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In this study, a flexible all-solid-state asymmetric supercapacitor (FASC) device has been successfully fabricated via full recycling of heated tobacco waste (HTW). Tobacco leaves and cellulose acetate tubes have been successfully carbonized (HTW-C) and mixed with metal oxides (MnO2 and Fe3O4) to obtain highly active materials for supercapacitors. Moreover, poly(lactic acid) (PLA) filters have been successfully dissolved in an organic solvent and mixed with the as-prepared active materials using a simple paste mixing method. In addition, flexible MnO2- and Fe3O4-mixed HTW-C/PLA electrodes (C-MnO2/PLA and C-Fe3O4/PLA) have been successfully fabricated using the drop-casting method. The as-synthesized flexible C-MnO2/PLA and C-Fe3O4/PLA electrodes have exhibited excellent electrical conductivity of 378 and 660 μS cm−1, and high specific capacitance of 34.8 and 47.9 mF cm−2 at 1 mA cm−2, respectively. A practical FASC device (C-MnO2/PLA//C-Fe3O4/PLA) has been assembled by employing the C-MnO2/PLA as the positive electrode and C-Fe3O4/PLA as the negative electrode. The as-prepared FASC device showed a remarkable capacitance of 5.80 mF cm−2 at 1 mA cm−2. Additionally, the FASC device manifests stable electrochemical performance under harsh bending conditions, verifying the superb flexibility and sustainability of the device. To the best of our knowledge, this is the first study to report complete recycling of heated tobacco waste to prepare the practical FASC devices. With excellent electrochemical performance, the experiments described in this study successfully demonstrate the possibility of recycling new types of biomass in the future.

Light detection and ranging (LiDAR) sensors utilize a near-infrared (NIR) laser with a wavelength of 905 nm. However, LiDAR sensors have weakness in detecting black or dark-tone materials with light-absorbing properties. In this study, SiO2/black TiO2 core/shell nanoparticles (SBT CSNs) were designed as LiDAR-detectable black materials. The SBT CSNs, with sizes of 140, 170, and 200 nm, were fabricated by a series of Stöber, TTIP sol-gel, and modified NaBH4 reduction methods. These SBT CSNs are detectable by a LiDAR sensor and, owing to their core/shell structure with intrapores on the shell (ca. 2–6 nm), they can effectively function as both color and NIR-reflective materials. Moreover, the LiDAR-detectable SBT CSNs exhibited high NIR reflectance (28.2 R%) in a monolayer system and true blackness (L* < 20), along with ecofriendliness and hydrophilicity, making them highly suitable for use in autonomous vehicles.

BACKGROUND: Respiratory mucosa defects result in airway obstruction and infection, requiring subsequent functional recovery of the respiratory epithelium. Because site-specific extracellular matrix (ECM) facilitates restoration of organ function by promoting cellular migration and engraftment, previous studies considered decellularized trachea an ideal ECM; however, incomplete cell removal from cartilage and mucosal-architecture destruction are frequently reported. Here, we developed a decellularization protocol and applied it to the respiratory mucosa of separated porcine tracheas. METHODS: The trachea was divided into groups according to decellularization protocol: native mucosa, freezing–thawing (FT), FT followed by the use of Perasafe-based chemical agents before mucosal separation (wFTP), after mucosal separation (mFTP), and followed by DNase decellularization (mFTD). Decellularization efficacy was evaluated by DNA quantification and hematoxylin and eosin staining, and ECM content of the scaffold was evaluated by histologic analysis and glycosaminoglycan and collagen assays. Biocompatibility was assessed by cell-viability assay and in vivo transplantation. RESULTS: The mFTP mucosa showed low antigenicity and maintained the ECM to form a proper microstructure. Additionally, tonsil-derived stem cells remained viable when cultured with or seeded onto mFTP mucosa, and the in vivo host response showed a constructive pattern following implantation of the mFTP scaffolds. CONCLUSION: These results demonstrated that xenogenic acellular respiratory mucosa matrix displayed suitable biocompatibility as a scaffold material for respiratory mucosa engineering.

Herein, unique three-dimensional (3D) hierarchically structured carbon nanofiber (CNF)/metal oxide/conducting polymer composite materials were successfully synthesized by combinations of various experimental methods. Firstly, base CNFs were synthesized by carbonization of electrospun PAN/PVP fibers to attain electric double-layer capacitor (EDLC) characteristics. To further enhance the capacitance, tin oxide (SnO2) and iron oxide (Fe2O3) were coated onto the CNFs via facile hydrothermal treatment. Finally, polypyrrole (PPy) was introduced as the outermost layer by a dispersion polymerization method under static condition to obtain 3D-structured CNF/SnO2/PPy and CNF/Fe2O3/PPy materials. With each synthesis step, the morphology and dimension of materials were transformed, which also added the benign characteristic for supercapacitor application. For the practical application, as-synthesized CNF/SnO2/PPy and CNF/Fe2O3/PPy were applied as active materials for supercapacitor electrodes, and superb specific capacitances of 508.1 and 426.8 F g−1 (at 1 A g−1) were obtained (three-electrode system). Furthermore, an asymmetric supercapacitor (ASC) device was assembled using CNF/SnO2/PPy as the positive electrode and CNF/Fe2O3/PPy as the negative electrode. The resulting CNF/SnO2/PPy//CNF/Fe2O3/PPy device exhibited excellent specific capacitance of 101.2 F g−1 (at 1 A g−1). Notably, the ASC device displayed a long-term cyclability (at 2000 cycles) with a retention rate of 81.1%, compared to a CNF/SnO2//CNF/Fe2O3 device of 70.3% without an outermost PPy layer. By introducing the outermost PPy layer, metal oxide detachment from CNFs were prevented to facilitate long-term cyclability of electrodes. Accordingly, this study provides an effective method for manufacturing a high-performance and stable supercapacitor by utilizing unique 3D hierarchical materials, comprised of CNF, metal oxide, and conducting polymer.

Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.

최근에는 특정 전공을 미리 정하지 않고 입학하여 진로를 탐색한 후 전공을 선택하는 무전공 입학 대학이나 자율전공학부를 둔 대학이 점차 늘고 있다. 본 연구는 전공을 선택하지 않고 대학 신입생 시기에 진로탐색을 하는 대학교의 학생들을 대상으로 진로태도성숙 향상을 위한 진로집단상담 프로그램을 개발하고, 그 효과성을 검증하였다. 이를 위해 사회인지이론을 통해 자기이해를 제공하면서도 보다 역동적인 집단활동을 이루기 위한 예술심리치료적 접근을 활용하는 집단 프로그램을 개발하였다. 연구대상으로는 개발된 프로그램에 참여한 실험집단과 비교집단 각각 12명을 선정하였고, 연구방법으로는 프로그램에 참여한 집단의 효과성을 검증하기 위해 유사 실험 설계를, 각 집단의 사전-사후검사를 비교하기 위해 비모수 통계검증 방법인 Wilcoxon Matched Pairs Signed Rank Test를 실시하였다. 또한, 합의적 질적 분석(Consensual Qualitative Research)을 사용함으로써 혼합 연구를 진행하였다. 연구 결과로는 진로집단상담 프로그램에 참여한 집단이 비교집단에 비해 진로태도성숙도가 유의하게 높아졌다. 프로그램 참여자의 진로발달 관련 경험에 대해 면담을 실시한 결과, 6개의 영역과 8개의 중심개념이 도출되었다. 본 프로그램은 전공과 진로를 탐색해야 하는 시기의 대학 신입생들의 진로태도성숙을 가져오기 위한 집단 프로그램을 제안하고, 이를 양적-질적 혼합방법으로 확인해봄으로 추후에 유사한 대학 신입생 집단에 접목해볼 방법을 제시함에 의의를 둘 수 있다.

Since the discovery of stem cells and multipotency characteristics of mesenchymal stem cells (MSCs), there has been tremendous development in regenerative medicine. MSCs derived from bone marrow have been widely used in various research applications, yet there are limitations such as invasiveness of obtaining samples, low yield and proliferation rate, and questions regarding their practicality in clinical applications. Some have suggested that MSCs from other sources, specifically those derived from palatine tonsil tissues, that is, tonsil‐derived MSCs (TMSCs), could be considered as a new potential therapeutic tool in regenerative medicine due to their superior proliferation rate and differentiation capabilities with low immunogenicity and ease of obtaining. Several studies have determined that TMSCs have differentiation potential not only into the mesodermal lineage but also into the endodermal as well as ectodermal lineages, expanding their potential usage and placing them as an appealing option to consider for future studies in regenerative medicine. In this review, the differentiation capacities of TMSCs and their therapeutic competencies from past studies are addressed. stem cells 2019;37:1252–1260, Schematic illustration of lineage differentiation of tonsil‐derived mesenchymal stem cells.

For the sustainable management of pavements, predicting the condition of the pavement structure using a consistent and accurate method is necessary. The intermediate layer situated immediately below the surface layer has the greatest effect on the condition of the pavement structure. As a result, to accurately predict the condition of a pavement structure, the mechanistic properties of the intermediate layer are very important. Fracture toughness (FT)—a mechanistic property of the intermediate layer—is an important factor in predicting the distress that develops on the pavement surface. However, measuring FT consistently is practically impossible by coring asphalt pavement over the entire pavement section. Therefore, an artificial neural network (ANN) model—developed by using pavement surface conditions and traffic volume—can predict the FT of the intermediate layer of expressway asphalt pavements. Several ANN models have been developed by applying various optimizers, ANN structures, and preprocessing methods. The optimal model was selected by analyzing the predictive performance, error stability, and distribution of the developed models. The final selected model showed small stable errors, and the distributions of the predicted and measured FTs were similar. Furthermore, FT limits were set with outliers. Future asphalt pavement conditions can be predicted throughout the expressway network by using the proposed model without coring samples.

Exon 20 genomic insertions of both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are oncogenic drivers and are most commonly found in non-small cell lung cancer (NSCLC). NSCLC patients with exon 20 insertions have a worse prognosis compared to those with other activating EGFR mutations. Moreover, approximately one-third of patients with exon 20 insertion mutations develop central nervous system (CNS) metastases over the course of their disease. Unfortunately, current therapeutics lack sufficient brain exposure for treating this patient population. ORIC-114 is a brain penetrant, orally bioavailable, irreversible small molecule inhibitor designed to target exon 20 insertions in EGFR and HER2. Notably, ORIC-114 is highly selective for the EGFR family of receptors, with excellent kinome selectivity compared to other reported exon 20 inhibitors, reducing the risk of off-target kinase liabilities. The superior brain penetration and free unbound exposure of ORIC-114 in preclinical studies also differentiates it from comparator EGFR and HER2 exon 20 targeted agents. To further characterize ORIC-114, in vivo studies were undertaken to assess activity in both subcutaneous and intracranial NSCLC tumor patient-derived xenograft (PDX) models. Consistent with in vitro potency and selectivity, once daily oral administration of 3 mg/kg ORIC-114 induced robust tumor regressions with greater than 100% tumor growth inhibition in the absence of significant body weight loss in an EGFR exon 20 insertion H773_V774insNPH NSCLC PDX model. In this subcutaneous model, ORIC-114 was superior to CLN-081 in efficacy and tolerability, and superior to BDTX-189 in efficacy. To investigate whether the brain-penetrant attributes of ORIC-114 translated into antitumor activity in the CNS, we utilized an intracranial PC-9 luciferase-labeled EGFR del 19 mutant cell line model. Once daily oral administration of ORIC-114 significantly regressed established intracranial NSCLC tumors and demonstrated greater efficacy than TAK-788, commensurate with the superior brain exposure of ORIC-114. We further explored dosing regimens in this intracranial model and found that ORIC-114 demonstrated equivalent regressions at 1.5 mg/kg twice daily and 3 mg/kg once daily, and strong efficacy with 1.5 mg/kg once daily dosing. Taken together, these data confirm ORIC-114 as a potent, selective, irreversible, brain penetrant exon 20 inhibitor, and a promising therapeutic candidate, including for patients with CNS metastases. Based upon these data, ORIC-114 is entering a Phase 1/1b clinical trial in genetically defined cancers. Citation Format: Jason E. Long, Soochan Kim, Ha Yeong Kim, Dong Guk Shin, Dong Hyun Park, Robert Warne, Akash Das, Ganapati Hegde, Padmini Narayanan, Lidia Sambucetti, Brenda Chan, Xi Chen, Jae H. Chang, Paul Gibbons, Jessica Sun, Matthew Panuwat, Lori S. Friedman, Melissa R. Junttila. ORIC-114, an orally bioavailable, irreversible kinase inhibitor, has superior brain penetration and antitumor activity in subcutaneous and intracranial NSCLC models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3335.

Objective Aesthetic reconstruction of the external ear is challenging due to the complex anatomical shape of the auricle. Recently, artificial scaffolds such as Medpor (Stryker, Kalamasoo, MI, USA) have become widely used in ear reconstruction. However, the Medpor scaffold is stiffer than the natural ear, which may lead to discomfort, and moreover has uniform design for every patient. In this study, we investigated whether three-dimensional (3D)-printed artificial polyurethane (PU) scaffolds are suitable for auricular reconstruction. Methods PU scaffolds were fabricated using 3D printing according to a design derived from a digital imaging and communications in medicine (DICOM) image of the human auricle. The microstructure of the scaffolds was observed using scanning electron microscopy, and the porosity was examined. Cell proliferation on the scaffolds was assessed in vitro using tonsil-derived mesenchymal stem cells to evaluate the biocompatibility of the scaffolds. The scaffolds were implanted in C57BL/6 mice, and histological analysis was performed. Results The structural study revealed that the 3D-printed porous PU scaffolds have rectangular microstructure with regular pitch and line, as well as high porosity (56.46% ± 10.22%) with a pore diameter of 200 µm. The mechanical properties of the 3D-printed PU scaffolds were similar to those of the human auricle cartilage. Cell proliferation on the PU scaffolds was greater than that on Medpor scaffolds. Histological evaluation demonstrated that the porous parts of the PU scaffolds became filled with collagen and vascular tissue. Conclusion Elastic, porous PU scaffolds can be obtained using 3D printing, have biomechanical properties similar to those of the natural ear, and are suitable for use in auricular reconstruction. Level of evidence NA Laryngoscope, 129:351-357, 2019.

Glucosinolates are well known functional food components that were discovered in Cruciferae and have been the object of study from diverse disciplinary perspectives, including metabolism, quantitative analysis, and breeding. However, the effects of the growth environment and post-harvest processes on glucosinolate production in Chinese cabbage are not well studied. Hence, this study aimed to identify the major factors that affect glucosinolate accumulation in Chinese cabbage during growth, and to optimize growth conditions in order to maximize glucosinolate content. Therefore, we measured glucosinolate content in cabbage grown in five environmental conditions that altered electrical conductivity, pH, cultivation time, temperature, and relative humidity. We used principal component analysis (PCA) to identify the variables primarily affecting growth, followed by response surface methodology (RSM) to determine optimal growth conditions that maximize glucosinolate content in Chinese cabbage. Results from PCA indicated that cultivation time, temperature, and relative humidity were the principal components that explained 85.8% of the total variance, suggesting these are the most significant environmental factors that affect glucosinolate accumulation. Moreover, RSM indicated that the total model for evaluating glucosinolate content was significant (R2 = 0.934) and showed that the optimal temperature and relative humidity for maximizing glucosinolate content are 28 °C, and 66%, respectively. This study provided practical information of optimal condition for producing functional Chinese cabbage intensifying glucosinolate.

Background and aims Osteoporosis, which is a disease characterized by weakening of the bone, affects a large portion of the senior population. The current therapeutic options for osteoporosis have side effects, and there is no effective treatment for severe osteoporosis. Thus, we urgently need new treatment strategies, such as topical therapies and/or safe and effective stem cell therapies. Methods We investigated the therapeutic potential of directly injecting human tonsil-derived mesenchymal stem cells (TMSC) into the right proximal tibias of ovariectomized postmenopausal osteoporosis model mice. Injections were given once (1×) or twice (2×) during the 3-month experimental period. At the end of the experiment, micro-computed tomographic images revealed some improvement in the proximal tibias and more significant improvement in the femoral heads of treated mice. Results Osteogenic effect was qualitatively and quantitatively more pronounced in TMSC/2×-treated mice. Furthermore, TMSC/2× mice exhibited significant recovery of the serum osteocalcin level, which is pathologically elevated in osteoporosis, and increased serum alkaline phosphatase, which indicates bone formation. TMSC therapy was generally well tolerated and caused no apparent toxicity in the experimental mice. Moreover, TMSC therapy reduced visceral fat. Conclusion Our results demonstrate that double injection of TMSC directly into the proximal tibia triggers recovery of osteoporosis, and thus could be a potential therapeutic approach for severe bone loss.

Cereblon (CRBN) has a pleiotropic role in important cellular processes and is a potential therapeutic target in several diseases, including mental retardation, cancer, and metabolic disorders. The role of CRBN in polymicrobial sepsis induced by cecal ligation and puncture (CLP) was investigated using CRBN-deficient (KO) mice. Survival following CLP was significantly higher in KO mice compared to wild-type (WT) controls (50% vs 0% at day 6 after CLP). The improved survival of KO mice was accompanied by reduced peripheral blood bacterial load and lung injury. Serum tumor necrosis factor (TNF)-α and high mobility group box 1 (HMGB1) concentrations were significantly lower in KO mice than in WT mice. Peritoneal macrophages from KO mice with CLP-induced septic mouse had higher levels of activation of AMPK and heme oxygenase-1 (HO-1). Forced expression of CRBN in macrophage of KO mice suppressed activation of 5′ adenosine monophosphate-activated protein kinase (AMPK) and HO-1 and augmented expression of TNF-α and HMGB1 as inhibition of AMPK by compound C. These studies demonstrate the contribution of CRBN expression to the pathogenesis of CLP-induced sepsis and peritoneal macrophage responses and suggest a novel therapeutic modality for polymicrobial sepsis.

Adolescent depression is a prevalent cause of illness and disability for teenagers. Getting treatment at the earliest sign helps prevent depression from worsening. Depression symptoms can be difficult to tell apart from ups and downs that are part of adolescence thus not being able to contact a professional at the earliest sign. Smartphone applications, are easily available to users of all ages. With an Android application we propose an easily accessible depression screening method for adolescents. Using a widely used depression scale and Naive Bayes classifier, we compare previous data to the current situation of the user to produce an estimation of the user’s situation.

BACKGROUND: Stem cell engineering is appealing consideration for regenerating damaged endothelial cells (ECs) because stem cells can differentiate into EC-like cells. In this study, we demonstrate that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into EC-like cells under optimal physiochemical microenvironments. METHODS: TMSCs were preconditioned with Dulbecco’s Modified Eagle Medium (DMEM) or EC growth medium (EGM) for 4 days and then replating them on Matrigel to observe the formation of a capillary-like network under light microscope. Microarray, quantitative real time polymerase chain reaction, Western blotting and immunofluorescence analyses were used to evaluate the expression of gene and protein of EC-related markers. RESULTS: Preconditioning TMSCs in EGM for 4 days and then replating them on Matrigel induced the formation of a capillary-like network in 3 h, but TMSCs preconditioned with DMEM did not form such a network. Genome analyses confirmed that EGM preconditioning significantly affected the expression of genes related to angiogenesis, blood vessel morphogenesis and development, and vascular development. Western blot analyses revealed that EGM preconditioning with gelatin coating induced the expression of endothelial nitric oxide synthase (eNOS), a mature EC-specific marker, as well as phosphorylated Akt at serine 473, a signaling molecule related to eNOS activation. Gelatin-coating during EGM preconditioning further enhanced the stability of the capillary-like network, and also resulted in the network more closely resembled to those observed in human umbilical vein endothelial cells. CONCLUSION: This study suggests that under specific conditions, i.e., EGM preconditioning with gelatin coating for 4 days followed by Matrigel, TMSCs could be a source of generating endothelial cells for treating vascular dysfunction.

To restore damaged parathyroid function, parathyroid tissue engineering is the best option. Previously, we reported that differentiated tonsil-derived mesenchymal stem cells (dTMSC) restore in vivo parathyroid function, but only if they are embedded in a scaffold. Because of the limited biocompatibility of Matrigel, however, here we developed a more clinically applicable, scaffold-free parathyroid regeneration system. Scaffold-free dTMSC spheroids were engineered in concave microwell plates made of polydimethylsiloxane in control culture medium for the first 7 days and differentiation medium (containing activin A and sonic hedgehog) for next 7 days. The size of dTMSC spheroids showed a gradual and significant decrease up to day 5, whereafter it decreased much less. Cells in dTMSC spheroids were highly viable (>80%). They expressed high levels of intact parathyroid hormone (iPTH), the parathyroid secretory protein 1, and cell adhesion molecule, N-cadherin. Furthermore, dTMSC spheroids-implanted parathyroidectomized (PTX) rats revealed higher survival rates (50%) over a 3-month period with physiological levels of both serum iPTH (57.7–128.2 pg/mL) and ionized calcium (0.70–1.15 mmol/L), compared with PTX rats treated with either vehicle or undifferentiated TMSC spheroids. This is the first report of a scaffold-free, human stem cell-based parathyroid tissue engineering and represents a more clinically feasible strategy for hypoparathyroidism treatment than those requiring scaffolds. Statement of Significance Herein, we have for the first time developed a scaffold-free parathyroid tissue spheroids using differentiated tonsil-derived mesenchymal stem cells (dTMSC) to restore in vivo parathyroid cell functions. This new strategy is effective, even for long periods (3 months), and is thus likely to be more feasible in clinic for hypoparathyroidism treatment. Development of TMSC spheroids may also provide a convenient and efficient scaffold-free platform for researchers investigating conditions involving abnormal calcium homeostasis, such as osteoporosis.

Objective In this study, we assessed the effectiveness of a tonsil-derived mesenchymal stem cell (TMSC)-transplanted polycaprolactone/beta-tricalcium phosphate prosthesis (specifically designed for easier fixing and grafting with a single scaffold) on rabbit mandible osteogenesis. Methods The mandibles of 18 rabbits were exposed, and 10 × 8-mm bone defects were made. Two rabbits did not receive implants; four were reconstructed with the scaffold control (SC) (SC group); four were reconstructed with scaffolds soaked in peripheral blood (PB) (PB group); four were reconstructed with TMSC-transplanted scaffolds (TMSC group); and four were reconstructed with differentiated osteocyte-transplanted scaffolds (DOC) (DOC group). Each rabbit was sacrificed 12 weeks after surgery, and the area of new bone formation was investigated by mechanical testing, histology, and micro-computed tomography. Results More extended and denser new bone masses were observed in the TMSC and DOC groups, although fibrosis and vascular formation levels were similar in all groups, suggesting that the dual-structured scaffold alone provides a good environment for bone attachment and regeneration. The bone volumes of representative scaffolds from the SC, PB, TMSC, and DOC groups were 43.12, 48.35, 53.10, and 57.44% of the total volumes, respectively. Conclusion The design of the scaffold resulted in effective osteogenesis, and TMSCs showed osteogenic potency, indicating that their combination could enable effective bone regeneration. Level of evidence NA Laryngoscope, 130:358-366, 2020.

Hypoparathyroidism is a deficiency of the parathyroid hormone (PTH) in the body. We previously reported the possibility of treating it using tonsil-derived mesenchymal stem cells (TMSCs) differentiated into PTH-releasing cells. The purpose of this study was to evaluate the feasibility of using autologous plasma gel as scaffold material in treatment of hypoparathyroidism with TMSC. We obtained plasma by venous sampling of autologous blood and centrifuged and fabricated the plasma gel using a sinusoidal pattern heating machine. After we created the hypoparathyroidism animal model, we administered undifferentiated TMSCs and TMSCs differentiated into parathyroid cells at each rat dorsum by intramuscular injection with and without the plasma gel. In the plasma gel groups, intact PTH was detected from on day 21 after TMSC injection; we did not detect intact PTH in the groups that were only transplanted with TMSCs during the entire experimental period. Serum calcium was higher and phosphorous was lower in the TMSC with plasma gel groups than in the groups with TMSCs alone. We detected PTH and chromogranin A in the TMSC-plasma gel-transplanted areas on immunohistochemistry and immunofluorescence stain. Plasma gel can be considered as a cell-delivery scaffold for treating hypoparathyroidism with tonsil-derived mesenchymal stem cells.

Background/aims Far-infrared (FIR) irradiation has been reported to exhibit various biological effects including improvement of cardiovascular function. However, its effect on the differentiation of stem cells has not been studied. Using tonsil-derived mesenchymal stem cells (TMSC), we examined whether and how FIR irradiation affects adipogenic or osteogenic differentiation. Methods TMSC were exposed to FIR irradiation (3-25 μm wavelength) for various times (0, 30, or 60 min), and then adipogenic or osteogenic differentiation was induced for 14 days with its respective commercially available differentiation medium. At the end of the differentiation, the cells were stained using Oil red O or Alizarin red S solution, and the expression of differentiation-specific proteins was analyzed by western blotting. Results FIR irradiation did not alter cell viability or the expression of MSC-specific surface antigens (CD14, CD34, CD45, CD73, CD90, and CD105) in TMSC. However, FIR irradiation significantly inhibited adipogenic differentiation of TMSC, as evidenced by decreased Oil red O staining as well as protein expression of peroxisome proliferator-activated receptor γ and fatty acid binding protein 4. In contrast, FIR irradiation induced osteogenic differentiation, as evidenced by increased Alizarin red S staining as well as protein expression of osteocalcin and alkaline phosphatase. Treatment with heat alone did not inhibit the adipogenic differentiation of TMSC, suggesting that the inhibitory effect on adipogenic differentiation was not due to heat induced by FIR irradiation. However, heat alone did stimulate osteogenic differentiation, but to a lesser extent than FIR irradiation. Furthermore, FIR irradiation increased intracellular Ca²⁺ levels and the activity of protein phosphatase 2B (PP2B) in TMSC. Treatment with cyclosporin A, a specific PP2B inhibitor, reversed the inhibitory effect of FIR irradiation on adipogenic differentiation of TMSC, but had no effect on osteogenic differentiation. Conclusion Our data demonstrate that FIR irradiation inhibits adipogenic differentiation but enhances osteogenic differentiation of TMSC; the inhibitory effect on adipogenic differentiation is non-thermal and mediated at least in part by activation of Ca²⁺-dependent PP2B.

Aesthetic reconstruction of the external ear is challenging due to the complex anatomical shape of the auricle. Recently, artificial scaffolds such as Medpor (Stryker, Kalamasoo, MI, USA) have become widely used in ear reconstruction. However, the Medpor scaffold is stiffer than the natural ear, which may lead to discomfort, and moreover has uniform design for every patient. In this study, we investigated whether three-dimensional (3D)-printed artificial polyurethane (PU) scaffolds are suitable for auricular reconstruction.PU scaffolds were fabricated using 3D printing according to a design derived from a digital imaging and communications in medicine (DICOM) image of the human auricle. The microstructure of the scaffolds was observed using scanning electron microscopy, and the porosity was examined. Cell proliferation on the scaffolds was assessed in vitro using tonsil-derived mesenchymal stem cells to evaluate the biocompatibility of the scaffolds. The scaffolds were implanted in C57BL/6 mice, and histological analysis was performed.The structural study revealed that the 3D-printed porous PU scaffolds have rectangular microstructure with regular pitch and line, as well as high porosity (56.46% ± 10.22%) with a pore diameter of 200 µm. The mechanical properties of the 3D-printed PU scaffolds were similar to those of the human auricle cartilage. Cell proliferation on the PU scaffolds was greater than that on Medpor scaffolds. Histological evaluation demonstrated that the porous parts of the PU scaffolds became filled with collagen and vascular tissue.Elastic, porous PU scaffolds can be obtained using 3D printing, have biomechanical properties similar to those of the natural ear, and are suitable for use in auricular reconstruction.NA Laryngoscope, 129:351-357, 2019.

Parathyroid cells release parathyroid hormone (PTH), which controls calcium homeostasis. Loss of parathyroid cells results in hypoparathyroidism and consequent low-turnover bone disease. Here, we investigated whether our recently-established human tonsil-derived mesenchymal stem cells (TMSC) restore in vivo parathyroid cell function in rats with parathyroidectomy (PTX). Compared with undifferentiated control TMSC, TMSC differentiated with activin A and soluble sonic hedgehog induced a significant release of PTH as early as day 7, with increased PTH release occurring in response to lower calcium levels and vice versa. Released PTH increased osteocalcin expression and alizarin red S staining in preosteoblastic cells, indicating its functional activity. PTX rats fed calcium-free diet only survived for ∼10 days. Subcutaneous injection with TMSC alone did not increase their survival rates, regardless of differentiation. However, survival rates increased for up to 28 days in response to TMSC embedded in Matrigel (TMSC-MA), showing 40% and 80% in control and differentiated TMSC-MA, respectively. When compared with continuous increases by control TMSC-MA, stable levels of secreted PTH and serum ionized calcium were found in PTX rats with differentiated TMSC-MA. This is the first report that differentiated TMSC resemble parathyroid cells and, if embedded in Matrigel, restore in vivo parathyroid function.

Highly uniform Bi2Te3 nanotubes with various morphologies are synthesized via a solution process using Te nanowires as a sacrificial template. The morphology of Bi2Te3 nanotubes can be controlled by varying the solvent system. The reaction between Bi and Te in triethylene glycol (TEG) produces Bi2Te3 nanotubes with plate-like surface morphology, whereas rough surface morphology of the Bi2Te3 nanotubes is obtained by the reaction in ethylene glycol (EG). The crystal structures and morphologies of nanotubes are investigated X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM). The effect of solvent on the evolution of morphology of the Bi2Te3 nanotubes is investigated. The effect of surface morphology on the thermoelectric properties is discussed.

Three new canthinone type alkaloids, canthin-6-one-1-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside (1), canthin-6-one-1-O-[6-O-(3-hydroxy-3-methylglutaryl)]-β-D-glucopyranoside (2) and canthin-6-one-1-O-[2-β-D-apiofuranosyl-6-O-(3-hydroxy-3-methylglutaryl)]-β-D-glucopyranoside (3) were isolated from the stem barks of Ailanthus altissima together with four quassinoids (4-7), seven phenylpropanoids (8-14) and a lignan of previously known structure (15). The inflammatory activities of the 15 isolates were screened on LPS-induced nitric oxide (NO), a proinflammatory mediator, in RAW 264.7 cells.

Tussilagone, extracted from Tussilago farfara is an oriental medicine used for asthma and bronchitis. We investigated its mechanism of action, its inhibitory effects on lipopolysaccharide-induced inflammation in macrophages, and its impact on viability in a cecal ligation and puncture (CLP)-induced mouse model of sepsis. Tussilagone suppressed the expression of the inflammatory mediators, nitric oxide and prostaglandin E2, and the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and high-mobility group box 1 (HMGB1), in lipopolysaccharide-stimulated RAW 264.7 cells and peritoneal macrophages. Tussilagone also reduced the activation of the mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) involved in the activation of various inflammatory mediators in activated macrophages. Moreover, tussilagone administration (1 mg/kg and 10 mg/kg) produced decreased mortality and lung injury in CLP-activated septic mice. Augmented expression of cyclooxygenase (COX)-2 and TNF-α in pulmonary alveolar macrophages of septic mice were attenuated by tussilagone administration. Tussilagone also suppressed the induction of nitric oxide, prostaglandin E2, TNF-α and HMGB1 in the serum of the septic mice. Overall, tussilagone exhibited protective effects against inflammation and polymicrobial sepsis by suppressing inflammatory mediators possibly via the inhibition of NF-κB activation and the MAP kinase pathway. These results suggest the possible use of tussilagone for developing novel therapeutic modalities for sepsis and other inflammatory diseases.

We examined the challenge of preparing CO2-selective bifunctional three-dimensional Cu-metal–organic frameworks (Cu-MOFs) for use in mixed-matrix membranes (MMMs) fabricated on an asymmetric polymer support. Two different gas-selective micro-sized frameworks, [{Cu2(Glu)2(µ-bpa)}·(CH3CN)]n (Cu-MOF1) and [{Cu2(Glu)2(µ-bpp)}·(C3H6O)]n (Cu-MOF2) (Glu=glutarate, bpa=1,2-bis(4-pyridyl)ethane, bpp=1,3-bis(4-pyridyl)propane), were synthesised and dispersed in polyoxazoline (POZ), as a matrix for the fabrication of the MMMs. SEM imaging indicated relatively good adhesion between the Cu-MOFs and POZ, without any surface treatment. The ideal selectivity of CO2/N2 was enhanced significantly in the Cu-MOF/POZ MMM, compared to that in a pristine POZ asymmetric membrane. Improvement in the CO2/N2 selectivity of the membranes was achieved via both high adsorption selectivity of CO2 over N2 by the Cu-MOFs, and the difference in pore sizes. The fabrication methods that use gas-selective MOFs may create new opportunities for gas-selective MOF/polymer combinations for MMMs with useful properties for large volume separations.

Although mesenchymal stem cells (MSC) isolated from bone marrow and adipose tissues are known to be subjected to in vitro culture-related alterations in their stem cell properties, such data have not been reported in human tonsil-derived MSC (T-MSC). Here, we investigated the culture-related changes of phenotypes, the senescence, and the differentiation potential of T-MSC. T-MSC were serially passaged by a standard protocol, and their characteristics were assessed, including MSC-specific surface antigen profiles, the senescence, and the differentiation potentials into adipocytes, chondrocytes and osteocytes. Up to at least passage 15, we found no alterations in either MSC-specific surface marker, CD14, CD34, CD45, CD73 and CD90, or the mRNA expression of embryonic stem cell gene markers, Nanog, Oct4-A and Sox-2. However, the expression of CD146, recently identified another MSC marker, dramatically decreased with increasing passages from ∼ 23% at passage 3 to ∼ 1% at passage 15. The average doubling time increased significantly from ∼ 38 h at passage 10 to ∼ 46 h at passage 15. From passage 10, the cell size increased slightly and SA-β-gal staining was evident. Both Alizarin Red S staining and osteocalcin expression showed that the osteogenic differentiation potential increased up to passage 10 and decreased thereafter. However, the adipogenic and chondrogenic differentiation potential decreased passage-dependently from the start, as evidenced by staining of Oil Red O and Alcian Blue, respectively. Consistent with a passage-dependent osteogenic differentiation, the expression of CCN1, an angiogenic protein known to be related to both senescence and osteogenesis, also increased up to passage 10. Furthermore, ectopic expression of small interfering RNA against CCN1 at passage 10 significantly reversed Alizarin Red S staining and osteocalcin expression. Altogether, our study demonstrates the characterization of long-term in vitro cultured T-MSC and that CCN1 may be involved in mediating a passage-dependent increase in osteogenic potential of T-MSC.

We wish to make the following corrections to this paper [...]

N-doped ZnO–SBA-15 materials (denoted as n N– x ZnO–SBA-15, where n is number of urea treatments and x is the weight ratio of ZnO/(ZnO+SBA-15)) were successfully synthesized by a two-step procedure. First, x ZnO–SBA-15 was prepared by impregnating SBA-15 with Zn(NO 3 ) 2 , followed by calcinating at 550 °C. In the second step, x ZnO–SBA-15 was modified n times by doping nitrogen with the assistance of urea. The resulting n N– x ZnO–SBA-15 materials prepared with various numbers of urea treatments were characterized by XRD, TEM, SEM, EDS, N 2 adsorption/desorption at 77 K, diffuse reflectance UV–vis, and XPS. The results show that the n N– x ZnO–SBA-15 maintains its ordered hexagonal mesostructure and exhibits light absorbance in the visible region. The n N– x ZnO–SBA-15 samples were investigated with the photodegradation of methylene blue under visible light, and exhibited significant photocatalytic activity. The kinetics of the reaction obeyed the Langmuir–Hinshelwood model.

Poly(methacrylic acid)-functionalized SBA-15 silicas (denoted as P-x-PMA/SBA-15 where x is molar ratio of TSPM/(TEOS+TSPM) in percentage in the initial mixture) were synthesized by co-condensation of tetraethoxysilane and varying contents of 3-(trimethoxysilyl)propyl methacrylate in acidic medium with the block copolymer Pluronic 123 as a structure directing agent and then polymerization by methacrylic acid in the presence of ammonium persulfate as an initiator. The functionalized materials were characterized by PXRD, TEM, SEM, IR, and adsorption-desorption at 77 K. The investigation of phenol adsorption in aqueous solution on the materials showed that the poly(methacrylic acid)-functionalized mesoporous silicas possess strong adsorption ability for phenol with interaction of various kinds of hydrogen bonds. The adsorption data were fitted to Langmuir isotherms and the maximum adsorption capacity of the three functionalized materials P-5-PMA/SBA-15, P-10-PMA/SBA-15, and P-15-PMA/SBA-15 to be 129.37 mg/g, 187.97 mg/g, and 78.43 mg/g, respectively, were obtained. The effect of the pH on phenol adsorption was studied.

Semiconducting SnO2 nanowires deposited with Pd and Sn nanoparticles on their surface are shown to be a highly sensitive hydrogen sensor with fast response time at room temperature. Compared with the SnO2 nanowire deposited with Pd or Sn nanoparticles alone, the Pd/Sn-deposited SnO2 nanowire exhibits a significant improvement in the sensitivity and reversibility of sensing hydrogen gas in the air at room temperature. Our investigation indicates that two factors are responsible for the synergistic effect of Pd/Sn codeposition on SnO2 nanowires. One is that in the presence of Pd the oxidation of Sn nanoparticles on the surface of the SnO2 nanowire is incomplete leading only to suboxides SnOx (1 ≤ x < 2), and the other is that the surface of the Pd/Sn-deposited SnO2 nanowire is almost perfectly hydrophobic.

The use of five flexible α,ω-alkane (or alkene)-dicarboxylates (succinate (2), fumarate (3), adipate (5), and muconate (6)) produced three-dimensional (3-D) ZnII frameworks with 1,2-bis(4-pyridyl)ethane pillars, whereas glutarate gave a two-dimensional (2-D) ZnII compound (4). Structures 2 and 5 are 4-fold interpenetrated networks, and 3 and 6 are 5-fold interpenetrated networks. Both 5 and 6 displayed good CO2 sorption capabilities at 196 K, as evidenced by S-shape adsorption isotherms. Both compounds also exhibited selective CO2 sorption over N2 at low temperature, while 5 containing an adipate ligand showed higher CO2 uptake at 273 and 298 K than 6 with a more rigid muconate ligand. The isosteric heats of CO2 adsorption for 5 and 6 were 23.1 kJ mol–1 and 30.7 kJ mol–1, respectively. A photoluminescence study showed the emissions of 2, 4, and 5 to be blue-shifted relative to both the free acids and ligand, while 3 had ligand-based luminescence properties. The thermal stabilities of these complexes were ...

Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, KoreaReceived April 22, 2013, Accepted April 30, 2013Key Words : Cyperus rotundus, Cyperaceae, Sesquiterpene, Nitric oxide, InflammationThe rhizomes of Cyperus rotundus L. (Cyperaceae) havebeen used in traditional Chinese medicine as an estrogenicand anti-inflammatory agent for the treatment of women'sdiseases and also used for treatment of stomach ache, boweldisorders, and menstrual disorders.

Four three-dimensional ZnII frameworks containing malonates and various bipyridyl pillars (4,4′-bipyridine (1), 1,2-bis(4-pyridyl)ethane (2), 1,2-bis(4-pyridyl)ethylene (3) and 1,3-bis(4-pyridyl)propane (4)) have been prepared, and their structures were determined by X-ray crystallography. In all four frameworks, malonate ligands bridge three Zn ions to form two-dimensional layers, and these layers are connected by bipyridyl pillars to form three-dimensional frameworks with the general formula [{Zn(H2O)(μ-malonate)}2(μ-bipyridyl)] and which also contain water or acetonitrile solvates. Reactivity studies of compounds 1–4 showed that they catalyzed a heterogeneous transesterification reaction of phenyl acetate and could be reused without any significant loss of activity through five runs. Emissions were observed at 347–365 nm (λex = 313 nm) for 2 and 363 nm (λex = 328 nm) for 3, while compounds 1 and 4 showed no luminescence properties. The thermal stabilities of these complexes were also examined.

A ready-made, acellular patch-type prosthesis is desirable in repairing partial tracheal defects in the clinical setting. However, many of these prostheses may not show proper biological integration and biomechanical function when they are transplanted. In this study, we developed a novel 3D printed polyurethane (PU) tracheal scaffold with micro-scale architecture to allow host tissue infiltration and adequate biomechanical properties to withstand physiological tracheal condition. A half-pipe shaped PU scaffold (1.8 cm of height, 0.18 cm thickness, and 2 cm of diameter) was fabricated by 3D printing of PU 200 μm PU beam. The 3D printed tracheal scaffolds consisted of a porous inner microstructure with 200 × 200 × 200 μm3 sized pores and a non-porous outer layer. The mechanical properties of the scaffolds were 3.21 ± 1.02 MPa of ultimate tensile strength, 2.81 ± 0.58 MPa of Young's modulus, and 725% ± 41% of elongation at break. To examine the function of the 3D printed tracheal scaffolds in vivo, the scaffolds were implanted into 1.0 × 0.7 cm2 sized anterior tracheal defect of rabbits. After implantation, bronchoscopic examinations revealed that the implanted tracheal scaffolds were patent for a 16 week-period. Histologic findings showed that re-epithelialization after 4 weeks of implantation and ciliated respiratory epithelium with ciliary beating after 8 weeks of implantation were observed at the lumen of the implanted tracheal scaffolds. The ingrowth of the connective tissue into the scaffolds was observed at 4 weeks after implantation. The biomechanical properties of the implanted tracheal scaffolds were continually maintained for 16 week-period. The results demonstrated that 3D printed tracheal scaffold could provide an alternative solution as a therapeutic treatment for partial tracheal defects.