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ABSTRACTSystemic sclerosis (SSc) is a chronic autoimmune disease characterized by skin and internal organ fibrosis and obliterative vasculopathy. Few effective treatments are currently available for fibrosis in SSc, therefore, demand persists for novel therapies. Although use of Ginkgo biloba extract (GBE) has been reported to improve blood circulation and alleviate liver and lung fibrosis, its effect on skin fibrosis in SSc remains unclear. In this study, the effects and underlying mechanisms of GBE on skin fibrosis in bleomycin (BLM)-induced mouse model of SSc was investigated. GBE significantly reduced dermal thickness and protein levels of profibrotic factors in the BLM-induced SSc mouse model. Moreover, GBE inhibited the gene expression of profibrotic factors, such as COL1A1, α-SMA, and connective tissue growth factor (CTGF), in fibroblasts by suppressing transforming growth factor (TGF)-β signaling. Furthermore, GBE inhibited the transdifferentiation of adipocytes into myofibroblasts. Thus, our findings suggest that GBE is a promising therapeutic candidate for the treatment of SSc.

Abstract Background Home-based primary care (HBPC) is an emerging patient-centered, interprofessional healthcare service model that can address unmet medical needs and care burdens for homebound older adults. In December 2022, the Ministry of Health and Welfare in South Korea launched the Home-Based Medical Center Demonstration project to provide a new bundle payment for physician home visits. In this study, we seek to determine whether the recently introduced HBPC services in South Korea have been associated with a reduction in long-term care (LTC) facility admissions and acute hospitalizations among homebound older adults. Methods The study is a community-based, multicenter, two-arm, randomized encouragement design trial with a 12-month follow-up period (n = 600). Eligible study participants are community-dwelling LTC recipients with multimorbidity and functional deterioration. Study participants are recruited from five HBPC centers located in urban areas (Northeast Seoul, West Seoul, Daejeon, Wonju, and Paju). The study participants are randomly assigned to either the HBPC group or the usual care group with a 1:1 allocation ratio. Those assigned to the HBPC group receive longitudinal home visits at least once a month by an interprofessional HBPC team according to the Widely Integrated Services in Home (WISH) intervention protocol. This protocol adheres to the Integrated Care for Older People principles, which call for a person-centered assessment and broader integration of health and LTC services at the micro-, meso- and macro-levels. Primary outcomes of the trial are 1) between-group community survival days and 2) between-group potentially avoidable hospitalizations. Results of the treatment are estimated by both modified intention-to-treat and complier average causal effect analytic methods. Discussion This study aims to investigate the real-world effectiveness of HBPC on the reduction of LTC facility admissions and acute care hospitalizations in the community setting. The findings may inform healthcare policy decisions to expand HBPC services in South Korea and other countries. Trial Registration CRIS KCT0007921.

This paper examines the periodical Clinical Internal Medicine published by the Department of Internal Medicine at Keijo Imperial University in colonial Korea. Previous studies on medical research at Keijo Imperial University have primarily focused on preclinical departments such as anatomy, hygiene, pharmacology, and microbiology which produced knowledge that supported Japan’s imperialistic expansion. This approach has overlooked the research contributions of clinical departments, often viewing the roles of preclinical and clinical departments through a dichotomy between research versus clinician training. However, Clinical Internal Medicine demonstrates that the Department of Internal Medicine at Keijo Imperial University was actively engaged in research. By analyzing the purpose and content of Clinical Internal Medicine, this paper reveals that its publication was an effort by the Department of Internal Medicine to address the demand for practical knowledge among clinicians practicing outside the university. At the same time, it reflects a commitment to enhancing the academic value of clinical experience and critiques the blind pursuit of experimental medicine in the Japanese medical community in the 1920s and 1930s. The case of the Department of Internal Medicine at Keijo Imperial University illustrates the transformation of clinical experience into “worthy” academic knowledge in colonial Korea. Based on these findings, this paper provides insights into the role of clinical departments at Keijo Imperial University in research and post-graduation education.

Attending to heartbeats for interoceptive awareness initiates distinct electrophysiological responses synchronized with the R-peaks of an electrocardiogram (ECG), such as the heartbeat-evoked potential (HEP). Beyond HEP, this study proposes heartbeat-related spectral perturbation (HRSP), a time–frequency map of the R-peak locked electroencephalogram (EEG), and explores its characteristics in identifying interoceptive attention states using a classification approach. HRSPs of EEG brain components specified by independent component analysis (ICA) were used for the offline and online classification of interoceptive states. A convolutional neural network (CNN) designed specifically for HRSP was applied to publicly available data from a binary-state experiment (attending to self-heartbeats and white noise) and data from our four-state classification experiment (attending to self-heartbeats, white noise, time passage, and toe) with diverse input feature conditions of HRSP. From the dynamic state perspective, we evaluated the primary frequency bands of HRSP and the minimal number of averaging epochs required to reflect changing interoceptive attention states without compromising accuracy. We also assessed the utility of group ICA and models for classifying HRSP in new participants. The CNN for trial-by-trial HRSP with actual R-peaks demonstrated significantly higher classification accuracy than HRSP with sham, i.e., randomly positioned, R-peaks. Gradient-weighted class activation mapping highlighted the prominent role of theta and alpha bands between 200–600 ms post-R-peak—features absent in classifications using sham HRSPs. Online classification benefits from employing a group ICA and classification model, ensuring reliable accuracy without individual EEG precollection. These results suggest HRSP’s potential to reflect interoceptive attention states, proposing transformative implications for clinical applications.

Abstract Background Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations. Methods AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment. Results Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p

In this paper, we propose a dual-band shared-aperture antenna composed of array elements with high electromagnetic (EM) transparency. To increase EM transparency, the antenna consists of an optimized substrate with low effective permittivity by combining thin dielectric sheets and air-gap layers. To further improve the EM transparency, thin dual-loop radiators with optimized widths and lengths are adopted for the S-band element, and an E-shaped patch antenna is employed for an X-band element. This configuration minimize the pattern distortion in the X-band elements while enhancing antenna bandwidths. In addition, a calibration layer comprising four monopole probes and microstrip transmission lines is included for monitoring the phase and amplitude errors of each element. To verify the feasibility, the proposed antenna is fabricated to measure antenna characteristics, such as reflection coefficients, beam steering performance, and mutual coupling in a full anechoic chamber. The fractional bandwidths of the antenna in the S- and X-bands are 16.4% and 26.8%, respectively. The array gains at the bore-sight are 16.0 dBi in the S-band and 24.0 dBi in the X-band.

Abstract In mammals, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) execute sequential thermogenesis to maintain body temperature during cold stimuli. BAT rapidly generates heat through brown adipocyte activation, and further iWAT gradually stimulates beige fat cell differentiation upon prolonged cold challenges. However, fat depot-specific regulatory mechanisms for thermogenic activation of two fat depots are poorly understood. Here, we demonstrate that E3 ubiquitin ligase RNF20 orchestrates adipose thermogenesis with BAT- and iWAT-specific substrates. Upon cold stimuli, BAT RNF20 is rapidly downregulated, resulting in GABPα protein elevation by controlling protein stability, which stimulates thermogenic gene expression. Accordingly, BAT-specific Rnf20 suppression potentiates BAT thermogenic activity via GABPα upregulation. Moreover, upon prolonged cold stimuli, iWAT RNF20 is gradually upregulated to promote de novo beige adipogenesis. Mechanistically, iWAT RNF20 mediates NCoR1 protein degradation, rather than GABPα, to activate PPARγ. Together, current findings propose fat depot-specific regulatory mechanisms for temporal activation of adipose thermogenesis.

Additive manufacturing technology has advanced beyond creating optimized features, from strengthening materials to make them lightweight to fabricating multi-material combinations that offer functionalities beyond the capabilities of individual materials. In this study, a lamination method for laser-directed energy deposition (LDED) is developed to achieve dense multi-material features, and a design that combines different and dissimilar materials is developed. To evaluate these novel developments, two materials—AISI 316L stainless steel and Inconel 625—are introduced. Tensile specimens, fabricated via multi-material additive manufacturing using LDED, are subjected to tensile tests that are recorded on video for digital image correlation. After the tests, fracture surface analyses of the fractured specimens are performed via scanning electron microscopy, and optical monitoring analyses are performed on the specimens that are not subjected to the tensile tests. The results indicate that the specimens demonstrate varied mechanical properties due to the influence of lamination direction and order, which affect the formation of critical cracks and pores.

Two intact male dogs were evaluated for symptoms, including hematuria, prostatomegaly, anuria, lethargy, and abdominal mass. Presurgical evaluations, including complete physical examinations, blood examinations, abdominal radiography with contrast (only in Case 2), ultrasonography, and computed tomography and magnetic resonance imaging (only in Case 1), were performed. A paraprostatic cyst was diagnosed initially, and laparoscopic exploration and surgery were performed. Complete resection was performed in case 1, whereas partial resection with omentalization was performed in case 2. Histopathological examination of the tissue samples confirmed the presence of paraprostatic pseudocysts in both cases, with no evidence of an epithelial lining. These two cases represent the first documented instances of laparoscopic treatment for extraparenchymal prostatic cysts. The laparoscopic treatment proved feasible even in the case of a giant cyst causing anuria (Case 2). Paraprostatic cysts should be considered a potential differential diagnosis for abnormal urination accompanied by an abdominal mass, and long-term postoperative follow-up is necessary.

Abstract Adipose tissue invariant natural killer T (iNKT) cells are a crucial cell type for adipose tissue homeostasis in obese animals. However, heterogeneity of adipose iNKT cells and their function in adipocyte turnover are not thoroughly understood. Here, we investigate transcriptional heterogeneity in adipose iNKT cells and their hierarchy using single-cell RNA sequencing in lean and obese mice. We report that distinct subpopulations of adipose iNKT cells modulate adipose tissue homeostasis through adipocyte death and birth. We identify KLRG1+ iNKT cells as a unique iNKT cell subpopulation in adipose tissue. Adoptive transfer experiments showed that KLRG1+ iNKT cells are selectively generated within adipose tissue microenvironment and differentiate into a CX3CR1+ cytotoxic subpopulation in obese mice. In addition, CX3CR1+ iNKT cells specifically kill enlarged and inflamed adipocytes and recruit macrophages through CCL5. Furthermore, adipose iNKT17 cells have the potential to secrete AREG, and AREG is involved in stimulating adipose stem cell proliferation. Collectively, our data suggest that each adipose iNKT cell subpopulation plays key roles in the control of adipocyte turnover via interaction with adipocytes, adipose stem cells, and macrophages in adipose tissue.

This study explores the effectiveness of community-based exercise programs for individuals with spinal cord injury (SCI) following hospital discharge. Given the rising incidence of SCI, particularly in South Korea, and the associated long-term disabilities, the necessity for comprehensive post-discharge rehabilitation is paramount. The study focuses on a pilot randomized multicenter double-blind controlled trial, targeting SCI patients who have completed inpatient rehabilitation and are living in the community. The primary aim is to evaluate the impact of structured exercise programs on physical fitness, functional capacity, and overall recovery. The research introduces the SpinalFit program, a community-based intervention designed to enhance muscle strength, cardiopulmonary endurance, and mobility through a combination of aerobic and resistance training. This program addresses the critical need for safe and effective rehabilitation options outside the hospital setting, utilizing circuit training with resistance bands and body-weight exercises tailored to each participant’s capacity. The study also investigates barriers to physical activity in the community for SCI patients and the potential role of community exercise centers in bridging this gap. Preliminary findings from this pilot trial are expected to provide valuable insights into optimizing exercise regimens for SCI patients, informing future large-scale studies and contributing to improved post-discharge rehabilitation strategies.

This study investigated whether economic motivations are a key factor in international migration decisions. Applying the selectivity-corrected expected income for migrants and stayers, the difference in expected income for an individual in origin and destination countries was analyzed. This study used data from the U.S. and Canada to empirically test the role of income gaps in migration decisions. The main difficulty in analyzing the role of the gaps lies in collecting both income streams for the same individual, since once an individual migrates to a different country, their potential income in the origin country cannot be observed; and vice versa for stayers. Therefore, directly applying the average income of migrants (conditionally relying on their observed characteristics) to estimate the income of stayers if they had migrated results in a biased estimate of stayers’ income. Hence, there is a need to account for selectivity in the migration decision and calculate selectivity-corrected income. The key finding in this study is that the expected income gap is positively associated with, and statistically significant for, international migration decisions for the U.S. and Canada. One of the main reasons may be the easy transfer of labor skills between countries that have similar labor environments and cultural backgrounds.

This study investigates the properties of various adhesives and assesses the effects of the coating and drying conditions of aluminum surface treatment agents on adhesion strength and chemical resistance. The adhesion between aluminum and the polymer film is improved through the application of a surface treatment agent to the aluminum surface. This study examines the initial adhesive strength of a manufactured pouch film with respect to the drying temperature and time and evaluates its adhesive strength in the presence of moisture. The results indicate that the residual moisture on the aluminum surface weakens the adhesive strength and significantly affects electrolyte resistance. A noticeable reduction in strength was observed after water spraying, when the drying temperature and time were relatively low during the initial strength measurement. Among the adhesives used for aluminum and CPP lamination, olefin adhesives exhibit less susceptibility to electrolyte effects and have higher adhesive strengths compared to urethane and ester adhesives. Leveraging these characteristics, flexible pouch cells were manufactured and their stability was evaluated. The results confirm that the flexible cells demonstrate excellent stability, exhibiting potential for application in wearable devices.

Spinal cord injury (SCI) patients require continuous rehabilitation post-discharge to ensure optimal recovery. This study investigates the effectiveness of home-based virtual reality fitness training (VRFT) as a convenient and accessible rehabilitation method for SCI patients. This randomized, double-blind, multicenter trial will enroll 120 participants, assigning them to either an 8-week VRFT program (exercise group) or a control group engaging in regular daily activities. The outcomes measured include muscle function, cardiopulmonary fitness, body composition, and physical performance. Our study will determine the safety and feasibility of VRFT in a home setting for SCI patients and evaluate whether these patients can effectively participate in such a program post-discharge. The results of this study are expected to inform future exercise protocols for SCI rehabilitation, offering valuable insights into the utility of VRFT as a therapeutic tool.

Abstract Excessive polyethylene terephthalate (PET) waste causes a variety of problems. Extensive research focused on the development of superior PET hydrolases for PET biorecycling has been conducted. However, template enzymes employed in enzyme engineering mainly focused on IsPETase and leaf-branch compost cutinase, which exhibit mesophilic and thermophilic hydrolytic properties, respectively. Herein, we report a PET hydrolase from Cryptosporangium aurantiacum (CaPETase) that exhibits high thermostability and remarkable PET degradation activity at ambient temperatures. We uncover the crystal structure of CaPETase, which displays a distinct backbone conformation at the active site and residues forming the substrate binding cleft, compared with other PET hydrolases. We further develop a CaPETaseM9 variant that exhibits robust thermostability with a T m of 83.2 °C and 41.7-fold enhanced PET hydrolytic activity at 60 °C compared with CaPETaseWT. CaPETaseM9 almost completely decompose both transparent and colored post-consumer PET powder at 55 °C within half a day in a pH-stat bioreactor.

Pyramidal neurons, a mainstay of cortical regions, receive a plethora of inputs from various areas onto their morphologically distinct apical and basal trees. Both trees differentially contribute to the somatic response, defining distinct anatomical and possibly functional sub-units. To elucidate the contribution of each tree to the encoding of visual stimuli at the somatic level, we modeled the response pattern of a mouse L2/3 V1 pyramidal neuron to orientation tuned synaptic input. Towards this goal, we used a morphologically detailed computational model of a single cell that replicates electrophysiological and two-photon imaging data. Our simulations predict a synergistic effect of apical and basal trees on somatic action potential generation: basal tree activity, in the form of either depolarization or dendritic spiking, is necessary for producing somatic activity, despite the fact that most somatic spikes are heavily driven by apical dendritic spikes. This model provides evidence for synergistic computations taking place in the basal and apical trees of the L2/3 V1 neuron along with mechanistic explanations for tree-specific contributions and emphasizes the potential role of predictive and attentional feedback input in these cells.

Despite hyperglycemia has been associated to breast cancer, the underlying mechanisms are not completely understood. Here, the authors show that epigenetic regulation of Nrg1 gene during hyperglycemia promotes breast cancer development.

Abstract Radio-resistance resulting from radiotherapy-induced fibrosis is a major clinical obstacle in breast cancer treatment because it typically leads to cancer recurrence, treatment failure, and patient death. Transforming growth factor-β (TGF-β) is a key signal messenger in fibrosis, which plays an important role in radiation-induced fibrosis and cancer stem cell (CSC) development, may be mediated through the generation of oxidative stress. This study was conducted to confirm the efficacy of vactosertib, a TGF-β/ALK5 inhibitor, as a potent inhibitor in radiation-induced oxidative stress generation, fibrosis and CSC development. We used a 4T1-Luc allograft BALB/c syngeneic mouse model and 4T1-Luc and MDA-MB-231 cells for histological analysis, qRT-PCR, western blotting, ROS analysis, mammosphere formation analysis, monolayer fluorescence imaging analysis. Radiotherapy induces TGF-β signaling, oxidative stress markers (4-HNE, NOX2, NOX4, PRDX1, NRF2, HO-1, NQO-1), fibrosis markers (PAI-1, α-SMA, FIBRONECTIN, COL1A1), and CSC properties. However, combination therapy with vactosertib not only inhibits these radiation-induced markers and properties by blocking TGF-β signaling, but also enhances the anticancer effect of radiation by reducing the volume of breast cancer. Therefore, these data suggest that vactosertib can effectively reduce radiation fibrosis and resistance in breast cancer treatment by inhibiting radiation-induced TGF-β signaling and oxidative stress, fibrosis, and CSC.

Abstract Background Respiratory disorders result in rehospitalization and premature death of patients with cervical spinal cord injuries (CSCI). Community game-based respiratory muscle training (RMT) programs could reduce secondary complications. Methods We examined the feasibility and preliminary efficacy of RMT as a community-based exercise program. Among the 10 included participants (eight male and two female), four, one, one, and four reported C3, C4, C5, and C6 complete injuries, respectively (eight graded by American Spinal Injury Association impairment scale [ASIA] A and two by ASIA B). Their mean age was 43 ± 12.3 y. The time since injury was 10 ± 6.7 y. The participants completed an RMT program for 60 min/day, twice weekly, for 8 weeks. The participants were trained in the use of a newly developed game-based RMT device. The device provides consistent pressure for respiratory muscle strength and endurance training. Seven RMT devices were modified to allow 10 game-based RMT programs. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), vital capacity (VC), inspiratory capacity (IC), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and peak cough flow (PCF) were measured. Results There were improvements after RMT compared to pre-RMT in FVC (p = 0.027, 10.62%, 0.22 effect size [ES]), PEF (p = 0.006, 23.21%, 0.45 ES), VC (p = 0.002, 35.52%, 0.60 ES), IC (p = 0.001, 46.94%, 0.81 ES), IRV (p = 0.001, 90.53%, 1.22 ES), MIP (p = 0.002, 97.25%, 1.32 ES), MEP (p = 0.005, 141.12%, 1.07 ES), and PCF (p = 0.001, 35.60%, 0.74 ES). The participants reported a positive impact of the program. Conclusions Community game-based RMT for individuals with CSCI appears to be safe and feasible. Community exercise with RMT use may have a positive impact on the respiratory measures for patients with CSCI who are vulnerable to respiratory compromise. Trial registration KCT0005980.

ObjectiveWe investigated the changes in circulating irisin levels after community-based exercise and the association of these levels with improvements in muscle strength, cardiorespiratory endurance, and body composition in people with ischemic stroke.MethodsTwenty participants were randomly assigned to either a control or an exercise group. The community-based exercise program (CEP) consisted of 8 weeks of 1 h sessions for 3 days a week. Irisin levels, muscle strength, cardiorespiratory endurance, and body composition were assessed before and after the intervention.ResultsSignificant improvements were observed in the leg and trunk strength, peak oxygen consumption values, and body composition of the exercise group compared with the control group. In addition, circulating irisin levels were observed to have increased in the exercise group, positively correlated with muscle strength and cardiorespiratory endurance.ConclusionCEP might be an effective intervention to increase irisin levels and prevent a stroke-related decline in muscle function.

Abstract Background Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic. Methods We recruited COVID-19 convalescent individuals who received one or two doses of an mRNA vaccine within 6 or around 18 months after a diagnosis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Their samples were assessed for IgG-binding or neutralizing activity and cell-mediated immune responses against SARS-CoV-2 wild-type and variants of concern. Results A total of 43 COVID-19 convalescent individuals were analyzed in the present study. The results showed that humoral and cellular immune responses against SARS-CoV-2 wild-type and variants of concern, including the Omicron variant, were comparable among patients vaccinated within 6 versus around 18 months. A second dose of vaccine did not significantly increase immune responses. Conclusion One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.

It is essential for stroke patients to maintain their therapy even after discharging inpatient rehabilitation. This is because recovery is an ongoing process that requires consistent effort. Virtual reality exergame training (VRET) is becoming widely used in stroke rehabilitation to improve physical, social, and psychological outcomes. Home-based VRET may be a more convenient and accessible option for stroke rehabilitation. This study will aim to determine the effectiveness of home-based VRET for patients with stroke who have been discharged from the hospital. This trial will randomly assign 120 participants to 8 weeks of either a VRET (intervention group) or daily life (control group). The study will measure cardiopulmonary endurance, muscular strength, functional capacity, gait, activities of daily living, and quality of life. Our main objective is to determine whether it is safe for patients to undergo VRET at home after they have been discharged from the hospital with a doctor’s note. Additionally, we aim to examine whether stroke patients are capable of exercising at home after being discharged from the hospital. This study’s outcome could pave the way for developing more comprehensive exercise protocols for stroke patients. Our findings will provide valuable insights into the efficacy of VRET as a therapeutic tool for stroke patients.

Rice, one of the most widely consumed staples worldwide, serves as a versatile gluten-free substitute. However, review articles on technological developments in grain-free production focusing on rice are scarce. This review assesses various research results concerning the quality attributes of rice-based gluten-free foods, including bread, pasta, and beer. To optimize the key attributes in processed products, such as dough leavening in bread and the physical and cooking properties of noodles and pasta, research has focused on blending different gluten-free grains and incorporating additives that mimic the gluten function. Additionally, various processing technologies, such as starch preprocessing and extrusion puffing processes, have been employed to boost the quality of rice-based gluten-free products. Today, a variety of products, including bread, noodles, and beer, use rice as a partial replacement for barley or wheat. With rapid advancements in technology, a noticeable portion of consumers now shows a preference for products containing rice as a substitute. This trend indicates that rice-based gluten-free foods can be enhanced by leveraging the latest developments in gluten-free product technologies, particularly in countries where rice is a staple or is predominantly cultivated.

Elucidation of the interplay between viruses and host cells is crucial for taming viruses to benefit human health. Cancer therapy using adenovirus, called oncolytic virotherapy, is a promising treatment option but is not robust in all patients. In addition, inefficient replication of human adenovirus in mouse hampered the development of an in vivo model for preclinical evaluation of therapeutically engineered adenovirus. nc886 is a human non-coding RNA that suppresses Protein Kinase R (PKR), an antiviral protein. In this study, we have found that nc886 greatly promotes adenoviral gene expression and replication. Remarkably, the stimulatory effect of nc886 is not dependent on its function to inhibit PKR. Rather, nc886 facilitates the nuclear entry of adenovirus via modulating the kinesin pathway. nc886 is not conserved in mouse and, when xenogeneically expressed in mouse cells, promotes adenovirus replication. Our investigation has discovered a novel mechanism of how a host ncRNA plays a pro-adenoviral role. Given that nc886 expression is silenced in a subset of cancer cells, our study highlights that oncolytic virotherapy might be inefficient in those cells. Furthermore, our findings open future possibilities of harnessing nc886 to improve the efficacy of oncolytic adenovirus and to construct nc886-expressing transgenic mice as an animal model.

Abstract Background Physical activity is required to maintain health; however, resources needed for physical activity (e.g. facilities, instructors, and programmes) are scarce for persons with disabilities (PWD), particularly those who require rehabilitation following hospital discharge and those with severe disabilities. The Republic of Korea presently lacks a legal and administrative framework that supports the implementation of health services for PWD. Therefore, it is necessary to develop such a framework based on the perspectives of PWD, medical and physical education experts, facility managers, and government organisations. Thus, this study aimed to establish expert consensus on the development of rehabilitation sports public services (RSPS) in the Republic of Korea by reviewing previous studies and expert statements. Methods Using the Delphi method, we reviewed the literature to identify the critical roles and factors required for planning efficient RSPS programmes, including coordinators, physicians, facility managers, rehabilitation exercise and physical education instructors, and integrated information systems for facilities, instructors, and programmes. We developed a Delphi questionnaire with closed-ended questions, based on the factors derived from the literature review and supplementary open-ended questions, which was administered to a panel of 26 experts. Results The panel reached a consensus on most factors (i.e. coordinators, physicians, facility managers, rehabilitation exercise and physical education instructors, and integrated information systems for facilities, instructors, and programmes). However, no consensus was reached regarding ‘when an applicant can continue/discontinue an RSPS programme’, ‘establishing information systems to manage physical fitness of PWD’, and ‘joint operation of the to-be-established system by the Ministry of Health and Welfare and Ministry of Culture, Sports, and Tourism’, leaving room for further debate. Conclusions By identifying the factors and roles necessary for RSPS, this study is expected to offer valuable information for state-led pilot projects and contribute to promoting physical activity and quality of life among PWD.

Abstract When primary cancer faces limited oxygen and nutrient supply, it undergoes an epithelial–mesenchymal transition, which increases cancer cell motility and invasiveness. The migratory and invasive cancer cells often exert aggressive cancer development or even cancer metastasis. In this study, we investigated a novel compound, 3-acetyl-5,8-dichloro-2-((2,4-dichlorophenyl)amino)quinolin-4(1H)-one (ADQ), that showed significant suppression of wound healing and cellular invasion. This compound also inhibited anchorage-independent cell growth, multicellular tumor spheroid survival/invasion, and metalloprotease activities. The anti-proliferative effects of ADQ were mediated by inhibition of the Akt pathway. In addition, ADQ reduced the expression of mesenchymal markers of cancer cells, which was associated with the suppressed expression of Twist1. In conclusion, ADQ successfully suppressed carcinogenic activity by inhibiting the Akt signaling pathway and Twist1, which suggests that ADQ may be an efficient candidate for cancer drug development.

Purpose This study aimed to systematically develop an obesity prevention program for adolescents to promote healthy eating and physical activity in schools. Methods The development of the Let's Eat Healthy and Move at School program for adolescents followed the six steps of intervention mapping (IM). IM is a widely used protocol for developing systematic and effective interventions based on theories and evidence. Results To better understand the problem and identify the needs of adolescents, interviews were conducted with teachers, school nurses, and students (step 1). In step 2, the desired behaviors and their determinants were established and combined into a matrix comprising 16 change objectives. In step 3, theoretical methods such as persuasive communication and consciousness-raising were chosen. The program was segmented into three educational activity sessions in step 4. In step 5, an implementation manual was developed for program instructors to ensure effective and accurate implementation. Finally, practices for evaluating the program's effectiveness and procedures were designed in step 6. Conclusion The Let’s Eat Healthy and Move at School program will provide adolescents with guidelines to promote healthy living and prevent obesity in everyday life using strategies for sustainable adolescent obesity prevention and management.

A 6-year-old castrated male Shih-Tzu dog weighing 6. 5 kg presented with chief complaints of pollakiuria and urine dribbling. He had a history of urolithiasis for 3 years, which was confirmed by the presence of ammonium urate in the urinary stone analysis, performed 2 years prior to the presentation. Blood examination showed high values of fasting ammonia, post-prandial bile acid, and low blood urea nitrogen. Microhepatica and urolithiasis were identified on plain radiography and ultrasonography. A computed tomography angiography demonstrated a shunting vessel, diameter up to 9.6 mm, originated from the splenic vein, and linked with the phrenic vein. A surgical attenuation with a thin-film banding was performed under laparoscopic visualization. Left triangular ligament was incised, and one stay suture was placed to the stomach to expose the vessel. The shunting vessel was dissected before it entered the diaphragm, and a thin-film band was applied around the vessel. The patient recovered uneventfully without post-attenuation neurologic signs. Portal vein diameter increased with time, and complete closure of the shunting vessel was identified on computed tomography angiography performed at 14 months after attenuation. The patient was doing well for 31 months after surgery without protein restriction. This is a report of laparoscopic attenuation for splenophrenic type of canine congenital extrahepatic portosystemic shunt with a favorable outcome using thin-film banding.

Social acceptance (vs. rejection) is assumed to have widespread positive effects on the recipient; however, ethnic/racial minorities often react negatively to social acceptance by White individuals. One possibility for such reactions might be their lack of trust in the genuineness of White individuals’ positive evaluations. Here, we examined the role that oxytocin—a neuropeptide putatively linked to social processes—plays in modulating reactions to acceptance or rejection during interracial interactions. Black participants (N = 103) received intranasal oxytocin or placebo and interacted with a White, same-sex stranger who provided positive or negative social feedback. After positive feedback, participants given oxytocin (vs. placebo) tended to display approach-oriented cardiovascular responses of challenge (vs. threat), exhibited more cooperative behavior, and perceived the partner to have more favorable attitudes toward them after the interaction. Following negative feedback, oxytocin reduced anger suppression. Oxytocin did not modulate testosterone reactivity directly, but our exploratory analysis showed that the less participants suppressed anger during the interaction with their partner, the greater testosterone reactivity they displayed after the interaction. These results survived the correction for multiple testing with a false discovery rate (FDR) of 20%, but not with a rate of 10 or 5%. Discussion centers on the interplay between oxytocin and social context in shaping interracial interactions.

This study aimed to explore suitable processing materials for rice beer (RB) production by analyzing the starch structure of the raw materials utilized for brewing beer and the quality characteristics of RB. We used malt, employing the Heugho cultivar as the main ingredient, and produced beer containing 30% rice. The regular amylose-containing cultivars Samgwang (SA) and Hangaru (HA) and the high-amylose-containing cultivar Dodamssal (DO) were used as adjuncts. Distribution of the short molecular chains of the starch amylopectin was the highest for SA and malt at 29.3% and 27.1%, respectively. Glucose content was the highest in the wort prepared with 100% malt and 30% SA + 70% malt. The alcohol content in SA RB and HA RB was higher than that in beer prepared with 100% malt. DO RB had the least bitterness and volatile components, such as acetaldehyde and ethyl acetate. The three rice cultivars tested in this study are suitable as starch adjuncts for RB production. The characteristics of RBs varied depending on the molecular structure of the ingredients, irrespective of their amylose contents. SA could be considered a craft beer with quality characteristics and rich flavor components, similar to 100% malt beer, compared to other RBs.

As neighborhood walkability has gradually become an important topic in various fields, many cities around the world are promoting an eco-friendly and people-centered walking environment as a top priority in urban planning. The purpose of this study is to visualize physical and perceived walkability in detail and analyze the differences to prepare alternatives for improving the neighborhood’s walking environment. The study area is Jeonju City, one of the medium-sized cities in Korea. For the evaluation of perceived walkability, 196,624 street view images were crawled and 127,317 pairs of training datasets were constructed. After developing a convolutional neural network model, the scores of perceived walkability are predicted. For the evaluation of physical walkability, eight indicators are selected, and the score of overall physical walkability is calculated by combining the scores of the eight indicators. After that, the scores of perceived and physical walkability are visualized, and the difference between them is analyzed. This study is novel in three aspects. First, we develop a deep learning model that can improve the accuracy of perceived walkability using street view images, even in small and medium-sized cities. Second, in analyzing the characteristics of street view images, the possibilities and limitations of the semantic segmentation technique are confirmed. Third, the differences between perceived and physical walkability are analyzed in detail, and how the results of our study can be used to prepare alternatives for improving the walking environment is presented.

Abstract An abdominal binder could be used effectively in a patient showing CSF leakage in the coccygeal area with post‐dural puncture headache, which is not controlled by conventional compressive dressing.

Abstract This study develops an improved Feldkamp–Davis–Kress (FDK) reconstruction algorithm using non-local total variation (NLTV) denoising and a cubic B-spline interpolation-based backprojector to enhance the image quality of low-dose cone-beam computed tomography (CBCT). The NLTV objective function is minimized on all log-transformed projections using steepest gradient descent optimization with an adaptive control of the step size to augment the difference between a real structure and noise. The proposed algorithm was evaluated using a phantom data set acquired from a low-dose protocol with lower milliampere-seconds (mAs).The combination of NLTV minimization and cubic B-spline interpolation rendered the enhanced reconstruction images with significantly reduced noise compared to conventional FDK and local total variation with anisotropic penalty. The artifacts were remarkably suppressed in the reconstructed images. Quantitative analysis of reconstruction images using low-dose projections acquired from low mAs showed a contrast-to-noise ratio with spatial resolution comparable to images reconstructed using projections acquired from high mAs. The proposed approach produced the lowest RMSE and the highest correlation. These results indicate that the proposed algorithm enables application of the conventional FDK algorithm for low mAs image reconstruction in low-dose CBCT imaging, thereby eliminating the need for more computationally demanding algorithms. The substantial reductions in radiation exposure associated with the low mAs projection acquisition may facilitate wider practical applications of daily online CBCT imaging.

Abstract Breast cancer is one of the most common cancers in women and is associated with a high mortality rate. The majority of deaths resulting from breast cancer are attributable to metastatic growth; in addition, chemoresistance is a major concern in the treatment of patients with breast cancer. However, limited drugs are available for the treatment of metastatic breast cancer. In this study, the chemoadjuvant effects of a methanolic extract from the leaves of Pseudolysimachion rotundum var. subintegrum (NC13) and an active component isolated from the plant, verminoside (Vms), were evaluated. Furthermore, their potent anti-metastatic activities were validated in vitro and in vivo in animal models. The anti-metastatic and chemosensitizing activities of NC13 and Vms on cisplatin treatment were found to be partly mediated by suppression of the epithelial–mesenchymal transition of cancer cells. Collectively, our results implied that NC13 and its bioactive component Vms could be developed as effective chemoadjuvants in combination with conventional therapeutics.

Liver disease: Collagen fragment spurs liver inflammation and fibrosis Localized buildup in the liver of a collagen-derived cleavage fragment plays a critical role in accelerating the development of tissue scarring and liver cancer in mice. Using a transgenic mouse model of fatty liver disease, a team led by Philipp Scherer from the University of Texas Southwestern Medical Center, Dallas, USA, and Jiyoung Park of Ulsan National Institute of Science and Technology, South Korea, showed that liver-specific accumulation of a collagen fragment known as endotrophin leads to activation of inflammatory and fibrotic pathways. The mice subsequently develop metabolic dysfunction, insulin resistance and, with time, cancerous nodules in the liver. The findings suggest that endotrophin accumulation, when it occurs in liver tissue that already contains large depositions of fat, can overwhelm normal liver physiology and accelerate organ damage.

Purpose Community child centers (CCCs) were introduced to provide after-school activities and care, including meal services to children from low-income families. The assistant cooks, who have the main responsibility for making and serving food at CCCs, are a major factor influencing the eating habits of children using CCCs. In this study, we tried to identify and understand who the assistant cooks are, what their job responsibilities are, and what they need in order to be able to provide children with healthy meals. Methods Three focus group interviews were held with 17 workfare program participants who worked as assistant cooks at CCCs, and content analysis methods were applied using the NVivo 12 qualitative data analysis software. Results The assistant cooks reflected on their perceptions of the children’s health at the CCCs, their own cooking style, and their role at the CCCs. Additionally, barriers to the optimal provision of their services were pointed out, and improvements were suggested. Conclusion The results of this study can be used as a fundamental resource for the development of tailored interventions that consider a child’s unique environment to address health disparities, specifically with respect to childhood obesity.

Purpose This study was conducted to investigate nurses’ perceptions and performance of family-centered care (FCC) at a children’s hospital in Sri Lanka and to explore the feasibility of implementing FCC in the context of the Sri Lankan healthcare system. Methods A convergent, parallel, mixed-methods design was applied to understand Sri Lankan nurses’ perspectives on FCC. In total, 157 nurses working at a large teritagy children’s hospital responded to a self-report survey and 18 nurses participated in focus group interviews. Results Of the factors of FCC, family participation in caring for children received the highest score (4.09±0.51) for perceptions, and information-sharing received the highest score (3.54±0.55) for performance. The qualitative data revealed the following five themes: (a) importance of the family in caring for children; (b) helping families during children’s hospitalization; (c) taking steps to implement FCC, even with imperfect knowledge; (d) barriers in the current situation; and (e) suggested strategies to promote FCC. Conclusion Participants endorsed the concept of FCC and demonstrated some aspects of it in their day-to-day practice. The results indicate a clear knowledge deficit and several challenges, which need to be addressed to effectively implement FCC.

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are becoming increasingly prevalent worldwide. Despite the different etiologies, their spectra and histological feature are similar, from simple steatosis to more advanced stages such as steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Studies including peroxiredoxin knockout models revealed that oxidative stress is crucial in these diseases, which present as consequences of redox imbalance. Protein tyrosine phosphatases (PTPs) are a superfamily of enzymes that are major targets of reactive oxygen species (ROS) because of an oxidation-susceptible nucleophilic cysteine in their active site. Herein, we review the oxidative inactivation of two tumor suppressor PTPs, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and T-cell protein tyrosine phosphatase (TCPTP), and their contribution to the pathogenicity of ALD and NAFLD, respectively. This review might provide a better understanding of the pathogenic mechanisms of these diseases and help develop new therapeutic strategies to treat fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear. Methods: Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that MIR20B specifically targets PPARA. MIR20B mimic and anti-MIR20B were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high-fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of MIR20B in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by Mir20b and the synergic effect of combination of fenofibrate with anti-Mir20b in NAFLD mouse model. Results: We revealed that MIR20B specifically targets PPARA through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of MIR20B was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of MIR20B significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, MIR20B significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARA. In Mir20b-introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of Mir20b significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti-Mir20b exhibited the synergic effect on improvement of NAFLD in MCD-fed mice. Conclusions: Taken together, our results demonstrate that the novel MIR20B targets PPARA, plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD. Funding: This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340, NRF-2021R1I1A2041463, 2020R1I1A1A01074940, 2016M3C9A394589324), and the Future-leading Project Research Fund (1.210034.01) of UNIST.

We demonstrated in our previous reports that dimeric form of translationally controlled tumor protein (dTCTP) initiates a variety of allergic phenomena. In the present study, we examined whether and how dTCTP’s role in allergic inflammation can be modulated or negated. The possible potential of cardamonin as an anti-allergic agent was assessed by ELISA using BEAS-2B cells and OVA-challenged allergic mouse model. The interaction between cardamonin and dTCTP was confirmed by SPR assay. Cardamonin was found to reduce the secretion of IL-8 caused by dTCTP in BEAS-2B cells by interacting with dTCTP. This interaction between dTCTP and cardamonin was confirmed through kinetic analysis (KD = 4.72 ± 0.07 μM). Also, cardamonin reduced the migration of various inflammatory cells in the bronchoalveolar lavage fluid (BALF), inhibited OVA specific IgE secretion and bronchial remodeling. In addition, cardamonin was observed to have an anti-allergic response by inhibiting the activity of NF-κB. Cardamonin exerts anti-allergic anti-inflammatory effect by inhibiting dTCTP, suggesting that it may be useful in the therapy of allergic diseases.

Dimerized translationally controlled tumor protein (dTCTP) amplifies allergic responses through activation of several types of immune cells and release of inflammatory mediators. In particular, dTCTP plays an important role in histamine release by triggering mast cells and has been proposed as a target in the treatment of allergic diseases. dTCTP-binding peptide 2 (dTBP2) is known to attenuate severe allergic rhinitis and asthma through inhibition of dTCTP activity on airway epithelial cells and T cells; however, it is unclear whether dTBP2 affects mast cell function and mast cell disease. In this study, we explored the effects of dTBP2 on mast cell degranulation and allergen-induced anaphylactic reactions. We found that bacterial product lipopolysaccharide increased the expression of dTCTP in mast cells and rapidly released dTCTP by the mast cell stimulator compound 48/80. Interestingly, the released dTCTP further promoted mast cell degranulation in an autocrine activation manner and increased calcium mobilization in mast cells, which is essential for degranulation. Furthermore, dTBP2 directly and dose-dependently inhibited in vitro mast cell degranulation enhanced by compound 48/80, suggesting a direct and potent anti-anaphylactic activity of dTBP2. dTBP2 also significantly suppressed the dTCTP-induced degranulation and histamine release through inhibition of the p38 MAPK signaling pathway and suppression of lysosomal expansion and calcium mobilization in mast cells. More importantly, in vivo administration of dTBP2 decreased mortality and significantly attenuated histamine release and inflammatory cytokine production in compound 48/80-induced systemic anaphylactic reactions. These results suggest that dTBP2 is beneficial for the control of anaphylaxis with increased dTCTP.

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. In addition, NAFLD may increase the risk of cardiovascular and liver-related diseases, and displays features of metabolic syndrome. In NAFLD, oxidative stress is primarily caused by excessive free fatty acids. The oxidation of fatty acids is usually caused by β-oxidation of mitochondria under normal conditions, resulting in the production of energy. However, when the inflow of fatty acids in NAFLD becomes excessive, the β-oxidation of mitochondria becomes saturated and the oxidation process increases at sites including peroxisomes and microsomes, thereby increasing production of reactive oxygen species (ROS). Thus, hepatic mitochondrial ROS play an important role in the pathogenesis of NAFLD. Eliminating mitochondrial ROS may improve NAFLD, but the underlying mechanism remains unclear. We examined the effect of mitochondrial ROS on NAFLD by focusing on peroxiredoxin (Prx), an antioxidant protein that can remove hydrogen peroxide. The protective effect and pathological phenomenon of mitochondrial peroxiredoxin in methionine-choline deficient diet (MCD)-induced liver injury was assessed in a mouse model of NAFLD. In these mice, mitochondrial peroxiredoxin deficiency significantly increased hepatic steatosis and fibrosis. In addition, ablation of Prx III enhances susceptibility to MCD diet-induced oxidative stress and exacerbates NAFLD progression by promoting inflammation. The binding assay results also showed that Prx III-deficient mice had more severe liver damage than Prx III-abundant mice in MCD diet liver injury models. The present data suggest that mitochondrial peroxiredoxin III could be a therapeutic target for preventing and suppressing diet-induced NAFLD.

A survey of the macrozoobenthos communities in the Maritsa River (South Bulgaria) was carried out in the summer of 2021. Benthic samples were collected and physicochemical parameters (water temperature, pH, conductivity, dissolved oxygen and nutrients) were measured at 15 sites located on the main river and its tributary system. The studied sites belonged to different river types and characterised the diversity of the ecological conditions—from unaffected to anthropogenically influenced river stretches. In addition, data from a study conducted in the summer of 2020 were used to analyse species–factor interactions in the river ecosystems and to assess the bio-indicative potential of the aquatic invertebrates. The dynamics of the taxonomic composition and abundance of the macrozoobenthos were analysed in relation to environmental factors. The physicochemical conditions of the water environment changed during the period of high water, which led to a reduction in the composition of the macrozoobenthos. Plecoptera and Trichoptera decreased in richness and abundance downstream and under human impacts. Ephemeroptera and Chironomidae were permanently present along the whole river. Oligochaeta increased in the lower river reaches and at sites with a greater amount of organic matter. The ecological status determined by the macrozoobenthos varied from high (site 1) to good, moderate and bad (site 13) at the studied sites.

In vivo laser ablation of dendrites in single L2/3 pyramidal neurons reveals that neuronal orientation tuning in V1 is robust to loss of dendritic input. Orientation tuning functions remain unchanged following apical dendrite ablation and change only slightly upon loss of two primary basal dendrites.

Activation of thermogenic beige adipocytes within white adipose tissue increases energy expenditure. Here, the authors show that expression of TonEBP in adipocytes is increased when mice are fed a high fat diet and that it suppresses expression of beta3-adrenoreceptor.

Dopamine is a neurotransmitter that helps cells to transmit pulsed chemicals. Therefore, dopamine detection is crucial from the viewpoint of human health. Dopamine determination is typically achieved via chromatography, fluorescence, electrochemiluminescence, colorimetry, and enzyme-linked methods. However, most of these methods employ specific biological enzymes or involve complex detection processes. Therefore, non-enzymatic electrochemical sensors are attracting attention owing to their high sensitivity, speed, and simplicity. In this study, a simple one-step fabrication of a Bi2Te3-nanosheet/reduced-graphene-oxide (BT/rGO) nanocomposite was achieved using a hydrothermal method to modify electrodes for electrochemical dopamine detection. The combination of the BT nanosheets with the rGO surface was investigated by X-ray diffraction, X-ray photoelectron spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and Fourier-transform infrared spectroscopy. Electrochemical impedance spectroscopy, cyclic voltammetry, and differential pulse voltammetry were performed to analyze the electrochemical-dopamine-detection characteristics of the BT/rGO nanocomposite. The BT/rGO-modified electrode exhibited higher catalytic activity for electrocatalytic oxidation of 100 µM dopamine (94.91 µA, 0.24 V) than that of the BT-modified (4.55 µA, 0.26 V), rGO-modified (13.24 µA, 0.23 V), and bare glassy carbon electrode (2.86 µA, 0.35 V); this was attributed to the synergistic effect of the electron transfer promoted by the highly conductive rGO and the large specific surface area/high charge-carrier mobility of the two-dimensional BT nanosheets. The BT/rGO-modified electrode showed a detection limit of 0.06 µM for dopamine in a linear range of 10–1000 µM. Additionally, it exhibited satisfactory reproducibility, stability, selectivity, and acceptable recovery in real samples.

Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID) used to treat inflammatory diseases induces cellular toxicity by increasing the production of reactive oxygen species (ROS) and impairing autophagic flux. In this study, we investigated whether diclofenac induces cancer cell death and the mechanism by which diclofenac causes cell death. We observed that diclofenac induces mitotic arrest with a half-maximal effective concentration of 170 μM and cell death with a half-maximal lethal dose of 200 µM during 18-h incubation in HeLa cells. Cellular microtubule imaging and in vitro tubulin polymerization assays demonstrated that treatment with diclofenac elicits microtubule destabilization. Autophagy relies on microtubule-mediated transport and the fusion of autophagic vesicles. We observed that diclofenac inhibits both phagophore movement, an early step of autophagy, and the fusion of autophagosomes and lysosomes, a late step of autophagy. Diclofenac also induces the fragmentation of mitochondria and the Golgi during cell death. We found that diclofenac induces cell death further in combination with 5-fuorouracil, a DNA replication inhibitor than in single treatment in cancer cells. Pancreatic cancer cells, which have high basal autophagy, are particularly sensitive to cell death by diclofenac. Our study suggests that microtubule destabilization by diclofenac induces cancer cell death via compromised spindle assembly checkpoints and increased ROS through impaired autophagy flux. Diclofenac may be a candidate therapeutic drug in certain type of cancers by inhibiting microtubule-mediated cellular events in combination with clinically utilized nucleoside metabolic inhibitors, including 5-fluorouracil, to block cancer cell proliferation.

Development of small molecules that inhibit inflammatory cytokines is a desirable strategy for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). Following up a previous study, we synthesized 10 novel compounds with a 2,5-diaminobenzoxazole moiety and evaluated their biological activities. Among them, compound 3e showed potent inhibitory activity on Interleukin 6 (IL-6)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling inhibition (71.5%), and 3a showed excellent inhibitory activity on Interleukin 1 (IL-1β) (92.1%). To test in vivo anti-inflammatory activity, compounds 3a and 3e were administered by intraperitoneal (IP) injection after subcutaneous (SC) injection of zymosan A into the right footpad of mice. Inflammation on the footpad was reduced after administration of compounds 3a and 3e. Especially, compound 3a showed a significant ameliorative effect on zymosan-induced inflammation. From the in vivo and in vitro test results, we confirmed that our synthesized compounds are effective on the RA animal model through inhibition of the IL-6/STAT3 signaling pathway. Since drugs developed with small molecule inhibitors have several advantages over biological drugs, further study on these compounds is needed for the development of potent SMI drugs on RA.

Phosphatase and tensin homologs deleted on chromosome 10 (PTEN) is a potent tumor suppressor and often dysregulated in cancers. Cellular PTEN activity is restrained by the oxidation of active-site cysteine by reactive oxygen species (ROS). Recovery of its enzymatic activity predominantly depends on the availability of cellular thioredoxin (Trx) and peroxiredoxins (Prx), both are important players in cell signaling. Trx and Prx undergo redox-dependent conformational changes through the oxidation of cysteine residues at their active sites. Their dynamics are essential for protein functionality and regulation. In this review, we summarized the recent advances regarding the redox regulation of PTEN, with a specific focus on our current state-of-the-art understanding of the redox regulation of PTEN. We also proposed a tight association of the redox regulation of PTEN with Trx dimerization and Prx hyperoxidation, providing guidance for the identification of novel therapeutic targets.

Purpose: The purpose of this study was to identify trends in health-related interventions on children attending Community Child Care (CCC) centers, which are part of a health policy to provide after-school care for vulnerable children in South Korea. Methods: From 2007, 109 papers were analyzed using the scoping study method. Results: The number of studies increased steadily between 2007 and 2016. Most studies were based on the social sciences, and the participants were mainly elementary school students. Psychological and social interventions were the most common types of interventions with socio-psychological indicators as measurements. In addition, only a few studies had a clearly defined conceptual framework. The majority of studies did not explicitly indicate that they followed ethical considerations. Conclusion: It is necessary to develop health-related interventions for children attending CCC centers using diverse subjects, types, and evaluation methods, along with improvements in the quality of research methodology. Furthermore, it is essential to clearly articulate and implement ethical considerations in research targeting vulnerable children.