Two-dimensional hierarchical porous carbon sheets (FHPCs) have been prepared by using nano-MgO sheet as template and coal tar pitch as carbon precursor coupled with KOH activation. The weight ratio ...of pitch with potassium hydroxide (KOH) exerts a marked effect on the porosity of the carbon. The FHPCs materials show some advantages for electrochemical energy storage including a specific surface area of 1454∼1604m2g−1, sheet structure, hierarchical porosity with macro/meso/micropores, rich O-doping (19wt%). Resulting from the multiple synergistic effects of these advantages, the FHPC1:2 electrode can achieve a high capacitance of 290Fg−1 and 250Fg−1at 1Ag−1, 20Ag−1, respectively, and excellent rate capability with 86% retention rate in 6M KOH electrolyte. The FHPC1:2 symmetric supercapacitor displays a high energy density of 20.28 Wh kg−1at a power density of 873Wkg−1 and retains as high as 8.87 Wh kg−1at 6389Wkg−1 in 1M Na2SO4 electrolyte. Our work demonstrates that KOH activation coupled with flake-like MgO template can act as an excellent route to prepare hierarchical porous carbon sheets from coal tar pitch for high performance supercapacitors.
Flexible electronics are drawing tremendous interest for various applications in wearable healthcare biomonitoring, on‐demand therapy, and human–machine interactions. However, conventional plastic ...substrates with uncomfortableness, mechanical mismatches, and impermeability have limited the application of flexible on‐skin electronic devices for healthcare biomonitoring and on‐demand therapy. Herein, flexible breathable electronic devices with the capabilities of real‐time temperature sensing and timely on‐demand anti‐infection therapy at wound sites are presented. These devices are assembled from a crosslinked electrospun moxifloxacin hydrochloride (MOX)‐loaded thermoresponsive polymer nanomesh film with a conductive pattern. The conductive polymer nanomesh film demonstrates excellent flexibility, reliable breathability, and robust environmental stability. Furthermore, the assembled temperature sensor displays a linear relationship between the electrical resistance and temperature, potentially enabling real‐time biomonitoring of tissue temperature at the wound site. Smart artificial electronic skins (E‐skins) are assembled from the thermoresponsive polymer nanomesh film for spatial touching sensing mapping of temperature changes. Furthermore, the flexible temperature sensor is coupled with a wireless transmitter for real‐time wireless temperature monitoring. Notably, the thermoresponsive polymer nanomesh film can also be assembled as a highly efficient flexible heater to trigger the on‐demand release of antibiotics loaded in the fibers to eliminate bacterial colonization in the wound site once infection has occurred.
Flexible breathable nanomesh electronic devices with the capabilities of real‐time temperature sensing and timely on‐demand therapy at wound sites are assembled. They exhibit excellent flexibility, reliable breathability, environmental stability, highly sensitive wireless temperature sensing capability to potentially monitor tissue temperature, temperature sensing mapping ability when assembled as electronic skin, and robust heating efficiency to trigger on‐demand drug release at the wound site.
With recent advancements in the automotive world and the introduction of autonomous vehicles, automotive security has become a real and important issue. Modern vehicles have tens of Electronic ...Control Units (ECUs) connected to in-vehicle networks. As a de facto standard for in-vehicle network communication, the Controller Area Network (CAN) has become a target of cyber attacks. Anomaly-based Intrusion Detection System (IDS) is considered as an effective approach to secure CAN and detect malicious attacks. Currently, there are two primary approaches used for intrusion detection: rule-based and machine learning-based. Rule-based approach is efficient but limited in the detection accuracy while machine learning-based detection has comparably higher detection accuracy but higher computation cost at the same time. In this paper, we propose a novel hybrid IDS that combines the benefits of both rule-based and machine learning-based approaches. More specifically, we use machine learning methods to achieve a high detection rate while keeping the low computational requirement by offsetting the detection with a rule-based component. Our experiments with CAN traces collected from four different vehicle models demonstrate the effectiveness and efficiency of the proposed hybrid IDS.
Nonalcoholic fatty liver disease (NAFLD), a series of liver metabolic disorders manifested by lipid accumulation within hepatocytes, has become the primary cause of chronic liver diseases worldwide. ...About 20%-30% of NAFLD patients advance to nonalcoholic steatohepatitis (NASH), along with cell death, inflammation response and fibrogenesis. The pathogenesis of NASH is complex and its development is strongly related to multiple metabolic disorders (e.g. obesity, type 2 diabetes and cardiovascular diseases). The clinical outcomes include liver failure and hepatocellular cancer. There is no FDA-approved NASH drug so far, and thus effective therapeutics are urgently needed. Bile acids are synthesized in hepatocytes, transported into the intestine, metabolized by gut bacteria and recirculated back to the liver by the enterohepatic system. They exert pleiotropic roles in the absorption of fats and regulation of metabolism. Studies on the relevance of bile acid disturbance with NASH render it as an etiological factor in NASH pathogenesis. Recent findings on the functional identification of bile acid receptors have led to a further understanding of the pathophysiology of NASH such as metabolic dysregulation and inflammation, and bile acid receptors are recognized as attractive targets for NASH treatment. In this review, we summarize the current knowledge on the role of bile acids and the receptors in the development of NAFLD and NASH, especially the functions of farnesoid X receptor (FXR) in different tissues including liver and intestine. The progress in the development of bile acid and its receptors-based drugs for the treatment of NASH including bile acid analogs and non-bile acid modulators on bile acid metabolism is also discussed.
Heterodimeric tryptophan‐containing diketopiperazines (HTDKPs) are an important class of bioactive secondary metabolites. Biosynthesis offers a practical opportunity to access their bioactive ...structural diversity, however, it is restricted by the limited substrate scopes of the HTDKPs‐forming P450 dimerases. Herein, by genome mining and investigation of the sequence‐product relationships, we unveiled three important residues (F387, F388 and E73) in these P450s that are pivotal for selecting different diketopiperazine (DKP) substrates in the upper binding pocket. Engineering these residues in NasF5053 significantly expanded its substrate specificity and enabled the collective biosynthesis, including 12 self‐dimerized and at least 81 cross‐dimerized HTDKPs. Structural and molecular dynamics analysis of F387G and E73S revealed that they control the substrate specificity via reducing steric hindrance and regulating substrate tunnels, respectively.
The biosynthesis of heterodimeric tryptophan‐containing diketopiperazines (HTDKPs) is restricted by the limited substrate scopes of the HTDKP‐forming P450 dimerases. Engineering of three important residues (F387, F388, and E73) in NasF5053 significantly expanded its substrate specificity and enabled the collective biosynthesis of at least 93 HTDKPs.
A novel and efficient one-pot three-enzyme cascade method for the synthesis of β-alanine from maleic acid was developed. Two recombinant E. coli strains were constructed. The E. coli (MaiA-AspA) ...co-expressing maleic cis-trans isomerase (MaiA) and L-aspartase (AspA) catalyzed the biotransformation of maleic acid to L-aspartate via fumaric acid, and E. coli (ADC) expressing L-aspartate-α-decarboxylase (ADC) catalyzed the bioconversion of L-aspartate to β-alanine. After systematic optimization of reaction conditions for each strain, the whole cells of two strains were combined for one-pot synthesis of β-alanine. It was found that the ratio of the two kinds of cells as well as the cell amount play critical roles in the reaction rate and yield of β-alanine. Adding two kinds of cells in one-pot at the beginning of the reaction was better than adding step by step. Under optimal conditions, the concentration of β-alanine reached 751 mM after a 9 h reaction, corresponding to a 93.9% yield and 178 g/L/d space-time yield. The developed new route showed application potential for green and efficient biosynthesis of β-alanine from a cheap substrate by tandem biocatalysts.
To determine the expressions of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) genes in human and mouse ocular cells and comparison to ...other tissue cells.
Human conjunctiva and primary pterygium tissues were collected from pterygium patients who underwent surgery. The expression of ACE2 and TMPRSS2 genes was determined in human primary conjunctival and pterygium cells, human ocular and other tissue cell lines, mesenchymal stem cells as well as mouse ocular and other tissues by reverse transcription-polymerase chain reaction (RT-PCR) and SYBR green PCR.
RT-PCR analysis showed consistent expression by 2 ACE2 gene primers in 2 out of 3 human conjunctival cells and pterygium cell lines. Expression by 2 TMPRSS2 gene primers could only be found in 1 out of 3 pterygium cell lines, but not in any conjunctival cells. Compared with the lung A549 cells, similar expression was noted in conjunctival and pterygium cells. In addition, mouse cornea had comparable expression of Tmprss2 gene and lower but prominent Ace2 gene expression compared with the lung tissue.
Considering the necessity of both ACE2 and TMPRSS2 for SARS-CoV-2 infection, our results suggest that conjunctiva would be less likely to be infected by SARS-CoV-2, whereas pterygium possesses some possibility of SARS-CoV-2 infection. With high and consistent expression of Ace2 and Tmprss2 in cornea, cornea rather than conjunctiva has higher potential to be infected by SARS-CoV-2. Precaution is necessary to prevent possible SARS-CoV-2 infection through ocular surface in clinical practice.
Cyclopropanes represent a class of versatile building blocks in modern organic synthesis. While the release of ring strain offers a thermodynamic driving force, the control of selectivity for C-C ...bond cleavage and the subsequent regiochemistry of the functionalization remains difficult, especially for unactivated cyclopropanes. Here we report a photoredox-coupled ring-opening oxo-amination of electronically unbiased cyclopropanes, which enables the expedient construction of a host of structurally diverse β-amino ketone derivatives. Through one electron oxidation, the relatively inert aryl cyclopropanes are readily converted into reactive radical cation intermediates, which in turn participate in the ensuing ring-opening functionalizations. Based on mechanistic studies, the present oxo-amination is proposed to proceed through an S
2-like nucleophilic attack/ring-opening manifold. This protocol features wide substrate scope, mild reaction conditions, and use of dioxygen as an oxidant both for catalyst regeneration and oxygen-incorporation. Moreover, a one-pot formal aminoacylation of olefins is described through a sequential cyclopropanation/oxo-amination.
Hepatocellular carcinoma (HCC) is a common malignant tumor with characteristics of poor prognosis, high morbidity and mortality worldwide. In particular, only a few systemic treatment options are ...available for advanced HCC patients, and include sorafenib and the recently described atezolizumab plus bevacizumab regimen as possible first-line treatments. We here propose acteoside, a phenylethanoid glycoside widely distributed in many medicinal plants as a potential candidate against advanced HCC.
Cell proliferation, colony formation and migration were analyzed in the three human HCC cell lines BEL7404, HLF and JHH-7. Angiogenesis assay was performed using HUVESs. The BEL7404 or JHH-7 xenograft nude mice model was established to analyze the possible antitumor effects of acteoside. qRT-PCR and western blotting were used to reveal the potential antitumor mechanisms of acteoside.
Acteoside inhibited cell proliferation, colony formation and migration in all the three human HCC cell lines BEL7404, HLF and JHH-7. The prohibition of angiogenesis by acteoside was revealed by the inhibition of tube formation and cell migration of HUVECs. The combination of acteoside and sorafenib produced stronger inhibition of cell colony formation and migration of the HCC cells as well as of angiogenesis of HUVECs. The in vivo antitumor efficacy of acteoside was further demonstrated in BEL7404 or JHH-7 xenograft nude mice model, with an enhancement when combined with sorafenib in inhibiting the growth of JHH-7 xenograft. Further treatment of JHH-7 cells with acteoside revealed an increase in the level of tumor suppressor protein p53 as well as a decrease of kallikrein-related peptidase (KLK1, 2, 4, 9 and 10) gene level with no significant changes of the rest of KLK1-15 genes.
Acteoside exerts an antitumor effect possibly through its up-regulation of p53 levels as well as inhibition of KLK expression and angiogenesis. Acteoside could be useful as an adjunct in the treatment of advanced HCC in the clinic.
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