Fluorine-Containing Ionogels with Stretchable, Solvent-Resistant, Wide Temperature Tolerance, and Transparent Properties for Ionic Conductors.

Stretchable ionogels, as soft ion-conducting materials, have generated significant interest. However, the integration of multiple functions into a single ionogel, including temperature tolerance, self-adhesiveness, and stability in diverse environments, remains a challenge. In this study, a new class of fluorine-containing ionogels was synthesized through photo-initiated copolymerization of fluorinated hexafluorobutyl methacrylate and butyl acrylate in a fluorinated ionic liquid 1-butyl-3-methyl imidazolium bis (trifluoromethylsulfonyl) imide. The resulting ionogels demonstrate good stretchability with a fracture strain of ~1300%. Owing to the advantages of the fluorinated network and the ionic liquid, the ionogels show excellent stability in air and vacuum, as well as in various solvent media such as water, sodium chloride solution, and hexane. Additionally, the ionogels display impressive wide temperature tolerance, functioning effectively within a wide temperature range from -60 to 350 °C. Moreover, due to their adhesive properties, the ionogels can be easily attached to various substrates, including plastic, rubber, steel, and glass. Sensors made of these ionogels reliably respond to repetitive tensile-release motion and finger bending in both air and underwater. These findings suggest that the developed ionogels hold great promise for application in wearable devices.

Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a major challenge threatening the global healthcare system. Respiratory virus infection is the most common cause of asthma attacks, and thus COVID-19 may contribute to an increase in asthma exacerbations. However, the mechanisms of COVID-19/asthma comorbidity remain unclear. METHODS: The "Limma" package or "DESeq2" package was used to screen differentially expressed genes (DEGs). Alveolar lavage fluid datasets of COVID-19 and asthma were obtained from the GEO and GSV database. A series of analyses of common host factors for COVID-19 and asthma were conducted, including PPI network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis and drug candidate prediction. Finally, the key host factors were verified in the GSE152418 and GSE164805 datasets. RESULTS: 192 overlapping host factors were obtained by analyzing the intersection of asthma and COVID-19. FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5 as host factors were tightly connected in the PPI network. Module analysis identified five modules with different biological functions and pathways. According to the degree values ranking in the PPI network, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were considered as the key cohost factors for COVID-19 and asthma. The H2O2, VEGF, IL-1 and Wnt signaling pathways had the strongest activities in the upstream pathways. Tissue-specific enrichment analysis revealed the different expression levels of the five critical host factors. LY294002, wortmannin, PD98059 and heparin might have great potential to evolve into therapeutic drugs for COVID-19 and asthma comorbidity. Finally, the validation dataset confirmed that the expression of five key host factors were statistically significant among COVID-19 groups with different severity and healthy control subjects. CONCLUSIONS: This study constructed a network of common host factors between asthma and COVID-19 and predicted several drugs with therapeutic potential. Therefore, this study is likely to provide a reference for the management and treatment for COVID-19/asthma comorbidity.

Self-cleaning expanded polytetrafluoroethylene-based hybrid membrane for water filtration.

Membrane surface fouling is a key problem for water filtration. Compositing photocatalytic substances with a base membrane is a widely used strategy, but most of the membrane will be decomposed by photocatalysis. Herein, expanded polytetrafluoroethylene (ePTFE) with extremely stable chemical properties is grafted with polyacrylic acid (PAA) and then modified with titanium dioxide (TiO2) to realize a self-cleaning TiO2-PAA-ePTFE filtration membrane. It can recover its flux under UV irradiation after fouling. With 20 rounds of self-cleaning, the membrane microstructure still remains intact. Moreover, in addition to retaining bovine serum albumin, TiO2 particles on the membrane surface are capable of absorbing small organic pollutants and degrading them. Thus, this membrane is potentially used as an anti-fouling membrane for water filtration.

Waterproof and Breathable Wound Dressing Composited By Expanded Polytetrafluoroethylene Backing and Hydrogel.

Wound dressings with waterproof, breathable, and bacterial-resistant properties are still rarely realized. In this work, a newly hydrogel-based dressing is designed with a backing of expanded polytetrafluoroethylene (ePTFE) film. The ePTFE grafting with polyvinylpyrrolidone (PVP) brush is composited with hydrogel successfully with an adhesion energy of ≈80 kJ m-2 . In this resultant composite, the ePTFE backing contributes excellent breathability, water resistance, and bacterial barrier property. The water vapor transmission rate of the composite is 4.83 × 103  g m-2 × 24 h, which can maintain the moist environment of wound and relieve pain by evaporating water. Notably, it can withstand 500 mm water column for over 300 s, which is obviously better than the commonly used nonwoven fabric backing materials. It can also prevent the invasion of bacteria, because the pores of ePTFE backing are smaller than those of most common bacterial. As a result, the composite with an ePTFE film backing has a positive effect in accelerating wound healing, promoting the reconstruction of intact epidermis and reducing inflammation.

Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology.

BACKGROUND: Chinese medicine Xuebijing (XBJ) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases. But the bioactive compounds and potential mechanisms of XBJ for COVID-19 prevention and treatment are unclear. This study aimed to examine the potential effector mechanisms of XBJ on COVID-19 based on network pharmacology. METHODS: We searched Chinese and international papers to obtain the active ingredients of XBJ. Then, we compiled COVID-19 disease targets from the GeneCards gene database and via literature searches. Next, we used the SwissTargetPrediction database to predict XBJ's effector targets and map them to the abovementioned COVID-19 disease targets in order to obtain potential therapeutic targets of XBJ. Cytoscape software version 3.7.0 was used to construct a "XBJ active-compound-potential-effector target" network and protein-protein interaction (PPI) network, and then to carry out network topology analysis of potential targets. We used the ClueGO and CluePedia plugins in Cytoscape to conduct gene ontology (GO) biological process (BP) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of XBJ's effector targets. We used AutoDock vina and PyMOL software for molecular docking. RESULTS: We obtained 144 potential COVID-19 effector targets of XBJ. Fourteen of these targets-glyceraldehyde 3-phosphate dehydrogenase (GAPDH), albumin (ALB), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), Caspase-3 (CASP3), signal transducer and activator of transcription 3 (STAT3), MAPK8, prostaglandin-endoperoxide synthase 2 (PTGS2), JUN, interleukin-2 (IL-2), estrogen receptor 1 (ESR1), and MAPK14 had degree values > 40 and therefore could be considered key targets. They participated in extracellular signal-regulated kinase 1 and 2 (ERK1, ERK2) cascade, the T-cell receptor signaling pathway, activation of MAPK activity, cellular response to lipopolysaccharide, and other inflammation- and immune-related BPs. XBJ exerted its therapeutic effects through the renin-angiotensin system (RAS), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), MAPK, phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt)-vascular endothelial growth factor (VEGF), toll-like receptor (TLR), TNF, and inflammatory-mediator regulation of transient receptor potential (TRP) signaling pathways to ultimately construct a "drug-ingredient-target-pathway" effector network. The molecular docking results showed that the core 18 effective ingredients had a docking score of less than - 4.0 with those top 10 targets. CONCLUSION: The active ingredients of XBJ regulated different genes, acted on different pathways, and synergistically produced anti-inflammatory and immune-regulatory effects, which fully demonstrated the synergistic effects of different components on multiple targets and pathways. Our study demonstrated that key ingredients and their targets have potential binding activity, the existing studies on the pharmacological mechanisms of XBJ in the treatment of sepsis and severe pneumonia, could explain the effector mechanism of XBJ in COVID-19 treatment, and those provided a preliminary examination of the potential effector mechanism in this disease.

Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology.

BACKGROUND: Chinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach. METHODS: TCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a "drug-active ingredient-potential target" network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape. RESULTS: A total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of "drug-component-target-biological process-signaling pathway". Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway. CONCLUSIONS: Our study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.

[Bioinformatic analysis of differentially expressed genes and Chinese medicine prediction for ulcerative colitis].

The aim of this paper was to analyze the microarray data between ulcerative colitis(UC) patients and healthy people by bioinformatics technology, screen the differentially expressed genes of UC, and predict the potential Chinese medicines for UC. The GSE36807 gene expression profile was downloaded from the gene expression database(GEO) and the differentially expressed(both up-regulated and down-regulated) genes(DEGs) were analyzed by using R language software. The core genes in the DEGs were obtained by using String database, Cytoscape software and its plug-in analysis, and the gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) were used to analyze the core genes. Moreover, the core genes and the medical ontology information retrieval platform(Coremine Medical) were mapped to each other to screen the traditional Chinese medicines and its active ingredients for treating UC. A total of 648 DEGs were screened, including 397 up-regulated genes and 251 down-regulated genes. Up-regulation of DEGs yielded 15 core genes including CXCL8, IL1 B, MMP9, CXCL1, CXCL10, CXCL9, CXCL2, CXCL5, TIMP1, CXCL11, STAT1,LCN2, IL1 RN, MMP1 and IDO1. Their biological processes and pathways were mainly enriched in interleukins, chemokine ligands and cytokines, chemokine-mediated signaling pathways, and were closely related to inflammatory responses, defense responses, cell chemotaxis, secretory granules, IL17 signaling pathways, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and TNF signaling pathway. Potential Chinese medicines for the treatment of UC include Curcumae Longae Rhizoma, Coptidis Rhizoma, Scutellariae Radix, Dendrobii Caulis, Sanguisorbae Radix, Phellodendri Chinensis Cortex, Bletillae Rhizoma and Atractylodis Rhizoma. The analysis of DEGs and core genes could promote our understanding on pathogenesis of UC. This study provides potential gene targets and research ideas for the development of new drugs of Chinese medicine intervention for UC.

The Prognostic Value of Autophagy-Related Markers Bclin-1 and LC-3 in Colorectal Cancers: A Systematic Review and Meta-analysis.

OBJECTIVE: At present, the relationship between autophagosomes and the prognosis of various cancers has become a subject of active investigation. A series of studies have demonstrated the correlation between autophagy microtubule-associated protein light chain 3 (LC-3), Beclin-1, and colorectal cancer (CRC). Since autophagy has dual regulatory roles in tumors, the results of this correlation are also uncertain. Hence, we summarized the relationship between Beclin-1, LC-3, and CRC using systematic reviews and meta-analysis to clarify their prognostic significance in it. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched online up to April 1, 2019. The quality of the involving studies was assessed against the Newcastle-Ottawa Scale (NOS). Pooled hazard ratio (HR) and 95% confidence interval (CI) in a fixed or random effects model were used to assess the strength of correlation between Beclin-1, LC-3, and CRC. RESULTS: A total of 9 articles were collected, involving 2,297 patients. Most literatures scored more than 6 points, suggesting that the quality of our including research was acceptable. Our finding suggested that the expression of Beclin-1 was not associated with overall survival (HR = 0.68, 95% CI (0.31-1.52), P=0.351). Nonetheless, LC-3 expression exerted significant impact on OS (HR = 0.51, 95% CI (0.35-0.74), P < 0.05). Subgroup analysis exhibited that Beclin-1 expression was associated with OS at TNM stage III (HR = 0.04, 95% CI = 0.02-0.08, P < 0.05), surgical treatment (HR = 1.53, 95% CI (1.15-2.02), P=0.003), and comprehensive treatment (HR = 0.27 95% CI (0.08-0.92), P=0.036), respectively. Similarly, the results showed the increased LC-3 expression in CRC was related to OS in multivariate analyses (HR = 0.44, 95% CI (0.34-0.57), P < 0.05), stages (HR = 0.51, 95% CI (0.35-0.74), P < 0.05), and comprehensive treatment (HR = 0.44, 95% CI (0.34-0.57), P < 0.05). CONCLUSIONS: Autophagy-related proteins of LC-3 might be an important marker of CRC progression. However, since the number of the original studies was limited, more well-designed, large-scale, high-quality studies are warranted to provide more convincing and reliable information.

[Meta-analysis and trial sequential analysis of modified Sangbaipi Decoction for treating acute exacerbation of chronic obstructive pulmonary disease].

The randomized controlled trials about modified Sangbaipi Decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) patients were collected from 7 databases( PubMed,CNKI,et al) from the establishment to December 5,2018. All the studies searched were strictly evaluated. Literatures were independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. To systematically review the efficacy of modified Sangbaipi Decoction in treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 25 RCTs involving 1 784 patients were included. According to the results of Meta-analysis,compared with the control groups,the trial group had a higher clinical efficacy in AECOPD patients( RR =1. 18,95%CI[1. 13,1. 22],P = 0),improved pulmonary functions including forced expiratory volume in one second( FEV1,WMD =0. 44,95%CI[0. 01,0. 87],P = 0. 046),and the forced vital capacity( FVC,WMD = 0. 42,95%CI[0. 07,0. 22],P = 0),but no statistical significance in the percentage of forced expiratory volume in one second( FEV1%,P = 0. 067) and the first seconds breathing volume percentage of forced vital capacity( FEV1/FVC,P = 0. 238); it improved the arterial oxygen partial pressure( PaO2,SMD =0. 85,95%CI[0. 41,1. 30],P = 0) and decreased the arterial partial pressure of carbon dioxide( PaCO2,SMD =-0. 94,95% CI[-1. 70,-0. 18],P= 0. 016); and in terms of inflammatory markers,it improved the white blood cell count( WBC,WMD=-0. 94,95%CI[-1. 17,-0. 70],P = 0). The trial sequential analysis showed that the studies included with the improvement of clinical efficacy had passed the conventional and TSA threshold,so as to further confirm the evidence. According to the findings,in addition to conventional Western medicine treatment,modified Sangbaipi Decoction could improve the efficiency in treating acute exacerbation patients with chronic obstructive pulmonary disease,increase PaO2,and decrease PaCO2,with a high safety but no effect on pulmonary function. However,restricted by the low quality of studies included,this conclusion shall be further verified by more high-quality clinical trials.

Nomogram to predict overall survival and disease-specific survival with appendiceal mucinous adenocarcinoma.

To predict the survival of appendiceal mucinous adenocarcinoma (AMA) by prognostic nomogram.A total of 3234 patients with AMA were collected from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2015. Univariate and multivariate Cox proportional hazards (PH) regression analyses were used to generate independent prognostic factors. These variables were included in the nomogram to predict overall survival (OS) and disease-specific survival (DSS) at 1-, 3-, and 5- years. These data are validated both internally and externally. The consistency index (C-index) and calibration chart were used to estimate the accuracy of the nomogram.The study cohort was randomly divided into the training (n = 2155) and validation group (n = 1799). According to univariate and multivariate analyses, age at diagnosis, marital status, sex, histological differentiation, SEER extent of disease, number of local lymph nodes examined, whether they were positive, and surgical methods were independent prognostic factors for OS and DSS. These factors were incorporated into the nomogram. Internal validation in the training cohort showed that the C-index values for nomogram predictions of OS and DSS were 0.73 (95% CI 0.70-0.76) and 0.77 (95% CI 0.73-0.81), respectively. Similarly, the corresponding C-index values in the external validation cohort were 0.76 (95% CI 0.70-0.81) and 0.75 (95% CI 0.71-0.80). The Calibration plots revealed that the actual survival and nomogram prediction had a good consistency.Build a nomogram in the SEER database to predict OS and DSS in patients with AMA. It can provide accurate and personalised survival prediction for clinicians and patients.

[Systematically review of modified Sanzi Yangqin Decoction for treating acute exacerbation of chronic obstructive pulmonary disease].

The randomized controlled trials( RCTs) about modified Sanzi Yangqin Decoction in the treatment of patients with exacerbation of chronic obstructive pulmonary disease( AECOPD) were collected from 7 databases( PubMed,CNKI,etc.) till December25,2018 from their inception. All the studies searched were strictly evaluated and independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. In order to systematically review the efficacy and safety of modified Sanzi Yangqin Decoction for treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 22 RCTs involving 2 012 patients were included. The results of Meta-analysis suggested that: as compared with the control group,the clinical symptoms in AECOPD patients were improved( RR = 1. 19,95%CI[1. 15,1. 24],P = 0); the pulmonary functions including forced expiratory volume in one second( FEV_1)( SMD= 0. 96,95%CI[0. 39,1. 52],P= 0. 001),the percentage of forced expiratory volume in one second( FEV_1%)( SMD =0. 80,95%CI[0. 20,1. 41],P = 0. 009),forced vital capacity( FVC)( SMD = 0. 69,95% CI[0. 06,1. 31],P = 0. 032),first seconds breathing volume percentage of forced vital capacity( FEV_1/FVC) were improved( SMD = 0. 81,95%CI[0. 64,0. 97],P = 0);the arterial oxygen partial pressure( PaO_2) was improved( SMD= 0. 87,95%CI[0. 41,1. 32],P= 0); the arterial partial pressure of carbon dioxide( PaCO_2) was decreased( SMD =-0. 91,95%CI[-1. 33,-0. 49],P = 0) in the trial group. In addition,the incidence of adverse reactions in the experimental group was low,and there were no serious adverse events. The trial sequential analysis( TSA) showed that the studies included in the improvement of clinical efficacy had passed the conventional and TSA threshold at the same time,further confirming the efficacy of trial group. This research showed that,conventional Western medicine treatment,combined with modified Sanzi Yangqin Decoction in treating acute exacerbation patients with chronic obstructive pulmonary disease could improve the clinical efficiency and pulmonary functions,improve the PaO_2,decrease the PaCO_2,with a high safety. However,the quality of existing research is low,requiring more high quality clinical trials for further validation.

Self-Healing, Adhesive, and Highly Stretchable Ionogel as a Strain Sensor for Extremely Large Deformation.

Fabricating a strain sensor that can detect large deformation over a curved object with a high sensitivity is crucial in wearable electronics, human/machine interfaces, and soft robotics. Herein, an ionogel nanocomposite is presented for this purpose. Tuning the composition of the ionogel nanocomposites allows the attainment of the best features, such as excellent self-healing (>95% healing efficiency), strong adhesion (347.3 N m-1 ), high stretchability (2000%), and more than ten times change in resistance under stretching. Furthermore, the ionogel nanocomposite-based sensor exhibits good reliability and excellent durability after 500 cycles, as well as a large gauge factor of 20 when it is stretched under a strain of 800-1400%. Moreover, the nanocomposite can self-heal under arduous conditions, such as a temperature as low as -20 °C and a temperature as high as 60 °C. All these merits are achieved mainly due to the integration of dynamic metal coordination bonds inside a loosely cross-linked network of ionogel nanocomposite doped with Fe3 O4 nanoparticles.

Fe3 O4 Anisotropic Nanostructures in Hydrogels: Efficient Catalysts for the Rapid Removal of Organic Dyes from Wastewater.

Fe3 O4 anisotropic nanostructures that exhibit excellent catalytic performance are rarely used to catalyze Fenton-like reactions because of the inevitable drawbacks resulting from traditional preparation methods. In this study, a facile, nontoxic, water-based approach is developed for directly regulating a series of anisotropic morphologies of Fe3 O4 nanostructures in a hydrogel matrix. In having the advantages of both the catalytic activity of Fe3 O4 and the adsorptive capacity of an anionic polymer network, the hybrid nanocomposites have the capability to effect the rapid removal of cationic dyes, such as methylene blue, from water samples. Perhaps more interestingly, hybrid nanocomposites loaded with Fe3 O4 nanorods exhibit the highest catalytic activity compared to those composed of nanoneedles and nanooctahedra, revealing the important role of nanostructure morphology. By means of scanning electrochemical microscopy, it is revealed that Fe3 O4 nanorods can efficiently catalyze H2 O2 decomposition and thus generate more free radicals ((.) OH, (.) HO2 ) for methylene blue degradation, which might account for their high catalytic activity.

Exceptionally tough and notch-insensitive magnetic hydrogels.

Most existing magnetic hydrogels are weak and brittle. The development of strong and tough magnetic hydrogels would extend their applications into uncultivated areas, such as in actuators for soft machines and guided catheters for magnetic navigation systems, which is still a big challenge. Here a facile and versatile approach to fabricating highly stretchable, exceptionally tough and notch-insensitive magnetic hydrogels, Fe(3)O(4)@Fe-alginate/polyacrylamide (PAAm), is developed, by dispersing alginate-coated Fe(3)O(4) nanoparticles into the interpenetrating polymer networks of alginate and PAAm, with hybrid physical and chemical crosslinks. A cantilever bending beam actuator as well as a proof-of-concept magnetically guided hydrogel catheter is demonstrated. The method proposed in this work can be integrated into other strong and tough magnetic hydrogels for the development of novel hydrogel nanocomposites with both desirable functionality and superior mechanical properties.

Tough Al-alginate/poly(N-isopropylacrylamide) hydrogel with tunable LCST for soft robotics.

Tough Al-alginate/poly(N-isopropylacrylamide) (PNIPAM) hydrogel has been synthesized by introducing an interpenetrating network with hybrid physically cross-linked alginate and chemically cross-linked PNIPAM. Varying the concentration of AlCl3 regulates the mechanical properties of the tough hydrogel and tunes its lower critical solution temperature (LCST) as well. The tough Al-alginate/PNIPAM exhibits 6.3 ± 0.3 MPa of compressive stress and 9.95 of uniaxial stretch. Tunability of LCST is also achieved in a wide range within 22.5-32 °C. A bending beam actuator and a four-arm gripper made of bilayer (Na-alginate/PNIPAM)/(Al-alginate/PNIPAM) hydrogel as prototype of all-hydrogel soft robotics are demonstrated. A finite element (FE) simulation model is developed to simulate the deformation of the soft robotics. The FE simulation not only reproduces the deformation process of performed experiments but also predicts more complicated devices that can be explored in the future. This work broadens the application of temperature-responsive PNIPAM-based hydrogels.

Edwardsiella tarda Eta1, an in vivo-induced antigen that is involved in host infection.

Edwardsiella tarda, a Gram-negative bacterium, is a severe fish pathogen that can also infect humans. In this study, we identified, via in vivo-induced antigen technology, an E. tarda antigen, Eta1, and analyzed its function in a Japanese flounder (Paralichthys olivaceus) model. Eta1 is composed of 226 residues and shares homology with putative bacterial adhesins. Quantitative real-time reverse transcriptase (RT)-PCR analysis indicated that when cultured in vitro, eta1 expression was growth phase dependent and reached maximum at mid-logarithmic phase. During infection of flounder lymphocytes, eta1 expression was drastically increased at the early stage of infection. Compared to the wild type, the eta1-defective mutant, TXeta1, was unaffected in growth but exhibited attenuated overall virulence, reduced tissue dissemination and colonization capacity, and impaired ability to invade flounder lymphocytes and to block the immune response of host cells. The lost virulence of TXeta1 was restored when a functional eta1 gene was reintroduced into the strain. Western blot and immunodetection analyses showed that Eta1 is localized to the outer membrane and exposed on the surface of E. tarda and that recombinant Eta1 (rEta1) was able to interact with flounder lymphocytes. Consistent with these observations, antibody blocking of Eta1 inhibited E. tarda infection at the cellular level. Furthermore, when used as a subunit vaccine, rEta1 induced strong protective immunity in flounder against lethal E. tarda challenge. Taken together, these results indicate that Eta1 is an in vivo-induced antigen that mediates pathogen-host interaction and, as a result, is required for optimal bacterial infection.

Inv1: an Edwardsiella tarda invasin and a protective immunogen that is required for host infection.

Invasin is an outer membrane protein that is known to mediate entry of enteric bacteria into mammalian cells. In this study, we analyzed the function and immunoprotective potential of the invasin Inv1 from Edwardsiella tarda, a serious fish pathogen that can also infect humans. In silico analysis indicated that Inv1 possesses a conserved N-terminal DUF3442 domain and a C-terminal group 1 bacterial Ig-like domain. Subcellular localization analysis showed that Inv1 is exposed on cell surface and could be recognized by specific antibodies. Mutation of inv1 had no effect on bacterial growth but attenuates overall bacterial virulence and impaired the ability of E. tarda to attach and invade into host cells. Consistent with these observations, antibody blocking of Inv1 inhibited E. tarda infection of host cells. To examine the immunoprotective potential of Inv1, recombinant Inv1 (rInv1) corresponding to the DUF3442 domain was purified and used to vaccinate Japanese flounder (Paralichthys olivaceus). The results showed that rInv1 induced strong protection against lethal-dose challenge of E. tarda. ELISA analysis showed that rInv1-vaccinated fish produced specific serum antibodies that could enhance the serum bactericidal activity against E. tarda. Taken together, these results indicate that Inv1 is a surface-localized virulence factor that is involved in host infection and can induce effective immunoprotection when used as a subunit vaccine.

The two Dps of Edwardsiella tarda are involved in resistance against oxidative stress and host infection.

DNA-binding protein from starved cells (Dps) is a member of ferritin-like proteins that exhibit properties of nonspecific DNA binding and iron oxidation and storage. Although studies of Dps from many bacterial species have been reported, no investigations on Dps from fish pathogens have been documented. In this study, we examined the biological function of two Dps proteins, Dps1 and Dps2, from Edwardsiella tarda, an important fish bacterial pathogen that can also infect humans. Dps1 and Dps2 are, respectively, 163- and 174-residue in length and each contains the conserved ferroxidase center of Dps. Expression of dps1 and dps2 was growth phase-dependent and reached high levels in stationary phase. Purified recombinant Dps1 and Dps2 were able to mediate iron oxidation by H(2)O(2) and bind DNA. Compared to the wild type strain, (i) the dps1 mutant (TXDps1) and the dps2 mutant (TXDps2) were unaffected in growth, while the dps2 mutant with interfered dps1 expression (TXDps2RI) exhibited a prolonged lag phase; (ii) TXDps1, TXDps2, and especially TXDps2RI were significantly reduced in H(2)O(2) and UV tolerance and impaired in the capacity to invade into host tissues and replicate in head kidney macrophages; (iii) TXDps1, TXDps2, and TXDps2RI induced stronger macrophage respiratory burst activity and thus were defective in the ability to block the bactericidal response of macrophages. Taken together, these results indicate that Dps1 and Dps2 are functional analogues that possess ferroxidase activity and DNA binding capacity and are required for optimum oxidative stress resistance and full bacterial virulence.

Evaluation of housekeeping genes as references for quantitative real time RT-PCR analysis of gene expression in Japanese flounder (Paralichthys olivaceus).

Japanese flounder (Paralichthys olivaceus) is an important economic fish species cultured worldwide. In this report, we compared the potentials of ten housekeeping genes as quantitative real time RT-PCR (qRT-PCR) references for the study of gene expression in Japanese flounder under normal physiological conditions and during bacterial infection. For this purpose, the expression of the ten genes in eight flounder tissues (liver, spleen, kidney, heart, muscle, brain, gill, and intestine) was determined by qRT-PCR before and after bacterial infection. The expression levels of the housekeeping genes were then compared and evaluated with geNorm and NormFinder algorithms. The results showed that before bacterial infection, the tested genes exhibited tissue-specific expressions to various degrees, with ß-actin and ubiquitin-conjugating enzyme being ranked as the most stable genes across tissue types. Following bacterial challenge, all the tested genes varied in expression levels in tissue-dependent manners and no cross-all-tissue type reference gene was identified among the examined panel of housekeeping genes; however, α-tubulin was recognized as the most stable gene in four (spleen, heart, muscle, and gill) of the eight examined tissues. These results indicate that for qRT-PCR analysis of gene expression in Japanese flounder as a function of bacterial infection, the choice of reference genes should be made according to tissue type.