Multifunctional nanocoatings with synergistic controlled release of zinc ions and cytokines for precise modulation of vascular intimal reconstruction.

Vascular stent implantation remains the major therapeutic method for cardiovascular diseases currently. We here introduced crucial biological functional biological function factors (SDF-1α, VEGF) and vital metal ions (Zn2+) into the stent surface to explore their synergistic effect in the microenvironment. The combination of the different factors is known to effectively regulate cellular inflammatory response and selectively regulate cell biological behavior. Meanwhile, in the implemented method, VEGF and Zn2+ were loaded into heparin and poly-l-lysine (Hep-PLL) nanoparticles, ensuring a controlled release of functional molecules with a multi-factor synergistic effect and excellent biological functions in vitro and in vivo. Notably, after 150 days of implantation of the modified stent in rabbits, a thin and smooth new intima was obtained. This study offers a new idea for constructing a modified surface microenvironment and promoting tissue repair.

An Experimental and Density Functional Theory Simulation Study of NO Reduction Mechanisms over Fe0 Supported on Graphene with and without CO.

NO reduction over highly dispersed zerovalent iron (Fe0) supported on graphene (G), with and without the presence of CO in the reacting stream, was systematically studied using a fixed-bed reactor, and the reaction mechanism was examined with the aid of in situ Fourier transform infrared (FTIR) spectroscopy and density functional theory (DFT) calculations. The in situ FTIR results showed that NO adsorbed on the Fe0 site is reduced to form active surface oxygen species (O*), which is then reduced by carbon in graphene to form CO2. The presence of CO in the reacting stream helps to reduce the oxidized Fe(O) sites to regenerate Fe0 sites, making NO reduction easier. It was revealed that NO and CO2 are easily adsorbed on the active surface oxygen species (O*) to form nitrate and carbonate, inhibiting their reduction by CO and deactivating the catalyst. The DFT calculations results suggest that the role of Fe is to reduce the energy barrier of the NO adsorption and decomposition, which controls the formation of active surface oxygen species and N2. The combined FTIR and DFT results offer new insights into the possible mechanism of catalytic NO reduction over graphene loaded with Fe, with and without CO.

Proactive Hemocompatibility Platform Initiated by PAMAM Dendrimer Adapting to Key Components in Coagulation System.

Surface modification manipulates the application performance of materials, and thrombosis caused by material contact is a key risk factor of biomaterials failure in blood-contacting/implanting devices. Therefore, building a safe and effective hemocompatibility platform is still urgent. Owing to the unique properties of polyamidoamine (PAMAM) dendrimers, in this study, modified surfaces with varying dendrimer densities were interacted with elements maintaining blood homeostasis. These included the plasma proteins bovine serum albumin and fibrinogen, cells in blood (platelets and erythrocyte), as well as endothelial cells (ECs), and the objective was to evaluate the blood compatibility of the chosen materials. Whole blood test and dynamic blood circulation experiment by the arteriovenous shunt mode of rabbit were also conducted, based on the complexity and fluidity of blood. The PAMAM-modified substrates, particularly that with a high density of PAMAM (N1.0), adsorbed proteins with lessened fibrinogen adsorption, reduced platelet activation and aggregation, and suppressed clotting in whole blood and dynamic blood testing. Furthermore, the designed PAMAM dendrimer densities were safe and showed negligible erythrocyte lysis. Concurrently, PAMAM modification could maintain EC growth and did not trigger the release of procoagulant factors. These results suggest that the PAMAM-modified materials are compatible for maintaining blood homeostasis. Thus, PAMAM dendrimers can work as excellent surface modifiers for constructing a hemocompatibility platform and even a primer layer for desired functional design, promoting the service performance of blood-contacting devices.

Chitosan/Alginate Hydrogel Dressing Loaded FGF/VE-Cadherin to Accelerate Full-Thickness Skin Regeneration and More Normal Skin Repairs.

The process of full-thickness skin regeneration is complex and has many parameters involved, which makes it difficult to use a single dressing to meet the various requirements of the complete regeneration at the same time. Therefore, developing hydrogel dressings with multifunction, including tunable rheological properties and aperture, hemostatic, antibacterial and super cytocompatibility, is a desirable candidate in wound healing. In this study, a series of complex hydrogels were developed via the hydrogen bond and covalent bond between chitosan (CS) and alginate (SA). These hydrogels exhibited suitable pore size and tunable rheological properties for cell adhesion. Chitosan endowed hemostatic, antibacterial properties and great cytocompatibility and thus solved two primary problems in the early stage of the wound healing process. Moreover, the sustained cytocompatibility of the hydrogels was further investigated after adding FGF and VE-cadherin via the co-culture of L929 and EC for 12 days. The confocal 3D fluorescent images showed that the cells were spherical and tended to form multicellular spheroids, which distributed in about 40-60 µm thick hydrogels. Furthermore, the hydrogel dressings significantly accelerate defected skin turn to normal skin with proper epithelial thickness and new blood vessels and hair follicles through the histological analysis of in vivo wound healing. The findings mentioned above demonstrated that the CS/SA hydrogels with growth factors have great potential as multifunctional hydrogel dressings for full-thickness skin regeneration incorporated with hemostatic, antibacterial, sustained cytocompatibility for 3D cell culture and normal skin repairing.

Reducing Endogenous Labile Zn May Help to Reduce Smooth Muscle Cell Injury around Vascular Stents.

Vascular stent service involves complex service environments and performance requirements, among which the histocompatibility of the stent could seriously affect the therapeutic effect. In the pathology of vascular disease, the thin fiber cap is easily ruptured, exposing the necrotic core below, and triggering a series of dangerous biochemical reactions. In contrast, the thin neointima, considered an essential structure growing on the stent, may evolve into vulnerable plaque structures due to lesions induced by the stent. Therefore, the reduction of necrosis around the stent below the thin neointima is indispensable. In this work, different cell model experiments suggested that the content of endogenous labile Zn positively correlated with cell injury. Zinquin-Zn fluorescence experiments and zinc ion channels research suggested that the change in the content of endogenous labile Zn in smooth muscle cells is affected by different stent coatings. The content of endogenous labile Zn in cells negatively correlated with cell viability. Animal experiments indirectly verified the increase in endogenous labile Zn by detecting the expression of Zn regulatory protein (metallothionein) in the necrotic tissues. Reducing the content of endogenous labile Zn may favor a reduction in smooth muscle cell injury and necrosis. This biochemical mechanism is effective in improving the therapeutic effect of vascular stents.

Using honeypots to model botnet attacks on the internet of medical things.

Corona Virus Disease 2019 (COVID-19) has led to an increase in attacks targeting widespread smart devices. A vulnerable device can join multiple botnets simultaneously or sequentially. When different attack patterns are mixed with attack records, the security analyst produces an inaccurate report. There are numerous studies on botnet detection, but there is no publicly available solution to classify attack patterns based on the control periods. To fill this gap, we propose a novel data-driven method based on an intuitive hypothesis: bots tend to show time-related attack patterns within the same botnet control period. We deploy 462 honeypots in 22 countries to capture real-world attack activities and propose an algorithm to identify control periods. Experiments have demonstrated our method's efficacy. Besides, we present eight interesting findings that will help the security community better understand and fight botnet attacks now and in the future.

Three dimensional polymer waveguide using hybrid lithography.

A three dimensional polymer waveguide with taper structure was demonstrated and fabricated by a reliable and effective hybrid lithography. The hybrid lithography consists of lithography to fabricate a polymer waveguide and gray scale lithography to fabricate a polymer taper structure. Laser ablation and shadow aluminum evaporation were designed for gray scale lithography. The length of the gray scale region ranging from 20 to 400 µm could be controlled by the laser power, the ablation speed, and the aluminum thickness. The slope angle was determined by the length of the gray scale region and the thickness of the photoresist. The waveguide taper structure could be transferred to the lower layer by the etching method. The taper structure can be used for integration of the waveguide with different dimensions.

Study of Dynamic Failure Behavior of a Type of PC/ABS Composite.

PC/ABS composites are commonly used in airbag covers. In this paper, uniaxial tensile experiments of a PC/ABS composite at different temperatures and strain rates were conducted. The results showed that the temperature and loading rate affect the mechanical properties of the PC/ABS composite. As the temperature increases, the yield stress decreases and the strain at the moment of fracture increases, but the strain rate at the same temperature has a relatively small effect on the mechanical properties, which are similar to ductile materials. The experimental results were applied to the Abaqus model which considered thermal effects and the exact Johnson-Cook constitutive parameters were calculated by applying the inverse method. Based on the constitutive model and the failure analysis findings acquired by DIC, the uniaxial tensile test at the room temperature and varied strain rates were simulated and compared to the test results, which accurately reproduced the test process. The experiment on target plate intrusion of the PC/ABS composite was designed, and a finite-element model was established to simulate the experimental process. The results were compared with the experiments, which showed that the constitutive and the failure fracture strains were valid.

Comparing the effect of biosurfactant and chemical surfactant on bubble hydrodynamics in a flotation column.

Bubble hydrodynamics is fundamental to the performance of the flotation process widely used in the separation industry. To compare the effect of biosurfactants and chemical synthetic surfactants on bubble hydrodynamics in the flotation process, the motion of a single bubble and the size distribution of bubble swarms in various surfactants (rhamnolipid, tea saponin and Triton X-100) solutions were observed directly using a high-speed video camera in a laboratory scale flotation column. Bubble trajectory, dimensions, velocity and size distribution were then determined through image analysis. The results indicated that the addition of biosurfactants had the same significant effects on bubble motion and size distribution as chemosynthetic surfactants. The biosurfactant effect on bubble behavior was also found to depend on their type and concentration. In general, the effect of tea saponin was stronger than another biosurfactant (rhamnolipid) used in the present study. The present findings implied that some biosurfactants like tea saponin can replace chemosynthetic surfactants in controlling bubble behavior in flotation operation. This will contribute to promoting the use of green environmentally friendly flotation agents in the separation industry.

Recent Advances: From Cell Biology to Cell Therapy in Atherosclerosis Plaque via Stent Implantation.

Atherosclerosis is a multifactorial result of complicated pathophysiology. Changes in the expression of polygenes, coupled with environmental and lifestyle factors, trigger a cascade of adverse events involving a variety of cell types, such as vascular endothelial cells, smooth muscle cells, and macrophages. In this review, we summarize the function and therapeutic targets of atherosclerotic cells. This article reviews the role of endothelial cells, smooth muscle cells, macrophages and foam cells in the development of atherosclerosis and the progress in the treatment of atherosclerosis by targeting these cells. Atherosclerotic plaque involves a variety of cells and biomolecules, and its complex biological environment is a difficult point for the study and treatment of atherosclerosis. For treating atherosclerosis, a large number of studies emerged based on blocking or inhibiting factors affecting the formation and development of plaque. Cardiovascular stent intervention is currently the main method for the treatment of atherosclerosis. In recent decades, numerous studies on cardiovascular, stents mainly involve drug coating or biomolecular modification of stents to enhance anti-thrombosis, anti-restenosis and endothelialization. This paper introduces the research status of cardiovascular stents and new strategies for surface modification. The treatment of atherosclerosis based on the level of molecular biology and cell biology is becoming a research hotspot in the coming decades.

Effects of surfactant on bubble hydrodynamic behavior under flotation-related conditions in wastewater.

Bubble behavior is fundamental to the performance of froth flotation operations used in wastewater treatment processes. To fully understand and characterize bubble behavior under flotation-related conditions in wastewater, the high-speed photographic method has been employed to examine the motion of single bubbles and size distribution of bubble swarms with intermediate sizes ranging from 1 to 4 mm in the presence of surfactants in a laboratory scale flotation column. Both distilled water and synthetic municipal wastewater have been used to make solutions as well as two types of common surfactants. The instantaneous bubble motion has been recorded by a high speed camera. Subsequently, bubble trajectory, dimensions, velocity and distribution have been determined from the recorded frames using the image analysis software. The experimental results show that the addition of surfactant into wastewater has similar effects on bubble hydrodynamic behavior as in pure water (e.g., improving trajectory stabilization, dampening bubble deformation, slowing down terminal velocity, reducing bubble size and increasing the specific surface area of bubble swarm) due to the Marangoni effect. However, it is interesting to note that surfactant effects on single bubble hydrodynamics in wastewater are slightly stronger than those in pure water while surfactant effects on size parameters of bubble swarms in wastewater are significantly stronger than those in pure water. This finding suggests that besides surfactant, inorganic salts present in synthetic wastewater have an important influence on bubble dispersion.

Biofunctionalized fibrin gel co-embedded with BMSCs and VEGF for accelerating skin injury repair.

Rapid and effective repair of epithelial tissue is desirable for improving the success rate of operation and reducing postoperative complications. Hydrogel is a widely studied wound repair material, especially as a wound dressing for damaged epithelial tissue. Based on the catalytic effect of thrombin on fibrinogen, in this study, a three-dimensional fibrin gel which of adequate epithelial cell compatibility was constructed by using thrombin and fibrinogen under the cross-linking action of calcium ion. Immunofluorescence staining and hematoxylin-eosin (H&E) staining showed that bone marrow mesenchymal stem cell (BMSC) was embedded in fibrin gel. Furthermore, vascular endothelial growth factor (VEGF) was used to induce BMSC to differentiate into CD31+ and vWF+ endothelial cell (EC) in fibrin gel. The results showed that the fibrin gel surface may effectively promote the adhesion and proliferation of EC and smooth muscle cell (SMC). After 15 days of culture, it was found that the BMSC embedded in the hydrogel had differentiated into EC. The results of in vivo skin wound experiment in rats further proved that the fibrin gel containing BMSC could promote wound healing and repair, and showed the potential to promote neovascularization at the injured site. The construction method of hydrogel materials proposed in this study has potential application value in the field of regenerative medicine.

A catheter side wall tactile sensor: design, modeling and experiments.

Intravascular neurosurgery is a new and important technique of minimally invasive surgery. The current surgical device, however, does not provide realistic tactile feedback, which makes the operation a very difficult task, and the surgeon must exert extreme caution in order to avoid medical accidents. In this paper, a novel tactile sensor, which is based on polyvinylidene fluoride, is developed to measure the pressure on the side wall of the catheter for intravascular neurosurgery. The relationship between the input force and the output charge signals is identified based on the composite laminate theory, shell theory and linear piezoelectric theory. The design, mathematical model, interface circuit and calibrating experiment of the tactile sensor are presented in detail. With this sensor, surgeons will be able to "feel" the contact force between the side wall of the catheter and the blood vessel. Experimental results show that the tactile sensor measures the pressure well when it contacts the side wall of blood.

Heparin/poly-l-lysine nanoplatform with growth factor delivery for surface modification of cardiovascular stents: The influence of vascular endothelial growth factor loading.

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

Computational study on microscale behavior of bubble generated by aeration in a plug-flow aeration tank.

The microscale hydrodynamics of bubbles generated by aeration is directly related to the oxygen transfer efficiency and the overall performance of the activated sludge wastewater treatment process. To gain a deeper insight on the microscale phenomena of dispersed bubble occurring in this process, a three-dimensional direct simulation method is developed to study the effects of the liquid cross-flow on microscale behavior of bubble generation in a plug-flow aeration tank. The numerical simulations are performed using the level set method coupling with the governing equations of a single fluid with variable properties. The governing equations are solved using the finite-volume technique. The simulation results are validated through comparison with experimental observations. The study indicates that the liquid cross-flow has a strong impact on the bubble generation. Compared to that generated under quiescent liquid conditions, the bubble under liquid cross-flow conditions grows downstream along the tilted axis. The bubble generation time tends to decrease noticeably and the bubble at detachment has significantly smaller size. The bubble size and generation time also increase with the increase of gas velocity. The relation of such results to the oxygen transfer efficiency of the wastewater treatment process is also discussed.

[Cloning and analysis of the Vibrio harveyi dam gene].

The DNA adenine methylase (dam) gene was cloned by degenerate PCR from Vibrio harveyi strain T4. The gene was 840bp in length and encoded a putative protein of 279 amino acids that shared relatively high homology with the Dam of other Vibrios, especially with that of V. parahaemolyticus (96% in identity). The V. harveyi dam gene was subcloned into plasmid pBR322 and the resulting plasmid pBD was introduced into the E. coli strain ER2925 in which the dam gene had been knocked out. Dpn I, Dpn II, and Sau3A I restriction enzyme analysis of the genomic DNA of ER2925 transformed with pBD indicated that the cloned V. harveyi dam gene could functionally complement the E. coli dam mutant and methylate E. coli chromosome at the GATC sites. The 3251 bp upstream region of V. harveyi dam was obtained by genome walking and analyzed at the sequence level. It was found that this 3251 bp region contained two complete open reading frames (ORF): one was of 1101 bp in length and the other was of 1503 bp in length. The predicted amino acid sequence of ORF1101 shared 91% identity with the 3-dehydroquinate synthase of V. parahaemolyticus. The amino acid sequence of ORF1503 shared 80% identity with V. parahaemolyticus DamX. A truncated ORF was found at the upstream of ORF1101, encoding 169 amino acids that shared 94% identity with the shikimate kinase of V. parahaemolyticus. These three genes, together with dam, were arranged in the order of shikimate kinase-3-dehydroquinate synthase-damX-dam. The region immediate upstream of the V. harveyi dam structural gene was cloned in three fragments of different length: 78bp, 112 bp and 477bp (named P78, P112, and P477, respectively) and tested for promoter activity. The results showed that, while all the three fragments had detectable promoter activities, the activity of P78 appeared to be higher than that of P112 and P477.

Construction of an attenuated Pseudomonas fluorescens strain and evaluation of its potential as a cross-protective vaccine.

Ferric uptake regulator (Fur) is a global transcription regulator that is ubiquitous to Gram-negative bacteria and regulates diverse biological processes, including iron uptake, cellular metabolism, stress response, and production of virulence determinants. As a result, for many pathogenic bacteria, Fur plays a crucial role in the course of infection and disease development. In this study, the fur gene was cloned from a pathogenic Pseudomonas fluorescens strain, TSS, isolated from diseased Japanese flounder cultured in a local farm. TSS Fur can partially complement the defective phenotype of an Escherichia coli fur mutant. A TSS fur null mutant, TFM, was constructed. Compared to TSS, TFM exhibits reduced growth ability, aberrant production of outer membrane proteins, decreased resistance against host serum bactericidal activity, impaired ability to disseminate in host blood and tissues, and drastic attenuation in overall bacterial virulence in a Japanese flounder infection model. When used as a live vaccine administered via the injection, immersion, and oral routes, TFM affords high levels of protection upon Japanese flounder against not only P. fluorescens infection but also Aeromonas hydrophila infection. Furthermore, a plasmid, pJAQ, was constructed, which expresses the coding element of the Vibrio harveyi antigen AgaV-DegQ. TFM harboring pJAQ can secret AgaV-DegQ into the extracellular milieu. Vaccination of Japanese flounder with live TFM/pJAQ elicited strong immunoprotection against both V. harveyi and A. hydrophila infections.