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Non-Schmid effects in a representative refractory multi-principal element alloy (MPEA), MoNbTi, are investigated using molecular statics (MS) and phase field dislocation dynamics (PFDD). In addition to imposing a statistical distribution for the energetic barrier to slip, incorporating properties of the screw dislocation core is critical in capturing the wide range of MS-predicted non-Schmid effects. PFDD energy terms are enhanced to better capture the varying screw dislocation core-widths under loading as informed by MS. These enhancements demonstrate that incorporating the details of screw dislocation cores, in different chemical environments, has the strongest effect on representing the MS-predicted range of non-Schmid effects.Impact StatementVarying degrees of non-Schmid effects, unique to refractory MPEAs, are studied for the first time using atomistic and mesoscale models and are shown to result from environment-dependent properties of screw dislocation cores.

Abstract Methylation patterns in cell-free DNA (cfDNA) have emerged as a promising genomic feature for detecting the presence of cancer and determining its origin. The purpose of this study was to evaluate the diagnostic performance of methylation-sensitive restriction enzyme digestion followed by sequencing (MRE-Seq) using cfDNA, and to investigate the cancer signal origin (CSO) of the cancer using a deep neural network (DNN) analyses for liquid biopsy of colorectal and lung cancer. We developed a selective MRE-Seq method with DNN learning-based prediction model using demethylated-sequence-depth patterns from 63,266 CpG sites using SacII enzyme digestion. A total of 191 patients with stage I–IV cancers (95 lung cancers and 96 colorectal cancers) and 126 noncancer participants were enrolled in this study. Our study showed an area under the receiver operating characteristic curve (AUC) of 0.978 with a sensitivity of 78.1% for colorectal cancer, and an AUC of 0.956 with a sensitivity of 66.3% for lung cancer, both at a specificity of 99.2%. For colorectal cancer, sensitivities for stages I–IV ranged from 76.2 to 83.3% while for lung cancer, sensitivities for stages I–IV ranged from 44.4 to 78.9%, both again at a specificity of 99.2%. The CSO model's true-positive rates were 94.4% and 89.9% for colorectal and lung cancers, respectively. The MRE-Seq was found to be a useful method for detecting global hypomethylation patterns in liquid biopsy samples and accurately diagnosing colorectal and lung cancers, as well as determining CSO of the cancer using DNN analysis. Trial registration: This trial was registered at ClinicalTrials.gov (registration number: NCT 04253509) for lung cancer on 5 February 2020, https://clinicaltrials.gov/ct2/show/NCT04253509 . Colorectal cancer samples were retrospectively registered at CRIS (Clinical Research Information Service, registration number: KCT0008037) on 23 December 2022, https://cris.nih.go.kr , https://who.init/ictrp . Healthy control samples were retrospectively registered.

The growth of digital media usage has accelerated the development of big data technology. According to the agenda-setting theory, news media inform the public regarding major agendas and business cycles. This study investigated 168,786 news documents from 2016 to 2020 related the South Korea fashion business using Python. A total of 19 topics were extracted through latent Dirichlet allocation and then transformed into structured data using a time series approach to analyze significant changes in trends. The results indicate that major fashion industry topics include business management strategies to increase sales, diversification of the retail structure, influence of CEOs, and merchandise marketing activities. Thereafter, statistically significant hot and cold topics were derived to identify the shifts in topic themes. This study expands the fashion business contexts with agenda-setting theory through big data time series analyses and can be referenced for the government agencies to support fashion industry policies.

One of the remarkable choices for active smart window technology is adopting a metal active layer via reversible metal electrodeposition (RME). As the metal layer efficiently blocks the solar energy gain, even a hundred-nanometer-thick scale, RME-based smart window has great attention. Recent developments are mainly focused on the various cases of electrolyte components and composition meeting technological standards. As metal nanostructures formed through the RME process involve plasmonic phenomena, advanced analysis, including plasmonic optics, which is beyond Beer–Lambert’s law, should be considered. However, as there is a lack of debates on the plasmonic optics applied to RME smart window technology, as research is mainly conducted through an exhaustive process. In this paper, in order to provide insight into the RME-based smart window development and alleviate the unclear part of plasmonic optics applied to the field, finite-difference time-domain electromagnetic simulations are conducted. In total, two extremely low-quality (Cr) and high-quality (Mg) plasmonic materials based on a nanoparticle array are considered as a metal medium. In addition, optical effects caused by the metal active layer, electrolyte, and nanoparticle embedment are investigated in detail. Overall simulations suggest that the effective refractive index is a decisive factor in the performance of RME-based smart windows.

Perovskite solar cells (PSCs) have been significantly improved by utilizing an inorganic hole-transporting layer (HTL), such as nickel oxide. Despite the promising properties, there are still limitations due to defects. Recently, research on self-assembled monolayers (SAMs) is being actively conducted, which shows promise in reducing defects and enhancing device performance. In this study, we successfully engineered a p-i-n perovskite solar cell structure utilizing HC-A1 and HC-A4 molecules. These SAM molecules were found to enhance the grain morphology and uniformity of the perovskite film, which are critical factors in determining optical properties and device performance. Notably, HC-A4 demonstrated superior performance due to its distinct hydrophilic properties with a contact angle of 50.3°, attributable to its unique functional groups. Overall, the HC-A4-applied film exhibited efficient carrier extraction properties, attaining a carrier lifetime of 117.33 ns. Furthermore, HC-A4 contributed to superior device performance, achieving the highest device efficiency of 20% and demonstrating outstanding thermal stability over 300 h.

The goal of this study was to examine the effect of engaging students in socially engaged art (SEA) education to create 3D virtual worlds for fostering creative problem-solving (CPS) skills. The study was conducted with 135 students (aged 16) of boys’ high school in Korea who participated in the SEA program through four stages: Stage 1- appreciation and interpretation of artwork about social issues; Stage 2 - discussion on the potential solution to the selected social issue; Stage 3 - creating a 3D virtual world k to express proposed solutions; and Stage 4 - experiencing and sharing 3D virtual worlds. The following research questions guided the study: (1) What is the effect of SEA education with VR on students’ CPS? (2) How are the students’ CPS as expressed in their artifact (essay and VR work)? (3) What are the relationships between students’ CPS and their artifact (essay and VR work)? For data collection, we administered the instrument to measure students’ CPS skills in three areas (higher-order thinking, divergent thinking, and problem-solving) and also evaluated student essays and VR work to examine CPS specific to art education. Overall, the results indicate that the students improved their CPS skills significantly after participating in the SEA program. The CPS skills had significant relationships with the essay scores, whereas only one significant relationship was found between CPS and VR work. This study provides empirical findings concerning how the formal school curriculum can introduce students to an authentic context concerning social issues through artmaking practices with VR.

Abstract After the development of Web 2.0 and social networks, analyzing consumers’ responses and opinions in real-time became profoundly important to gain business insights. This study aims to identify consumers’ preferences and perceptions of genderless fashion trends by text-mining, Latent Dirichlet Allocation-based topic modeling, and time-series linear regression analysis. Unstructured text data from consumer-posted sources, such as blogs and online communities, were collected from January 1, 2018 to December 31, 2020. We examined 9722 posts that included the keyword “genderless fashion” with Python 3.7 software. Results showed that consumers were interested in fragrances, fashion, and beauty brands and products. In particular, 18 topics were extracted: 13 were classified as fashion categories and 5 were derived from beauty and fragrance sectors. Examining the genderless fashion trend development among consumers from 2018 to 2020, “perfume and scent” was revealed as the hot topic, whereas “bags,” “all-in-one skin care,” and “set-up suit” were cold topics, declining in popularity among consumers. The findings contribute to contemporary fashion trends and provide in-depth knowledge about consumers’ perceptions using big data analysis methods and offer insights into product development strategies.

Brain aging is a complex biological process that is affected by both genetic background and environment. The transcriptomic analysis of aged human and rodent brains has been applied to identify age-associated molecular and cellular processes for which intervention could possibly restore declining brain functions induced by aging. However, whether these age-associated genetic alterations are indeed involved in the healthy aging of the brain remains unclear. We herein characterized a naturally occurring, extremely long-lived (34 months of age) but healthy mouse group retaining well-preserved motor functions. Strikingly, these long-lived mice maintained tyrosine hydroxylase expression and dopaminergic fiber densities, even in the presence of persistent neuroinflammation and expression of aging markers. Combined with Endeavor gene prioritization, we identified the following midbrain-specific longevity-associated genes in the midbrain of these mice: aimp2, hexb, cacybp, akt2, nrf1, axin1, wwp2, sp2, dnajb9, notch, traf7, and lrp1. A detailed biochemical analysis of the midbrain of these long-lived mice confirmed the increased expression of Nrf1 and the activation of Akt1 and 2. Interestingly, dopaminergic neuroprotective and age-associated E3 ubiquitin ligase parkin expression was retained at high levels in the aforementioned midbrains, possibly supporting the suppression of its toxic substrates AIMP2 and PARIS. In contrast, the 24-month-old mice with dopaminergic neurite deficits failed to maintain parkin expression in the midbrain. AIMP2-induced cytotoxicity, mitochondrial stress, and neurite toxicity can be prevented by overexpression of parkin, Akt1, and Nrf1 in SH-SY5Y and PC12 cells, and basal expression of parkin, Akt1, and Nrf1 is required for maintenance of mitochondrial function and neurite integrity in PC12 cells. Taken together, this longevity-associated pathway could be a potential target of intervention to maintain nigrostriatal dopaminergic fibers and motor ability to ensure healthy longevity.

The aggregation of aminoacyl transfer RNA synthetase complex-interacting multifunctional protein-2 (AIMP2) accelerates α-synuclein aggregation via direct interaction, leading to enhanced dopaminergic neurotoxicity in Parkinson’s disease (PD). Thus, it would be beneficial to prevent AIMP2 aggregation to suppress α-synucleinopathy in PD. In this study, we screened small compounds that could inhibit the in vitro aggregation of AIMP2 using a 1909 small-compound library. The AIMP2 inhibitors (SAI-04, 06, and 08) with the most effective inhibition of AIMP2 aggregation bind to AIMP2, disaggregate the pre-formed AIMP2 aggregates, and prevented AIMP2/α-synuclein coaggregation and cytotoxicity in SH-SY5Y cells. Moreover, AIMP2 inhibitors prevented α-synuclein preformed fibril (PFF)-induced pathological AIMP2 aggregation in both mouse cortical and embryonic stem cell-derived human dopaminergic neurons, thereby blocking PFF-induced α-synuclein aggregation and neurotoxicity. Collectively, our results suggest that the use of brain-permeable AIMP2 aggregation inhibitors may serve as an effective therapeutic strategy for α-synucleinopathy in PD.

Abstract Flexible displays on a polyimide (PI) substrate are widely regarded as a promising next-generation display technology due to their versatility in various applications. Among other bendable materials used as display panel substrates, PI is especially suitable for flexible displays for its high glass transition temperature and low coefficient of thermal expansion. PI cured under various temperatures (260 °C, 360 °C, and 460 °C) was implemented in metal–insulator–metal (MIM) capacitors, amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFT), and actual display panels to analyze device stability and panel product characteristics. Through electrical analysis of the MIM capacitor, it was confirmed that the charging effect in the PI substrates intensified as the PI curing temperature increased. The threshold voltage shift (ΔVth) of the samples was found to increase with rising curing temperature under negative bias temperature stress (NBTS) due to the charging effect. Our analyses also show that increasing ΔVth exacerbates the image sticking phenomenon observed in display panels. These findings ultimately present a direct correlation between the curing temperature of polyimide substrates and the panel image sticking phenomenon, which could provide an insight into the improvement of future PI-substrate-based displays.

Abstract In this paper, we investigate the Vth shift of p-type LTPS TFTs fabricated on a polyimide (PI) and glass substrate considering charging phenomena. The Vth of the LTPS TFTs with a PI substrate positively shift after a bias temperature stress test. However, the Vth with a glass substrate rarely changed even with increasing stress. Such a positive Vth shift results from the negative charging of fluorine stemmed from the PI under the gate bias. In fact, the C–V characterization on the metal–insulator-metal capacitor reveals that charging at the SiO2/PI interface depends on the applied gate bias and the PI material, which agrees well with the TCAD simulation and SIMS analyses. As a result, the charging at the SiO2/PI interface contributes to the Vth shift of the LTPS TFTs leading to image sticking.

Abstract Background The microbiota of the lower respiratory tract in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) has not been fully evaluated. We explored the role of the lung microbiota in NTM-PD by analyzing protected specimen brushing (PSB) and bronchial washing samples from patients with NTM-PD obtained using a flexible bronchoscope. Results Bronchial washing and PSB samples from the NTM-PD group tended to have fewer OTUs and lower Chao1 richness values compared with those from the control group. In both bronchial washing and PSB samples, beta diversity was significantly lower in the NTM-PD group than in the control group (P = 2.25E-6 and P = 4.13E-4, respectively). Principal component analysis showed that the PSBs and bronchial washings exhibited similar patterns within each group but differed between the two groups. The volcano plots indicated differences in several phyla and genera between the two groups. Conclusions The lower respiratory tract of patients with NTM-PD has a unique microbiota distribution that is low in richness/diversity.

The energetic sulfide vapor process on colloidal indium arsenide (InAs) quantum dots (QDs) for integrated optoelectronic devices is demonstrated. X‐ray photoemission spectroscopy supports the presence of sulfur on QD surface, which increases the air stability, and ultraviolet photoemission spectroscopy and field‐effect transistor analysis confirm n‐type charge transport of corresponding QD films with higher electron mobilities. Photoconductivity of the same devices in near‐infrared wavelength shows gate bias‐dependent recombination of photogenerated carriers, coming from charge accumulation and depletion transition of QD channels. The synergetic approach of the vapor process on colloidal QD solids opens a promising opportunity for scalable and complementary metal‐oxide semiconductor‐compatible optoelectronic devices.

Previous evidence suggests a potential dual impact of aging and vitamin B6 (B6) deficiency on polyunsaturated fatty acid (PUFA) metabolism; gender may influence PUFA biosynthesis. Perturbation of PUFA compositions during B6 deficiency could be linked to age-related health outcomes. However, little is known about the interrelationships between vitamin B6, PUFA, and gender in the older population. Therefore, we investigated whether gender-specific associations of B6 intake and plasma pyridoxal 5’-phosphate (PLP) concentration, respectively, with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA) existed in older adults. We further examined the relationships of adequate B6 status (PLP ≥ 20 nmol/L) with high (above median) plasma PUFA relative to deficient B6 status. This cross-sectional study analyzed 461 participants aged ≥60 years from NHANES 2003–2004. Nutrient intakes were assessed using two 24-h recalls and supplement questionnaires. PLP and PUFA concentrations were measured. Multivariate linear regression assessed the association of B6 intake and PLP with PUFA; multivariate logistic regression evaluated the relationship of adequate B6 status with high plasma PUFA, adjusting for demographic, socioeconomic, and dietary factors; physical activity; smoking; alcohol; medication; and BMI. There were interactions between gender and B6 intake on EPA (P-interaction = 0.008) and AA (P-interaction = 0.004) only, whereas no interaction existed between gender and PLP on PUFA. PLP was directly associated with EPA (β = 0.181, P = 0.002), DHA (β = 0.109, P = 0.005), EPA + DHA (β = 0.14, P = 0.002), EPA/AA (β = 0.186, P = 0.004), and (EPA + DHA)/AA (β = 0.13, P = 0.026). The odds of having high plasma EPA (adjusted (a) OR: 2.03, P = 0.049) and EPA/AA (aOR: 3.83, P < 0.0001) were greater in those with adequate B6 status compared to those with deficient B6 status. In conclusion, in US older adults, a higher PLP level was associated with a greater level of EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA. Adequate B6 status was associated with high EPA and EPA/AA status. These findings suggest that sufficient vitamin B6 status may positively influence PUFA metabolism in older adults.

In this paper, the dependence of threshold voltage (Vth) changes to amorphous-indium gallium zinc oxide (a-IGZO) thin film transistors (TFTs) under positive bias light illumination (PBIS) on the height of the conduction band offset was studied. Using SiO2, HfO2, and Al2O3 as gate dielectrics, three different types of a-IGZO TFTs were used in the experiment. Electrical parameters and the density of states of each TFT were measured. Of the devices studied, the interface characteristics between the a-IGZO and the gate dielectric were the best using SiO2 and the worst using Al2O3. HfO2 had the smallest conduction band offsets (CBO) of 2.26 eV. We also performed PBS and PBIS evaluation to confirm the stability of TFTs. The Vth shift in the three samples was insignificant under PBS, but the Vth shifts occurred under PBIS in the order of HfO2, Al2O3, and SiO2. The interfacial characteristics of a-IGZO and the dielectric did not change after PBIS in all three devices; the lower the CBO height, the greater the Vth shift after PBIS. The predominant cause of the Vth shift under PBIS is the accumulation of injected photoelectrons that have sufficient energy to tunnel the CBO barrier into the gate dielectric by positive gate bias.

Abstract Dysfunctional parkin due to mutations or post-translational modifications contributes to dopaminergic neurodegeneration in Parkinson’s disease (PD). Overexpression of parkin provides protection against cellular stresses and prevents dopamine cell loss in several PD animal models. Here we performed an unbiased high-throughput luciferase screening to identify chemicals that can increase parkin expression. Among promising parkin inducers, hydrocortisone possessed the most favorable profiles including parkin induction ability, cell protection ability, and physicochemical property of absorption, distribution, metabolism, and excretion (ADME) without inducing endoplasmic reticulum stress. We found that hydrocortisone-induced parkin expression was accountable for cell protection against oxidative stress. Hydrocortisone-activated parkin expression was mediated by CREB pathway since gRNA to CREB abolished hydrocortisone’s ability to induce parkin. Finally, hydrocortisone treatment in mice increased brain parkin levels and prevented 6-hydroxy dopamine induced dopamine cell loss when assessed at 4 days after the toxin’s injection. Our results showed that hydrocortisone could stimulate parkin expression via CREB pathway and the induced parkin expression was accountable for its neuroprotective effect. Since glucocorticoid is a physiological hormone, maintaining optimal levels of glucocorticoid might be a potential therapeutic or preventive strategy for Parkinson’s disease.

Vitamin B6-restricted diets and low plasma pyridoxal 5′-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20–59 years; 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires; plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (β) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (β = 0.138, b = 0.104, p = 0.0004), DHA (β = 0.101, b = 0.058, p = 0.036), EPA + DHA (β = 0.125, b = 0.073, p = 0.005), EPA/AA (β = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (β = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.

Limited knowledge is available on the regeneration of Korean fir (Abies koreana Wilson), an endemic plant species, growing on the upper part of Mt. Hallasan, a volcanic mountain, located in the central part of Jeju Island, Korea. A forest stand with the size of 1 ha dominated by Korean fir trees was established and all the trees with DBH 2 cm or larger were mapped and surveyed. Initial analysis indicated that the numbers of saplings with their DBHs between 2 cm and 10 cm were very small and that there was a big gap in the frequency of the number of saplings regenerated from the forest stand. It seems clear that the regeneration of the Korean fir trees was disturbed for longer than the last two decades, potentially by the browsing of the seedlings by ungulate including Siberian roe deer and by the physical hindrance of the dwarf bamboo to the development of the saplings of the Korean fir. Urgent measures and extensive studies are needed to promote the natural regeneration of the tree species on the dynamics of the forest regeneration and the mechanism of forest development of the forests on the Mt. Hallasan, Jeju Island, Korea.

The progressive neurodegeneration in Parkinson’s disease (PD) is accompanied by neuroinflammation and endothelial vascular impairment. Although the vitamin D receptor (VDR) is expressed in both dopamine neurons and brain endothelial cells, its role in the regulation of endothelial biology has not been explored in the context of PD. In a 6-hydroxydopamine (6-OHDA)-induced PD mouse model, we observed reduced transcription of the VDR and its downstream target genes, CYP24 and MDR1a. The 6-OHDA-induced transcriptional repression of these genes were recovered after the VDR ligand—1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment. Similarly, reduced vascular protein expression of P-glycoprotein (P-gp), encoded by MDR1a, after 6-OHDA administration was reversed by 1,25(OH)2D3. Moreover, marked reduction of endothelial P-gp expression with concomitant α-synuclein aggregation was found in a combinatorial AAV-αSyn/αSyn preformed fibril (PFF) injection mouse model and postmortem PD brains. Supporting the direct effect of α-synuclein aggregation on endothelial biology, PFF treatment of human umbilical vein endothelial cells (HUVECs) was sufficient to induce α-synuclein aggregation and repress transcription of the VDR. PFF-induced P-gp downregulation and impaired functional activity in HUVECs completely recovered after 1,25(OH)2D3 treatment. Taken together, our results suggest that a dysfunctional VDR-P-gp pathway could be a potential target for the maintenance of vascular homeostasis in PD pathological conditions.

The increasing lifespan in developed countries results in age-associated chronic diseases. Biological aging is a complex process associated with accumulated cellular damage by environmental or genetic factors with increasing age. Aging results in marked changes in brain structure and function. Age-related neurodegenerative diseases and disorders (NDDs) represent an ever-growing socioeconomic challenge and lead to an overall reduction in quality of life around the world. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are most common degenerative neurological disorders of the central nervous system (CNS) in aging process. The low levels of acetylcholine and dopamine are major neuropathological feature of NDDs in addition to oxidative stress, intracellular calcium ion imbalance, mitochondrial dysfunction, ubiquitin-proteasome system impairment and endoplasmic reticulum stress. Current treatments minimally influence these diseases and are ineffective in curing the multifunctional pathological mechanisms. Synthetic neuroprotective agents sometimes have negative reactions as an adverse effect in humans. Recently, numerous ethnobotanical studies have reported that herbal medicines for the treatment or prevention of NDDs are significantly better than synthetic drug treatment. Medicinal herbs have traditionally been used around the world for centuries. Radix Glycyrrhizae (RG) is the dried roots and rhizomes of Glycyrrhiza uralensis or G. glabra or G. inflata from the Leguminosae/Fabaceae family. It has been used for centuries in traditional medicine as a life enhancer, for the treatment of coughs and influenza, and for detoxification. Diverse chemical constituents from RG have reported including flavanones, chalcones, triterpenoid saponins, coumarines, and other glycosides. Among them, flavanone liquiritigenin (LG) and its precursor and isomer chalcone isoliquiritigenin (ILG) are the main bioactive constituents of RG. In the present review, we summarize evidence in the literature on the structure and phytochemical properties and pharmacological applications of LG and ILG in age-related diseases to establish new therapeutics to improve human health and lifespan.

In 2013, the epidemics of pine wilt disease caused by the pine wood nematodes (Bursaphelenchus xylophilus) resulted in damages to the forests of black pine (Pinus thunbergii Parl.) trees in Jeju Island, Korea. Among the affected trees, an old black pine tree at Cave Temple on Mt. Sanbangsan was included and died due to the prevalence of pine wilt disease. The tree was on Mt. Sanbangsan, which was designated as a National Scenic Place with the Number 77 and was believed to be more than 400 years old in age. By examining the disc of the tree stem obtained from the height of 2 m, we counted the tree rings from 4 different directions and cross-dated the readings by comparing the records of drought simulated from the BROOK Model. Our analysis indicates that the tree seems to have grown since late 1860s. Contrary to the belief of the general public, we can conclude that the age of the tree was estimated to be at maximum 150 years, which means that it was not the same old tree as was shown in the painting of the Tam-Ra-Sun-Ryeok-Do (an old painting book for the Inspection Tour of Jeju Island) published in 1702. Discussion was extended to the life history of the tree in growth and leaning and the measures to protect the tree species from the damages of the pine wilt disease caused by pine wood nematodes.

A solitary skin metastasis is a rare manifestation of papillary thyroid carcinoma (PTC). A 55-year-old woman presented with a movable subcutaneous nodule in her anterior neck for several months. Three years ago, she underwent total thyroidectomy and remnant ablation for classical PTC (pT3N0M0) and was under thyroxine suppression therapy without any evidence of recurrent disease. The subcutaneous nodule was 0.4 cm in size, firm, and movable without any change in the overlying skin. Recurrent PTC was confirmed after excision biopsy. Eight months after, she got a new nodule along the previous excision site. After punch biopsy, metastatic PTC was confirmed in the deep dermis and was re-excised with a clear resection margin. This is the first report of a case of solitary skin metastasis of PTC in Korea. Although solitary skin metastasis of PTC is rare, it should be considered in patients with a skin nodule.

The motor and nonmotor symptoms of Parkinson’s disease (PD) correlate with the formation and propagation of aberrant α-synuclein aggregation. This protein accumulation is a pathological hallmark of the disease. Our group recently showed that peucedanocoumarin III (PCIII) possesses the ability to disaggregate β sheet aggregate structures, including α-synuclein fibrils. This finding suggests that PCIII could be a therapeutic lead compound in PD treatment. However, the translational value of PCIII and its safety information have never been explored in relevant animal models of PD. Therefore, we first designed and validated a sequence of chemical reactions for the large scale organic synthesis of pure PCIII in a racemic mixture. The synthetic PCIII racemate facilitated clearance of repeated β sheet aggregate (β23), and prevented β23-induced cell toxicity to a similar extent to that of purified PCIII. Given these properties, the synthetic PCIII’s neuroprotective function was assessed in 6-hydroxydopamine (6-OHDA)-induced PD mouse models. The PCIII treatment (1 mg/kg/day) in a 6-OHDA-induced PD mouse model markedly suppressed Lewy-like inclusions and prevented dopaminergic neuron loss. To evaluate the safety profiles of PCIII, high dose PCIII (10 mg/kg/day) was administered intraperitoneally to two-month-old mice. Following 7 days of PCIII treatment, PCIII distributed to various tissues, with substantial penetration into brains. The mice that were treated with high dose PCIII had no structural abnormalities in the major organs or neuroinflammation. In addition, high dose PCIII (10 mg/kg/day) in mice had no adverse impact on motor function. These findings suggest that PCIII has a relatively high therapeutic index. Given the favorable safety features of PCIII and neuroprotective function in the PD mouse model, it may become a promising disease-modifying therapy in PD to regulate pathogenic α-synuclein aggregation.

Ring finger protein 146 (RNF146) is an E3 ubiquitin ligase whose activity prevents poly (ADP-ribose) polymerase 1 (PARP1)-dependent neurodegeneration in Parkinson’s disease (PD). Previously, we reported that rhododendrin is a chemical inducer that increases RNF146 expression. However, the molecular mechanism of rhododendrin-induced RNF146 expression is largely unknown and its translational application for the treatment of Parkinson’s disease remains unexplored. Here we found that rhododendrin increased RNF146 expression via estrogen receptor β (ERβ) activation. Rhododendrin stimulated ERβ nuclear translocation and binding to the RNF146 promoter, thereby enhancing its transcription. Rhododendrin is cytoprotective against 6-hydroxydopamine (6-OHDA)-induced cell death, which is largely dependent on ERβ activity and RNF146 expression. Finally, we demonstrated that rhododendrin treatment resulted in RNF146 expression in dopaminergic neurons in mice. Moreover, dopaminergic neuron viability was markedly enhanced by pretreatment with rhododendrin in 6-OHDA-induced mouse models for PD. Our findings indicate that estrogen receptor activation plays a neuroprotective role and that rhododendrin could be a potential therapeutic agent in preventing PARP1-dependent dopaminergic cell loss in PD.

Rice blast fungus, Magnaporthe oryzae, inflicts serious damage to global rice production. Due to high variability of this fungal pathogen, resistance of newly-released rice cultivars is easily broken down. To understand the population structure of M. oryzae, we analyzed the genetic diversity of the Korean population using multilocus microsatellite typing. Eleven microsatellite markers were applied to the population of 190 rice isolates which had been collected in Korea for two decades since the 1980’s. Average values of gene diversity and allele frequency were 0.412 and 6.5, respectively. Comparative analysis of the digitized allele information revealed that the Korean population exhibited a similar level of allele diversity to the integrated diversity of the world populations, suggesting a particularly high diversity of the Korean population. Therefore, these microsatellite markers and the comprehensive collection of field isolates will be useful genetic resources to identify the genetic diversity of M. oryzae population.

Background and Objective Cardiac autonomic regulation is altered in psychophysiological insomnia. We evaluated whether successful non-pharmacological treatment for psychophysiological insomnia could stabilize cardiac autonomic regulation. Methods Subjects were 26 patients with psychophysiological insomnia who underwent four sessions of non-pharmacological treatment. We measured subjects’ heart rate variability (HRV) at baseline and post-treatment. Based on the post-treatment Insomnia Severity Index (ISI) score, we categorized subjects into responder (n = 16, post-ISI < 8) and non-responder (n = 10) groups. Results At baseline, we found no significant differences between responder and non-responder groups in age, sex, body mass index, insomnia severity, and features of HRV time and frequency domains. In the responders group, we observed significant increases in the standard deviation of the normal sinus to normal sinus interval (SDNN) (p = 0.02), the proportion of the number of interval differences of successive normal sinus to normal sinus intervals greater than 50 ms by the total number of normal sinus to normal sinus intervals (pNN50) (p = 0.02), total power (p < 0.01), and very low frequency (p = 0.02) and a significant decrease in low frequency (p = 0.04) after successful non-pharmacological treatment for insomnia. However, in the non-responders group, there were no significant changes in HRV features after treatment. Conclusions The successful non-pharmacological treatment of insomnia may reduce the risk of cardiovascular complications in patients with psychophysiological insomnia.

Aging is considered the major risk factor for neurodegenerative diseases including Parkinson’s disease (PD). Telomere shortening is associated with cellular senescence. In this regard, pharmacological or genetic inhibition of telomerase activity has been used to model cellular aging. Here, we employed CRISPR-Cas9 technology to instantly remove the telomere to induce aging in a neuroblastoma cell line. Expression of both Cas9 and guide RNA targeting telomere repeats ablated the telomere, leading to retardation of cell proliferation. Instant deletion of telomere in SH-SY5Y cells impaired mitochondrial function with diminished mitochondrial respiration and cell viability. Supporting the pathological relevance of cell aging by CRISPR-Cas9 mediated telomere removal, alterations were observed in the levels of PD-associated proteins including PTEN-induced putative kinase 1, peroxisome proliferator-activated receptor γ coactivator 1-α, nuclear respiratory factor 1, parkin, and aminoacyl tRNA synthetase complex interacting multifunctional protein 2. Significantly, α-synuclein expression in the background of telomere removal led to the enhancement of protein aggregation, suggesting positive feed-forward interaction between aging and PD pathogenesis. Collectively, our results demonstrate that CRISPR-Cas9 can be used to efficiently model cellular aging and PD.

Cu/Zn superoxide dismutase (Sod1) is a highly conserved and abundant antioxidant enzyme that detoxifies superoxide (O2 •-) by catalyzing its conversion to dioxygen (O2) and hydrogen peroxide (H2O2). Using Saccharomyces cerevisiae and mammalian cells, we discovered that a major aspect of the antioxidant function of Sod1 is to integrate O2 availability to promote NADPH production. The mechanism involves Sod1-derived H2O2 oxidatively inactivating the glycolytic enzyme, GAPDH, which in turn reroutes carbohydrate flux to the oxidative phase of the pentose phosphate pathway (oxPPP) to generate NADPH. The aerobic oxidation of GAPDH is dependent on and rate-limited by Sod1. Thus, Sod1 senses O2 via O2 •- to balance glycolytic and oxPPP flux, through control of GAPDH activity, for adaptation to life in air. Importantly, this mechanism for Sod1 antioxidant activity requires the bulk of cellular Sod1, unlike for its role in protection against O2 •- toxicity, which only requires <1% of total Sod1. Using mass spectrometry, we identified proteome-wide targets of Sod1-dependent redox signaling, including numerous metabolic enzymes. Altogether, Sod1-derived H2O2 is important for antioxidant defense and a master regulator of metabolism and the thiol redoxome. [ABSTRACT FROM AUTHOR]

Efficient multiphase green phosphors based on strontium thiogallate are prepared by solid state reaction with carbon as a reduction atmosphere. The study has shown that the multiphase green phosphor based on strontium thiogallate can be used for solid state lighting and display devices with higher intensity and better chromaticity coordinates in comparison with the known commercial phosphors.

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying K+ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants. [ABSTRACT FROM AUTHOR]

Aggregates of disease-causing proteins dysregulate cellular functions, thereby causing neuronal cell loss in diverse neurodegenerative diseases. Although many in vitro or in vivo studies of protein aggregate inhibitors have been performed, a therapeutic strategy to control aggregate toxicity has not been earnestly pursued, partly due to the limitations of available aggregate models. In this study, we established a tetracycline (Tet)-inducible nuclear aggregate (β23) expression model to screen potential lead compounds inhibiting β23-induced toxicity. Highthroughput screening identified several natural compounds as nuclear β23 inhibitors, including peucedanocoumarin III (PCIII). Interestingly, PCIII accelerates disaggregation and proteasomal clearance of both nuclear and cytosolic β23 aggregates and protects SH-SY5Y cells from toxicity induced by β23 expression. Of translational relevance, PCIII disassembled fibrils and enhanced clearance of cytosolic and nuclear protein aggregates in cellular models of huntingtin and α-synuclein aggregation. Moreover, cellular toxicity was diminished with PCIII treatment for polyglutamine (PolyQ)-huntingtin expression and α-synuclein expression in conjunction with 6-hydroxydopamine (6-OHDA) treatment. Importantly, PCIII not only inhibited α-synuclein aggregation but also disaggregated preformed α-synuclein fibrils in vitro. Taken together, our results suggest that a Tet-Off β23 cell model could serve as a robust platform for screening effective lead compounds inhibiting nuclear or cytosolic protein aggregates. Brain-permeable PCIII or its derivatives could be beneficial for eliminating established protein aggregates. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the effectiveness of using multi-functional correlation nanoscopy in investigating the optical and structural properties of nanostructures.

Conventional platinum (Pt) or emerging materials for the counter electrodes (CEs) of dye-sensitized solar cells (DSSCs) have been fabricated on a fluorine-doped tin oxide (FTO) substrate. In this study, carbon paper with three-dimensional (3D) carbon fiber networks, which is highly porous, but has sufficient space for efficient transportation of electrolytes, is used in replace of the conventional heavy, rigid and expensive FTO/glass substrate in DSSC CEs. To prove the advantages of these highly conductive carbon paper electrodes, a thin poly(3,4-ethylenedioxythiophene) (PEDOT) film is uniformly coated on the surface of 3D carbon paper via a chemical polymerization method. The catalytic properties of the PEDOT/carbon paper as the CE in a DSSC are studied using cyclic voltammetry,J-V, and IPCE measurements. Interestingly, the PEDOT/carbon paper CE exhibits better functionality as a CE for tri-iodide reduction as compared to conventional Pt/FTO-based CEs. The controlled DSSC with a PEDOT/carbon paper CE exhibits a power conversion efficiency of 8.05% under 100 mW·cm-2illumination, which is higher than that of conventional DSSCs with standard Pt/FTO CEs (7.41%). [ABSTRACT FROM AUTHOR]

Protonic currents play a vital role in electrical signalling in living systems. It has been suggested that succinoglycan plays a specific role in alfalfa root nodule development, presumably acting as the signaling molecules. In this regard, charge transport and proton dynamics in the biopolymer exopolysaccharide succinoglycan have been studied by means of electrical measurements and nuclear magnetic resonance (NMR) spectroscopy. In particular, a dielectric dispersion in the system has revealed that the electrical conduction is protonic rather electronic. Besides, our laboratory- and rotating-frame ¹H NMR measurements have elucidated the nature of the protonic conduction, activation of the protonic motion being associated with a glass transition. [ABSTRACT FROM AUTHOR]

Increased adipose tissue positively correlates with circulating inflammatory cytokines such as IL-6. We previously reported that adipose stem cells from genetically obese ob/ob mice produce significantly higher levels of IL-6 compared with other cell types such as adipocytes and macrophages within adipose tissue. We also demonstrated that (n-3) PUFA have anti-inflammatory effects on adipocyte IL-6 secretion. Based on these findings, we hypothesized that EPA 120:5 (n-3)] and stearidonic acid ESDA, 18:4 (n-3)1 would decrease LPS (200 μg/L)-induced IL-6 secretion and IL-6 mRNA content in the adipose stem cells. SDA (100 μmol/L) and EPA (100 μmol/L) significantly reduced LPS-induced IL-S secretion and decreased I L-6 mRNA expression. To determine the underlying intracellular mechanisms, we tested whether LPS-induced Toll-like-receptor (TLR) 4 and TLR2 expression were modulated by these fatty acids using Western-blot analysis. EPA and SDA suppressed LPS-induced TLR2 but not TLR4 protein expression in the adipose stem cells. Furthermore, SDA and EPA significantly lowered the activation and translocation of NE-κB, a TLR2 downstream signaling target, while protein expression of extracellular signal-regulated kinases-1/2 were unaffected. Collectively, our results suggest that EPA and SDA inhibit [PS-induced l[-6 secretion and IL-6 mRNA expression in the adipose stem cells by decreasing TRL2-mediated signaling pathways. [ABSTRACT FROM AUTHOR]

Tea catechin is one of the compounds that are closely related to obesity and insulin sensitivity. In order to determine the effect of catechin on adipocyte differentiation, we treated 3T3-L1 preadipocytes with different kinds of catechins. Our results showed that catechins, especially epigallocatechin gallate (EGCG), significantly reduced intracellular lipid accumulation and repressed the activity of glycerol-3-phosphate dehydrogenase, an enzyme involved in lipid synthesis. Furthermore, glucose and fatty acid transport were also suppressed by catechin. We then analyzed the activity of transcription factors—forkhead transcription factor class O1 (FoxO1) and sterol regulatory element-binding protein-1c (SREBP1c)—which are involved in adipocyte differentiation and lipid synthesis, respectively. The transcriptional activities of both these factors significantly decreased by EGCG. Western blot analysis revealed that EGCG induced the insulin signal-mediated phosphorylation of FoxO1 (Thr24, Ser256). These results suggest that EGCG suppresses the differentiation of adipocytes through the inactivation of FoxO1 and SREBP1c. [ABSTRACT FROM AUTHOR]

A cluster of oligonucleotide repeat sequences was identified that is linked to the melon ( Cucumis melo L.) andromonoecious ( a) locus, which controls andromonoecy. Six different repeat units, ranging from 11 to 49 base pairs, were clustered within a 0.6-kb intergenic region. The number of repeat units varied from two to six. After sequence analysis of diverse melon germplasms, four haplotypes of this cluster were identified. Length variations among the four haplotypes resulted from insertion or deletion of repeat sequences. Particularly, a tandem array of six repeats of 21 nucleotides was a hotspot for insertion/deletion mutations. A simple PCR-based marker was developed to identify haplotypes of this cluster based on the length polymorphism. In practice, this marker was successfully used in genetic purity tests of melon F1 hybrid cultivars. Four self-pollinated contaminants, which were confirmed by phenotypic examination in grow-out tests, were easily discriminated from 99 F1 hybrid individuals. In addition, the genetic distance between this marker and the andromonoecious ( a) locus was calculated as 7.9 cM, after analyzing melon F2 populations originating from a cross between monoecious and andromonoecious parental lines. Therefore, this marker will be useful as a recombinant selection marker in marker-assisted backcrossing of monoecy in melon breeding programs. [ABSTRACT FROM AUTHOR]

A male-sterile (MS) radish ( Raphanus sativus L.) was found in an accession collected from Uzbekistan. Unlike Ogura MS radishes in which no pollen grain is typically visible during anthesis, a small number of pollen grains stuck together in the dehiscing anthers was observed in the newly identified MS radish. Fluorescein diacetate tests and scanning electron micrographs showed that pollen grains in the new MS radish were severely deformed and non-viable. Cytological examination of pollen development stages showed a clear difference in the defective stage from that seen in Ogura male-sterility. Reciprocal cross-pollination with diverse male-fertile lines indicated that pollen grains of the new MS radish were completely sterile, and the female organs were fully fertile. When the new MS radish and Ogura MS lines were cross-pollinated with a set of eight breeding lines, all F1 progeny originating from crosses with the new MS radish were male-sterile. In contrast, most of the F1 progeny resulting from crosses with Ogura MS lines were male-fertile. These results demonstrated that factors associated with induction of the newly identified male-sterility are different from those of Ogura male-sterility. The lack of restorer lines for the newly identified male-sterility led us to predict that it might be a complete cytoplasmic male-sterility without restorer-of-fertility genes in nuclear genomes. However, cross-pollination with more diverse radish germplasm identified one accession introduced from Russia that could completely restore fertility, proving the existence of restorer-of-fertility gene(s) for the new male-sterility. Meanwhile, the PCR amplification profile of molecular markers for the classification of radish mitochondrial genome types revealed that the new MS radish contained a novel mitotype. [ABSTRACT FROM AUTHOR]

Studies showed that monocyte chemotactic protein-1 (MCP-1) concentrations are increased in obesity. In our current study, we demonstrate that plasma MCP-1 level in leptin-deficient ob/ob mice is significantly higher than in lean mice. Furthermore, we determined that basal adipose tissue MCP-1 mRNA levels are significantly higher in ob/ob mice compared with lean mice. To determine the mechanisms underlying obesity-associated increases in plasma and adipose tissue MCP-1 levels, we determined adipose tissue cell type sources of MCP-1 production. Our data show that adipose tissue stem cells (CD34+), macrophages (F4/80+), and stromal vascular fraction (SVF) cells express significantly higher levels of MCP-l compared with adipocytes under both basal and lipopolysaccharide (LPS)-stimulated conditions. Furthermore, basal and LPS-induced MCP-1 secretion levels were the same for both adipose F4/80+ and CD34+ cells, whereas adipose CD34+ cells have twofold higher cell numbers (30% of total SVF cells) compared with F4/80+ macrophages (15%). Our data also show that CD34+ cells from visceral adipose tissue depots secrete significantly higher levels of MCP-1 ex vivo when compared with CD34+ cells from subcutaneous adipose tissue depots. Taken together, our data suggest that adipose CD34+ stem cells may play an important role in obesity-associated increases in plasma MCP-1 levels. [ABSTRACT FROM AUTHOR]

Protoheme (hereafter referred to as heme) is an essential cellular cofactor and signaling molecule that is also potentially cytotoxic. To mitigate heme toxicity, heme synthesis and degradation are tightly coupled to heme utilization in order to limit the intracellular concentration of "free" heme. Such a model, however, would suggest that a readily accessible steady-state, bioavailable labile heme (LH) pool is not required for supporting heme-dependent processes. Using the yeast Saccharomyces cerevisiae as a model and fluorescent heme sensors, site-specific heme chelators, and molecular genetic approaches, we found here that 1) yeast cells preferentially use LH in heme-depleted conditions; 2) sequestration of cytosolic LH suppresses heme signaling; and 3) lead (Pb2+) stress contributes to a decrease in total heme, but an increase in LH, which correlates with increased heme signaling. We also observed that the proteasome is involved in the regulation of the LH pool and that loss of proteasomal activity sensitizes cells to Pb2+ effects on heme homeostasis. Overall, these findings suggest an important role for LH in supporting heme-dependent functions in yeast physiology. [ABSTRACT FROM AUTHOR]

Mechanistic details of intramembrane aspartyl protease (IAP) chemistry, which is central to many biological and pathogenic processes, remain largely obscure. Here, we investigated the in vitro kinetics of a microbial intramembrane aspartyl protease (mIAP) fortuitously acting on the renin substrate angiotensinogen and the C-terminal transmembrane segment of amyloid precursor protein (C100), which is cleaved by the presenilin subunit of γ-secretase, an Alzheimer disease (AD)-associated IAP. mIAPvariants with substitutions in active-site and putative substrate- gating residues generally exhibit impaired, but not abolished, activity toward angiotensinogen and retain the predominant cleavage site (His-Thr). The aromatic ring, but not the hydroxyl substituent, within Tyr of the catalytic Tyr-Asp (YD) motif plays a catalytic role and the hydrolysis reaction incorporates bulk water as in soluble aspartyl proteases. mIAP hydrolyzes the transmembrane region of C100 at two major presenilin cleavage sites, one corresponding to the AD-associated Aβ42 peptide (Ala-Thr) and the other to the non-pathogenic AMechanistic details of intramembrane aspartyl protease (IAP) chemistry, which is central to many biological and pathogenic processes, remain largely obscure. Here, we investigated the in vitro kinetics of a microbial intramembrane aspartyl protease (mIAP) fortuitously acting on the renin substrate angiotensinogen and the C-terminal transmembrane segment of amyloid precursor protein (C100), which is cleaved by the presenilin subunit of γ-secretase, an Alzheimer disease (AD)-associated IAP. mIAPvariants with substitutions in active-site and putative substrate- gating residues generally exhibit impaired, but not abolished, activity toward angiotensinogen and retain the predominant cleavage site (His-Thr). The aromatic ring, but not the hydroxyl substituent, within Tyr of the catalytic Tyr-Asp (YD) motif plays a catalytic role and the hydrolysis reaction incorporates bulk water as in soluble aspartyl proteases. mIAP hydrolyzes the transmembrane region of C100 at two major presenilin cleavage sites, one corresponding to the AD-associated Aβ42 peptide (Ala-Thr) and the other to the non-pathogenic Aβ48 (Thr-Leu). For the former site, we observed more favorable kinetics in lipid bilayer-mimicking bicelles than in detergent solution, indicating that substrate-lipid and substrate-enzyme interactions both contribute to catalytic rates. High-resolution MS analyses across four substrates support a preference for threonine at the scissile bond. However, results from threoninescanning mutagenesis of angiotensinogen demonstrate a competing positional preference for cleavage. Our results indicate that IAP cleavage is controlled by both positional and chemical factors, opening up new avenues for selective IAP inhibition for therapeutic interventions. (Thr-Leu). For the former site, we observed more favorable kinetics in lipid bilayer-mimicking bicelles than in detergent solution, indicating that substrate-lipid and substrate-enzyme interactions both contribute to catalytic rates. High-resolution MS analyses across four substrates support a preference for threonine at the scissile bond. However, results from threoninescanning mutagenesis of angiotensinogen demonstrate a competing positional preference for cleavage. Our results indicate that IAP cleavage is controlled by both positional and chemical factors, opening up new avenues for selective IAP inhibition for therapeutic interventions. [ABSTRACT FROM AUTHOR]