Whitening and moisturizing enhancing effects of three-dimensional human adipose-derived mesenchymal stem cell-conditioned medium-containing cream.

BACKGROUND: High-functional cosmetic products combined with the concept of "treatment" cosmetics are being introduced to the market. Cosmetic products containing a skin-derived microbiome, a three-dimensional (3D) stem cell culture medium, and low-molecular-weight collagen are being introduced, and these products are leading the cosmeceutical market. We aimed to confirm the potential of a 3D stem cell culture medium-containing cream as a skin-whitening and moisturizing product. AIM: To determine the enhancing effects of a cream containing 3D adipose tissue-derived mesenchymal stem cell-conditioned media (3D ADMSC-CM) on whitening and moisturization. METHODS: The inhibitory activities of tyrosinase (TYR) and melanin were confirmed using 3D ADMSC-CM. Furthermore, hyaluronic acid expression in 3D ADMSC-CM was verified. The clinical efficacy of the cream containing 3D ADMSC-CM was established by evaluating its antioxidant properties and effects on skin tone, radiance, freckles, and moisturization. RESULTS: The use of 3D ADMSC-CM suppressed the inhibitory effects of TYR and melanin by approximately 24% and 33%, respectively, and increased the expression of hyaluronic acid synthase. A significant difference was observed after 4 weeks of using 3D ADMSC-CM in the skin antioxidant evaluation. After 2 and 4 weeks of use, skin tone and radiance increased and skin freckles decreased significantly. Under extremely cold and dry weather conditions, the use of the cream increased skin moisturization. CONCLUSIONS: The 3D ADMSC-CM cream evaluated in an environment similar to the human body was found to enhance skin whitening and moisturization and can therefore be used in the skin care and cosmetic industries as a biocosmetic product.

Identification of a novel trait associated with phytotoxicity of an insecticide etofenprox in soybean.

Synthetic insecticides are widely used to control pests in various crop fields. Especially in soybean [Glycine max (L.) Merr.] fields, the insecticide etofenprox, which is a pyrethroid derivative, has been used to manage hemiptera pests. To date, soybean phytotoxicity response has not been reported to etofenprox derivatives, two Korean cultivars, Danbaek and Kwangan, were first identified to show leaf shape shrinkage damage after etofenprox application. We confirmed that the causal substance for phytotoxicity is etofenprox and that it had dosage effects. Through genetic analysis using three F2 populations, sensitivity to etofenprox is confirmed to be managed by a single dominant gene, and that gene is the same in Danbaek and Kwangan. Although further genetic research is required to identify the gene responsible for sensitivity to etofenprox, the results of this study will help to elucidate the interaction between plants and chemicals when breeding new cultivars or developing pesticides.

Enhancing the recruitment of postgraduate researchers from diverse countries: managing the application process.

International students form an important element of most universities' internationalisation strategies, especially for research and the recruitment of high calibre PhD students (PGRs). Despite the numerous studies of PGRs' post-arrival experiences, there is a major dearth of research into their pre-arrival, application experiences. Given the worldwide competition for high calibre PGRs, along with impact posed by the Covid-19 pandemic and by Brexit for the UK, it is vital for universities to ensure that factors clearly under their control, such as the information on their websites and the way they communicate, are as informative and helpful as possible. In this article, we draw on social media data to examine the challenges and uncertainties that Korean PGR applicants experienced in navigating the process of applying to UK universities. The paper compares their confusions with information available on university websites and recommends a series of points that higher education institutions should check for. It also reveals and discusses issues associated with communication. While the data has been collected from Korean social media websites, we argue that our paper has broader relevance for the following reasons. First, the same fundamental intercultural issues-different educational systems and different background knowledge-apply to PGR applicants from other countries and so their queries are likely to be similar or comparable. Second, the insights gained from social media websites to facilitate the application process and thereby enhance recruitment can usefully be applied to other countries and levels of study, in a way that has rarely been done to date.

Hybrid neural network with cost-sensitive support vector machine for class-imbalanced multimodal data.

Although deep learning exhibits advantages in various applications involving multimodal data, it cannot effectively solve the class-imbalance problem. Herein, we propose a hybrid neural network with a cost-sensitive support vector machine (hybrid NN-CSSVM) for class-imbalanced multimodal data. We used a fused multiple-network structure obtained by extracting the features of different modality data, and used cost-sensitive support vector machines (SVMs) as a classifier. To alleviate the insufficiency of learning from minority-class data, our proposed cost-sensitive SVM loss function reflects different weights of misclassification errors from both majority and minority classes, by controlling cost parameters. Additionally, we present a theoretical setting of the cost parameters in our model. The proposed model is validated on real datasets that range from low to high imbalance ratios. By exploiting the complementary advantages of two architectures, the hybrid NN-CSSVM performs excellently, even with data having a minor-class proportion of only 2%.

Comparison of Amyloid in Cerebrospinal Fluid, Brain Imaging, and Autopsy in a Case of Progressive Supranuclear Palsy.

Cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aß1-42) and amyloid positron emission tomography (PET) are the 2 main Alzheimer disease amyloid biomarkers that have been validated in neuropathologically confirmed Alzheimer disease cases. Although many studies have shown concordance of amyloid positivity or negativity between CSF Aß1-42 and amyloid PET, several studies also reported discrepancies between these 2 Aß biomarkers. We conducted a comparison of CSF Aß1-42 level, amyloid PET, and autopsy findings in a case with progressive supranuclear palsy in which biomarker acquisition and postmortem pathologic examination were conducted almost at the same time. Our case with antemortem CSF Aß1-42 (+)/amyloid PET (-) who was pathologically confirmed with Aß pathology in the cerebral cortex may indicate CSF Aß1-42 is more sensitive for assessing in vivo Aß than amyloid PET.

Diffusion-weighted imaging negative M232R familial Creutzfeldt-Jakob disease.

The familial Creutzfeldt-Jakob disease (fCJD) usually has similar clinical and neuroimaging features as sporadic CJD (sCJD). A 57-year-old man presented with a four-month history of rapidly progressive dementia (RPD). Laboratory tests for RPD were all normal. Brain MRI demonstrated diffuse cortical atrophy and no abnormal cortical or striatal hyperintensities on fluid-attenuated inversion recovery (FLAIR)/diffusion weighted imaging (DWI). Electroencephalography revealed intermittent slow waves in the bilateral hemispheres. Cerebrospinal fluid (CSF) examination showed elevated cell counts and protein concentrations. After 10 days of empirical treatment with antiviral agents, the patient was eventually diagnosed with fCJD with M232R mutation based on the results of positivity for 14-3-3 protein, CSF PrPsc in real-time quaking-induced conversion assay and genetic test for PRNP gene. The striatal or cortical FLAIR/DWI hyperintensities are reliable radiographic markers in the diagnosis of both sCJD and fCJD. However, this case suggests that clinical work-up for CJD including genetic test is essential to do a differential diagnosis of RPD, regardless of FLAIR/DWI findings.

Tunable Emission of Bluish Zn-Cu-Ga-S Quantum Dots by Mn Doping and Their Electroluminescence.

On the basis of bluish-emitting double-shelled quantum dots (QDs) of Zn-Cu-Ga-S (ZCGS)/ZnS/ZnS, Mn doping into ZCGS host with different Mn/Cu concentrations is implemented via surface adsorption and lattice diffusion. The resulting double-shelled Mn-doped ZCGS (ZCGS/Mn) QDs exhibit a distinct Mn2+ 4T1-6A1 emission as a consequence of effective lattice incorporation simultaneously with host intragap states-involving emissions of free-to-bound and donor-acceptor pair recombinations. The relative contribution of Mn emission to the overall photoluminescence (PL) is consistently proportional to its concentration, resulting in tunable PL from bluish, white, to reddish white. Regardless of Mn doping and its concentration, all QDs possess high PL quantum yield levels of 74-79%. Those undoped and doped QDs are then employed as an emitting layer (EML) of all-solution-processed QD-light-emitting diodes (QLEDs) with hybrid charge transport layers and their electroluminescence (EL) is compared. Compared to undoped QDs, doped analogues give rise to a huge spectral disparity of EL versus PL, specifically showing a near-complete quenching of Mn2+ EL. This unexpected observation is rationalized primarily by considering unbalanced carrier injection to QD EML on the basis of energetic alignment of the present QLED and rapid trapping of holes injected at intragap states of QDs.

Electroluminescence from two I-III-VI quantum dots of A-Ga-S (A=Cu, Ag).

Together with III-V InP, chalcopyrite I-III-VI metal chalcogenides particularly with the compositions of A-B-S (A=Cu+, Ag+, B=In3+, Ga3+) are regarded as an emerging non-Cd class for synthesis of visible-emitting colloidal quantum dots (QDs) and the following fabrication of QD-light-emitting diodes (QLEDs). To date, the composition of I-III-VI QDs which were exploited for QLED fabrication remains highly limited, with most devices demonstrated from Cu-In-S-based ones. Herein, we explore the synthesis of two Ga-based I-III-VI QDs of Ag-Ga-S (AGS) and Cu-Ga-S (CGS) QDs and their application to QLED fabrication. Using cyan AGS/ZnS and azure CGS/ZnS core/shell QDs, all-solution-processed, multilayered QLEDs with a hybrid combination of organic hole transport layer and inorganic electron transport layer are fabricated and compared. We observe that CGS QLED by far outperforms in luminance and efficiency its AGS counterpart, which is ascribable to the differences in both electronic band structure and core/shell structure between two comparative QDs.

Clinical Implications of Basilar Artery Plaques in the Pontine Infarction with Normal Basilar Angiogram: A High-Resolution Magnetic Resonance Imaging Study.

BACKGROUND: Using high-resolution magnetic resonance imaging (HR-MRI), we investigated the impact of basilar artery plaques that were not detected by magnetic resonance angiography (MRA) on the functional outcomes of patients with acute pontine infarction. METHODS: A total of 40 patients with acute pontine infarction and normal basilar findings on MRA prospectively underwent HR-MRI for detection of basilar artery plaques. A relevant plaque was defined as one on the dorsal side of basilar artery, the same side of the ischemic lesion, and the same axial slices of the ischemic lesion. We analyzed the relationship between the relevant basilar artery plaques and the functional outcomes at 3 months. RESULTS: The initial National Institutes of Health Stroke Scale score (3.5 versus 2.0, P = .012), and the incidences of neurological deterioration (42.9% versus 6.3%, P = .031) and unfavorable functional outcome (71.4% versus 12.5%, P = .001) were higher in patients with relevant basilar artery plaques than in those without. On multiple regression analysis, the relevant basilar artery plaque was a significant and independent predictor of unfavorable functional outcome (odds ratio, 6.662; 95% confidence interval, 1.117-39.735; P = .037). CONCLUSIONS: The presence of a relevant basilar artery plaque was closely related with unfavorable functional outcome in patients with acute pontine infarction even if the patients' MRA showed normal basilar findings.

Simvastatin inhibits sphingosylphosphorylcholine-induced differentiation of human mesenchymal stem cells into smooth muscle cells.

Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle-like cells expressing α-smooth muscle actin (α-SMA) via transforming growth factor-ß1/Smad2- and RhoA/Rho kinase-dependent mechanisms. 3-Hydroxy-3-methylglutaryl- coenzyme A reductase inhibitors (statins) have been known to have beneficial effects in the treatment of cardiovascular diseases. In the present study, we examined the effects of simvastatin on the SPC-induced α-SMA expression and Smad2 phosphorylation in hASCs. Simvastatin inhibited the SPC-induced α-SMA expression and sustained phosphorylation of Smad2 in hASCs. SPC treatment caused RhoA activation via a simvastatin-sensitive mechanism. The SPC-induced α-SMA expression and Smad2 phosphorylation were abrogated by pretreatment of the cells with the Rho kinase inhibitor Y27632 or overexpression of a dominant negative RhoA mutant. Furthermore, SPC induced secretion of TGF-ß1 and pretreatment with either Y27632 or simvastatin inhibited the SPC-induced TGF-ß1 secretion. These results suggest that simvastatin inhibits SPC-induced differentiation of hASCs into smooth muscle cells by attenuating the RhoA/Rho kinase-dependent activation of autocrine TGF-ß1/Smad2 signaling pathway.

Comparison of mesenchymal-like stem/progenitor cells derived from supernumerary teeth with stem cells from human exfoliated deciduous teeth.

AIMS: Dental tissue has been the focus of attention as an easily accessible postnatal tissue source of high-quality stem cells. Since the first report on the dental pulp stem cells (DPSCs) from permanent third molar teeth, stem cells from human exfoliated deciduous teeth (SHED) were identified as a population distinct from DPSCs. In this study, we compared DPSCs from supernumerary teeth and SHED in three age- and sex-matched patients. PATIENTS & METHODS: Dental samples were obtained from the three patients, who were 6 years old and male, with the parental consent of the three donors, and then isolated cells from dental pulp for comparative analysis between supernumerary DPSCs and SHED. RESULTS: Colony-forming unit fibroblast levels and the proliferation rate of supernumerary DPSCs were slightly lower than that of SHED. The expression of cell surface antigens in supernumerary DPSCs and SHED were almost identical. Cells were mainly expressing endogenous mesodermal and ectodermal lineage markers. Differentiation capacity to osteogenic, adipogenic and chondrogenic lineage was similar in the SHED and supernumerary DPSCs. Migration assay revealed that both supernumerary DPSCs and SHED rapidly migrated toward wounded areas. Supernumerary DPSCs were altered in cell growth after storage for 2 years. Specially, the population doubling time of supernumerary DPSCs increased while that of SHED remained nearly unchanged. CONCLUSION: Both supernumerary teeth and deciduous teeth share many characteristics, such as highly proliferative clonogenic cells with a similar immunophenotype to that of mesenchymal stem cells, although they are inferior to SHED for long-term banking. Our findings suggest that supernumerary teeth are also easily accessible and noninvasive sources of postnatal stem cells with multipotency and regenerative capacity.

Synovial fluid of patients with rheumatoid arthritis induces alpha-smooth muscle actin in human adipose tissue-derived mesenchymal stem cells through a TGF-beta1-dependent mechanism.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-beta1 (TGF-beta1) is a secreted protein that promotes differentiation of synovial fibroblasts to alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts to repair the damaged joints. Synovial fluid from patients with RA (RA-SF) induced expression of alpha-SMA in human adipose tissue-derived mesenchymal stem cells (hASCs). RA-SF-induced alpha-SMA expression was abrogated by immunodepletion of TGF-beta1 from RA-SF with anti-TGF-beta1 antibody. Furthermore, pretreatment of hASCs with the TGF-beta type I receptor inhibitor SB431542 or lentiviral small hairpin RNA-mediated silencing of TGF-beta type I receptor expression in hASCs blocked RA-SF-induced alpha-SMA expression. Small interfering RNA-mediated silencing of Smad2 or adenoviral overexpression of Smad7 (an inhibitory Smad isoform) completely inhibited RA-SF-stimulated alpha-SMA expression. These results suggest that TGF-beta1 plays a pivotal role in RA-SF-induced differentiation of hASCs to alpha-SMA-positive cells.

Lysophosphatidic acid mediates migration of human mesenchymal stem cells stimulated by synovial fluid of patients with rheumatoid arthritis.

Migration of mesenchymal stem cells plays a key role in regeneration of injured tissues. Rheumatoid arthritis (RA) is a chronic inflammatory disease and synovial fluid (SF) reportedly contains a variety of chemotactic factors. This study was undertaken to investigate the role of SF in migration of human bone marrow-derived mesenchymal stem cells (hBMSCs) and the molecular mechanism of SF-induced cell migration. SF from RA patients greatly stimulated migration of hBMSCs and the SF-induced migration was completely abrogated by pretreatment of the cells with the lysophosphatidic acid (LPA) receptor antagonist Ki16425 and by small interfering RNA- or lentiviral small hairpin RNA-mediated silencing of endogenous LPA(1)/Edg2. Moreover, SF from RA patients contains higher concentrations of LPA and an LPA-producing enzyme autotoxin than normal SF. In addition, SF from RA patients increased the intracellular concentration of calcium through a Ki16425-sensitive mechanism and pretreatment of the cells with the calmodulin inhibitor W7 or calmodulin-dependent protein kinase II inhibitor KN93 abrogated the SF-induced cell migration. These results suggest that LPA-LPA(1) plays a key role in the migration of hBMSCs induced by SF from RA patients through LPA(1)-dependent activation of calmodulin-dependent protein kinase II.

Emergency department visits: the cost of trauma centers.

Crowded emergency departments (EDs) have become a serious problem in the current U.S. healthcare system. Patient wait times and periods of ED diversion have increased, raising concerns about the timeliness, efficiency, and quality of ED treatment. This study addresses the question of whether there are economies of scale (EOS) in ED care, and the extent to which such economies vary across different types of EDs. A hospital cost function approach is taken to evaluate average and marginal costs of EDs designated as trauma centers. Data comes from acute care hospitals in Texas for the period 1998-2004. Cost functions corresponding to four different levels of ED trauma care are estimated using a translog panel data model with hospital fixed effects. The marginal costs (in 2004 dollars) of each trauma center level are: $53 (Level I), $177 (Level II), $119 (Level III), and $258 (Level IV). Average cost per ED visit for trauma centers exceeds marginal cost at all Levels, indicating the presence of EOS. The results support a possible expansion of ED size policy in order to improve the cost efficiency of ED services.