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Jin G Choi,1,2 Pathik Amin,3 Alaina Tarantino,4 Mary Qiu3 1Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; 2Department of Ophthalmology, California Pacific Medical Center, San Francisco, CA, USA; 3Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL, USA; 4Ambulatory Pharmacy Services, University of Chicago, Chicago, IL, USACorrespondence: Mary Qiu, Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL, USA, Tel +1 (773) 702-3937, Email mary.qiu@gmail.comPurpose: A major barrier to glaucoma medication adherence is the patient’s out-of-pocket costs. At the University of Chicago Medical Center (UCMC), the institutional pharmacy piloted a program to query out-of-pocket costs for each patient’s medication list based on their insurance coverage. This study aims to describe the impact of this collaboration between the glaucoma service and the outpatient pharmacy service.Methods: This study is a single institution, retrospective chart review of glaucoma patients with a formulary inquiry placed by a single glaucoma specialist between 4/1/2020 and 2/28/2022. Main outcome measures included medications before and after formulary inquiries, additional steps required to access the medications (ie, formulary exceptions, prior authorizations, tier exceptions), and out-of-pocket costs.Results: A total of 343 formulary inquiries, representing 568 individual medication inquiries, were conducted. Out of the 568 medication inquiries, only 78 could be filled for an affordable price without any additional steps. For 45 inquiries, additional steps were required for the medication to become covered at an affordable price. The remaining 445 inquires required additional steps with subsequent denial or prohibitive out-of-pocket costs.Conclusion: The UCMC workflow provided transparent out-of-pocket costs for patients to access glaucoma medications. This workflow may be cost-effective as it minimizes the burden on the overall system by reducing the number of patients who are unable to fill a prescription at the pharmacy due to issues with coverage or affordability. This model of physician-pharmacy collaboration can guide other institutions to implement similar workflows which directly mitigate costs and improve quality of care.Keywords: medication, access, cost

Jong Yeup Kim,1 Dong Won Yang,1 Sangjae Kim,2 Jong Gwon Choi3 1Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea; 2Department of Research and Development, Teloid Inc., Los Angeles, CA, 90010, USA; 3Department of Oncology-Hematology, Konyang University Hospital, Daejeon, Republic of KoreaCorrespondence: Jong Gwon Choi, Oncology-Hematology, Konyang University Hospital, 158 Gwanjeodong-Ro, Seo-Gu, Daejeon, Republic of Korea, Email jabuss@naver.comPurpose: Telomerase activation, a critical step in cancer progression, occurs in approximately 95% of breast cancer cases. Telomerase is an attractive therapeutic target for breast cancer owing to its unique expression pattern. GV1001, a telomerase-derived peptide, is loaded onto human leukocyte antigen (HLA) class II antigen-presenting cells and binds to CD4+ T cell activating immune responses. This study aimed to evaluate the effectiveness and safety of co-administration of GV1001 and cytotoxic chemotherapy in patients with heavily-treated metastatic breast cancer.Patients and methods: We analyzed 63 patients with breast cancer who received both GV1001 and cytotoxic chemotherapy. The GV 1001 administration methods involves 0.56 mg intradermal injection three times during the first week, one time at weeks 2, 3, 4, and 6, and then once every 28 days. The primary endpoint of this study was quality of life according to EORTC QLO-C30 and EQ-5D, while the secondary endpoint was the antitumor response according to RECIST 1.1, progression-free survival, overall survival, and toxicity profile.Results: In 34 patients with HR+ breast cancer evaluable for tumor response, the disease control rate (DCR) and overall response rate (ORR) were 58.8% and 26.4%, respectively. The DCR and ORR were 66.6% and 28.5% in 21 patients with HER-2+ and 50% and 25% in patients with triple-negative breast cancer (TNBC), respectively. The median progression free survival was 10.4, 8.7, and 5.6 months in HR+, HER-2+, TNBC, respectively. The overall survival was 19.7, 13.2, and 9.4 months for patients with HR+, HER-2+, and TNBC, respectively. Most patients had an improved quality of life with statistically significant differences in some variables. The patients in this study experienced no additional toxicities other than the cytotoxic chemotherapy-associated side effects.Conclusion: GV1001 is a relatively safe anticancer vaccine for patients with heavily-treated breast cancer and can to improve the quality of life.Keywords: telomerase, GV1001, quality of life, safety, breast cancer

Seong-Lan Yu,1 Dong Chul Lee,2 Seung Woo Baek,3 Do Yeun Cho,3 Jong Gwon Choi,3 JaeKu Kang1 1Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea; 2Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; 3Department of Oncology-Hematology, Konyang University Hospital, Daejeon, Republic of Korea Purpose: The PI3K/AKT/mTOR pathway is frequently activated in various squamous cell carcinomas (SCCs). Although mTOR inhibitors are suggested as effective treatments in immunosuppressed patients with metastatic SCC, they are still not proven to be favorable in treating skin SCC patients not undergoing immunosuppressive therapy. Moreover, the exact mechanism of the mTOR signaling pathway in SCC has not yet been identified. In this study, we aimed to determine the genes associated with mTOR inhibitors in skin SCC.Materials and methods: The identification of cell viability according to concentration of everolimus and Western blot was done. To analyze the global gene expression profiles, A431 and HSC-1 cells were treated with dimethyl sulfoxide (DMSO) or 100 nM of everolimus for 72 hours. Furthermore, differentially expressed genes (DEGs) were identified using Affymetrix analysis. To identify the gene network associated with everolimus resistance in SCC cells, pathway analysis was performed using the Ingenuity Pathway Analysis (IPA) tool.Results: The effects of cell death with respect to the mTOR inhibitor concentration were observed in the HSC-1 cell line; however, the mTOR inhibitor did not show effective cytotoxic activity in the A431 cell line. p-mTOR concentration also diminished with respect to everolimus concentrations in the HSC-1 cell line. Moreover, the microarray results showed that the MYC/CCND1/TP73/NUPR1/SBD/ERBB2/CDKN2B genes were related to mTOR inhibitor resistance. However, CCND1 gene overexpression was most closely related to mTOR inhibitor resistance.Conclusion: We identified mTOR inhibitor resistance genes, and our findings may help select therapeutic targets in skin SCC. Keywords: mTOR inhibitor, squamous cell carcinoma, gene profiling, CCND1 gene

Highly pathogenic avian influenza (H5N1) among wild birds emerged simultaneously with outbreaks in domestic poultry in South Korea during November 2010-May 2011. Phylogenetic analysis showed that these viruses belonged to clade 2.3.2, as did viruses found in Mongolia, the People's Republic of China, and Russia in 2009 and 2010. [ABSTRACT FROM AUTHOR]

This study focuses on the elucidation of the structure and antiviral properties of six nitrogen-containing compounds including amino acid derivates (1 and 2) and heterocyclic compounds (3-6) isolated from the fruiting bodies of Sarcodon imbricatus, particularly Compound 2, an (S)-2-(hydroxyimino)-3-methylpentanoic acid ethyl ester. Their antiviral effects were tested against influenza A virus (IAV) in A549 cells. Particularly, Compound 2 exhibited significant antiviral activity in post-treatment assays, reducing viral protein expression and inhibiting viral replication with an IC 50 of 14.9 μmol/L. Additionally, it demonstrated anti-inflammatory effects by reducing levels of cytokines such as TNF-α, IL-6 and IL-1β as well as the oxidative stress induced by IAV infection, while inhibiting necroptosis, a form of programmed cell death associated with inflammation. Thus, our findings demonstrate the antiviral and anti-inflammatory properties of Compound 2, making it a promising candidate for further research as an anti-influenza agent., Competing Interests: Declaration of Competing Interest The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Rapid expansion of digital information density has led to a growing demand for multi-valued logic (MVL) systems, which aim to minimize energy and time consumption for computations. Heterojunction transistors represent a class of device architectures for MVL circuits; however, partially layered structures can be realized only for vacuum-deposited organic and transferred 2D materials due to the constraints of patterning processes. In this study, a novel Cu x O/IGZO heterojunction-based ternary inverter is presented via a sol-gel technique and direct patterning process using a self-assembled monolayer (SAM). This approach allows for a promising alternative to conventional photolithography, with the electrical characteristics of SAM-processed oxide thin-film transistors closely matching those of pristine devices. Structural investigations validate the partially overlapped heterojunction and its smoothness. Depth profiling with x-ray photoelectronspectroscopy highlights an oxidation gradient in Cu x O, suggesting enhanced hole introduction at the IGZO interface. This mechanism potentially supports efficient hole transport and negative differential transconductance, foundational for MVL systems. Such advancements signify the potential for solution-processable digital electronics that offer streamlined fabrication at an affordable budget., (© 2024 Wiley‐VCH GmbH.)

Skin-conformal organic electrochemical transistors (OECTs) have attracted significant attention for real-time physiological signal monitoring and are vital for health diagnostics and treatments. However, mechanical harmonization amid the inherent dynamic nature of the skin surface and the acquisition of intrinsic physiological signals are significant challenges that hinder the integration of the ultimate skin interface. Thus, this study proposes a novel 4-terminal (4-T) vertical Corbino OECT, exhibiting high transconductance (>400 mS) and offering remarkable resilience and operational stability at an extremely low voltage of 10 mV (1.9% of minimal current change after 10 4 biasing cycles and endurance up to 10 3 cycles of repetitive deformation with a 5 µm bending radius). Consequently, ultralow-power, motion-resistant epidermal electrocardiogram, electromyogram, and electrooculogram sensors are developed with an exceptional signal-to-noise ratio of 40.1 dB. The results of this study present a significant stride in non-invasive, skin-interfaced health-monitoring technologies and herald a new era in integrative health technologies., (© 2024 Wiley‐VCH GmbH.)

Chestnut honey has various benefits, such as antioxidative, anti-inflammatory, immunomodulatory, antibacterial, and antiviral effects. However, the effects of chestnut honey or the ethyl acetate fraction of chestnut honey (EACH) on neurodegenerative diseases and their related cognitive impairment and neurotoxicity have not yet been established. Therefore, in this study, we investigated the mitigating effect of the EACH on scopolamine (SCO)-injected cognitive decline in mice and glutamate-exposed neurotoxicity in HT22 cells. EACH administration significantly reversed SCO-induced cognitive decline in mice, as demonstrated through the Morris water maze and passive avoidance tests. The EACH treatment showed a significant alleviation effect by recovering more than 80% of the cell viability decrease induced by glutamate exposure in the HT22 neuronal cell model. Furthermore, the EACH significantly reduced reactive oxygen species accumulation, lactate dehydrogenase release, mitochondrial depolarization, and neuronal apoptosis. The EACH regulated the level of apoptosis-related proteins, induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf-2) and the expression of related antioxidant proteins, and induced the phosphorylation of tropomyosin-related kinase receptor B (TrkB)/cAMP-calcium response element-binding protein (CREB) and the expression of brain-derived neurotrophic factor. These data indicate that the EACH can prevent neurons from oxidative damage and improve cognitive dysfunction by activating Nrf-2 and TrkB/CREB signaling pathways. Therefore, the EACH demonstrates potential therapeutic value in mitigating oxidative stress-induced neurotoxicity, cognitive decline, and related neurodegenerative diseases.

Escherichia coli is a significant pathogen in extraintestinal infections, and ESBL-producing E. coli poses a major clinical challenge due to its antibiotic resistance. This study comprehensively analyzed E. coli isolates from urine and blood samples of patients with urinary tract and bloodstream infections at three major tertiary hospitals in South Korea. The goal was to provide insights into the distribution, antibiotic resistance, and virulence factors of these strains. Our analysis identified CTX-M and TEM as the dominant ESBL types, found in 71.7% and 61.7% of isolates, respectively, with 46.7% showing co-occurrence. Multilocus sequence typing (MLST) revealed the predominance of high-risk clones such as ST131, ST69, ST73, and ST95, with rare sequence types like ST410 and ST405 also identified. The high prevalence of virulence factors, including iutA (80.8%) and kpsMII (74.2%), further highlights the complexity of these strains. In addition, 38.3% of clinical isolates contained a combination of siderophore, adhesin, protectin, and toxin-related genes. There was no significant difference between urinary tract and bloodstream infections or regional differentiation in Korea. This study highlights the importance of controlling ESBL-producing E. coli infections, especially given the increasing incidence among patients with underlying medical conditions and older adults who are more susceptible to urinary tract infections. These findings serve as valuable indicators for pathogen analysis, especially those harboring antibiotic resistance and toxin genes. The insights gained are expected to contribute significantly to the development of infectious disease prevention and control strategies., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

GaAs thin-film solar cells have high efficiency, reliability, and operational stability, making them a promising solution for self-powered skin-conformal biosensors. However, inherent device thickness limits suitability for such applications, making them uncomfortable and unreliable in flexural environments. Therefore, reducing the flexural rigidity becomes crucial for integration with skin-compatible electronic devices. Herein, this study demonstrated a novel one-step surface modification bonding methodology, allowing a streamlined transfer process of ultra-thin (2.3 µm thick) GaAs solar cells on flexible polymer substrates. This reproducible technique enables strong bonding between dissimilar materials (GaAs-polydimethylsiloxane, PDMS) without high external pressures and temperatures. The fabricated solar cell showed exceptional performance with an open-circuit voltage of 1.018 V, short-circuit current density of 20.641 mA cm -2 , fill factor of 79.83%, and power conversion efficiency of 16.77%. To prove the concept, the solar cell is integrated with a skin-compatible organic electrochemical transistor (OECT). Competitive electrical outputs of GaAs solar cells enabled high current levels of OECT under subtle light intensities lower than 50 mW cm -2 , which demonstrates a self-powered electrocardiogram sensor with low noise (signal-to-noise ratio of 32.68 dB). Overall, this study presents a promising solution for the development of free-form and comfortable device structures that can continuously power wearable devices and biosensors., (© 2024 Wiley‐VCH GmbH.)

Background: This study aimed to analyze the immunostimulatory activity of gamisoyosan (GSS) on the activation of macrophages in RAW 264.7 cells and its underlying mechanisms., Methods: The effects of GSS on the secretion of nitric oxide (NO), immunomodulatory mediators, cytokines and mRNAs, and related proteins were assessed using the Griess assay, Western blotting, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and H 2 DCFDA, respectively. The level of phagocytosis was determined by the neutral red method while the immune function of GSS was determined using adhesion and wound-healing assays., Results: GSS-treated macrophages significantly increased the production of NO, immunomodulatory enzymes, cytokines, and intracellular reactive oxygen species without causing cytotoxicity. GSS effectively improved macrophage immune function by increasing their phagocytic level, adhesion function, and migration activity. Mechanistic studies via Western blotting revealed that GSS notably induced the activation of the Toll-like receptor (TLR) 4-mediated mitogen-activated protein kinase, nuclear factor-κB, and protein kinase B signaling pathways., Conclusions: Overall, our results indicated that GSS could activate macrophages through the secretion of immune-mediated transporters via TLR4-dependent signaling pathways. Thus, GSS has potential value as an immunity-enhancing agent.

Background: Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive., Methods: In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities., Results: We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy., Conclusions: Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients., (© 2024. The Author(s).)

Gwakhyangjeonggi-san (GJS) is a traditional herbal medicine used in East Asia for the treatment of symptoms involving lower intestinal abnormalities; however, the effects of GJS on innate immunity and its cellular mechanisms of action have not been elucidated. In this study, we assessed the immune-enhancing activity and underlying mechanisms of GJS using RAW 264.7 murine macrophages. The results showed that GJS treatment significantly increased the secretion of nitric oxide and cytokines and their mRNA expression in macrophage RAW 264.7 cells without causing cytotoxicity. GJS treatment also significantly increased the production of reactive oxygen species, as well as inducing phagocytic activity, adhesion function, and migration ability, all of which improved the immune response. In addition, GJS activated nuclear factor-κB by promoting the phosphorylation and degradation of inhibitor of nuclear factor-κB alpha. Furthermore, GJS markedly increased the phosphorylation of mitogen-activated protein kinase in RAW 264.7 cells. These findings indicate that GJS has potential value as a dietary supplement for strengthening immunity.

Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host's trigeminal ganglion, can lead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerative diseases like Alzheimer's. The virus generates reactive oxygen species (ROS) that significantly impact viral replication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related factor 2 (Nrf2), an oxidative stress regulator, can prevent and treat HSV-1 infection by activating the passive defense response in the early stages of infection., Methods and Results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity in host cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenoside Rg5 inhibited ROS/NF-κB signaling and reduced inflammatory cytokines through NRF2 induction. Interestingly, the Nrf2 inhibitor ML385 suppressed the expression of NAD(P)H quinone oxidoreductase 1(NQO1) and enhanced the expression of KEAP1 in HSV-1 infected cells. This led to the reversal of VP16 expression inhibition, a protein factor associated with HSV-1 infection, thereby promoting HSV-1 replication., Conclusion: These findings suggest for the first time that ginsenoside Rg5 may serve as an antiviral against HSV-1 infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Background: Mycobacterium avium complex (MAC), including Mycobacterium intracellulare is a member of slow-growing mycobacteria and contributes to a substantial proportion of nontuberculous mycobacterial lung disease in humans affecting immunocompromised and elderly populations. Adaptation of pathogens in hostile environments is crucial in establishing infection and persistence within the host. However, the sophisticated cellular and molecular mechanisms of stress response in M. intracellulare still need to be fully explored. We aimed to elucidate the transcriptional response of M. intracellulare under acidic and oxidative stress conditions., Results: At the transcriptome level, 80 genes were shown [FC] ≥ 2.0 and p < 0.05 under oxidative stress with 10 mM hydrogen peroxide. Specifically, 77 genes were upregulated, while 3 genes were downregulated. In functional analysis, oxidative stress conditions activate DNA replication, nucleotide excision repair, mismatch repair, homologous recombination, and tuberculosis pathways. Additionally, our results demonstrate that DNA replication and repair system genes, such as dnaB, dinG, urvB, uvrD2, and recA, are indispensable for resistance to oxidative stress. On the contrary, 878 genes were shown [FC] ≥ 2.0 and p < 0.05 under acidic stress with pH 4.5. Among these genes, 339 were upregulated, while 539 were downregulated. Functional analysis highlighted nitrogen and sulfur metabolism pathways as the primary responses to acidic stress. Our findings provide evidence of the critical role played by nitrogen and sulfur metabolism genes in the response to acidic stress, including narGHIJ, nirBD, narU, narK3, cysND, cysC, cysH, ferredoxin 1 and 2, and formate dehydrogenase., Conclusion: Our results suggest the activation of several pathways potentially critical for the survival of M. intracellulare under a hostile microenvironment within the host. This study indicates the importance of stress responses in M. intracellulare infection and identifies promising therapeutic targets., (© 2024. The Author(s).)

Background: The use of electric scooters (e-scooters) continues to increase as a simple, inexpensive means of transport, resulting in a sharp increase in the incidence of scooter-related accidents. No study to date has closely examined the injury extent to the lower leg, joints, and extremities from e-scooter-related accidents. Here, we investigated the epidemiology and injury patterns of such accidents, focusing on injuries to the ankle and foot., Methods: Based on data from a single tertiary hospital's database, the demographics of 563 patients with scooter-associated injuries were analyzed retrospectively. Among the patients, 229 patients who were injured by e-scooter riding were further investigated. Based on the data, the general demographics of whole scooter-associated injuries and the injury characteristics and fracture cases of the lower leg, ankle, and foot were analyzed., Results: During the 4-year study period, the number of patients injured by e-scooters increased every year. Lower extremities were the most common injury site (67.2%) among riders, whereas injuries to the head and neck (64.3%) were more common in riders of non-electric scooters. Among the lower leg, ankle, and foot injuries of riders (52 cases), the ankle joint (53.8%) was the most commonly injured site, followed by the foot (40.4%) and lower leg (21.2%). The fracture group scored significantly higher on the Abbreviated Injury Scale than the non-fracture group ( p < 0.001). Among the fracture group (20 cases), ankle fractures (9 cases) were most common, including pronation external rotation type 4 injuries (4 cases) and pilon fractures (2 cases). Five patients (25%) had open fractures, and 12 patients (60%) underwent surgical treatment., Conclusions: The ankle and foot are the most common injury sites in e-scooter-related accidents. Given the high frequency and severity of e-scooter-related ankle and foot injuries, we suggest that more attention be paid to preventing these types of injuries with greater public awareness of the dangers of using e-scooters., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Background: The emergence of immune checkpoint inhibitors, a novel class of immunotherapy drugs, represents a major breakthrough in cancer immunotherapy, substantially improving patient survival post-treatment. Blocking programmed death-ligand 1 (PD-L1) and programmed death protein-1 (PD-1) has demonstrated promising clinical results in various human cancer types. The US FDA has recently permitted only monoclonal antibody (mAb)-based PD-L1 or PD-1 blockers. Although these antibodies exhibit high antitumor efficacy, their size- and affinity-induced side effects limit their applicability., Purpose: As small-molecule-based PD-1/PD-L1 blockers capable of reducing the side effects of antibody therapies are needed, this study focuses on exploring natural ingredient-based small molecules that can target hPD-L1/PD-1 using herbal medicines and their components., Methods: The antitumor potential of evening primrose (Oenothera biennis) root extract (EPRE), a globally utilized traditional herbal medicine, folk remedy, and functional food, was explored. A coculture system was established using human PD-L1-expressed murine MC38 cells (hPD-L1-MC38s) and CD8 + tumor-infiltrating T lymphocytes (CD8 + TILs) expressing humanized PD-1. The in vivo experiments utilized a colorectal cancer (CRC) C57BL/6 J mouse model bearing MC38 cells expressing humanized PD-L1 and PD-1 proteins., Results: EPRE and its active compound oenothein B effectively hindered the molecular interaction between hPD-L1 and hPD-1. EPRE stimulated tumor-specific T lymphocytes of a hPD-L1/PD-1 CRC mice. This action resulted in the elevated infiltration of cytotoxic CD8 + T lymphocytes and subsequent tumor growth reduction. Moreover, the combined therapy of oenothein B, a PD-1/PD-L1 blocker, and FOLFOX (5-fluorouracil plus oxaliplatin) cooperatively suppressed hPD-L1-MC38s growth in the ex vivo model through activated CD8 + TIL antitumor immune response. Oenothein B exhibited a high binding affinity for hPD-L1 and hPD-1. We believe that this study is the first to uncover the inhibitory effects of EPRE and its component, oenothein B, on PD-1/PD-L1 interactions., Conclusion: This study identified a promising small-molecule candidate from natural products that blocks the hPD-L1/PD-1 signaling pathway. These findings emphasize the potential of EPRE and oenothein B as effective anticancer drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Tolerance induction is critical for mitigating T cell-mediated inflammation. Treatments based on anti-CD3 monoclonal antibody (mAb) play a pivotal role in inducing such tolerance. Anti-CD3 mAb conjugated with dextran-coated magnetic nanoparticles (MNPs) may induce inflammatory tolerance is posited. MNPs conjugated with anti-CD3 mAb (Ab-MNPs) are characterized using transmission and scanning electron microscopy, and their distribution is assessed using a nanoparticle tracking analyzer. Compared to MNPs, 90% of Ab-MNPs increased in size from 54.7 ± 0.5 to 71.7 ± 2.7 nm. The in vitro and in vivo studies confirmed the therapeutic material as nontoxic and biocompatible. Mice are administered various dosages of Ab-MNPs before receiving concanavalin-A (ConA), an inflammation inducer. Preadministration of Ab-MNPs, as opposed to MNPs or anti-CD3 mAb alone, significantly reduced the serum levels of interferon-γ and interleukin-6 in ConA-treated mice. Additionally, the transdermal stamp patch as an effective delivery system for Ab-MNPs is validated. This study demonstrates the utility of the Ab-MNP complex in pathologies associated with T cell-mediated hyperinflammation, such as organ transplantation and COVID-19., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The common human coronavirus (HCoV) exhibits mild disease with upper respiratory infection and common cold symptoms. HCoV-OC43, one of the HCoVs, can be used to screen drug candidates against SARS-CoV-2. We determined the antiviral effects of FDA/EMA-approved drug anastrozole (AZ) on two human coronaviruses, HCoV-OC43 and HCoV-229E, using MRC-5 cells in vitro. The AZ exhibited antiviral effects against HCoV-OC43 and HCoV-229E infection. Subsequent studies focused on HCoV-OC43, which is related to the SARS-CoV-2 family. AZ exhibited anti-viral effects and reduced the secretion of inflammatory cytokines, TNF-α, IL-6, and IL-1β. It also inhibited NF-κB translocation to effectively suppress the inflammatory response. AZ reduced intracellular calcium and reactive oxygen species (ROS) levels, including mitochondrial ROS and Ca 2+ , induced by the virus. AZ inhibited the expression of NLRP3 inflammasome components and cleaved IL-1β, suggesting that it blocks NLRP3 inflammasome activation in HCoV-OC43-infected cells. Moreover, AZ enhanced cell viability and reduced the expression of cleaved gasdermin D (GSDMD), a marker of pyroptosis. Overall, we demonstrated that AZ exhibits antiviral activity against HCoV-OC43 and HCoV-229E. We specifically focused on its efficacy against HCoV-OC43 and showed its potential to reduce inflammation, inhibit NLRP3 inflammasome activation, mitigate mitochondrial dysfunction, and suppress pyroptosis in infected cells.

The bluetongue virus (BTV) is a significant animal pathogen with economic implications in the ruminant industry. Despite global reports on BTV detection and epidemiologic investigations, limited studies have focused on the virus in the ROK. In this study, BTV epidemiological research was conducted on blood samples from cattle and goat farms across nine regions during 2013-2014. The results showed that 3.33% of bovine blood samples (194/5824) and 0.19% of goat blood samples (2/1075) tested positive for BTV antibodies using ELISA. In Jeju-do, BTV RNA amplification occurred in 51 of 422 samples (12.1%) using real-time reverse transcription (RT-qPCR). The isolation of one sample revealed it as serotype 3, as indicated by the sequence of segments 2 (Seg-2) and 6 (Seg-6), associated with the eastern BTV topotype. However, based on Seg-1, -3, -4, -5, -7, -8, -9, and -10 analyses, the BTV-3/JJBB35 strain is more closely related to distinct BTV strains. These findings imply BTV circulation and that the Korean-isolated BTV might originate from Asian BTV strains due to multiple reassortment events. This study provides foundational data for ongoing BTV monitoring and disease-control policies in the ROK.

For optimizing steady-state performance in organic electrochemical transistors (OECTs), both molecular design and structural alignment approaches must work in tandem to minimize energetic and microstructural disorders in polymeric mixed ionic-electronic conductor films. Herein, a series of poly(diketopyrrolopyrrole)s bearing various lengths of aliphatic-glycol hybrid side chains (PDPP-mEG; m = 2-5) is developed to achieve high-performance p-type OECTs. PDPP-4EG polymer with the optimized length of side chains exhibits excellent crystallinity owing to enhanced lamellar and backbone interactions. Furthermore, the improved structural ordering in PDPP-4EG films significantly decreases trap state density and energetic disorder. Consequently, PDPP-4EG-based OECT devices produce a mobility-volumetric capacitance product ([µC*]) of 702 F V -1 cm -1 s -1 and a hole mobility of 6.49 ± 0.60 cm 2 V -1 s -1 . Finally, for achieving the optimal structural ordering along the OECT channel direction, a floating film transfer method is employed to reinforce the unidirectional orientation of polymer chains, leading to a substantially increased figure-of-merit [µC*] to over 800 F V -1 cm -1 s -1 . The research demonstrates the importance of side chain engineering of polymeric mixed ionic-electronic conductors in conjunction with their anisotropic microstructural optimization to maximize OECT characteristics., (© 2023 Wiley-VCH GmbH.)

Immunotherapies, particularly those concerning immune checkpoint inhibitors, have transformed cancer treatment in recent years. Programmed death-ligand 1 (PD-L1) is a key target for immunotherapy that is overexpressed in the cells of colorectal cancer, a widespread malignant cancer that poses a significant healthcare challenge. This study investigated the effects of cosmosiin treatment on colorectal cancer cell lines. Cosmosiin is a naturally occurring flavone glycoside compound that has potential health benefits, including antioxidant and immunomodulatory effects. This study showed that cosmosiin effectively suppresses the expression of PD-L1 and triggers apoptosis, which is facilitated through pathways that are related to reactive oxygen species. These outcomes suggest that cosmosiin could be a promising candidate for an immune checkpoint inhibitor in the treatment of colorectal cancer.

Nanoscale heterojunction networks are increasingly regarded as promising functional materials for a variety of optoelectronic and photocatalytic devices. Despite their superior charge-carrier separation efficiency, a major challenge remains in the optimization of their surface properties, with surface defects playing a major role in charge trapping and recombination. Here, we report the effective engineering of the photocatalytic properties of nanoscale heterojunction networks via deep ultraviolet photoactivation throughout their cross-section. For the first time, in-depth XPS analysis of very thick (∼10 μm) Ni x O y -ZnO films reveals localized p-n nanoheterojunctions with tunable oxygen vacancies (V o ) originating from both Ni x O y and ZnO nanocrystals. Optimizing the amount of oxygen vacancies leads to a 30-fold increase in the photochemoresistive response of these networks, enabling the detection of representative analyte concentrations down to 2 and 20 ppb at an optimal temperature of 150 °C and room temperature, respectively. Density functional theory calculations reveal that this performance enhancement is presumably due to an 80% increase in the analyte adsorption energy. This flexible nanofabrication approach in conjunction with straightforward vacancy control via photoactivation provides an effective strategy for engineering the photocatalytic activity of porous metal oxide semiconductor networks with applications in chemical sensors, photodetectors, and photoelectrochemical cells.

Background: Recent studies suggesting the importance of the gut-microbiome in intestinal aggregated alpha synuclein (α-syn) have led to the exploration of the possible role of the gut-brain axis in central nervous system degeneration. Proteus mirabilis (P. mirabilis), a gram-negative facultative anaerobic bacterium, has been linked to brain neurodegeneration in animal studies. We hypothesised that P. mirabilis-derived virulence factors aggregate intestinal α-synuclein and could prompt the pathogenesis of dopaminergic neurodegeneration in the brain., Methods: We used vagotomised- and antibiotic-treated male murine models to determine the pathogenesis of P. mirabilis during brain neurodegeneration. The neurodegenerative factor that is driven by P. mirabilis was determined using genetically mutated P. mirabilis. The pathological functions and interactions of the virulence factors were determined in vitro., Findings: The results showed that P. mirabilis-induced motor dysfunction and neurodegeneration are regulated by intestinal α-syn aggregation in vagotomised- or antibiotic-treated murine models. We deduced that the specific virulence factor, haemolysin A (HpmA), plays a role in the pathogenesis of P. mirabilis. HpmA is involved in α-synuclein oligomerisation and membrane pore formation, resulting in the activation of mTOR-mediated autophagy signalling in intestinal neuroendocrine cells., Interpretation: Taken together, the results of the present study suggest that HpmA can interact with α-syn and act as a possible indicator of brain neurodegenerative diseases that are induced by P. mirabilis., Funding: This study was supported by a grant from the National Research Foundation of Korea., Competing Interests: Declaration of interests EH, JGC, DHK and MSO are inventors with a provisional patent, “Method for diagnosing neurodegenerative disease using HpmA” that is licensed to MetaCen Therapeutics. MGP is a co-founder of MetaCen Therapeutics., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Chronic subdural hematoma (CSDH) is a common clinical situation in neurosurgical practice, but the optimal treatment option is controversial. This study aimed to evaluate the effect of cholesterol-lowering medications on and how they affected the prognoses of CSDH patients., Methods: In this multi-institutional observational study performed in Korea, data from recently treated CSDH patients were gathered from 5 hospitals. A total of 462 patients were collected from March 2010 to June 2021. Patient clinical characteristics, history of underlying diseases and their treatments, radiologic features, and surgical outcomes were analyzed., Results: Seventy-five patients experienced recurrences, and 62 had reoperations after the initial burr hole surgery. Among these, 15 patients with recurrences and 12 with reoperations were taking cholesterol-lowering medications. However, the use of medications did not significantly affect recurrence or reoperation rates (P = 0.350, P = 0.336, respectively). When analyzed by type of medication, no clinically relevant differences in total cholesterol (TC), triglyceride (TG), or low-density lipoprotein cholesterol (LDL-C) levels were identified. The combination of a statin drug and ezetimibe significantly elevated high-density lipoprotein cholesterol (HDL-C) levels (P = 0.004). TC, LDL-C, and TG levels did not significantly affect patient prognoses. However, HDL-C levels and recurrence (odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.94-0.99; p = 0.010) were negatively correlated. An HDL-C level of 42.50 mg/dL was identified as the threshold for recurrence and reoperation., Conclusions: In this study, using cholesterol-lowering medications did not significantly impact the prognosis of patients who underwent surgical management for a chronic subdural hematoma. However, the findings showed that the higher the HDL-C level, the lower the probability of recurrence and reoperation., (© 2023. The Author(s).)

Four new 26-carboxylated ergostane-type sterols (Sarcodonol A-D) were isolated from 70% ethanol extracts of dried fruiting bodies of Sarcodon imbricatus. Their chemical structures were elucidated using 1D- and 2D-nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry, and confirmed by comparison with previously reported data. As far as we know, this is the first instance of isolating a 26-carboxylated ergostane-type sterol from nature. The determined antiviral efficacy of sarcodonol A-D (1-4) against HCoV-OC43 in MRC-5 cells confirmed that sarcodonol D (4) had significant antiviral activity. Notably, sarcodonol D (4) potently blocked virus infection at low-micromolar concentration and showed high SI (IC 50  = 2.26 μM; CC 50  > 100 μM; SI > 44.2). In addition, this research shows that the antiviral effect of sarcodonol D (4) via reduced apoptosis increased by viral infection is through mitochondrial stress regulation. This suggests that sarcodonol D (4) is a potential candidate for use as an antiviral treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Chronic subdural hematoma (CSDH) patients using antithrombotic agents (AT) at high risk for cardiovascular disease are increasing. The authors aimed to analyze the factors influencing outcome by targeting patients using AT and to establish a desirable treatment strategy., Methods: A retrospective analysis was performed on data from 462 patients who underwent burr hole trephination (BHT) surgery for CSDH at five hospitals from March 2010 to June 2021. Outcomes included incidence of postoperative acute bleeding, recurrence rate, and morbidity or mortality rate. Patients were divided into the following four groups based on their history of AT use : no AT. Only antiplatelet agents (AP), only anticoagulants (AC), both of AP and AC. In addition, a concurrent literature review was conducted alongside our cohort study., Results: Of 462 patients, 119 (119/462, 25.76%) were using AT. AP prescription did not significantly delay surgery (p=0.318), but AC prescription led to a significant increase in the time interval from admission to operation (p=0.048). After BHT, AP or AC intake significantly increased the period required for an in-dwelling drain (p=0.026 and p=0.037). The use of AC was significantly related to acute bleeding (p=0.044), while the use of AP was not (p=0.808). Use of AP or AC had no significant effect on CSDH recurrence (p=0.517 and p=1.000) or reoperation (p=0.924 and p=1.000). Morbidity was not statistically correlated with use of either AP or AC (p=0.795 and p=0.557, respectively), and there was no significant correlation with mortality for use of these medications (p=0.470 and p=1.000)., Conclusion: Elderly CSDH patients may benefit from maintenance of AT therapy during BHT due to reduced thromboembolic risk. However, the use of AC necessitates individualized due to potential postoperative bleeding. Careful post-operative monitoring could mitigate prognosis and recurrence impacts.

Herpes simplex virus 1 (HSV-1) is double-stranded DNA virus that belongs to the Orthoherpesviridae family. It causes serious neurological diseases of the central nervous system, such as encephalitis. The current U.S. Food and Drug Administration (FDA)-approved drugs for preventing HSV-1 infection include acyclovir (ACV) and valacyclovir; however, their long-term use causes severe side effects and often results in the emergence of drug-resistant strains. Therefore, it is important to discover new antiviral agents that are safe and effective against HSV-1 infection. Korean chestnut honey (KCH) has various pharmacological activities, such as antioxidant, antibacterial, and anti-inflammation effects; however, antiviral effects against HSV-1 have not yet been reported. Therefore, we determined the antiviral activity and mechanism of action of KCH after HSV-1 infection on the cellular level. KCH inhibited the HSV-1 infection of host cells through binding and virucidal steps. KCH decreased the production of reactive oxygen species (ROS) and calcium (Ca 2+ ) following HSV-1 infection and suppressed the production of inflammatory cytokines by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) activity. Furthermore, we found that KCH inhibited the expression of the nod-like receptor protein 3 (NLRP3) inflammasome during HSV-1 infection. Taken together, the antiviral effects of KCH occur through multiple targets, including the inhibition of viral replication and the ROS-mediated NLRP3 inflammasome pathway. Our findings suggest that KCH has potential for the treatment of HSV-1 infection and related diseases.

The new velocity fields based on the Generalized Ekman (GE) theory to trace floating algae were derived and verified by drifter observations and compared to reanalysis datasets in the Yellow Sea (YS). Two velocity fields using diagnostic approaches and two velocity fields from reanalysis datasets were examined. The results revealed that the diagnostic velocity fields had comparable accuracy to the reanalysis datasets, even locally better. Then, we applied each velocity field to trace green algae, Ulva prolifera, in July 2011 and brown algae, Sargassum horneri, in May 2017 using particle tracking experiments. In addition, drifter trajectories were simulated, and error accumulation speed was estimated for each velocity field. Simulation results using the diagnostic velocity fields consistently showed better agreement with satellite images and in situ observations than those using reanalysis datasets, demonstrating that the diagnostic velocity could be a superior tool for simulating surface-floating substances and organisms. The approach to derive diagnostic velocity fields can be easily applied instead of relying on heavy computing numerical models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Since the first African swine fever (ASF) outbreak occurred at a pig farm in South Korea in September 2019, as of 31 January 2023, 31 ASF cases have occurred at pig farms, while 2799 ASF virus (ASFV)-infected wild boars have been identified. The circulation of ASFV in wild boar populations poses a high risk of spillover to pig farms in the country. However, information on the changes in the pathogenicity of Korean ASFV strains from wild boars is not available. Investigating the pathogenicity of ASFV strains from pig farms is the only way to predict their alterations. In a previous study, no changes in the pathogenicity of ASFV strains circulating during 2019-2021 were identified through animal experiments. In this study, we chose two ASFV strains with potentially reduced pathogenicity among ten viruses obtained from pig premises from 2022 to January 2023 and estimated their pathogenicities and pathological characteristics. All the inoculated pigs died 8-10 days post-inoculation after showing pyrexia, depression, anorexia, and recumbency together with the common pathological lesions of enlarged hemorrhagic lymph nodes and splenomegaly with infarction. These results support that the pathogenicity among ASFV isolates in South Korea still remained unchanged during the study period.

Photodynamic therapy (PDT) has shown promise in reducing metastatic colorectal cancer (CRC); however, the underlying mechanisms remain unclear. Modulating tumor-infiltrating immune cells by PDT may be achieved, which requires the characterization of immune cell populations in the tumor microenvironment by single-cell RNA sequencing (scRNA-seq). Here, we determined the effect of Chlorin e6 (Ce6)-mediated PDT on tumor-infiltrating T cells using scRNA-seq analysis. We used a humanized programmed death-1/programmed death ligand 1 (PD-1/PD-L1) MC38 cell allograft mouse model, considering its potential as an immunogenic cancer model and in combination with PD-1/PD-L1 immune checkpoint blockade. PDT treatment significantly reduced tumor growth in mice containing hPD-1/PD-L1 MC38 tumors. scRNA-seq analysis revealed that the PDT group had increased levels of CD8 + activated T cells and CD8 + cytotoxic T cells, but decreased levels of exhausted CD8 + T cells. PDT treatment also enhanced the infiltration of CD8 + T cells into tumors and increased the production of key effector molecules, including granzyme B and perforin 1. These findings provide insight into immune-therapeutic modulation for CRC patients and highlight the potential of PDT in overcoming immune evasion and enhancing antitumor immunity.

Influenza is an acute respiratory disorder caused by the influenza virus and is associated with prolonged hospitalization and high mortality rates in older individuals and chronically ill patients. Vaccination is the most effective preventive strategy for ameliorating seasonal influenza. However, the vaccine is not fully effective in cases of antigenic mismatch with the viral strains circulating in the community. The emergence of resistance to antiviral drugs aggravates the situation. Therefore, developing new vaccines and antiviral drugs is essential. Castanea crenata honey (CH) is an extensively cultivated food worldwide and has been used as a nutritional supplement or herbal medicine. However, the potential anti-influenza properties of CH remain unexplored. In this study, the in vitro and in vivo antiviral effects of CH were assessed. CH significantly prevented influenza virus infection in mouse Raw264.7 macrophages. CH pretreatment inhibited the expression of the viral proteins M2, PA, and PB1 and enhanced the secretion of proinflammatory cytokines and type-I interferon (IFN)-related proteins in vitro . CH increased the expression of RIG-1, mitochondrial antiviral signaling (MAVS) protein, and IFN-inducible transmembrane protein, which interferes with virus replication. CH reduced body weight loss by 20.9%, increased survival by 60%, and decreased viral replication and inflammatory response in the lungs of influenza A virus-infected mice. Therefore, CH stimulates an antiviral response in murine macrophages and mice by preventing viral infection through the RIG-1-mediated MAVS pathway. Further investigation is warranted to understand the molecular mechanisms involved in the protective effects of CH on influenza virus infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kwon, Kim, Kim, Kim, Han, Lee, Choi and Choi.)

Introduction: Parkinson's disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in the absence of a crucial noninvasive biomarker. Here, we used non-targeted metabolomics profiling to identify metabolic alterations in the colon and plasma samples of Proteus mirabilis ( P. mirabilis )-treated mice, which is a possible animal model for investigating the microbiota-gut-brain axis., Methods: We performed gas chromatography-mass spectrometry to analyze the samples and detected metabolites that could reflect P. mirabilis -induced disease progression and pathology., Results and Discussion: Pattern, correlation and pathway enrichment analyses showed significant alterations in sugar metabolism such as galactose metabolism and fructose and mannose metabolism, which are closely associated with energy metabolism and lipid metabolism. This study indicates possible metabolic factors for P. mirabilis -induced pathological progression and provides evidence of metabolic alterations associated with P. mirabilis -mediated pathology of brain neurodegeneration., Competing Interests: MP was employed by MetaCen Therapeutics Inc. R&D Center. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huh, Choi, Lee, Kim, Choi, Ju, Eo, Park, Kim, Park, Lee and Oh.)

Military accidents are often associated with stress and depressive psychological conditions among soldiers, and they often fail to adapt to military life. Therefore, this study analyzes whether there are differences in EEG and pulse wave indices between general soldiers and three groups of soldiers who have not adapted to military life and are at risk of accidents. Data collection was carried out using a questionnaire and a device that can measure EEG and pulse waves, and data analysis was performed using SPSS. The results showed that the concentration level and brain activity indices were higher in the general soldiers and the soldiers in the first stage of accident risk. The body stress index was higher for each stage of accident risk, and the physical vitality index was higher for general soldiers. Therefore, it can be seen that soldiers who have not adapted to military life and are at risk of accidents have somewhat lower concentration and brain activity than general soldiers, and have symptoms of stress and lethargy. The results of this study will contribute to reducing human accidents through EEG and pulse wave measurements not only in the military but also in occupations with a high risk of accidents such as construction.

Objective: Chemotherapeutic agents such as docetaxel (DTX) can trigger chemotherapy-induced peripheral neuropathy (CIPN), which is characterized by unbearable pain. This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation (LFMNS) on DTX-induced tactile hypersensitivity in mice., Methods: To produce CIPN, DTX was administered intraperitoneally 4 times, once every 2 d, to male ICR mice. LFMNS was performed on the wrist area, and the pain response was measured using von Frey filaments on both hind paws. Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brain-derived neurotrophic factor (BDNF)., Results: Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area., Conclusions: LFMNS might be an effective non-pharmaceutical option for treating patients suffering from CIPN regulating the expression of peripheral and central BDNF.

Parkinson's disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus mirabilis ( P. mirabilis ) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis -induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by amyloid-β (Aβ) deposition, accompanied by neuroinflammation and memory dysfunction. Houttuyniae Herba (aerial parts of Houttuynia cordata, also known as fish mint; HH), an herbal medicine traditionally used to treat fever, urinary disorders, and pus, is revealed to protect neurons from Aβ toxicity and regulate cholinergic dysfunction in AD models. In this study, we aimed to investigate the effects of HH on excessive accumulation of Aβ followed by neuroinflammation, synaptic degeneration, and memory impairment. Two-month-old 5xFAD transgenic mice were administered HH at 100 mg/kg for 4 months. We observed that HH treatment ameliorated memory impairment and reduced Aβ deposits in the brains of the mice. HH directly inhibited Aβ aggregation in vitro using the Thioflavin T assay and indirectly suppressed the amyloidogenic pathway by increasing alpha-secretase expression in the mice brain. In addition, HH exerted antineuroinflammatory effects by reducing of glial activation and p38 phosphorylation. Moreover, HH treatment increased the expression of synaptophysin, a presynaptic marker protein. Overall, HH alleviates memory impairment in AD by facilitating nonamyloidogenic pathway and inhibiting neuroinflammation. Therefore, we suggest that HH can be a promising herbal drug for patients with AD requiring multifaceted improvement., (© 2023 John Wiley & Sons Ltd.)

Type 2 diabetes mellitus (T2DM) is one of the biggest public health issues worldwide and closely related to development of other chronic diseases such as cardiovascular diseases, cancer and neurodegenerative diseases. Considerable percentage of T2DM patients undergo have suffered from binge eating disorder which exacerbates insulin resistance and metabolic challenges. Longan ( Dimocarpus longan L. ) and its constituents are reported for their various health benefits. However, it is still unknown whether longan fruit supplementation can ameliorate glucose homeostasis and binge eating disorder found in T2DM. The current study aimed to investigate whether longan fruit extract (LE) supplementation can improve diabetic hyperglycemia through modulation of feeding center located in hypothalamus of db/db T2DM mice. As a result, LE supplementation ameliorated fasting blood glucose levels and reduced excessive epididymal fat accumulation. In addition, LE administration improved glucose tolerance and insulin sensitivity in db/db mice. Especially, LE supplemented mice showed less food consumption which was in line with increase of pro-opiomelanocortin (POMC) neuronal activities and decrease of agouti-related peptide (AgRP) neuronal activities. Furthermore, LE supplementation reduced hypothalamic endoplasmic reticulum (ER) stress which was stimulated in db/db mice. As ER stress is a crucial factor involving in appetite control and glucose homeostasis, the effect of LE supplementation on circulating glucose levels and feeding behavior might be mediated by suppression of hypothalamic ER stress. Collectively, these findings suggest that LE could be a potential nutraceutical for improvement of T2DM as well as patients with satiety issues., Competing Interests: SK, JC, SWK, and MS are employed by MThera Pharma Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Eo, Kim, Ju, Huh, Kim, Choi, Kim, Son and Oh.)

Spin Seebeck effect (SSE) refers to the generation of an electric voltage transverse to a temperature gradient via a magnon current. SSE offers the potential for efficient thermoelectric devices because the transverse geometry of SSE enables to utilize waste heat from a large-area source by greatly simplifying the device structure. However, SSE suffers from a low thermoelectric conversion efficiency that must be improved for widespread application. Here we show that the SSE substantially enhances by oxidizing a ferromagnet in normal metal/ferromagnet/oxide structures. In W/CoFeB/AlO x structures, voltage-induced interfacial oxidation of CoFeB modifies the SSE, resulting in the enhancement of thermoelectric signal by an order of magnitude. We describe a mechanism for the enhancement that results from a reduced exchange interaction of the oxidized region of ferromagnet, which in turn increases a temperature difference between magnons in the ferromagnet and electrons in the normal metal and/or a gradient of magnon chemical potential in the ferromagnet. Our result will invigorate research for thermoelectric conversion by suggesting a promising way of improving the SSE efficiency., (© 2023. The Author(s).)

Biocompatible field-effect-transistor-based biosensors have drawn attention for the development of next-generation human-friendly electronics. High-performance electronic devices must achieve low-voltage operation, long-term operational stability, and biocompatibility. Herein, we propose an electrolyte-gated thin-film transistor made of large-area solution-processed indium-gallium-zinc oxide (IGZO) semiconductors capable of directly interacting with live cells at physiological conditions. The fabricated transistors exhibit good electrical performance operating under sub-0.5 V conditions with high on-/off-current ratios (>10 7 ) and transconductance (>1.0 mS) over an extended operational lifetime. Furthermore, we verified the biocompatibility of the IGZO surface to various types of mammalian cells in terms of cell viability, proliferation, morphology, and drug responsiveness. Finally, the prolonged stable operation of electrolyte-gated transistor devices directly integrated with live cells provides the proof-of-concept for solution-processed metal oxide material-based direct cellular interfaces., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Repetitive sequence-based PCR (rep-PCR) is a potential epidemiological technique that can provide high-throughput genotype fingerprints of heterogeneous Mycobacterium strains rapidly. Previously published rep-PCR primers, which are based on nucleotide sequences of Gram-negative bacteria may have low specificity for mycobacteria. Moreover, it was difficult to ensure the continuity of the study after the commercial rep-PCR kit was discontinued. Here, we designed a novel rep-PCR for Mycobacterium intracellulare , a major cause of nontuberculous mycobacterial pulmonary disease with frequent recurrence. We screened the 7,645 repeat sequences for 200 fragments from the genome of M. intracellulare ATCC 13950 in silico , finally generating five primers with more than 90% identity for a total of 226 loci in the genome. The five primers could make different band patterns depending on the genome of three different M. intracellulare strains using an in silico test. The novel rep-PCR with the five primers was conducted using 34 bacterial samples of 7 species containing 25  M. intracellulare clinical isolates, compared with previous published rep-PCRs. This shows distinguished patterns depending on species and blotting assay for 6 species implied the sequence specificity of the five primers. The Designed rep-PCR had a 95-98% of similarity value in the reproducibility test and showed 7 groups of fingerprints in M. intracellulare strains. Designed rep-PCR had a correlation value of 0.814 with VNTR, reference epidemiological method. This study provides a promising genotype fingerprinting method for tracing the recurrence of heterogeneous M. intracellulare ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shin, Ha, Kim, Choi, Park, Park, Park, Byun, Jung, Baik, Lee, Kang, Yoo and Shin.)