Toxic effects of fragmented polyethylene terephthalate particles on the marine rotifer Brachionus koreanus: Based on ingestion and egestion assay, in vivo toxicity test, and multi-omics analysis.

Microplastics (MPs) are a major concern in marine ecosystem because MPs are persistent and ubiquitous in oceans and are easily consumed by marine biota. Although many studies have reported the toxicity of MPs to marine biota, the toxicity of environmentally relevant types of MPs is little understood. We investigated the toxic effects of fragmented polyethylene terephthalate (PET) MP, one of the most abundant MPs in the ocean, on the marine rotifer Brachionus koreanus at the individual and molecular level. No significant rotifer mortality was observed after exposure to PET MPs for 24 and 48 h. The ingestion and egestion assays showed that rotifers readily ingested PET MPs in the absence of food but not when food was supplied; thus, there were also no chronic effects of PET MPs. In contrast, intracellular reactive oxygen species levels and glutathione S-transferase activity in rotifers were significantly increased by PET MPs. Transcriptomic and metabolomic analyses revealed that genes and metabolites related to energy metabolism and immune processes were significantly affected by PET MPs in a concentration-dependent manner. Although acute toxicity of PET MPs was not observed, PET MPs are potentially toxic to the antioxidant system, immune system, and energy metabolism in rotifers.

Comprehensive feasibility evaluation of small-diameter 3D templated vascular graft via physical characterizations andin-vivoexperiments.

3D printing (3DP) technology for tissue engineering applications has been extensively studied for materials and processes. However, clinical application to the vascular system was limited owing to mechanical inconsistency and toxicity. Here, we characterized 3D templated artificial vascular grafts (3D grafts), which were fabricated by an integrative method involving 3DP, dip coating, and salt leaching method. The as-fabricated grafts were featured with micrometer-scale porosity enabling tissue-mimetic mechanical softness comparable with native blood vessels. In terms of mechanical properties and water permeability, the fabricated 3D grafts exhibited comparable or superior performances compared to the commercialized grafts. Furthermore, thein-vivostability of the 3D graft was validated through a toxicity test, and the small-diameter 3D graft was transplanted into a rat to confirm the implant's performance. Overall, the experimental results demonstrated the clinical feasibility of the 3D graft with retaining the mechanical biocompatibility and also revealed the possibility of patient-specific customization.

In-situ ionic crosslinking of 3D bioprinted cell-hydrogel constructs for mechanical reinforcement and improved cell growth.

Hydrogels are commonly used in 3D bioprinting technology owing to their ability to encapsulate living cells. However, their inherent delicate properties limit their applicability in the fabrication of mechanically reliable tissue engineering constructs. Herein, we propose a novel reinvented layering integration method for the functional enhancement of 3D cell-hydrogel bioprinting. This was implemented by inserting electrospun microfiber sheets with a crosslinker between the 3D bioprinted layers. When surface-modified microfiber sheets were combined with Ca2+ ionic crosslinkers, the as-printed cell-hydrogel strand was immediately crosslinked when it contacted the sheet surface. The in-situ crosslinking in the bioprinting process not only improved the overall structural stability, but also reinforced the compressive strength and elastic modulus. The enhanced structural stability guaranteed the shape fidelity of the 3D architecture, which included the internal channel network, resulting in improved perfusion conditions for cell growth. The growth of NIH3T3 fibroblasts in 3D bioconstructs with in-situ crosslinking increased by up to five times compared to that of normally bioprinted constructs. The strengthened structural integrity was distinctly sustainable during the cell culture period owing to the sustained release of Ca2+ ions from the embedded microfiber sheets. The synergistic effect of the reinforced mechanical properties with enhanced cell growth is expected to extend the applicability of the proposed hydrogel-based bioprinting technique for soft tissue engineering.

Soft Biomimetic 3D Free-Form Artificial Vascular Graft Using a Highly Uniform Microspherical Porous Structure.

This study presents a biomimetic 3D customizable artificial vascular graft with a highly porous and uniform microscale structure. The structural features were obtained by dip coating of a highly close-packed microsphere suspension on a 3D printed sacrificial template. Considering the structured arrangement of microspherical porogens in the coating layer, the microsphere-leached constructs showed higher uniformity and porosity than the conventionally particulate-leached structures, leading to ultrasoft mechanical compliance. Considering biomechanical compatibility, the resulting elastic moduli were at the sub-MPa level, comparable with those of native vascular tissues. In addition, the developed porous graft was reinforced selectively at the edge regions using a nonporous coating to secure its practical sutureability for clinical use. The sufficiently low cytotoxicity was clinically confirmed to alleviate the stiffness mismatch issues at the anastomotic interface between the native tissue and the artificial graft, thus overcoming the relevant clinical complications. Furthermore, the overall superior properties could be implemented on the 3D printed template for patient-specific medicare, thus implying the manufacturability of patient-specific vascular grafts.

Smoothened (SMO) regulates insulin-like growth factor 1 receptor (IGF1R) levels and protein kinase B (AKT) localization and signaling.

The oncoprotein Smoothened (SMO), a Frizzled-class-G-protein-coupled receptor, is the central transducer of hedgehog (Hh) signaling. While canonical SMO signaling is best understood in the context of cilia, evidence suggests that SMO has other functions in cancer biology that are unrelated to canonical Hh signaling. Herein, we provided evidence that elevated levels of human SMO show a strong correlation with elevated levels of insulin-like growth factor 1 receptor (IGF1R) and reduced survival in diffuse large B-cell lymphoma (DLBCL). As an integral component of raft microdomains, SMO plays a fundamental role in maintaining the levels of IGF1R in lymphoma and breast cancer cells as well IGF1R-associated activation of protein kinase B (AKT). Silencing of SMO increases lysosomal degradation and favors a localization of IGF1R to late endosomal compartments instead of early endosomal compartments from which much of the receptor would normally recycle. In addition, loss of SMO interferes with the lipid raft localization and retention of the remaining IGF1R and AKT, thereby disrupting the primary signaling context for IGF1R/AKT. This activity of SMO is independent of its canonical signaling and represents a novel and clinically relevant contribution to signaling by the highly oncogenic IGF1R/AKT signaling axis.

Evaluation of 3D Templated Synthetic Vascular Graft Compared with Standard Graft in a Rat Model: Potential Use as an Artificial Vascular Graft in Cardiovascular Disease.

Although the number of vascular surgeries using vascular grafts is increasing, they are limited by vascular graft-related complications and size discrepancy. Current efforts to develop the ideal synthetic vascular graft for clinical application using tissue engineering or 3D printing are far from satisfactory. Therefore, we aimed to re-design the vascular graft with modified materials and 3D printing techniques and also demonstrated the improved applications of our new vascular graft clinically. We designed the 3D printed polyvinyl alcohol (PVA) templates according to the vessel size and shape, and these were dip-coated with salt-suspended thermoplastic polyurethane (TPU). Next, the core template was removed to obtain a customized porous TPU graft. The mechanical testing and cytotoxicity studies of the new synthetic 3D templated vascular grafts (3DT) were more appropriate compared with commercially available polytetrafluoroethylene (PTFE) grafts (ePTFE; standard graft, SG) for clinical use. Finally, we performed implantation of the 3DTs and SGs into the rat abdominal aorta as a patch technique. Four groups of the animal model (SG_7 days, SG_30 days, 3DT_7 days, and 3DT_30 days) were enrolled in this study. The abdominal aorta was surgically opened and sutured with SG or 3DT with 8/0 Prolene. The degree of endothelial cell activation, neovascularization, thrombus formation, calcification, inflammatory infiltrates, and fibrosis were analyzed histopathologically. There was significantly decreased thrombogenesis in the group treated with the 3DT for 30 days compared with the group treated with the SG for 7 and 30 days, and the 3DT for 7 days. In addition, the group treated with the 3DT for 30 days may also have shown increased postoperative endothelialization in the early stages. In conclusion, this study suggests the possibility of using the 3DT as an SG substitute in vascular surgery.

Overlap between EBV-positive diffuse large B-cell lymphoma, NOS, in a young patient and angioimmunoblastic T-cell lymphoma: A diagnostic pitfall.

There may be significant histopathologic overlap between EBV-positive DLBCL, NOS, and other diagnoses including angioimmunoblastic T-cell lymphoma (AITL). Resolution of this differential diagnosis may be particularly challenging and require extensive investigation of clinicopathologic features.

Rapid development of dual porous poly(lactic acid) foam using fused deposition modeling (FDM) 3D printing for medical scaffold application.

The poor melt property and brittleness of poly(lactic acid) (PLA) cause difficulties in extrusion foaming and decrease product performance in industrial and research fields. In this paper, the rheological properties of PLA resin were improved using an epoxy chain extension reaction, which led to the improvement of pore properties such as morphology and foamability. Reinforced PLA was extruded in a porous filament, and a scaffold was fabricated with design freedom, one-step processing, and dual porosity by extrusion foaming and 3D printing. In addition, in vitro cell culture tests were performed to verify the cell biology assessment and confirm the potential of the scaffold for application as medical scaffolds.

3D bioprinted complex constructs reinforced by hybrid multilayers of electrospun nanofiber sheets.

Despite the usefulness of hydrogels for cell-based bioprinting, the fragility of their resulting constructs has hindered their practical applications in tissue engineering research. Here, we suggest a hybrid integration method based on cell-hydrogel bioprinting that includes alternate layering of flexible nanofiber (NF) sheets. Because the bioprinting was implemented on a nanofibrous surface, the hydrogel-based materials could be printed with enhanced shape resolution compared to printing on a bare hydrogel. Furthermore, the insertion of NF sheets was effective for alleviating the shrinkage distortion of the hydrogel construct, which is inherently generated during the crosslinking process, thereby enhancing shape fidelity throughout the three-dimensional (3D) architecture. In addition to the structural precision, the NF-embedded constructs improved the mechanical properties in terms of compressive strength, modulus, and resilience limit (up to four-fold enhancement). With structural and mechanical supports, we could 3D fabricate complex constructs, including fully opened internal channels, which provided a favorable perfusion condition for cell growth. We confirmed the enhanced bioactivity of the NF-embedded bioprinted construct via cell culture experiments with 80% enhanced proliferation compared to the monolithic one. The synergistic combination of the two flexible materials, NFs and hydrogels, is expected to have extensive applicability in soft tissue engineering.

PolySTAT-modified chitosan gauzes for improved hemostasis in external hemorrhage.

Positively-charged chitosan gauzes stop bleeding from wounds by electrostatically interacting with negatively-charged cell membranes of erythrocytes to cause erythrocyte agglutination and by sealing wounds through tissue adhesion. In the following work, nonwoven chitosan gauze was impregnated with PolySTAT, a synthetic polymer that enhances coagulation by cross-linking fibrin, to generate PolySTAT/chitosan gauzes with improved hemostatic efficacy. When comparing nonwoven chitosan and PolySTAT/chitosan to a commercially-available chitosan-containing gauze (Celox® Rapid), no appreciable differences were observed in fiber size, morphology, and pore size. However, PolySTAT/chitosan demonstrated more rapid blood absorption compared to Celox® Rapid. In a rat model of femoral artery injury, PolySTAT/chitosan gauzes reduced blood loss and improved survival rate compared to non-hemostatic controls and Celox® Rapid. While Celox® Rapid had stronger adherence to tissues compared to PolySTAT/chitosan gauzes, blood loss was greater due to hematoma formation under the Celox® dressing. Animals treated with PolySTAT/chitosan gauzes required less saline infusion to restore and maintain blood pressure above the target blood pressure (60mmHg) while other treatment groups required more saline due to continued bleeding from the wound. These results suggest that PolySTAT/chitosan gauzes are able to improve blood clotting and withstand increasing arterial pressure with the addition of a fibrin cross-linking hemostatic mechanism. STATEMENT OF SIGNIFICANCE: Blood loss remains one of the leading causes of death after traumatic injury in civilian populations and on the battlefield. Advanced biomaterials that interact with blood components and/or accelerate the clotting process to form a hemostatic plug are necessary to staunch bleeding after injury. Chitosan-based gauzes, which stop bleeding by causing red blood cell aggregation, are currently used on the battlefield and have shown variable performance under high pressure arterial blood flow in animal studies, suggesting that red blood cell aggregates require further mechanical stabilization for more reliable performance. In this work, we investigate the binding and cross-linking of fibrin, a major component in blood clots, on chitosan gauze fiber surfaces to structurally reinforce red blood cell aggregates.

Toxic Effect of Cadmium Assay in Contaminated Soil Earthworm Cell Using Modified Sensor.

A voltammetric toxic metal of cadmium detection was studied using a fluorine doped graphite pencil electrode (FPE) in a seawater electrolyte. In this study, square wave (SW) stripping and chronoamerometry were used for determination of Cd(II) in seawater. Affordable pencils and an auxiliary electrode were used as reference. All experiments in this study could be performed at reasonable cost by using graphite pencil. The application was performed on the tissue of contaminated soil earthworm. The results show that the method can be applicable for vegetables and in vivo fluid or medicinal diagnosis.

Combination treatment using bipolar radiofrequency-based intense pulsed light, infrared light and diode laser enhanced clinical effectiveness and histological dermal remodeling in Asian photoaged skin.

BACKGROUND: Combined optical and bipolar radiofrequency (RF) devices have been effective for rejuvenation, but a single modality in one session cannot solve three-dimensional skin complaints, resulting in time-consuming visits. OBJECTIVE: To evaluate the safety and efficacy of single-session triple treatment using bipolar RF-based optical (intense pulsed light [IPL], infrared light, and diode laser) combination devices for treatment of photoaged Asian skin. MATERIALS AND METHODS: In a split-face trial, 11 women received four treatments at 3-week intervals consisting of the combination of sequential IPL, infrared light, and diode laser, all with RF, in one session. Outcome assessments included photography, global evaluation by blinded investigators, patient assessment, and objective biophysical measurements of color and elasticity. Punch biopsies were obtained from both sides of the face 1 month after the last treatment session. RESULTS: All patients showed statistically significant reduction in photoaging global score. Objective biophysical measurements showed significant improvements in melanin index and elasticity (R5, R7), as well as increases in the levels of procollagen type I and III and elastin. CONCLUSION: A combination of three different energy sources, with bipolar RF, in one session is effective without further downtime for solving multiple problems including tone, texture, and laxity observed in photoaged Asian skin.

Erdheim-chester disease.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis of unknown etiology, characterized by multi-organ involvement. ECD is usually diagnosed on the basis of characteristic radiologic and histopathological findings. Lesions may be skeletal and/or extraskeletal in location, and may include the skin, lung, heart, and central nervous system. We describe here a 68-year-old man with multiple yellowish plaques and a pinkish nodule on his face and scalp. He had been previously diagnosed with diabetes insipidus, and recently complained of coughing and dyspnea. Imaging studies showed multiple osteosclerotic lesions of the bones, a moderate amount of pericardial effusion, and multifocal infiltrative lesions in the perirenal space. Histopathological examination of the skin lesions revealed dermal infiltration of foamy histiocytes with multinuclear giant cells. Moreover, laparoscopic biopsy of the perirenal tissue revealed fibrosis with infiltrating foamy histiocytes being CD68-positive and S100-negative. Based on these findings, he was diagnosed with ECD with extraskeletal manifestations, and treated with interferon-alpha.

Dermatopathic lymphadenitis with generalized erythroderma in a patient with epstein-barr virus-associated hemophagocytic lymphohistiocytosis.

Here, we describe a patient with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) who simultaneously presented with generalized erythroderma and dermatopathic lymphadenitis (DL). A 63-year-old Korean woman presented at our hospital with fever, hepatosplenomegaly, axillary lymphadenopathy, and generalized erythrodermic eruption. The bone marrow biopsy findings were consistent with the diagnosis of HLH, and EBV DNA was detected using the polymerase chain reaction. Based on serologic tests that indicated a primary EBV infection, the patient was diagnosed with EBV-associated HLH. Histopathologic analysis of enlarged lymph nodes was consistent with DL, and EBV-encoded small nuclear RNA-positive mononuclear cells were detected. We assume that activated histiocytes, lymphocytes, and proinflammatory cytokines in HLH may have important roles in the development of generalized erythroderma and DL. Disrupted epidermal/dermal junctions owing to erythroderma may also be involved in the development of DL.