2,4,6-Triphenyl-1-hexene, an Anti-Melanogenic Compound from Marine-Derived Bacillus sp. APmarine135.

Although melanin protects against ultraviolet radiation, its overproduction causes freckles and senile lentigines. Recently, various biological effects of metabolites derived from marine microorganisms have been highlighted due to their potential for biological and pharmacological applications. In this study, we discovered the anti-melanogenic effect of Bacillus sp. APmarine135 and verified the skin-whitening effect. Fractions of APmarine135 showed the melanin synthesis inhibition effect in B16 melanoma cells, and 2,4,6-triphenyl-1-hexene was identified as an active compound. The melanogenic capacity of 2,4,6-triphenyl-1-hexene (1) was investigated by assessing the intracellular melanin content in B16 cells. Treatment with 5 ppm of 2,4,6-triphenyl-1-hexene (1) for 72 h suppressed the α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin increase to the same level as in the untreated control group. Additionally, 2,4,6-triphenyl-1-hexene (1) treatment suppressed the activity of tyrosinase, the rate-limiting enzyme for melanogenesis. Moreover, 2,4,6-triphenyl-1-hexene (1) treatment downregulated tyrosinase, Tyrp-1, and Tyrp-2 expression by inhibiting the microphthalmia-associated transcription factor (MITF). Furthermore, 2,4,6-triphenyl-1-hexene (1) treatment decreased the melanin content in the three-dimensional (3D) human-pigmented epidermis model MelanoDerm and exerted skin-whitening effects. Mechanistically, 2,4,6-triphenyl-1-hexene (1) exerted anti-melanogenic effects by suppressing tyrosinase, Tyrp-1, and Tyrp-2 expression and activities via inhibition of the MITF. Collectively, these findings suggest that 2,4,6-triphenyl-1-hexene (1) is a promising anti-melanogenic agent in the cosmetic industry.

Low-Temperature, Universal Synthetic Route for Mesoporous Metal Oxides by Exploiting Synergistic Effect of Thermal Activation and Plasma.

Mesoporous metal oxides exhibit excellent physicochemical properties and are widely used in various fields, including energy storage/conversion, catalysis, and sensors. Although several soft-template approaches are reported, high-temperature calcination for both metal oxide formation and template removal is necessary, which limits direct synthesis on a plastic substrate for flexible devices. Here, a universal synthetic approach that combines thermal activation and oxygen plasma to synthesize diverse mesoporous metal oxides (V2O5, V6O13, TiO2, Nb2O5, WO3, and MoO3) at low temperatures (150-200 °C), which can be applicable to a flexible polymeric substrate is introduced. As a demonstration, a flexible micro-supercapacitor is fabricated by directly synthesizing mesoporous V2O5 on an indium-tin oxide-coated colorless polyimide film. The energy storage performance is well maintained under severe bending conditions.

Fiber support prevents colloid-facilitated contamination induced by dissolution-precipitation of a calcium phosphate adsorbent.

During the adsorptive removal of hazardous metal contaminants, dissolution-precipitation of sparingly soluble adsorbents may result in the formation of toxic colloidal suspensions, triggering secondary pollution. Therefore, we studied the prevention of colloid-facilitated contamination in a model adsorption system of dicalcium phosphate dihydrate (DCPD, CaHPO4·2H2O) and Cd2+ as an adsorbent and adsorbate. Upon adding pure DCPD powder into a 500 mg L-1 Cd2+ solution of pH â‰Œ 7.0, aggregates of spheroidal Cd-bearing primary particles, within 0.040-0.95 µm size range, were generated via dissolution-precipitation. The accumulated volume of these submicron particles (10.8%) was greater than that of the submicron particles from the exposure of DCPD to deionized water (4.48%). While the Cd-carrying submicron particles, which are responsible for colloidal recontamination, appeared to form via homogeneous nucleation, their formation was suppressed using polyacrylonitrile fibers (PANFs) as supporting substrates. Thus, heterogeneous nucleation on PANFs formed hexagonal columnar microparticles of a new phase, pentacadmium dihydrogen tetrakis (phosphate) tetrahydrate (Cd5H2(PO4)4·4H2O). Together with dissolution-precipitation on the native DCPD, nucleation and growth on the PANFs accelerated the depletion of the dissolved species, reducing the degree of supersaturation along the DCPD-water interface. Although the PANFs decreased the Cd adsorption capacity to 56.7% of that of DCPD, they prevented the formation of small aggregates of Cd-bearing particles. Other sparingly soluble adsorbents can be compounded with PANF to prevent the generation of toxic colloids.

Facile synthesis of porous transition metal hydroxides from a poly(4-vinyl pyridine) film by controlling pH.

Non-noble transition metal hydroxides have been widely used in electrochemical devices because of low cost and multiple redox states. In particular, self-supported porous transition metal hydroxides are used to improve the electrical conductivity, as well as achieving fast electron and mass transfer and a large effective surface area. Herein, we introduce facile synthesis of self-supported porous transition metal hydroxides using a poly(4-vinyl pyridine) (P4VP) film. We used metal cyanide as a transition metal precursor capable of forming metal hydroxide anions in aqueous solution, which is the seed for transition metal hydroxides. To increase the coordination between P4VP and the transition metal cyanide precursors, we dissolved the precursors in buffer solutions with various pH. When the P4VP film was immersed in the precursor solution with lower pH, the metal cyanide precursors were sufficiently coordinated with the protonated nitrogen in P4VP. When reactive ion etching was performed on the precursor-containing P4VP film, the P4VP region without coordination was etched out and became pores. Then, the coordinated precursors were aggregated as metal hydroxide seeds and became the metal hydroxide backbone, resulting in the formation of porous transition metal hydroxide structures. We successfully fabricated various self-supported porous transition metal hydroxides (Ni(OH)2, Co(OH)2, and FeOOH). Finally, we prepared a pseudo-capacitor based on self-supported porous Ni(OH)2, which showed a good specific capacitance (780 F g-1 at 5 A g-1).

Block Copolymer-Directed Facile Synthesis of N-Doped Mesoporous Graphitic Carbon for Reliable, High-Performance Zn Ion Hybrid Supercapacitor.

Ordered mesoporous carbons (OMCs) are promising materials for cathode materials of a Zn ion hybrid capacitor (Zn HC) due to their high surface area and interconnected porous structure. Graphitization of the framework and nitrogen doping have been used to improve the energy storage performance of the OMCs by enhancing electrical conductivity, pseudocapacitive reaction sites, and surface affinity toward aqueous electrolytes. Thus, when both methods are simultaneously implemented to the OMCs, the Zn HC would have improved energy storage performance. Herein, we introduce a facile synthetic method for N-doped mesoporous graphitic carbon (N-mgc) by utilizing polystyrene-block-poly(2-vinlypyridine) copolymer (PS-b-P2VP) as both soft-template and carbon/nitrogen sources. Co-assembly of PS-b-P2VP with Ni precursors for graphitization formed a mesostructured composite, which was converted to N-doped graphitic carbon through catalytic pyrolysis. After selective removal of Ni, N-mgc was prepared. The obtained N-mgc exhibited interconnected mesoporous structure with high nitrogen content and high surface area. When N-mgc was employed as a cathode material in Zn ion HC, excellent energy storage performance was achieved: a high specific capacitance (43 F/g at 0.2 A/g), a high energy density of 19.4 Wh/kg at a power density of 180 W/kg, and reliable cycle stability (>3000 cycles).

Serum proteins for monitoring and predicting visual function in patients with recent optic neuritis.

It is unclear whether serum proteins can serve as biomarkers to reflect pathological changes and predict recovery in inflammation of optic nerve. We evaluated whether serum proteins could monitor and prognosticate optic neuritis (ON). We prospectively recruited consecutive patients with recent ON, classified as ON with anti-aquaporin-4 antibody (AQP4-ON), ON with anti-myelin oligodendrocyte glycoprotein antibody (MOG-ON), and double-seronegative ON (DSN-ON). Using ultrasensitive single-molecule array assays, we measured serum neurofilament light chain and glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF). We analyzed the markers according to disease group, state, severity, and prognosis. We enrolled 60 patients with recent ON (15 AQP4-ON; 14 MOG-ON; 31 DSN-ON). At baseline, AQP4-ON group had significantly higher serum GFAP levels than did other groups. In AQP4-ON group, serum GFAP levels were significantly higher in the attack state than in the remission state and correlated with poor visual acuity. As a prognostic indicator, serum BDNF levels were positively correlated with follow-up visual function in the AQP4-ON group (r = 0.726, p = 0.027). Serum GFAP reflected disease status and severity, while serum BDNF was identified as a prognostic biomarker in AQP4-ON. Serum biomarkers are potentially helpful for patients with ON, particularly those with AQP4-ON.

Disease characteristics of idiopathic transverse myelitis with serum neuronal and astroglial damage biomarkers.

Despite its close association with CNS inflammatory demyelinating disorders (CIDDs), pathogenic characteristics of idiopathic transverse myelitis (ITM) remain largely unknown. Here, we investigated serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) in patients with ITM to unravel the disease characteristics of ITM. We prospectively recruited 70 patients with ITM, 62 with AQP4 + NMOSD and 85 with RRMS-including 31 patients with acute TM attacks-along with 30 HCs. We measured sNfL and sGFAP levels using single-molecular arrays and compared these levels per lesion volume between the disease groups during attacks. Compared to HCs, ITM patients showed higher sNfL and sGFAP during acute attacks (sNfL: p < 0.001, sGFAP: p = 0.024), while those in remission (sNfL: p = 0.944, sGFAP: p > 0.999) did not, regardless of lesion extents and presence of multiple attacks. ITM patients demonstrated lower sGFAP/volume (p = 0.011) during acute attacks and lower sGFAP (p < 0.001) in remission compared to AQP4 + NMOSD patients. These findings suggest that both neuronal and astroglial damages occur in patients with acute ITM attacks at a similar level to those with RRMS, distinct from AQP4 + NMOSD. However, active neuroinflammatory process was not remarkable during remission in this cohort.

Facile Fabrication of Titanium Nitride Nanoring Broad-Band Absorbers in the Visible to Near-Infrared by Shadow Sphere Lithography.

Plasmonic broad-band absorbers have received much attention because of their high absorption and potential applications for light-absorbing devices such as thermophotovoltaics, solar energy harvesting, and thermal emitters. However, the fabrication of complex structures in a large area and thermostability remains a great challenge. Here, we report a titanium nitride nanoring broad-band absorber that has over 95% average absorption in the visible and near-infrared regions (400-900 nm). Nanoring structures in a large area (inch2) are fabricated by shadow sphere lithography, which can innovatively increase fabrication efficiency. The nanoring absorber showed over 2.3 times higher-temperature increases than flat film under the irradiation of light. These large-scale and broad-band absorbers have potential applications for solar energy conversion devices such as thermophotovoltaics and photothermal devices.

Soft Template-Assisted Fabrication of Mesoporous Graphenes for High-Performance Energy Storage Systems.

Graphene is a promising active material for electric double layer supercapacitors (EDLCs) due to its high electric conductivity and lightweight nature. However, for practical uses as a power source of electronic devices, a porous structure is advantageous to maximize specific energy density. Here, we propose a facile fabrication approach of mesoporous graphene (m-G), in which self-assembled mesoporous structures of poly(styrene)-block-poly(2-vinylpyridine) copolymer (PS-b-P2VP) are exploited as both mesostructured catalytic template and a carbon source. Notably, the mesostructured catalytic template is sufficient to act as a rigid support without structural collapse, while PS-b-P2VP converts to graphene, generating m-G with a pore diameter of ca. 3.5 nm and high specific surface area of 186 m2/g. When the EDLCs were prepared using the obtained m-G and ionic liquids, excellent electrochemical behaviors were achieved even at high operation voltages (0 ∼ 3.5 V), including a large specific capacitance (130.2 F/g at 0.2 A/g), high-energy density of 55.4 W h/kg at power density of 350 W/kg, and excellent cycle stability (>10,000 cycles). This study demonstrates that m-G is a promising material for high-performance energy storage devices.

Triboelectric Nanogenerators: Enhancing Performance by Increasing the Charge-Generating Layer Compressibility.

Triboelectric nanogenerators (TENGs) have received significant attention for next-generation wearable electronics due to their simple device structure and low cost. Although the performance of TENGs is intimately tied to compressibility effects in the charge-generating layer, achieving high compressibility with conventional elastomers is challenging because molecular entanglements place a lower bound on the softness of cross-linked networks. Here, we demonstrate that bottlebrush elastomers are efficient charge-generating layers that improve the output performance of TENGs, including voltage, current, and surface potential, by minimizing entanglements and decreasing the compressive modulus (E). For example, a cross-linked bottlebrush with poly(dimethylsiloxane) side chains yielded TENGs with an output voltage (120 V) more than two times larger than a linear PDMS network (55 V). In conclusion, this study highlights the advantage of designing new charge-generating layers with improved compressibility to enhance TENG performance.

Quality of life of patients with multiple sclerosis and neuromyelitis optica spectrum disorders: Cross-sectional and longitudinal analysis.

BACKGROUND: Multiple sclerosis (MS) and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders (NMOSD), which have different pathogenic mechanisms, both negatively affect patients during their lifetime. We aimed to analyze and compare the quality of life (QoL) of patients with MS and NMOSD, its longitudinal course, and associated factors between the two diseases. METHODS: Between June 2018 and April 2020, patients with MS and NMOSD who visited a tertiary hospital were prospectively enrolled. The EuroQoL-5 Dimension (EQ-5D) utility index, of which low values represent poor QoL, Expanded Disability Status Scale (EDSS), and the Hospital Anxiety and Depression Scale (HADS) were collected at enrollment and at follow-up with a 6-12-month interval. At baseline, the degree of QoL and its determinants were analyzed and compared between the MS and NMOSD groups. We also analyzed the longitudinal alteration of the EQ-5D utility indices over time and the factors associated with the follow-up QoL. RESULTS: During the study period, 171 patients (MS, 120; NMOSD, 51) were included. The median age was 46 years, and median EDSS score and follow-up duration were 2.5 and 8 months, respectively. At baseline, the EQ-5D utility indices were low and comparable between the MS and NMOSD groups (median: 0.86 vs. 0.82, p = 0.823). A higher HADS total score (more severe anxiety/depression symptoms) showed an independent and significant association with the baseline EQ-5D utility index in both disease groups. Longitudinally, the EQ-5D utility indices remained low. Although they did not significantly change over time at a group level, more than 50% of patients showed a longitudinal change in their EQ-5D indices in both disease groups. Of note, a higher HADS total score at enrollment was an independent predictor for poor QoL at follow-up in both disease groups. CONCLUSIONS: The QoL was similarly impaired between patients with MS and those with NMOSD and remained low during the follow-up period. A higher total scale of HADS was an independent risk factor for a lower QoL at baseline and at follow-up in both disease conditions, suggesting that clinicians should pay more attention to anxiety and depression in patients with MS and those with NMOSD in the long term.

Various Coating Methodologies of WO3 According to the Purpose for Electrochromic Devices.

Solution-processable electrochromic (EC) materials have been investigated widely for various applications, such as smart windows, reflective displays, and sensors. Among them, tungsten trioxide (WO3) is an attractive material because it can form a film via a solution process and relative low temperature treatment, which is suitable for a range of substrates. This paper introduces the slot-die and electrostatic force-assisted dispensing (EFAD) printing for solution-processable methods of WO3 film fabrication. The resulting films were compared with WO3 films prepared by spin coating. Both films exhibited a similar morphology and crystalline structure. Furthermore, three different processed WO3 film-based electrochromic devices (ECDs) were prepared and exhibited similar device behaviors. In addition, large area (100 cm2) and patterned ECDs were fabricated using slot-die and EFAD printing. Consequently, slot-die and EFAD printing can be used to commercialize WO3 based-ECDs applications, such as smart windows and reflective displays.

Voltage-Tunable Dual Image of Electrostatic Force-Assisted Dispensing Printed, Tungsten Trioxide-Based Electrochromic Devices with a Symmetric Configuration.

Electrostatic force-assisted dispensing (EFAD)-printed tungsten trioxide (WO3)-based electrochromic devices (ECDs) displaying a dual image depending on the applied voltage are demonstrated. We first print WO3 via EFAD printing, in which the width of the printed lines can be tuned by adjusting the printing speed. The performance of the ECDs is characterized while varying the thickness of the printed WO3 film. It is determined that ∼550 nm thick WO3 is the optimal film considering maximum transmittance contrast (ΔTmax), device dynamic responses, efficiency, and long-term coloration/bleaching cyclic stability. More significantly, the coloration of the devices in this work can alternatively appear due to the use of electrolyte-soluble anodic species (here, dimethyl ferrocene, dmFc), for which WO3 films should be deposited on both electrodes and a part of the electrodes should be exposed to the electrolyte for the oxidation of dmFc. To take advantage of such features of the devices, we successfully demonstrate EFAD-printed, flexible WO3 ECDs alternately displaying a dual image, which is expected to have high potential as a functional component of printed electronics.

Tetrathiafulvalene: effective organic anodic materials for WO3-based electrochromic devices.

Finding a new, effective anodic species is a challenge for achieving simpler low-voltage tungsten trioxide (WO3)-based electrochromic devices (ECDs). In this work, we utilize tetrathiafulvalene (TTF) and demonstrate its reversible redox behaviors as an electrolyte-soluble anodic species. The concentration of TTF in the electrolyte is varied to optimize device performance. When the TTF concentration is low (0.01 M), a smaller maximum transmittance difference (ΔT max ∼ 34.2%) and coloration efficiency (η ∼ 59.6 cm2 C-1) are measured. Although a better performance of ΔT max ∼ 93.7% and η ∼ 74.5 cm2 C-1 is achieved at 0.05 M TTF, the colored state could no longer return to its original form. We conclude that 0.03 M of TTF is the appropriate concentration for high-performance WO3 ECDs with high optical contrast and reversible EC behaviors. The irreversible EC transition at high concentrations of TTF is attributed to the agglomeration of TTF molecules.

Electrostatic-Force-Assisted Dispensing Printing of Electrochromic Gels for Low-Voltage Displays.

In this study, low-voltage, printed, ion gel-based electrochromic devices (ECDs) were successfully fabricated. While conventional dispensing printing provides irregularly printed electrochromic (EC) gels, we improved the adhesion between the printed gel and the substrate by applying an external voltage. This is called electrostatic-force-assisted dispensing printing. As a result, we obtained well-defined, printed, EC gels on substrates such as indium tin oxide-coated glass. We fabricated a gel-based ECD by simply sandwiching the printed EC gel between two transparent electrodes. The resulting ECD, which required a low coloration voltage (∼0.6 V), exhibited a high coloration efficiency (η) of 161 cm2/C and a large transmittance contrast (∼82%) between the bleached and colored states at -0.7 V. In addition, electrostatic-force-assisted dispensing printing was utilized to fabricate directly patterned ECDs.

Effect of Coronal Scoliotic Curvature on Sagittal Spinal Shape: Analysis of Parameters in Mature Adolescent Scoliosis Patients.

STUDY DESIGN: A radiographic analysis with scoliosis patients. OBJECTIVES: To analyze correlations between sagittal spinal alignment and coronal scoliotic curvature. SUMMARY OF BACKGROUND DATA: Sagittal spinal alignment and scoliosis may have a significant relationship, and schematic analysis is needed. METHODS: The study group was comprised of 163 patients with adolescent idiopathic scoliosis. Subjects underwent anteroposterior and lateral radiographs of the whole spine including hip joints. The radiographic parameters used were magnitude, location and direction of curve, thoracic kyphosis, thoracolumbar kyphosis, lumbar lordosis, sagittal balance, sacral slope, and pelvic angle. Subjects were classified into 4 groups according to the severity of coronal curvature: Cobb angle ≤20 degrees, Cobb angle 21-40 degrees, Cobb angle 41-60 degrees, and Cobb angle >60 degrees. In addition, subjects were divided into 4 subgroups according to Roussouly's classification (types 1-4) of sagittal spinal shape. Schematic analysis was performed to determine the relationship between coronal and sagittal parameters. RESULTS: Analysis of parameters with severity of coronal curvature, thoracic kyphosis, and sacral slope were significantly higher in high-grade scoliosis (P<0.05). However, the pelvic angle was higher in low-grade scoliosis, and sagittal balance showed a significantly higher positive value in low-grade scoliosis (P<0.05). In the analysis of sagittal spinal shapes, Roussouly groups 3 and 4 showed more severe scoliosis with higher lumbar lordosis and thoracic kyphosis (P<0.05). In addition, Roussouly group 1 demonstrated a significantly higher incidence of low-grade scoliosis, whereas groups 3 and 4 had a higher incidence of high-degree scoliosis by cross-relation analysis (P<0.05). CONCLUSIONS: A significant relationship exists between sagittal spinal shape and coronal curvature in scoliosis. Understanding the biplanar shapes of scoliosis may be helpful to the surgeons.

Enhancement of DNA vaccine potency by antigen linkage to IFN-γ-inducible protein-10.

DNA vaccines have emerged as an attractive approach to generate antigen-specific T-cell immune response. Nevertheless, the potency of DNA vaccines still needs to be improved for cancer immunotherapy. In this study, we explored whether functional linkage of a Th1-polarizing chemokine, IP-10, to a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, enhanced DNA vaccine potency. IP-10 linkage changed the location of E7 from the nucleus to the endoplasmic reticulum and led to the secretion of functionally chemoattractive chimeric IP-10/E7 protein. In addition, this linkage drastically enhanced the endogenous processing of E7 antigen through MHC class I. More importantly, we found that C57BL/6 mice intradermally vaccinated with IP-10/E7 DNA exhibited a dramatic increase in the number of E7-specific CD4(+) Th1 T-cells and CD8(+) T-cells and, consequently, were strongly resistant over the long term to E7-expressing tumors compared to mice vaccinated with wild-type E7 DNA. Thus, because of the increase in tumor antigen-specific T-cell immune responses obtained through both enhanced antigen presentation and chemoattraction, vaccination with DNA encoding IP-10 linked to a tumor antigen holds great promise for treating tumors.

Enhancement of DC vaccine potency by activating the PI3K/AKT pathway with a small interfering RNA targeting PTEN.

Dendritic cell (DC)-based cancer vaccines have become important as an immunotherapeutics in generating anti-tumor immune responses. Due to a short lifespan of DCs, however, clinical application of current DC vaccines has been limited. Recently, activation of AKT/protein kinase B (PKB), a major effector of phosphatidylinositol 3-kinase (PI3K), has been reported as a critical factor in both activation and survival of DCs. We here improved the potency of a DC vaccine with a small interfering RNA (siRNA) targeting phosphatase and tensin homologue (PTEN), which is known to be a central negative regulator of the PI3K/AKT signal transduction cascade. Down-regulation of PTEN in DCs resulted in AKT dependent maturation, which in turn caused a significant up-regulation of surface expression in co-stimulatory molecules and the chemokine receptor, CCR7, leading to an increase of in vitro T cell activation activity and in vivo migration to a draining lymph node, respectively. Moreover, these PTEN siRNA-transfected DCs (DC/siPTEN) acquired an increased survival from the apoptotic death caused by GM-CSF deprivation or antigen-specific CD8(+) T cell killing. Most importantly, DC/siPTEN generated more tumor antigen-specific CD8(+) T cells and stronger anti-tumor effects in vaccinated mice than did control DCs (DC/siGFP). Thus, our data indicate that manipulation of the PI3K/AKT pathway via siRNA system could improve the efficacy of a DC-based tumor vaccine.