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This study aimed to investigate the effect of Cordyceps militaris extract on the proliferation and apoptosis of non–small cell lung cancer (NSCLC) cells and determine the underlying mechanisms. We performed a CCK-8 assay to detect cell proliferation, detection of morphological changes through transmission electron microscopy (TEM), annexin V–FITC/PI double staining to analyze apoptosis, and immunoblotting to measure the protein expression of apoptosis and hedgehog signaling–related proteins, with C militaris treated NSCLC cells. In this study, we first found that C militaris reduced the viability and induced morphological disruption in NSCLC cells. The gene expression profiles indicated a reprogramming pattern of genes and transcription factors associated with the action of TCTN3 on NSCLC cells. We also confirmed that the C militaris –induced inhibition of TCTN3 expression affected the hedgehog signaling pathway. Immunoblotting indicated that C militaris –mediated TCTN3 downregulation induced apoptosis in NSCLC cells, involved in the serial activation of caspases. Moreover, we demonstrated that the C militaris negatively modulated GLI1 transcriptional activity by suppressing SMO/PTCH1 signaling, which affects the intrinsic apoptotic pathway. When hedgehog binds to the PTCH1, SMO dissociates from PTCH1 inhibition at cilia. As a result, the active GLI1 translocates to the nucleus. C militaris clearly suppressed GLI1 nuclear translocation, leading to Bcl-2 and Bcl-xL down-regulation. These results suggested that C militaris induced NSCLC cell apoptosis, possibly through the downregulation of SMO/PTCH1 signaling and GLI1 activation via inhibition of TCTN3. Taken together, our findings provide new insights into the treatment of NSCLC using C militaris .

Objective To estimate the prevalence of objectively confirmed olfactory and gustatory dysfunction in US adults reporting chronic rhinosinusitis (CRS) symptoms in a nationally representative database. Study Design Cross-sectional epidemiologic analysis. Setting Data were analyzed from the smell and taste component of the 2013-2014 NHANES data set (National Health and Nutrition Examination Survey). Methods Individuals reporting the presence of ≥2 cardinal CRS symptoms (nasal blockage, sinus pain, discolored mucus, and dysosmia) were identified as patients with a potential diagnosis of CRS. Associations were examined between the presence of CRS symptoms and both self-reported and objectively measured smell and taste. Results One-third (33%) of adults who have ≥2 CRS symptoms report subjective olfactory impairment, though only 18% of these adults have quantifiable olfactory dysfunction on objective testing. Of these adults, 27% report subjective taste impairment, but just 17% have quantifiable gustatory dysfunction on objective testing. The presence of ≥2 CRS symptoms was not significantly associated with objective olfactory or gustatory dysfunction, although the individual symptoms of subjective dysosmia and discolored mucus were associated with objectively confirmed olfactory dysfunction. Conclusion The prevalence of objective olfactory and gustatory dysfunction was higher among adults reporting the presence of ≥2 CRS symptoms, but the differences were not statistically significant. Specific sinonasal symptoms, including discolored mucus and subjective smell dysfunction, were significantly associated with objective smell impairment.

Most coronavirus vaccines focus on the spike (S) antigen, but the frequent mutations in S raise concerns about the vaccine efficacy against new variants. Although additional antigens with conserved sequences are have been tested, the extent to which these vaccines can provide immunity against different coronavirus species remains unclear. In this study, we assessed the potential of nucleocapsid (N) as a coronavirus vaccine antigen. Immunization with MERS-CoV N induced robust immune responses, providing significant protection against MERS-CoV. Notably, MERS-CoV N elicited cross-reactive T cell responses to SARS-CoV-2 N and significantly reduced lung inflammation following a SARS-CoV-2 challenge in the transient hACE2 mouse model. However, in K18-hACE transgenic mice, the vaccine showed limited protection. Collectively, our findings suggest that coronavirus N can be an effective vaccine antigen against homologous viruses, but its efficacy may vary across different coronaviruses, highlighting the need for further research on pan-coronavirus vaccines using conserved antigens., 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 Elsevier B.V. All rights reserved.)

Gastrointestinal disorders are widespread globally, with inflammatory diseases being particularly prominent. This study aimed to investigate the effect of Kjellmaniella crassifolia hot water extract (KCH) on lipopolysaccharide (LPS)-induced inflammation in human intestinal epithelial (Caco-2) cells and loperamide-induced constipation in BALB/c mice. The study's findings revealed that KCH dose-dependently increased the cell viability and reduced the NO production by decreasing the iNOS and COX-2 expression in LPS-stimulated Caco-2 cells. Also, KCH downregulated the mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) by regulating the activation of MAPK and NF-κB signaling pathways in LPS-stimulated Caco-2 cells. In addition, KCH increased the expression levels of tight junction proteins, occludin, ZO-1, and claudin-1 in a dose-dependent manner. Furthermore, in vivo study outcomes demonstrated that KCH improved intestinal transit, increased fecal moisture content, and reduced fecal impaction in constipated mice. KCH decreased the mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), thereby increasing the expression levels of intestinal tight junction proteins (occludin, ZO-1, and claudin-1) in the small intestine tissues of the experimental mice. These proteins may help regulate intestinal motility and improve stool passage, thus reducing constipation. These findings suggest that KCH could be a promising functional food ingredient for managing intestinal inflammation, inflammation-related disorders, constipation, and the pathophysiology of constipation.

Introduction/aims: The care burden of people living with amyotrophic lateral sclerosis (pALS) increases with disease progression. This study aimed to investigate the home care status and preparedness of care partners of pALS (cALS) in Korea., Methods: An online survey was conducted with family care partners of patients diagnosed with ALS for over 1 year in 2022. The data collected included care time, depression evaluated using the patient health questionnaire-9 (PHQ-9), preparedness for caregiving scale (PCS), and caregiver competence scale (CCS). Results were compared based on whether the pALS underwent a tracheostomy or not., Results: Ninety-eight cALS of 98 pALS participated in the study, of whom 59 pALS had undergone tracheostomy. Among the cALS, 60.2% were spouses, and 34.7% were children. The cALS took care of the patients for 13 (8-20) hours/day (median, interquartile range [IQR]) on weekdays and 15 (10-24) h/day on weekends. Among the cALS, 91.8% were depressed, and 28.6% had severe depression. The median (IQR) PCS and CCS scores were low (11/32 (8-15) and 8/20 (8-11), respectively), and both were lower in those caring for patients without than with tracheostomy (p < .001 and p < .02, respectively). Most cALS (77.6%) wished to continue caring for their pALS at home., Discussion: Family care partners of pALS spend more than half of each day caring for patients and are often depressed. Most cALS preferred providing care at home, but felt ill-prepared. Designing home-based medical care is necessary for pALS to thrive at home., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Three-dimensional optical nanostructures have garnered significant interest in photonics due to their extraordinary capabilities to manipulate the amplitude, phase, and polarization states of light. However, achieving complex three-dimensional optical nanostructures with bottom-up fabrication has remained challenging, despite its nanoscale precision and cost-effectiveness, mainly due to inherent limitations in structural controllability. Here, we report the optical characteristics of intricate two- and three-dimensional nanoarchitectures made of colloidal quantum dots fabricated with multi-dimensional transfer printing. Our customizable fabrication platform, directed by tailored interface polarity, enables flexible geometric control over a variety of one-, two-, and three-dimensional quantum dot architectures, achieving tunable and advanced optical features. For example, we demonstrate a two-dimensional quantum dot nanomesh with tuned subwavelength square perforations designed by finite-difference time-domain calculations, achieving an 8-fold enhanced photoluminescence due to the maximized optical resonance. Furthermore, a three-dimensional quantum dot chiral structure is also created via asymmetric stacking of one-dimensional quantum dot layers, realizing a pronounced circular dichroism intensity exceeding 20°., (© 2024. The Author(s).)

Anti-tumor therapies reliant on reactive oxygen species (ROS) as primary therapeutic agents face challenges due to a limited oxygen substrate. Photodynamic therapy (PDT) is particularly hindered by inherent hypoxia, while chemodynamic therapy (CDT) encounters obstacles from insufficient endogenous hydrogen peroxide (H 2 O 2 ) levels. In this study, we engineered biodegradable tumor microenvironment (TME)-activated hollow mesoporous MnO 2 -based nanotheranostic agents, designated as HAMnO 2 A. This construct entails loading artemisinin (ART) into the cavity and surface modification with a mussel-inspired polymer ligand, namely hyaluronic acid-linked poly(ethylene glycol)-diethylenetriamine-conjugated (3,4-dihydroxyphenyl) acetic acid, and the photosensitizer Chlorin e6 (mPEG-HA-Dien-(Dhpa/Ce6)), facilitating dual-modal imaging-guided PDT/CDT synergistic therapy. In vitro experimentation revealed that HAMnO 2 A exhibited ideal physiological stability and enhanced cellular uptake capability via CD44-mediated endocytosis. Additionally, it was demonstrated that accelerated endo-lysosomal escape through the pH-dependent protonation of Dien. Within the acidic and highly glutathione (GSH)-rich TME, the active component of HAMnO 2 A, MnO 2 , underwent decomposition, liberating oxygen and releasing both Mn 2+ and ART. This process alleviates hypoxia within the tumor region and initiates a Fenton-like reaction through the combination of ART and Mn 2+ , thereby enhancing the effectiveness of PDT and CDT by generating increased singlet oxygen ( 1 O 2 ) and hydroxyl radicals (•OH). Moreover, the presence of Mn 2+ ions enabled the activation of T 1 -weighted magnetic resonance imaging. In vivo findings further validated that HAMnO 2 A displayed meaningful tumor-targeting capabilities, prolonged circulation time in the bloodstream, and outstanding efficacy in restraining tumor growth while inducing minimal damage to normal tissues. Hence, this nanoplatform serves as an efficient all-in-one solution by facilitating the integration of multiple functions, ultimately enhancing the effectiveness of tumor theranostics., 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 Elsevier Inc. All rights reserved.)

Background: There is a significant demand for intermediate-scale bioreactors in academic and industrial institutions to produce cells for various applications in drug screening and/or cell therapy. However, the application of these bioreactors in cultivating hiPSC-derived immune cells and other blood cells is noticeably lacking. To address this gap, we have developed a xeno-free and chemically defined intermediate-scale bioreactor platform, which allows for the generation of standardized human iPSC-derived hematopoietic organoids and subsequent continuous production of macrophages (iPSC-Mac)., Methods: We describe a novel method for intermediate-scale immune cell manufacturing, specifically the continuous production of functionally and phenotypically relevant macrophages that are harvested on weekly basis for multiple weeks., Results: The continuous production of standardized human iPSC-derived macrophages (iPSC-Mac) from 3D hematopoietic organoids also termed hemanoids, is demonstrated. The hemanoids exhibit successive stage-specific embryonic development, recapitulating embryonic hematopoiesis. iPSC-Mac were efficiently and continuously produced from three different iPSC lines and exhibited a consistent and reproducible phenotype, as well as classical functionality and the ability to adapt towards pro- and anti-inflammatory activation stages. Single-cell transcriptomic analysis revealed high macrophage purity. Additionally, we show the ability to use the produced iPSC-Mac as a model for testing immunomodulatory drugs, exemplified by dexamethasone., Conclusions: The novel method demonstrates an easy-to-use intermediate-scale bioreactor platform that produces prime macrophages from human iPSCs. These macrophages are functionally active and require no downstream maturation steps, rendering them highly desirable for both therapeutic and non-therapeutic applications., (© 2024. The Author(s).)

2D van der Waals heterojunctions (vdWH) have emerged as an attractive platform for the realization of optoelectronic synaptic devices, which are critical for energy-efficient computing systems. Photogating induced by charge traps at the interfaces indeed results in ultrahigh responsivity and tunable photoconductance. Yet, optical potentiation and depression remain mostly modulated by gate bias, requiring relatively high energy inputs. Thus, advanced all-optical synapse switching strategies are still needed. In this work, a reversible switching between positive photoconductivity (PPC) and negative photoconductivity (NPC) is achieved in graphene/WSe 2 vdWH solely through light-intensity modulation. Consequently, the graphene/WSe 2 synaptic device shows tunable optical potentiation and depression behavior with an ultralow power consumption of 127 aJ. The study further unravels the complex interplay of gate bias and incident light power in determining the sign and magnitude of the photocurrent, showing the critical role of charge trapping and photogating at interfaces. Interestingly, it is found that switching between PPC to NPC can be also obtained at 0 mV drain-source voltage. Overall, the reversible potentiation/depression effect based on light intensity modulation and its combination with additional gate bias tunability is very appealing for the development of energy-efficient optical communications and neuromorphic computing., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Objectives: This study systematically reviewed the literature on the effect of home-based supportive care (HbSC) programmes on the quality of life (QoL) of patients with advanced cancer., Methods: The research question 'Do home-based supportive care programmes for patients with advanced cancer improve their QoL?' was addressed. After registering the plan with PROSPERO (CRD42022341237), literature published from 1 January 1990 to 30 May 2023 was searched on PubMed, Embase, Cochrane database, CINAHL and Web of Science, and reviewed for inclusion based on predefined criteria. This review only included trial studies published in English., Results: Of 5,276 articles identified, 17 studies were judged suitable for inclusion in this review. The components of HbSC programmes included home visits, patient and caregiver education, home nursing, psychotherapy, exercise, telephone consultation, and multidisciplinary team meetings. Nine studies reported improvements in QoL, including social functioning, emotional functioning, and subjective QoL., Conclusion: HbSC programmes appear to enable the improvement of the QoL of patients with advanced cancer. The area of QoL that shows improvement could vary depending on the HbSC components. More studies that address HbSC programmes are needed to select patients at the proper time and provide suitable programmes for patients to benefit most., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the treatment efficacy of intra-arterial (IA) trastuzumab treatment using multiparametric magnetic resonance imaging (MRI) in a human breast cancer xenograft model., Materials and Methods: Human breast cancer cells (BT474) were stereotaxically injected into the brains of nude mice to obtain a xenograft model. The mice were divided into four groups and subjected to different treatments (IA treatment [IA-T], intravenous treatment [IV-T], IA saline injection [IA-S], and the sham control group). MRI was performed before and at 7 and 14 d after treatment to assess the efficacy of the treatment. The tumor volume, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) MRI parameters (Ktrans, Kep, Ve, and Vp) were measured., Results: Tumor volumes in the IA-T group at 14 d after treatment were significantly lower than those in the IV-T group (13.1 mm3 [interquartile range 8.48-16.05] vs. 25.69 mm3 [IQR 20.39-30.29], p = 0.005), control group (IA-S, 33.83 mm3 [IQR 32.00-36.30], p<0.01), and sham control (39.71 mm3 [IQR 26.60-48.26], p <0.001). The ADC value in the IA-T group was higher than that in the control groups (IA-T, 7.62 [IQR 7.23-8.20] vs. IA-S, 6.77 [IQR 6.48-6.87], p = 0.044 and vs. sham control, 6.89 [IQR 4.93-7.48], p = 0.004). Ktrans was significantly decreased following the treatment compared to that in the control groups (p = 0.002 and p<0.001 for vs. IA-S and sham control, respectively). Tumor growth was decreased in the IV-T group compared to that in the sham control group (25.69 mm3 [IQR 20.39-30.29] vs. 39.71 mm3 [IQR 26.60-48.26], p = 0.27); there was no significant change in the MRI parameters., Conclusion: IA treatment with trastuzumab potentially affects the early response to treatment, including decreased tumor growth and decrease of Ktrans, in a preclinical brain tumor model., Competing Interests: The authors have no conflicts of interest to declare., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We theoretically describe and experimentally demonstrate a graphene-integrated metasurface structure that enables electrically-tunable directional control of thermal emission. This device consists of a dielectric spacer that acts as a Fabry-Perot resonator supporting long-range delocalized modes bounded on one side by an electrostatically tunable metal-graphene metasurface. By varying the Fermi level of the graphene, the accumulated phase of the Fabry-Perot mode is shifted, which changes the direction of absorption and emission at a fixed frequency. We directly measure the frequency- and angle-dependent emissivity of the thermal emission from a fabricated device heated to 250 °C. Our results show that electrostatic control allows the thermal emission at 6.61 μm to be continuously steered over 16 ° , with a peak emissivity maintained above 0.9. We analyze the dynamic behavior of the thermal emission steerer theoretically using a Fano interference model, and use the model to design optimized thermal steerer structures., (© 2024. The Author(s).)

Background: Daily usage of facial masks during coronavirus disease 2019 pandemic influenced on facial dermatoses., Objective: This study investigated the impact of mask-wearing habits on facial dermatoses., Methods: A nationwide, observational, questionnaire-based survey was conducted from July through August 2021, involving 20 hospitals in Korea., Results: Among 1,958 facial dermatoses, 75.9% of patients experienced aggravation or development of new-onset facial dermatoses after wearing masks. In aggravated or newly developed acne patients (543 out of 743), associated factors were healthcare provider, female gender, and a long duration of mask-wearing. Irritating symptoms, xerosis, and hyperpigmentation were more frequently observed in this group. Aggravated or newly developed rosacea patients (515 out of 660) were likely to be female, young, and have a long duration of mask-wearing per day. Seborrheic dermatitis patients who experienced aggravation or de novo development (132 out of 184) were younger, and they more frequently involved the chin and jaw in addition to the nasolabial folds and both cheeks. Contact dermatitis patients (132 out of 147) with aggravation or de novo development tended to be female, involve both cheeks, and complain of pruritus. Aggravated or newly developed atopic dermatitis patients (165 out of 224) were more likely to be female, and had a higher baseline investigator global assessment score before mask-wearing., Conclusion: Clinical features and factors related to aggravation were different according to the types of facial dermatoses., Competing Interests: The authors have nothing to disclose., (© 2024 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

The recent advancements in large-scale activity imaging of neuronal ensembles offer valuable opportunities to comprehend the process involved in generating brain activity patterns and understanding how information is transmitted between neurons or neuronal ensembles. However, existing methodologies for extracting the underlying properties that generate overall dynamics are still limited. In this study, we applied previously unexplored methodologies to analyze time-lapse 3D imaging (4D imaging) data of head neurons of the nematode Caenorhabditis elegans. By combining time-delay embedding with the independent component analysis, we successfully decomposed whole-brain activities into a small number of component dynamics. Through the integration of results from multiple samples, we extracted common dynamics from neuronal activities that exhibit apparent divergence across different animals. Notably, while several components show common cooperativity across samples, some component pairs exhibited distinct relationships between individual samples. We further developed time series prediction models of synaptic communications. By combining dimension reduction using the general framework, gradient kernel dimension reduction, and probabilistic modeling, the overall relationships of neural activities were incorporated. By this approach, the stochastic but coordinated dynamics were reproduced in the simulated whole-brain neural network. We found that noise in the nervous system is crucial for generating realistic whole-brain dynamics. Furthermore, by evaluating synaptic interaction properties in the models, strong interactions within the core neural circuit, variable sensory transmission and importance of gap junctions were inferred. Virtual optogenetics can be also performed using the model. These analyses provide a solid foundation for understanding information flow in real neural networks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Toyoshima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Purpose: Despite the growing demands and challenges faced by patients with amyotrophic lateral sclerosis (ALS) in accessing healthcare services, our understanding of this access remains poor. This study aimed to investigate the healthcare utilization patterns and timing of nutritional and respiration support in patients with ALS in South Korea., Methods: A retrospective cohort study was conducted on patients diagnosed with ALS at a single tertiary hospital between 2016 and 2019 and followed up for 2 years. We evaluated patient characteristics, healthcare utilization (hospital admissions, outpatient visits, and emergency department [ED] visits), and the timing of nutritional and respiration support (noninvasive positive pressure ventilation [NIPPV], tracheostomy, gastrostomy, and nasogastric tube) at 6-month intervals from the first outpatient visit., Results: Among the 143 included patients, 73.4% were admitted at least once, 18.9% experienced unplanned admissions, and 30.1% visited the ED at least once during the study period. The most-common reason for ED visits was neurological symptoms during the first 6 months (59.1%), followed by respiratory symptoms. One fifth of patients who visited the ED underwent tracheostomy (20.9%) or NIPPV (20.9%). Two years after the first visit, 32.2% used a ventilator, and 13.3%, 26.6%, and 6.3% had undergone tracheostomy, gastrostomy, and nasogastric tube insertion, respectively., Conclusions: During the 2 years following their first outpatient visit, 20% of patients with ALS experienced unplanned admissions and 30% visited the ED. An active and prompt supportive-care program should be implemented to ensure timely functional support in order to reduce these risks of unplanned admissions., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Neurological Association.)

Background: More than half of acne patients have truncal acne on their chest, back, and shoulders. However, since most studies on acne have focused on the face, data on clinical characteristics and proper management for truncal acne are insufficient., Objective: To establish a Korean Acne Rosacea Society (KARS) consensus for experts' perception and treatment patterns of truncal acne., Methods: We conducted two rounds of the Dephi technique to gather expert opinion and reach a consensus on truncal acne. The first round comprised 48 questionnaires focusing on various aspects such as epidemiology, clinical features, diagnosis, treatment, prognosis and more, while second rounds consisted of 26 questionnaires., Results: A total of 36 dermatologists (36/38 KARS members, 94.7%) completed this survey. In the first-round survey, consensus was reached on 20 out of the 48 questions (41.7%). In the second-round questionnaire, consensus was achieved on 9 of the 26 questions (34.6%). The most unresponsive lesion to truncal acne treatment was scars (atrophic/hypertrophic). The most commonly used treatments for each non-inflammatory and inflammatory truncal acne lesions were selected to use topical retinoids (78.1% of the responders) and oral antibiotics (93.8% of the responders)., Conclusion: Our study has yielded valuable insights into the epidemiology, clinical manifestations, diagnosis, treatment, and quality of life of patients with truncal acne. We anticipate that this study will inspire further comprehensive research for individuals with truncal acne., Competing Interests: The authors declare the potential conflicts of interest, including a financial relation with Galderma., (© 2024 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: Macrophages have recently become attractive therapeutics in cancer immunotherapy. The potential of macrophages to infiltrate and influence solid malignancies makes them promising targets for the chimeric antigen receptor (CAR) technology to redirect their stage of polarization, thus enhancing their anticancer capacities. Given the emerging interest for CAR-macrophages, generation of such cells so far mainly depends on peripheral blood monocytes, which are isolated from the respective donor prior to genetic manipulation. This procedure is time-intensive and cost-intensive, while, in some cases, insufficient monocyte amounts can be recovered from the donor, thus hampering the broad applicability of this technology. Hence, we demonstrate the generation and effectiveness of CAR-macrophages from various stem cell sources using also modern upscaling technologies for next generation immune cell farming., Methods: Primary human hematopoietic stem and progenitor cells and induced pluripotent stem cells were used to derive anti-CD19 CAR-macrophages. Anticancer activity of the cells was demonstrated in co-culture systems, including primary material from patients with leukemia. Generation of CAR-macrophages was facilitated by bioreactor technologies and single-cell RNA (scRNA) sequencing was used to characterize in-depth response and behavior of CAR-macrophages., Results: Irrespective of the stem-cell source, CAR-macrophages exhibited enhanced and antigen-dependent phagocytosis of CD19 + target cancer cells with increased pro-inflammatory responses. Phagocytic capacity of CAR-macrophages was dependent on target cell CD19 expression levels with superior function of CAR-macrophages against CD19 + cancer cell lines and patient-derived acute lymphocytic leukemia cancer cells. scRNA sequencing revealed CAR-macrophages to be distinct from eGFP control cells after co-culture with target cells, which includes the activation of pro-inflammatory pathways and upregulation of chemokines and cytokines associated with adaptive immune cell recruitment, favoring the repolarization of CAR-macrophages to a pro-inflammatory state. Taken together, the data highlight the unique features of CAR-macrophages in combination with the successful upscaling of the production pipeline using a three-dimensional differentiation protocol and intermediate scale bioreactors., Conclusion: In summary, our work provides insights into the seminal use and behavior of CAR-macrophages which are derived from various sources of stem cells, while introducing a unique technology for CAR-macrophage manufacturing, all dedicated to the clinical translation of CAR-macrophages within the field of anticancer immunotherapies., Competing Interests: Competing interests: NL, MA and TM have filled a patent application on the generation of human iPSC-derived macrophages. All other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We prepared a long-arm octopus Jangjorim prototype (LOJP) by optimizing the ratio of ingredients for seasoning and establishing heat sterilization parameters. The optimal amounts of purified water (2.9-56.6%, A), starch syrup (0.3-37.8%, B), and soy sauce (25.5-71.5%, C) for the production of seasoning soy sauce were obtained using response surface analysis. The LOJP was prepared by combining A, B, and C under the optimal conditions and evaluated for consumer preferences and physicochemical, nutritional, and microbiological properties and compared with Korea's legal management standards for geriatric nutrition. The hardness of the LOJP produced using the optimal mixing ratio of purified water (51.2%, 154.0 g), starch syrup (29.3%, 308.0 g), and soy sauce (19.5%, 256.9 g) was 36.7 × 1000 N/m 2 . This value was lower than the hardness of raw octopus (2153.6 × 1000 N/m 2 ) by 2116.9 × 1000 N/m 2 . It received the highest score (8.7) in the preference evaluation of older consumers. The LOJP was classified as level 2, allowing consumption through the gums of elderly consumers per Korea's food standards for the elderly. The LOJP was the product highly preferred by elderly consumers with chewing disorders due to its ease of intake and nutritional content.

We, for the first time, report the nanoscopic imaging study of anomalous infrared (IR) phonon enhancement of bilayer graphene, originated from the charge imbalance between the top and bottom layers, resulting in the enhancement of E 1u mode of bilayer graphene near 0.2 eV. We modified the multifrequency atomic force microscope platform to combine photo-induced force microscope with electrostatic/Kelvin probe force microscope constituting a novel hybrid nanoscale optical-electrical force imaging system. This enables to observe a correlation between the IR response, doping level, and topographic information of the graphene layers. Through the nanoscale spectroscopic image measurements, we demonstrate that the charge imbalance at the graphene interface can be controlled by chemical (doping effect via Redox mechanism) and mechanical (triboelectric effect by the doped cantilever) approaches. Moreover, we can also diagnosis the subsurface cracks on the stacked few-layer graphene at nanoscale, by monitoring the strain-induced IR phonon shift. Our approach provides new insights into the development of graphene-based electronic and photonic devices and their potential applications., (© 2023. The Author(s).)

The worldwide health, economic, and societal consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have been devastating. The primary strategy to prevent new infectious diseases is to vaccinate the majority of people worldwide. However, the significant hurdles that are faced include vaccine safety concerns and vaccine reluctance. Among the various types of vaccines, the recombinant vesicular stomatitis virus (rVSV) is a promising candidate owing to its safety and efficacy. Therefore, we investigated the toxicity, immunogenicity, and local tolerance of the rVSVInd(GML)-mspSGtc vaccine against SARS-CoV-2. New Zealand White (NZW) rabbits were administered single or three repeated intramuscular injections of rVSVInd(GML)-mspSGtc every 2 weeks, followed by a 4-week recovery period. Male and female rabbits were randomly assigned into three groups: a control group and two dose-level groups (1 × 10 9 and 4 × 10 9 PFU/mL). Treatment-related changes included a temporary increase in body temperature and local inflammation at the injection site. These findings indicated recovery or a trend toward recovery, with no overt systemic toxicity. Immunogenicity analysis results suggested that rVSVInd(GML)-mspSGtc elicited a robust dose-dependent immune response in terms of neutralizing antibodies and IgG antibodies against the SARS-CoV-2 spike protein. In addition, the immune response intensity was increased by repeated vaccine administration. In conclusion, both the approximate lethal dose and the no observed adverse effect level for rVSVInd(GML)-mspSGtc exceeded 4 × 10 9 PFU/mL in NZW rabbits. Overall, rVSVInd(GML)-mspSGtc induced no adverse effects at the maximum dosage tested; however, its efficacy warrants further clinical evaluation., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We present an electrochemical method to functionalize single-crystal graphene grown on copper foils with a (111) surface orientation by chemical vapor deposition (CVD). Graphene on Cu(111) is functionalized with 4-iodoaniline by applying a constant negative potential, and the degree of functionalization depends on the applied potential and reaction time. Our approach stands out from previous methods due to its transfer-free method, which enables more precise and efficient functionalization of single-crystal graphene. We report the suggested effects of the Cu substrate facet by comparing the reactivity of graphene on Cu(111) and Cu(115). The electrochemical reaction rate changes dramatically at the potential threshold for each facet. Kelvin probe force microscopy was used to measure the work function, and the difference in onset potentials of the electrochemical reaction on these two different facets are explained in terms of the difference in work function values. Density functional theory and Monte Carlo calculations were used to calculate the work function of graphene and the thermodynamic stability of the aniline functionalized graphene on these two facets. This study provides a deeper understanding of the electrochemical behavior of graphene (including single-crystal graphene) on Cu(111) and Cu(115). It also serves as a basis for further study of a broad range of reagents and thus functional groups and of the role of metal substrate beneath graphene.

Metasurface-based color splitters are emerging as next-generation optical components for image sensors, replacing classical color filters and microlens arrays. In this work, we report how the design parameters such as the device dimensions and refractive indices of the dielectrics affect the optical efficiency of the color splitters. Also, we report how the design grid resolution parameters affect the optical efficiency and discover that the fabrication of a color splitter is possible even in legacy fabrication facilities with low structure resolutions., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Author(s).)

This was a cross-sectional study conducted to evaluate the association between hearing impairment and low back pain (LBP) using data from the Korean National Health and Nutrition Examination Survey. A total of 5,504 middle-aged and older Korean adults (aged ≥50 years old) who underwent plain radiography of the lumbar spine and pure tone audiometry were included. The presence of LBP was evaluated using a questionnaire, which included a question on whether the patient had experienced LBP that lasted for more than 30 days during the past three months. Patients with age-related hearing loss (ARHL) were defined as those with bilateral hearing impairment who met the following criteria: 1) normal otologic examination results, 2) average pure-tone hearing thresholds of ≤15 dB in both ears, and 3) no occupational noise exposure. Multivariable logistic regression analysis showed that ARHL was not associated with LBP (odds ratio, 1.33; 95% CI, 0.94-1.89) after adjusting for potential confounders in the final model. However, when participants without both ARHL and tinnitus were defined as the reference group, the results showed that the participants with both ARHL and tinnitus were more likely to have LBP (OR, 1.86; 95% CI, 1.11-3.11). These results indicate that ARHL with tinnitus is significantly associated with LBP. We recommend that elderly patients with ARHL and tinnitus increase their daily physical activities and engage in more muscle-strengthening exercises to prevent LBP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Noh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Considering the need for developing new senior-friendly processed seafood, this study aimed to develop octopus pulpo with high preference and excellent quality characteristics for elderly individuals by optimizing the vinegar immersion and sous vide softening treatment conditions for octopus ( Octopus vulgaris ) arms. The optimal sous vide heating temperature (70.0-100.0 °C), time (69.5-170.5 min), and vinegar concentration (0.2-0.8%) were established using response surface methodology (RSM). The pulpo prototype was produced using an octopus arm softened under optimal conditions and seasoned with a potato and olive oil sauce. The physicochemical and nutritional properties of the prototype were evaluated, followed by sensory evaluation and safety assessments. The hardness of softened octopuses obtained by 0.48% vinegar immersion and sous vide treatment (84.3 °C, 139.8 min), determined using RSM, was 394.5 × 1000 N/m 2 , showing a reduction of 83.0%; this was confirmed by electron microscopic observation. The texture of the pulpo prototype with softened octopus arms showed the highest preference (8.4 points) and high physicochemical and nutritional properties. Overall, the octopus pulpo a La Gallega prototype produced using texture-modified octopus arms was suitable for consumption by elderly people with chewing disorders and could help improve their quality of life.

The coronavirus disease 2019 pandemic has resulted in the introduction of several naïve methods of vaccine development, which have been used to prepare novel viral vectors and mRNA-based vaccines. However, reluctance to receive vaccines owing to the uncertainty regarding their safety is prevalent. Therefore, rigorous safety evaluation of vaccines through preclinical toxicity studies is critical to determine the safety profiles of vaccine candidates. This study aimed to evaluate the toxicity profile of HuVac-19, a subunit vaccine of SARS-CoV-2 utilizing the receptor-binding domain as an antigen, in rats, rabbits, and dogs using single- and repeat-dose study designs. Repeat-dose toxicity studies in rats and rabbits showed transient changes in hematological and serum biochemical parameters in the adjuvant and/or vaccine groups; however, these changes were reversed or potentially reversible after the recovery period. Moreover, temporary reversible changes in absolute and relative organ weights were observed in the prostate of rats and the thymus of rabbits. Gross examination of the injection sites in rats and rabbits treated with the adjuvant- and HuVac-19 showed discoloration and foci, whereas histopathological examination showed granulomatous inflammation, inflammatory cell infiltration, and myofiber degeneration/necrosis. This inflammatory response was local, unassociated with other toxicological changes, and resolved. In a pharmacological safety study, no toxicological or physiological changes associated with HuVac-19 administration were observed. In conclusion, HuVac-19 was not associated with any major systemic adverse effects in the general toxicity and safety pharmacology evaluation, demonstrating that HuVac-19 is a vaccine candidate with sufficient capacity to be used in human clinical trials., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Laser sails propelled by gigawatt-scale ground-based laser arrays have the potential to reach relativistic speeds, traversing the solar system in hours and reaching nearby stars in years. Here, we describe the danger interplanetary dust poses to the survival of a laser sail during its acceleration phase. We show through multiphysics simulations how localized heating from a single optically absorbing dust particle on the sail can initiate a thermal runaway process that rapidly spreads and destroys the entire sail. We explore potential mitigation strategies, including increasing the in-plane thermal conductivity of the sail to reduce the peak temperature at hot spots and isolating the absorptive regions of the sail that can burn away individually.

Tumor phototheranostics is usually compromised by the hypoxic tumor microenvironment and poor theranostic efficiency. The interplay between organic polymers and inorganic nanoparticles in novel nanocomposites has proven to be advantageous, overcoming previous limitations and harnessing their full potential through activation via the tumor microenvironment. This study successfully fabricated hypoxia-activated nanocolloids called HOISNDs through a process of self-assembly involving superparamagnetic iron oxide nanoparticles (SPIONs) and an organic polymer ligand called tetrakis(4-carboxyphenyl) porphyrin (TCPP)-engineered organic polymer ligand [methoxy poly(ethyleneglycol)- block -poly(dopamine-ethylenediamine-conjugated-4-nitrobenzyl chloroformate)-l-glutamate, mPEG- b -P(Dopa-EDA- co -NBCF)LG-TCPP)]. The SPIONs act as an oxygen generator to overcome the challenges posed by hypoxic tumors and enable the use of hypoxic-activatable MR/fluorescence dual-modal imaging-guided photodynamic therapy (PDT). The colloid stability of these HOISNDs proved to be exceptional in diverse biomimetic environments. Furthermore, they not only augment T 2 -weighted contrast capability as an MRI contrast agent but also function as an oxygen-producing device to amplify the generation and release of reactive oxygen species (ROS). The HOISNDs can significantly target to tumor sites through the enhanced permeability and retention (EPR) effect with prolonged blood circulation time and subsequently are effectively endocytosed into a hypoxic intracellular environment that "turn on" the imaging function and photodynamic activity. Moreover, HOISNDs possess the ability to effectively decompose naturally occurring H 2 O 2 into oxygen (O 2 ) within the tumor utilizing the Fenton reaction. This method can mitigate the impact of hypoxia on oxygen-dependent PDT. The outcomes of in vivo diagnostic and therapeutic evaluations indicated that HOISNDs are a highly promising tool for dual-model imaging-guided cancer theranosis by ameliorating hypoxic conditions and augmenting PDT efficiency.

In this study, unique hypoxia-activated hyaluronic acid nanogels (HANGs) were reported for CD44-targeted delivery of photosensitizers (chlorin e6, Ce6) for diagnostic imaging and photodynamic therapy (PDT) of cancers. Through the use of a hypoxia-responsive cross-linker (AZO-CDI), the HANGs were prepared by chemically cross-linking primary amine groups-functionalized hyaluronic acid (HA). Under normoxic condition, fluorescence of Ce6 conjugated on the HANGs was highly quenched, and level of reactive oxygen species (ROS) generated from the HANGs was rather low after laser irradiation. However, under hypoxic condition, the HANGs underwent rapid disassociation, and fluorescence of Ce6 conjugated on the HANGs was recovered, triggering high-level singlet oxygen generation after laser irradiation. Due to the presence of HA, the HANGs showed much higher cellular uptake by CD44-positive cancer cells (A549 cells) than that by CD44-negative cancer cells (HepG2 cells). In addition, the HANGs could generate higher level of ROS in A549 cells because of improved cancer cell uptake. This excellent tumor-targeting and singlet oxygen-generating ability of the HANGs was favorable to hypoxia-activated PDT of CD44-positive cancers with significant inhibition of tumor growth within the whole treatment period. Taken together, the HANGs are safe and effective tools in treating CD44-positive cancers., 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 B.V. All rights reserved.)

Objectives: This study aimed to investigate the correlation between the Comprehensive Attention Test, Korean-Wechsler Intelligence Scale for Children-Fourth Edition, and Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale-IV scores in children and adolescents with ADHD., Methods: Fifty-five children and adolescents diagnosed with ADHD and not taking psychiatric medications were included in this retrospective study. A correlation analysis was performed., Results: Although simple visual and auditory selective attention have diagnostic value in traditional continuous performance tests, this study revealed that inhibition-sustained attention and interference-selective attention are also effective in evaluating ADHD. Furthermore, the correlation between the attention and intelligence test scores varied depending on the use of visual or auditory stimuli., Conclusion: The findings of this study contribute to clarifying our understanding of the cognitive characteristics of children and adolescents with ADHD and can be used in future research., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Academy of Child and Adolescent Psychiatry.)

Near-perfect light absorbers (NPLAs), with absorbance, [Formula: see text], of at least 99%, have a wide range of applications ranging from energy and sensing devices to stealth technologies and secure communications. Previous work on NPLAs has mainly relied upon plasmonic structures or patterned metasurfaces, which require complex nanolithography, limiting their practical applications, particularly for large-area platforms. Here, we use the exceptional band nesting effect in TMDs, combined with a Salisbury screen geometry, to demonstrate NPLAs using only two or three uniform atomic layers of transition metal dichalcogenides (TMDs). The key innovation in our design, verified using theoretical calculations, is to stack monolayer TMDs in such a way as to minimize their interlayer coupling, thus preserving their strong band nesting properties. We experimentally demonstrate two feasible routes to controlling the interlayer coupling: twisted TMD bi-layers and TMD/buffer layer/TMD tri-layer heterostructures. Using these approaches, we demonstrate room-temperature values of [Formula: see text]=95% at λ=2.8 eV with theoretically predicted values as high as 99%. Moreover, the chemical variety of TMDs allows us to design NPLAs covering the entire visible range, paving the way for efficient atomically-thin optoelectronics., (© 2023. The Author(s).)

Increasing the light extraction efficiency has been widely studied for highly efficient organic light-emitting diodes (OLEDs). Among many light-extraction approaches proposed so far, adding a corrugation layer has been considered a promising solution for its simplicity and high effectiveness. While the working principle of periodically corrugated OLEDs can be qualitatively explained by the diffraction theory, dipolar emission inside the OLED structure makes its quantitative analysis challenging, making one rely on finite-element electromagnetic simulations that could require huge computing resources. Here, we demonstrate a new simulation method, named the diffraction matrix method (DMM), that can accurately predict the optical characteristics of periodically corrugated OLEDs while achieving calculation speed that is a few orders of magnitude faster. Our method decomposes the light emitted by a dipolar emitter into plane waves with different wavevectors and tracks the diffraction behavior of waves using diffraction matrices. Calculated optical parameters show a quantitative agreement with those predicted by finite-difference time-domain (FDTD) method. Furthermore, the developed method possesses a unique advantage over the conventional approaches that it naturally evaluates the wavevector-dependent power dissipation of a dipole and is thus capable of identifying the loss channels inside OLEDs in a quantitative manner.

The ongoing COVID-19 has not only caused millions of deaths worldwide, but it has also led to economic recession and the collapse of public health systems. The vaccines and antivirals developed in response to the pandemic have improved the situation markedly; however, the pandemic is still not under control with recurring surges. Thus, it is still necessary to develop therapeutic agents. In our previous studies, we designed and synthesized a series of novel 2-anilinoquinazolin-4(3H)-one derivatives, and demonstrated inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and MERS-CoV in vitro. We then conducted in vivo studies using modified compounds that are suitable for oral administration. These compounds demonstrated no toxicity in rats and inhibited viral entry. Here, we investigated the in vivo efficacy of these drug candidates against SARS-CoV-2. Three candidate drugs, 7-chloro-2-((3,5-dichlorophenyl)amino)quinazolin-4(3H)-one (1), N-(7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-N-(3,5-dichlorophenyl)acetamide (2), and N-(7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-N-(3,5-difluorophenyl)acetamide (3) were administered orally to hACE2 transgenic mice at a dose of 100 mg/kg. All three drugs improved survival rate and reduced the viral load in the lungs. These results show that the derivatives possess in vivo antiviral efficacy similar to that of molnupiravir, which is currently being used to treat COVID-19. Overall, our data suggest that 2-anilinoquinazolin-4(3H)-one derivatives are promising as potential oral antiviral drug candidates against SARS-CoV-2 infection., (© 2023 Wiley Periodicals LLC.)

Competing Interests: The authors have nothing to disclose.

Background: Since the start of the COVID-19 pandemic, virtual reality simulation, including web-based simulation, has increased in nursing education. This study explored nursing students' self-directed problem-solving in web-based virtual simulation experiences., Method: Convenience sampling yielded 16 Korean senior nursing students who had experienced clinical practice in the last semester. Data were collected from August 2020 to January 2021 through in-depth Zoom video interviews and organized using NVivo version 12.0. Thematic analysis was applied to analyze the data., Results: The following four themes were identified from nursing students' learning experiences during the web-based virtual simulations: "self-awareness of a lack of nursing competency in virtual reality," "applying new learning strategies learned from failure," "voluntary learning behavior," and "cognitive shift toward a holistic understanding." Web-based virtual simulations activated various cognitive and metacognitive factors of self-directed learning, and the system's prompt feedback and students' reflections facilitated learning effects. Nursing students corrected their cognitive errors while learning from their failures and mistakes and gained a holistic view of nursing practice., Conclusion: In this study, web-based self-directed learning activated the metacognition of nursing students in a virtuous cycle. The virtual environment with no actual harm to the patient has become a space for learners to experience a sense of confidence, achievement, and satisfaction. Web-based virtual simulation can be an effective teaching method to improve nursing students' self-directed learning abilities and nursing competency., (© 2022 Japan Academy of Nursing Science.)

Hirame novirhabdovirus (HIRRV) is a significant viral pathogen of Japanese flounder ( Paralichthys olivaceus ). In this study, seven monoclonal antibodies (mAbs) against HIRRV (isolate CA-9703) were produced and characterized. Three mAbs (1B3, 5G6, and 36D3) were able to recognize nucleoprotein (N) (42 kDa) and four mAbs (11-2D9, 15-1G9, 17F11, and 24-1C6) recognized matrix (M) protein (24 kDa) of HIRRV. Western blot, Enzyme-linked immunosorbent assay, and indirect fluorescent antibody technique (IFAT) results indicated that the developed mAbs were specific to HIRRV without any cross-reactivity against other different fish viruses and epithelioma papulosum cyprini cells. All the mAbs comprised IgG1 heavy chain and κ light chain except 5G6, which has a heavy chain of IgG2a class. These mAbs can be very useful in development of immunodiagnosis of HIRRV infection.

Objective: To identify the clinical characteristics of patients with recurrent Kawasaki disease (KD)., Design: A nationwide, population-based, cohort study using the Korean National Health Insurance claims database between 2013 and 2016., Patients: A total of 19 456 patients under the age of 5 years who were diagnosed with initial episode of KD were included. A minimum follow-up period of 3 years was mandatory for inclusion., Main Outcome Measures: The epidemiological and clinical profiles were compared between KD patients with and without recurrence., Results: The overall recurrence rate of KD was 3.84% (n=748), and the median interval to recurrence was 498 days (IQR: 257-860 days). Approximately 70% of all recurrences occurred within 2 years of the initial diagnosis. The annual proportions of recurrence were 40%, 28%, 18%, 8% and 4% from the first to the fifth year following the initial episode, respectively. Recurrence rates were significantly higher in patients aged <1 year than in those aged 4-5 years (4.65% vs 2.22%) and those who showed resistance to an initial dose of intravenous immunoglobulin (IVIG) (10.00% vs 3.18%). Allergic comorbidities and coronary artery complications at the initial episode were not associated with increased rates of recurrence., Conclusions: We clearly identified the annual recurrence rates and their intervals from the initial episode according to the various factors identified, including young age and resistance to initial IVIG. Our results, based on a nationwide cohort, can be used as reference for follow-up management in patients with KD and in future studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Modulating semiconducting channel potential has been used for electrical switching in transistors without biological plasticity operations that are critical for energy-efficient neuromorphic computing. To achieve efficient data processing, alternative transport mechanisms, such as tunneling and thermionic emission, have been introduced with 2D materials. Here, a polymorphic memtransistor based on atomically thin Mo 0.91 W 0.09 Te 2 is presented, where the lattice and electronic structures of the lateral device channel can be tuned as either metallic (1T') or semiconducting (2H) phases by electrical gating. The structural and electronic phase change of the channel material, optimized in Mo 0.91 W 0.09 Te 2 , is explored using transport and optical measurements at the device scale. Based on the phase transition, the polymorphic memtransistor demonstrates a high on/off ratio (up to 10 5 ), low subthreshold swing (down to 80 mV dec -1 ), and various memristive behaviors, which are distinguished from traditional phase-change memory, transistors, and passive memristors for diverse neuromorphic and in-memory computing., (© 2023 Wiley-VCH GmbH.)