ATAXIA TELANGIECTASIA MUTATED PROTECTS AGAINST LIPOPOLYSACCARIDE-INDUCED BLOOD-BRAIN BARRIER DISRUPTION BY REGULATING ATK/DRP1-MEDIATED MITOCHONDRIAL HOMEOSTASIS.

ABSTRACT: Background: Protein kinase ataxia telangiectasia mutated (ATM) regulates the function of endothelial cells and responds quickly to endotoxin. However, the function of ATM in lipopolysaccharide (LPS)-induced blood-brain barrier (BBB) disruption remains unknown. This study aimed to investigate the role and underlying mechanism of ATM in the regulation of the BBB function in sepsis. Methods: We used LPS to induce BBB disruption in vivo and to establish an in vitro model of cerebrovascular endothelial cells. Blood-brain barrier disruption was assessed by measuring Evans blue leakage and expression of vascular permeability regulators. To investigate the role of ATM, its inhibitor AZD1390 and clinically approved doxorubicin, an anthracycline that can activate ATM, were administered as scheduled. To explore the underlying mechanism, protein kinase B (AKT) inhibitor MK-2206 was administered to block the AKT/dynamin-related protein 1 (DRP1) pathway. Results: Lipopolysaccharide challenge induced significant BBB disruption, ATM activation, and mitochondrial translocation. Inhibiting ATM with AZD1390 aggravated BBB permeability as well as the following neuroinflammation and neuronal injury, while activation of ATM by doxorubicin abrogated these defects. Further results obtained in brain microvascular endothelial cells showed that ATM inhibition reduced the phosphorylation of DRP1 at serine (S) 637, promoted excessive mitochondrial fission, and resulted in mitochondrial malfunction. By activating ATM, doxorubicin increased the protein binding between ATM and AKT and promoted the phosphorylated activation of AKT at S473, which could directly phosphorylate DRP1 at S637 to repress excessive mitochondrial fission. Consistently, the protective role of ATM was abolished by the AKT inhibitor MK-2206. Conclusions: Ataxia telangiectasia mutated protects against LPS-induced BBB disruption by regulating mitochondrial homeostasis, at least in part, through the AKT/DRP1 pathway.

Influence of the Maillard Reaction on Properties of Air-Assisted Electrospun Gelatin/Zein/Glucose Nanofibers.

To develop biodegradable, sustainable, and environment-friendly functional food-packaging materials, gelatin/zein/glucose nanofibers were fabricated through air-assisted electrospinning and then crosslinked by the Maillard reaction under mild conditions (60 °C and 50% relative humidity) in this study. Compared to traditional electrospinning, air-assisted electrospinning increased the yield of nanofibers by 10 times, and the average diameter from 263 nm to 664 nm, while the airflow facilitated uniform and smooth nanofiber formation. During the Maillard reaction in 0-5 days, the gelatin/zein/glucose showed no morphology change. Fourier transform infrared spectra analysis indicated that gelatin interacted with zein through hydrogen bonding and the occurrence of the Maillard reaction among the protein and glucose molecules. After four days of Maillard reaction, the nanofibers presented higher thermal stability, the most hydrophobic surface (water contact angle: 133.6°), and stiffer network structure (elastic modulus of 38.63 MPa, tensile strength of 0.85 MPa). Overall, Maillard-reaction-crosslinked gelatin/zein/glucose nanofibers showed favorable physical properties, which suggests their potential for application in food-active packaging.

Autotandem Catalyst: From Acylhydrazones to N',N'-Methylaliphatic Acylhydrazides via Transfer Hydrogenation/N-Methylation with Methanol Catalyzed by a Cp* Iridium Complex Bearing a Functional Ligand.

A new strategy for the synthesis of N',N'-methylaliphatic acylhydrazides from acylhydrazones via transfer hydrogenation/N-methylation with methanol as both the hydrogen source and the methylating reagent has been proposed and accomplished. In the presence of [Cp*Ir(2,2'-bpyO)(H2O)] (1 mol %) and Cs2CO3 (0.3 equiv), a range of desired products were obtained in high yields. It was also confirmed that functional units in the bpy ligand of the catalyst are crucial for the catalytic activity of iridium complexes. The mechanistic investigation and practical application of the present catalytic system were also presented.

Comparative Study on the Generation and Characteristics of Debris Induced by Fretting and Sliding.

Objectives: The aim of the present work was to comparatively investigate the generation and characteristics of fretting and sliding wear debris produced by CuNiAl against 42CrMo4. Methods: Tribological tests were conducted employing a self-developed tribometer. Most experimental conditions were set the same except for the amplitudes and number of cycles. Morphological, chemical, microstructural and dimensional features of the worn area and debris were investigated using optical microscope (OM), X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) and a laser particle sizer. Outcomes: Not only wear scar profiles but also the wear debris color, distribution and generated amount under fretting and sliding wear modes were quite different, which can be attributed to the significant difference in wear mechanisms. Particle size analysis indicates that the fretting debris has a smaller size distribution range; the biggest detected fretting and sliding wear debris sizes were 141 µm and 355 µm, respectively. Both fretting and sliding debris are mainly composed of copper and its oxides, but the former shows a higher oxidation degree.

The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis.

Sepsis is a heterogeneous syndrome induced by a dysregulated host response to infection. Glycolysis plays a role in maintaining the immune function of macrophages, which is crucial for severely septic patients. However, how the pathways that link glycolysis and macrophages are regulated is still largely unknown. Here, we provide evidence to support the function of KLF14, a novel Krüppel-like transcription factor, in the regulation of glycolysis and the immune function of macrophages during sepsis. KLF14 deletion led to significantly increased mortality in lethal models of murine endotoxemia and sepsis. Mechanistically, KLF14 decreased glycolysis and the secretion of inflammatory cytokines by macrophages by inhibiting the transcription of HK2. In addition, we confirmed that the expression of KLF14 was upregulated in septic patients. Furthermore, pharmacological activation of KLF14 conferred protection against sepsis in mice. These findings uncover a key role of KLF14 in modulating the inflammatory signaling pathway and shed light on the development of KLF14-targeted therapeutics for sepsis.

Demalonylation of DDX3 by Sirtuin 5 promotes antiviral innate immune responses.

Rationale: Hosts defend against viral infection by sensing viral pathogen-associated molecular patterns and activating antiviral innate immunity through TBK1-IRF3 signaling. However, the underlying molecular mechanism remains unclear. Methods: SiRNAs targeting Sirt1-7 were transfected into macrophages to screen the antiviral function. Sirt5 deficient mice or macrophages were subjected to viral infection to assess in vivo and in vitro function of Sirt5 by detecting cytokines, viral replicates and survival rate. Immunoprecipitation, WesternBlot and luciferase reporter assay were used to reveal molecular mechanism. Results: In this study, we functionally screened seven Sirtuin family members, and found that Sirtuin5 (Sirt5) promotes antiviral signaling and responses. Sirt5 deficiency leads to attenuated antiviral innate immunity in vivo and in vitro upon viral infection by decreasing TBK1-IRF3 activation and type I IFN production. Sirt5 overexpression increased antiviral innate immunity. Mechanism investigation revealed that Sirt5 interacts with DDX3 and demalonylates DDX3, which is critical for TBK1-IRF3 activation. Mutation of the demalonylation lysine sites (K66, K130, and K162) of DDX3 increased ifnß transcription. Furthermore, the acetylation on lysine 118 of DDX3 positively regulated ifnß transcription, whereas Sirt5 could not deacetylate this site. Conclusion: Sirt5 promotes anti- RNA and DNA virus innate immune responses by increasing TBK1 signaling through demalonylating DDX3, which identifies a novel regulatory pathway of antiviral innate immune response.

Fabrication and characterization of dextran/zein hybrid electrospun fibers with tailored properties for controlled release of curcumin.

BACKGROUND: In recent years, there has been considerable interest in the use of biopolymer electrospun nanofibers for various food applications due to the biocompatibility, biodegradability, and high loading capacity. Herein, we fabricated and characterized novel hybrid electrospun fibers from dextran (50%, w/v) and zein (0-30%, w/v) solutions, and the effects of various zein concentrations on the properties of the hybrid electrospun fibers were investigated. RESULTS: When zein was added at low concentrations (5% and 10%), dextran and zein showed poor miscibility, as reflected by significantly decreased viscosity of the solutions, and the poor mechanical properties of the derived fiber membranes. When zein was added at medium concentrations (15-25%), hydrogen bonds were formed between dextran and zein molecules, as indicated by the red shift of Fourier-transform infrared bands and ß-sheet to α-helix structural transformations. The fiber membranes electrospun from a solution with 25% zein showed the most hydrophobic surface, with a water contact angle of 116.9°. The homogenous dispersion of dextran and zein resulted in improved mechanical properties for fibers electrospun from a solution with 30% zein. Curcumin encapsulating dextran/zein electrospun fibers exhibited effective radical scavenging activity and ferric reducing power, along with the desired controlled release behavior for curcumin delivery. CONCLUSION: Food grade dextran/zein hybrid electrospun fibers demonstrated tunable properties, and appear to be promising as delivery systems for bioactive and edible antimicrobial food packaging. © 2021 Society of Chemical Industry.

Preparation of discrete cage-like oxidized hollow carbon spheres with vertically aligned graphene-like nanosheet surface for high performance Pb2+ absorption.

A novel oxidized hollow carbon sphere (OHCS) as absorbent for the removal of Pb2+ was fabricated from the mixture of coal-tar pitch and aluminum isopropoxide followed by nitric acid oxidation. The as-prepared OHCSs were characterized by FESEM, TEM, BET, TG, FTIR and XPS, and meanwhile the effects of adsorption conditions on the Pb2+ removal were investigated by batch experiments. Results show that the OHCSs prepared possess discrete cage-like structures and well-defined inner/outer surface features, exhibiting vertically aligned graphene-like nanosheets on their surfaces with mesoporous nature and high hydrophobicity. The maximum absorption capacity for Pb2+ of the OHCSs can reach 280.79 mg g-1 at the optimum condition. The adsorption kinetic of Pb2+ onto the OHCSs was found to be well modeled by pseudo-second-order kinetic model, and the experimental equilibrium data were represented well by Langmuir isotherm model. Moreover, the OHCSs still exhibit excellent adsorption ability and stability after recycling 5 times, indicating its excellent reusability performance. Overall, the OHCS is a promising adsorbent for Pb2+ removal.

MicroRNA expression profile of urinary exosomes in Type IV lupus nephritis complicated by cellular crescent.

BACKGROUND: Type IV lupus nephritis (LNIV) is a severe disease characterized by diffuse proliferative lesions, and its prognosis is worse with cellular crescent (LNIV-CC) involvement. Urinary exosomes have been shown to reflect the degree of kidney injury. This study was aimed to identify non-invasive diagnostic markers for LNIV-CC. We analysed the expression profile of microRNAs (miRNAs) isolated from urinary exosomes in patients with LNIV-CC and LNIV, and healthy individuals using high-throughput sequencing. RESULTS: A total of 66 differentially expressed miRNAs were identified, which were significantly enriched in 15 signalling pathways. Bioinformatic analysis revealed a co-expression network of miRNAs, predicted transcription factors and target mRNAs. Expression of three miRNAs including miR-3135b, miR-654-5p, and miR-146a-5p were further analysed and validated by reverse transcription-quantitative polymerase chain reaction. ROC analysis suggested these as candidate biomarkers for LNIV-CC. CONCLUSIONS: LNIV-CC has a unique miRNA expression profile of urinary exosome and complex regulatory network. miR-3135b, miR-654-5p and miR-146a-5p in urinary exosomes could be used as novel non-invasive diagnostic markers for LNIV-CC.

2-Benzoyl-amino-N-[5-(4-bromo-phen-yl)-1,3,4-thia-diazol-2-yl]ethanamide.

In the structure of the title compound, C(17)H(13)BrN(4)O(2)S, the dihedral angle between the two benzene rings is 38.5 (1)°; the angle between the 4-bromo-benzene and thia-diazole rings is 1.3 (1)°. The conformations of the N-H and C=O bonds are anti with respect to each other. The structure displays inter-molecular N-H⋯O and C-H⋯O hydrogen bonding, with both interactions leading to inversion dimers.

[Study on the strategy of interrupting schistosomiasis transmission in a hilly new endemic area of Taoyuan County].

OBJECTIVE: To develop a strategy for interrupting the transmission of schistosomiasis japonica in a hilly new endemic area. METHODS: Since 1996, chemotherapy with praziquantel (adult 40 mg/kg, child 50 mg/kg, cattle 30 mg/kg, once a year) on human beings in Taoyuan County who had ever contacted with infectious water and cattle which were herded in endemic situation was the major intervention, with focal control of Oncomelania snails in susceptible areas as supplementary one. RESULTS: The positive rate of stool examination for schistosomiasis in human and cattle reduced from 5.69% and 6.76% in 1996 to 0.04% and 0 in 2005 respectively. The positive rate of indirect hemagglutination test (IHA) in human dropped from 7.45% in 1996 to 1.61% in 2004. Though living snails were still found in most habitats, the density of infected snails decreased from 0.0036/0.11m2 in 1997 to 0 in 2005 and no infected snails were found since 2000. CONCLUSION: Due to less movement of human and cattle populations and the hilly area relatively isolated, chemotherapy combined with focal mollusciciding have been highly effective in eliminating the infection sources and interrupting transmission of schistosomiasis.