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Abstract Commercial wearable biosignal sensing technologies encounter challenges associated with irritation or discomfort caused by unwanted objects in direct contact with the skin, which can discourage the widespread adoption of wearable devices. To address this issue, we propose a fabric-based lamina emergent MXene-based electrode, a lightweight and flexible shape-morphing wearable bioelectrode. This work offers an innovative approach to biosignal sensing by harnessing the high electrical conductivity and low skin-to-electrode contact impedance of MXene-based dry electrodes. Its design, inspired by Nesler’s pneumatic interference actuator, ensures stable skin-to-electrode contact, enabling robust biosignal detection in diverse situations. Extensive research is conducted on key design parameters, such as the width and number of multiple semicircular legs, the radius of the anchoring frame, and pneumatic pressure, to accommodate a wide range of applications. Furthermore, a real-time wireless electrophysiological monitoring system has been developed, with a signal-to-noise ratio and accuracy comparable to those of commercial bioelectrodes. This work excels in recognizing various hand gestures through a convolutional neural network, ultimately introducing a shape-morphing electrode that provides reliable, high-performance biosignal sensing for dynamic users.

Purpose Children with comorbidities have a higher risk of severe, coronavirus disease 2019 (COVID-19). This study investigated the clinical features and outcomes of COVID-19 in children and adolescents with diabetes between January and March 2022. Methods We retrospectively reviewed the medical records of 123 children and adolescents (73 with type 1 diabetes and 50 with type 2 diabetes, 59 males and 64 females) aged

Abstract Continuous Glucose Monitoring (CGM) systems are revolutionizing the real‐time tracking of blood glucose levels, a cornerstone in effective diabetes management and optimal glycemic control. Transitioning from the “intermittent readings” offered by traditional Blood Glucose Monitoring (BGM) methods, CGM delivers an “uninterrupted flow” of glucose data, enabling a “more detailed” strategy for meeting treatment goals. Initially, the “uptake of CGM faced hurdles due to doubts about its precision, but continuous advancements in technology have not only resolved these concerns but also confirms CGM as a dependable and impactful instrument in diabetes management”. Concurrently, advancements in insulin pump technology have improved their portability and ease of use, greatly increasing patient adoption. The market reflects a growing demand for such innovative healthcare solutions, driven by an increased awareness of diabetes management and bolstered by supportive healthcare policies. Future prospects for CGM and insulin pump technologies are incredibly promising, offering the potential for highly personalized care and sophisticated treatment strategies. This paper aims to explore how the synergy between ongoing technological developments and evolving market dynamics is set to redefine the diabetes care paradigm, positioning CGM and insulin pumps as essential elements in enhancing the quality of life for individuals with diabetes.

Abstract The use of water-based chemistry in photolithography during semiconductor fabrication is desirable due to its cost-effectiveness and minimal environmental impact, especially considering the large scale of semiconductor production. Despite these benefits, limited research has reported successful demonstrations of water-based photopatterning, particularly for intrinsically water-soluble materials such as Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) due to significant challenges in achieving selective dissolution during the developing process. In this paper, we propose a method for the direct patterning of PEDOT:PSS in water by introducing an amphiphilic Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO-PPO-PEO, P123) block copolymer to the PEDOT:PSS film. The addition of the block copolymer enhances the stretchability of the composite film and reduces the hydrophilicity of the film surface, allowing for water absorption only after UV exposure through a photoinitiated reaction with benzophenone. We apply this technique to fabricate tactile and wearable biosensors, both of which benefit from the mechanical stretchability and transparency of PEDOT:PSS. Our method represents a promising solution for water-based photopatterning of hydrophilic materials, with potential for wider applications in semiconductor fabrication.

AbstractThe urgent demand for effective countermeasures against metallo-β-lactamases (MBLs) necessitates development of novel metallo-β-lactamase inhibitors (MBLIs). This study is dedicated to identifying critical chemical moieties within previously developed MBLIs, and critical MBLs should serve as the target in MBLI evaluations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic literature analysis was conducted, and the NCBI RefSeq genome database was exploited to access the abundance profile and taxonomic distribution of MBLs and their variant types. Through the implementation of two distinct systematic approaches, we elucidated critical chemical moieties of MBLIs, providing pivotal information for rational drug design. We also prioritised MBLs and their variant types, highlighting the imperative need for comprehensive testing to ensure the potency and efficacy of the newly developed MBLIs. This approach contributes valuable information to advance the field of antimicrobial drug discovery.

Abstract Colloidal nanocrystals (NCs) can be used to prepare high-color-purity metal halide perovskites (MHPs) for light-emitting displays. However, the NCs have a finite particle-size distribution, which broadens the linewidth of photoluminescence spectra under strong quantum confinement, and thereby degrades the color purity of the MHPs. This paper presents a simple method to quantify this externally-introduced broadening of linewidth $${{{{{{\boldsymbol{\Gamma }}}}}}}_{{{{{{\bf{SD}}}}}}}$$ Γ SD by combining experimental size-distribution histogram with size-dependent photoluminescence-wavelength (PL- $${{{{{\boldsymbol{\lambda }}}}}}$$ λ ) curve. We develop a semi-empirical method to estimate the other three contributions to the experimentally-measured full-width at half-maximum, $${{{{{{\boldsymbol{\Gamma }}}}}}}_{{{{{{\bf{EXP}}}}}}}$$ Γ EXP . Namely: the intrinsic linewidth $${{{{{{\boldsymbol{\Gamma }}}}}}}_{{{{{{\bf{LO}}}}}}}$$ Γ LO caused by exciton-longitudinal optical (LO) phonon Fröhlich coupling; the inhomogeneous linewidth $${{{{{{\boldsymbol{\Gamma }}}}}}}_{{{{{{\bf{o}}}}}}}$$ Γ o caused by imperfections-related scattering, and the broadening $${{{{{{\boldsymbol{\Gamma }}}}}}}_{{{{{{\bf{QC}}}}}}}$$ Γ QC due to the quantum-confinement effect. We show that $${{{{{{\boldsymbol{\Gamma }}}}}}}_{{{{{{\bf{LO}}}}}}}$$ Γ LO of a nanocrystal decreases together with the particle size, disappearing at 1.6 nm radius. Finally, we show that $${{{{{{\boldsymbol{\Gamma }}}}}}}_{{{{{{\bf{LO}}}}}}}$$ Γ LO is correlated with the degree of Fröhlich-polaron formation, hence proportional to the long-range LO-phonon-electron coupling.

Wearable electronics for the Internet of Things (IoT) have spurred interest in optimizing stretchable substrates, electrodes, and sensing materials. Specifically, wearable gas sensors are valuable for real-time monitoring of hazardous chemicals. For wearable gas sensors, a stable operation under mechanical deformation is required. Here, we introduce strain-insensitive Kirigami-structured gas sensors decorated with titanium dioxide (TiO2) functionalized carbon nanotubes (CNTs) for NO2 sensing. The Kirigami-shaped substrate is used to ensure mechanical stability when stretched. The developed device shows only a 1.3 % change in base resistance under 80 % strain. In addition, the impact of electro-thermal properties at various strain levels is analyzed to aid the understanding of the device's performance. The CNT-TiO2 composite induced alterations in p-n heterojunctions, improving the measurement sensitivity by approximately 250 % compared to a bare CNT sensor. Additionally, the sensors exhibited a 10-fold faster desorption rate due to the enhanced photocatalytic effect of TiO2 under UV exposure. Remarkably, the Kirigami-structured gas sensors maintained stable and repetitive sensing operation even under 80 % strain, which would be enough to be used in various wearable applications.

Abstract Surface electromyography (sEMG) sensors play a critical role in diagnosing muscle conditions and enabling prosthetic device control, especially for lower extremity robotic legs. However, challenges arise when utilizing such sensors on residual limbs within a silicon liner worn by amputees, where dynamic pressure, narrow space, and perspiration can negatively affect sensor performance. Existing commercial sEMG sensors and newly developed sensors are unsuitable due to size and thickness, or susceptible to damage in this environment. In this paper, our sEMG sensors are tailored for amputees wearing sockets, prioritizing breathability, durability, and reliable recording performance. By employing porous PDMS and Silbione substrates, our design achieves exceptional permeability and adhesive properties. The serpentine electrode pattern and design are optimized to improve stretchability, durability, and effective contact area, resulting in a higher signal-to-noise ratio (SNR) than conventional electrodes. Notably, our proposed sensors wirelessly enable to control of a robotic leg for amputees, demonstrating its practical feasibility and expecting to drive forward neuro-prosthetic control in the clinical research field near future.

Abstract The nuclear‐contaminated water in the seawater near the site of the Fukushima nuclear power plant (NPP) accident is being investigated for treating the radioactive material. One of the most important considerations in the treatment is the management of the vast aquatic area of the oceanic scale. There are two methods in the application of osmosis and filtration for the modeling. There is the molecule quantity by the water volume where the list of transition of quantities is shown, where it decreases to 10% from the reversed osmosis method and to 0.01% from the filtration method in 9 days. In the filtrations, the discharge variations in the sea are described as the maximum and minimum values within 100 square velocities. A design for the general radioactive contaminated seawater treatment facility is introduced.

Hepatitis B virus (HBV) infects approximately 300 million people worldwide, causing chronic infections. The HBV X protein (HBx) is crucial for viral replication and induces reactive oxygen species (ROS), leading to cellular damage. This study explores the relationship between HBx-induced ROS, p53 activation, and HBV replication. Using HepG2 and Hep3B cell lines that express the HBV receptor NTCP, we compared ROS generation and HBV replication relative to p53 status. Results indicated that HBV infection significantly increased ROS levels in p53-positive HepG2-NTCP cells compared to p53-deficient Hep3B-NTCP cells. Knockdown of p53 reduced ROS levels and enhanced HBV replication in HepG2-NTCP cells, whereas p53 overexpression increased ROS and inhibited HBV replication in Hep3B-NTCP cells. The ROS scavenger N-acetyl-L-cysteine (NAC) reversed these effects. The study also found that ROS-induced degradation of the HBx is mediated by the E3 ligase Siah-1, which is activated by p53. Mutations in p53 or inhibition of its transcriptional activity prevented ROS-mediated HBx degradation and HBV inhibition. These findings reveal a p53-dependent negative feedback loop where HBx-induced ROS increases p53 levels, leading to Siah-1-mediated HBx degradation and HBV replication inhibition. This study offers insights into the molecular mechanisms of HBV replication and identifies potential therapeutic targets involving ROS and p53 pathways.

Today’s research on human-robot teaming requires the ability to test artificial intelligence (AI) algorithms for perception and decision-making in complex real-world environments. Field experiments, also referred to as experiments “in the wild,” do not provide the level of detailed ground truth necessary for thorough performance comparisons and validation. Experiments on pre-recorded real-world data sets are also significantly limited in their usefulness because they do not allow researchers to test the effectiveness of active robot perception and control or decision strategies in the loop. Additionally, research on large human-robot teams requires tests and experiments that are too costly even for the industry and may result in considerable time losses when experiments go awry. The novel Real-Time Human Autonomous Systems Collaborations (RealTHASC) facility at Cornell University interfaces real and virtual robots and humans with photorealistic simulated environments by implementing new concepts for the seamless integration of wearable sensors, motion capture, physics-based simulations, robot hardware and virtual reality (VR). The result is an extended reality (XR) testbed by which real robots and humans in the laboratory are able to experience virtual worlds, inclusive of virtual agents, through real-time visual feedback and interaction. VR body tracking by DeepMotion is employed in conjunction with the OptiTrack motion capture system to transfer every human subject and robot in the real physical laboratory space into a synthetic virtual environment, thereby constructing corresponding human/robot avatars that not only mimic the behaviors of the real agents but also experience the virtual world through virtual sensors and transmit the sensor data back to the real human/robot agent, all in real time. New cross-domain synthetic environments are created in RealTHASC using Unreal Engine™, bridging the simulation-to-reality gap and allowing for the inclusion of underwater/ground/aerial autonomous vehicles, each equipped with a multi-modal sensor suite. The experimental capabilities offered by RealTHASC are demonstrated through three case studies showcasing mixed real/virtual human/robot interactions in diverse domains, leveraging and complementing the benefits of experimentation in simulation and in the real world.

Abstract The genotype–phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype–phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P

Monogenic diabetes is commonly caused by single-gene mutations. This disease ranges from 1% to 5% in all cases of diabetes and is less affected by behavior and environment. Neonatal diabetes mellitus (NDM) and maturity-onset diabetes of the young (MODY) account for a major proportion of monogenic diabetes, while syndromic diabetes constitutes a smaller proportion. Diagnosis of monogenic diabetes has improved from being based on clinical phenotypes to molecular genetics, with significant advancement of genome sequencing skills. Precise medication for monogenic diabetes is based on genetic testing; therefore, an accurate diagnosis is essential. Due to the basic clinical criteria (diagnosed < 6 months of age), genetic testing and precision treatment for NDM are fast and uncomplicated. The MODY probability calculator was developed; however, it remains challenging to distinguish MODY from type 1 and 2 diabetes due to the lack of a single diagnostic criteria and genetic testing. Additionally, the high cost and complicated interpretation of these genetic test results add to these challenges. This review will discuss the distinct etiology and subgroups that contribute to predicting and treating clinical phenotypes associated with monogenic diabetes. Furthermore, we will review the recent Korean studies and suggest methods of prioritizing patient screening for genetic testing.

Ewart et al. assess the performance of a human Liver-Chip for predictive toxicology. They also perform an economic analysis to demonstrate its potential financial value for the pharmaceutical industry.

Following the climate-related disasters considered by several efforts, the nuclear capacity needs to double by 2050 compared to 2015. So, it is reasonable to investigate global warming incorporated with the fuzzy set theory for nuclear energy consumption in the aspect of fuzziness and nonlinearity of temperature variations. The complex modeling is proposed for the enhanced assessment of climate change where simulations indicate the degree of influence with the Boolean values between 0.0 and 1.0 in the designed variables. In the case of OIL, there are many 1.0 values between 20th and 60th months in the simulations where there are 10 times more for a 1.0 value in influence. Hence, the temperature variable can give the effective time using this study for 100 months. In the analysis, the 1.0 value in NUCLEAR means the highest influence of the modeling as the temperature increases resulting in global warming. In detail, the first influence happens near the 8th month and then there are four times more influences than effects in the early part of the temperature mitigation. Eventually, in the GLOBAL WARMING, the highest peak is around the 20th month, and then it is stabilized.

Abstract The nuclear dismantling assessment is analyzed with the fuzzy set and deep‐learning algorithm, where the project preference time search (PPTS) has been constructed. Artificial intelligence (AI) management is applied to nuclear decommissioning for the best estimation. The basic data are from three factors, Licensee, NRC, and Public. In the analysis, the highest OUTPUT value is 0.0513151 in the 72nd year, which is the best time for decommissioning, because the confidence value in the 37th year is 78.76% compared to that of the 72nd year. In the other case of membership functions with right‐shift values, the change rate is higher in the 72nd year as being similar to the value in the 37th year near 0.09 in final confidence value. The trend is a new function that shows two peaks compared to the previous one. The other cases could be made by comparing in the interested time. Finally, the list of reactor decommissions processes with numbering is used to find out the very confident time using the final confidence value as the PPTS method.

Hepatitis C virus (HCV) is constantly exposed to considerable oxidative stress, characterized by elevated levels of reactive oxygen species, including hydrogen peroxide (H2O2), during acute and chronic infection in the hepatocytes of patients. However, the effect of oxidative stress on HCV replication is largely unknown. In the present study, we demonstrated that H2O2 downregulated HCV Core levels to inhibit HCV replication. For this purpose, H2O2 upregulated p53 levels, resulting in the downregulation of both the protein and enzyme activity levels of DNA methyltransferase 1 (DNMT1), DNMT3a, and DNMT3b, and activated the expression of E6-associated protein (E6AP) through promoter hypomethylation in the presence of HCV Core. E6AP, an E3 ligase, induced the ubiquitin-dependent proteasomal degradation of HCV Core in a p53-dependent manner. The inhibitory effect of H2O2 on HCV replication was almost completely nullified either by treatment with a representative antioxidant, N-acetyl-L-cysteine, or by knockdown of p53 or E6AP using a specific short hairpin RNA, confirming the roles of p53 and E6AP in the inhibition of HCV replication by H2O2. This study provides insights into the mechanisms that regulate HCV replication under conditions of oxidative stress in patients.

Pseudomonas aeruginosa is the primary opportunistic human pathogen responsible for a range of acute and chronic infections; it poses a significant threat to immunocompromised patients and is the leading cause of morbidity and mortality for nosocomial infections. Its high resistance to a diverse array of antimicrobial agents presents an urgent health concern. Among the mechanisms contributing to resistance in P. aeruginosa, the horizontal acquisition of antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) has gained recognition as a substantial concern in clinical settings, thus indicating that a comprehensive understanding of ARG dissemination within the species is strongly required for surveillance. Here, two approaches, including a systematic literature analysis and a genome database survey, were employed to gain insights into ARG dissemination. The genome database enabled scrutinizing of all the available sequence information and various attributes of P. aeruginosa isolates, thus providing an extensive understanding of ARG dissemination within the species. By integrating both approaches, with a primary focus on the genome database survey, mobile ARGs that were linked or correlated with MGEs, important sequence types (STs) carrying diverse ARGs, and MGEs responsible for ARG dissemination were identified as critical factors requiring strict surveillance. Although human isolates play a primary role in dissemination, the importance of animal and environmental isolates has also been suggested. In this study, 25 critical mobile ARGs, 45 critical STs, and associated MGEs involved in ARG dissemination within the species, are suggested as critical factors. Surveillance and management of these prioritized factors across the One Health sectors are essential to mitigate the emergence of multidrug-resistant (MDR) and extensively resistant (XDR) P. aeruginosa in clinical settings.

The hepatitis B virus (HBV) is constantly exposed to significant oxidative stress characterized by elevated levels of reactive oxygen species (ROS), such as H2O2, during infection in hepatocytes of patients. In this study, we demonstrated that H2O2 inhibits HBV replication in a p53-dependent fashion in human hepatoma cell lines expressing sodium taurocholate cotransporting polypeptide. Interestingly, H2O2 failed to inhibit the replication of an HBV X protein (HBx)-null HBV mutant, but this defect was successfully complemented by ectopic expression of HBx. Additionally, H2O2 upregulated p53 levels, leading to increased expression of seven in absentia homolog 1 (Siah-1) levels. Siah-1, an E3 ligase, induced the ubiquitination-dependent proteasomal degradation of HBx. The inhibitory effect of H2O2 was nearly abolished not only by treatment with a representative antioxidant, N-acetyl-L-cysteine but also by knockdown of either p53 or Siah-1 using specific short hairpin RNA, confirming the role of p53 and Siah-1 in the inhibition of HBV replication by H2O2. The present study provides insights into the mechanism that regulates HBV replication under conditions of oxidative stress in patients.

Background The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. Methods This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. Results Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. Conclusions Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Purpose Sphingosine kinase is a lipid kinase that phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). S1P regulates pancreatic islet β-cell endoplasmic reticulum stress and proliferation. Type 1 and type 2 diabetes share some key pathogenic processes. In this study, we investigated whether secretion of insulin and production of S1P is altered in alloxan and glucose-treated cells from the rat pancreatic β-cell line RIN-5F. Methods RIN-5F cells were treated with 2 mM alloxan and 20 mM glucose for 6 hours or 24 hours before being evaluated by enzyme linked immunosorbent assay (ELISA) and Western blotting. Results Insulin secretion and expression was higher in RIN-5F cells treated with glucose compared to control cells. In contrast, alloxan treatment did not affect insulin secretion and expression in RIN-5F cells. Interestingly, compared with normal control levels, S1P/EDG-5 was increased in both alloxan and glucose-treated pancreatic β cell than normal control. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibition strongly decreased the expression of insulin and S1P in glucose- or alloxan-treated RIN-5F cells. Conclusions We observe that production of S1P is increased in both diabetic cell models. In addition, MAPK/ERK signaling regulates secretion of insulin and S1P expression in pancreatic β-cells. Based on the literature and our findings, S1P may be a promising agent for the treatment of insulin-related disorders.

Exercise-based cardiac rehabilitation (CR) improves the clinical outcomes in patients with cardiovascular diseases. However, few data exist regarding the role of early short-term CR in patients undergoing pacemaker (PM) implantation. We assessed whether short-term CR following PM implantation was sufficient to improve both physical function and quality of life (QOL). A total of 27 patients with a 6-minute walking distance (6MWD) of less than 85% of the predicted value on the day following PM implantation were randomly assigned to either the CR group (n = 12, 44.4%) or the non-CR group (n = 15, 55.6%). The CR group involved individualized exercise-based training with moderate intensity for 4 weeks after PM implantation. Cardiopulmonary exercise test (CPET), 6MWD, muscle strength, and Short Form (SF)-36 were assessed at baseline and at the 4-week follow-up. After a mean follow-up period of 38.3 days, both groups showed significantly improved 6MWD. Peak oxygen uptake improved in both groups on CPET, but the difference was not statistically significant. Knee extension power and handgrip strength were similar in both groups. Regarding QOL, only the CR group showed improved SF-36 scores in the items of vitality and mental health. There was no difference in any subscale in the non-CR group. Neither lead dislodgement nor significant changes in PM parameters were observed in any patient. Early short-term CR following PM implantation was associated with improved psychological subscales and can be safely performed without increasing the risk of procedure-related complications.

ABSTRACT Most clinical and experimental studies have suggested that hepatitis C virus (HCV) is dominant over hepatitis B virus (HBV) during coinfection, although the underlying mechanism remains unclear. In this study, we found that the HBV X protein (HBx) upregulates the levels of the HCV core protein to stimulate HCV replication during coinfection in human hepatoma cells. For this purpose, HBx upregulated both the protein levels and enzyme activities of cellular DNA methyltransferase 1 (DNMT1) and DNMT3b, and this subsequently reduced the expression levels of the E6-associated protein (E6AP), an E3 ligase of the HCV core protein, via DNA methylation. The ubiquitin-dependent proteasomal degradation of the HCV core protein was severely impaired in the presence of HBx, whereas this effect was not observed when E6AP was either ectopically expressed or restored by treatment with 5-aza-2′dC or DNMT1 knockdown. The effect of HBx on the HCV core protein was accurately reproduced in HBV/HCV coinfection systems, which were established by either monoinfection by HCV in Huh7D cells transfected with a 1.2-mer HBV replicon or coinfection by HBV and HCV in Huh7D-Na+-taurocholate cotransporting polypeptide cells, providing evidence for the stimulation of HCV replication by HBx. The present study may provide insights into understanding HCV dominance during HBV/HCV coinfection in patients. IMPORTANCE Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human pathogens that cause a substantial proportion of liver diseases worldwide. As the two hepatotropic viruses have the same modes of transmission, coinfection is often observed, especially in areas and populations where HBV is endemic. High-risk populations include people who inject drugs. Both clinical and experimental studies have shown that HCV is more dominant than HBV during coinfection, but the underlying mechanism remains unclear. In this study, we show that HBV X protein (HBx) stimulates HCV replication by inhibiting the expression of E6-associated protein (E6AP) via DNA methylation, thereby protecting the HCV core protein from proteasomal degradation, which can contribute to HCV dominance during HBV/HCV coinfection.

Abstract Reconfigurability of a device that allows tuning of its shape and stiffness is utilized for personal electronics to provide an optimal mechanical interface for an intended purpose. Recent approaches in developing such transformative electronic systems (TES) involved the use of gallium liquid metal, which can change its liquid–solid phase by temperature to facilitate stiffness control of the device. However, the current design cannot withstand excessive heat during outdoor applications, leading to undesired softening of the device when the rigid mode of operation is favored. Here, a gallium‐based TES integrated with a flexible and stretchable radiative cooler is presented, which offers zero‐power thermal management for reliable rigid mode operation in the hot outdoors. The radiative cooler can both effectively reflect the heat transfer from the sun and emit thermal energy. It, therefore, allows a TES‐in‐the‐air to maintain its temperature below the melting point of gallium (29.8 ℃) under hot weather with strong sun exposure, thus preventing unwanted softening of the device. Comprehensive studies on optical, thermal, and mechanical characteristics of radiative‐cooler‐integrated TES, along with a proof‐of‐concept demonstration in the hot outdoors verify the reliability of this design approach, suggesting the possibility of expanding the use of TES in various environments.

All-trans retinoic acid (ATRA), the most biologically active metabolite of vitamin A, is known to abolish the potential of HBx to downregulate the levels of p14, p16, and p21 and to stimulate cell growth during hepatitis B virus (HBV) infection, contributing to its chemopreventive and therapeutic effects against HBV-associated hepatocellular carcinoma. Here, we demonstrated that ATRA antagonizes HBx to inhibit HBV replication. For this effect, ATRA individually or in combination with HBx upregulated p53 levels, resulting in upregulation of seven in absentia homolog 1 (Siah-1) levels. Siah-1, an E3 ligase, induces ubiquitination and proteasomal degradation of HBx in the presence of ATRA. The ability of ATRA to induce Siah-1-mediated HBx degradation and the subsequent inhibition of HBV replication was proven in an in vitro HBV replication model. The effects of ATRA became invalid when either p53 or Siah-1 was knocked down by a specific shRNA, providing direct evidence for the role of p53 and Siah-1 in the negative regulation of HBV replication by ATRA.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a self-limiting lymphadenitis. It is a benign disease mainly characterized by high fever, lymph node swelling, and leukopenia. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease with clinical symptoms similar to those of KFD, but it requires a significantly more aggressive treatment. A 19-year-old Korean male patient was hospitalized for fever and cervical lymphadenopathy. Variable-sized lymph node enlargements with slightly necrotic lesions were detected on computed tomography. Biopsy specimen from a cervical lymph node showed necrotizing lymphadenitis with HLH. Bone marrow aspiration showed hemophagocytic histiocytosis. The clinical symptoms and the results of the laboratory test and bone marrow aspiration met the diagnostic criteria for HLH. The patient was diagnosed with macrophage activation syndrome—HLH, a secondary HLH associated with KFD. He was treated with dexamethasone (10 mg/m2/day) without immunosuppressive therapy or etoposide-based chemotherapy. The fever disappeared within a day, and other symptoms such as lymphadenopathy, ascites, and pleural effusion improved. Dexamethasone was reduced from day 2 of hospitalization and was tapered over 8 weeks. The patient was discharged on day 6 with continuation of dexamethasone. The patient had no recurrence at the 18-month follow-up.

Dual infection of hepatitis B virus (HBV) and hepatitis C virus (HCV) is closely associated with an increased risk of hepatocellular carcinoma; however, the underlying mechanism is poorly understood. In the present study, we found that HBV X protein (HBx) and HCV core protein work together to inhibit E-cadherin expression in human hepatoma cells. For this effect, they additively increased both the level and activity of enzymes, DNA methyltransferase 1, 3a, and 3b to induce promoter hypermethylation of E-cadherin in a p53-dependent fashion. Their additive effect on E-cadherin levels was reproduced in an in vitro HBV/HCV dual infection system using Huh7D-NTCP cells. As a result, HBV and HCV additively upregulated mesenchymal marker such as N-cadherin, Snail, Twist and Vimentin but cooperatively downregulated epithelial markers such as E-cadherin, Slug and Plakoglobin. In addition, the coinfected cells exhibited faster cell migration and higher invasion ability, as compared with monoinfection, which are hallmarks of epithelial-mesenchymal transition required for the initiation of metastasis in cancer progression.

Not applicable.

Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders, characterized by hypopigmentation of the eyes, skin, and hair, which result in ocular abnormalities and a risk of developing skin cancer. Currently, there is no ophthalmologic procedure or drug that prevents the clinical features of OCA. Here, we report a new type of OCA in two, unrelated Korean families with the same OCA2 mutation. Affected individuals in this study are different from those of previous reports in two aspects: an inheritance pattern and clinical presentation. All reported patients with OCA have shown an autosomal recessive inheritance pattern, while our patients showed an autosomal dominant inheritance pattern. Small amounts of pigment can be acquired with age in OCA, but there is no substantial variation from adolescence to adulthood in this regard. A case where the patient attained normal pigmentation levels has never been reported. However, our patients displayed completely normal pigmentation in their late twenties. Whole exome sequencing and in-silico analysis revealed a novel mutation, OCA2 c.2338G>A p.(G780S) (NM_000275) with a high likelihood of pathogenicity. Sanger sequencing of p.G780S identified the same mutation in the affected individuals, which was not found in the family members with normal phenotype. We hypothesize that OCA2 G780S not only acts as a pathogenic variant of OCA but also induces pigmentation by enhancing the melanogenesis gene expression of other modifier genes, such as SLC45A2 and TPC2. These findings may provide further understanding of melanin biosynthesis and new treatment methods for OCA.

In this paper, we present an electric field analysis for the optimal structural design of lightning rods for high performance with a charge transfer system (CTS). In the case of a conventional rod that is produced with an empirical design and structure without quantitative data because the design is structurally very simple, only the materials and radius of curvature of the lightning rod to concentrate the electric field at the tip part of the rod are considered. Recently, the development of new types of lightning rods, such as early streamer emission (ESE) and charge transfer system (CTS), has been introduced through simulation analysis and experiments, but detailed specifications and information about the optimal design and structure have not been fully reported. In this paper, we performed an electric field analysis of the structures and materials for the optimal structural design of lightning rods with a function of CTS through computer software analysis with consideration for the radius of curvature, the size of corona ring, and optimal position (X-axis and Y-axis) of the floating electrode. For optimal structural design of lightning rods based on electric field analysis, we used a source of lightning voltage with 1.2/50 µs based on a double exponential equation. The results revealed that the electric field on the relaxation part decreases as the radius of curvature and corona ring increases. For the radius of curvature, the electric field first decreases and then increases with increasing radius of curvature and reaches a minimum at 7 mm and a maximum above 8 mm. For the case of the corona ring, the electric field decreases with increasing corona ring, and the optimal size of the corona ring was selected as 4 mm; the size of the 4 mm corona ring uniformly formed the electric field both at the tip part of the ground current collector and the corona ring. For the electric field concentration part, we found that the optimal X-axis position of the floating electrode and the Y-axis position between the ionizer conductor and floating electrode are 7 mm and 0.1 mm, respectively. These simulation results in this paper are expected to provide useful information for the design of optimized CTS-type lightning rods.

Background Short stature is defined as a height below the 3rd percentile or more than two standard deviations below the mean for a given age, sex, and population. There have been inconsistent results regarding craniofacial morphology in short-statured children. This study aimed to analyze the differences between short-statured children with growth hormone deficiency, idiopathic short-statured children, and normal children. Methods Thirty-one short-statured children with growth hormone deficiency, 32 idiopathic short-statured children, and 32 healthy children were enrolled in this study. The measurements of their craniofacial structures from lateral cephalograms were evaluated. Results There were statistically significant differences among the three groups seven variables (anterior cranial base length, posterior cranial base length, total cranial base length, upper posterior facial height, posterior total facial height, mandibular ramus length, and overall mandibular length) in the linear measurement and five variables (saddle angle, gonial angle, mandibular plane angle, position of mandible, and maxilla versus mandible) in the angular measurement. Conclusion Compared to the control group, many linear and angular measurements of the craniofacial structures were significantly different in the two short-statured groups (p

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Gastrointestinal effects associated with Coronavirus Disease 2019 (COVID-19) are highly variable for reasons that are not understood. In this study, we used intestinal organoid-derived cultures differentiated from primary human specimens as a model to examine interindividual variability. Infection of intestinal organoids derived from different donors with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) resulted in orders of magnitude differences in virus replication in small intestinal and colonic organoid-derived monolayers. Susceptibility to infection correlated with angiotensin I converting enzyme 2 (ACE2) expression level and was independent of donor demographic or clinical features. ACE2 transcript levels in cell culture matched the amount of ACE2 in primary tissue, indicating that this feature of the intestinal epithelium is retained in the organoids. Longitudinal transcriptomics of organoid-derived monolayers identified a delayed yet robust interferon signature, the magnitude of which corresponded to the degree of SARS-CoV-2 infection. Interestingly, virus with the Omicron variant spike (S) protein infected the organoids with the highest infectivity, suggesting increased tropism of the virus for intestinal tissue. These results suggest that heterogeneity in SARS-CoV-2 replication in intestinal tissues results from differences in ACE2 levels, which may underlie variable patient outcomes.

In December 2019, the first coronavirus disease- 2019 (COVID-19) patient was reported in Wuhan, Hubei Province, China. Since then, the number of patients who suffered severe acute respiratory syndrome caused by the novel Coronavirus (SARS-CoV-2 or 2019-nCoV) has increased dramatically in Korea. This new variant virus induces pulmonary diseases, including cough, sore throat, rhinorrhea, dyspnea, and pneumonia. Because SARS-CoV-2 is an RNA virus, real-time reverse- transcriptase PCR has been used widely to diagnose COVID-19. As the Korea Centers for Disease Prevention and Control (KCDC) and Ministry of Food & Drug Safety (MFDS) approved emergency use authorization, clinical specimens collected from COVID-19 patients and even healthy people have been clinically diagnosed by laboratory medicine. Based on a literature search, this paper reviews the epidemiology, symptoms, molecular diagnostics approved by KCDC, a current diagnosis of COVID-19 in the laboratories, the difference between molecular and serological diagnosis, and guidelines for clinical specimens. In addition, the Korean guidelines of biosafety for clinical laboratory scientists are evaluated to prevent healthcare-associated infection. The author’s experience and lessons as clinical laboratory scientists will provide valuable insights to protect the domestic and international health community in this COVID-19 pandemic around the world.

Longitudinal bone growth is primarily mediated by the growth plate, which is a specialized cartilaginous structure. Aggrecan, encoded by ACAN, is a primary proteoglycan component of the extracellular matrix in both the growth plate and articular cartilage. Aggrecanopathies have emerged as a phenotype of genetic skeletal disease in humans. A heterozygous ACAN mutation causes short stature, premature growth cessation, and accelerated bone age maturation. We report the case of a 15-year-old boy with familial short stature, with height of 149 cm (Korean standard deviation score [SDS] of -3.6) and weight of 50.5 kg (-1.48 SDS). He presented with mild midfacial hypoplasia, frontal bossing, a broad chest, and a short neck. The father's and mother's heights were 150 cm (-4.8 SDS) and 153 cm (-1.69 SDS), respectively. The patient's bone age was 2–3 years more advanced than his chronological age, and no endocrine abnormalities were detected. Whole-exome sequencing followed by Sanger sequencing revealed a heterozygous ACAN mutation, c.512C>T (p.Ala171Val), in both the proband and his father. Short stature is generally associated with a delayed bone age, and this case suggests that ACAN mutations may be the most likely etiology among patients with short stature and an advanced bone age and should warrant early treatment.

Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of monogenic disorders characterized by ß-cell dysfunction. MODY accounts for between 2% and 5% of all diabetes cases, and distinguishing it from type 1 or type 2 diabetes is a diagnostic challenge. Recently, MODY-causing mutations have been identified in 14 different genes. Sanger DNA sequencing is the gold standard for identifying the mutations in MODY-related genes, and may facilitate the diagnosis. Despite the lower frequency among diabetes mellitus cases, a correct genetic diagnosis of MODY is important for optimizing treatment strategies. There is a discrepancy in the disease-causing locus between the Asian and Caucasian patients with MODY. Furthermore, the prevalence of the disease in Asian populations remains to be studied. In this review, the current understanding of MODY is summarized and the Asian studies of MODY are discussed in detail.

It is analyzed for the energy pattern affected by the social matters of the disease trend where the epidemic behavior is significantly important to present the prospect especially for the epidemic of the Coronavirus Disease 2019 (COVID-19). In this work, there are three kinds of data for the modeling where the power transactions, power plant type, and pandemic data are considered by the energy mix of South Korea. The COVID-19 based modeling for Electricity and Nuclear Energy vs. Energy shows that the energy trend decreases until 16.50th week and then it is in the peak point at 32.50th week. Otherwise, the nuclear energy trend decreases until 11.50th week and then it is in the peak point at 27.50th week. The nuclear energy trend increases after 44.25th week. So, the nuclear energy has a better prospect in energy markets. Therefore, the characteristics of an energy source can make an important impact on the market.

In this paper, we present the optimized air space of the lightning protection rod (SK-AOR380) with the function of a charge transfer system (CTS). For evaluation of CTS in the laboratory setting, some studies have focused on the modification of the structure and shape of the CTS; the air space is designed (>2 mm) as an empirical design without quantitative data. However, in this paper, we have focused on the air space between the ionizer conductor and current collector to control the inception and occurrence position of corona discharge in air insulation. This is because the performance, such as the initial corona discharge inception of CTS, is determined by the air space. The simulation analysis was performed in a narrow, micro-sized air space as a first step, where the air space was reduced to the extent possible for simulation. To evaluate the performance of SK-AOR380 according to the narrow air space, we considered the numerical analysis method. The fundamental equations consist of Poisson’s equation and the charge continuity equation. Poisson’s equation for electric fields is a fully coupled numerical model based on the charge continuity equations for a positively charged ion, negatively charged ion, and free electron. Fowler–Nordheim electron emission was employed for the boundary condition at the surface of the ionizer conductor. To simulate the corona discharge behavior under standard lightning impulse voltage, we used a source of lightning voltage with 1.2/50 μs based on a double exponential equation; the corona discharge behaviors (electric field distribution, free electron density, positive and negative ion density) were investigated dependent on each time step (0.5, 1 and 1.2 μs) until 3.5 μs. The results revealed that the characteristics graph of free electron density, positive and negative ion density showed similar trends, with lightning impulse voltage increasing with increasing time steps until 1.2 μs and each density resulted in a decreasing trend from 1.2 μs to 3.5 μs. The SK-AOR380 is improved with a decreasing air space in terms of electric field distribution, electron, and ion density. In other words, the 0.0005 mm air space created a non-uniform electric field distribution with a large field enhancement, causing ionization to initiate corona discharge. In addition, in the case of a 0.0005 mm air space, the electric field and electron density are increased by 1.3 and 1.9 times, respectively, than that of 0.001 mm. However, there was no longer a significant difference under 0.0005 mm in the simulation results. To improve the CTS, we suggest the air space between the ionizer conductor and current collector should be less than 2 mm than that of conventional CTS from our research work.

Objective: Clinical and radiological findings on neurosyphilis are fairly non-specific and there is a paucity of functional neuroimaging studies on neurosyphilis other than case reports and case series. The purpose of this study was to investigate brain perfusion abnormalities in patients with neurosyphilis.Methods: Four HIV-negative neurosyphilis patients and 4 healthy controls underwent clinical evaluation, brain technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission computed tomography (SPECT) imaging, and neuropsychological assessments which included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating—Sum of Boxes (CDR-SOB), and Global Deterioration Scale (GDS). Voxel-wise differences in regional cerebral blood flow were compared between the two groups.Results: Neuropsychological test results indicated cognitive impairment in all patients. SPECT analysis revealed multifocal hypoperfusion predominantly in the frontal, insular, and posterior cingulate regions in neurosyphilis patients compared with healthy controls (family-wise error corrected p < 0.05).Conclusions: Together with previous findings, our results suggest that the hypoperfusion in the frontal, insular, and posterior cingulate regions may reflect cognitive impairments observed in neurosyphilis patients. Further studies with larger samples are needed to confirm our findings.

Parkinson’s disease (PD), a neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons. The pathogenesis of PD is associated with several factors including oxidative stress, inflammation, and mitochondrial dysfunction. Ca2+ signaling plays a vital role in neuronal signaling and altered Ca2+ homeostasis has been implicated in many neuronal diseases including PD. Recently, we reported that apamin (APM), a selective antagonist of the small-conductivity Ca2+-activated K+ (SK) channel, suppresses neuroinflammatory response. However, the mechanism(s) underlying the vulnerability of DA neurons were not fully understood. In this study, we investigated whether APM affected 1-methyl-4-phenyl pyridinium (MPP+)-mediated neurotoxicity in SH-SY5Y cells and rat embryo primary mesencephalic neurons. We found that APM decreased Ca2+ overload arising from MPP+-induced neurotoxicity response through downregulating the level of CaMKII, phosphorylation of ERK, and translocation of nuclear factor NFκB/signal transducer and activator of transcription (STAT)3. Furthermore, we showed that the correlation of MPP+-mediated Ca2+ overload and ERK/NFκB/STAT3 in the neurotoxicity responses, and dopaminergic neuronal cells loss, was verified through inhibitors. Our findings showed that APM might prevent loss of DA neurons via inhibition of Ca2+-overload-mediated signaling pathway and provide insights regarding the potential use of APM in treating neurodegenerative diseases.

HBx, a multifunctional regulatory protein, plays an essential role in the replication and pathogenesis of the hepatitis B virus (HBV). In this study, we found that in human hepatoma cells, the tumor suppressor p53 downregulates HBx via ubiquitin-dependent proteasomal degradation. p53 transcriptional activity that results from HBV infection was not essential for this effect. This was shown by treatment with a potent p53 inhibitor, pifithrin-α. Instead, we found that p53 facilitated the binding of E6-associated protein (E6AP), which is an E3 ligase, to HBx and induced E6AP-mediated HBx ubiquitination in a ternary complex of p53, E6AP, and HBx. The ability of p53 to induce E6AP-mediated downregulation of HBx and inhibit HBV replication was demonstrated in an in vitro HBV infection system. This study may provide insights into the regulation of HBx and HBV replication, especially with respect to p53 status, which may also help in understanding HBV-associated tumorigenesis in patients.

Abstract For wearable electronics/optoelectronics, thermal management should be provided for accurate signal acquisition as well as thermal comfort. However, outdoor solar energy gain has restricted the efficiency of some wearable devices like oximeters. Herein, wireless/battery‐free and thermally regulated patch‐type tissue oximeter (PTO) with radiative cooling structures are presented, which can measure tissue oxygenation under sunlight in reliable manner and will benefit athlete training. To maximize the radiative cooling performance, a nano/microvoids polymer (NMVP) is introduced by combining two perforated polymers to both reduce sunlight absorption and maximize thermal radiation. The optimized NMVP exhibits sub‐ambient cooling of 6 °C in daytime under various conditions such as scattered/overcast clouds, high humidity, and clear weather. The NMVP‐integrated PTO enables maintaining temperature within ≈1 °C on the skin under sunlight relative to indoor measurement, whereas the normally used, black encapsulated PTO shows over 40 °C owing to solar absorption. The heated PTO exhibits an inaccurate tissue oxygen saturation (StO2) value of ≈67% compared with StO2 in a normal state (i.e., ≈80%). However, the thermally protected PTO presents reliable StO2 of ≈80%. This successful demonstration provides a feasible strategy of thermal management in wearable devices for outdoor applications.