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Water-soluble polyvinyl alcohol/carboxymethyl chitosan (PVA/CMCS) blend fiber films were successfully prepared using a plane-collection centrifugal spinning machine. The addition of CMCS significantly increased the shear viscosity of the PVA/CMCS blend solution. The effects of spinning temperature on the shear viscosity and the centrifugal spinnability of PVA/CMCS blend solution were discussed. The PVA/CMCS blend fibers were uniform, and their average diameters ranged from 1.23 μm to 29.01 μm. It was found that the CMCS was distributed evenly in the PVA matrix and increased the crystallinity of PVA/CMCS blend fiber films. The hydrogen bonds between the hydroxyl group of PVA and the carboxymethyl group of CMCS were also detected. An in vitro cell study of human skin fibroblast cells on the PVA/CMCS blend fiber films confirmed biocompatibility. The maximum tensile strength and elongation at break of PVA/CMCS blend fiber films could reach 3.28 MPa and 29.52 %, respectively. The colony-plate-count tests indicated that the PVA16-CMCS2 presented 72.05 % and 21.36 % antibacterial rates against Staphylococcus aureus (10 4  CFU/mL) and Escherichia coli (10 3  CFU/mL), respectively. These values indicated that the newly prepared PVA/CMCS blend fiber films are promising materials for cosmetic and dermatological applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Hydrogel adhesives integrating both rapid and strong adhesion to blooding tissues and biocompatibility are highly desired for fast hemostasis. Herein, a flexible hyaluronic acid hydrogel adhesive is fabricated via photocrosslinking of the solution originating from dopamine-conjugated maleic hyaluronic acid (DMHA) in situ. The introduction of acrylate groups with high substitutions into the hydrogel matrix endows the adhesive with rapid gelation and strong tissue adhesion properties through photopolymerization. Moreover, the high substitution of catechol groups with unoxidized state can not only induce red blood cell aggregation and platelets adhesion but also adhere to wound tissue to further enhance hemostasis. Based on its bio-adhesion and procoagulant activity, the DMHA hydrogel formed in situ reveals superior hemostatic performance in the rat liver injury model and noncompressible hemorrhage model, and rabbit femoral artery puncture model, compared to commercial products (gauze, absorbable gelatin sponge) and oxidized DMHA (SMHA) hydrogel. Besides, the hydrogel exhibited good adaptability, biodegradability, and superior cytocompatibility as well as negligible inflammation. This hydrogel adhesive is a promising biological adhesive for hemorrhage control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The development of environmentally friendly, green, and nontoxic adhesives with excellent dry and wet adhesion properties is of great attraction. In nature, barnacles and mussels exhibit strong adhesion by secreting a hydroxyl-rich dopa. Inspired by their adhesion mechanism, a simple biobased MAG-PETMP (MP) adhesive was prepared from magnolol (MAG) and pentaerythritol tetra (3-mercaptopropionate) (PETMP) by a thiol-ene click chemistry reaction. MP as an adhesive exhibits high bond strength with other substrates due to hydrogen bonds formed by the abundant hydroxyl groups at the interface and shows an inherent thermosetting network structure. Since MP has a thermosetting network, it exhibits excellent thermal stability, solvent resistance, and high mechanical strength, which make the adhesive stable in a humid environment. The cross-linking degree of MP can be easily controlled by adjusting the molar ratio of MAG and PETMP. Among the synthesized samples, the elongation at break of the MP 1 formulation is 174.27%, which makes it promising for use as a flexible adhesive. Moreover, the inherent antibacterial properties of MAG enable MP to exhibit antimicrobial properties and antibacterial adhesion to some extent. This work provides a simple biomimetic strategy that could enable the application of MAG for adhesives.

Death from lethal hemorrhage remains a major problem in various emergency scenarios. There is a continuous interest in the development of absorbable hemostatic dressings that can control hemorrhage rapidly and can be left in the wound site without removal. In this study, we report a hemostatic gauze dressing based on N -carboxyethyl chitosan (CECS) gelling fibers. The CECS fibrillar gauze combines ultra-hydrophilic, cationic chemical property of the fiber components with the fluffy nonwoven material form, exhibiting good conformability for wound filling, high fluid uptaking capacity, and enhanced blood-concentrating effect. In a swine femoral artery injury model, the CECS fibrillar gauze achieves shorter time to hemostasis and less blood loss compared with commercially available hemostatic dressings. This chitosan gelling fiber gauze demonstrates comparable bioabsorbability to clinically used absorbable hemostat and thus may be applied to treat fatal hemorrhage both in emergency medical services and in internal surgical procedures.

Of the three branches of unfolded protein response (UPR) that were reportedly activated by porcine epidemic diarrhea virus (PEDV), PERK is recently shown to act as an upstream regulator of oxidative response of the cells. However, it remains unknown if and how PERK activation during PEDV infection would result in oxidative stress, and whether activation of PERK and its downstream molecules affect PEDV replication. Here, we demonstrate that infection with the PEDV strain YJH/2015 triggered UPR in Vero E6 cells by activating the PERK/eIF2α pathway and led to significant increase in the expression of proapoptotic protein C/EBP homologous protein (CHOP) and ER oxidoreductase 1 alpha (ERO1α). Inhibition of PERK by short hairpin RNA (shRNA) or GSK2606414 and knockdown of CHOP by small interfering RNA reduced expression of ERO1α and generation of ROS in PEDV-infected cells. Inhibition of ERO1α by shRNA or EN460 decreased PEDV-induced ROS generation. Genetic or pharmacological inhibition of each component of PERK, CHOP, ERO1α, and ROS led to significant suppression of PEDV replication. Collectively, our study provides the first evidence that PEDV manipulates endoplasmic reticulum to perturb its redox homeostasis via the PERK-CHOP-ERO1α-ROS axis in favor of its replication., (© 2023. The Author(s).)

Bovine viral diarrhea virus (BVDV) is an important pathogen responsible for significant economic loss to cattle. BVDV infection in pregnant cattle leads to fetal infection and reproductive losses, including early embryonic death, abortion, and stillbirth. Importantly, vaccinated heifers could not provide fetal protection against BVDV. It can be divided into two genotypes (BVDV-1 and BVDV-2) and two biotypes (cytopathic (CP) and non-cytopathic (NCP)). Infection with NCP-BVDV during gestation, the fetus becomes persistently infected (PI) and sheds BVDV throughout life, serving as the main source of infection for other cattle. BVDV potentially induces immunosuppression and aggravates bovine respiratory disease (BRD). Accordingly, BVDV infection results in a heterogeneous range of clinical signs and immune responses. Interferon (IFN) plays a vital role by mediating the innate immune response against antiviral infection through the Janus Kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. BVDV infection can reportedly exert variable degrees of influence on IFN response. Interestingly, reports have suggested that IFN can exert a significant inhibitory effect on various viruses. Human IFN-α was used to restrain BVDV in vitro. In this article, we summarized the latest researches on IFN response during BVDV infection., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Porcine circovirus type 2 (PCV2), the causative agent of porcine circovirus-associated diseases (PCVAD), is known to induce oxidative stress, activate p53 with induction of cell cycle arrest, and trigger the PERK (protein kinase R-like endoplasmic reticulum kinase) branch of the endoplasmic reticulum (ER) stress pathway. All these cellular responses could enhance PCV2 replication. However, it remains unknown whether PERK activation by PCV2 is involved in p53 signaling with subsequent changes of cell cycle. Here, we demonstrate that PCV2 infection induced cell cycle arrest at S phase to favor its replication via the PERK-reactive oxygen species (ROS)-p53 nexus. PCV2 infection promoted phosphorylation of p53 (p-p53) at Ser15 in porcine alveolar macrophages. Inhibition of PERK by RNA silencing downregulated total p53 (t-p53) and p-p53. Treatment with the MDM2 inhibitor nutlin-3 led to partial recovery of t-p53 in perk -silenced and PCV2-infected cells. perk silencing markedly downregulated ROS production. Scavenging of ROS with N -acetylcysteine (NAC) of PCV2-infected cells downregulated t-p53 and p-p53. Increased accumulation of p-p53 in the nuclei during PCV2 infection could be downregulated by silencing of perk or NAC treatment. Further studies showed that perk silencing or NAC treatment alleviated S phase accumulation and downregulated cyclins E1 and A2 in PCV2-infected cells. These findings indicate that the PCV2-activated PERK-ROS axis promotes p-p53 and contributes to cell cycle accumulation at S phase when more cellular enzymes are available to favor viral DNA synthesis. Overall, our study provides a novel insight into the mechanism how PCV2 manipulates the host PERK-ROS-p53 signaling nexus to benefit its own replication via cell cycle arrest. IMPORTANCE Coinfections or noninfectious triggers have long been considered to potentiate PCV2 infection, leading to manifestation of PCVAD. The triggering mechanisms remain largely unknown. Recent studies have revealed that PERK-mediated ER stress, oxidative stress, and cell cycle arrest during PCV2 infection are conducive to viral replication. However, how PCV2 employs such host cell responses requires further research. Here, we provide a novel mechanism of PCV2-induced ER stress and enhanced viral replication: the PCV2-activated PERK-ROS-p53 nexus increases S phase cell population, a cell cycle period of DNA synthesis favorable for PCV2 replication. The fact that PCV2 deploys the simple ROS molecules to activate p53 to benefit its replication provides novel insights into the triggering factors, that is, certain stimuli or management measures that induce ER stress with subsequent generation of ROS would exacerbate PCVAD. Use of antioxidants is justified on farms where PCVAD is severe.

Porcine circovirus type 2 (PCV2) infection induces endoplasmic reticulum (ER) stress and oxidative stress. These cellular responses could be connected with apoptosis. However, the mechanisms that link ER stress and oxidative stress in PCV2-induced apoptosis are poorly characterized. Here, we demonstrate that PCV2 infection increased expression of proapoptotic protein C/EBP homologous protein (CHOP) and ER oxidoreductase 1 alpha (ERO1α). Inhibition of CHOP by RNA silencing or inhibition of ERO1α by short hairpin RNA or EN460 repressed PCV2-induced reactive oxygen species (ROS) generation, cytosolic calcium level, and apoptotic rate in PK-15 cells. Overexpression of ERO1α enhanced PCV2-induced oxidative stress, caspase-3 cleavage, and apoptosis rate. Treatment of PCV2-infected cells with ROS scavenger N-acetyl-L-cysteine downregulated PCV2-induced ROS production, cytosolic calcium level, and apoptosis rate, but intriguingly decreased expression of CHOP and ERO1α. Thus, we propose that PCV2 induces apoptosis through ER Stress via CHOP-ERO1α-ROS signaling in host cells., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Biodegradable porous scaffolds with different structure, porosity, and strength play a critical role in the repair and regeneration of defects in bone tissue engineering by changing the proliferation condition for cell. In this study, polylactic acid (PLA) scaffold with directional porous structure is designed and fabricated using the method of ice template and phase inversion for speeding up bone repair by promoting the growth and proliferation of bone cells. The morphology, mechanical properties, hydrophilicity, and wicking properties of PLA scaffolds were characterized by scanning electron microscope, universal testing machine, contact angle tester and wicking rate test, respectively. In vitro biocompatibility has been investigated through measuring cell adhesion, proliferation, and viability on PLA scaffold with directional porous structure. Prepared PLA scaffold was implanted into animals to observe the repair mechanism of large-sized bone defects. This study proposes a novel bioporous scaffold design to induce osteocyte growth at the rat calvaria with a directional pore structure, and the scaffold edges were integrated with the calvaria at week 12, effectively promoting the repair and regeneration of defective bone tissue., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The development of natural hydrogels with sufficient strength and self-healing capacity to accelerate skin wound healing is still challenging. Herein, a hyaluronic acid nanocomposite hydrogel was developed based on aldehyde-modified sodium hyaluronate (AHA), hydrazide-modified sodium hyaluronate (ADA), and aldehyde-modified cellulose nanocrystals (oxi-CNC). This hydrogel was formed in situ using dynamic acylhydrazone bonds via a double-barreled syringe. This hydrogel exhibited improved strength and excellent self-healing ability. Furthermore, platelet-rich plasma (PRP) can be loaded in the hyaluronic acid nanocomposite hydrogels (ADAC) via imine bonds formed between amino groups on PRP ( e . g ., fibrinogen) and aldehyde groups on AHA or oxi-CNC to promote skin wound healing synergistically. As expected, ADAC hydrogel could protect and release PRP sustainably. In animal experiments, ADAC@PRP hydrogel significantly promoted full-thickness skin wound healing through enhancing the formation of granulation tissue, facilitating collagen deposition, and accelerating re-epithelialization and neovascularization. This self-healing nanocomposite hydrogel with PRP loading appears to be a promising candidate for wound therapy.

Introduction: Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication., Methods: In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H 2 O 2 ) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID 50 , and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot., Results: The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H 2 O 2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi., Conclusion: These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications., Competing Interests: The authors declare no competing financial interests and no conflicts of interest for this work., (© 2022 Shao et al.)

Hyaluronic acid (HA) hydrogel is preferred for biomedicine applications, as it possesses biodegradability, biocompatibility, and cell-regulated capacity as well as high hydration nature similar to the native extracellular matrix. However, HA hydrogel fabricated via a 3D printing technique often faces poor printing properties. In this study, maleiated sodium hyaluronate (MHA) with a high substituted degree of the acrylate group (i.e., 2.27) and thiolated sodium hyaluronate (SHHA) were synthesized. By blending these modified HAs, the MHA/SHHA hydrogels were prepared via pre-crosslinking through thiol-acrylate Michael addition and subsequently covalent crosslinking using thiol-acrylate and acrylate-acrylate photopolymerization mechanisms. Rheological properties, swelling behaviors, and mechanical properties can be modulated by altering the molar ratio of the thiol group and acrylate group. The results showed that the MHA/SHHA hydrogel precursors have rapidly gelling capacity and improved compressive strength. Based on these results, high-resolution hydrogel scaffolds with good structural stability were prepared by extrusion-based 3D printing. This HA hydrogel is cytocompatible and capable of supporting adherence of L929 cells, indicating its great potential for tissue engineering scaffolds.

Ultraviolet (UV) shielding, superhydrophobic and antimicrobial cotton fabrics were fabricated using functional coatings combined with advantages of polyvinylsilsesquioxane and ZnO nanoparticles by solution immersion. The influence of composite coatings on surface morphology, water-repellence, UV shielding property, mechanical property, thermal degradation behavior and antibacterial property of the cotton fabrics was investigated respectively. It is evidently found that the cotton fabrics functionalized by composite coatings exhibited excellent UV shielding, durable superhydrophobic and antimicrobial properties as compared to the reference materials. Most notably, the mechanical properties of cotton fabrics was significantly improved by surface treatment of the composite coatings without compromising their thermal stability as compared to the pristine cotton fabric. This strategy for fabricating UV shielding and superhydrophobic cotton fabrics will guide for developing advanced functional textile in the future work, which will likely be found in many applications such as advanced protective textiles, oil/water separation, water-proof, antibacterial and self-cleaning fields., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Photocrosslinkable hydrogels composed of natural materials exhibit great application potential in tissue engineering scaffolds. However, weak formation and poor mechanical property can usually be a limitation. Herein, the photo-clickable thiol-ene hydrogels based chitosan were synthesized using photopolymerization of maleic chitosan (MCS) and thiol-terminated poly (vinyl alcohol) (TPVA) in the presence of a biocompatible photoinitiator. Rheological property and absorbing behavior of the MCS/TPVA hydrogels could be tailored by varying the amount of TPVA in the feed. There was strong intermolecular hydrogen bonding between the molecules of MCS and TPVA. Notably, the MCS/TPVA hydrogel (MT-3) exhibited rapid gelation behavior (<120 s), improved stiff (G' = ∼5500 Pa) and compressive strength (0.285 ± 0.014 MPa), which were important for hydrogel scaffolds, especially for injectable hydrogel scaffolds. Photocrosslinked MCS/TPVA hydrogels was cytocompatible and could promote the L929 cells attachment and proliferation, showing their potential as tissue engineering scaffolds., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Autophagy is a homeostatic process that has been shown to be vital in the innate immune defense against pathogens. However, little is known about the regulatory role of autophagy in porcine teschovirus 2 (PTV-2) replication. In this study, we found that PTV-2 infection induces a strong increase in GFP-LC3 punctae and endogenous LC3 lipidation. However, PTV-2 infection did not enhance autophagic protein degradation. When cellular autophagy was pharmacologically inhibited by wortmannin or 3-methyladenine, PTV-2 replication increased. The increase in virus yield via autophagy inhibition was further confirmed by silencing atg5, which is required for autophagy. Furthermore, PTV-2 replication was suppressed when autophagy was activated by rapamycin. Together, the results suggest that PTV-2 infection activates incomplete autophagy and that autophagy then inhibits further PTV-2 replication.

Protein-based composites have always been desirable biomaterials as they can be fabricated into a wide range of biomaterials with tunable properties, including modulation of mechanical properties and control of cell responses. Both egg white protein (EW) and silk fibroin (SF) are biocompatible, biodegradable, non-toxic and naturally abundant biopolymers. In order to obtain biocompatible composite films with tunable performance, EW and SF were blended at various ratios. Raising the SF ratio in the composite films significantly increased breaking strength, but impaired flexibility. Conversely, increasing the EW ratio remarkably enhanced elasticity of the composite films. Furthermore, the biological assays based on endothelial cells showed that the incorporation of EW promoted cell viability. These make them potential materials with controllable mechanical property and enhanced bioactivity, providing useful options for the fabrication of tissue engineering scaffolds., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Biocompatible carboxyethyl chitosan/poly(vinyl alcohol) (CECS/PVA) nanofibers were successfully prepared by electrospinning of aqueous CECS/PVA solution. The composite nanofibrous membranes were subjected to detailed analysis by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). SEM images showed that the morphology and diameter of the nanofibers were mainly affected by the weight ratio of CECS/PVA. XRD and DSC demonstrated that there was strong intermolecular hydrogen bonding between the molecules of CECS and PVA. The crystalline microstructure of the electrospun fibers was not well developed. The potential use of the CECS/PVA electrospun fiber mats as scaffolding materials for skin regeneration was evaluated in vitro using mouse fibroblasts (L929) as reference cell lines. Indirect cytotoxicity assessment of the fiber mats indicated that the CECS/PVA electrospun mat was nontoxic to the L929 cell. Cell culture results showed that fibrous mats were good in promoting the cell attachment and proliferation. This novel electrospun matrix would be used as potential wound dressing for skin regeneration.