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Abstract Spin current, converted from charge current via spin Hall or Rashba effects, can transfer its angular momentum to local moments in a ferromagnetic layer. In this regard, the high charge‐to‐spin conversion efficiency is required for magnetization manipulation for developing future memory or logic devices including magnetic random‐access memory. Here, the bulk Rashba‐type charge‐to‐spin conversion is demonstrated in an artificial superlattice without centrosymmetry. The charge‐to‐spin conversion in [Pt/Co/W] superlattice with sub‐nm scale thickness shows strong W thickness dependence. When the W thickness becomes 0.6 nm, the observed field‐like torque efficiency is about 0.6, which is an order larger than other metallic heterostructures. First‐principles calculation suggests that such large field‐like torque arises from bulk‐type Rashba effect due to the vertically broken inversion symmetry inherent from W layers. The result implies that the spin splitting in a band of such an ABC‐type artificial SL can be an additional degree of freedom for the large charge‐to‐spin conversion.

Targeted protein degradation is a promising approach for basic research and therapeutic applications. Here, the authors develop a targeted protein degradation platform called AUTOTAC to degrade oncoproteins and neurodegeneration-associated proteins via the p62-dependent autophagy-lysosome system.

Abstract Background This study aimed to evaluate the efficacy of viscosupplementation after arthroscopic partial meniscectomy. Method A randomized controlled trial of 47 patients who underwent arthroscopic partial meniscectomy was conducted between March 2020 and March 2021. Patients were randomized into two groups: a viscosupplementation group (n = 23) and a control group (n = 24). A single-dose intraarticular hyaluronic acid injection was used as viscosupplementation. The 100 mm visual analogue scale (VAS) for pain assessment was measured at baseline and at 1 day, 2 weeks, 6 weeks, and 3 months post-surgery. The International Knee Documentation Committee (IKDC), Tegner, Lysholm, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores and range of motion (ROM) of the knee were measured at baseline, 2 weeks, 6 weeks, and 3 months. Results The 100 mm VAS score for pain was significantly lower in the viscosupplementation group at 2 weeks post-surgery (27.5 mm vs. 40.7 mm, P = 0.047). ROM was significantly greater in the viscosupplementation group than in the control group at 2 weeks (131.5° vs. 121.0°, P = 0.044) post-surgery. No significant differences were observed in the IKDC or in the Tegner, Lysholm, and WOMAC scores between the two groups. Conclusions Viscosupplementation after arthroscopic partial meniscectomy significantly reduced pain at 2 weeks post-surgery and improved ROM of the knee at 2 weeks post-surgery. There might be some benefits in terms of pain and functional recovery of viscosupplementation after arthroscopic surgery. Study design Randomized controlled trial; Level of evidence, 1. Trial registration This randomized controlled trial was registered at cris.nih.go.kr # KCT0004921 .

Abstract Uveal melanoma(UM) is the most common primary intraocular malignancy in adults. However, the incidence of UM in Asia is 10 to 20 times less than in Western populations. Therefore, for the first time, we report our whole exome sequencing (WES) data analysis to discover differences in the molecular features of Asian and Western UM, and to determine the disparities between the primary tumor before brachytherapy and enucleated samples after brachytherapy. WES of 19 samples (13 primary tumors, 5 enucleation samples after brachytherapy, and 1 liver metastasis) from 13 patients diagnosed with UM and treated between 2007 and 2019 at the Yonsei University Health System (YUHS) were analyzed using bioinformatics pipelines. We identified significantly altered genes in Asian UM and changes in mutational profiles before and after brachytherapy using various algorithms. GNAQ, BAP1, GNA11, SF3B1 and CYSLTR2 were significantly mutated in Asian UM, which is similar that reported frequently in previous Western-based UM studies. There were also similar copy number alterations (M3, 1p loss, 6p gain, 8q gain) in both groups. In paired comparisons of the same patients, DICER1 and LRP1B were distinctly mutated only in tumor samples obtained after brachytherapy using rare-variant association tests (P = 0.01, 0.01, respectively). The mutational profiles of Asian UM were generally similar to the data from previous Western-based studies. DICER1 and LRP1B were newly mutated genes with statistical significance in the regrowth samples after brachytherapy compared to the primary tumors, which may be related to resistance to brachytherapy.

Abstract Dzyaloshinskii–Moriya interaction (DMI) is considered as one of the most important energies for specific chiral textures such as magnetic skyrmions. The keys of generating DMI are the absence of structural inversion symmetry and exchange energy with spin–orbit coupling. Therefore, a vast majority of research activities about DMI are mainly limited to heavy metal/ferromagnet bilayer systems, only focusing on their interfaces. Here, we report an asymmetric band formation in a superlattices (SL) which arises from inversion symmetry breaking in stacking order of atomic layers, implying the role of bulk-like contribution. Such bulk DMI is more than 300% larger than simple sum of interfacial contribution. Moreover, the asymmetric band is largely affected by strong spin–orbit coupling, showing crucial role of a heavy metal even in the non-interfacial origin of DMI. Our work provides more degrees of freedom to design chiral magnets for spintronics applications.

Although SiOx is a well-known promising anode material for Li-ion batteries because of its high energy density and cyclic stability, the inferior electron transport kinetics and morphologically unstable solid-electrolyte interphase (SEI) layer formed on the SiOx anode result in inadequate electrochemical performance. Herein, to overcome the poor electron transport kinetics, a carbon-incorporated/carbon-coated SiOx((C-SiOx)@C) composite is fabricated. In addition, the (C-SiOx)@C electrode is pre-lithiated using a charging circuit under an optimized resistance to form a structurally durable SEI layer with high Li+ diffusivity during the charge–discharge processes. Thus, the (C-SiOx)@C composite exhibits highly improved cycle performance.

The most pressing concerns in environmental remediation are the design and development of catalysts with benign, low-cost, and efficient photocatalytic activity. The present study effectively generated a flower-like indium oxide (In2O3-MF) catalyst employing a convenient MOF-based solvothermal self-assembly technique. The In2O3-MF photocatalyst exhibits a flower-like structure, according to morphology and structural analysis. The enhanced photocatalytic activity of the In2O3-MF catalyst for 4-nitrophenol (4-NP) and methylene blue (MB) is likely due to its unique 3D structure, which includes a large surface area (486.95 m2 g−1), a wide spectrum response, and the prevention of electron–hole recombination compared to In2O3-MR (indium oxide-micro rod) and In2O3-MD (indium oxide-micro disc). In the presence of NaBH4 and visible light, the catalytic performances of the In2O3-MF, In2O3-MR, and In2O3-MD catalysts for the reduction of 4-NP and MB degradation were investigated. Using In2O3-MF as a catalyst, we were able to achieve a 99.32 percent reduction of 4-NP in 20 min and 99.2 percent degradation of MB in 3 min. Interestingly, the conversion rates of catalytic 4-NP and MB were still larger than 95 and 96 percent after five consecutive cycles of catalytic tests, suggesting that the In2O3-MF catalyst has outstanding catalytic performance and a high reutilization rate.

Abstract Magnoliae Flos (MF) is a traditional medicinal herb used for managing rhinitis, sinusitis and headache. The purpose of the present study was to determine the neuroprotective effect of MF against glutamate-induced oxidative stress and to assess the underlying mechanism. Glutamate is a major endogenous excitatory neurotransmitter in the brain and contributes to the development of neurodegenerative diseases by excessive activation. MF extract was subjected to a neuroprotective effect assay in HT22 mouse hippocampal cells. The mechanism underlying the neuroprotective effect of MF extract was evaluated by assaying reactive oxygen species (ROS) levels, intracellular Ca2+ levels, mitochondrial membrane potential, glutathione level and antioxidant enzyme activity in HT22 cells. MF extract significantly decreased glutamate-induced death of HT22 cells (80.83 ± 7.34% relative neuroprotection). MF extract reduced the intracellular ROS and Ca2+ levels and increased the glutathione level and glutathione reductase and glutathione peroxide activities. Moreover, MF extract attenuated the mitochondrial membrane potential in HT22 cells. These results suggested that MF extract exerts a neuroprotective effect against oxidative stress HT22 cells, which was mediated by its antioxidant activity.

Abstract Mineral fertilizers are expensive and last only a relatively short time. Proper handling of fertilizers has a direct impact on crop quality and profitability. Currently, straight fertilizers are divided into types, A and B, based on the fertilizer’s sedimentation properties when mixed. Therefore, to solve these flaws, we developed a vitamin C-substrate organo-mineral fertilizer, AGH-Ringer. This study consisted of a fertilizer equivalency test, which lasted 15 weeks of soil cultivation in a farm field, using lettuce (Lactuca sativa L., ‘Jeok Chi Ma’) with AGH-Ringer as a test fertilizer. This fertilizer was based on powder compound-type fertilizer r-Ringer and manufactured by chelating essential minerals with a vitamin C substrate to have NPK contents in a ratio of 18.9:14:4.0. In the onsite evaluation, the superiority of AGH-Ringer was demonstrated through an effect of growth stimulation in both aerial and rhizosphere parts of the plants at suitable soil temperatures. This fertilizer also increased yield, even in inadequate low-temperature conditions. In addition, AGH-Ringer increased the absorption and bioavailability of minerals in lettuce leaves at harvest. The mineral absorption ability showed a uniform pattern during the entire harvest period. It has been confirmed that AGH-Ringer, manufactured with vitamin C as a substrate, is a fertilizer with excellent efficacy that increases growth and harvest simultaneously, solving the existing problems of chemical fertilizers such as sedimentation and lack of mineral absorptivity in nutrient solution systems.

The treatment of neuropathic pain is one of the urgent unmet medical needs and T-type calcium channels are promising therapeutic targets for neuropathic pain. Several potent T-type channel inhibitors showed promising in vivo efficacy in neuropathic pain animal models and are being investigated in clinical trials. Herein we report development of novel pyrrolidine-based T-type calcium channel inhibitors by pharmacophore mapping and structural hybridisation followed by evaluation of their Cav3.1 and Cav3.2 channel inhibitory activities. Among potent inhibitors against both Cav3.1 and Cav3.2 channels, a promising compound 20n based on in vitro ADME properties displayed satisfactory plasma and brain exposure in rats according to in vivo pharmacokinetic studies. We further demonstrated that 20n effectively improved the symptoms of neuropathic pain in both SNL and STZ neuropathic pain animal models, suggesting modulation of T-type calcium channels can be a promising therapeutic strategy for the treatment of neuropathic pain.

Abstract Background Glutamate (an endogenous excitatory neurotransmitter) at high concentrations contributes to the development of neurodegenerative diseases. Aronia melanocarpa (A. melanocarpa) berries contain anthocyanins and have high antioxidant activities. In this study, we evaluated whether A. melanocarpa berries could protect neuronal cells against glutamate-induced oxidative stress. Method A. melanocarpa berries exerted a protective effect against cytotoxicity in HT22 mouse hippocampal cells by MTT assay. We evaluated oxidative stress parameters including ROS level, intracellular Ca2+ level, glutathione level and antioxidant enzyme activity in HT22 cells to elucidate the mechanism of its neuroprotective effect. Results A. melanocarpa berries decreased glutamate-induced death of HT22 cells. In addition, A. melanocarpa berries reduced ROS and intracellular Ca2+ levels. Glutathione level, antioxidant enzymes, glutathione reductase and glutathione peroxide activities and mitochondrial membrane potential were also increased in HT22 cells. Conclusion These results suggested that A. melanocarpa berries protected HT22 cells by exerting an antioxidant effect.

Nelumbo nucifera has a variety of biological activities. So it was importantly used as various herbal medicines since traditional times. A simple, fast, and sensitive high-performance liquid chromatographic (HPLC) method was developed in this study for efficient quality control of N. nucifera. Four different compounds, including neferine, 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl) methyl]-2-methyl-7-isoquinolinol, 1-hydroxy-2-methylpropene, and 3-(prop-1-enyl)benzene-1,2,4,5-tetrol, were simultaneously determined. The four compounds were isolated through a Dionex C18 column by gradient elution with 0.1% TFA-water and methanol. The flow rate was 1.0 mL/min, and the wavelength was detected at 205, 254, 280, and 330 nm. The chromatograms were acquired at 205 nm. The four compounds showed good linear relationships (r2>0.96) over five different concentrations, and an average recovery of the method ranged from 96.27% to 108.78%. Through the analysis validation test and application of the method, the optimized conditions verified that it is efficient to isolate the compounds of N. nucifera seed embryos.

Piezo1 belongs to mechano-activatable cation channels serving as biological force sensors. However, the molecular events downstream of Piezo1 activation remain unclear. In this study, we used biosensors based on fluorescence resonance energy transfer (FRET) to investigate the dynamic modes of Piezo1-mediated signaling and revealed a bimodal pattern of Piezo1-induced intracellular calcium signaling. Laser-induced shockwaves (LIS) and its associated shear stress can mechanically activate Piezo1 to induce transient intracellular calcium (Ca[i] ) elevation, accompanied by an increase in FAK activity. Interestingly, multiple pulses of shockwave stimulation caused a more sustained calcium increase and a decrease in FAK activity. Similarly, tuning the degree of Piezo1 activation by titrating either the dosage of Piezo1 ligand Yoda1 or the expression level of Piezo1 produced a similar bimodal pattern of FAK responses. Further investigations revealed that SHP2 serves as an intermediate regulator mediating this bimodal pattern in Piezo1 sensing and signaling. These results suggest that the degrees of Piezo1 activation induced by both mechanical LIS and chemical ligand stimulation may determine downstream signaling characteristics.

A general method for the assay of deubiquitinating enzymes was described in detail using 125I-labeled ubiquitin-fused &agr;NH-MHISPPEPESEEEEEHYC (referred to as Ub-PESTc) as a substrate. Since the tyrosine residue in the PESTc portion of the fusion protein was almost exclusively radioiodinated under a mild labeling condition, such as using IODO-BEADS, the enzymes could be assayed directly by simple measurement of the radioactivity released into acid soluble products. Using this assay protocol, we could purify six deubiquitinating enzymes from chick skeletal muscle and yeast and compare their specific activities. Since the extracts of E. coli showed little or no activity against the substrate, the assay protocol should be useful for identification and purification of eukaryotic deubiquitinating enzymes cloned and expressed in the cells.

Sequential recommendation systems aim to predict users’ subsequent interactions by analyzing their historical behavior. Significant advancements have been achieved in this field through the utilization of models such as RNN, GRU, and models incorporating the self-attention mechanism. Most state-of-the-art methods enhance recommendation effectiveness by incorporating side information, such as category or brand, within the attention layer to enrich item representations. However, in our pilot experiments, we found that increasing the amount of side information could negatively impact the recommendation performance when integrated directly into the attention layer due to the learning of interdependency among them. To alleviate this problem, we propose Independent Representation of side Information on each item for Sequential recommendation (IRIS). IRIS learns pairs of both item and side information independently, without any fusion among side information in attention layer. In contrast to existing approaches, IRIS avoids direct fusion among side information in the attention layer, opting instead for a novel strategy of learning independent pairs of both item and side information. Our proposed method constructs an attention layer specifically designed to learn these pairs, thus avoiding potential distortions to item representations caused by intermixing side information. Experiments on four public datasets show that IRIS outperforms state-of-the-art sequential recommendation models. Ablation study also indicates robust scalability of side information within IRIS.

The human colonic commensal enterotoxigenic Bacteroides fragilis (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the Bacteroides fragilis toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling. ETBF promotes colon tumorigenesis via interleukin 17A (IL-17A)/CXCL-dependent inflammation, but its bioactive therapeutics in ETBF-promoted tumorigenesis remain unexplored. In the current study, we investigated the caffeic acid phenethyl ester (CAPE) in the murine model of ETBF colitis and tumorigenesis. In this study, we observed that CAPE treatment mitigated inflammation induced by ETBF in mice. Additionally, our findings indicate that CAPE treatment offers protective effects against ETBF-enhanced colon tumorigenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sulfate sodium. Notably, the decrease in colon tumorigenesis following CAPE administration correlates with a reduction in the expression of IL-17A and CXCL1 in the gastrointestinal tract. The molecular mechanism for CAPE-induced protection against ETBF-mediated tumorigenesis is mediated by IL-17A/CXCL1, and by NF-κB activity in intestinal epithelial cells. Our findings indicate that CAPE may serve as a preventive agent against the development of ETBF-induced colitis and colorectal cancer (CRC).

Universities around the world face a common challenge -- producing graduates with the necessary practical skills for employment. Cooperative education and work-integrated learning (WIL) make a valuable contribution to increasing graduate employability, however, there are differences in the level of cooperation from industry and government commitment. A comparative study of WIL in Germany, Australia, and South Korea, focusing predominantly on three universities, showed differences in the approaches to achieving practical experience and increasing graduate employability. The data underlying the research was derived from questionnaires, a focus group session, and the development of a descriptive, multi-case study. This allowed comparisons and contrasts between the three universities to be identified. The results and conclusions outlined in this paper aim to highlight best practice in cooperative education and WIL and provide recommendations for the future development of cooperative education, in order to improve graduate employability.

Keratinocytes, the predominant cell type of the epidermis, migrate to reinstate the epithelial barrier during wound healing. Mechanical cues are known to regulate keratinocyte re-epithelialization and wound healing; however, the underlying molecular transducers and biophysical mechanisms remain elusive. Here, we show through molecular, cellular, and organismal studies that the mechanically activated ion channel PIEZO1 regulates keratinocyte migration and wound healing. Epidermal-specific Piezo1 knockout mice exhibited faster wound closure while gain-of-function mice displayed slower wound closure compared to littermate controls. By imaging the spatiotemporal localization dynamics of endogenous PIEZO1 channels, we find that channel enrichment at some regions of the wound edge induces a localized cellular retraction that slows keratinocyte collective migration. In migrating single keratinocytes, PIEZO1 is enriched at the rear of the cell, where maximal retraction occurs, and we find that chemical activation of PIEZO1 enhances retraction during single as well as collective migration. Our findings uncover novel molecular mechanisms underlying single and collective keratinocyte migration that may suggest a potential pharmacological target for wound treatment. More broadly, we show that nanoscale spatiotemporal dynamics of Piezo1 channels can control tissue-scale events, a finding with implications beyond wound healing to processes as diverse as development, homeostasis, disease, and repair.