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A novel hydrogen-bonded organic frameworks (HOFs) FJU-200 has been constructed from N,N'-bis(5-isophthalic acid)naphthalimide (H4L). FJU-200 has a good dual-function of aniline and ultraviolet detection. FJU-200 is the first case of HOF with dual sensing of visual color changes and photoluminescence quenching for aniline detection, and the detection limit of aniline can reach 5.5 × 10−4 mol/L. Under ultraviolet FJU-200 will rapidly change from light yellow to rustic brown, which makes it possible to use FJU-200 to achieve minute-level ultraviolet detection. Moreover, for more convenient use, FJU-200 test papers are prepared. Using them, convenient and fast aniline or ultraviolet detection can be realized. The single-crystal X-ray structures show that compared with the original FJU-200, both PhNH2@FJU-200 and UV-FJU-200 have larger pore sizes, and the dihedral angles of the H2L2− in framework has been changed.

Terrain derivative calculations from triangulated irregular network (TIN)-based digital elevation models (DEMs) have been extensively explored in geomorphometry. However, most calculation methods f...

It is challenging to obtain isomers in a pure form because of the similarities in their physicochemical properties. meta-Xylene (MX) accounts for the largest proportion of commercial xylene, which ...

Carbon nano-onions (CNOs) are a relatively new member in zero-dimensional carbon nanomaterials. Each constituent unit of CNOs is a multi-layer concentric spherical structure composed of multiple fullerene-like carbon spheres. CNOs are widely used for electronic components applications due to their large specific surface area and high electric conductivity. But a few works of CNOs on thermal conduction property in electronic device applications were studied. Therefore, we prepared the CNOs/epoxy composites by blending and casting method, and investigated the thermal conduction mechanism of CNOs in the epoxy matrix. The results show that the thermal conductivity of epoxy composite with 30 wt% CNOs loading reaches 0.59 W m−1 K−1 due to the formation of an effective thermal network of CNOs in epoxy resin, increasing by 320% in comparison with neat epoxy. In view of excellent thermal conduction performance, CNOs may be enable used as thermal conductive filler for the thermal management of electronic components.

Two-dimensional nanomaterials is an intensive research area, but the anisotropy of two-dimensional nanomaterials limits its performance release and application. As a typical two-dimensional nanomat...

Selective cleavage and functionalization of C-C bonds have important applications in organic synthesis and biomass utilization. However, functionalization of C-C bonds by controlled cleavage remains difficult and challenging because they are inert. Herein, we describe an unprecedented efficient protocol for the breaking of successive C-C bonds in alcohols to form esters with one or multiple carbon atoms less using heterogeneous cobalt nanoparticles as catalyst with dioxygen as the oxidant. A wide range of alcohols including inactive long-chain alkyl aryl alcohols undergo smoothly successive cleavage of adjacent -(C-C)n - bonds to afford the corresponding esters. The catalyst was used for seven times without any decrease in activity. Characterization and control experiments disclose that cobalt nanoparticles are responsible for the successive cleavage of C-C bonds to achieve excellent catalytic activity, while the presence of Co-Nx has just the opposite effect. Preliminary mechanistic studies reveal that a tandem sequence reaction is involved in this process.

J.C.W. thanks EaStCHEM for financial support and D.P.C. thanks the US National Science Foundation. Computational support was provided through the EaStCHEM Research Computing Facility. The boron-centered radicals derived from alkenyl N-heterocyclic carbene (NHC)-boranes bearing ester substituents were recently found to ring close in 5-endo mode by addition to the oxygen atoms of the ester substituents. The inference from this was that NHC-boryl radicals might add intermolecularly to carbonyl-containing substrates. Several different NHC-boryl radicals were generated by H-atom abstraction from NHC-ligated trihydroborates. Electron paramagnetic resonance (EPR) spectroscopy proved that these did indeed add to the oxygen atoms of diaryl ketones with production of the corresponding bora-ketyl radicals. The same unusual regioselectivity of addition was observed with monoaryl ketones, but no bora-ketyls were observed with dialkyl ketones. Similarly, no bora-ketyl adduct radicals were observed with esters, even esters of benzoic acid. EPR spectroscopic evidence suggested that NHC-boryl radicals were also added to the O-atoms of aromatic aldehydes. Amine-boryl and phosphine-boryl radicals were also observed to add to the O-atom of benzophenone with production of the corresponding ketyl radicals. Postprint

With the rapid growth in electronic device performance, there has been an increasing demand for thermally conductive polymer composites to handle the thermal management issue, thus contributing to the great importance to develop the graphene framework, which is evaluated as the most promising reinforcements for enhancing the thermal conductivity of polymer. Vacuum filtration is a common method to fabricate graphene framework, whereas, it is available to prepare a framework with centimeter-scale thickness by filtrating the graphene-water dispersion, due to the fact of sample cracking caused by the mismatch of surface tension between graphene and water. In this work, a surfactant-assisted strategy was proposed by adjusting the surface tension of the water close to that of graphene first, then performing a conventional filtration process, to fabricate graphene framework. As a result, a thick graphene framework (thickness: 3 cm) was successfully prepared, and after embedding into epoxy, the framework endows the composite (13.6 wt%) with a high in-plane thermal conductivities of 12.4 W/mK, which is equivalent to ≈ 64 times higher than that of neat epoxy. Our method is simple and compatible with the conventional filtration process, suggesting great potential for the mass-production of graphene framework to meet the practical application requirements.

The rapid development of chip technology has all put forward higher requirements for highly thermally conductive materials. In this work, a new type of material of Fishbone-like silicon carbide (SiC) material was used as the filler in a polyvinylidene fluoride (PVDF) matrix. The silicon carbide/polyvinylidene fluoride (SiC/PVDF) composites were successfully prepared with different loading by a simple mixing method. The thermal conductivity of SiC/PVDF composite reached 0.92 W m−1 K−1, which is 470% higher than that of pure polymer. The results show that using the filler with a new structure to construct thermal conductivity networks is an effective way to improve the thermal conductivity of PVDF. This work provides a new idea for the further application in the field of electronic packaging.

As the power density and integration level of electronic devices increase, there are growing demands to improve the thermal conductivity of polymers for addressing the thermal management issues. On the basis of the ultrahigh intrinsic thermal conductivity, graphene has exhibited great potential as reinforcing fillers to develop polymer composites, but the resultant thermal conductivity of reported graphene-based composites is still limited. Here, an interconnected and highly ordered graphene framework (HOGF) composed of high-quality and horizontally aligned graphene sheets was developed by a porous film-templated assembly strategy, followed by a stress-induced orientation process and graphitization post-treatment. After embedding into the epoxy (EP), the HOGF/EP composite (24.7 vol %) exhibits a record-high in-plane thermal conductivity of 117 W m-1 K-1, equivalent to ≈616 times higher than that of neat epoxy. This thermal conductivity enhancement is mainly because the HOGF as a filler concurrently has high intrinsic thermal conductivity, relatively high density, and a highly ordered structure, constructing superefficient phonon transport paths in the epoxy matrix. Additionally, the use of our HOGF/EP as a heat dissipation plate was demonstrated, and it achieved 75% enhancement in practical thermal management performance compared to that of conventional alumina for cooling the high-power LED.

Radical hydroboration reactions have only recently been reported and are still rare. Here we describe a photoredox radical hydroboration of α,β-unsaturated esters, amides, ketones, and nitriles with NHC-boranes that uses only an organocatalyst and visible light. The conditions are mild, the substrate scope is broad, and the α/β regioselectivity is high. The reaction requires only the organocatalyst; there is no costly metal, and there are no other additives (base, cocatalyst, initiator).

Given the thermal management problem aroused by increasing power densities of electronic components in the system, graphene-based papers have raised considerable interest for applications as thermal interface materials (TIMs) to solve interfacial heat transfer issues. Significant research efforts have focused on enhancing the through-plane thermal conductivity of graphene paper, however, for practical thermal management applications, reducing the thermal contact resistance between graphene paper and the mating surface is also a challenge to be addressed. Here, a strategy aimed at reducing the thermal contact resistance between graphene paper and the mating surface to realize enhanced heat dissipation was demonstrated. For this, graphene paper was decorated with polydopamine EGaIn nanocapsules using a facile dip-coating process. In practical TIM application, there was a decrease in the thermal contact resistance between the TIMs and mating surface after decoration (from 46 to 15 K mm2 W−1), which enabled the decorated paper to realize a 26% enhancement of cooling efficiency compared with the case without decoration. This demonstrated that this method is a promising route to enhance the heat dissipation capacity of graphene-based TIMs for practical electronic cooling applications.

We have used functionalized carbazoles and indenoquonoxalines as the main building units and enthynyl groups as the π-linkages to construct two novel dendritic fluorophores and studied their degenerate multi-photon absorption properties in both the solution phase and the neat-film state within femtosecond and nanosecond regions. In our experiments, these model compounds are found to manifest strong and widely dispersed two-photon absorption as well as effective power-limiting properties against ultra-short laser pulses in the near-IR region. In addition, both chromophores exhibit medium to strong three-photon-induced fluorescence, indicating such scaffold may serve as a reference structural motif for the development of three-photon materials.

Maslinic acid is a pentacyclic triterpenoid that is distributed in the peel of olives. Previous studies found that maslinic acid inhibited inflammatory response and antioxidant effects. We investigated whether maslinic acid ameliorates nonalcoholic fatty liver disease in mice with high-fat-diet (HFD)–induced obesity and evaluated the regulation of lipogenesis in hepatocytes. Male C57BL/6 mice fed a normal diet or HFD (60% fat, w/w) were tested for 16 wk. After the fourth week, mice were injected intraperitoneally with maslinic acid for 12 wk. In another experiment, HepG2 cells were treated with oleic acid to induce lipid accumulation or maslinic acid to evaluate lipogenesis. Maslinic acid significantly reduced body weight compared with HFD-fed mice. Maslinic acid reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis. Furthermore, serum glucose, leptin, and free fatty acid concentrations significantly reduced, but the serum adiponectin concentration was higher, in the maslinic acid group than in the HFD group. In liver tissue, maslinic acid suppressed transcription factors involved in lipogenesis and increased adipose triglyceride lipase. In vitro, maslinic acid decreased lipogenesis by activating AMPK. These findings suggest that maslinic acid acts against hepatic steatosis by regulating enzyme activity involved in lipogenesis, lipolysis, and fatty acid oxidation in the liver.—Liou, C.-J., Dai, Y.-W., Wang, C.-L., Fang, L.-W., Huang, W.-C. Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway.

Reactions of readily available alkenyl triflates with N-heterocyclic carbene (NHC)-boranes in the presence of diisopropyl ethyl amine provided about three dozen stable α-NHC-boryl ketones. Isolated yields were typically 40-56% for B-unsubstituted NHC-boranes (NHC-BH

Purpose of reviewThe purpose of this review is to highlight the recent findings of one of the most promising therapeutic targets in LDL cholesterol (LDL-C) management, proprotein convertase subtilisin/kexin type 9 (PCSK9).Recent findingsEndoplasmic reticulum cargo receptor, surfeit locus protein 4 i

Background Non-alcoholic fatty liver disease (NAFLD) is a common hepatic disease with an increasing prevalence but an unclear aetiology. This study aimed to investigate the functional implications of microRNA-122 (miR-122) in the pathogenesis of NAFLD and the possible molecular mechanisms. Methods Both in vitro and in vivo models of NAFLD were generated by treating HepG2 and Huh-7 cells with free fatty acids (FFA) and by feeding mice a high-fat diet (HFD), respectively. HE and Oil Red O staining were used to examine liver tissue morphology and lipid deposition, respectively. Immunohistochemical (IHC) staining was used to examine Sirt1 expression in liver tissues. qRT-PCR and Western blotting were employed to measure the expression of miR-122, Sirt1, and proteins involved in lipogenesis and the AMPK pathway. Enzyme-linked immunosorbent assay (ELISA) was used to quantify triglyceride (TG) levels in HepG2 and Huh-7 cells and in liver tissues. The interaction between miR-122 and the Sirt1 gene was further examined by a dual luciferase reporter assay and RNA-immunoprecipitation (RIP). Results NAFLD hepatic tissues and FFA-treated HepG2 and Huh-7 cells presented excess lipid production and TG secretion, accompanied by miR-122 upregulation, Sirt1 downregulation, and potentiated lipogenesis-related genes. miR-122 suppressed Sirt1 expression via binding to its 3′-untranslated region (UTR). Knockdown of miR-122 effectively mitigated excessive lipid production and suppressed the expression of lipogenic genes in FFA-treated HepG2 and Huh-7 cells via upregulating Sirt1. Furthermore, miR-122 knockdown activated the LKB1/AMPK signalling pathway. Conclusion The inhibition of miR-122 protects hepatocytes from lipid metabolic disorders such as NAFLD and suppresses lipogenesis via elevating Sirt1 and activating the AMPK pathway. These data support miR-122 as a promising biomarker and drug target for NAFLD.

J.C.W. thanks EaStCHEM for financial support, and D.P.C. thanks the US National Science Foundation. Computational support was provided through the EaStCHEM Research Computing Facility. Radical H atom abstraction from a set of N-heterocyclic carbene (NHC) complexes of alkenylboranes bearing two tert-butyl ester substituents was studied by EPR spectroscopy. The initial boraallyl radical intermediates rapidly ring closed onto the O atoms of their distal ester groups in 5-endo mode to yield 1,2-oxaborole radicals. Unexpectedly, two structural varieties of these radicals were identified from their EPR spectra. These proved to be two stable rotamers, in which the carbonyl group of the tert-butyl ester was oriented toward and away from the NHC ring. These rotamers were akin to the s-trans and s-cis rotamers of α,β-unsaturated carbonyl compounds. Their stability was attributed to the quasi-allylic interaction of their unpaired electrons with the carbonyl units of their adjacent ester groups. EPR spectroscopic evidence for two rotamers of the analogous methyl ester containing NHC-oxaborole radicals was also obtained. An improved synthetic procedure for preparing rare NHC-boralactones was developed involving treatment of the alkenyl NHC-boranes with AIBN and tert-dodecanethiol. Postprint

Efficient heat dissipation is a prerequisite for further improving the integration of devices. However, the polymer composites are not satisfying heat dissipation. For that reason, high-thermal-tra...

Rationale: Glucagon is a key hormone that regulates the adaptive metabolic responses to fasting. In addition to maintaining glucose homeostasis, glucagon participates in the regulation of cholesterol metabolism; however, the molecular pathways underlying this effect are incompletely understood. Objective: We sought to determine the role of hepatic Gcgr (glucagon receptor) signaling in plasma cholesterol regulation and identify its underlying molecular mechanisms. Methods and Results: We show that Gcgr signaling plays an essential role in LDL-C (low-density lipoprotein cholesterol) homeostasis through regulating the PCSK9 (proprotein convertase subtilisin/kexin type 9) levels. Silencing of hepatic Gcgr or inhibition of glucagon action increased hepatic and plasma PCSK9 and resulted in lower LDLR (LDL receptor) protein and increased plasma LDL-C. Conversely, treatment of wild-type (WT) mice with glucagon lowered LDL-C levels, whereas this response was abrogated in Pcsk9 −/− and Ldlr −/− mice. Our gain- and loss-of-function studies identified Epac2 (exchange protein activated by cAMP-2) and Rap1 (Ras-related protein-1) as the downstream mediators of glucagon’s action on PCSK9 homeostasis. Moreover, mechanistic studies revealed that glucagon affected the half-life of PCSK9 protein without changing the level of its mRNA, indicating that Gcgr signaling regulates PCSK9 degradation. Conclusions: These findings provide novel insights into the molecular interplay between hepatic glucagon signaling and lipid metabolism and describe a new posttranscriptional mechanism of PCSK9 regulation.

High thermal conductivity polymer composites at low filler loading are of considerable interest because of their wide range of applications. The construction of three-dimensional (3D) interconnected networks can offer a high-efficiency increase for the thermal conductivity of polymer composites. In this work, a facile and scalable method to prepare graphene foam (GF) via sacrificial commercial polyurethane (PU) sponge templates was developed. Highly thermally conductive composites were then prepared by impregnating epoxy resin into the GF structure. An ultrahigh thermal conductivity of 8.04 W m-1 K-1 was obtained at a low graphene loading of 6.8 wt%, which corresponds to a thermal conductivity enhancement of about 4473% compared to neat epoxy. This strategy provides a facile, low-cost and scalable method to construct a 3D filler network for high-performance composites with potential to be used in advanced electronic packaging.

The rapid development of integrated circuits and electronic devices creates a strong demand for highly thermally conductive yet electrically insulating composites to efficiently solve "hot spot" problems during device operation. On the basis of these considerations, hexagonal boron nitride nanosheets (BNNS) have been regarded as promising fillers to fabricate polymer matrix composites. However, so far an efficient approach to prepare ultrahigh-aspect-ratio BNNS with large lateral size while maintaining an atomically thin nature is still lacking, seriously restricting further improvement of the thermal conductivity for BNNS/polymer composites. Here, a rapid and high-yield method based on a microfluidization technique is developed to obtain exfoliated BNNS with a record high aspect ratio of ≈1500 and a low degree of defects. A foldable and electrically insulating film made of such a BNNS and poly(vinyl alcohol) (PVA) matrix through filtration exhibits an in-plane thermal conductivity of 67.6 W m

The antipsychotic drug olanzapine was reported to induce nonalcoholic fatty liver disease (NAFLD), whereas the underlying mechanism remains incompletely understood. This study investigated whether apolipoprotein A5 (apoA5) and sortilin, two interactive factors involved in NAFLD pathogenesis, are implicated in olanzapine-induced NAFLD. In the present study, at week 8, olanzapine treatment successfully induced hepatic steatosis in male C57 BL/6J mice, even when fed a normal chow diet, which was independent of animal body weight gain. Likewise, olanzapine effectively mediated hepatocyte steatosis in human HepG2 cells in vitro, characterized by substantially elevated intracellular lipid droplets. Increased plasma triglyceride concentration and decreased plasma apoA5 levels were observed in mice treated for 8 weeks with olanzapine. Surprisingly, olanzapine markedly enhanced hepatic apoA5 protein levels in mice, without a significant effect on rodent hepatic ApoA5 mRNA expression. Our in vitro study showed that olanzapine reduced apoA5 protein levels in the medium and enhanced apoA5 protein expression in hepatocytes, whereas this drug exerted no effect on hepatocyte APOA5 mRNA expression. By transfecting APOA5 siRNA into HepG2 cells, it was demonstrated that APOA5 knockdown effectively reversed olanzapine-induced hepatocyte steatosis. In addition, olanzapine drastically increased sortilin mRNA and protein levels in vivo and in vitro. Interestingly, SORT1 knockdown reduced intracellular apoA5 protein expression and increased medium apoA5 protein levels in vitro, without affecting intracellular APOA5 mRNA expression. Furthermore, SORT1 knockdown greatly ameliorated hepatocyte steatosis in vitro. This study provides the first evidence that sortilin inhibits the hepatic apoA5 secretion that is attributable to olanzapine-induced NAFLD, which provides new insight into effective strategies against NAFLD for patients with schizophrenia administered olanzapine.

This study was funded by a COVID-19 Rapid Response Grant to ZZ from the Medical College of Wisconsin Cardiovascular Center through the Cullen Run Foundation, a startup fund to ZZ from the Medical College of Wisconsin and Blood Research Institute through the Advancing a Healthier Wisconsin Endowment, a Fellow Scholar Award to ZZ from the American Society of Hematology, and a Career Development Award (19CDA34660043) to ZZ from the American Heart Association. The Medical College of Wisconsin Clinical Research Data Warehouse was supported by the NIH National Center for Advancing Translational Sciences (to Clinical & Translational Science Institute of Southeast Wisconsin, UL1TR001436). Background. Alteration in blood triglyceride levels have been found in patients with coronavirus disease 2019 (COVID-19). However, the association between hypertriglyceridemia and mortality in COVID-19 patients is unknown. Objective. To investigate the association between alteration in triglyceride level and mortality in hospitalized COVID-19 patients. Methods. We conducted a retrospective study of 600 hospitalized patients with COVID-19 diagnosis (ICD10CM:U07.1) and/or SARS-CoV-2 positive testing results between March 1, 2020 and December 21, 2020 at a tertiary academic medical center in Milwaukee, Wisconsin. De-identified data, including demographics, medical history, and blood triglyceride levels were collected and analyzed. Of the 600 patients, 109 patients died. The triglyceride value on admission was considered the baseline and the peak was defined as the highest level reported during the entire period of hospitalization. Hypertriglyceridemia was defined as greater than 150 mg/dl. Logistic regression analyses were performed to evaluate the association between hypertriglyceridemia and mortality. Results. There was no significant difference in baseline triglyceride levels between non-survivors (n=109) and survivors (n=491) [Median 127 vs. 113 mg/dl, p=0.213]. However, the non-survivors had significantly higher peak triglyceride levels during hospitalization [Median 179 vs. 134 mg/dl, p

The Cuonadong Sn-W-Be polymetallic deposit is the first rare-metal deposit with an extraordinary metallogenic potential that has been discovered in the Tethyan Himalayan metallogenic belt. The deposit shows a wide range of different mineralization types, including greisen-, pegmatite-, skarn-, and hydrothermal vein-type mineralization. Of these mineralization types, the skarn-type has the largest inferred resources. In order to constrain the source and evolution of the ore-forming fluid, we conducted a detailed study of the skarn-hosted scheelite, including cathodoluminescence imaging, in-situ trace elemental analysis, and bulk Sr isotope analysis. In addition, bulk Sr isotope analysis of fluorite, phlogopite 40Ar-39Ar dating, and marble whole-rock geochemical analysis were also conducted. Phlogopite 40Ar-39Ar dating indicates that the skarn was formed at ca. 15 Ma, which is close to the formation age of the Cuonadong muscovite granite reported in previous studies. Cathodoluminescence images indicate that skarn-hosted scheelite can be subdivided into an older type 1 scheelite and a younger type 2 scheelite. Type 1 scheelite is characterized by a negative Eu anomaly, whereas type 2 scheelite shows a positive Eu anomaly. Considering the close temporal and spatial relationship between the Cuonadong Miocene leucogranite and the ore-bearing skarn, and their similar lanthanide tetrad effect as observed in the REE patterns, we propose that the negative Eu anomaly was inherited from the Cuonadong Miocene leucogranite, while the positive Eu anomaly resulted from the addition of Eu2+ to the ore-forming fluid during greisenization. Sr isotope data show that the fluorite (87Sr/86Sr)i value of 0.728885 is within the range of the Cuonadong Miocene leucogranite (87Sr/86Sr)i values, while scheelite (87Sr/86Sr)i values (0.709717-0.713480) are similar to those of the Cuonadong marble (0.709525-0.712146). Since scheelite is intergrown with fluorite, we propose that the hydrothermal fluid that exsolved from the Cuonadong Miocene leucogranite is responsible for formation of both fluorite and scheelite. Water-rock interaction between this magma-derived fluid and the marble is responsible for the loss of the scheelite magmatic Sr isotopic signature.

Graphene is usually embedded into polymer matrices for the development of thermally conductive composites, preferably forming an interconnected and anisotropic framework. Currently, the directional self‐assembly of exfoliated graphene sheets is demonstrated to be the most effective way to synthesize anisotropic graphene frameworks. However, achieving a thermal conductivity enhancement (TCE) over 1500% with per 1 vol% graphene content in polymer matrices remains challenging, due to the high junction thermal resistance between the adjacent graphene sheets within the self‐assembled graphene framework. Here, a multiscale structural modulation strategy for obtaining highly ordered structure of graphene framework and simultaneously reducing the junction thermal resistance is demonstrated. The resultant anisotropic framework contributes to the polymer composites with a record‐high thermal conductivity of 56.8–62.4 W m−1 K−1 at the graphene loading of ≈13.3 vol%, giving an ultrahigh TCE per 1 vol% graphene over 2400%. Furthermore, thermal energy management applications of the composites as phase change materials for solar‐thermal energy conversion and as thermal interface materials for electronic device cooling are demonstrated. The finding provides valuable guidance for designing high‐performance thermally conductive composites and raises their possibility for practical use in thermal energy storage and thermal management of electronics., The dual‐assembled graphene framework (DAGF), which combines a highly oriented graphene structure along the vertical direction and a low junction thermal resistance between the graphene building blocks, exhibits excellent performance in improving the thermal conductivity of polymers. The resultant composites have a record‐high thermal conductivity of 56.8–62.4 W m−1 K−1(≈13.3 vol%), significantly outperforming previously reported results.

Alcoholic liver fibrosis (ALF) is commonly associated with long-term alcohol consumption and the activation of hepatic stellate cells (HSCs). Inhibiting the activation and proliferation of HSCs is a critical step to alleviate liver fibrosis. Increasing evidence indicates that ecto-5′-nucleotidase (CD73) plays a vital role in liver disease as a critical component of extracellular adenosine pathway. However, the regulatory role of CD73 in ALF has not been elucidated. In this study, both ethanol plus CCl4-induced liver fibrosis mice model and acetaldehyde-activated HSC-T6 cell model were employed and the expression of CD73 was consistently elevated in vivo and in vitro. C57BL/6 J mice were intraperitoneally injected with CD73 inhibitor Adenosine 5′-(α, β-methylene) diphosphate sodium salt (APCP) from 5th week to the 8th week in the development of ALF. The results showed APCP could inhibit the activation of HSCs, reduce fibrogenesis marker expression and thus alleviate ALF. Silencing of CD73 inhibited the activation of HSC-T6 cells and promoted apoptosis of activated HSC-T6 cells. What's more, the proliferation of HSC-T6 cells was inhibited, which was characterized by decreased cell viability and cycle arrest. Mechanistically, Wnt/β-catenin pathway was activated in acetaldehyde-activated HSC-T6 cells and CD73 silencing or overexpression could regulate Wnt/β-catenin signaling pathway. Collectively, our study unveils the role of CD73 in HSCs activation, and Wnt/β-catenin signaling pathway might be involved in this progression.

As a eukaryotic elongation factor 2 kinase (eEF2K) inhibitor and a mitochondrial uncoupler, oncologists have extensively studied rottlerin. Neuroscientists, however, have accumulated scarce data on the role of rottlerin in affective and cognitive functions. Only two prior studies have, respectively, documented its antidepressant-like effect and how it impairs psychostimulant-supported memory. Whether or not rottlerin would affect aversive memory remains unknown. Hence, we sought to investigate the effects of rottlerin on aversive memory in the inhibitory avoidance (IA) task in mice. Male C57BL/6J mice were trained to acquire the IA task. Rottlerin (5 mg/kg, i.p. or 3 μg bilaterally in the hippocampus) or the vehicle was administered before footshock training (acquisition), after footshock training (consolidation), after the memory reactivation (reconsolidation), and before the test (retrieval) in the IA task. Systemic and intrahippocampal rottlerin impaired the acquisition, consolidation, and retrieval of IA memory, without affecting the reconsolidation process. Rottlerin (5 mg/kg, i.p.) induced a fast-onset and long-lasting increase in the brain-derived neurotrophic factor (BDNF) protein levels in the mouse hippocampus. Systemic injection of 7,8-dihydroxyflavone (7,8-DHF, 30 mg/kg), a BDNF tropomyosin receptor kinase B (TrkB) agonist impaired IA memory consolidation, and treatment with K252a (5 μg/kg), a Trk receptor antagonist, reversed the suppressing effect of rottlerin on IA memory consolidation. Rottlerin impairs IA memory consolidation through the enhancement of BDNF signaling in the mouse hippocampus. Excessive brain BDNF levels can be detrimental to cognitive function. Rottlerin is likely to affect the original memory-associated neuroplasticity. Thus, it can be combined with exposure therapy to facilitate the forgetting of maladaptive aversive memory, such as post-traumatic stress disorder (PTSD).

Reactions of N-heterocyclic carbene boranes (NHC-boranes) with electron-poor aromatic rings under photoredox conditions provide dearomatized 3-NHC-boryl-1,5-cycohexadienes, which are formally products of 1,4-hydroboration reactions. When regioisomers are possible, the more crowded (doubly ortho-substituted) product is formed preferably or exclusively. The mechanism may involve oxidation of the NHC-borane to an NHC-boryl radical, reduction of the electron-poor aromatic ring to a radical anion, coupling of the radical and the radical anion to give a cyclohexadienyl anion, and finally regioselective protonation.

Graphene has been demonstrated as an effective reinforcement for metal matrix composites, due to its excellent mechanical properties, robust chemical inertness, thermal stability, and self-lubricating. Nevertheless, the limiting factor for its further use in metal matrix composites, is to realize the homogeneous dispersion of graphene for taking advantage of its exceptional and fascinating properties, because of the poor wettability and density contrast between metal matrix and graphene. Herein, we design a gel-assisted route to synthesize high-quality graphene nanoplatelets modified monodispersed copper particles, followed by hot pressing to fabricate graphene reinforced copper matrix composites bulk. This simple route with high efficiency and low cost, offers a new solution for the mass-production of graphene reinforced copper matrix composites and other graphene-based composites on an industrial scale. Significantly enhanced tensile strength of 253 MPa, and yield strength of 145 MPa, accompanied by the low friction coefficient and improved wear resistance, can be simultaneously achieved in the composites. For the real electrical contact performance test, the service life of electrical contacts made of graphene reinforced copper matrix composites, is 10 times longer as that of the commercial pure copper electrical contacts and almost comparable to CuAg20 contacts, demonstrating its superior ability to solve the electrical contact issues in electrical engineering systems.

Polymer composites with high thermal conductivity possess light weight, easy process and high chemical resistance, which has a huge demand in electronic packaging fields. Therefore, the development of new filler for improving the thermal conductivity has attracted lots of attentions in the field of polymer composites. In this work, a new hybrid filler was prepared through depositing nano-crystalline diamonds on SiC nanowires by hot filaments chemical vapor deposition . The results of SEM and TEM characterizations showed that the filler has a novel structure which is similar as a string of “sugar-coated haws on a stick” (a kind of Chinese candied fruit, named Tanghulu). Polymer composites containing the filler with the Tanghulu-like structure presented the high thermal conductivity of 0.57 W m −1 K−1 under 25 wt% filler contents. The excellent thermal conduction performance is attributed to the regional continuous networks formed by filler with the Tanghulu-like structure. Infrared images and a cooling radiator were utilized to further confirm the high thermal transportation performance of the polymer composites. The development of Tanghulu-like diamond@silicon carbide nanowires proposes a new strategy to prepare polymer composites with enhanced thermal conductivity, which will further promote the application in electronic packaging fields.

Glycoprotein130 (gp130) is an important signal transducer in the interleukin-6 (IL-6) trans-signaling pathway, which plays a crucial role in chronic inflammation in atherosclerosis. Studies suggest that estrogen can inhibit IL-6/gp130 signaling and reduce the risk of coronary artery disease, but the precise mechanism is unclear. The aim of this study was to investigate whether and how estrogen regulates gp130 in human umbilical vein endothelial cells (HUVECs). HUVECs were first treated with IL-6 and soluble IL-6 receptor (sIL-6R) to induce inflammation, then treated with estradiol. We then measured the expression of gp130, a disintegrin and metalloproteinase 10 (ADAM10) and 17 (ADAM17) by RT-PCR and western blot. Levels of soluble gp130 (sgp130) in the culture supernatant were measured by ELISA. We found that IL-6 and sIL-6R increased expression of gp130 protein and decreased levels of sgp130 protein, without affecting gp130 mRNA levels. Estradiol treatment reversed these effects in a concentration- and time-dependent manner. These effects were regulated by ADAM10 and ADAM17 via an estrogen receptor α/β-dependent mechanism. These results shed further light on the mechanism underlying the clinical effects of estrogen therapy in atherosclerosis and coronary artery disease.

Apolipoprotein C3 (apoC3) and apolipoprotein A5 (apoA5), encoded byAPOA1/C3/A4/A5gene cluster, are two critical regulators of plasma triglyceride (TG) metabolism. Deficiency of apoC3 or apoA5 led to significant decreased or increased plasma TG levels, respectively. Recent studies indicated apoC3 and apoA5 also played roles in plasma remnant cholesterol, high density lipoprotein (HDL) and hepatic TG metabolisms. Moreover, large scale population genetic studies indicated that loss of function mutations inAPOC3andAPOA5gene conferred decreased and increased risk of coronary artery disease (CAD), respectively. This manuscript mainly reviewed existing evidences suggesting the opposite role of apoC3 and apoA5 in lipid metabolism and CAD risk, and discussed the potential correlation between these two apolipoproteins.

Clinical and experimental studies suggested that testosterone or estradiol alone supplementation may have antidepressant-like effects. However, the synergistic effect of testosterone/estradiol on the treatment of depression and the underlying mechanism remain largely unknown. Here, we hypothesized that an appropriate dosage of testosterone combined with estradiol may became a new therapeutic strategy in depression. Our results indicated that an appropriate testosterone/estradiol ratio of 10:1 (10−8 mol/L testosterone and 10−9 mol/L estradiol) was found, which has a significant synergistic anti-apoptotic effect on PC12 cells injury stimulated by corticosterone. We then confirmed the synergistic effect of the defined testosterone/estradiol ratio in PC12 cells mainly depend on the inhibitory activation of Traf6/TAK1 signaling pathway. Furthermore, we found that the defined testosterone/estradiol ratio could suppress the expression and ubiquitination of Traf6 protein through AR/ERα-mediated pathways. Finally, endogenous interactions of Traf6 with AR/ERα in PC12 cells were found using co-immunoprecipitation assays, and further verified how the defined testosterone/estradiol ratio plays a synergistic role in injury of PC12 cells. The current study demonstrated that an appropriate testosterone/estradiol ratio has a synergistic effect on PC12 cells injury induced by corticosterone through suppressing the activation of Traf6/TAK1 signaling pathway, suggesting that testosterone/estradiol might synergistically protect against neuronal apoptosis to ameliorate depressive symptoms.

Thrombotic and thromboembolic complications in patients diagnosed with coronavirus disease 2019 (COVID-19) are emerging as important sequelae that contribute to mortality, including disseminated intravascular coagulation, pulmonary embolism, deep vein thrombosis, ischemic stroke, and myocardial infraction. Reported incidence of thrombotic and thromboembolic complications in moderate/severe COVID-19 patients is from 21% to 49%, while even higher incidence in non-surviving COVID-19 patients. However, the underlying mechanism between thrombosis and COVID-19 is still unclear. Tissue-type plasminogen activator (tPA) plays an important role on initiating fibrinolysis by converting zymogen plasminogen to plasmin, a serine protease that degrades the fibrin clot, and therefore preventing excessive pathological blood clots. A homologous protein to plasminogen is apolipoprotein(a) [apo(a)], a major component of lipoprotein(a). The apo(a) inhibits fibrinolysis and exacerbates thrombosis through blocking the conversion from Glu-plasminogen to Lys-plasminogen, which has a higher binding affinity to fibrin and is a better substrate to tPA. The population distribution of plasma apo(a) level is positively skewed (most values are clustered around the left tail of the distribution close to zero), and the plasma apo(a) level in most people is less than 300 μg/mL. High plasma concentration of apo(a) (> 300 μg/mL), or genetic variants of LPA, the gene that encodes for apo(a), correlates with thrombotic cardiovascular risk and thromboembolic risk in many population-based clinical or genetic studies. To investigate the potential correlation between infection of SARS-COV-2 and thrombosis, we tested de-identified plasma samples collected from hospitalized patients with or without positivity of SARS-CoV-2 testing results and COVID-19 diagnosis (ICD10CM:U07.1) through the COVD-19 Tissue Bank at the Medical College of Wisconsin. The tPA enzymatic activity was measured by the release of p-nitroaniline chromophore from a plasmin-specific synthetic substrate with exogenous human plasminogen, with the intensity of color proportional to tPA activity. The apo(a) concentration is measured by ELISA capturing total apo(a) antigen. Our results show that the SARS-CoV-2-positive inpatients have higher plasma tPA concentration than the SARS-CoV-2 negative inpatients (6.0 versus 3.0 ng/mL, p In summary, our study shows lower tPA enzymatic activity and higher apo(a) concentration in SARS-CoV-2-positive hospitalized patients compared to SARS-CoV-2-negative hospitalized patients. Among the survived patients, the reduction of apo(a) concentration after recovering from COVID-19 is accordance with the increase of tPA enzymatic activity. Considering the role of apo(a) in inhibiting fibrinolysis through limiting tPA-mediated plasminogen to plasmin conversion, the alteration in apo(a) concentration provide a possible explanation of change of tPA activity in patients with severe COVID-19. Figure 1 Figure 1. Disclosures Baumann Kreuziger: CSL Behring: Consultancy; Quercegen Pharmaceuticals: Consultancy; Vaccine Injury Compensation Program: Consultancy.

We know surprisingly little about the sex differences in the neurobiology of cocaine addiction, except females are more susceptible to the rewarding effects of cocaine than their male counterparts. Only a handful of recent studies have examined the neurobiology of cocaine-induced conditioned place preference (CPP) memory among female rodents. We contribute to this emerging line of research by documenting sex differences in cocaine-associated memory and illustrating the underlying signaling pathways in five experiments. Rimonabant (Rim), a cannabinoid CB1 antagonist and inverse agonist, exerted a facilitating effect for low-dose cocaine and an impairing effect for high-dose cocaine CPP memory in male mice, as in our previous study, but not in female mice. Nor did we observe the effect exist among CB1 knockout male mice, which indicated that the CB1 receptors played a mediating role. We also found that the metabotropic glutamate receptor 5 (mGluR5) was located in the same signaling pathway as CB1 in male mice. To clarify the mechanisms behind the sex differences, we used ovariectomized (OVX) female mice with estradiol benzoate (EB) replacement. In the OVX female mice, we showed that Rim-alone and EB-alone, but not Rim-and-EB-combined, facilitated the low-dose cocaine CPP memory. Moreover, 4-hydroxytamoxifen (4-OHT), an estrogen receptor (ER) antagonist, blocked Rim's and EB's facilitating effect. Finally, 2-methyl-6-(phenylethynyl)pyridine (MPEP), an mGluR5 antagonist, partially blocked EB's facilitating effect. In sum, we identified sex-specific effects of Rim on cocaine-induced CPP memory and the respective signaling pathways: mGluR5-CB1 for male mice and ER-mGluR5-CB1 for female mice. These findings may have merits for the development of sex-specific treatment for cocaine addiction.

Remediation of polycyclic aromatic hydrocarbon (PAH) contamination in soil remains expensive and difficult. Sulfate radical advanced oxidation processes (SR-AOPs) can be used for in situ PAH oxidation but their efficiency and ecological impacts require evaluation. Here, we tested the remediation efficiency and ecological impacts of an SR-AOP combining sodium persulfate and ferrous sulfate (FS), the FS SR-AOP with the chelating agent citric acid (FS+CA), and the FS SR-AOP with chelating agent and the surfactant IGEPALCA-720 (FS+CA+IG) compared with natural attenuation (control, CK). We measured PAH, soil physicochemical properties (pH, soil organic matter [SOM]), and soil biological properties (polyphenol oxidase [PPO] activity, peroxidase [POD] activity, soil microbes) in contaminated soil samples after incubation with FS, FS+CA, FA+CA+IG, or CK for 1, 15, and 30 d. Compared with CK, all SR-AOPs significantly decreased PAH after 1 d, with FS+CA+IG showing the highest efficiency (80.8%) and PAH removal peaking at 15 d. FS+CA+IG treatment reduced SOM the least and soil pH the most; after 30 d, SOM recovered to ~80% of the level observed in CK, but soil pH decreased further. PPO and POD activities were highest after 15 and 30 d of FS+CA+IG treatment. Real-time quantitative PCR demonstrated that SR-AOPs significantly decreased quantities of PAH-degrading bacteria, soil bacteria, fungi, and actinobacteria at 1 d, but after 30 d, the microbes recovered to levels similar to those observed in CK, with no significant differences among SR-AOPs. SR-AOPs reduced bacterial diversity and changed the dominant phylum from Acidobacteria to Firmicutes. In summary, SR-AOP treatment with both the chelating agent and the surfactant produced the best PAH removal and least SOM destruction but the largest pH decrease, although some factors recovered with longer incubation. This study provides key information for improving PAH remediation and evaluating its ecological impact

Heat sink materials with superior thermal conductivity and excellent mechanical strength with low cost, are desirable for electronic packaging and thermal management in electronic and electrical engineering systems. In this work, the graphene paper (GP)/copper (Cu) composites were prepared by using a vacuum hot pressing. A zebra skin structure was constructed for improving the thermal transportation performance of GP/Cu composites. In virtue to its unique zebra skin structure, the ultrahigh thermal conductivity of 968 W m -1 K-1 was achieved for the GP/Cu composite at 70 vol% graphene loading. Furthermore, the GP/Cu composite retains high flexural strength (88 MPa) due to the good interface compatibility between the surface chemical treated GP and Cu paper. Our work provides a new method to significantly improve the in-plane thermal conductivity of thermal management materials.

Owing to the unfavorable wetting and density difference between graphene and copper, it remains challenging to achieve homogeneous dispersion of graphene for utilizing the unique nature of graphene in copper matrix composites. Here, we design an in-situ process to fabricate graphene-like carbon (GLC) reinforcing copper matrix composites: GLC can be directly fabricated on commercial copper particles using modified PECVD method followed by vacuum hot pressing, which is high-efficiency and can be massively produced for graphene reinforced metal matrix composites in industrial level. After hot pressing, the GLC with ultralow content (170 to 350 ppm) can be uniformly dispersed and tightly embedded within the copper matrix. A remarkable thermal conductivity enhancement efficiency of 85% and enhanced thermal conductivity (439 W m−1 K−1), accompanied by the higher wear resistance, can be obtained in our GLC reinforced copper matrix composites. In actual arc ablation performance measurement, the breakdown strength and relative arc ablation resistance of GLC/Cu composites can be significantly improved by 106.5% and 33.3% than pure copper, respectively, demonstrating GLC/Cu composites a promising candidate for application as high voltage electrical contacts.

Apolipoprotein A5 (apoA5) has been implicated in the formation of hepatocyte lipid droplets, a histological hallmark of non-alcoholic fatty liver disease (NAFLD). Recent evidence demonstrated that liver X receptor α (LXRα), a transcription factor involved in down-regulation of APOA5 mRNA, is activated by AMP-activated protein kinase (AMPK) that contributes to metformin-related antihyperglycemic effects. In this study we investigated the role of apoA5 and AMPK/LXRα signaling pathway in metformin-related improvement of NAFLD. Leptin-deficient (ob/ob) obese mice with NAFLD were treated with metformin, and signaling pathways were compared with non-metformin treated mice. Additionally, we determined cellular apoA5 and triglyceride (TG) levels in mouse hepatocytes in vitro and the effects of metformin, with or without an AMPK inhibitor or LXRα siRNA, on these levels. We found that metformin dose-dependently ameliorated hepatosteatosis and liver dysfunction in ob/ob mice, with a significant reduction in hepatic apoA5 expression and TG level. Metformin also dose-dependently increased phosphorylation of hepatic AMPK and LXRα in ob/ob mice. Similarly, metformin decreased apoA5 expression and TG level in mouse hepatocytes, with increased phosphorylation of cellular AMPK and LXRα. Addition of AMPK inhibitor or siRNA knockdown of LXRα significantly attenuated metformin-induced down-regulation of cellular apoA5 expression and TG level. AMPK inhibitor also significantly inhibited metformin-induced LXRα phosphorylation in these hepatocytes. Therefore, our findings indicate that metformin improves obesity-related NAFLD via inhibition of hepatic apoA5 synthesis as part of the AMPK/LXRα signaling pathway.

Nanotechnology has been applied to many aspects of human life. Meanwhile, concerns regarding the toxicity of engineered nanomaterials to the environment have also been growing. Herein, an economic and convenient approach based on quantitative structure–activity relationship for nanomaterials (nano-QSAR) was proposed to evaluate the cytotoxicity of metal oxide nanoparticles (MONPs) to E. coli. Six molecular descriptors of 17 MONPs were selected and calculated using Gaussian98 software and DFT-B3LYP method on the LANL2DZ basis set. Two multivariable models, linear and nonlinear, were built based on the calculated molecular descriptors using multiple linear regression (MLR) and support vector machine (SVM) methods, respectively. Results demonstrated that both models presented high reliability, good predictive performance, and fine generalization ability, with all R2values greater than 0.84. It was also revealed that the lowest unoccupied molecular orbital (LUMO) and molar heat capacity (Cp) were the two key descriptors influencing the cytotoxicity of MONPs.

A manganese complex with a porphyrin-like ligand that catalyzes the highly chemoselective and enantioselective oxidation of heteroaromatic sulfides, including imidazole, benzimidazole, indole, pyridine, pyrimidine, pyrazine, sym-triazine, thiophene, thiazole, benzothiazole, and benzoxazole, with hydrogen peroxide is described, furnishing the corresponding sulfoxides in good to excellent yields and enantioselectivities (up to 90% yield and up to >99% ee) within a short reaction time (0.5 h). The practical utility of the method has been demonstrated in the gram-scale synthesis of chiral sulfoxide. Mechanistic studies, performed with 18O-labeled water (H218O), hydrogen peroxide (H218O2), and cumyl hydroperoxide, reveal that a high-valent manganese–oxo species is generated as the oxygen atom delivering agent via carboxylic acid assisted heterolysis of O–O bonds. Density functional theory (DFT) calculations were also carried out to give further insight into the mechanism of manganese-catalyzed sulfoxidation. O...

Here meso-N/C-900 derived from polypyridyl ligand DAA has been developed as a metal-free catalyst, for the first time, exhibiting good performance in catalytic ammoxidation of alcohols to nitriles. Systematic characterization suggests that the accessible mesopores and the effective pyridinic/pyrrolic-N are responsible for the unprecedented performance.