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Summary Although advances in coating technologies have allowed us to match—or even exceed—the lubricity of Nature’s low-friction surfaces, the performance of synthetic materials inevitably diminishes over time as the surfaces are worn and damaged by irreversible breakage of covalent bonds. Synthetic systems lack the bespoke repair mechanisms that replenish hydration lubrication surfaces in Nature. Here, we demonstrate dynamic repair of low-friction surfaces prepared through a surface-selective self-assembly strategy. Monolayers of lubricating polymers associate with functionalized surfaces through strong and specific host–guest interactions, leading to hydration lubrication surfaces with low coefficients of friction (0.024–0.028). Following friction-induced dissociation of the polymers, the polymer-to-surface interaction is restored by the reformation of host–guest complexes, thus repairing the monolayer, renewing the lubricity, and reducing the effects of wear. Such dynamically restored low-friction materials will be an essential tool in decreasing global energy use—a fifth of which is expended overcoming friction.

Surface contact with virus is ubiquitous in the transmission pathways of respiratory diseases such as Coronavirus Disease 2019 (COVID-19), by which contaminated surfaces are infectious fomites intensifying the transmission of the disease. To date, the influence of surface wettability on fomite formation remains elusive. Here, we report that superhydrophobicity prevents the attachment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on surfaces by repelling virus-laden droplets. Compared to bare surfaces, superhydrophobic (SHPB) surfaces exhibit a significant reduction in SARS-CoV-2 attachment of up to 99.99995%. We identify the vital importance of solid-liquid adhesion in dominating viral attachment, where the viral activity (N) is proportional to the cube of solid-liquid adhesion (A), N ∝ A3. Our results predict that a surface would be practically free of SARS-CoV-2 deposition when solid-liquid adhesion is ≤1 mN. Engineering surfaces with superhydrophobicity would open an avenue for developing a general approach to preventing fomite formation against the COVID-19 pandemic and future ones.

Cadmium (Cd) is a widespread heavy metal pollutant in the environment that damages human health. In this study, the bioaccessibility and bioavailability of Cd in different Cd-contaminated rice (low pollution level cadmium rice (Rice-L, 0.111 mg/kg), medium pollution level cadmium rice (Rice-M, 0.400 mg/kg), and high pollution level cadmium rice (Rice-H, 0.655 mg/kg)) were estimated and determined by an in vitro digestion model Rijksinstituut voor volksgezondheiden milieu (RIVM), Caco-2 cell model, and mouse model. The results indicated that Cd in the oral cavity (15.65-28.28%) displayed the lowest bioaccessibility comparing with small intestine (90.04-94.73%) and the stomach (99.30-100.70%) in vitro after cooking. In addition, the results showed that the bioaccessibility of Cd in CdCl2 , CdCl2 +normal rice (Rice-N), Rice-H, Rice-M, Rice-L group were 99.29%, 92.57%, 90.04%, 94.73%, and 91.11%, respectively; the in vitro bioavailability of Cd in CdCl2 , CdCl2 +Rice-N, Rice-H, Rice-M, and Rice-L group were 27.50%, 20.78%, 21.90%, 26.90%, 36.46%, respectively, we found that the group of CdCl2 is significantly higher than CdCl2 +Rice-N and Rice-H (p

This paper applies mechanism design to the supply chain enterprise’s pollution abatement problem with carbon tax. To maximize the government’s expected utility, an uncertain contract model is presented in the framework of principal-agent theory, where the government’s assessment of the supply chain enterprise’s carbon emission level is described as an uncertain variable. Afterwards, the equivalent model is provided to obtain the optimal contract for the uncertain pollution abatement problem. The results demonstrate that the supply chain enterprise’s optimal output decreases with the carbon emission level. Furthermore, the government’s optimal transfer payment decreases with the carbon emission level if the carbon tax is low. In contrast, if the carbon tax is high, the optimal transfer payment increases with the carbon emission level. In addition, an increase in the carbon emission level decreases the optimal utilities of both the government and the supply chain enterprise and also leads to the supply chain enterprise’s incremental marginal utility. Finally, we provide a numerical example, which illustrates the effectiveness and practicability of the proposed model.

Background Among various cooking methods, steaming is favored by many because it can cause less damage to nutrient components in muscle, retain the inherent food flavor, and reduce the generation of harmful substances. Steaming conditions are closely related to fish flavor, fat and protein oxidation, and digestibility. Results The black carp steamed for 4 to 14 min was studied in this article based on sensory assessment, electronic tongue, free amino acids, adenosine triphosphate (ATP)-related compounds, total nitrogen and non-protein nitrogen to explore the effect of steaming time on the taste substances and protein degradation of pickled black carp. The experimental result showed that the meat steamed within 8 min tasted better, showing high tastiness. The sensory assessment score increased significantly to the maximum value of 82.33 at 6 min. The content of umami and sweet amino acids increased significantly to the maximum value of 1.6801 g kg-1 at 6 min. In the meantime, the IMP (inosine monophosphate) content was 1.9128 g kg-1 , with its taste activity value (TAV) reaching 7.65, which proved that IMP affected the taste most. Furthermore, the total nitrogen content was 30.77 g kg-1 , which meant protein degraded a great deal. Based on equivalent umami concentration (EUC) and its TAV, the meat tasted best at 6-8 min. The longer the steaming time, the faster the protein degradation and the more the flavor precursors. Conclusion The black carp pickled products (with a weight of 20 g, with the size of 3 cm × 3 cm × 2 cm) is suggested to be steamed for 6 to 8 min. This conclusion provides a theoretical basis for its better taste quality. © 2020 Society of Chemical Industry.

Objective: The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. Methods: C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. Results: Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. Conclusion: YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.

Clinical investigations have shown that a nonimmunogenic "cold" tumor is usually accompanied by few immunopositive cells and more immunosuppressive cells in the tumor microenvironment (TME), which is still the bottleneck of immune activation. Here, a fluorine assembly nanocluster was explored to break the shackles of immunosuppression, reawaken the immune system, and turn the cold tumor "hot." Once under laser irradiation, FS@PMPt produces sufficient reactive oxygen species (ROS) to fracture the ROS-sensitive linker, thus releasing the cisplatin conjugated PMPt to penetrate into the tumors and kill the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Meanwhile, ROS will induce potent immunogenic cell death (ICD) and further promote the accumulation of dendritic cells (DCs) and T cells, therefore not only increasing the infiltration of immunopositive cells from the outside but also reducing the immunosuppressive cells from the inside to break through the bottleneck of immune activation. The FS@PMPt nanocluster regulates the immune process in TME from negative to positive, from shallow to deep, to turn the cold tumor into a hot tumor and provoke a robust antitumor immune response.

The superlubrication property of articular cartilage is attributed to the hydration lubrication mechanism. This involves the complexation of biomacromolecules with phosphatidylcholine lipids to form a lubricating boundary layer on the surface. Based on this mechanism, a branched polyelectrolyte polymer – PEI-PMPC was synthesised in this study to enhance lubrication via tert-butyl hydroperoxide-initiated grafting polymerisation of 2-methacryloyloxyethyl phosphorylcholine (MPC) onto polyethyleneimine (PEI) with various molecular weights. Following the characterisation of the polymer using nuclear magnetic resonance, a series of tribological tests were performed under different normal loads and different scan rates. The results showed that the PEI-PMPC polyelectrolyte polymer in aqueous solution could effectively reduce the friction coefficient and wear generation between the polyethylene ball and the silica wafer. Additionally, an improvement in the lubrication performance was detected for the PEI-PMPC polyelectrolyte polymer when high molecular weight PEI was used during the reaction, which was attributed to the formation of the hydration shells surrounding the zwitterionic charges of PMPC and the viscosity of the polymer. In conclusion, the PEI-PMPC polyelectrolyte polymer developed herein was characterised by enhanced lubrication, and may be potentially used for biomedical applications such as intra-articular injection to restore joint lubrication.

Methamphetamine (Meth), a highly addictive drug, can induce irreversible neuronal damage and cause neuropsychiatric and cognitive disorders. Meth's effects on modulating microglial neuroimmune functions and eliciting neuroinflammation have attracted considerable attention in recent years. Recent evident of the effect of the non-dependent domain containing adaptor inducing interferon (TRIF)/Pellino1 (Peli1) signaling axis on pro-inflammatory cytokine production provides novel clues for inflammation. Therefore, our study investigated Meth-induced neurotoxicity from a neuropathological perspective by examining TLR4-TRIF-Peli1 axis signaling activation. Meth significantly activated microglia accompanied by marked increase of TLR4 and TRIF expression, NF-kB and MAPK pathways activation and the production of IL-1β, TNF-α and IL-6. Peli1 was involved in Meth-mediated neuroinflammation and knockdown of Peli1 strongly reversed NF-kB and MAPK pathways activation and pro-inflammatory cytokine excretion. Intriguingly, Peli1 upregulation induced by Meth was dependent on TRIF rather than the myloid differentiation factor 88 (MyD88) pathway, since the silencing of TRIF significantly suppressed Meth-induced Peli1 upregulation, while MyD88 knockdown had no obvious impact. Additionally, an in vivo study verified TLR4-TRIF-Peli1 axis activation and an enhanced level of downstream cytokine expression in the cortex after Meth treatment. Therefore, these findings provide new insight regarding the specific contributions of the TRIF-Peli1 pathway to Meth-mediated neuroinflammation.

Grass carp is the most important freshwater fish in China, and salting is the main processing method. This study investigated the effect of brine injection on flavor of grass carp muscle compared with brining at low temperature (4°C) and room temperature (20°C) respectively. Salt content, free amino acids, nucleotides, equivalent umami concentration (EUC) and texture were evaluated as flavor indicators during salting. The results showed that brine injection groups reached equilibrium in 3 h and 5 h at 20°C and 4°C, respectively. Brining groups reached equilibrium in 5 h and 7 h at 20°C and 4°C, respectively. The equilibrium salt content was about 1.76%, and there was no significant deterioration in terms of the other indicators mentioned above by two different methods. The results of this research indicate the feasibility and the great economic potential of brine injection, and also provide the theoretical basis to promote this method in processing of aquatic products.

Monolayer (ML)-scale GaN/AlN multiple quantum well (MQW) structures for electron-beam-pumped ultraviolet (UV) emitters are grown on c-sapphire substrates by using plasma-assisted molecular beam epitaxy under controllable metal-rich conditions, which provides the spiral growth of densely packed atomically smooth hillocks without metal droplets. These structures have ML-stepped terrace-like surface topology in the entire QW thickness range from 0.75–7 ML and absence of stress at the well thickness below 2 ML. Satisfactory quantum confinement and mitigating the quantum-confined Stark effect in the stress-free MQW structures enable one to achieve the relatively bright UV cathodoluminescence with a narrow-line (~15 nm) in the sub-250-nm spectral range. The structures with many QWs (up to 400) exhibit the output optical power of ~1 W at 240 nm, when pumped by a standard thermionic-cathode (LaB6) electron gun at an electron energy of 20 keV and a current of 65 mA. This power is increased up to 11.8 W at an average excitation energy of 5 µJ per pulse, generated by the electron gun with a ferroelectric plasma cathode at an electron-beam energy of 12.5 keV and a current of 450 mA.

Present study aims to investigate the effect of nanoparticles (zein nanoparticles, nanocellulose, nano-TiO2, nano-SiO2) incorporation on rheological properties of film-forming solutions and physicochemical properties of konjac glucomannan (KGM) based films, and to evaluate the effect of KGM/nanoparticles blend film on cherry tomatoes preservation. The results showed that the blend film-forming solutions exhibited shear-thinning behavior, and KGM/zein nanoparticle film-forming solution showed the lowest crossover frequency value of storage (G′) and loss (G") moduli due to enhanced molecular interaction and entanglement. The nanoparticles were dispersed homogeneously in the KGM continuous matrix and had good compatibility with KGM, thereby improving physicochemical properties of KGM based films. KGM/zein nanoparticle blend film (KNZ) showed the best properties, such as smoother surface and denser cross-section, the highest glass transition temperature and elongation at break, as well as the best moisture and oxygen barrier. In comparison with the control and polyethylene film packaging, cherry tomatoes in KNZ film packaging showed lower weight loss and firmness reduction, and had relatively stable content of total soluble solids, vitamin C content and pH value during storage up to 10 days at 26 °C. The results suggested the high potential of KNZ film for application in cherry tomatoes preservation.

Leaf size and flatness directly affect photosynthesis and are closely related to agricultural yield. The final leaf size and shape are coordinately determined by cell proliferation, differentiation, and expansion during leaf development. Lettuce (Lactuca sativa L.) is one of the most important leafy vegetables worldwide, and lettuce leaves vary in shape and size. However, the molecular mechanisms of leaf development in lettuce are largely unknown. In this study, we showed that the lettuce APETALA2 (LsAP2) gene regulates leaf morphology. LsAP2 encodes a transcriptional repressor that contains the conserved EAR motif, which mediates interactions with the TOPLESS/TOPLESS-RELATED (TPL/TPR) corepressors. Overexpression of LsAP2 led to small and crinkly leaves, and many bulges were seen on the surface of the leaf blade. LsAP2 physically interacted with the CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factors and inhibited their transcriptional activation activity. RNA sequencing analysis showed that LsAP2 affected the expression of auxin- and polarity-related genes. In addition, LsAP2 directly repressed the abaxial identity gene KANADI2 (LsKAN2). Together, these results indicate that LsAP2 regulates leaf morphology by inhibiting CIN-like TCP transcription factors and repressing LsKAN2, and our work provides insights into the regulatory mechanisms of leaf development in lettuce.

In this work, a simple and rapid method based on the lateral flow assay (LFA) has been developed for the detection of dual antibiotics. To achieve the quantitative assay and to reduce the non-specific adsorption, an internal system has been developed. A non-specific DNA was exploited as an internal standard and could be recognized by the DNA marker that was coated at the internal line. Two different kinds of aptamers were applied to recognize ampicillin (AMP) and kanamycin (KAM), and the distance between the detection line and conjugate pad was then optimized. Under the optimum conditions, the quantitative assays of AMP (R2 = 0.984) and KAM (R2 = 0.990) were achieved with dynamic ranges of 0.50 to 500.0 ng/L, and of 0.50 to 1000.0 ng/L, respectively. The LOQs of AMP and KAM were 0.06 ng/L and 0.015 ng/L, respectively. Finally, the proposed method has been successfully applied to analyze aquaculture water, tap water, and lake water, and hospital wastewater, indicating the established method could be used to monitor the environment.

Avian leukemia virus (ALV) is a retrovirus that infects a variety of poultry, and is a vertical transmission of poultry-borne disease. The harm of ALV gradually magnifies with the increase of generations. siRNA with high efficiency, high safety, silence specificity, and unlimited targets have aroused increasing attention from the medical profession, However, there is no suitable vehicle to assist ALV-targeted siRNA for cell internalization. In this paper, ALV-targeted siRNA was first loaded by 13 nm Au NPs layer by layer to synthesize Au@PRP NPs with good stability (78 nm, ζ= +38), which provided an opportunity for the safe diffusion of Au@PRP NPs into cells and specific binding with ALV. Au @PRP NPs could effectively deliver siRNA to DF-1 cells (92.1%) and contain 20 pmol Cy3-siRNA/per million. The strong polyelectrolyte on the surface of Au@PRP NPs can effectively capture cells and co-infect with ALV as high as 88-100%. Moreover, Au@PRP NPs can locate C/E chicken embryo fibroblasts (DF-1 cells) with ALV, and have a significant inhibitory effect on the release of virus particles. Au@PRP NPs will bring new opportunity to research how the multifunctional load design and tracking path of gold nanoparticles influence the uptake/inhibition mechanisms of ALV and the other poultry diseases and guide different target genes to exert their effects.

Exudate regulation, which helps maintain an optimal moisture content in the wound bed and protects the surrounding skin from maceration, is a prerequisite for wound healing. In this study, inspired by the natural hierarchical structure of sugarcane, in which vascular bundles are responsible for transporting water and parenchyma cells are responsible for storing sucrose, we fabricated a continuously self-draining sugarcane stem-based dressing to remove exudates from overhydrated wounds. Sugarcane cellulosic frameworks (SCF), obtained via alkali and de-sugaring treatments of natural sugarcane substrates (SS), were coated with gold nanorods (AuNRs) to facilitate photothermal responsiveness under near-infrared (NIR) irradiation. By mimicking plant transpiration and incorporating a stimulus-responsive feature, natural SS were transformed into exudate-managing dressing materials for accelerated wound healing. As the obtained sugarcane frameworks (Au@SCF) contained abundant vascular bundles and exhibited photothermal responsiveness, it was able to self-drain exudates continuously with a high evaporation efficiency (95%). In order to endow the dressing with antibacterial properties, Ag nanoparticles (AgNPs) was incorporated with Au@SCF to form Ag@Au@SCF. The healing process in a wound model was more rapid with Ag@Au@SCF with NIR irradiation than with a commercial dressing. Moreover, as the parenchyma cells in Ag@Au@SCF formed closed chambers after de-sugaring, Ag@Au@SCF facilitated effective thermal insulation (thermal conductivity of 0.04 W m−1k−1) for protecting the underlying wound, even when the temperature of the top surface was high (53 °C). As this hierarchical structure is naturally existent in other Poaceae plants, which are sustainable green resources, our findings may provide a new strategy for the fabrication of versatile and efficient self-draining dressings for exudate management and wound healing.

Aims Myosin phosphatase targeting protein 1 (MYPT1) was identified to function as a tumor suppressor in several kinds of cancers, but its role and the molecular mechanisms in non-small cell lung cancer (NSCLC) remain undiscovered. Herein, we aimed to reveal MYPT1 expression pattern and role in NSCLC, and investigate the underlying mechanisms. Main methods Sixty-eight paired NSCLC tissues and the adjacent normal tissues were included in this study. Western blotting and quantitative reverse transcription-polymerase chain (qPCR) technologies were applied for protein and RNA detection. CCK-8, colony formation, flow cytometry, wound healing, transwell chambers coated with Matrigel and in vivo experiments were applied to detect cell viability, colony formation, apoptosis, migration, invasiveness and tumorigenesis, respectively. Key findings MYPT1 expressed at a lower level in NSCLC tissues as compared with the adjacent normal tissues, which predicted advanced clinic process and poor prognosis. Overexpression of MYPT1 resulted in obvious inhibitions in cell viability, colony formation, migration, invasiveness and tumorigenesis, and induced cell apoptotic rates, as well as decreased the expression levels of β-catenin and TCF4. Besides, overexpression of β-catenin weakened the above roles of MYPT1. In addition, the luciferase gene reporter assay verified that MYPT1 was a target of miR-19b-3p. Further experiments showed that miR-19b-3p promoted cell viability, invasiveness and migration and repressed cell apoptosis by targeting MYPT1. Significance In conclusion, this study demonstrates that MYPT1, regulated by miR-19b-3p, inhibits the progression of NSCLC via inhibiting the activation of wnt/β-catenin signaling.

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs., Here, using lung epithelial cells and ex vivo tissue explants, the authors show that, in addition to ACE2, host heparan sulfate is directly involved in SARS-CoV-2 attachment and entry and provide data suggesting that host sialic acids may act as viral restriction factor in lung tissues.

Heme Oxygenase-1 (HO-1) is a ubiquitously expressed enzyme which plays important functions in antioxidant, anti-inflammatory and anti-apoptosis. Recent studies have demonstrated that HO-1 also has significant antiviral properties, inhibiting the replication of some kinds of viruses such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and dengue fever virus (DFV). In this study, we evaluated the role of HO-1 in Duck Tembusu virus (DTMUV) replication in vitro. The results showed that, the mRNA expression level of HO-1 was transient up-regulated and then significantly decreased in duck embryo fibroblast (DEF) infected with DTMUV. HO-1 induction by transfection of HO-1 over-expression plasmid or treatment with cobalt protoporphyrin (CoPP), a potent HO-1 inducer, could inhibit DTMUV replication effectively. In contrast, HO-1 siRNA knockdown in DEF increased DTMUV replication, implied that HO-1 was an important cellular factor against DTMUV replication. Furthermore, we found that ferric ion (Fe3+) but not biliverdin and carbon monoxide, products of heme degradation by HO-1, mediated the HO-1-induced anti-DTMUV effect. Overall, these finding revealed that a drug induced the HO-1 signal pathway was a promising strategy for treating DTMUV infection.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome as an arising health issue globally. Obesity and diabetes seem coherent with high NAFLD occurrence. Currently, its underlying mechanism of cause and progression remains to be elicited and effective therapy is unavailable. Huge investment on studying its pathogenesis and innovative therapy is underway. As mechanistic studies are more difficult or unethical to be performed in humans, animal model that recapitulates the human disease is urgently needed. Nonhuman primates (NHPs) with NAFLD can highly mimic the human disease. This study aimed to induce NAFLD by various diets (Table 1) in normoglycemic and diabetic NHPs with biomarker and histopathology assays to quantify NAFLD occurrence. Our data show that diabetic monkeys with high-fat-high-fructose (HFHF) diet developed NAFLD which could assemble to the human disease and be highly valuable for NAFLD research. However, low choline (LC), LC+10% fructose, LC+low methionine (LCM)+10% fructose diets for 31 weeks had no significant effects on liver function, except significant decrease in body weight and food intake in LCM+10%F group and some increase in liver histological scores in LC+10%F group (Table 1). In summary, normal diet with LC or LCM ± high fructose is hardly to induce NAFLD in normoglycemic NHPs, at least in 31 weeks. HFHF could induce or enhance NAFLD in diabetic NHPs. Disclosure J. Gao: Employee; Self; Crown Bioscience. D. Wang: Employee; Self; Crown Bioscience. Y. Ji: Employee; Self; Crown Bioscience. X. Zhang: Employee; Self; Crown Bioscience. C. Yang: None. J. Zhang: Employee; Self; Crown Bioscience. W. Ye: Employee; Self; Crown Bioscience. F. Shi: Employee; Self; Crown Bioscience. M. Jiang: Employee; Self; Crown Bioscience. Q. Jin: Employee; Self; Crown Bioscience. D. Zhang: None. X. Wang: None. W. Song: Employee; Self; Crown Bioscience. K. Chng: None. H. Jiang: Employee; Self; SYSE Bio-tec Co., Ltd. Y. Wang: None. Y. Xiao: Employee; Self; Crown Bioscience.

MS-NASH mouse is a leptin pathway intact model of spontaneous metabolic diseases. Our previous work developed a nonalcoholic steatohepatitis (NASH) model in MS-NASH mice fed with western diet and fructose drinking water (WDF). This study showed aggravated liver cholesterol content and fibrosis score by using a modified Amylin diet (GAN). Liver Cholesterol was increased from 10.11±1.58 mg/g to 14.07±0.81 mg/g and fibrosis score increased from 1.5±0.3 to 2.1±0.2 when comparing GAN with WDF and with C57Bl/6 mice. Administration of 30 mg/kg Obeticholic Acid (OCA, QD, PO) or 30 mg/kg Elafibranor (GFT-505, QD, PO) for 8 weeks significantly reduced serum liver enzymes, liver lipids and fibrosis scores. Conclusion: The GAN diet fed MS-NASH mice can be a better NASH model for novel compound efficacy. Disclosure G. Zhang: None. K. Chng: None. Y. Wang: None.

DNA code design aims to generate a set of DNA sequences (codewords) with minimum likelihood of undesired hybridizations among sequences and their reverse-complement (RC) pairs (cross-hybridization). Inspired by the distinct hybridization affinities (or stabilities) of perfect double helix constructed by individual single-stranded DNA (ssDNA) and its RC pair, we propose a novel similarity significance (SS) model to measure the similarity between DNA sequences. Particularly, instead of directly measuring the similarity of two sequences by any metric/approach, the proposed SS works in a way to evaluate how more likely will the undesirable hybridizations occur over the desirable hybridizations in the presence of the two measured sequences and their RC pairs. With this SS model, we construct thermodynamically stable DNA codes subject to several combinatorial constraints using a sorting-based algorithm. The proposed scheme results in DNA codes with larger code sizes and wider free energy gaps (hence better cross-hybridization performance) compared to the existing methods., To appear in ISIT 2020

Background: Trials reported there are beneficial effects of the addition of bevacizumab to chemotherapy in advanced cervical cancer but might have adverse effects. The purposes of the study were to evaluate the treatment response and safety of the addition of bevacizumab to paclitaxel plus carboplatin in advanced cervical cancer women. Methods: Data on treatment response, adverse effects, and overall survival of women who received paclitaxel plus carboplatin every 3 weeks (ACT cohort, n = 161) or paclitaxel, carboplatin, and bevacizumab every 3 weeks (PCB cohort, n = 127) until disease progression or severe adverse events were collected and analyzed. Results: The treatment response of paclitaxel plus carboplatin increased on addition of bevacizumab ( P = .037). Neutropenia (grade ≥3, P = .001), leukopenia (grade 4, P = .041), anemia (grade ≥3, P = .031), hypertension (grade ≥2, P = .002), and gastrointestinal fistula (grade ≥2, P = 0.006) are reported in the PCB cohort. Women of ACT and PCB cohorts reported an overall survival of 20.11 ± 3.15 months and 24.52 ± 4.05 months, respectively. Conclusions: Addition of bevacizumab increases the treatment response of paclitaxel and carboplatin chemotherapy and overall survival of women with advanced cervical cancers, but it is not well tolerated.

Corneal endothelial disease is a global sight-threatening disease, and corneal transplantation using donor corneas remains the sole therapeutic option. A previous work demonstrated that N (2)-alanyl-glutamine (Ala-Gln) protected against apoptosis and cellular stress, and maintained intestinal tissue integrity. In this pursuit, the present study aimed to examine the effect of Ala-Gln in the protection of the corneal endothelium and expand its range of potential clinical applications. Mice in the control group were intracamerally irrigated with Ringers lactate injection, whereas those in the experimental group were irrigated with Ringers lactate injection containing Ala-Gln. The mean intraocular pressure increased to 44 ± 3.5 mm Hg during intracameral irrigation (normal range 10.2 ± 0.4 mmHg). In vivo confocal microscopy results showed that the addition of Ala-Gln protected the morphology, structure, and density of the corneal endothelial cells. Optical Coherence Tomography (OCT) measurements showed that corneal thickness was not significantly different between the two groups, because of the immediate corneal edema after irrigation, but the addition of Ala-Gln obviously promoted the recovery of the corneal edema. Scanning electron microscopy indicated that the corneal endothelial cells were severely ruptured and exfoliated in the Ringer's group accompanied with cellular edema, when compared with the Ala-Gln group. The intracameral irrigation using Ala-Gln protected the structure and expression of cytoskeleton and Na-K-ATPase, which exhibited a regular distribution and significantly increased expression in comparison to Ringer's group. Furthermore, Ala-Gln maintained the mitochondrial morphology and increased the activity of mitochondria. Moreover, transmission electron microscopy showed that intracameral irrigation of Ala-Gln reversed the ultrastructural changes induced by the acute ocular hypertension in mice. Our study demonstrates that the intracameral irrigation of Ala-Gln effectively maintained the corneal endothelial pump function and barrier function by protecting the mitochondrial function and preventing the rearrangement of cytoskeleton in acute ocular hypertension in mice.

Wound dressings play a critical role in the cutaneous healing process. The uncertainty of an injury leads to an irregular wound. However, incomplete contact between a general dressing and wound reduces the effectiveness of the dressing. Therefore, self-adapting hydrogels that are adhesive, injectable, and self-healable are being developed to efficiently treat irregular skin wounds. Here, we present an approach based on dynamic Schiff-base bond formation to prepare self-adapting hydrogel dressings that automatically adapt to irregular wounds under natural conditions and sustain total contact with the injured site. Spectroscopic investigations suggested the formation of dynamic covalent Schiff-base bonds, which are closely associated with the rapid formation of the hydrogel, between the aldehyde groups of oxidized konjac glucomannan and amine groups in the backbone of protonated chitosan and protonated tranexamic acid. Rheological analysis confirmed the self-healing property of the hydrogel, that is, the recovery of the broken hydrogel network. Histological analysis indicated that this self-adapting hydrogel provides a clear advantage over the commercial hydrogel dressing (AquacelAg™) in the in vivo wound-healing process. Our rapidly gelating hydrogel formulations with self-healing ability, tissue adhesiveness, and antibacterial activity are very promising self-adapting biomaterials for repairing irregular wounds.

Core-shell structural capsules can encapsulate various food ingredients (e.g., nutrients), thus being highly potential for the design of many food products. This work reports how the gum (xanthan, locust bean or gellan) inclusion tailors the practical features of agar/konjac glucomannan (KGM) system for fabricating the core-shell structural capsules. The rheological and textural analyses revealed that xanthan gum inclusion could simultaneously increase the sol-gel transition point and gel strength (ca. 1.6 times higher) of agar/KGM system. The composite gels were dehydrated to generate shell materials. The materials including xanthan or locust bean gum showed stronger chain interactions than did that including gellan gum, accompanied by weakened crystalline features for the different shell materials. Again, compared to the agar/KGM counterpart, the shell materials including xanthan gum could display a similar tensile strength (close to 50 MPa) but an evidently increased elongation at break (ca. 2.5 times higher). Then, these agar/KGM based systems were used to prepare core-shell structural capsules. The capsules based on agar/KGM/xanthan gum materials exhibited the highest roundness and breaking stress. Regarding this, the increased sol-gel point reduced the time required for droplet hardening (to generate core-shell gel balls); such fact, together with the higher gel strength, weakened the deformation of gel balls and thus increased the roundness and breaking stress of capsules (resulting from drying of gel balls).

Proliferative diabetic retinopathy (PDR) is the leading cause of blindness and accounts for approximately 12% of all new cases of blindness. Prostaglandin E2 (PGE2) and nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes have been long considered to be associated with PDR. Levels of pro-inflammatory mediators were examined by Enzyme-linked immunosorbent assay (ELISA) measurements. PGE2 levels were analyzed by using the Prostaglandin E2 Monoclonal EIA Kit. Human retinal microvascular endothelial cells (HRMECs) were stained with Annexin V/propidium iodide and analyzed by flow cytometry for testing the apoptosis. Expression levels of NLRP3 inflammasome components under various conditions were detected by Western blot and real-time PCR. Inflammasome markers and PGE2 were highly expressed in the vitreous of PDR patients. PGE2 and NLRP3 induced apoptosis of HRMECs. PGE2 upregulated the expression of NLRP3 inflammasome components and inflammatory chemokines. Knockdown of NLRP3 attenuated the expression of NLRP3 inflammasome components and inhibited the effect of PGE2. Our results suggest that PGE2 levels and NLRP3 inflammasome activation are closely related to the pathogenesis of PDR and nonsteroidal anti-inflammatory drugs may have a potential therapeutic effect on PDR.

Molybdenum sulfide/reduced graphene oxide (MoS2/RGO) porous film was in-situ deposited on fluorine-doped tin oxide (FTO) substrates via a one-pot hydrothermal method. Due to the oxygen-containing groups distributing on graphene oxide (GO) surface, the MoS2 sheets could nucleate and grow taking GO as substrates and the MoS2/RGO film can be strongly linked to the FTO. Based on the electrochemical investigations, the enhanced cell performance could be ascribed to the improved electrical conductivity, catalytic active sites and electrolyte diffusion rate, which finally contribute to the high catalytic performance on the reduction of I−/I3− couples in the electrolyte. Therefore, the cell adopting as-prepared MoS2/RGO as counter electrode demonstrated high power conversion efficiencies (PCE) of 7.63%, which indicates ∼14% enhancement compared with the MoS2-based (6.68%) device.

We report the development of a small interfering RNA (siRNA) delivery vector based on cationic perfluorocarbon nanoemulsions. We have prepared perfluorodecalin (PFD) emulsions with a positive surface charge provided by a fluorinated poly(ethylenimine) (F-PEI). The fluorinated emulsion (F-PEI@PFD) reduced cytotoxicity of F-PEI and demonstrated effective binding with siRNAs to form nanosized emulsion polyplexes. The prepared emulsion polyplexes enhanced cellular uptake and improved endosomal escape of the siRNA. In addition to increased reporter gene silencing in multiple cancer cell lines, when compared with control F-PEI and PEI polyplexes, the siRNA emulsion polyplexes showed an excellent resistance to serum deactivation and maintained high activity, even in high-serum conditions. The F-PEI@PFD emulsion polyplexes carrying an siRNA to silence the expression of Bcl2 gene induced apoptosis and inhibited tumor growth in a melanoma mouse model in vivo and showed potential for in vivo ultrasound imaging. This study demonstrates the potential of F-PEI@PFD emulsions as a multifunctional theranostic nanoplatform for safe siRNA delivery, with integrated ultrasound imaging functionality.

Effect of indium (In) droplets on InGaN thin films grown by molecular beam epitaxy (MBE) has been investigated. The surface of InGaN covered by In droplets shows a smoother topography than that without droplets, indicating that the presence of In droplets is beneficial to the two dimensional growth. Beneath the In droplets, many ring-like structures are observed. The arrangement of these “ring” shows the movement of the In droplets during the InGaN growth. A qualitative growth model is proposed to explain the evolution of the InGaN surface morphology in In-droplet-induced-epitaxy process, giving an explanation that a local vapor-liquid-solid (VLS) system is preferentially formed at the edge of the droplets, leading to a high growth rate. Furthermore, the energy dispersive X-ray spectroscopy results reveal that the relatively higher In/Ga flux ratio in the region covered by the In droplet results in a locally higher In content.

Bacteria-based therapy has shown great promise in treating various diseases by regulating intestinal flora balance in pre-clinical and clinical studies. However, weak resistance against stress in the gastrointestinal (GI) tract and limited retention time in the intestine result in low bacteria availability and persistence, restricting further clinical application. Here, we report a double-layer coating strategy employing tannic acid (TA) and enteric L100 for probiotics encapsulation to address the delivery challenges after oral administration. The Escherichia coli Nissle 1917 (EcN) sequentially encapsulated by TA and L100 layers display robust resistances against the harsh external environment of the GI tract. Furthermore, the pH-responsive degradation of the outer L100 layer leads to the selective delivery of TA-EcN to the intestine, where the strong mucoadhesive capability of the TA layer prolongs the retention time of EcN without compromising the viability and proliferation capabilities of EcN, resulting in superior efficacy of prophylactic and treatment efficacy against colitis. To mitigate the potential side effects caused by long-term mucoadhesion of TA, the TA layer can be further removed by addition of ethylenediaminetetraacetic acid (EDTA). The spatiotemporal delivery of probiotics through double-layer encapsulation can augment the therapeutic efficacy of bacteria-based therapy against GI tract-related diseases.

Currently, Coronavirus Disease 2019 (COVID-19) – a respiratory contagion spreading through expiratory droplets – has evolved into a global pandemic, severely impacting the public health. Importantly, the emerging of immune evasion SARS-CoV-2 variants and the limited effect of current antivirals against SARS-CoV-2 in clinical trials suggested that alternative strategies in addition to the conventional vaccines and antivirals is required to successfully control the COVID-19 pandemic. Here, we propose to use liquid-repellent coatings to prevent the spread of disease in the absence of effective vaccines, anti-microbial agents or therapeutics, wherein the deposition and penetration of pathogen droplets are prohibited. We use SARS-CoV-2 as a model pathogen and find that SARS-CoV-2 remnants are reduced by seven orders of magnitude on coated surfaces, yielding a repelling efficacy far outperforming the inactivation rate of disinfectants. The SARS-CoV-2 remnant scales exponentially with the liquid/solid adhesion, uncovering the mechanism and effective means for minimizing pathogen attachment. The anti-pathogen coating that both repels and inactivates pathogens is demonstrated by incorporating the super-liquid-repellent coating with anti-pathogen additives. Together with its versatility over a wide range of substrates and pathogens, the novel anti-pathogen coating is of considerable value for infection control in everyday life as well as during pandemics., Graphical abstract Image 1

An in situ hydrothermal method is employed to vertically grow Few-layer MoS2 (3–5 layers) sheets on three dimensional graphene. Oxygen atoms are spontaneously incorporated into the MoS2 layers due to the inert Mo O bonds from the precursor and the abundant oxygen-content groups distributed on the graphene oxide sheets, which reduces the bandgap and improves the conductivity and catalyzing activity of the MoS2. In addition, the three dimensional composite exhibits good mechanical strength, interconnected electron transfer network, high surface area of 117.9 cm2 g−1, and multi-level porous structures from micro- to macro- scale, which enhances the charge and mass transport when used as counter electrode for quantum dot sensitized solar cells. Therefore, an optimized power conversion efficiency of 4.13% is demonstrated, indicating ∼63% and ∼34% enhancement compared with Pt and pure MoS2 counter electrodes.

Background Endoglin is a co-receptor for TGFbeta/BMP9/10 signalling and ENG mutations lead to the vascular disorder hereditary haemorrhagic telangiectasia type I (HHT). Endoglin is also required for normal vascular development and angiogenesis, but little is known about endoglin's role in quiescent adult vascular endothelium. Purpose The goal of this present study is to determine how endoglin maintains vessel calibre in adult life to prevent AVM formation and thereby protect heart function. Methods To investigate this role, tamoxifen was administered to adult Cdh5(PAC)-CreERT2; Engfl/fl mice to generate endothelial-specific depletion of endoglin (Eng-iKOe). Cardiac magnetic resonance imaging, myography, vascular casting, microsphere injection, immunohistology, qPCR and aortic telemetry were used to evaluate cardiovascular changes after endoglin knockdown. Results Endothelial-specific loss of endoglin leads to an enlarged heart and cardiomyocyte hypertrophy within 5 weeks, progressing to high output heart failure (HOHF). In vivo aortic telemetry revealed significant loss of aortic pressure within a few days of endoglin depletion. Increased cardiac size and reduced cardiac afterload were confirmed by ventricular pressure loop analysis. As HOHF could result from arteriovenous malformations (AVMs), and these are found primarily in mucocutaneous and pulmonary tissues in HHT, we systematically screened for AVMs using microspheres and vascular casting. Although AVMs were absent in the majority of tissues, they were observed in the pelvic region and may account for the rapid increase in cardiac output. The pelvic cartilaginous symphysis is a noncapsulated cartilage with a naturally high endogenous expression of vascular endothelial growth factor (VEGF). Development of pelvic AVMs in this region of high VEGF expression occurred because loss of endoglin in endothelial cells leads to increased sensitivity to VEGF and a hyper-proliferative response. Finally, we found that inhibition of VEGFR2 was protective against AVMs development, enlargement of the heart and dilatation of the ventricles. Conclusion Our results showed the essential role of endoglin in the maintenance of adult cardio-vasculature through crosstalk with the VEGF signalling pathway. Acknowledgement/Funding British Heart Foundation, Cure HHT, The Swedish Research Council, The Cardiovascular Programme at Karolinska Institutet, The Swedish Cancer Society

DNA has become an attractive medium for long-term data archiving due to its extremely high storage density and longevity. Short single-stranded DNAs, called oligonucleotides (oligos), have been designed and synthesized to store digital data. Previous works designed the oligos with a pair of primer binding sites (PBSs) (each with a length of around 200) attached at the two ends of each basic readable data block. The addition of PBSs decreases the data density significantly because in the current DNA synthesis, the maximum length of a synthesized oligo in good quality is around 200. Furthermore, the maximum homopolymer run allowed by the existing experiments has been reported to be three nucleotides. In this work, to increase the data density, we have devised and tested an oligo design for DNA-based storage with the basic readable data block appended by a single PBS at one end only, while allowing the maximum homopolymer run to be increased to 4. We also present an oligo assembly algorithm that can reconstruct oligos with a single PBS from the error-prone raw readouts obtained from the sequencing process. We have conducted a wet lab experiment to validate the proposed design, where we tested with 398KB of data stored into 10,750 oligos. The experimental results show that it is possible to recover over 99 percent of the oligo sequences without error, which proves that one PBS is sufficient for implementing a DNA-based data storage system with maximum homopolymer run relaxed to 4. The use of single PBS leads to a significant data density gain from 14.3 to 140.2 percent over the existing short-strand DNA data storage schemes by reserving more nucleotides for storing information bits.

Background Recurrent pregnancy loss (RPL) refers to two or more spontaneous abortions that occur consecutively with the same spouse. RPL severely affects human reproduction health, and causes extreme physical and mental suffering to patients and their families. Methods We used isobaric tags for relative and absolute quantitation (iTRAQ), which was coupled with liquid chromatography mass spectrometry (LC-MS) proteomic analysis, in order to identify differentially expressed proteins. Moreover, we used western blot to analyze differentially expressed proteins. Results Of the 2350 non-redundant proteins identified, 38 proteins were significantly altered and were identified as potential biomarkers for RPL. The protein-protein interaction network constructed using GeneMANIA revealed that 35.55% displayed similar co-expression, 30.87% were predicted, and 20.95% had physical interaction characteristics. Based on Gene ontology classification and KEGG pathway enrichment analyses, the majority of these differentially expressed proteins were found to be related to biological regulation, metabolic and cellular processes, protein binding and different enzymes activities, as well as disorder of fat and glucose metabolic pathways. It is noteworthy that three metabolism related biomarkers (HK1, ACLY, and FASN) were further confirmed through western blot analysis. Conclusions These results suggest that these differentially expressed proteins may be used as biomarkers for RPL, and related signaling pathways may play crucial roles in male induced RPL. Electronic supplementary material The online version of this article (10.1186/s12958-019-0496-5) contains supplementary material, which is available to authorized users.

Carbon Tetrachloride (CCl4) is a common hepatotoxin used in liver injury and fibrosis animal models, but it is rare to observe obesity and liver fat accumulation in CCl4-induced liver fibrosis models since weight loss is also provoked. Nonalcoholic Steatohepatitis (NASH) is an epidemic disease coincides with obesity and type 2 diabetes (T2D) causing liver steatosis and inflammation. There are no perfect animal models that capture all steatosis, inflammation and following fibrosis stages of NASH disease, our recent study developed an accelerated fibrotic model in previously established NASH model of western diet fed FATZO/pco mice. Using a dose of 0.08 mL/kg (IP, 2/week) CCl4 on 8-week western diet fed FATZO/pco mice, the average histology fibrosis score increased from 1.2±0.2 to 3.0±0.0, average lobular inflammation score increased from 1.4±0.7 to 1.9±0.1, while average steatosis score remained stable. Hepatotoxicity of CCl4 affected the hepatocyte ballooning score due to increased necrosis, reducing ballooning score from 1.6±0.4 to 1.0±0.0. It is also interesting to find out the FATZO/pco strain tolerated CCl4 challenges better than the control C57Bl/6 strain. Conclusion: The study developed an accelerated NASH mice model with balanced performance in all stages of histopathology and provides better translational values in comparison with human patients. Disclosure G. Zhang: None. K. Chng: None. Y. Wang: None.

The konjac glucomannan (KGM)-based aerogel as an air filtration material was fabricated through sol-gel and freeze-drying methods. Results showed that gelatin and starch addition could increase the filtration efficiency and compressive strength of aerogel significantly, due to the appearance of more microporous structure and the formation of dense structure in aerogel. The addition of wheat straw could decrease the filtration resistance and increase the breathability of KGM-based aerogel, which was attributed to the multi-cavities of wheat straw. The aerogel with wheat straw had a filtration efficiency of 93.54% for particle matters ≥ 0.3 μm, a filtration resistance 29 Pa, and an air permeability 271.42 L/s·m2. Okara addition could increase the hydrophobicity of KGM-based aerogel by increasing the water contact angle and decreasing the equilibrium water content. The water contact angle of the aerogel containing okara reached 105.4°, and the equilibrium water content was decreased by 17.03%–81.10% compared with that without okara, with relative humidity 0%–80%. The results demonstrated that the KGM-based aerogel had good performance on filtration, mechanical and hydrophobic properties, indicating high potential application as an air filtration material.

Osteoarthritis (OA) is a chronic joint disease resulting from joint inflammation and damage. In this study, we employed a boundary lubricant known as a 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) liposome for loading of an anti-inflammatory drug D-glucosamine sulphate (GAS) to construct a treatment strategy allowing for sustained anti-inflammation and reduced damage. This kind of drug-loaded nanocarrier integrates the anti-inflammatory effect of the GAS and the lubrication ability of DSPC liposomes without the involvement of complex synthesis processes leading to easier popularization. Our experimental results indicated that the GAS-loaded DSPC liposomes could release GAS in a sustained manner while providing good lubrication in pure water (H2O) and phosphate buffered saline (PBS). Moreover, the GAS-loaded DSPC liposomes prepared at a 2 : 8 molar ratio in PBS exhibited a greater entrapment efficiency, lower GAS release rate and smaller friction coefficient as compared to those prepared in H2O. The superiority of the drug release and lubrication ability achieved with the GAS-loaded DSPC liposomes in PBS were elucidated on the basis of salt-induced enhancement in liposomal stability and hydration lubrication by the hydrated salt ions. Such GAS release accelerated the viability and proliferation of primary mouse chondrocytes while also providing the anti-inflammatory and chondroprotective potential for tumor necrosis factor (TNF-α) induced chondrocyte degeneration through the down-regulation of pro-inflammatory cytokines, pain related gene and catabolic proteases, as well as the up-regulation of anabolic components. We envision that the GAS-loaded DSPC liposomes could represent a promising new strategy for clinical treatment of OA in the future.

Diabetic retinopathy is a diabetes complication. During diabetic retinopathy development, the TLR4/NF-κB pathway is up-regulated. Apocynin is a nicotinamide adenine dinucleotide phosphate oxidase blocker which can reduce the superoxide radicals. It is demonstrated that apocynin can inhibit TLR4/NF-κB pathway in rats. We aim to figure out whether apocynin treatment is benefit for the diabetic retinopathy in rat model. The diabetes in rats was induced by streptozotocin. The treatment of apocynin (16 mg/kg/day) or vehicle in diabetic rat model was maintained for 12 weeks. The expression levels of relative genes in this research were shown through Western blot and qRT-PCR. Morphology of the retinas was shown by Hematoxylin-Eosin staining. The treatment of apocynin ameliorated biochemical indexes in diabetic rats and rescued the morphology of the retinas. After a 12 weeks apocynin treatment, the cell apoptosis, oxidative stress, and inflammatory in retina was reduced in diabetic rats. TLR4/NF-κB signaling pathway activity in diabetic rat retina was inhibited by apocynin. Based on our study, the treatment of apocynin ameliorates diabetic retinopathy in rats. The TLR4/NF-κB signaling pathway inhibition by apocynin is involved in this process. This result indicated a great therapeutic potential of apocynin in diabetic retinopathy treatment.

Background and aims Alpha 7 nicotinic acetylcholine receptor (α7nAChR) stimulation can regulate acute inflammation, and lack of α7nAChR accelerates atherosclerosis in mice. In this study, we aimed to investigate the effects of the novel α7nAChR agonist, AZ6983, on atherosclerosis and assess its possible immune-modulating effects. Methods AZ6983 was tested in vitro in LPS-challenged mouse and human blood and in vivo using the acute inflammatory air pouch model. Thereafter, long-term effects of AZ6983 treatment on atherosclerosis and immune responses were assessed in apoE −/− mice after 8 and 12 weeks. Atherosclerosis was investigated in the aortic root and thoracic aorta, serum levels of cytokines were analysed and RNAseq was used to study aortic gene expression. Further, bone-marrow-derived macrophages were used to assess phagocytosis in vitro . Results α7nAChR activation by AZ6983 decreased pro-inflammatory cytokines in acute stimulations of human and mouse blood in vitro , as well as in vivo using the air pouch model. Treating apoE −/− mice with AZ6983 decreased atherosclerosis by 37–49% and decreased serum cytokine levels. RNAseq analysis of aortae suggested the involvement of several specific myeloid cell functions, including phagocytosis. In line with this, AZ6983 significantly increased phagocytosis in bone marrow-derived macrophages. Conclusions This study demonstrates that activation of α7nAChR with AZ6983 inhibits atherosclerosis in apoE −/− mice and that immune-modulating effects on myeloid cells, such as enhanced phagocytosis and suppression of inflammatory cytokines, could be part of the athero-protective mechanisms. The observed anti-inflammatory effect in human blood supports the idea that AZ6983 may decrease disease also in humans.

Conventional thermosets consisting of polymer networks with robust and irreversible chemical linkages are incapable of reshaping or reprocessing once formed. In contrast, reversible non-covalent crosslinks can impart structurally flexible and reconfigurable feature to the networks, but at the expense of certain mechanical strength. The integration of fixed covalent bonds and noncovalent bonds into these materials can usually attain enhanced mechanical properties and meanwhile provide dynamic and adaptable functions, such as responsive and healing ability to external stimuli. Here a double-cross-linked frustrated Lewis pair network (FLPN) is developed through a specific three-component reaction among triarylborane, triarylphosphine, and CO2 , which is composed of permanent chemical crosslinks and dynamic CO2 gas-bridged connections. The amount of CO2 added can regulate the density of supramolecular node in such FLPN, so as to control the strength and toughness of the gel material. Moreover, the broken gel can be rapidly healed by CO2 stimulus through the reconstruction of dynamic covalent network. This study will inspire a new way to create gas-based smart materials by incorporating frustrated Lewis pair chemistry into traditional gel system.