Nitric Oxide-Releasing Porous Coating with Antibacterial Activity and Blood Compatibility.

Nitric oxide (NO)-releasing coating is promising to enhance the biocompatibility of medical devices. In this study, polyurethane (PU) and S-nitrosated keratin (KSNO) were dissolved with dimethyl sulfoxide (DMSO) and tetrahydrofuran (THF) to prepare a coating solution. This solution is facile to form a porous coating on various substrates based on solvent-evaporation-induced phase separation (SEIPS). The coating could continuously release NO up to 200 h in the presence of ascorbic acid (Asc). In addition, the coating could accelerate endothelialization by promoting the viability of human umbilical vein endothelial cells (HUVECs) while inhibiting the proliferation of human umbilical artery smooth muscle cells (HUASMCs). Furthermore, the coating had good antibacterial activity and blood compatibility. Taken together, this universal coating provides wider potential applications in the field of cardiovascular implants.

Microplastics induced apoptosis in macrophages by promoting ROS generation and altering metabolic profiles.

The ubiquitous presence of Microplastics (MPs) in various environments documented in recent years has recently raised significant concerns about their toxic effects. While macrophages serve as the first line of defense against toxic substances and pathogens, the impact and mechanisms of microplastics on these immune cells remain unclear. This study aims to explore whether MPs induce macrophage apoptosis through the promotion of reactive oxygen species (ROS) generation and alterations in metabolic profiles. The viability of RAW264.7 cells decreased as the concentration of 0.5 µm or 5 µm MPs ranged from 0.2 to 1.5 mg/mL, with a more pronounced effect observed in the 0.5 µm MPs group. Zebrafish exposed to 0.5 µm or 5 µm MPs at a concentration of 0.5 mg/mL exhibited decreased macrophage abundance and increased apoptosis, accompanied by alterations in the expression of inflammatory and apoptosis-related genes. While 0.5 µm MPs were observed to enter macrophages, 5 µm MPs only adhered to the cell membrane surface. Both particle sizes induced ROS generation and disrupted cellular metabolism in RAW264.7 cells. Notably, macrophages exhibited a more pronounced response to 0.5 µm MPs, characterized by heightened ROS generation, increased secretion of pro-inflammatory mediators, and a significant decrease in sphingolipid metabolism. These findings suggest that the adverse effects on macrophages are greater with 0.5 µm MPs compared to 5 µm MPs, possibly attributed to particle size effects. This study contributes additional evidence on the impact of MPs on human immune cells.

Determination of Dipicolinic Acid through the Antenna Effect of Eu(III) Coordination Polymer.

Bacillus anthracis is a Gram-positive bacterium that can cause acute infection and anthracnose, which is a serious concern for human health. Determining Bacillus anthracis through its spore biomarker dipicolinic acid (DPA) is crucial, and there is a strong need for a method that is rapid, sensitive, and selective. Here, we created Eu(III)-coordination polymers (Eu-CPs) with surfaces that have abundant carboxyl and hydroxyl groups. This was achieved by using citric acid and europium nitrate hexahydrate as precursors in a straightforward one-pot hydrothermal process. These Eu-CPs were then successfully utilized for highly sensitive DPA determination. The fluorescence (FL) emission of Eu-CPs, which is typically weak due to the coordination of Eu(III) with water molecules, was significantly enhanced in the presence of DPA. This enhancement is attributed to the competitive binding between DPA's carboxyl or hydroxyl groups and water molecules. As a result, the absorbed energy of DPA, when excited by 280 nm ultraviolet light, is transferred to Eu-CPs through an antenna effect. This leads to the emission of the characteristic red fluorescence of Eu3+ at 618 nm. A strong linear relationship was observed between the enhanced FL intensity and DPA concentration in the range of 0.5-80 µM. This relationship allowed for a limit of detection (LOD) of 15.23 nM. Furthermore, the Eu-CPs we constructed can effectively monitor the release of DPA from Bacillus subtilis spores, thereby further demonstrating the potential significance of this strategy in the monitoring and management of anthrax risk. This highlights the novelty of this approach in practical applications, provides a valuable determination technique for Bacillus anthracis, and offers insights into the development cycle of microorganisms.

Multiresponsive Keratin-Polysulfobetaine Conjugate-Based Micelles as Drug Carriers with a Prolonged Circulation Time.

A protein-polymer conjugate combines the chemical properties of a synthetic polymer chain with the biological properties of a protein. In this study, the initiator terminated with furan-protected maleimide was first synthesized through three steps. Then, a series of zwitterionic poly[3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate] (PDMAPS) was synthesized via atom transfer radical polymerization (ATRP) and optimized. Subsequently, well-controlled PDMAPS was conjugated with keratin via thiol-maleimide Michael addition. The keratin-PDMAPS conjugate (KP) could self-assemble in an aqueous solution to form micelles with low critical micelle concentration (CMC) values and good blood compatibility. The drug-loaded micelles exhibited triple responsiveness to pH, glutathione (GSH), and trypsin under tumor microenvironments. In addition, these micelles showed high toxicity against A549 cells while low toxicity on normal cells. Furthermore, these micelles performed prolonged blood circulation.

A systematic review of microbial markers for risk prediction of colorectal neoplasia.

BACKGROUND: Substantial evidence indicates that dysbiosis of the gut microbial community is associated with colorectal neoplasia. This review aims to systematically summarise the microbial markers associated with colorectal neoplasia and to assess their predictive performance. METHODS: A comprehensive literature search of MEDLINE and EMBASE databases was performed to identify eligible studies. Observational studies exploring the associations between microbial biomarkers and colorectal neoplasia were included. We also included prediction studies that constructed models using microbial markers to predict CRC and adenomas. Risk of bias for included observational and prediction studies was assessed. RESULTS: Forty-five studies were included to assess the associations between microbial markers and colorectal neoplasia. Nine faecal microbiotas (i.e., Fusobacterium, Enterococcus, Porphyromonas, Salmonella, Pseudomonas, Peptostreptococcus, Actinomyces, Bifidobacterium and Roseburia), two oral pathogens (i.e., Treponema denticola and Prevotella intermedia) and serum antibody levels response to Streptococcus gallolyticus subspecies gallolyticus were found to be consistently associated with colorectal neoplasia. Thirty studies reported prediction models using microbial markers, and 83.3% of these models had acceptable-to-good discrimination (AUROC > 0.75). The results of predictive performance were promising, but most of the studies were limited to small number of cases (range: 9-485 cases) and lack of independent external validation (76.7%). CONCLUSIONS: This review provides insight into the evidence supporting the association between different types of microbial species and their predictive value for colorectal neoplasia. Prediction models developed from case-control studies require further external validation in high-quality prospective studies. Further studies should assess the feasibility and impact of incorporating microbial biomarkers in CRC screening programme.

Tannic Acid-Assisted Immobilization of Copper(II), Carboxybetaine, and Argatroban on Poly(ethylene terephthalate) Mats for Synergistic Improvement of Blood Compatibility and Endothelialization.

Due to thrombosis and intimal hyperplasia, small-diameter vascular grafts have poor long-term patency. A combination strategy based on nitric oxide (NO) and anticoagulants has the potential to address those issues. In this study, poly(ethylene terephthalate) (PET) mats were prepared by electrospinning and coated with tannic acid (TA)/copper ion complexes. The chelated copper ions endowed the mats with sustained NO generation by catalytic decomposition of endogenous S-nitrosothiol. Subsequently, zwitterionic carboxybetaine acrylate (CBA) and argatroban (AG) were immobilized on the mats. The introduced AG and CBA had synergistic effects on the improvement of blood compatibility, resulting in reduced platelet adhesion and prolonged blood clotting time. The biocomposite mats selectively promoted the proliferation and migration of human umbilical vein endothelial cells while inhibiting the proliferation and migration of human umbilical arterial smooth muscle cells under physiological conditions. In addition, the prepared mats exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. Collectively, the prepared mats hold great promise as artificial small-diameter vascular grafts.

Development and application of a colloidal-gold dual immunochromatography strip for detecting African swine fever virus antibodies.

African swine fever (ASF) is an acute and highly contagious infectious disease caused by the African swine fever virus (ASFV). Currently, there is no vaccine against ASF worldwide, and no effective treatment measures are available. For this reason, developing a simple, rapid, specific, and sensitive serological detection method for ASFV antibodies is crucial for the prevention and control of ASF. In this study, a 1:1 mixture of gold-labeled p30 and p72 probes was used as the gold-labeled antigen. The p30 and p72 proteins and their monoclonal antibodies were coated on a nitrocellulose membrane (NC) as a test (T) line and control (C) line, respectively. A colloidal-gold dual immunochromatography strip (ICS) for ASFV p30 and p72 protein antibodies was established. The results showed that the colloidal-gold dual ICS could specifically detect ASFV antibodies within 5-10 min. There was no cross-reaction after testing healthy pig serum; porcine reproductive and respiratory syndrome virus (PRRSV), foot-and-mouth disease type A virus (FMDV-A), foot-and-mouth disease type O virus (FMDV-O), porcine circovirus type 2 (PCV-2), and classical swine fever virus (CSFV) positive sera. A positive result was obtained only for the positive control P1. The sensitivity of the test strips was 1:256, which was equivalent to that of commercially ELISA kits. Their coincidence rate with the two commercial ASFV ELISA antibodies detection kits was higher than 98%. The test strips were stably stored at 18-25 °C and 4 °C for 4 and 6 months, respectively. The colloidal-gold dual ICS prepared in this study had high sensitivity and specificity and were characterized by rapid detection, simple operation, and easy interpretation of results. Therefore, they are of great significance to diagnose, prevent, and control African swine fever. KEY POINTS: • We establish an antibody detection that is quick and can monitor an ASF infection. • We observe changes in two protein antibodies to dynamically monitor ASF infection. • We use diversified detection on a single test strip to detect both antibodies.

Metabolic profile of lung-targeted docetaxel liposomes in rabbits, rats and mice.

1. Docetaxel (DTX) liposome powder was stable over three months, and the liposome suspension was stable within 8 h.2. Rabbits, rats and mice were intravenously treated with DTX-LP or with a DTX injection (DTX-IN). Four major metabolites of DTX were identified in feces: M1, M2, M3 and M4. However, M4 was not found in the bile.3. The most abundant metabolite in the feces was M2 followed by M1/M3, with only a small amount of M4 observed. The most abundant metabolite in bile was also M2, followed by M1/M3.4. The liposomal delivery of DTX did not alter the in vivo drug metabolism, and there were no significant differences among the three species tested. This suggested that this formulation is pharmaceutically safe for clinical use. In contrast to the traditional injected formula, DTX-LP administration significantly delayed drug metabolism, as observed in feces and bile. This property will greatly enhance the DTX therapeutic efficacy and reduce the systemic side effects of NSCLC treatment.

Cyclodextrin-Based Star-Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages.

Effective delivery of therapeutic genes or small molecular drugs into macrophages is important for cell based immune therapy, but it remains a challenge due to the intracellular reactive oxygen species and endosomal degradation of therapeutics inside immune cells. In this report, the star-like amphiphilic biocompatible ß-cyclodextrin-graft-(poly(ε-caprolactone)-block-poly(2-(dimethylamino) ethyl methacrylate)x (ß-CD-g-(PCL-b-PDMAEMA)x ) copolymer, consisting of a biocompatible cyclodextrin core, hydrophobic poly(ε-caprolactone) PCL segments and hydrophilic PDMAEMA blocks with positive charge, is optimized to achieve high efficiency gene transfection with enhanced stability, due to the micelle formation by hydrophobic PCL segments. In comparison with lipofetamine, a currently popular nonviral gene carrier, ß-CD-g-(PCL-b-PDMAEMA)x copolymer, shows better transfection efficiency of plasmid desoxyribose nucleic acid in RAW264.7 macrophages. More interestingly, this delivery platform by ß-CD-g-(PCL-b-PDMAEMA)x not only shows low toxicity but also better dexamethasone delivery efficiency, which might indicate its great potential in immunotherapy.

Sodium alginate/carboxymethyl cellulose films containing pyrogallic acid: physical and antibacterial properties.

BACKGROUND: Antibacterial films were prepared using sodium alginate (SA) and carboxymethyl cellulose (CMC) as a matrix, glycerin as a plasticizer and CaCl2 as a cross-linking agent, and by incorporating the natural antibacterial agent pyrogallic acid (PA). The present study describes the microstructure and the physical, barrier, mechanical, optical and antibacterial properties of blended films prepared by incorporating different concentrations of PA into the SA/CMC matrix. RESULTS: The microstructure of the films was investigated by Fourier transform infrared spectroscopy and scanning electron microscopy, which revealed that PA interacts with the SA/CMC matrix through hydrogen bonding. Moreover, the incorporation of PA increased the moisture content, water vapor permeability and oxygen permeability of SA/CMC films. Films containing 40 g kg-1 of PA had the highest elongation at break result (39.60%). Compared with pure SA/CMC films, the incorporation of PA improved the barrier properties against ultraviolet light; however, it decreased the color parameter L* value and increased the a* and b* values of the films. Furthermore, films with PA, especially at higher concentrations, were more effective against Escherichia coli and Staphylococcus aureus. CONCLUSION: Antibacterial SA/CMC films incorporating PA appear to have good potential to enhance the safety of foods and food products. © 2016 Society of Chemical Industry.

Synchronous microencapsulation of multiple components in silymarin into PLGA nanoparticles by an emulsification/solvent evaporation method.

The development of polymeric carriers loaded with extracts suffers from the drawback not to be able to incorporate simultaneously various pharmacological compounds into the formulation. The aim of this study was therefore to achieve synchronous microencapsulation of multiple components of silymarin into poly (lactic-co-glycolic acid) nanoparticle, the most commonly used polymeric carrier with biodegradability and safety. The main strategy taken was to improve the overall entrapment efficiency and to reduce the escaping ratio of the components of different physicochemical properties. The optimized nanoparticles were spherical in morphology with a mean particle size of 150 ± 5 nm. Under common preparative conditions, silybin and isosilybin were entrapped in high efficiency, whereas taxifolin, silychristin and silydianin, especially taxifolin, showed less entrapment because they were more hydrophilic. By changing the pH of the outer aqueous phase and saturating it with silymarin, the entrapment efficiency of taxifolin, silychristin and silydianin could be significantly improved to over 90%, the level similar to silybin and isosilybin, thereby achieving synchronous encapsulation. It could be concluded that synchronous encapsulation of multiple components of silymarin was achieved by optimizing the preparative variables.

Dentin matrix proteins (DMPs) enhance differentiation of BMMSCs via ERK and P38 MAPK pathways.

Dentin, the predominant mineralized tissue of the tooth, comprises an extracellular matrix of collagen and a heterogeneous mixture of non-collagenous components, many of which have cellular signaling properties. These properties may be important in signaling stem cell involvement in tissue regeneration following injury and the present study investigates their morphogenic effects on differentiation of Bone Marrow Stromal Stem Cells (BMMSCs) in vitro. Non-collagenous dentin matrix proteins (DMPs) were isolated from healthy human teeth and their effects on BMMSCs behavior examined during in vitro culture. In vitro, DMPs enhanced alkaline phosphatase activity and mineralization in BMMSCs cultures as well as increasing the expression of dentinogenic and osteogenic differentiation markers (including runt-related transcription factor 2, osterix, bone sialoprotein, dentin sialophosphoprotein and osteocalcin) at both transcript and protein levels, with 10 µg/mL DMPs being the optimal stimulatory concentration. Expression of phosphor-ERK/phosphor-P38 in BMMSCs was up-regulated by DMPs and, in the presence of the ERK1/2- and p38-specific inhibitors, the differentiation of BMMSCs was inhibited. These data indicate that DMPs promote the dentinogenic/osteogenic differentiation of BMMSCs via the ERK/p38 MAPK pathways.

Genetic characterization of emerging coxsackievirus A12 associated with hand, foot and mouth disease in Qingdao, China.

To characterize the genetic properties of coxsackievirus A12 (CVA12) strains isolated from hand, foot and mouth disease (HFMD) patients in Qingdao during 2008-2011, the complete genome and VP1 coding region were sequenced and analyzed. Phylogenetic analysis showed that all strains from China clustered into three different branches, suggesting multiple lineages of CVA12 co-circulating in Asia. Sequence analysis indicated a monophyletic group only when the P1 region was examined, indicating possible recombination between CVA12 and other HEV-A serotypes. The emergence of CVA12 involved in an HFMD outbreak in China is a public-health issue.

Determination of fusaric acid in maize using molecularly imprinted SPE clean-up.

A new LC method to detect fusaric acid (FA) in maize is reported based on a molecularly imprinted SPE clean-up using mimic-templated molecularly imprinted polymers. Picolinic acid was used as a toxin analog for imprinting polymers during a thermolytic synthesis. Both acidic and basic functional monomers were predicted to have favorable binding interactions by MP2 ab initio calculations. Imprinted polymers synthesized with methacrylic acid or 2-dimethylaminoethyl methacrylate exhibited imprinting effects in SPE analysis. FA levels were determined using RP ion-pairing chromatography with diode-array UV detection and tetrabutylammonium hydrogen sulfate in the mobile phase. A method was developed to detect FA in maize using molecularly imprinted SPE analysis within the range of 1-100 µg/g with recoveries between 83.9 and 92.1%.

Causal relationship, shared genes between rheumatoid arthritis and pulp and periapical disease: evidence from GWAS and transcriptome data.

Objective: Patients with rheumatoid arthritis (RA) have an increased risk of developing pulp and periapical disease (PAP), but the causal relationship and shared genetic factors between these conditions have not been explored. This study aimed to investigate the bidirectional causal relationship between RA and PAP and to analyze shared genes and pathogenic pathways. Methods: We utilized GWAS data from the IEU Open GWAS Project and employed five Mendelian randomization methods (MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) to investigate the bidirectional causal relationship between RA and PAP. Transcriptome data for RA and irreversible pulpitis (IRP) were obtained from the GEO database. Hub genes were identified through differential analysis, CytoHubba, machine learning (ML), and other methods. The immune infiltration of both diseases was analyzed using the ssGSEA method. Finally, we constructed a regulatory network for miRNAs, transcription factors, chemicals, diseases, and RNA-binding proteins based on the identified hub genes. Results: RA was significantly associated with an increased risk of PAP (OR = 1.1284, 95% CI 1.0674-1.1929, p < 0.001). However, there was insufficient evidence to support the hypothesis that PAP increased the risk of RA. Integrating datasets and differential analysis identified 84 shared genes primarily involved in immune and inflammatory pathways, including the IL-17 signaling pathway, Th17 cell differentiation, and TNF signaling pathway. Using CytoHubba and three ML methods, we identified three hub genes (HLA-DRA, ITGAX, and PTPRC) that are significantly correlated and valuable for diagnosing RA and IRP. We then constructed a comprehensive regulatory network using the miRDB, miRWalk, ChipBase, hTFtarget, CTD, MalaCards, DisGeNET, and ENCORI databases. Conclusion: RA may increase the risk of PAP. The three key genes, HLA-DRA, ITGAX, and PTPRC, have significant diagnostic value for both RA and IRP.

Development of pH-responsive intelligent films based on κ-carrageenan/straw lignin and anthocyanin from Padus virginiana peel for real-time monitoring of chicken.

A series of intelligent films with pH-responsive properties were prepared using Padus virginiana peel extract (PVE) as a smart response factor, κ-carrageenan (κC) as a matrix, and complexed with rice straw lignin (SL). Following the addition of 5 mL PVE at a concentration of 430.99 mg/L, tensile strength and elongation at break of the films increased to a maximum value of 21.25 ± 0.75 MPa and 24.04 ± 0.69 %, respectively. The water vapour permeability of the films decreased with increasing PVE addition, and the minimum value was 5.85 ± 0.09 × 10-11 g m-1 s-1 Pa-1. All the films had favourable thermal stability, transparency, haze and antioxidant properties. PVE-containing films all exhibited excellent pH and ammonia response properties. The higher the humidity of the environment, the faster the ammonia response, and the films were capable of rapid discoloration at 75 % relative humidity. κC/SL-PVE5 can be used to monitor the freshness of chicken breast meat. When the total volatile basic nitrogen of chicken breast meat was increased to 14.27 mg/100 g, κC/SL-PVE5 changed from pink to greyish-yellow. In conclusion, κC/SL-PVE intelligent films hold great promise for real-time monitoring of meat freshness.

A chitosan derivative/phytic acid polyelectrolyte complex endowing polyvinyl alcohol film with high barrier, flame-retardant, and antibacterial effects.

Films with high barrier, flame-retardant, and antibacterial properties are beneficial in terms of food and logistics safety. Herein, a polyelectrolyte complex (PEC) of N-(2-hydroxyl)-propyl-3-trimethylammonium chitosan chloride (HTCC, chitosan derivative) and phytic acid (PA) was successfully prepared and then incorporated into a polyvinyl alcohol (PVA) matrix to fabricate a composite film with satisfactory barrier, fire-retardant, and antibacterial properties. The influence of HTCC/PA (HTPA) on the structural, physical and functional properties of the PVA matrix was investigated. Compared with the PVA film, PVA-HTPA6 film exhibited 3.38 times of flexibility and 83.33 % and 80.64 % of water vapor permeability and oxygen permeability, respectively. Benefiting from HTPA, the PVA-HTPA6 film exhibited outstanding flame-retardant capacity, with a high LOI value (33.30 %) and immediate self-extinguishing behaviour. Furthermore, the HTPA endowed the films with excellent antibacterial properties. Compared with other films, the PVA-HTPA6 film effectively maintained the quality of pork during storage at 4 °C for 9 days. Our findings indicate that the films are promising for packaging and logistics safety with oil-containing foods.

Microplastics exposure causes the senescence of human lung epithelial cells and mouse lungs by inducing ROS signaling.

Microplastics (MPs) are environmental pollutants and can be inhaled by humans to threaten health. The lung tissue, responsible for the gas exchange between the body and the environment, is vulnerable to MPs exposure. However, from the perspective of cellular senescence, the effect of MPs on lung cells and tissues has not yet been deeply dissected. In this study, we reported that all the four typical MPs exhibited the significant biological effects in term of inducing senescence of human lung derived cells A549 and BEAS-2B in vitro. We further found that polyvinyl chloride (PVC) increased the reactive oxygen species (ROS) level in A549 cells and that PVC-induced senescent characteristics could be largely reversed by antioxidant treatment. Importantly, intratracheal instillation of PVC MPs in mice could effectively impair their physical function, induce the increased systemic inflammation level, cause the accumulation of senescent cells. Our study demonstrates that MPs induce senescence in human lung epithelial cells and mouse lungs by activating ROS signaling, and provides new insight into the potential pathogenesis of MPs on lung diseases.

Recent advances in keratin for biomedical applications.

The development of keratin-based biomaterials provides an approach to addressing related environmental pollutants and turns waste into wealth. Keratin possesses various merits, such as biocompatibility, biodegradability, hemostasis, non-immunogenicity, antibacterial activity, antioxidation, multi-responsiveness, and abundance in nature. Additionally, keratin biomaterials have been extensively employed in various biomedical applications such as drug delivery, wound healing, and tissue engineering. This review focuses on the properties and biomedical applications of keratin biomaterials. It is anticipated to provide valuable insights for the research and development of keratin biomaterials.

Microplastics existence affected heavy metal affinity to ferrihydrite as a representative sediment mineral.

The coexistence of minerals, heavy metals and microplastics in sediment has been widely reported, while the interactions between minerals and heavy metals may be affected by the presence of microplastics. Therefore, to elucidate the effect of microplastics on the interactions between heavy metals and sediment minerals, this study conducted a series of experiments using polystyrene (PS) microplastics, Pb/Cr/Cd and ferrihydrite (Fh). The presence of PS microplastics with ferrihydrite (Fh-MPs200, mass ratio of ferrihydrite to PS of 200:1) improved the adsorption capacity of ferrihydrite, especially with an increase of 36 % for Pb. Morphological characterization demonstrated that the nano-ferrihydrite particles were dispersed on the surface of the PS microplastics, increasing the available reaction sites of the ferrihydrite particles. Furthermore, the results of zeta potential and pH effect showed that the reduction in electrostatic repulsion after adding PS was another critical reason for the increase in Pb adsorption by Fh-MP200. As a result, the presence of PS microplastics enhanced the complexation of Pb ions and the hydroxyl groups on the ferrihydrite surface. This study demonstrated that the presence of microplastics in the sedimentary environment can alter the dispersion and surface properties of minerals, thereby affecting the accumulation and transportation of heavy metals at the water-sediment interface.