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To tackle the dissolution problem of boron carbide particles in silicon infiltration process, carbon-coated boron carbide particles were fabricated for the preparation of the reaction-bonded boron carbide composites. The carbon coating can effectively protect the boron carbide from reacting with liquid Si and their dissolution, thus maintaining the irregular shape of boron carbide particles and preventing the growth of boron carbide particles and reaction formed SiC regions. Furthermore, the nano-SiC particles, originated from the reaction of the carbon coating and the infiltrated Si, uniformly coated on the surfaces of boron carbide particles, thus forming a ceramic skeleton of the nano-SiC particles-coated and -bonded boron carbide particles. The Vickers hardness, flexural strength and fracture toughness of the composites can be increased by 26 %, 45 %, and 37 % respectively, by using carbon-coated boron carbide particles as raw materials.

Mimicking the nitric oxide (NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis (ISR) effectively. However, the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component. Herein, we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species (e.g., Cu-DOTA coordination complex) and glycocalyx-like component (e.g., heparin) to create a durable endothelium-mimicking surface. The stent surface was firstly coated with polydopamine (pDA), followed by a surface chemical cross-link with polyamine (pAM) to form a durable pAMDA coating. Using a stepwise grafting strategy, Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry. Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules, this proposed strategy could provide 62.4% bioactivity retention ratio of heparin, meanwhile persistently generate NO at physiological level from 5.9 ± 0.3 to 4.8 ± 0.4 × 10−10 mol cm−2 min−1 in 1 month. As a result, the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis, inflammation, and intimal hyperplasia, enhanced re-endothelialization, and hence efficiently reduced ISR., Graphical abstract Image 1, Highlights • A durable endothelium-mimicking coating was developed for surface bioengineering of cardiovascular stents. • The durable endothelium-mimicking surface was realized by stepwise grafting of Cu-DOTA and heparin on a robust coating. • The durable endothelium-mimicking coating endows the vascular stents with ability to dramatically reduce restenosis.

The dependence of interfacial contact resistance (ICR) on contact materials between cathode and interconnect is systematically studied under both isothermal oxidation and thermal cycling conditions. Three kinds of cathode current-collecting layer (CCCL) are used, (La,Sr) (Co,Fe)O3 (LSCF), LSCF+10%Ag, and Ag, and tested in a SUS430/CCCL/SUS430 sandwich structure to simulate the actual operation of the solid oxide fuel cells (SOFCs). Experimental results show that the ICR of LSCF+10%Ag exhibits the smallest value, in comparison with the specimens with LSCF and Ag paste, as well as the sample without a CCCL. For LSCF+10%Ag contact, the ICR increases from 0.0069 mΩ cm2 to 3.74 mΩ cm2 under an isothermal condition for 150 h, then increases from 3.74 mΩ cm2 to 10.79 mΩ cm2 after 15 thermal cycles. This work provides information for the understanding of possible mechanisms of performance degradation of SOFCs.

Application of extracorporeal circuits and indwelling medical devices has saved many lives. However, it is accompanied with two major complications: thrombosis and infection. To address this issue, we apply therapeutic nitric oxide gas (NO) and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions. Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions (Cu-DOTA) and dibenzylcyclooctyne- (DBCO-) modified antimicrobial peptide based on carbodiimide and click chemistry respectively. The integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth, but also catalytically generate NO from endogenous s-nitrosothiols (RSNO) to reduce adhesion and activation of platelets, preventing the formation of thrombus. We envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices, with reduced clinical complications associated with thrombosis and infection., Graphical abstract Image 1, Highlights • We report a bionic surface strategy for blood-contacting devices by integrating anti-thrombogenic and anti-microbial dual functions. Here, we engineer an endothelium-mimicking surface by combination of the nitric oxide (NO)-generating property and anti-microbial functions of a healthy endothelium, in which the generated gas signal molecule NO and the anti-microbial peptide (AMP) jointly provide synergistic effects against thrombogenicity and biofouling. • An endothelium-bionic surface strategy is proposed for tailoring surface multi-functionalities. • Carbodiimide and click chemistries were used for realizing synergistic tethering of NO-generating species and bio-clickable antimicrobial peptide. • The integration of NO and antimicrobial peptide imparts the tubing surface with anti-thrombogenic and anti-fouling dual functions. The integration of NO releasing and AMP tethering endows the tubing surface with significant anti-thrombogenic and anti-fouling properties. We envision that this bio-inspired surface engineering strategy will provide a promising solution to address the clinical issues.

Because of their good performance, including biocompatibility and mechanical properties, polyurethanes (PUs) are widely used in medical devices. However, undesired compatibility troubles, including thrombus, inflammation, and hyperplasia, still limit the applications of PUs. In this study, copper‐mediated polyurethane (PU‐Cu) materials with enzyme‐like catalysis were prepared. The PU‐Cu materials effectively catalysed the nitric oxide (NO) released from endogenous NO donors because of the glutathione peroxidase (GPx)‐like function of copper ion. The PU‐Cu materials were respectively evaluated via platelet adhesion and endothelial cell (EC), smooth muscle cell (SMC), and macrophage (MA) cultures. Scanning electron microscopy results showed that PU‐Cu materials significantly inhibited platelet adhesion and activation. Meanwhile, PU‐Cu materials not only promote the proliferation of EC but also inhibit SMC growth. Moreover, MA culture results intuitively stated the anti‐inflammatory ability of PU‐Cu. In addition, experimental samples were implanted into the subcutaneous tissue of Sprague Dawley rats. The anti‐inflammatory function of PU‐Cu was further confirmed by haematoxylin‐eosin staining results. With regard to their excellent biological performance, PU‐Cu materials are proposed for biocompatibility improvement of blood‐contacting materials, which should in turn provide new ideas for advanced medical devices.

Titanium dioxide (TiO2) has a long history of application in blood contact materials, but it often suffers from insufficient anticoagulant properties. Recently, we have revealed the photocatalytic effect of TiO2 also induces anticoagulant properties. However, for long-term vascular implant devices such as vascular stents, besides anticoagulation, also anti-inflammatory, anti-hyperplastic properties, and the ability to support endothelial repair, are desired. To meet these requirements, here, we immobilized silver nanoparticles (AgNPs) on the surface of TiO2 nanotubes (TiO2-NTs) to obtain a composite material with enhanced photo-induced anticoagulant property and improvement of the other requested properties. The photo-functionalized TiO2-NTs showed protein-fouling resistance, causing the anticoagulant property and the ability to suppress cell adhesion. The immobilized AgNPs increased the photocatalytic activity of TiO2-NTs to enhances its photo-induced anticoagulant property. The AgNP density was optimized to endow the TiO2-NTs with anti-inflammatory property, a strong inhibitory effect on smooth muscle cells (SMCs), and low toxicity to endothelial cells (ECs). The in vivo test indicated that the photofunctionalized composite material achieved outstanding biocompatibility in vasculature via the synergy of photo-functionalized TiO2-NTs and the multifunctional AgNPs, and therefore has enormous potential in the field of cardiovascular implant devices. Our research could be a useful reference for further designing of multifunctional TiO2 materials with high vascular biocompatibility., Graphical abstract Image 1, Highlights • Photo-functionalized TiO2NTs@Ag composites showed excellent vascular compatibility. • UV irradiation greatly improved the anticoagulant properties of the composites. • Moderately loaded AgNPs strongly inhibited SMCs and MAs, but weakly inhibited ECs.

Chloramines applied to control microfiltration and reverse osmosis (RO) membrane biofouling in potable reuse trains form the potent carcinogen, N-nitrosodimethylamine (NDMA). In addition to degrading other contaminants, UV-based advanced oxidation processes (AOPs) strive to degrade NDMA by direct photolysis. The UV/chlorine AOP is gaining attention because of its potential to degrade other contaminants at lower UV fluence than the UV/hydrogen peroxide AOP, although previous pilot studies have observed that the UV/chlorine AOP was less effective for NDMA control. Using dimethylamine (DMA) as a model precursor and secondary municipal wastewater effluent, this study evaluated NDMA formation during the AOP treatment via two pathways. First, NDMA formation by UV treatment of monochloramine (NH2Cl) and chlorinated DMA (Cl-DMA) passing through RO membranes was maximized at 350 mJ/cm2 UV fluence, declining at higher fluence, where NDMA photolysis outweighed NDMA formation. Second, this study demonstrated that chlorine addition to the chloramine-containing RO permeate during the UV/chlorine AOP treatment initiated rapid NDMA formation by dark breakpoint reactions associated with reactive intermediates from the hydrolysis of dichloramine. At pH 5.7, this formation was maximized at a chlorine/ammonia molar ratio of 3 (out of 0-10), conditions typical for UV/chlorine AOPs. At 700 mJ/cm2 UV fluence, which is applicable to current practice, NDMA photolysis degraded a portion of the NDMA formed by breakpoint reactions. Lowering UV fluence to ∼350 mJ/cm2 when switching to the UV/chlorine AOP exacerbates effluent NDMA concentrations because of concurrent NDMA formation via the UV/NH2Cl/Cl-DMA and breakpoint chlorination pathways. Fluence >700 mJ/cm2 or chlorine doses greater than the 3:1 chlorine/ammonia molar ratios under consideration for the UV/HOCl AOP treatment are needed to achieve NDMA control.

Aim: To dynamically analyze the differential m6A methylation during the progression and reversal of hepatic fibrosis. Materials & methods: We induced hepatic fibrosis in C57/BL6 mice by intraperitoneal injection of CCl4. The reversal model of hepatic fibrosis was established by stopping drug after continuous injection of CCl4. Dynamic m6A methylation was evaluated using MeRIP-Seq in the progression and reversal of hepatic fibrosis at different stages. Result: During the hepatic fibrosis, differential m6A methylation was mainly enriched in processes associated with oxidative stress and cytochrome metabolism, while differential m6A methylation was mainly enriched in processes associated with immune response and apoptosis in the hepatic fibrosis reversal. Conclusion: m6A methylation plays an important role in the progression and reversal of hepatic fibrosis.

The controllable release is necessary for ideal drug delivery technologies. Because of their high specific surface area and high porosity, titanium dioxide nanotubes (TNTs) have been widely used as drug carriers in medical devices. By loading copper as the catalyst, nitric oxide (NO) generation was facilitated by catalyzing the decomposition of renewable endogenous NO donors

The rapid re-endothelialization of the vascular stent surface is desirable for preventing thrombosis or reducing restenosis. Many biological factors that promote the biological behavior of endothelial cells have been used for the surface modification of stents. Vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, induces strong vascular growth. In this study, we investigated different VEGF concentrations (50 to 500 ng/ml) to determine the optimum concentration for biocompatibility. First, VEGF-loaded heparin/poly-l-lysine (Hep-PLL) nanoparticles were created by electrostatic interactions. Then, the VEGF-loaded nanoparticles were immobilized on dopamine-coated 316 L stainless steel (SS) surfaces. The physical and chemical properties of the modified surface were characterized and the biocompatibility was evaluated in vitro. The results indicated that the VEGF-loaded nanoparticles were immobilized successfully on the 316LSS surface, as evidenced by the results of Alcian Blue staining and water contact angle (WCA) measurements. The low platelet adhesion and activation indicated that the modified surfaces had good blood compatibility. The modified surfaces showed a good inhibitory effect on smooth muscle cells, indicating that they inhibited tissue hyperplasia. In addition, the modified surfaces significantly promoted endothelial cell adhesion, proliferation, migration, and biological activity, especially VEGF concentration was 350 ng/ml (NPV350). The optical VEGF concentration of the surface modified Hep-PLL nanoparticles was 350 ng/ml. The proposed method shows promise for potential applications for cardiovascular devices.

Integration of two or more biomolecules with synergetic and complementary effects on a material surface can help to obtain multi-functions for various biomedical applications. However, the amounts of biomolecules integrated and their physiological functions are compromised due to the limited surface anchoring sites. Herein, we propose a novel concept of film engineering strategy “from surface to bulk synergetic modification”. This new concept is realized by employing the surface amine groups of plasma polymerized allylamine (PPAm) film for grafting a molecule e.g., thrombin inhibitor, bivalirudin (BVLD), meanwhile its bulk amine groups is used as a universal depot for storing and releasing therapeutic nitric oxide (NO) gas as supplement to the functions of BVLD. It is demonstrated that such a “from surface to bulk synergetic modification” film engineering can impart the modified-substrates with anti-platelet and anti-coagulant dual functions, giving rise to a highly endothelium-mimetic thromboresistant property. We believe that our research provides a very promising strategy to deliver multifunctional surface versatilely that require NO release in combination with other properties, which will find broad biomedical applications in blood-contacting devices, and et al. Moreover, it also provides a brand-new film engineering strategy for tailoring surface multi-functionalities of a wide range of materials., Graphical abstract Image 1, Highlights • A concept of “from surface to bulk synergetic modification” is proposed for tailoring surface multi-functionalities. • The surface amine groups of plasma polymerized allylamine (PPAm) film were used for grafting bivalirudin. • The bulk amine groups of PPAm film is utilized as the universal depots for storing and releasing nitric oxide.

α-Glucosidase is a crucial enzyme for the production of isomaltooligosaccharide. In this study, a novel method comprising eosin Y (EY) and α-D-methylglucoside (AMG) in glass plates was tested for the primary screening of α-glucosidaseproducing strains. First, α-glucosidase-producing Aspergillus niger strains were selected on plates containing EY and AMG based on transparent zone formation resulting from the solubilization of EY by the hydrolyzed product. Conventional methods that use trypan blue (TB) and p-nitrophenyl-α-D-glucopyranoside (pPNP) as indicators were then compared with the new strategy. The results showed that EY-containing plates provide the advantages of low price and higher specificity for the screening of α-glucosidase-producing strains. We then evaluated the correlation between the hydrolytic activity of α-glucosidase and diffusion distance, and found that good linearity could be established within a 6-75 U/ml enzyme concentration range. Finally, the hydrolytic and transglycosylation activities of α-glucosidase obtained from the target isolates were determined by EY plate assay and 3,5-dinitrosalicylic acid-Saccharomyces cerevisiae assay, respectively. The results showed that the diameter of the transparent zone varied among isolates was positively correlated with α-glucosidase hydrolytic activity, while good linearity could also be established between α-glucosidase transglycosylation activity and non-fermentable reducing sugars content. With this strategy, 7 Aspergillus niger mutants with high yield of α-glucosidase from 200 obvious single colonies on the primary screen plate were obtained.

NO is the earliest discovered gas signal molecule which is produced by normal healthy endothelial cells, and it has many functions, such as maintaining cardiovascular homeostasis, regulating vasodilation, inhibiting intimal hyperplasia and preventing atherosclerosis in the blood system. Insufficient NO release is often observed in the pathological environment, for instance atherosclerosis. It was discovered that NO could be released from the human endogenous NO donor by many compounds, and these methods can be used for the treatment of certain diseases in the blood system. In this work, a series of copper-loaded polydopamine (PDA) coatings were produced through self-polymerization time for 24, 48 and 72 h. The chemical composition and structure, coating thickness and hydrophilicity of the different copper-loaded PDA coatings surfaces were characterized by phenol hydroxyl quantitative, X-ray photoelectron spectroscopy, ellipsometry atomic force microscopy and water contact angles. The results indicate that the thickness and the surface phenolic hydroxyl density of the PDA coatings increased with the polymerization time.This copper-loaded coating has glutathione peroxidase-like activity, and it has the capability of catalyzing NO releasing from GSNO. The surface of the coating showed desirable hemocompatibility, the adhesion and activation of platelets were inhibited on the copper-loaded coatings. At the same time, the formation of the thrombosis was also suppressed. These copper-loaded PDA coatings could provide a promising platform for the development of blood contact materials.

The objective of this study was to explore the effect of Alpiniae oxyphyllae Fructus (AOF) on a rat model of chronic intermittent hypoxia (CIH)–induced enuresis. Findings of this study may help identify therapeutic targets in children with nocturnal enuresis (NE). Female rats were randomly divided into a control group (saline gavage, 4 weeks of normal air), CIH group (saline gavage, 4 weeks of CIH), and AOF group (AOF gavage, 4 weeks of CIH). The variables measured in this study included water intake, urine output, bladder leak point pressure (BLPP), malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity. The expression levels of the purinergic P2X3 receptor, muscarinic M3 receptor, and s3-adrenergic receptor (s3-AR) in the bladder were also measured. The bladder was subjected to haematoxylin and eosin (HE) and Weigert staining, and histological changes were observed under a light microscope to evaluate the morphological changes in the bladder in each group. Compared with the control group, urine output was increased, and the BLPP was decreased in the CIH group, but AOF administration decreased urine output and increased BLPP. In addition, the serum MDA level increased and the SOD activity decreased in the CIH group compared with the control group. Administration of AOF decreased the MDA level and increased the SOD activity. Additionally, compared with the control group, HE and Weigert staining in the CIH group showed that the bladder detrusor muscle bundles were disordered and loose, some muscle bundles were broken, the content of collagen fibres in the gap was reduced, and the gap was significantly widened. However, following the administration of AOF, the bladder detrusor muscle bundles were neatly arranged, and the content of collagen fibres in the gap was increased. Furthermore, compared with the control group, the purinergic P2X3 receptor and muscarinic M3 receptor were expressed at higher levels, and s3-AR was expressed at lower levels in the CIH group, but AOF administration decreased the expression of the purinergic P2X3 receptor and muscarinic M3 receptor and increased the expression of the s3-AR. AOF improves enuresis by inhibiting oxidative stress and regulating the expression of the purinergic P2X3 receptor, muscarinic M3 receptor, and s3 adrenergic receptor.

In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was originally developed for simultaneously quantitative analysis of twelve paralytic shellfish poisoning toxins, referring to STX, NEO, dcSTX, GTX1, GTX2, GTX3, GTX4, GTX5, C1, C2, dcGTX2, and dcGTX3 in bivalve molluscs. Chromatographic separations were performed on a TSK-Gel Amide-80 column (5 μm, 2.0 × 150 mm, Tosoh Corporation) by gradient elution with 2 mmol L−1 ammonium formate solution-acetonitrile (containing 0.1% formic acid) as mobile phases. The samples were pretreated by extraction with acetonitrile-water (80:20, v/v; containing 0.1% formic acid), followed by cleaning up using an Oasis HLB extraction cartridge (500 mg/6 mL). The present method showed good linearity (r2 > 0.99) with the limits of detection (LODs) and limits of quantification (LOQs) ranged from 1.03 to 10.65 μg/kg and 3.43–35.46 μg/kg, respectively for these toxins. Owing to its sensitivity and rapid properties, the presented method was applied to the determination of PSP toxins in bivalve molluscs involved in a food poisoning incident occurred in Zhangzhou, China, in June 2017.

In recent years, the natural ingredients are in high demand in formulating the cosmetic products. Seaweed polysaccharides signify the attractive natural ingredient with a wide range of functional properties that are expected for cosmeceutical formulations. The present work aimed to study the skin protection ability of polysaccharides extracted from Sargassum vachellianum (SvP), Sargassum horneri (ShoP) and Sargassum hemiphyllum (SheP). The extracted crude polysaccharides were characterized by HPLC and FTIR, which revealed that the polysaccharides are fucose-containing sulfated polysaccharides. Skin whitening and anti-wrinkling activity were analyzed by the ability to inhibit tyrosinase and elastase. The results revealed that the ShoP showed maximum tyrosinase inhibition (64.72 ± 0.46%) and SvP exhibited considerable elastase inhibition (30.12 ± 0.33%). The maximum moisture absorption (79.7 ± 0.62%) and retention (68.99 ± 0.64%) ability were observed in ShoP. The antioxidant activity was estimated by DPPH, superoxide radical scavenging, reducing power and total antioxidant activity. All the tested polysaccharides showed antioxidant activity in a dose-dependent manner, among them ShoP exhibited maximum total antioxidant (80.93 ± 0.17%) and superoxide radical scavenging activity (67.4 ± 0.42%) whereas SheP showed maximum DPPH radical scavenging activity (74.56 ± 0.10%). Therefore, the present study indicates the potential of polysaccharides, ShoP, SvP and SheP as a promising cosmetic ingredient in cosmeceuticals.

Environmentally responsive polymer films have received much attention, but the stability of such films and the sensitivity of the response still have to be improved. The preparation of responsive films for low pH changes still faces challenges. In this study, catechol groups were used to functionalize chitosan and hyaluronic acid for mussel-inspired, catechol based adhesion. The modified chitosan and the modified hyaluronic acid were deposited in a layer-by-layer manner. The chemical properties of the compounds and surface properties of the coatings were characterized by UV, IR, scanning electron microscopy and water contact angles. The assembly and stability of the film were investigated in situ using quartz crystal microbalance (QCM-D). The film had improved stability compared to the native polymers and it showed reversible pH-dependent swelling and shrinkage. The film was loaded with a drug and placed in PBS solutions of different pH for several days, and the amount of drug released by the drug-loaded film was different under different pH environments. This provides ideas for the intelligent application in materials science and biology, and has broad prospects in drug delivery systems and tissue engineering.

O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors. However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed. Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues. Our results identified 114 O-GlcNAcylated peptides belonging to 78 proteins and 3494 phosphorylated peptides in 2088 proteins. Interestingly, 41 proteins were modified by both O-GlcNAcylation and phosphorylation. These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization. In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1. Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro. Collectively, our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.

Amino trimethylene phosphonic acid (ATMP) was widely used as an antiscalant in reverse osmosis (RO) systems to prevent membrane scaling, and entered RO concentrate at elevated levels. However, phosphonate antiscalants in RO concentrate might aggravate phosphorus pollution, remobilize heavy metals, and adversely affect the sedimentation treatment of RO concentrate. Ozonation was found an efficient method for ATMP treatment. The ATMP removal efficiencies with 8 mg/L ozone were 100% and 86.5% for ultrapure water and RO concentrate, respectively. The ATMP mineralization efficiency reached 46.5% with 8 mg/L ozone. The rate constant for the reaction between ATMP and ozone was 1.92 × 106 M−1 s−1. Increasing the pH from 3 to 9 decreased the ATMP removal efficiency from 90% to 30.9% but increased the orthophosphate formation to ATMP removal ratio from 0.11 to 0.48. The ATMP intermediates generated with low ozone dosages exhibited moderate chelation and anti-precipitation capacity, and their chelation and anti-precipitation capacity could be further attenuated by increasing the ozone dosage. Ozonation alone enhanced the growth potential for microalgae in RO concentrate because orthophosphate formed. Combining ozonation and coagulation effectively removed 83.0% of the total phosphorus from RO concentrate. The maximum algal density of Scenedesmus sp. LX1 decreased by 78.7% by ozonation and coagulation.

Background Mycophenolate mofetil (MMF) is extensively used for induction and maintenance therapy in patients with lupus nephritis (LN). Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the adverse gastrointestinal effects of MMF. However, the therapeutic efficacy of MMF and EC-MPS in LN remains unclear. This study aimed to examine the treatment effects of EC-MPS in LN patients with prior MMF exposure. Methods In this medical records review study, we included 54 LN patients, of whom 34 converted from MMF to EC-MPS at equimolar doses in 2016-2018 (nonmedical switching group) and 20 received continuous MMF treatment. Patients achieving complete remission or partial remission before the conversion were categorized as responders, whereas those who had never achieved complete remission or partial remission were categorized as nonresponders. Results Baseline proteinuria was higher in the nonmedical switching group. Although elevation in proteinuria was observed after nonmedical switching, the serum creatinine concentration and estimated glomerular filtration rate both improved. Responders in the nonmedical switching group had lower proteinuria and higher complement 3 levels. In the subgroup analysis, albeit the modest increase in daily urine protein, anti-double-stranded DNA antibody levels, estimated glomerular filtration rate, and complements 3 and 4 seemed comparable after conversion. Conclusion Switching to EC-MPS demonstrated a similar short-term renal response to continuous MMF treatment in LN patients. Prospective randomized trials are required to verify our findings.

A series of d10 based metal-organic frameworks (MOFs), namely, [Cd2(dpc)(bipy)(H2O)3]n (Ⅰ), {[Cd2(dpc)(bib)(H2O)]·H2O}n (Ⅱ), {[Cd2(dpc)(bitb)1.5(H2O)2]·H2O}n (Ⅲ) (H4dpc = 2-(3′,4′-dicarboxylphenoxy)isophthalic acid, bipy = 4,4′-dipyridyl, bib = 1,4-bis (1-imidazolyl)benzene, bitb = 1,4-bis (imidazol-1-ylmethyl)benzene) have been designed and successfully synthesized using a flexible tetrabasic carboxylic acid along with three ancillary ligands under hydrothermal conditions, which exhibit structural diversities of targeted Cd-MOFs. Single-crystal X-ray diffraction analysis reveals that they contain building units of {CdN1O6} and {CdN1O5} (for I), {CdN1O5} (for II), as well as {CdN2O4} and {CdN5O1} (for Ⅲ), based on which to assemble microporous three-dimensional (3D) frameworks via covalent bonds and/or hydrogen bonds using multiple coordination modes of H4dpc ligand and auxiliary linkers. The solid-state luminescence performances of these Cd-MOFs were investigated at ambient temperature. Furthermore, luminescent sensing responses of Ⅰ-Ⅲ to amino acids and metal cations were systematically explored. Notably, Ⅰ and II may act as potential dual-functional luminescent sensors for Aspartic acid and Cu2+ cations as well as Aspartic acid and Fe3+ cations with high selectivity and sensitivity in aqueous solutions, respectively. The mechanisms of the quenching effect and sensing properties of the as-synthesized Cd-MOFs have also been discussed in this report.

In this work, we demonstrate a simple method to prepare carbon nanofiber (CNF) with multilevel gradient porous structure derived from polyvinylidene fluoride (PVDF)- polyvinyl pyrrolidone (PVP) /PVP core-shell nanofiber. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) have confirmed that the as-prepared CNF contains a hollow channel embraced by mesoporous and microporous structures. Its specific surface area reaches to 1084 m2/g with the mesoporous volume contribution of 59%. The as-prepared porous CNF shows a high capacitance of 331 F/g at 1 A/g and 99.6% capacitance retention after 10,000 cycles at 5 A/g, which is better than the corresponding CNF with irregularly arranged hierarchical pores. The all-solid-state symmetric supercapacitor assembled using the as-prepared porous CNF as electrodes exhibits an excellent high specific capacitance of 147.4F/g at 1 A/g with a high energy density of 13.1 W h/kg. The capacitance retention still maintains at 89.2% after 2000 cycles at a current density of 5 A/g. Meanwhile, the as-prepared porous CNF also shows a high CO2 adsorption uptake, 5.08 mmol/g at 0 °C and 1 bar. The possible reason and mechanism have been discussed.

Two simple methods are proposed to respectively impart external force-free reversible shape memory effect to commercial polyolefins: ultrahigh molecular weight polyethylene (UHMWPE) and polypropylene (PP). The key issues lie in the utilization of the partially entangled molecular chains of UHMWPE and the medium crystalline phases of PP as the reversible internal stress providers. The acquired reversible shape memory effect further proves to be applicable for assisting repeatedly self-healing of wider cracks. Compared to the conventional approaches, which used to introduce cross-linkages into the target materials, the present ones only need physical treatment, so that the valuable thermoplasticity of polyolefins is retained. This work can be regarded as an example of the concept "physically converting instead of chemically modifying" for the preparation of functional polymeric materials based on market available plastics.

The present work is focused on developing external stress-free two-way triple shape memory polymers (SMPs). Accordingly, a series of innovative approaches are proposed for the material design and preparation. Polyurethane prepolymers carrying crystalline polytetrahydrofuran (PTMEG) and poly(ε-caprolactone) (PCL) as the switching phases are respectively synthesized in advance and then cross-linked to produce the target material. The stepwise method is believed to be conducive to manipulation of the relative contribution of PCL and PTMEG. Moreover, the chain extender, 2-amino-5-(2-hydroxyethyl)-6-methylpyrimidin-4-ol (UPy), is incorporated to establish hydrogen bonds among the macromolecules. By straightforward stretching treatment at different temperatures, the hydrogen bond networks are successfully converted into an internal stress provider, which overcomes the challenge of stress relaxation of the melted low melting temperature polymer (i.e., PTMEG) and increases the efficiency of stress transfer. Meanwhile, the contraction force of the switching phases is tuned to match the internal tensile stress. As a result, the internal stress provider can closely collaborate with melting/recrystallization of the crystalline domains, leading to the repeated multiple shape memory effects. The cross-linked polyurethane is thus able to reversibly morph among three shapes and displays its potentials as soft robot and actuator. The strategy reported here has the advantages of easily accessible raw materials, simple reaction, and facile programing/deprograming/reprograming, so that it possesses wide applicability.

Pickering High Internal Phase Emulsions (HIPEs) stabilized by food-grade particles have received considerable attention. In this work, we first demonstrated the use of chitosan-caseinophosphopeptides (CS-CPP) nanocomplexes as particulate emulsifiers to stabilize the interface of natural oils and water. For this purpose, we developed the CS-CPP nanocomplexes through electrostatic interactions and demonstrated their application in the formation of stable Pickering HIPEs. The microstructures, e.g., interfacial frameworks, of the CS-CPP nanocomplexes partition between the continuous phase and interfacial region, and the states of the droplets of Pickering HIPEs were visualized by confocal laser scanning microscopy (CLSM) and an optical microscope. The compressed droplets in Pickering HIPEs formed a percolating 3D-network framework that endowed emulsions with viscoelastic, self-supporting, and ideal thixotropic features. In addition, the gelatinous state of Pickering HIPEs combined with robust and compact CS-CPP nanocomplexes formed an interfacial layer around the droplets, thus depressing the oxidation of linseed oil. The contents of primary and secondary oxidation products in HIPEs were lower than that in bulk oil and emulsions stabilized by surfactants. An in vitro gastrointestinal (GI) model was constructed to characterize the lipid oxidation, lipid digestion and curcumin bioaccessibility of Pickering HIPEs. Interestingly, this route enhanced the bioaccessibility of curcumin from 20.49% (bulk oil) to 49.21% (Pickering HIPEs). This work offers a facile method to develop Pickering HIPEs by food-grade particles, which help to fill the gap between the performance of CS-CPP nanocomplexes-stabilized Pickering HIPEs and potential applications as oral delivery systems of nutraceuticals.

Co-immobilization of two or more molecules with different and complementary functions to prevent thrombosis, suppress smooth muscle cell (SMC) proliferation, and support endothelial cell (EC) growth is generally considered to be promising for the re-endothelialization on cardiovascular stents. However, integration of molecules with distinct therapeutic effects does not necessarily result in synergistic physiological functions due to the lack of interactions among them, limiting their practical efficacy. Herein, we apply heparin and nitric oxide (NO), two key molecules of the physiological functions of endothelium, to develop an endothelium-mimetic coating. Such coating is achieved by sequential conjugation of heparin and the NO-generating compound selenocystamine (SeCA) on an amine-bearing film of plasma polymerized allylamine. The resulting surface combines the anti-coagulant (anti-FXa) function provided by the heparin and the anti-platelet activity of the catalytically produced NO. It also endows the stents with the ability to simultaneously up-regulate α-smooth muscle actin (α-SMA) expression and to increase cyclic guanylate monophosphate (cGMP) synthesis of SMC, thereby significantly promoting their contractile phenotype and suppressing their proliferation. Importantly, this endothelium-biomimetic coating creates a favorable microenvironment for EC over SMC. These features impressively improve the antithrombogenicity, re-endothelialization and anti-restenosis of vascular stents in vivo.

Surface modification with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is an effective method for improving hemocompatibility. Peptide GREDVY immobilized on Ti is of great benefit to endothelialization. Micropattern of PMPC and GREDVY can regulate cells distribution, behaviors, and nitric oxide (NO) release. Copper can be used as catalytic to release NO from a donor in vitro, which can inhibit platelets adhesion, activation, and aggregation. The Ti-PDA(Cu)-M/R(P) micropattern was fabricated with PMMPC-HD {PMMPC [monomer contain MPC and methacrylic acid (MA)] was cross-linked with hexamethylene diamine} and peptide Gly-Arg-Glu-Asp-Val-Tyr (GREDVY) using PDMS stamp, and it was characterized by SEM, FTIR, and XPS. The results demonstrated that the PMPC and peptide GREDVY were immobilized onto polydopamine successfully. Simultaneously, the copper existed in polydopamine was confirmed by XPS. The rate of NO release in vitro catalyzed by copper ions was 1.5–5.3 × 10−10 mol/(cm2 min). It will be beneficial to inhibiting platelets adhesion and proliferation of ECs.

Titanium oxide (Ti-O) films with different thicknesses were deposited on 316 L stainless steel and bare metal stents with the filtered cathodic vacuum arc technique. The adhesion of the Ti-O films with different thicknesses on the 316 L stainless steel sheets was studied by the tension test. The adhesion, corrosion resistance, and fatigue behavior of the Ti-O film-modified stents were then evaluated. The results show that a 25-nm-thick Ti-O film on stainless steel is tightly adhered on the stainless steel after 40% relative elongation of the steel substrate. The 25-nm-thick Ti-O film-modified bare metal stent has sufficient mechanical stability, good corrosion resistance, and can withstand 380 million cycles of pulsatile fatigue testing without film destruction and delamination. A clinical trial of the bilayer drug eluting stent (DES) with a titanium oxide base layer and an anti-proliferative sirolimus top layer shows that our DES tends to reduce the incidence of late thrombosis.

Chloramines applied to control membrane biofouling in potable reuse trains pass through reverse osmosis membranes, such that downstream ultraviolet (UV)/H2O2 advanced oxidation processes (AOPs) are de facto UV/H2O2-chloramine AOPs. Current models for UV/chloramine AOPs, which use inaccurate chloramine quantum yields and ignore the fate of •NH2, are unable to simultaneously predict the loss of chloramines and contaminants, such as 1,4-dioxane. This study determined quantum yields for NH2Cl (0.35) and NHCl2 (0.75). Incorporating these quantum yields and the formation from •NH2 of the radical scavengers, •NO and NO2-, was important for simultaneously modeling the loss of chloramines, H2O2, and 1,4-dioxane in the UV/H2O2-chloramine AOP. Although the level of radical production was higher for the UV/H2O2-chloramine AOP than for the UV/H2O2 AOP, the UV/H2O2 AOP was at least 2-fold more efficient with respect to 1,4-dioxane degradation, because chloramines efficiently scavenged radicals. At low chloramine concentrations, the UV/chloramine AOP efficiency increased with an increase in chloramine concentration, as the level of radical production increased relative to that of radical scavenging by the dissolved organic carbon in RO permeate. However, the efficiency leveled out at higher chloramine concentrations as radical scavenging by chloramines offset the increased level of radical production. The level of 1,4-dioxane degradation was ∼30-50% lower for the UV/chloramine AOP than for the UV/H2O2-chloramine AOP when the concentration of residual chloramines in RO permeate was ∼50 μM (3.3 mg/L as Cl2). Initial cost estimates indicate that the UV/chloramine AOP using the residual chloramines in RO permeate could be a cost-effective alternative to the current UV/H2O2-chloramine AOP in some cases, because the savings in reagent costs offset the ∼30-50% reduction in 1,4-dioxane degradation efficiency.

Sea container has been identified as a major pathway for the unintended entry and spread of alien ant species. In Japan, red imported fire ants, Solenopsis invicta Buren (Hymenoptera: Formicidae), which are among the most harmful alien ants, were first detected in a shipping container from China in May 2017, and the invasion into Japan via the trade pathway is still continuing. To prevent containers contaminated with S. invicta and its establishment in Japan, control measures, such as repellents, are urgently required. The present study is the first to evaluate repellency of microencapsulated allyl isothiocyanate (AITC) against S. invicta, as a preliminary step to use the innovative equipment for invasive species management in sea containers. In a field in Taiwan heavily infested with S. invicta, a repellent test of microencapsulated AITC using bait traps showed that the equipment completely prevents S. invicta from accessing the bait. Due to its volatility and irritancy, AITC, a safe natural repellant in wasabi (Eutrema japonicum (Miq.) Kiudz), has not been used for pest management in containerized cargo. However, the encapsulation of AITC solves this problem by allowing controlled vapor release. Microencapsulated AITC has considerable potential as an effective measure to stop the spread of S. invicta through global trade.

Nitric oxide (NO) is a highly potent, yet short-lived bioactive molecule with a broad spectrum of physiological functions. Continuous and controllable in situ generation of NO from vascular stent surface can effectively prevent restenosis and thrombosis after its implantation. In this study, inspired by the adhesion and protein cross-linking in the mussel byssus, through immersing the stents into an aqueous solution with dopamine (DA) and copper ions (Cu II), we developed a one-step metal-catecholamine assembled strategy to prepare a durable in situ NO-generating biomimetic coating (DA-Cu II). Due to the high NO catalytic efficacy and robust chelation of CuII into the DA-CuII network, the coated stents exhibited excellent hemocompatibility . The coating also catalytically decomposed endogenous S-nitrosothiols (RSNOs) from fresh blood, and locally generated NO for over 30 days with a flux comparable to its physiological range (0.5–4 × 10 −10 mol × cm−2 × min−1 ). Moreover, the optimized biomimetic coatings displayed specific cell selectivity to significantly enhance endothelial cell (EC) growth while substantially inhibit smooth muscle cell (SMC) growth and migration. This feature impressively promoted regeneration of a new endothelial cell layer after stent implantation , hence improved the anti-thrombogenic and anti-restenosis qualities of vascular stents in vivo. We envision that our long-term in situ NO-generating coatings could serve as biosurfaces for long-term prevention of stent thrombosis and restenosis.

Objective: To evaluate the long-term safety and effectiveness of tocilizumab (TCZ) for the treatment of rheumatoid arthritis (RA) in a real-world clinical setting in Taiwan. Method: All refractory RA patients who initiated intravenous TCZ between August 2012 and March 2015 were enrolled. Data on patient characteristics, drug safety and effectiveness were collected. Results: A total of 114 RA patients were recruited. Despite the majority of them (93%) had previous biologic failure, 43.75% of the patients were able to reach ACR50 after one year. Serious adverse events commonly found were bacterial pneumonia (4.24/100 patient-years) followed by cellulitis (2.12/100 patient-years). Twenty-three patients had old or latent TB infections, 11 patients had chronic hepatitis B. During the 3 years follow-up, none of them had reactivation of TB, or hepatitis B with concomitant use of isoniazid prophylaxis or pre-emptive antiviral treatment. Conclusion: In this 3-year real-world study on RA patients of Taiwan, we found a good long-term effectiveness and similar safety profiles for the TCZ treatment. With prophylactic strategy for latent TB and pre-emptive antiviral treatment for HBV carriers, the risk of reactivation of latent TB and HBV may be reassured. Keywords: Hepatitis B, Rheumatoid arthritis, Safety and effectiveness, Tocilizumab, Tuberculosis

Surface treatment with phenols can be a new controllable anticorrosion strategy for modulating the degradation rate of magnesium implants. In our previous work, the gallic acid (GA) and the hexamethylenediamine (HD) were used to fabricate the GAHD film on the surface of magnesium and exhibited good corrosion resistance. In this work, the mechanism of anticorrosion and controllability of the GAHD film was deeply investigated. The results of SEM, EDX and XPS show that large number of magnesium was chelated into the GAHD film by GA. And the higher content the GA was, the more magnesium was chelated. Furthermore, the results of electrochemical measures and immersion tests show that the GAHD film with higher GA content possessed stronger corrosion resistance. According to these results above, we found the GAHD film deposited on the magnesium was a kind of chemical conversion coating. In the body fluid environment, massive chelated magnesium would transform into insoluble magnesium hydroxide, which are known as a natural corrosion protection substance of magnesium and perform the effect of corrosion protection. And it could easily control the corrosion resistance of the GAHD conversion coating through regulating the content of GA in the coating.

Thrombosis and infections of extracorporeal circuits and indwelling medical devices are the two major life-threatening complications faced in clinical practice. Herein, we report a novel and facile metal–phenolic–amine surface modification strategy to engineer a multifunctional coating on these devices to combat thrombosis and infection. This strategy is inspired by the metal–catecholamine coordination complex of [Fe(dopa)3] in mussels, in which Cu(II) ions (metal), plant polyphenol gallic acid (phenol) and cystamine (amine) are employed to fabricate a copper–phenolic–amine network. Our in vitro and in vivo experiments reveal that the resultant Cu(II)-chelating coatings endow the modified tubing with not only durable antibacterial properties, but also capability to persistently generate anticoagulant therapeutic nitric oxide (NO) gas in the presence of endogenous S-nitrosothiols (RSNO) from fresh blood. We anticipate that our simple and multifunctional coating strategy will be a milestone in the development of surface engineering, especially that of biomedical devices.

Functionalizing cardiovascular biomaterials with an extracellular matrix (ECM) via in vitro decellularization has been applied as an effective method to improve the biocompatibility of implants. However, the current ECM modified materials used for surface engineering implants have functional restrictions compared with the natural blood vessel due to distinguished cell phenotypes in vitro. Herein, we are inspired by the natural vascular basement membrane which is composed of an ECM secreted by physiological endothelial cells (EC) and smooth muscle cells (SMC), preparing a novel ECM coating by successive cell culture and decellularization: appropriately scaled hyaluronic acid (HA) micro-patterns are used to regulate the SMC phenotype to contraction and simulate the blood flow shear stress (BFSS) effect to control the EC physiological phenotype. The nature-inspired ECM coating significantly improves the material's hemocompatibility, cytocompatibility and tissue compatibility, and may be promising to break the function limitation of a single ECM and address more clinical complications.

Skin surface is constantly exposed to environmental and secreted stressors such as UV, air pollution and peroxidized sebum. The current study aims to use reconstructed human skin equivalents to demonstrate topical stressor-induced hyperpigmentation and evaluate bioactives' potential protective effect. Given that polycyclic aromatic hydrocarbons are representative airborne particle-bound organic compounds with known relevance to pigmentation pathways, benzo(a)pyrene was selected as surrogate environmental toxin. On the other hand, squalene monohydroperoxides are well-characterized sebum peroxidation product under UV and pollutant exposure, thus are used as another representative skin stressor. With 3-day continuous exposure, 30 pmol/cm2 of benzo(a)pyrene and 3.4 nmol/cm2 of squalene monohydroperoxides induced significant viability loss, inflammatory response, and approximately 10 shades of pigmentation increase in pigmented living skin equivalents. At the same time, pretreatment and co-treatment with 12-hydroxystearic acid (12-HSA, 20 μmol/L) or niacinamide (5 mmol/L) ameliorated such stressor-induced consequences. Niacinamide was particularly effective against benzo(a)pyrene damage, probably as a substrate for important NAD+ dependent detoxification pathways, while 12-HSA was potent against squalene monohydroperoxides through barrier enhancing, anti-inflammatory, and anti-oxidative mechanisms. In summary, topical stressor-induced hyperpigmentation was achieved in vitro, with known bioactives showing protective benefits.

The development of a facile and versatile strategy to endow surfaces with synergistically anti-inflammatory, antimicrobial, and anticoagulant functions is of particular significance for blood-contacting biomaterials and medical devices. In this work, we report a simple and environmentally friendly "one-pot" method inspired by byssal cuticle chemistry, namely, [Fe(dopa)3] coordination chemistry for assembly of copper ions (Cu2+) and plant polyphenol (tannic acid)/catecholamine (dopamine or norepinephrine) to form metal-phenolic/catecholamine network-based coatings. This one-pot method enabled us to easily develop a multifunctional surface based on the combination of the characteristic functions of metal ions and plant polyphenol or catecholamine. The residual phenolic hydroxyl groups on the coatings imparted the modified surface with excellent antioxidant and anti-inflammatory functions. The robust chelation of copper ions to the metal-phenolic/catecholamine networks provided not only durable antibacterial property but also glutathione peroxidase like catalytic capability to continuously and controllably produce antithrombotic nitric oxide by catalyzing endogenous S-nitrothiol. The biological functions of such coatings could be well regulated by adjusting the ratios of the feed concentration of Cu2+ ions to plant polyphenol or catecholamine. We envision that our simple, multifunctional, and bioinspired coating strategy can hold great application promise for bioengineering blood-contacting devices.

Dodecyl dimethyl benzyl ammonium chloride (DDBAC), a non-oxidizing biocide, is commonly used in municipal wastewater reverse osmosis system. It has been used also as an ingredient in fabric softeners, disinfectants, detergents, phase transfer agent and numerous personal skin care products. In this study, the DDBAC degradation efficiency achieved using UV and persulfate (PS) oxidation processes was investigated. Substantial synergistic effects on DDBAC degradation were found when UV and PS oxidation processes were combined. During the UV/PS process, UV photolysis and reactions with radical species accounted for 42.7% and 57.3%, respectively, of DDBAC degradation. The OH and SO4 − radicals accounted for 4.6% and 52.7%, respectively, of DDBAC degradation. The calculated k OH,DDBAC and k SO 4 - ,DDBAC rate constants were (1.45 ± 0.16) × 109 and (1.51 ± 0.02) × 109 M−1 s−1, respectively. The kobs rate constant for DDBAC degradation increased from 0.047 to 0.150 min−1 when the PS dose was increased from 0.05 to 1.45 mM. The presence of natural organic matter (NOM), HCO3−/CO32−, and NO3− adversely affected DDBAC degradation. Five main intermediates were identified by high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The proposed DDBAC degradation pathway involves benzyl-nitrogen bond cleavage (or subtraction of hydrogen from the alkyl chain), demethylation, hydroxylation, and hydrogen subtraction. UV/PS treatment decreased the acute toxicity of the DDBAC solution in less than 15 min. However, the residual toxicity indicated that toxic oxidation transformation products were formed when DDBAC was treated using the UV/PS process.

Dendrimers, with their unique structure and polyfunctionality, have shown excellent performance in many biomedicinal applications, such as drug carriers and gene transfection. In this study, titanium dioxide (TiO2) films with four generations (G1, G2, G3, G4) of amino-terminated dendrimers were prepared in situ using a simple iterative Michael addition and aminolysis reaction for generational growth. The TiO2 films with different generations of dendrimers were characterized using X-ray diffraction, water contact angle measurements, and scanning electron microscopy. The chemical compositions of these films were confirmed by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. Blood compatibility was evaluated using platelet adhesion and activation assays utilizing platelet-rich plasma. The results indicated that the dendrimers immobilized on the surface of the TiO2 films effectively reduced platelet adhesion and aggregation. Endothelial cell culturing on the dendrimer-immobilized surfaces showed that the amino-terminated dendrimers exhibited a certain degree of cytotoxicity due to the positive charges of the amino groups. These results indicated that amino-terminated dendrimers immobilized on TiO2 films provided numerous functional groups for the future immobilization of specific biological molecules and may be used for manufacturing future blood-contacting implants.

A Correction to this paper has been published: https://doi.org/10.1038/s41427-021-00293-0

Thrombosis and infections are the main causes of implant failures (e.g., extracorporeal circuits and indwelling medical devices), which induce significant morbidity and mortality. In this work, an endothelium-mimicking surface is engineered, which combines the nitric oxide (NO)-generating property and anti-fouling function of a healthy endothelium. The released gas signal molecules NO and the glycocalyx matrix macromolecules hyaluronic acid (HA) jointly combine long- and short-distance defense actions against thrombogenicity and biofouling. The biomimetic surface is efficiently fabricated by cografting a NO-generating species (i.e., Tri-tert-butyl 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetate-chelated Cu2+ , DTris@Cu) and the macromolecular HA on an aminated tube surface through one-pot amide condensation chemistry. The active attack (i.e., NO release) and zone defense (i.e., HA tethering) system endow the tubing surface with significant inhibition of platelets, fibrinogen, and bacteria adhesion, finally leading to long-term anti-thrombogenic and anti-fouling properties over 1 month. It is envisioned that this endothelium-mimicking surface engineering strategy will provide a promising solution to address the clinical issues of long-term blood-contacting devices associated with thrombosis and infection.

Background Bacteria can respond to antibiotics in the environment by histidine kinase (HK) sensor then induce drug-resistance. In this article,antibiotic susceptibility and ESBLs genes of β-lactam-resistant E. coli interfered by I. japonica were investigated to reveal I. japonica can be HK inhibitor candidate[1]. Methods E-test were applied to measure the MIC of E. coli to penicillin G and cefotaxime sodium according to 2017CLSI. Microplate dilution methods were applied to explore sensitivity variation of penicillin G and cefotaxime sodium of Escherichia coli, which contain only one single β-lactamase gene. Real-time fluorescent quantitative PCR were performed to determine the inducing effects of penicillin G and cefotaxime sodium to E. coli TEM, SHV, CTX-M and KPC single gene expression, and the interrupting effect of I. japonica extracts. Immobilized metal ion affinity chromatography and bacterial protein phosphorylation detection kit were performed to determine the change of bacterial protein phosphorylation concentration of Escherichia coli, after the induction of 1/4 penicillin G and cefotaxime sodium, and the interrupting effect of I. japonica extracts,HK inhibitor closantel was used as the positive control. Results 1/4 MIC penicillin G or cefotaxime sodium could induce more than 10 times elevation of TEM, SHV and CTX-M mRNAs. While, I. japonica aqueous extracts (250 mg/mL) and ethanol extracts (100 µg/mL or 50 µg/mL) could decreased more than 40% of gene expression induced by antibiotics. I. japonica extracts could significantly enhance the sensitivity of β-lactam antibiotic-resistant E. coli strains to penicillin G or cefotaxime sodium, and could block the TEM, CTX-M and SHV mRNA induced by 1/4 MIC concentration antibiotics. Penicillin G and cefotaxime sodium at 1/4 MIC induced the protein phosphorylation of TEM, SHV and CTX-M promoted. Closantel (132.5 µg/mL), I. japonica aqueous extracts (250 mg/mL) and ethanol extracts (100 µg/mL) could inhibit the protein phosphorylation induced by above mentioned antibiotics. Conclusion I. japonica extracts can enhance the sensitivity of β-lactam antibiotic-resistant Escherichia coli. The mechanism may be that I. japonica extracts can be used as the inhibitor of HK phosphorylation, inhibit the transmission of antibiotic signal in TCSS, and reduce the expression of ESBLs gene.

Over the past few decades, plasma surface modification technique has been widely used to selectively improve surface properties and biocompatibility of materials. In this paper, at first a simple and effective method for the deposition of plasma-polymerized allylamine films onto 316L stainless steel (SS) from an allylamine/nitrogen gas mixture was developed. These amine-rich films were characterized by grazing incidence attenuated total reflection Fourier transform infrared spectroscopy (GATR-FTIR) and X-ray photoelectron spectroscopy (XPS), and the anticorrosion properties were demonstrated by electrochemical analysis. Micro-BCA and quartz crystal microbalance with dissipation (QCM-D) results showed that the higher density of amine groups of the allylamine-nitrogen plasma-polymerized film contributes to more serum protein adsorption which may enhance the adhesion and growth of cells on biomaterials. The in vitro and in vivo anti-inflammatory evaluation was performed and it has been confirmed that these nitrogen-rich surfaces could inhibit the activation of macrophages by down-regulation of the pro-inflammatory cytokines TNF-α and IL-6, and exhibit acceptable tissue-compatibility. It was found that with the help of nitrogen, plasma-polymerized allylamine films presented superior biological properties and provided a high potential application in surface modification of biomedical substrate with desirable clinical performance.

Protein-based Pickering emulsions have received considerable attention as nutraceutical vehicles. However, the oral bioavailability of nutraceuticals encapsulated in Pickering emulsions was not well established. In this work, a simulated gastrointestinal tract/Caco-2 cell culture model was applied to investigate the oral bioavailability of quercetin encapsulated in zein-based Pickering emulsions with quercetin in zein particles as the control. Pickering emulsions with shell (ZCP-QE) and core quercetin (ZCPE-Q) were constructed, and quercetin bioaccessibility, cell uptake and secretion, and the overall bioavailability were evaluated and compared. The overall oral bioavailability of quercetin was increased from 2.71% (bulk oil) to 38.18% (ZCPs-Q) and 18.97% (ZCPE-Q), particularly reached 41.22% for ZCP-QE. This work took new insights into the contributions of bioaccessibility and absorption (cell uptake plus secretion) to the overall oral bioavailability of quercetin. A schematic representation is proposed to relate the types of colloidal nanostructures in the digesta to the uptake, cell absorption, and overall oral bioavailability of quercetin. This study provided an attractive basis for identifying effective strategies to improve the oral bioavailability of hydrophobic nutraceuticals.

(1) Background: Antifolate methotrexate (MTX) is the most common disease-modifying antirheumatic drug (DMARD) for treating human rheumatoid arthritis (RA). The mitochondrial-produced formate is essential for folate-mediated one carbon (1C) metabolism. The impacts of MTX on formate homeostasis in unknown, and rigorously controlled kinetic studies can greatly help in this regard. (2) Methods: Combining animal model (8-week old female C57BL/6JNarl mice, n = 18), cell models, stable isotopic tracer studies with gas chromatography/mass spectrometry (GC/MS) platforms, we systematically investigated how MTX interferes with the partitioning of mitochondrial and cytosolic formate metabolism. (3) Results: MTX significantly reduced de novo deoxythymidylate (dTMP) and methionine biosyntheses from mitochondrial-derived formate in cells, mouse liver, and bone marrow, supporting our postulation that MTX depletes mitochondrial 1C supply. Furthermore, MTX inhibited formate generation from mitochondria glycine cleavage system (GCS) both in vitro and in vivo. Folinate selectively rescued 1C metabolic pathways in a tissue-, cellular compartment-, and pathway-specific manner: folinate effectively reversed the inhibition of mitochondrial formate-dependent 1C metabolism in mouse bone marrow (dTMP, methionine, and GCS) and cells (dTMP and GCS) but not methionine synthesis in liver/liver-derived cells. Folinate failed to fully recover hepatic mitochondrial-formate utilization for methionine synthesis, suggesting that the efficacy of clinical folinate rescue in MTX therapy on hepatic methionine metabolism is poor. (4) Conclusion: Conducting studies in mouse and cell models, we demonstrate novel findings that MTX specifically depletes mitochondrial 1C supply that can be ameliorated by folinate supplementation except for hepatic transmethylation. These results imply that clinical use of low-dose MTX may particularly impede 1C metabolism via depletion of mitochondrial formate. The MTX induced systematic and tissue-specific formate depletion needs to be addressed more carefully, and the efficacy of folinate with respect to protecting against such depletion deserves to be evaluated in medical practice.

Chemo and radiation therapies are the most commonly used therapies for cancer, but they can induce DNA damage, resulting in the apoptosis of host cells. DNA double-stranded breaks (DSBs) are the most lethal form of DNA damage in cells, which are constantly caused by a wide variety of genotoxic agents, both environmentally and endogenously. To maintain genomic integrity, eukaryotic organisms have developed a complex mechanism for the repair of DNA damage. Researches reported that many cellular long noncoding RNAs (lncRNAs) were involved in the response of DNA damage. The roles of lncRNAs in DNA damage response can be regulated by the dynamic modification of N6-adenosine methylation (m6A). The cellular accumulation of DNA damage can result in various diseases, including cancers. Additionally, lncRNAs also play roles in controlling the gene expression and regulation of autophagy, which are indirectly involved with individual development. The dysregulation of these functions can facilitate human tumorigenesis. In this review, we summarized the origin and overview function of lncRNAs and highlighted the roles of lncRNAs involved in the repair of DNA damage.

To investigate whether butyric acid could alleviate chronic intermittent hypoxia (CIH)-induced lipid formation in human preadipocytes-subcutaneous (HPA-s) through accumulation of human antigen R (HuR) and inactivation of AMP-activated protein kinase (AMPK) pathway, HPA-s were obtained and divided into three groups: Control group: cells were cultured under normal conditions; CIH group: cells were cultured in a three-gas incubator (10% O2); Butyric acid group: 10 mmol/l butyric acid added into cell culture medium. HuR-siRNA was futher transfected into CIH group for verification the function of HuR. Oil Red O was implemented for observation of lipid droplets within cells. Cell Counting Kit-8 (CCK8) assay was used for detecting cell viability. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) assay as well as flow cytometry analysis was employed for determining cell apoptosis. Western blotting was used for measurement of protein expression levels. RT-qPCR analysis was used for detecting mRNA expression. CIH treatment increased adipocytes proliferation, while butyric acid inhibited cell proliferation and promoted cell apoptosis. The treatment of butyric acid in CIH group down-regulated expression of inflammatory factors and increased cell apoptotic rate. Butyric acid treatment increased HuR expression in both cytoplasm and nucleus and decreased the level of p-AMPK and p-ACC, while transfection of AMPK activator or HuR-siRNA would down-regulate HuR expression. Moreover, butyric acid alleviated CIH-induced cell proliferation, lipid formation and inflammatory status and promoted cell apoptosis through regulating related genes including p21, PPARγ, C/EBPa, IL-1β, IL-6, TLR4, caspase-8 and caspase-3. In conclusion, butyric acid could alleviate CIH-induced inflammation, cell proliferation and lipid formation through accumulation of HuR and inactivation of AMPK pathway.

Endothelium can secrete vasoactive mediators and produce specific extracellular matrix, which contribute jointly to the thromboresistance and regulation of vascular cell behaviors. From a bionic point of view, introducing endothelium‐like functions onto cardiovascular stents represents the most effective means to improve hemocompatibility and reduce late stent restenosis. However, current surface strategies for vascular stents still have limitations, like the lack of multifunctionality, especially the monotony in endothelial‐mimic functions. Herein, a layer‐by‐layer grafting strategy to create endothelium‐like dual‐functional surface on cardiovascular scaffolds is reported. Typically, a nitric oxide (NO, vasoactive mediator)‐generating compound and an endothelial polysaccharide matrix molecule hyaluronan (HA) are sequentially immobilized on allylamine‐plasma‐deposited stents through aqueous amidation. In this case, the stents could be well‐engineered with dual endothelial functions capable of remote and close‐range regulation of the vascular microenvironment. The synergy of NO and endothelial glycocalyx molecules leads to efficient antithrombosis, smooth muscle cell (SMC) inhibition, and perfect endothelial cell (EC)‐compatibility of the stents in vitro. Moreover, the dual‐functional stents show efficient antithrombogenesis ex vivo, rapid endothelialization, and long‐term prevention of restenosis in vivo. Therefore, this study will provide new solutions for not only multicomponent surface functionalization but also the bioengineering of endothelium‐mimic vascular scaffolds with improved clinical outcomes., An endothelium‐mimicking coating NO‐releasing property and grafted glycocalyx molecules on a cardiovascular stent is reported. The dual functions endow the stent with antithrombosis, smooth muscle cell (SMC) inhibition, and endothelial cell (EC)‐compatibility, which result in efficient antithrombogenesis ex vivo, rapid endothelialization, and long‐term prevention of restenosis in vivo.

Numerous studies have investigated neurobehavioral toxicity of microplastics, but no studies have illustrated mechanism via brain-gut axis. Here, juvenile discus fish (Symphysodon aequifasciatus) were exposed for 96 h to microfibers (900 µm, fiber, MFs) or nanoplastics (~88 nm, bead, NPs) with three concentrations (0, 20 and 200 µg/L). Accumulation in fish gut was independent of plastics type and concentration. MFs reduced growth performance while NPs weakened swimming and predatory performance of post-exposed discus. For brain cholinesterase activity, acetylcholinesterase was activated by NPs while NPs/MFs exposure inhibited butyrylcholinesterase. Concentrations of neurotransmitters (acetylcholine, dopamine and γ-aminobutyric acid) increased in brain but decreased in gut after NPs or MFs exposure. For gut microbiota, increased richness under MFs exposure was observed. At phylum level, Proteobacteria proportion was lower in NPs but higher in MFs. Abundance of Clostridia and Fusobacteriia (Bacillus), potentially secreting neurotransmitters, increased in NPs but decreased in MFs. Brain transcriptomics revealed seven upregulated and four downregulated genes concerning neural-activities. Pathways of neuroactive ligand-receptor interaction and serotonergic synapse were enriched in both MFs and NPs, but dopaminergic synapse pathway was enriched only in MFs. These results established a novel mechanism by which microplastics might cause behavioral toxicities via brain-gut-microbiota axis.