however, remains unknown. Here, we aimed to clarify the pharmacological effects of nuciferine and its mechanisms of action in acute kidney injury. Experimental approach The effects of nuciferine on folic acid-induced acute kidney injury in mice were investigated. HK-2 human proximal tubular epithelial cells and HEK293T HEK cells were used to evaluate the protective effect of nuciferine on RSL3-induced ferroptosis. Key results Nuciferine treatment mitigated the pathological alterations, ameliorated inflammatory cell infiltration and improved kidney dysfunction in mice with folic acid-induced acute kidney injury. In HK-2 and HEK293T cells, nuciferine significantly prevented RSL3-induced ferroptotic cell death. Mechanistically, nuciferine significantly inhibited ferroptosis by preventing iron accumulation and lipid peroxidation in vitro and in vivo. Moreover, knockdown of glutathione (GSH) peroxidase 4 (GPX4) abolished the protective effect of nuciferine against ferroptosis. Conclusion and implications Nuciferine ameliorated renal injury in mice with acute kidney injury, perhaps by inhibiting the ferroptosis. Nuciferine may represent a novel treatment that improves recovery from acute kidney injury by targeting ferroptosis.

Developing high-performance cathode materials for magnesium (Mg) batteries is of great significance. Here, a novel rose-with-thorn ternary MoS2@C@polyaniline (PANI) nanocomposite composed of carbon and PANI nanoneedles co-coated on rose-like MoS2 is developed. The conductive PANI needles on the surface of MoS2 improve the conductivity, and the inner MoS2 is wrapped by a carbon layer which is beneficial for the aniline coating. The MoS2@C@PANI-based Mg battery cathode displays a good capacity of 114 mA h g−1 after 100 cycles, and a recoverable rate-performance after repeated measurements. In addition, a stable capacity of 105 mA h g−1 when cycled at a low temperature of −5 °C is also achieved, indicating good potential for applications.

Inflammatory caspase-11 senses and is activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis that has critical role in defensing against bacterial infection, whereas its excess activation under pathogenic circumstances may cause various inflammatory diseases. However, there are few known drugs that can control caspase-11 activation. We report here that scutellarin, a flavonoid from Erigeron breviscapus, acted as an inhibitor for caspase-11 activation in macrophages. Scutellarin dose-dependently inhibited intracellular LPS-induced release of caspase-11p26 (indicative of caspase-11 activation) and generation of N-terminal fragment of gasdermin D (GSDMD-NT), leading to reduced pyroptosis. It also suppressed the activation of non-canonical nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as evidenced by reduced apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and decreased interleukin-1 beta (IL-1β) and caspase-1p10 secretion, whereas the NLRP3-specific inhibitor MCC950 only inhibited IL-1β and caspase-1p10 release and ASC speck formation but not pyroptosis. Scutellarin also suppressed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells lacking ASC expression. Moreover, scutellarin treatment increased Ser/Thr phosphorylation of caspase-11 at protein kinase A (PKA)-specific sites, and its inhibitory action on caspase-11 activation was largely abrogated by PKA inhibitor H89 or by adenylyl cyclase inhibitor MDL12330A. Collectively, our data indicate that scutellarin inhibited caspase-11 activation and pyroptosis in macrophages at least partly via regulating the PKA signaling pathway., Graphical abstract Scutellarin inhibited caspase-11 activation via PKA signaling, thereby suppressing pyroptosis and non-canonical NLRP3 inflammasome activation culminating in reduced release of inflammatory components.Image 1

Electrochemical oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) has received increasing attention as it is an eco-friendly strategy for synthesizing a key monomer for the production of bio-based plastics. Developing efficient, low-cost and stable electrocatalysts is crucial for this electrochemical reaction. In this work, we have reported a facile process for the synthesis of hybrid nanosheet-structured NiCo2O4 on carbon fiber paper (NiCo2O4-CFP) for the efficient electrochemical conversion of HMF into FDCA. As a non-noble binary metal-based catalyst, NiCo2O4-CFP featured a nanosheet network and 3D nanosheet flower-like microspheres, showing 94.3% selectivity and 89.6% faradaic efficiency (FE) for FDCA, which outperformed its single component metal oxides NiO-CFP and Co3O4-CFP. And it also exhibited relatively high stability by maintaining over 80% FE after four successive cycles. The proposed mechanism suggested that the synergistic effect of Ni and Co elements in NiCo2O4 could facilitate HMF oxidation.

Iron overload in the brain and iron-induced oxidative damage have been considered to play key roles in the pathogenesis of Alzheimer's disease (AD). Hepcidin is a peptide that regulates systemic iron metabolism by interacting with iron exporter ferroportin 1 (FPN1). Studies have indicated that the astrocyte hepcidin could regulate brain iron intake at the blood-brain barrier and injection of hepcidin into brain attenuated iron deposition in the brain. However, whether overexpression of hepcidin in astrocytes of APP/PS1 transgenic mice can alleviate AD symptoms by reducing iron deposition has not been evaluated. In this study, we overexpressed hepcidin in astrocytes of APP/PS1 mice and investigated its effects on β-amyloid (Aβ) aggregation, neuronal loss, iron deposition and iron-induced oxidative damages. Our results showed that the elevated expression of astrocyte hepcidin in APP/PS1 mice significantly improved their cognitive decline, and partially alleviated the formation of Aβ plaques in cortex and hippocampus. Further investigations revealed that overexpression of hepcidin in astrocytes significantly reduced iron levels in cortex and hippocampus of APP/PS1 mice, especially iron content in neurons, which led to the reduction of iron accumulation-induced oxidative stress and neuroinflammation, and finally decreased neuronal cell death in the cortex and hippocampus of APP/PS1 mice. This study demonstrated that overexpression of hepcidin in astrocytes of APP/PS1 mice could partially alleviate AD symptoms and delay the pathological process of AD.

Ribosome recycling is the final step of the cyclic process of translation, where the post-termination complex (PoTC) is disassembled by the concerted action of ribosome recycling factor (RRF) and elongation factor G (EF-G) in the sub-second time range. Since, however, both the RRF and PoTC display highly dynamic action during this process, it is difficult to assess the molecular details of the interactions between the factors and the ribosome that are essential for rapid subunit separation. Here we characterized the molecular dynamics of RRF and PoTC by combined use of molecular dynamics simulations, single molecule fluorescence detection and single-particle cryo-EM analysis, with time resolutions in the sub-millisecond to minute range. We found that RRF displays two-layer dynamics: intra- and inter-molecular dynamics during ribosome splitting. The intra-molecular dynamics exhibits two different configurations of RRF: 'bent' and 'extended'. A single-site mutant of RRF increases its propensity to the 'extended' conformation and leads to a higher binding affinity of RRF to the PoTC. The inter-molecular dynamics between RRF and EF-G in the PoTC reveals that the domain IV of EF-G pushes against the domain II of RRF, triggering the disruption of the major inter-subunit bridge B2a, and catalyzes the splitting.

In this work, p-type Co \begin{document}$_3$\end{document} O \begin{document}$_4$\end{document} decorated n-type ZnO (Co \begin{document}$_3$\end{document} O \begin{document}$_4$\end{document} /ZnO) nanocomposite was designed with the assistance of bacterial cellulose template. Phase composition, morphology and element distribution were investigated by XRD, SEM, HRTEM, EDS mapping and XPS. Volatile organic compounds (VOCs) sensing measurements indicated a noticeable improvement of response and decrease of working temperature for Co \begin{document}$_3$\end{document} O \begin{document}$_4$\end{document} /ZnO sensor, in comparison with pure ZnO, i.e., the response towards 100 ppm acetone was 63.7 (at a low working temperature of 180 ℃), which was 26 times higher than pure ZnO (response of 2.3 at 240 ℃). Excellent VOCs response characteristics could be ascribed to increased surface oxygen vacancy concentration (revealed by defect characterizations), catalytic activity of Co \begin{document}$_3$\end{document} O \begin{document}$_4$\end{document} and the special p-n heterojunction structure, and bacterial cellulose provides a facile template for designing diverse functional heterojunctions for VOCs detection and other applications.

Selenium (Se) is an essential trace element that has a large number of biological functions for broilers. However, the absorption kinetics of Se from sodium selenite in the small intestine of broilers remains unclear. Therefore, two experiments were conducted with 28-d-old commercial male broilers to study the kinetics of Se absorption in ligated small intestinal segments. In experiment 1, the Se absorption in duodenal, jejunal, and ileal segments at different post-perfusion time points (0, 20, 40, 60, 80, 100 and 120 min) were compared. In experiment 2, a kinetic study of Se absorption was conducted with the duodenal, jejunal, and ileal loops perfused with solutions containing 0, 0.0375, 0.075, 0.15, 0.30, or 0.60 μg mL−1 of Se as sodium selenite, and Se contents in perfusates were determined at 100 min after perfusion. The results from experiment 1 showed that the Se absorption increased in an asymptotic response (P0.05) in the Se absorption rate among different ligated small intestinal segments perfused with solutions containing 0.0375–0.15 μg mL−1 of Se, however, the Se absorption rate was higher (P

As an effective solution toward the establishment of a sustainable society, the reductive transformation of CO2 into value-added products is certainly important and imperative. Herein, we report a porphyrin metal-organic framework composite Au@Ir-PCN-222, which is obtained through the in situ formation of Au nanoparticles in the coordination interspaces of Ir-PCN-222. Catalytic results show that Au@Ir-PCN-222 is highly efficient for CO2 reduction and aminolysis, giving rise to formamides in high yields and selectivities under room temperature and atmospheric pressure. Mechanistic studies disclose that the high efficiency of Au@Ir-PCN-222 is due to the synergistic catalysis of Au NPs and Ir-PCN-222, in which Au NPs can adsorb CO2 molecules on their surfaces and then increase the CO2 concentration in the cavities of the framework, and at the same time, Au NPs transfer electrons to Ir-porphyrin units and therefore increase the interactions with CO2 molecules.

Known for excellent stability, porosity and functionality, the high-valent Zr4+ metal-organic frameworks (Zr-MOFs) still meets synthetic challenge in modulating the strength of Zr-Ocarboxylate linkage. Herein we explore the unusual coordination dynamics of fluorinated Zr-MOFs by designing two trifluoromethyl modified ligands with distinct geometry preference to form a family of thermodynamic and kinetic products. The low-connecting kinetic Zr-MOFs possess substitutable coordination sites to endow Zr6 -cluster with extra dynamic behaviors, thus opening a post-synthetic pathway to sequential reassembly/disassembly processes. Comprehensive factors, including ligand geometry, Zr6 -cluster connectivity, acid modulator and reaction temperature/concentration, have been studied for controllable syntheses. The stability, hydrophobicity and gas adsorption/separation properties of obtained Zr-MOFs are explored. This work sheds light on the understanding of the dynamic coordination chemistry of Zr-MOFs beyond strong Zr-O bond, which poses a versatile platform for modification and functionalization of Zr-MOFs.

Cu2O rhombic dodecahedra, octahedra, and cubes were densely modified with conjugated 4-ethynylaniline (4-EA) for facet-dependent photocatalytic activity examination. Infrared spectroscopy affirms bonding of the acetylenic group of 4-EA onto the surface copper atoms. The photocatalytically inactive Cu2O cubes showed surprisingly high activity toward methyl orange photodegradation after 4-EA modification, while the already active Cu2O rhombic dodecahedra and octahedra exhibited a photocatalytic activity enhancement. Electron, hole, and radical scavenger experiments prove that the photocatalytic charge transport processes have occurred in the functionalized Cu2O cubes. Electrochemical impedance spectroscopy also indicates reduced charge transfer resistance of the functionalized Cu2O crystals. A band diagram constructed from UV–vis spectral and Mott–Schottky measurements reveals significant band energy shifts in all Cu2O samples after decorating with 4-EA. From density functional theory (DFT) calculations, a new band has emerged slightly above the valence band maximum within the band gap of Cu2O, which has been found to originate from 4-EA through band-decomposed charge density analysis. The increased charge density localized on the 4-EA molecule and the smallest electron transition energy to reach the 4-EA-generated band are factors making {100}-bound Cu2O cubes photocatalytically active. Proper molecular decoration represents a powerful approach to improving the photocatalytic efficiency of semiconductors., Inactive Cu2O cubes become highly photocatalytically active after 4-ethynylaniline modification due to formation of a new molecular band close in energy to the valence band within the Cu2O band gap.

The shuttle effect of polysulfides is a serious issue for lithium–sulfur (Li–S) batteries, because it leads to rapid capacity decay. Herein, we present a metal organic foam-derived ZnCo2S4 that is capable of forming polar bonds with soluble polysulfides and improving the binding force to suppress the shuttle effect. The ZnCo2S4 also has a smaller Li ion diffusion barrier energy than ZnCo2O4. ZnCo2S4 grown on conductive carbon cloth facilitates fast electron transfer, while its hierarchical structure accommodates the volumetric expansion of sulfur in Li–S batteries. The ZnCo2S4/S cathodes exhibit a stable capacity of 833 mAh g−1 after 100 cycles at 0.1C and a high Coulombic efficiency of 99.9%, along with a high rate-performance after repeated tests; these features indicate a good potential for energy storage applications.

A series of Si-Mn/C core–shell composites as anode materials is synthesized via a hydrothermal method combined with heating treatment. X-ray diffraction, Raman spectroscopy, x-ray photoelectron spectroscopy, scanning electron microscopy and transmission electron microscopy analysis are used to investigate the crystal structures and chemical compositions of all as-prepared composites. With the increase of Mn4Si7 alloy content in the Si-Mn/C composites, their cycle properties and rate capabilities increase first and then decrease. As a result, the obtained Si-Mn/C (9:1) displays the largest specific capacity of approximately 960 mAh/g after 100 cycles among all composites, and it can be sustained at 1 A/g with a reversible specific capacity of 460 mAh/g, demonstrating good electrochemical performance for Si-based anodes. Our study presents an ideal candidate to improve the mechanical integrity and electrochemical property of a Si-based anode for potential application in lithium-ion batteries.

Deferasirox (DFX) is an iron chelator approved for the treatment of iron overload diseases. However, the role of DFX in oxidative stress-induced cell apoptosis and the exact molecular mechanisms underlying these processes remain poorly understood and require further investigation. In this study, we found that DFX rendered resistant to H2O2-induced apoptosis in HEK293T cells, reduced the intracellular levels of the labile iron pool (LIP) and oxidative stress induced by H2O2. Furthermore, DFX inhibited the ubiquitination and degradation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) via modulation of the interaction of p21 with SCF-Skp2. DFX also showed the inhibition effect on the activation of c-Jun N-terminal kinase (JNK), pro-caspase-3 and related mitochondrial apoptosis pathway induced by H2O2. These results provide novel insights into the molecular mechanism underpinning iron-mediated oxidative stress and apoptosis, and they may represent a promising target for therapeutic interventions in related pathological conditions.

Although the photodimerization of acenaphthylene (ACE) has been known for 100 years, the asymmetric cycloaddition of its 1-substituted derivatives is unknown. Herein, we report a supramolecular photochirogenic approach in which a homochiral and photoactive Δ/Λ-[Pd6 (RuL3 )8 ]28+ metal-organic cage (Δ/Λ-MOC-16) is used as a supramolecular reactor for the enantioselective exited-state photocatalysis of 1-Br-ACE. Owing to preorganization of the substrates by the supramolecular cage, stereochemical control of the triplet state, and nanospace transfer of energy and chirality, the cycloaddition of ACE proceeded with high selectivity for the formation of anti over syn stereoisomers, whereas the regio-, stereo-, and enantioselective cycloaddition of unsymmetrical 1-Br-ACE showed effective enantiodifferentiation of a pair of anti head-to-head stereoisomers. The enzyme-mimicking photocatalysis was verified by catalytic turnover, rate enhancement, and competing-guest inhibition experiments.

Background Early diagnosis is important to lower the mortality rate of acute fatty liver of pregnancy (AFLP). The Swansea criteria is commonly used to diagnose AFLP, but some terms could only be reached when symptoms and signs have progressed, or are not efficient in clinical practice. Therefore, it is necessary to select cost effective tests to simplify and facilitate early suspicion of acute fatty liver of pregnancy. Methods This is a retrospective study of 28,800 medical records at the Second Xiangya Hospital from 2009 to 2015, including 41 patients with AFLP and 172 other diseases that could show similar symptoms to AFLP. The evaluated variables included past history of liver diseases, blood pressure, gastrointestinal symptoms, blood count, liver function test, coagulation function test and blood sugar test. The sensitivity, specificity, positive predict value and negative predict value were calculated for models in diagnosing AFLP. Results The significant variables associated with AFLP included gastrointestinal symptoms, blood pressure > 140/90 mmHg, aminotransferase> 42 IU/l, total bilirubin> 0.8 mg/dl, total bilirubin acid> 10.0 μmol/L, activated partial prothrombin time(APTT) > 34 s, prothrombin time(PT) > 14 s, white blood cells> 11 *106/l and blood sugar Conclusions Application of a statistical model including maternal symptoms, biochemical and haematological parameters has high diagnostic accuracy for earlier identification of AFLP. However, this finding needs to be tested in another cohort to determine whether this statistical model has the same performance.

Graphical abstract Schematic of H permeation of dense metallic membrane., Highlights • Interaction between H and V surface and bulk are fully studied. • H coverage (θ) effects the adsorption energy of H/V(1 0 0). • H solubility and diffusivity depend slightly on the H concentration., To investigate the H2 purification mechanism of V membranes, we studied the adsorption, dissociation, and diffusion properties of H in V, an attractive candidate for H2 separation materials. Our results revealed that the most stable site on the V (1 0 0) surface is the hollow site (HS) for both adsorbed H atoms and molecules. As the coverage range increases, the adsorption energy of H2 molecules first decreases and then increases, while that of H atoms remains unchanged. The preferred diffusion path of atoms on the surface, surface to first subsurface, and first subsurface to second subsurface is HS → bridge site (BS) → HS, BS → BS, and BS → tetrahedral interstitial site (TIS) → BS, respectively. In the V bulk, H atoms occupy the energetically favourable TIS, and diffuse along the TIS → TIS path, which has a lower energy barrier. This study facilitates the understanding of the interaction between H and metals and the design of novel V-based alloy membranes.

The group VB metals (V, Nb, Ta) are referred to as one of the most valuable hydrogen separation membrane materials because of their advantages over Pd. To evaluate the hydrogen-permeation performance of the three metals, their structure stability, H-solubility, H-diffusivity, H-permeability, and elastic stiffness tensors have been investigated using the first-principles method. Our results reveal that the tetrahedral interstitial site (TIS) is favorable position for H-occupying, but mainly because H-solution enthalpy is the lowest. H-diffusion coefficient follows the order of V > Nb > Ta, H-permeability and H-permeation flux follow the order of Nb > V > Ta. The attractive interactions between H atoms are weak, so it is impossible to form H2 molecules inside the metals, and all metal hydride phases present good ductility. The calculated Debye temperature is basically consistent with the experimental value. These results provide fundamental data for the further design of alloy membranes based on VB metals.

Cathode materials of Li-ion batteries are important for their overall Li-storage performance. However, current cathodes are still non-ideal with rapid capacity decay and poor stability. Herein, a composite cathode consisting of ternary LiMn 1/3 Co 1/3 Ni 1/3 O 2 particles anchored on reduced graphene oxide sheets is presented, which is prepared through a simple route. The composite cathode exhibits a stable capacity exceeding 120 mAh g −1 after 500 cycles at 0.2 C, along with a high Coulombic efficiency close to 100%, which are obviously improved compared to the pure LiMn 1/3 Co 1/3 Ni 1/3 O 2 . In addition, the rate-performance of the composite is also significantly enhanced. We believe that the good electrochemical performance and the general preparation approach are able to enable the composite to find significant applications in high-performance secondary batteries.

Vanadium-based materials are considered ideal for hydrogen separation membranes owing to their higher hydrogen permeability and mechanical strength and lower cost compared with other widely used materials such as Pd alloys. However, pure V exhibits severe hydrogen embrittlement, which is often solved by alloying. In the present study, we used first-principles method to systematically calculate the hydrogen solubility, diffusivity, and other mechanical properties of different V-based binary alloys, namely, V–Co, V–Mo, V–Pd, V–Ru, and V–W. The alloys were found to possess stable crystal structures, and on exposure to hydrogen, the H atoms preferentially occupied the tetrahedral interstitial sites (TISs) in both the pure V and alloy within the material matrix, preferentially diffusing between TISs. The hydrogen diffusion coefficients of the different alloys decreased in the order V–Pd > V–Co > V–Ru > V–Mo > V–W. The alloys and their hydrides also exhibited good mechanical properties, with their resistances to hydrogen embrittlement decreasing in the order V–Co > V–Ru > V–Pd > V–Mo > V–W. This revealed that the resistance to hydrogen embrittlement of the alloy increased with decreasing atomic size of the alloying element. The findings of this study promise to facilitate the development of novel V-alloy membranes for hydrogen separation and purification.

Small-bandwidth n-type PbTe-MnTe alloys effectively modify the valley shape, while it also inevitably aggravates the deterioration of carrier mobility as nonpolar phonons dominate the scattering. It is found that a trace amount of Cu doping can alleviate the compromises among thermoelectric parameters, thereby significantly optimizing the electrical-transport performance near room temperature of n-type PbTe-MnTe alloys. The single-Kane model reveals that the physical origin of performance improvement lies in the carrier mobility enhancement and self-optimization of carrier concentration. The Debye-Callaway model further quantifies the contribution of copper defect scattering to the lattice thermal conductivity. Notably, the high thermoelectric quality factor obtained in this work rationalizes their superior properties and reveals immense potential for achieving higher zT. Herein, an extremely high zT of ∼0.52 at room temperature and a maximum zTmax of ∼1.2 at 823 K are achieved in 0.3% Cu-intercalated n-type PbTe-MnTe. The mechanism in balancing compromise elaborated in principle contributes to an improvement of thermoelectric properties of the n-type PbTe alloys in a broad temperature range.

Vascular remodeling is a prominent trait during the development of hypertension, attributable to the phenotypic transition of vascular smooth muscle cells (VSMCs). Increasing studies demonstrate that microRNA plays an important role in this process. Here, we surprisingly found that smooth muscle cell-specific miR-214 knockout (miR-214 cKO) significantly alleviates angiotensin II (Ang II)-induced hypertension, which has the same effect as that of miR-214 global knockout mice in response to Ang II stimulation. Under the treatment of Ang II, miR-214 cKO mice exhibit substantially reduced systolic blood pressure. The vascular medial thickness and area in miR-214 cKO blood vessels were obviously reduced, the expression of collagen I and proinflammatory factors were also inhibited. VSMC-specific deletion of miR-214 blunts the response of blood vessels to the stimulation of endothelium-dependent and -independent vasorelaxation and phenylephrine and 5-HT induced vasocontraction. In vitro, Ang II-induced VSMC proliferation, migration, contraction, hypertrophy, and stiffness were all repressed with miR-214 KO in VSMC. To further explore the mechanism of miR-214 in the regulation of the VSMC function, it is very interesting to find that the TGF-β signaling pathway is mostly enriched in miR-214 KO VSMC. Smad7, the potent negative regulator of the TGF-β/Smad pathway, is identified to be the target of miR-214 in VSMC. By which, miR-214 KO sharply enhances Smad7 levels and decreases the phosphorylation of Smad3, and accordingly alleviates the downstream gene expression. Further, Ang II-induced hypertension and vascular dysfunction were reversed by antagomir-214. These results indicate that miR-214 in VSMC established a crosstalk between Ang II-induced AT1R signaling and TGF-β induced TβRI /Smad signaling, by which it exerts a pivotal role in vascular remodeling and hypertension and imply that miR-214 has the potential as a therapeutic target for the treatment of hypertension.

(1) Background: Wood decay is a serious issue that results from the presence of wood-destroying fungi and has a great influence on the international wood industry. The utilization of biological control methods offers good prospects for wood preservation. (2) Methods: The plate-screening experiment, the soil block test of the Chinese stand method (GB/T 13942.1), and the characterization of wood blocks were used to achieve biological control of brown rot and white rot. (3) Results: Through isolation, screening, and identification, the antagonistic bacterium Bacillus velezensis Nhw-B72 strain was obtained. In the plate-screening experiment, the inhibition zone diameter of Nhw-B72 for Gloeophyllum trabeum was 1.68 cm and that for Coriolus versicolor was 2.33 cm. After inhibition, the morphology of mycelia was distorted, malformed, and broken. In the soil block test, the average weight loss percentage of wood blocks in the control group was 61.66%. In the treatment group, the average weight loss percentage of the wood blocks with drying was 28.18% and that of the wood blocks without drying was 34.97%. (4) Conclusions: The strain has an obvious antagonistic effect on the wood-destroying fungi and the sterile fermentative liquid can effectively inhibit wood decay. In addition, compared to the drying of wood blocks, the air-drying of blocks after impregnation with the fermentative liquid had a better inhibition effect.

Long‑term hypertension leads to alterations in the structure and function of blood vessels, and abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are important factors for these changes. Linalool is a natural compound extracted from plants. The present study aimed to explore the role and underlying mechanism of linalool in the physiological behavior of VSMCs. Angiotensin II (Ang II) was utilized to treat VSMCs, and MTT and western blotting assays were then employed to detect the effect of linalool on the induced proliferation and migration of VSMCs. The target gene of linalool was predicted by the SwissTargetPrediction website, and its expression level in VSMCs was determined using reverse transcription‑quantitative PCR and western blotting. Next, the role of the target gene in the physiological behavior of VSMCs treated with linalool was examined, and the signaling pathway was explored. The results revealed that the proliferation and migration of VSMCs treated with Ang II were significantly promoted, and linalool could alleviate these effects in a dose‑dependent manner. Cholinergic receptor muscarinic 3 (CHRM3), as a predicted target, was found to be highly expressed in Ang II‑induced VSMCs, and CHRM3 overexpression could prevent the inhibitory effect of linalool on cell proliferation and migration. In addition, its overexpression caused an increase in the expression of proteins related to the MAPK signaling pathway. In conclusion, linalool inhibited the proliferation and migration of Ang II‑induced VSMCs and blocked the MAPK signaling pathway by downregulating CHRM3.

Hydrogen embrittlement causes deterioration of materials used in metal–hydrogen systems. Alloying is a good option for overcoming this issue. In the present work, first-principles calculations were performed to systematically study the effects of adding Ni on the stability, dissolution, trapping, and diffusion behaviour of interstitial/vacancy H atoms of pure V. The results of lattice dynamics and solution energy analyses showed that the V–Ni solid solutions are dynamically and thermodynamically stable, and adding Ni to pure V can reduce the structural stability of various VHx phases and enhance their resistance to H embrittlement. H atoms preferentially occupy the characteristic tetrahedral interstitial site (TIS) and the octahedral interstitial site (OIS), which are composed by different metal atoms, and rapidly diffuse along both the energetically favourable TIS → TIS and OIS → OIS paths. The trapping energy of monovacancy H atoms revealed that Ni addition could help minimise the H trapping ability of the vacancies and suppress the retention of H in V. Monovacancy defects block the diffusion of H atoms more than the interstitials, as determined from the calculated H-diffusion barrier energy data, whereas Ni doping contributes negligibly toward improving the H-diffusion coefficient.

Strict control of iron homeostasis is critical for the maintenance of normal lung function. Iron accumulates in the lungs of patients with idiopathic pulmonary fibrosis (PF), but the characteristics of iron metabolism in the pathogenesis of PF and related targeting therapeutics are not well studied. In this study, we investigated the cellular and molecular characteristics of iron metabolism in fibrotic lungs and further explored the efficacy of clioquinol (CQ) for the treatment of PF as well as its functional mechanism. Iron aggregates accumulated in the lungs of patients with idiopathic PF, and FTL (ferritin light chain) transcripts were increased in their pulmonary fibroblasts. In the bleomycin (BLM)-induced PF (BLM-PF) mouse model, pulmonary iron accumulation is a very early and concomitant event of PF. Labile iron pool levels in both fibroblasts and macrophages from the BLM-PF model were elevated, and iron metabolism was dysregulated. CQ attenuated PF induced by BLM and FITC, and iron-saturated CQ did not alleviate BLM-PF. Furthermore, CQ inhibited the activation of fibroblasts, including proliferation, fibrotic differentiation, proinflammatory cytokine secretion, and migration. In conclusion, our study demonstrated that CQ, acting as an iron chelator, attenuates experimental PF through inactivation of fibroblasts, providing support for targeting iron metabolism as a basis for PF treatment.

An efficiency droop in GaN-based light-emitting diodes (LED) was characterized by examining its general thermophysical parameters. An effective suppression of emission degradation afforded by the introduction of InGaN/GaN heterobarrier structures in the active region was attributable to an increase in the capture cross-section ratios. The Debye temperatures and the electron–phonon interaction coupling coefficients were obtained from temperature-dependent current-voltage measurements of InGaN/GaN multiple-quantum-well LEDs over a temperature range from 20 to 300 K. It was found that the Debye temperature of the LEDs was modulated by the InN molar fraction in the heterobarriers. As far as the phonons involved in the electron–phonon scattering process are concerned, the average number of phonons decreases with the Debye temperature, and the electron–phonon interaction coupling coefficients phenomenologically reflect the nonradiative transition rates. We can use the characteristic ratio of the Debye temperature to the coupling coefficient (DCR) to assess the efficiency droop phenomenon. Our investigation showed that DCR is correlated to quantum efficiency (QE). The light emission results exhibited the high and low QEs to be represented by the high and low DCRs associated with low and high injection currents, respectively. The DCR can be envisioned as a thermophysical marker of LED performance, not only for efficiency droop characterization but also for heterodevice structure optimization.

Monosodium urate (MSU) crystals, the etiological agent of gout, are formed in joints and periarticular tissues due to long-lasting hyperuricemia. Although MSU crystal-triggered NLRP3 inflammasome activation and interleukin 1β (IL-1β) release are known to have key roles in gouty arthritis, recent studies revealed that MSU crystal-induced necrosis also plays a critical role in this process. However, it remains unknown what forms of necrosis have been induced and whether combined cell death inhibitors can block such necrosis. Here, we showed that MSU crystal-induced necrosis in murine macrophages was not dependent on NLRP3 inflammasome activation, as neither genetic deletion nor pharmacological blockade of the NLRP3 pathway inhibited the necrosis. Although many cell death pathways (such as ferroptosis and pyroptosis) inhibitors or reactive oxygen species inhibitors did not have any suppressive effects, necroptosis pathway inhibitors GSK′872 (RIPK3 inhibitor), and GW806742X (MLKL inhibitor) dose-dependently inhibited MSU crystal-induced necrosis. Moreover, a triple combination of GSK′872, GW806742X, and IDN-6556 (pan-caspase inhibitor) displayed enhanced inhibition of the necrosis, which was further fortified by the addition of MCC950 (NLRP3 inhibitor), suggesting that multiple cell death pathways might have been triggered by MSU crystals. Baicalin, a previously identified inhibitor of NLRP3, inhibited MSU crystal-induced inflammasome activation and suppressed the necrosis in macrophages. Besides, baicalin gavage significantly ameliorated MSU crystal-induced peritonitis in mice. Altogether, our data indicate that MSU crystals induce NLRP3-independent necrosis, which can be inhibited by combined inhibitors for multiple signaling pathways, highlighting a new avenue for the treatment of gouty arthritis.

Molecular or supramolecular level photoluminescence (PL) modulation combining chemical and photonic input/output signals together in an integrated system can provide potential high-density data memorizing and process functions intended for miniaturized devices and machines. Herein, a PL-responsive supramolecular coordination cage has been demonstrated for complex interactions with redox-active guests. PL signals of the cage can be switched and modulated by adding or retracting Fc derivatives or converting TTF into different oxidation states through chemical or photochemical pathways. As a result, reversible or stepwise PL responses are displayed by these host-guest systems because of the occurrence of photoinduced electron-transfer (PET) or fluorescence resonance energy transfer (FREnT) processes, providing unique nanodevice models bearing off/on logic gates or memristor-like sequential memory and Boolean operation functions.

Osteoarthritis (OA) is a chronic degenerative joint disease. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of sensory nerve on OA progression at early stage in mice.OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6 mice. Sensory denervation was induced by subcutaneous injection of capsaicin (90 mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining. Four weeks after DMM, micro-CT scans, histological analysis, and RT-PCR tests were performed to evaluate OA progression.Subcutaneous injection of capsaicin successfully induced sensory denervation in tibia. The Osteoarthritis Research Society International (OARSI) score and synovitis score of the capsaicin+DMM group were significantly higher than the score of the vehicle+DMM group. The BV/TV of the tibial subchondral bone in the capsaicin+DMM group was significantly lower than in the vehicle+DMM group. In addition, the level of expression of inflammatory factors in the capsaicin+DMM group was significantly higher than in the vehicle+DMM group.Capsaicin-induced sensory denervation accelerated OA progression at early stage in mice. To put it another way, sensory nerve protects from OA progression at early stage in mice.

Nutritional factors such as extensively hydrolyzed casein (eHC) have been proposed to exert anti-inflammatory activity and affect clinical outcomes such as tolerance development in cow’s milk allergy. Granzyme B (GrB) induces apoptosis in target cells and also controls the inflammatory response. Whether eHC could affect the activity of granzyme B and play a role in GrB-mediated inflammatory responses in vitro was unknown. The activity of GrB was measured using the substrate Ac-IEPD-pNA. Inflammatory responses were induced with GrB in HCT-8 and THP-1 cells, and pro-inflammatory cytokines were determined at the transcriptional and protein level. GrB could induce the expression of IL-1β in HCT-8 cells, and IL-8 and MCP-1 in THP-1 cells, respectively. Interestingly, GrB acted synergistically on LPS-induced inflammation in HCT-8 cells and eHC reduced pro-inflammatory responses in both GrB and LPS-mediated inflammation. Further analyses revealed that eHC could inhibit the biological activities and cytotoxic activities of GrB and then could reduce GrB-mediated inflammatory response. The results from the current study suggest that anti-inflammatory activity of extensively hydrolyzed casein is, to a certain extent, mediated through modulation of granzyme B activity and responses.

Calcineurin acts as a calcium-activated phosphatase that dephosphorylates various substrates, including members of the nuclear factor of activated T cells (NFAT) family, to trigger their nuclear translocation and transcriptional activity. However, the detailed mechanism regulating the recruitment of NFATs to calcineurin remains poorly understood. Here, we report that calcineurin A (CNA), encoded by PPP3CB or PPP3CC, is constitutively ubiquitinated on lysine 327, and this polyubiquitin chain is rapidly removed by ubiquitin carboxyl-terminal hydrolase 16 (USP16) in response to intracellular calcium stimulation. The K29-linked ubiquitination of CNA impairs NFAT recruitment and transcription of NFAT-targeted genes. USP16 deficiency prevents calcium-triggered deubiquitination of CNA in a manner consistent with defective maintenance and proliferation of peripheral T cells. T cell–specific USP16 knockout mice exhibit reduced severity of experimental autoimmune encephalitis and inflammatory bowel disease. Our data reveal the physiological function of CNA ubiquitination and its deubiquitinase USP16 in peripheral T cells. Notably, our results highlight a critical mechanism for the regulation of calcineurin activity and a novel immunosuppressive drug target for the treatment of autoimmune diseases.