Photoactivated Controlled Dnazyme Platform for on-Demand Activation Sensitive Electrochemiluminescence mRNA Analysis.

Programming ultrasensitive and stimuli-responsive DNAzyme-based probes holds great potential for on-demand biomarker detection. Here, an optically triggered DNAzyme platform was reported for on-demand activation-sensitive electrochemiluminescence (ECL) c-myc mRNA analysis. In this design, the sensing and recognition function of the split DNAzyme (SDz) probe was silent by engineering a blocking sequence containing a photocleavable linker (PC-linker) group at a defined site that could be indirectly cleaved by 302 nm ultraviolet (UV) light. When the SDz probes were assembled on the Au nanoparticles and potassium (K) element doped graphitic carbon nitride nanosheet (K-doped g-C3N4) covered electrode, UV light activation induces the configurational switching and consequently the formation of an active DNAzyme probe with the help of target c-myc mRNA, allowing the cleavage of the substrate strand by magnesium ions (Mg2+). Thus, the release of a ferrocene (Fc)-labeled DNAzyme 2 strand contributed to an extreme ECL signal recovery. In the meantime, the released target c-myc mRNA combined another inactive SDz motif to form active DNAzyme and repeat the cyclic cleavage reaction, resulting in the signal amplification. Furthermore, according to the responses toward two other designed nPC-SDz and m-SDz probes, we demonstrated that controlled UV light mediated photoactivation of the DNAzyme biosensor "on demand" effectively constrained the ECL signal to the mRNA of interest. Moreover, false positive signals could also be avoided due to such a photoactivation design with UV light. Therefore, this study provided a simple methodology that may be broadly applicable for investigating the mRNA-associated physiological events that were difficult to access using traditional DNAzyme probes.

Integrating UPLC-Q-Orbitrap MS with serum pharmacochemistry network and experimental verification to explore the pharmacological mechanisms of Cynanchi stauntonii rhizoma et radix against sepsis-induced acute lung injury.

Introduction: Patients with sepsis are at an incremental risk of acute lung injury (ALI). Baiqian, also known as Cynanchi stauntonii rhizoma et radix (Csrer), has anti-inflammatory properties and is traditionally used to treat cough and phlegm. This study aimed to demonstrate the multicomponent, multitarget, and multi-pathway regulatory molecular mechanisms of Csrer in treating lipopolysaccharide (LPS)-induced ALI. Methods: The bioactive components of Csrer were identified by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). Active targets predicted from PharmMapper. DrugBank, OMIM, TTD, and GeneCards were used to identify potential targets related to ALI. Intersection genes were identified for Csrer against ALI. The PPI network was analysed to identify prime targets. GO and KEGG analyses were performed. A drug-compound-target-pathway-disease network was constructed. Molecular docking and simulations evaluated the binding free energy between key proteins and active compounds. The protective effect and mechanism of Csrer in ALI were verified using an ALI model in mice. Western blot, Immunohistochemistry and TUNEL staining evaluated the mechanisms of the pulmonary protective effects of Csrer. Results: Forty-six bioactive components, one hundred and ninety-two potential cross-targets against ALI and ten core genes were identified. According to GO and KEGG analyses, the PI3K-Akt, apoptosis and p53 pathways are predominantly involved in the "Csrer-ALI" network. According to molecular docking and dynamics simulations, ten key genes were firmly bound by the principal active components of Csrer. The "Csrer-ALI" network was revealed to be mediated by the p53-mediated apoptosis and inflammatory pathways in animal experiments. Conclusion: Csrer is a reliable source for ALI treatment based on its practical components, potential targets and pathways.

Saikosaponin a promotes neutrophil extracellular trap formation and bactericidal activity.

This study aimed to investigate the effects of SSa, one of the major triterpenoid saponins extracted from Radix bupleuri, on neutrophil extracellular trap (NET) formation and the mechanism associated with this process. Using Sytox green and immunofluorescence assays, we found SSa rapidly induced NET formation, which depended on NADPH oxidase (NOX)-independent ROS production and autophagy. Pharmacologic inhibitor studies indicated that ERK and PI3K/AKT signalling were also required for SSa-induced NET formation, whereas protein arginine deiminase 4 (PAD4) was not required. Furthermore, we found that SSa promoted neutrophil bactericidal activity mainly through NET formation. Based on flow cytometry and the Cell Counting Kit-8 (CCK-8) assays, the results demonstrated that SSa-induced NET formation occurred without neutrophil death. Taken together, these findings indicated that SSa could be a potential natural product to boost innate immune defense against pathogen attack via NET formation.

Efficient removal of cesium ions using Prussian blue loaded on magnetic porous biochar synthesized by one-step calcination.

Prussian blue (PB) is widely used for the selective removal of radioactive cesium ions (Cs+) from aqueous solutions. Due to its small size and easy dispersion in water, PB requires a carrier that is both inexpensive and easily separable. Magnetic porous biochar (MPBC) was formed by activating starch with FeCl3 through a one-step calcination method. MPBC can be used as a carrier for Prussian blue, which is easily separated from the solution. This composite material (PB/MPBC) has a rich pore structure and maintains effective surface area, which can facilitate the penetration of Cs+ into the adsorbent. Besides, PB/MPBC exhibits high selectivity and good adsorption capacity achieving a large removal capacity of 101.43 mg/g. Thus, this study provides a novel approach for preparing composites with efficient removal of Cs+.

Self-sacrificed BiOBr template-assisted synthesis of α-Bi2O3/Bi3O4Br heterojunctions with oxygen vacancies for enhanced photocatalytic nitrogen fixation.

The catalytic conversion of nitrogen to ammonia is one of the most significant processes in nature and the chemical industry. However, the traditional Haber-Bosch process of ammonia synthesis consumes substantial energy and emits a large amount of carbon dioxide. The efficiency of photocatalytic N2 activation is severely limited by the lack of N2 adsorption sites and poor carrier utilization. Herein, an efficient α-Bi2O3/Bi3O4Br heterojunction is proposed with a photocatalytic nitrogen fixation activity of 238.67 µmol·g-1·h-1. Compared with the BiOBr precursor, α-Bi2O3 and Bi3O4Br, the α-Bi2O3/Bi3O4Br heterojunction with oxygen vacancies can improve the adsorption and activation capacity of N2 and promote the separation efficiency of charge carrier pairs by accommodating photogenerated electrons under visible light through the mechanism of N-type semiconductors. Therefore, oxygen vacancies and heterojunction engineering of semiconductive nanomaterials provide a promising method for the rational design of photocatalysts to enhance the rate of ammonia synthesis under mild conditions.

Verbenalin alleviates acute lung injury induced by sepsis and IgG immune complex through GPR18 receptor.

Acute lung injury is significantly associated with the aberrant activation and pyroptosis of alveolar macrophages. Targeting the GPR18 receptor presents a potential therapeutic approach to mitigate inflammation. Verbenalin, a prominent component of Verbena in Xuanfeibaidu (XFBD) granules, is recommended for treating COVID-19. In this study, we demonstrate the therapeutic effect of verbenalin on lung injury through direct binding to the GPR18 receptor. Verbenalin inhibits the activation of inflammatory signaling pathways induced by lipopolysaccharide (LPS) and IgG immune complex (IgG IC) via GPR18 receptor activation. The structural basis for verbenalin's effect on GPR18 activation is elucidated through molecular docking and molecular dynamics simulations. Furthermore, we establish that IgG IC induces macrophage pyroptosis by upregulating the expression of GSDME and GSDMD through CEBP-δ activation, while verbenalin inhibits this process. Additionally, we provide the first evidence that IgG IC promotes the formation of neutrophil extracellular traps (NETs), and verbenalin suppresses NETs formation. Collectively, our findings indicate that verbenalin functions as a "phytoresolvin" to promote inflammation regression and suggests that targeting the C/EBP-δ/GSDMD/GSDME axis to inhibit macrophage pyroptosis may represent a novel strategy for treating acute lung injury and sepsis.

Boron Nitride Microspheres via Pyrolysis of Polymerized Precursors.

Microspheric BN materials have high application potential because they have better fluidity and dispersion ability to endow hexagonal boron nitride (h-BN) ceramics and h-BN/polymer composites with highly desired performance. In this work, a novel synthetic route to the BN microspheres has been developed by means of a controllable pyrolysis of polymerized spherical precursors. The precursor formation mechanism is proposed to be the F-127-induced self-assembling polymerization of a boric acid-melamine-formaldehyde (MF) colloid. It is found that ammonia-annealing of an air-pyrolysis (700 °C) intermediate causes higher BN phase transformation within final BN microspheres with more uniform diameter distribution compared to those of direct ammonia-pyrolysis of spherical precursors at the same temperatures of 1100 and 1500 °C. After ammonia-annealing and ammonia-pyrolyzed treatment at 1100 and 1500 °C, the obtained BN microspheres have a low specific surface area (SSA) property, but replacing part of melamine with dicyandiamide could increase their SSAs to more than 1000 m2/g. We believe that this new microspherical BN preparation with more facile and controllable operation would be well suited for industrialization.

Self-Powered DNAzyme Walker Enables Dual-Mode Biosensor Construction for Electrochemiluminescence and Electrochemical Detection of MicroRNA.

Herein, an electrochemiluminescence (ECL) and electrochemical (EC) dual-mode biosensor platform with a self-powered DNAzyme walking machine was established for accurate and sensitive detection of miRNA-21. By employing a magnesium ion (Mn2+)-dependent DNAzyme cleavage cycling reaction, the walking machine was built by assembling DNAzyme walking strands and ferrocene (Fc)-labeled substrate strands on the Au nanoparticles and graphitic carbon nitride nanosheet (g-C3N4 NS)-covered electrode. The DNAzyme walking strand was first prohibited by a blocker strand. After the addition of target miRNA-21 and Mn2+, the DNAzyme walker could be activated and produce autonomous movements along the electrode track fueled by Mn2+-dependent DNAzyme-catalyzed substrate cleavage without additional energy supply. Notably, each walking step resulted in the cleavage of a substrate strand and the release of a Fc-labeled DNA strand fragment, allowing us to acquire an extreme ECL signal recovery of g-C3N4 inhibited by Fc. Meanwhile, numerous Fc-labeled DNA fragments escaped from the surface of the electrode, directly producing an obvious decrease in the square wave voltammetry (SWV) signal from Fc on the same sensing platform. This work not only avoided difficultly assembling various signal indicators but also significantly improved the sensitivity through using self-powered DNAzyme-walker amplification. Moreover, the proposed design employed the same reaction to produce two signal output modes, which could eliminate the interference from diverse reactive pathways on the outcome to mutually improve the accuracy. Therefore, the dual-mode miRNA-21 biosensor exhibited wide detection ranges of 100 aM to 100 nM with low detection limits of 54.3 and 78.6 aM by ECL and SWV modes, respectively, which provided an efficient and universal biosensing approach with extensive applications in early disease diagnosis and bioanalysis.

Enhanced adsorption capacity of tetracycline on porous graphitic biochar with an ultra-large surface area.

Excessive tetracycline in the water environment may lead to the harming of human and ecosystem health. Removing tetracycline antibiotics from aqueous solution is currently a most urgent issue. Porous graphitic biochar with an ultra-large surface area was successfully prepared by a one-step method. The effects of activation temperature, activation time, and activator dosage on the structural changes of biochar were investigated by scanning electron microscopy, Brunauer-Emmett-Teller, X-ray powder diffraction, and Raman spectroscopy. The effect of the structure change, adsorption time, temperature, initial pH, and co-existing ions on the tetracycline removal efficiency was also investigated. The results show that temperature had the most potent effect on the specific surface area, pore structure, and extent of graphitization. The ultra-large surface area and pore structure of biochar are critical to the removal of tetracycline. The q e of porous graphitic biochar could reach 1122.2 mg g-1 at room temperature. The calculations of density functional theory indicate that π-π stacking interaction and p-π stacking interaction can enhance the tetracycline adsorption on the ultra-large surface area of graphitic biochar.

Highly Multifunctional Performances of Boron Nitride Nanosheets/Polydimethylsiloxane Composite Foams.

Although this kind of hexagonal boron nitride (h-BN)-filled polydimethylsiloxane (PDMS) multifunctional composite foam has been greatly expected, its development is still relatively slow as a result of the limitation of synthetic challenge. In this work, a new foaming process of BNNSs-PDMS, alcohol, and water three-phase emulsion system is employed to synthesize a series of high-quality BNNSs/PDMS composite foams (BSFs) filled with highly functional and uniformly distributed BNNSs. As a result of well-bonded interfaces between the BNNSs and PDMS, enhanced multiple functions of BSFs appeared. The BSFs can show complete resilience at a compressive strain of 90% and only 3.99% irreversible deformation after 100,000 compressing-releasing hyperelastic cycles at a strain of 60%. On the basis of their outstanding shape-memory properties, the maximum voltage value of compression-driven piezo-triboelectric (CDPT) responses of the BSFs is up to ∼20 V. Depending on the remarkable super-elastic and CDPT performances, the BSFs can be used for sensitive sensing of temperature difference and electromechanical responses. Also, in the range of 12-40 GHz, the BSF materials display ultralow dielectric constants between 1.1 and 1.4 with proper dielectric loss tangent values of <0.3 and exhibit an enhanced and broadened sound adsorption capacity ranging from 500 to 6500 Hz. Although BSFs have high porosities of >65%, their thermal conductivities can still reach up to 0.407 ± 0.039 W m-1 K-1. Moreover, the BSF materials display favorable thermal stability, obviously reduced coefficient of thermal expansion, and good flame retardancy. All of these properties render the BSFs as a new category of excellent multifunctional material.

One-Step Pyrolysis Fabrication of Magnetic Bagasse Biochar Composites with Excellent Lead Adsorption Performance.

In the present study, a magnetically separable adsorbent, manganese ferrite (MnFe2O4)/sugarcane bagasse biochar magnetic composites (MFSCBB-MCs), was fabricated through a one-step pyrolysis method. The characterization of the prepared adsorbents indicated that MnFe2O4 nanoparticles were successfully embedded into the biochar matrix, offering magnetic separability and increasing the negative charges on the surface relative to the pristine biochar. Batch adsorption tests indicated that the adsorption of lead on MFSCBB-MCs was pH- and dose-dependent. The experimental results were effectively fitted using the pseudo-second-order kinetic model (R 2 > 0.99) and the Langmuir isotherm equation (R 2 > 0.99), indicating the main chemisorption pathway and monolayer coverage process. Meanwhile, lead adsorption was found to be spontaneous and endothermic, as shown by the study of thermodynamic parameters. The maximum capacity, q m, calculated from the Langmuir model was 155.21 mg·g-1 at 25 °C, demonstrating excellent adsorption capability compared with several previously reported bagasse adsorbents. Based on adsorption mechanism analysis, physical adsorption, electrostatic attraction, and complexation were all involved in the lead(II) adsorption process on MFSCBB-MCs. Furthermore, the adsorbent was easily regenerated as indicated by the high magnetic separation and chemical desorption potential after five cycles, so it is a cost-effective and environmentally favorable adsorbent for wastewater lead removal.

Identification of immune-related endoplasmic reticulum stress genes in sepsis using bioinformatics and machine learning.

Background: Sepsis-induced apoptosis of immune cells leads to widespread depletion of key immune effector cells. Endoplasmic reticulum (ER) stress has been implicated in the apoptotic pathway, although little is known regarding its role in sepsis-related immune cell apoptosis. The aim of this study was to develop an ER stress-related prognostic and diagnostic signature for sepsis through bioinformatics and machine learning algorithms on the basis of the differentially expressed genes (DEGs) between healthy controls and sepsis patients. Methods: The transcriptomic datasets that include gene expression profiles of sepsis patients and healthy controls were downloaded from the GEO database. The immune-related endoplasmic reticulum stress hub genes associated with sepsis patients were identified using the new comprehensive machine learning algorithm and bioinformatics analysis which includes functional enrichment analyses, consensus clustering, weighted gene coexpression network analysis (WGCNA), and protein-protein interaction (PPI) network construction. Next, the diagnostic model was established by logistic regression and the molecular subtypes of sepsis were obtained based on the significant DEGs. Finally, the potential diagnostic markers of sepsis were screened among the significant DEGs, and validated in multiple datasets. Results: Significant differences in the type and abundance of infiltrating immune cell populations were observed between the healthy control and sepsis patients. The immune-related ER stress genes achieved strong stability and high accuracy in predicting sepsis patients. 10 genes were screened as potential diagnostic markers for sepsis among the significant DEGs, and were further validated in multiple datasets. In addition, higher expression levels of SCAMP5 mRNA and protein were observed in PBMCs isolated from sepsis patients than healthy donors (n = 5). Conclusions: We established a stable and accurate signature to evaluate the diagnosis of sepsis based on the machine learning algorithms and bioinformatics. SCAMP5 was preliminarily identified as a diagnostic marker of sepsis that may affect its progression by regulating ER stress.

Enhanced Performance of Li-S Batteries due to Synergistic Adsorption and Catalysis Activity within a Separation Coating Made of Hybridized BNNSs/N-Doping Porous Carbon Fibers.

Lithium-sulfur (Li-S) batteries with high theoretical energy density are considered as the most promising devices for rechargeable energy-storage systems. However, their actual applications are rather limited by the shuttle effect of lithium polysulfides (LiPSs) and the sluggish redox kinetics. Here, the boron nitride nanosheets are homodispersedly embedded into N-doping porous carbon fibers (BNNSs/CHFs) by an electrospinning technique and a subsequent in situ pyrolysis process. The hybridized BNNSs/CHFs can be smartly designed as a multifunctional separation coating onto the commercial PP membrane to enhance the electrochemical performance of Li-S batteries. As a result, the Li-S batteries with extra BNNSs/CHF modification deliver a highly reversible discharge capacity of 830.4 mA h g-1 at a current density of 1 C. Even under 4 C, the discharge specific capacity can reach up to 609.9 mA h g-1 and maintain at 553.9 mA h g-1 after 500 cycles, showing a low capacity decay of 0.01836% per cycle. It is considered that the excellent performance is attributed to the synergistic effect of adsorption and catalysis of the BNNSs/CHF coating used. First, this coating can efficiently reduce the charge transfer resistance and enhance Li-ion diffusion, due to increased catalytic activity from strong electronic interactions between BNNSs and N-doping CHFs. Second, the combination of polar BNNSs and abundant pore structures within the hybridized BNNSs/CHF networks can highly facilitate an adsorption for LiPSs. Here, we believed that this work would provide a promising strategy to increase the Li-S batteries' performance by introducing hybridized BNNSs/N-doping carbon networks, which could efficiently suppress the LiPSs' shuttle effect and improve the electrochemical kinetics of Li-S batteries.

Synthesis of galactoglucomannan-based latex via emulsion polymerization.

This is the first time to report a facile strategy to fabricate galactoglucomannan-based latex with highly transparent, hydrophobic and flexible characteristics by combining etherification with subsequent emulsion polymerization. The allylated galactoglucomannans (A-GGM) and galactoglucomannan-based latexes (GGM-L) were prepared and their chemical structure, substitution degree, molecular weight, conversion rate, particle size and zeta potential were characterized by ATR-FTIR, 1HNMR, quantitative 13CNMR, HP-SEC, HPLC and zeta-sizer nanometer analyzer, respectively. Furthermore, the effects of substitution degree on film surface roughness and homogeneity, water vapor permeability (WVP) and thermal stability were evaluated by AFM, SEM, WVP and TGA, respectively. The optimal GGM-L film exhibited 91.3% transmittance and 0.43% haze, 117° water contact angle, 31.2% elongation at break and 30.9 MPa ultimate tensile stress. The bio-based content of the GGM-L may reach about 99 wt%, which provides a promising avenue for polyolefin-based latex replacement for paper and paperboard applications.

Effect of the organic sulfur source on the photocatalytic activity of CdS.

By controlling the species of the organic sulfur source, CdS samples were produced with different photocatalytic performances by a low-temperature solvothermal method. Different species of the organic sulfur source were chosen as the coordination agent to control the interactions in the crystal growth process. Among them, thioacetamide was the best coordination agent. The hydrophobic chain could be good for reducing the resistance of charge transfer, and increasing the rate of surface charge transfer and the lifetime of the photoexcited electrons. Benefiting from the hydrophobic chain, CdS shows an excellent photocatalytic hydrogen evolution rate of 943.54 µmol h-1 g-1 and a rhodamine B photocatalytic degradation rate of 99.1% in 60 min, which is superior to the photocatalysis of pure CdS prepared by many other methods.

3,4-dihydroxyphenylethyl alcohol glycoside reduces acetaminophen-induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosis.

APAP is one of the most commonly used antipyretic and pain medications, but excessive use can cause liver toxicity and damage. 3,4-dihydroxyphenylethyl alcohol glycoside (DAG) is a component isolated from Sargentodoxa cuneata known to have anti-apoptotic, anti-oxidation and anti-inflammatory effects. However, the effects of DAG on acute liver failure (ALF) are largely unknown. The purpose of this study is to study the protective effects and mechanism of DAG on APAP-induced ALF in mice. We established an ALF model in adult male pathogen-free C57BL/6 mice treated with APAP (300 mg/kg) by intraperitoneal injection and resolved by 24 h. Hematoxylin and eosin (HE) staining was used to evaluate the pathological changes in mouse liver tissue. The infiltration of neutrophils in liver tissue and reactive oxygen species (ROS) in AML12 cells were analyzed by flow cytometry. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were analyzed using relevant kits. Our results show that DAG reduced APAP-induced serum ALT and AST levels, histopathological changes, liver neutrophil infiltration and proinflammatory cytokines production, also attenuated the accumulation of MDA and the exhaustion of GSH, CAT and SOD. In vitro experiment indicated that DAG dose-dependently inhibited APAP-induced the levels of pro-inflammatory factors (IL-1ß and IL18), and reactive oxygen species (ROS) and preventing GSH depletion in mouse AML12 hepatocytes. More interestingly, DAG inhibited the expression of ERK, HO-1, NLRP3, Caspase1 (p20) and Gasdermin-D and upregulated the expression of GPX4 in liver tissues and AML12hepatocytes. Therefore, our results indicate that DAG may act as a potential agent to treat ALF induced by APAP by inhibiting hepatocyte ferroptosis and pyroptosis.

miR-3065-3p promotes stemness and metastasis by targeting CRLF1 in colorectal cancer.

BACKGROUND: Colorectal cancer is one of the most common malignancy in the world. It has been reported that cancer stem cells (CSCs) serve as the primary drivers of tumorigenesis and tumor progression. There is an urgent need to explore novel molecules that regulate CSCs or their signatures. Increasing evidence has shown that miRNAs are involved in tumorigenesis and progression. Here, we aim to explore the regulatory effect and mechanism of miR-3065-3p on the stemness of colorectal cancer. METHODS: The expression of miR-3065-3p in colorectal cancer and the association of miR-3065-3p expression with prognosis of patients with colorectal cancer were analyzed using TCGA dataset or clinical cases. Gain or loss of function in different models, including colorectal cancer cell lines and orthotopic xenograft or liver metastatic mouse model, were used to investigate the effects of miR-3065-3p on colorectal cancer stemness and metastasis in vitro and in vivo. Cancer stemness was analyzed by detecting the ability of migration and invasion, NANOG, OCT4, and SOX2 expression, ALDH activity and sphere formation. In addition, the interaction of miR-3065-3p and cytokine receptor-like factor 1 (CRLF1) was analyzed theoretically and identified by the luciferase reporter assay. Moreover, the correlation between CRLF1 expression and miR-3065-3p was analyzed in colorectal cancer tissues. Finally, the effect of CRLF1 on the stemness and metastasis of colorectal cancer in vitro and in vivo was assessed. RESULTS: In this report, we found that miR-3065-3p was overexpressed in colorectal cancer and that its high expression was associated with poor prognosis of patients with colorectal cancer. miR-3065-3p promotes the stemness and metastasis of colorectal cancer. Furthermore, CRLF1 was the downstream target of miR-3065-3p and inhibited the stemness of colorectal cancer. In addition, CRLF1 expression was negatively correlated with miR-3065-3p in colorectal cancer tissues. And, CRLF1 mediated the effects of miR-3065-3p on promoting stemness of colorectal cancer cells. CONCLUSION: Our data suggest that miR-3065-3p promoted the stemness and metastasis of colorectal cancer by targeting CRLF1. miR-3065-3p might serve as a promising prognostic marker as well as a therapeutic target for colorectal cancer.

FTY720 induces neutrophil extracellular traps via a NADPH oxidase-independent pathway.

FTY720 is an immunosuppressive agent which has been approved to treat multiple sclerosis (MS). The main object of the present study is to investigate whether FTY720 has the potential to induce the formation of neutrophil extracellular traps (NETs) in vitro. Using Sytox Green assay and fluorescence microscopy, our results showed that FTY720 trigged the NET formation. In contrast to classic NET formation induced by Phorbol 12-myristate 13-acetate (PMA), FTY720-induced NETs were detected earlier and independent of NADPH oxidase (NOX) activity. Pharmacological inhibitor experiments indicated that autophagy was also required for the NET formation induced by FTY720. Moreover, p38 and AKT inhibitor significantly suppressed the NET formation by FTY720, whereas ERK inhibitor had no effect, suggesting that FTY720-induced NETs depended on the activation of p38 and AKT. We further found that citrullination of histone H3 and peptidylarginine deiminase 4 (PAD4) did not mediated FTY720-induced NET formation. Interestingly, necroptosis signaling activation was involved in the vital NET formation by FTY720, however, plasma membrane rupture resulting from necroptosis was not a major component of NET formation described here. Collectively, these findings indicated that FTY720 could be a potential antibacterial drug to protect host against pathogen infection.

(-)-Syringaresinol suppressed LPS-induced microglia activation via downregulation of NF-κB p65 signaling and interaction with ERß.

Albiziae Cortex (AC) is a well-known traditional Chinese medicine with sedative-hypnotic effects and neuroprotective ability. However, the bioactive components of AC responsible for the neuro-protective actitivity remain unknown. Here, we investigated the anti-neuroinflammatory effects of (-)-syringaresinol (SYR) extracted from AC in microglia cells and wild-type mice. As a result, (-)-SYR significantly reduced lipopolysaccharide (LPS)-induced production of interleukin - 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin -1 beta (IL-1ß), cycloxygenase-2 (COX-2), and nitric oxide (NO) in BV2 microglia cells. (-)-SYR also significantly reduced M1 marker CD40 expression and increased M2 marker CD206 expression. Moreover, we found that (-)-SYR inhibited LPS-induced NF-κB activation by suppressing the translocation of NF-κB p65 into the nucleus in a concentration-dependent manner. Meanwhile, estrogen receptor ß (ERß) was found to be implied in the anti-inflammatory activity of (-)-SYR in BV2 microglia. In vivo experiments revealed that administration of (-)-SYR in mice significantly reduced microglia/astrocytes activation and mRNA levels of proinflammatory mediators. Taken together, our data indicated that (-)-SYR exerted the anti-neuroinflammatory effects by inhibiting NF-κB activation and modulation of microglia polarization, and via interaction with ERß. The anti-neuroinflammatory activity of (-)-SYR may provide a new therapeutic avenue for the treatment of brain diseases associated with inflammation.

Highly Multifunctional and Thermoconductive Performances of Densely Filled Boron Nitride Nanosheets/Epoxy Resin Bulk Composites.

In the development of hexagonal boron nitride (h-BN)-based polymeric composites with high thermal conductivity, it is always challenging to achieve a dense filling of h-BN fillers to form a desired high-density thermal transfer network. Here, a series of boron nitride nanosheets (BNNSs)/epoxy resin (EP) bulk composites filled with ultrahigh BNNSs content (65-95 wt %) is successfully constructed through a well-designed mechanical-balling prereaction combined with a general pressure molding method. By means of this method, the highly filled BNNSs fillers are uniformly dispersed and strongly bonded with EP within the composites. As a result, the densely BNNSs-filled composites can exhibit multiple performances. They have excellent mechanical properties, and their maximum compression strength is 30-97 MPa. For a BNNSs/EP composite with filling ultrahigh BNNSs fraction up to 90 wt %, its highly in-plane thermal conductivities (TC) are 6.7 ± 0.1 W m-1 K-1 (at 25 °C) to 8.7 ± 0.2 W m-1 K-1 (200 °C), respectively. In addition, the minimum coefficient of thermal expansion of BNNSs/EP composites is 4.5 ± 1.3 ppm/°C (only ∼4% of that of the neat EP), while their dielectric constants are basically located between 3-4 along with their dielectric loss tangent values exceptionally <0.3 in the ultrahigh frequency range of 12-40 GHz. Additionally, these BNNSs/EP composites exhibit remarkable cycle stability in heat transfer during heating and cooling processes because of their structural robustness. Thus, this type of densely BNNSs-filled BNNSs/EP composite would have great potential for further practical thermal management fields.