Modulation of Local Overactive Inflammation via Injectable Hydrogel Microspheres.

Although injectable hydrogel microsphere has demonstrated tremendous promise in clinical applications, local overactive inflammation in degenerative diseases could jeopardize biomaterial implantation's therapeutic efficacy. Herein, an injectable "peptide-cell-hydrogel" microsphere was constructed by covalently coupling of APETx2 and further loading of nucleus pulposus cells, which could inhibit local inflammatory cytokine storms to regulate the metabolic balance of ECM in vitro. The covalent coupling of APETx2 preserved the biocompatibility of the microspheres and achieved a controlled release of APETx2 for more than 28 days in an acidic environment. By delivering "peptide-cell-hydrogel" microspheres to a rat degenerative intervertebral disc at 4 weeks, the expression of ASIC-3 and IL-1ß was significantly decreased for 3.53-fold and 7.29-fold, respectively. Also, the content of ECM was significantly recovered at 8 weeks. In summary, the proposed strategy provides an effective approach for tissue regeneration under overactive inflammatory responses.

Evolution and comparative genomics of the most common Trichoderma species.

BACKGROUND: The growing importance of the ubiquitous fungal genus Trichoderma (Hypocreales, Ascomycota) requires understanding of its biology and evolution. Many Trichoderma species are used as biofertilizers and biofungicides and T. reesei is the model organism for industrial production of cellulolytic enzymes. In addition, some highly opportunistic species devastate mushroom farms and can become pathogens of humans. A comparative analysis of the first three whole genomes revealed mycoparasitism as the innate feature of Trichoderma. However, the evolution of these traits is not yet understood. RESULTS: We selected 12 most commonly occurring Trichoderma species and studied the evolution of their genome sequences. Trichoderma evolved in the time of the Cretaceous-Palaeogene extinction event 66 (±15) mya, but the formation of extant sections (Longibrachiatum, Trichoderma) or clades (Harzianum/Virens) happened in Oligocene. The evolution of the Harzianum clade and section Trichoderma was accompanied by significant gene gain, but the ancestor of section Longibrachiatum experienced rapid gene loss. The highest number of genes gained encoded ankyrins, HET domain proteins and transcription factors. We also identified the Trichoderma core genome, completely curated its annotation, investigated several gene families in detail and compared the results to those of other fungi. Eighty percent of those genes for which a function could be predicted were also found in other fungi, but only 67% of those without a predictable function. CONCLUSIONS: Our study presents a time scaled pattern of genome evolution in 12 Trichoderma species from three phylogenetically distant clades/sections and a comprehensive analysis of their genes. The data offer insights in the evolution of a mycoparasite towards a generalist.

Successful treatment of refractory oral condyloma acuminatum through laser-photodynamic therapy combination.

Condyloma acuminatum (CA) is a sexually transmitted disease primarily caused by human papilloma virus (HPV) infection, predominantly affecting the genital and anal regions. However, the occurrence of oral condyloma acuminatum (OCA) is relatively infrequent, although its incidence has been gradually rising in recent years. OCA presents unique challenges in terms of treatment efficacy and recurrence prevention due to its concealed location and distinctive anatomical characteristics. In this manuscript, we present a case study involving the use of laser combined with photodynamic therapy (PDT) for managing hard palate OCA. The occurrence of warts in the hard jaw near the soft palate posed challenges during PDT due to involuntary swallowing and nausea. By modifying the conventional PDT approach and replacing the dressing with a cotton swab, the patient experience is more comfortable and therapeutic outcomes is more effective. Remarkably, the procedure resulted in minimal scarring post-operation. The combined approach of laser and PDT demonstrates promising results as a rapid and well-tolerated treatment modality for OCA.

The distinct plastisphere microbiome in the terrestrial-marine ecotone is a reservoir for putative degraders of petroleum-based polymers.

Research into plastic-degrading bacteria and fungi is important for understanding how microorganisms can be used to address the problem of plastic pollution and for developing new approaches to sustainable waste management and bioplastic production. In the present study, we isolated 55 bacterial and 184 fungal strains degrading polycaprolactone (PCL) in plastic waste samples from Dafeng coastal salt marshes, Jiangsu, China. Of these, Jonesia and Streptomyces bacteria also showed potential to degrade other types of petroleum-based polymers. The metabarcoding results proved the existence of plastisphere as a distinct ecological niche regardless of the plastic types where 27 bacterial and 29 fungal amplicon sequence variants (ASVs) were found to be significantly (p < 0.05) enriched, including some belonging to Alternaria (Ascomycota, Fungi) and Pseudomonas (Gammaproteobacteria, Bacteria) that were also mined out by the method of cultivation. Further assembly analyses demonstrated the importance of deterministic processes especially the environmental filtering effect of carbon content and pH on bacteria as well as the carbon and cation content on fungi in shaping the plastisphere communities in this ecosystem. Thus, the unique microbiome of the plastisphere in the terrestrial-marine ecotone is enriched with microorganisms that are potentially capable of utilizing petroleum-based polymers, making it a valuable resource for screening plastic biodegraders.

HE@PCL/PCE Gel-Nanofiber Dressing with Robust Self-Adhesion toward High Wound-Healing Rate via Microfluidic Electrospinning Technology.

Hydrogels have attracted increasing attention in the biomedical field due to their similarity in structure and composition to natural extracellular matrices. However, they have been greatly limited by their low mechanical strength and self-adhesion for further application. Here, a gel-nanofiber material is designed for wound healing, which synergistically combines the benefits of hydrogels and nanofibers and can overcome the bottleneck of poor mechanical strength and self-adhesion in hydrogels and inadequate healing environment created by nanofibers. First, a nanofiber scaffold composed of polycaprolactone/poly(citric acid)-ε-lysine (PCL/PCE) nanofibers is fabricated via a new strategy of microfluidic electrospinning, which could provide a base for hyaluronic acid-polylysine (HE) gel growth on nanofibers. The prepared HE@PCL/PCE gel-nanofiber possesses high tensile strength (24.15 ± 1.67 MPa), excellent air permeability (656 m3/m2 h kPa), outstanding self-adhesion property, and positive hydrophilicity. More importantly, the prepared gel-nanofiber dressing shows good cytocompatibility and antibacterial properties, achieving a high wound-healing rate (92.48%) and 4.685 mm granulation growth thickness within 12 days. This material may open a promising avenue for accelerating wound healing and tissue regeneration, providing potential applications in clinical medicine.

Tracheobronchial intubation using flexible bronchoscopy in children with Pierre Robin sequence: Nursing considerations for complications.

BACKGROUND: It has been shown that children with Pierre Robin sequence (PRS) have a higher risk of difficult intubation before surgery. When mask ventilation or tracheobronchial intubation is expected to be challenging, flexible bronchoscopy (FB) is advantageous in airway safety when it is used to guide tracheobronchial intubation (TI). AIM: To evaluate the complications of TI using FB in children with PRS and explore the effect of nursing services on postoperative complications. METHODS: One hundred and five children with PRS underwent TI using FB before early mandibular distraction osteogenesis. One hundred and eight children with common pneumonia who did not have a difficult airway were set as the control group. Demographic data, success rates of TI, time required for TI, number of TI attempts, and the incidence of postoperative complications were assessed. Besides, the strategies used to attenuate complications were investigated. RESULTS: The success rate of TI was 100% in children with PRS, while the success rate at the first attempt in the PRS group was significantly lower than that in the control group (88.6% vs 98.2%, P = 0.005). The time required for TI in the PRS group was markedly longer than that in the control group (P < 0.001). Children in the PRS group required repetitive operations to enter the glottis successfully (P = 0.017). The incidence of complications was noticeably higher in the PRS group (50/105, 47.6%) than in the control group (36/108, 33.3%) (P = 0.034). Seven of 105 PRS children experienced laryngeal edema (LE) (6.7%), compared with one (0.9%) in the control group (P = 0.034). Out of the seven patients who had LE, all were reintubated and managed with steroids: six recovered with inhaled steroids alone before extubated, and one was given systemic corticosteroids before recovery. CONCLUSION: FB contributes to a high success rate of TI in children with PRS. To prevent LE, operators should pay more attention to catheter material, catheter lubrication and intubation time.

Genetic Transformation of Trichoderma spp.

The production of biofuels from plant biomass is dependent on the availability of enzymes that can hydrolyze the plant cell wall polysaccharides to their monosaccharides. These enzyme mixtures are formed by microorganisms but their native compositions and properties are often not ideal for application. Genetic engineering of these microorganisms is therefore necessary, in which introduction of DNA is an essential precondition. The filamentous fungus Trichoderma reesei-the main producer of plant-cell-wall-degrading enzymes for biofuels and other industries-has been subjected to intensive genetic engineering toward this goal and has become one of the iconic examples of the successful genetic improvement of fungi. However, the genetic manipulation of other enzyme-producing Trichoderma species is frequently less efficient and, therefore, rarely managed. In this chapter, we therefore describe the two potent methods of Trichoderma transformation mediated by either (a) polyethylene glycol (PEG) or (b) Agrobacterium. The methods are optimized for T. reesei but can also be applied for such transformation-resilient species as T. harzianum and T. guizhouense, which are putative upcoming alternatives for T. reesei in this field. The protocols are simple, do not require extensive training or special equipment, and can be further adjusted for T. reesei mutants with particular properties.

ZnO nanoparticles stabilized oregano essential oil Pickering emulsion for functional cellulose nanofibrils packaging films with antimicrobial and antioxidant activity.

The growth and reproduction of microorganisms can cause food spoilage in the process of food transportation and storage. Active packaging is a good way to inhibit food spoilage and prolong the shelf lives of foods. In this study, O/W Pickering emulsion with ZnO nanoparticles as solid particles and oregano essential oil as the oil phase was prepared and used to functionalize cellulose nanofibrils (CNFs) film, and excellent antimicrobial and antioxidant activity was obtained. When the concentration of ZnO nanoparticles was 1.5 wt% and the mass fraction of the oil phase was 20%, the Pickering emulsion with a particle size of 26.85 µm exhibited strong standing stability. The Pickering emulsion was blended with the film-forming matrix CNFs to prepare active packaging films by casting. The Pickering emulsion evenly dispersed in the film to form microcapsules which encapsulated oregano essential oil entirely. The antimicrobial activity against Listeria monocytogenes was 89.61%, the DPPH radical scavenging rate was 58.52%, while the barrier properties of the developed films against oxygen, water vapor and visible light were improved. The active CNFs film prepared by Pickering emulsion could inhibit the growth of microorganism and prolong the shelf lives of foods.

From lignocellulose to plastics: Knowledge transfer on the degradation approaches by fungi.

In this review, we argue that there is much to be learned by transferring knowledge from research on lignocellulose degradation to that on plastic. Plastic waste accumulates in the environment to hazardous levels, because it is inherently recalcitrant to biological degradation. Plants evolved lignocellulose to be resistant to degradation, but with time, fungi became capable of utilising it for their nutrition. Examples of how fungal strategies to degrade lignocellulose could be insightful for plastic degradation include how fungi overcome the hydrophobicity of lignin (e.g. production of hydrophobins) and crystallinity of cellulose (e.g. oxidative approaches). In parallel, knowledge of the methods for understanding lignocellulose degradation could be insightful such as advanced microscopy, genomic and post-genomic approaches (e.g. gene expression analysis). The known limitations of biological lignocellulose degradation, such as the necessity for physiochemical pretreatments for biofuel production, can be predictive of potential restrictions of biological plastic degradation. Taking lessons from lignocellulose degradation for plastic degradation is also important for biosafety as engineered plastic-degrading fungi could also have increased plant biomass degrading capabilities. Even though plastics are significantly different from lignocellulose because they lack hydrolysable C-C or C-O bonds and therefore have higher recalcitrance, there are apparent similarities, e.g. both types of compounds are mixtures of hydrophobic polymers with amorphous and crystalline regions, and both require hydrolases and oxidoreductases for their degradation. Thus, many lessons could be learned from fungal lignocellulose degradation.

Effect of ultraviolet disinfection on the fouling of reverse osmosis membranes for municipal wastewater reclamation.

Membrane fouling is a prominent problem that hinders the stable and efficient operation of the reverse osmosis (RO) system for wastewater reclamation. Previous studies showed that chlorine disinfection, which was commonly used in industrial RO systems as pretreatment, could lead to significant change in microbial community structure and resulted in serious biofouling. In order to prevent biofouling during wastewater reclamation, the effect of ultraviolet (UV) disinfection on RO membrane fouling was investigated and the mechanism was also revealed in this study. With the disinfection pretreatment by UV of 20, 40 and 80 mJ/cm2, the bacteria in the feed water were inactivated significantly with a log reduction of 1.11, 2.55 and 3.61-log, respectively. However, RO membrane fouling aggravated with higher UV dosage. Especially, in the group with the UV dosage of 80 mJ/cm2, the normalized RO membrane flux decreased by 15% compared with the control group after 19-day operation. The morphology of the fouled RO membranes indicated serious biofouling in all groups. The analysis on the microbial amount of the foulants showed that the heterotrophic plate counts (HPC) and ATP content on the fouled RO membranes with and without UV disinfection were at the same level. However, the total organic carbon content of the foulants with the UV dosage of 40 and 80 mJ/cm2 was significantly higher than the control group, with higher content of proteins and polysaccharides as indicated by EEM and FTIR spectrum. Microbial community structure analysis showed that some typical UV-resistant bacteria were selected and remained on the RO membrane after disinfection with high UV dosage, including. These residual bacteria after disinfection with high UV dosage showed higher extracellular polymeric substances (EPS) secretion compared with those without UV disinfection, and thus aggravated RO membrane fouling. Thicker EPS could decrease the transmission of UV rays, and thus bacteria with higher EPS secretion might be selected after UV disinfection.

Superhydrophobic thermoplastic polyurethane films with transparent/fluorescent performance.

In this paper, we report a simple and versatile route for the fabrication of superhydrophobic thermoplastic polyurethane (TPU) films. The approach is based on octadecanamide (ODAA)-directed assembly of nanosilica/TPU/ODAA hybrid with a well-defined sheetlike microstructure. The superhydrophobic hybrid film shows a transparent property, and its water contact angle reaches as high as 163.5° without any further low surface energy treatment. In addition, the superhydrophobic TPU hybrid film with fluorescent properties is achieved by smartly introducing CdTe quantum dots, which will extend potential application of the film to optoelectronic areas. The resulting fluorescent surface produced in this system is stable and has a water contact angle of 172.3°. This assembly method to control surface structures represents an intriguing and valuable route to tune the surface properties of organic-inorganic hybrid films.

Microenvironment-responsive immunoregulatory electrospun fibers for promoting nerve function recovery.

The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.

Large-Scale Fabrication of Robust Artificial Skins from a Biodegradable Sealant-Loaded Nanofiber Scaffold to Skin Tissue via Microfluidic Blow-Spinning.

Given that many people suffer from large-area skin damage, skin regeneration is a matter of high concern. Here, an available method is developed for the formation of large-area robust skins through three stages: fabrication of a biodegradable sealant-loaded nanofiber scaffold (SNS), skin tissue reconstruction, and skin regeneration. First, a microfluidic blow-spinning strategy is proposed to fabricate a large-scale nanofiber scaffold with an area of 140 cm × 40 cm, composed of fibrinogen-loaded polycaprolactone/silk fibroin (PCL/SF) ultrafine core-shell nanofibers with mean diameter of 65 nm. Then, the SNS forms, where the gelling reaction of fibrin sealant occurs in situ between thrombin and fibrinogen on PCL/SF nanofiber surface, to promote the migration and proliferation of fibroblasts, accelerating skin regeneration. Through an in vivo study, it is shown that the SNS can rapidly repair acute tissue damage such as vascular bleeding and hepatic hemorrhage, and also promote angiogenesis, large-area abdominal wall defect repair, and wound tissue regeneration for medical problems in the world. Besides, it avoids the risk of immune rejection and secondary surgery in clinical applications. This strategy offers a facile route to regenerate large-scale robust skin, which shows great potential in abdominal wall defect repair.

Recent developments in regenerative ophthalmology.

Regenerative medicine (RM) is one of the most promising disciplines for advancements in modern medicine, and regenerative ophthalmology (RO) is one of the most active fields of regenerative medicine. This review aims to provide an overview of regenerative ophthalmology, including the range of tools and materials being used, and to describe its application in ophthalmologic subspecialties, with the exception of surgical implantation of artificial tissues or organs (e.g., contact lens, artificial cornea, intraocular lens, artificial retina, and bionic eyes) due to space limitations. In addition, current challenges and limitations of regenerative ophthalmology are discussed and future directions are highlighted.

The in vitro study of Her-2 targeted gold nanoshell liquid fluorocarbon poly lactic-co-glycolic acid ultrasound microcapsule for ultrasound imaging and breast tumor photothermal therapy.

Antibody-mediated targeting therapy has been successful in treating patients with breast cancer by improving the specificity and clinical efficacy. In this study, we constructed the human epidermal growth factor receptor-2 (Her2) antibody-conjugated ultrasound contrast agent with lactic-co-glycolic acid (PLGA) as film forming and perfluorocty bromide (PFOB) as internal material, which was coated by gold nanoshell (Her2-PFOB@PLGA@Au), to realize the integration of diagnosis and treatment. The contrast agent was spherical, with the diameter was 256.8 ± 53.4 nm, and had a good dispersion; Ultrasound imaging experiments in vitro showed that the gold nanoshell polylactic acid microcapsule was suitable for ultrasound contrast imaging with the exquisite and uniform dot intensive high echo. The agent had a great photothermal effect under the near-infrared (NIR) with no obvious biological toxicity for both Her2-positive and negative tumor cells; Moreover, both the results of laser scanning confocal microscope (LSCM) and flow cytometer (FCM) demonstrated the great specificity of Her2-PFOB@PLGA@Au conjugating with Her2 positive breast cancer cells (SKBR3). In conclusion, the successful synthesis of the Her2-PFOB@PLGA@Au microcapsule, offered a new therapeutic strategy of combining diagnosis with therapy for fighting against the breast cancer.

Treatment of gastric varices by endoscopic sclerotherapy using butyl cyanoacrylate: 10 years' experience of 635 cases.

BACKGROUND: Gastric varices (GV) are life-threatening for patients with portal hypertension. Endoscopic injection with butyl cyanoacrylate (BC), the mainstay of the therapy for GV, has been reported to be effective for hemostasis of bleeding varices, but its efficacy in the obliteration of GV and impact on the survival of patients still needs clarification. Here we summarized our experience of 10 years' practice to evaluate the efficacy and safety of endoscopic therapy using BC for GV patients. METHODS: From January 1997 to April 2006, GV cases treated with endoscopic injection using BC were collected. The "sandwich method" and the "modified sandwich method" were used to inject BC intravascularly. Retrograde analysis was made on the data of treatment and follow-up. RESULTS: A total of 635 GV cases treated with endoscopic injection using BC were collected, most of them (90.2%) suffered from post-hepatitis cirrhosis. Emergency hemostasis was achieved in 139 out of 146 sessions (95.2%). Complications occurred in 32 cases (5.2%), including hemorrhage due to early expulsion of tissue glue (3.1%), septicemia (1%) and ectopic thrombosis (0.5%), such as spleen infarction. Endoscopic follow-up in 503 patients showed complete disappearance (76.9%), collapse (17.3%) or remnants (5.8%) of gastric varices. A total of 550 patients were followed up clinically for 3 to 115 months. Of these patients, 44 had recurrent bleeding (8.0%) and 44 died from hepatic failure, recurrent bleeding, hepatic carcinoma or other causes. The longest survival was 115 months, with a median survival of 25 months. Survival rates at 1, 2, 3, 4 and 5 year were 95%, 92%, 90%, 83% and 81%, respectively. CONCLUSIONS: Endoscopic sclerotherapy with BC is effective for the hemostasis of bleeding GV, as well as obliteration of GV which contributes to less rebleeding and better survival. The modified sandwich method may be useful to minimize ectopic embolism, which we speculated to result from excess iodized oil.

Ultrasensitive, passive and wearable sensors for monitoring human muscle motion and physiological signals.

Flexible sensors have attracted more and more attention as a fundamental part of anthropomorphic robot research, medical diagnosis and physical health monitoring. Here, we constructed an ultrasensitive and passive flexible sensor with the advantages of low cost, lightness and wearability, electric safety and reliability. The fundamental mechanism of the sensor is based on triboelectric effect inducing electrostatic charges on the surfaces between two different materials. Just like a plate capacitor, current will be generated while the distance or size of the parallel capacitors changes caused by the small mechanical disturbance upon it and therefore the output current/voltage will be produced. Typically, the passive sensor unambiguously monitors muscle motions including hand motion from stretch-clench-stretch, mouth motion from open-bite-open, blink and respiration. Moreover, this sensor records the details of the consecutive phases in a cardiac cycle of the apex cardiogram, and identify the peaks including percussion wave, tidal wave and diastolic wave of the radial pulse wave. To record subtle human physiological signals including radial pulsilogram and apex cardiogram with excellent signal/noise ratio, stability and reproducibility, the sensor shows great potential in the applications of medical diagnosis and daily health monitoring.

Antiproliferative, antiinvasive, and proapoptotic activity of folate receptor α-targeted liposomal doxorubicin in nonfunctional pituitary adenoma cells.

There is an urgent need for novel therapeutic strategies for the treatment of nonfunctional pituitary adenomas (NFPAs), especially those that are invasive. The folate receptor (FR)α is overexpressed in several cancers, including NFPA. The aim of this study was to determine the efficacy of FRα-targeted liposomes loaded with doxorubicin (F-L-DOX) in the treatment of NFPA. We evaluated targeting, cytotoxicity, antiinvasive, and proapoptotic activity of F-L-DOX in 25 primary cell lines derived from patients with NFPAs. We found that these liposomes effectively targeted NFPA cells through FRα and that endocytosis of the liposomes was blocked by 1mM free folic acid. F-L-DOX inhibited proliferation of NFPA cells and promoted apoptosis through activation of caspase-8, caspase-9, and caspase-3/7 more effectively than L-DOX. Furthermore, F-L-DOX also exerted greater antiinvasive ability in NFPA cells than L-DOX through suppression of the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9. Addition of 1mM free folic acid significantly reduced the pleotropic effects of F-L-DOX in NFPA cells, suggesting that FRα plays a critical role in mediating the antitumor effect of F-L-DOX. Our findings warrant further investigation of F-L-DOX as an alternative therapeutic strategy for the treatment of NFPAs that express FRα.

Facile access to versatile fluorescent carbon dots toward light-emitting diodes.

We report the facile synthesis of carbon dots with tunable fluorescence from unzipping of photonic crystals and their application in LEDs, which may provide an insight into the creation of multifunctional carbon dots adapted for various applications such as in optoelectronics, sensing, or bioimaging.