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Kyoung-Hee Sohn,1 Myung-Nam Lee,2 Da Woon Sim,3 Sujeong Kim,4 You Sook Cho,5 Hyouk-Soo Kwon,5 Sang-Heon Kim6 1Division of Pulmonology and Allergy, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, South Korea; 2Department of Nursing, College of Health Science, Kangwon National University Samcheok, Samcheok-si, Gangwon-do, South Korea; 3Department of Allergy and Clinical Immunology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, South Korea; 4Division of Allergy and Clinical Immunology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea; 5Department of Allergy and Clinical Immunology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; 6Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South KoreaCorrespondence: Hyouk-Soo Kwon, Department of Allergy and Clinical Immunology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea, Email kwonhs21@naver.com Sang-Heon Kim, Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea, Email sangheonkim@hanyang.ac.kr

CONTEXT:. PICUs across Canada restricted family presence (RFP) in response to the COVID-19 pandemic from allowing two or more family members to often only one family member at the bedside. The objective of this study was to describe the experiences and impact of RFP on families of critically ill children to inform future policy and practice. HYPOTHESIS:. RFP policies negatively impacted families of PICU patients and caused moral distress. METHODS AND MODELS:. National, cross-sectional, online, self-administered survey. Family members of children admitted to a Canadian PICU between March 2020 and February 2021 were invited to complete the survey. RFP-attributable distress was measured with a modified distress thermometer (0–10). Closed-ended questions were reported with descriptive statistics and multivariable linear regression assessed factors associated with RFP-attributable distress. Open-ended questions were analyzed using inductive content analysis. RESULTS:. Of 250 respondents who experienced RFP, 124 (49.6%) were restricted to one family member at the bedside. The median amount of distress that families attributed to RFP policies was 6 (range: 0–10). Families described isolation, removal of supports, and perception of trauma related to RFP. Most families (183, 73.2%) felt that policies were enforced in a way that made them feel valued by PICU clinicians, which was associated with less RFP-attributable distress. Differential impact was seen where families with lower household income indicated higher RFP-attributable distress score (2.35; 95% CI, 0.53–4.17; p = 0.03). Most respondents suggested that future policies should allow at least two family members at the bedside. INTERPRETATIONS AND CONCLUSIONS:. Families of children admitted to PICUs during the COVID-19 pandemic described increased distress, trauma, and removal of supports due to RFP policies. Vulnerable families showed an increased odds of higher distress. Healthcare professionals played an important role in mitigating distress. Allowance of at least two family members at the bedside should be considered for future policy.

Virtual care became a routine method for healthcare delivery during the coronavirus disease 2019 (COVID-19) pandemic. Patient preferences are central to delivering patient-centered and high-quality care. The pandemic challenged healthcare organizations and providers to quickly deliver safe healthcare to COVID-19 patients. This resulted in varied implementation of virtual healthcare services. With an increased focus on remote COVID-19 monitoring, little research has examined patient experiences with virtual care. This scoping review examined patient experiences and preferences with virtual care among community-based self-isolating COVID-19 patients. We identified a paucity of literature related to patient experiences and preferences regarding virtual care. Few articles focused on patient experiences and preferences as a primary outcome. Our research suggests that (1) patients view virtual care positively and to be feasible to use; (2) patient access to technology impacts patient satisfaction and experiences; and (3) to enhance the patient experience, healthcare organizations and providers need to support patient use of technology and resolve technology-related issues. When planning virtual care modalities, purposeful consideration of patient experiences and preferences is needed to deliver quality patient-centered care.

Abstract The issue of pinned field image binarization for signature generation in the ownership verification of the protected image is investigated. The pinned field explores the texture information of the protected image and can be employed to enhance the watermark robustness. In the proposed method, four optimization schemes are utilized to determine the threshold values for transforming the pinned field into a binary feature image, which is then utilized to generate an effective signature image. Experimental results show that the utilization of optimization schemes can significantly improve the signature robustness from the previous method (Lee and Chang, Opt. Eng. 49 (9), 097005, 2010). While considering both the watermark retrieval rate and the computation speed, the genetic algorithm is strongly recommended. In addition, compared with Chang and Lin's scheme (J. Syst. Softw. 81 (7), 1118-1129, 2008), the proposed scheme also has better performance.

Background: Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A(225)) acetylates HIF-1alpha, triggering its degradation, and thus may play a role in decreased expression of VEGFA.Methods: We generated Apc(Min/+)/mARD1A(225) transgenic mice and quantified growth of intestinal polyps. Human gastric MKN74 and murine melanoma B16F10 cells overexpressing mARD1A(225) were injected into mice, and tumor growth and metastasis were measured. VEGFA expression and microvessel density in tumors were assessed using immunohistochemistry. To evaluate the role of mARD1A(225) acetylation of Lys532 in HIF-1alpha, we injected B16F10-mARD1A(225) cell lines stably expressing mutant HIF-1alpha/K532R into mice and measured metastasis. All statistical tests were two-sided, and P values less than .05 were considered statistically significant.Results: Apc(Min/+)/mARD1A(225) transgenic mice (n = 25) had statistically significantly fewer intestinal polyps than Apc(Min/+) mice (n = 21) (number of intestinal polyps per mouse: Apc(Min/+) mice vs Apc(Min/+)/mARD1A(225) transgenic mice, mean = 83.4 vs 38.0 polyps, difference = 45.4 polyps, 95% confidence interval [CI] = 41.8 to 48.6; P < .001). The growth and metastases of transplanted tumors were also statistically significantly reduced in mice injected with mARD1A(225)-overexpressing cells than in mice injected with control cells (P < .01). Moreover, overexpression of mARD1A(225) decreased VEGFA expression and microvessel density in tumor xenografts (P < .04) and Apc(Min/+) intestinal polyps (P = .001). Mutation of lysine 532 of HIF-1alpha in B16F10-mARD1A(225) cells prevented HIF-1alpha degradation and inhibited the antimetastatic effect of mARD1A(225) (P < .001).Conclusion: mARD1A(225) may be a novel upstream target that blocks VEGFA expression and tumor-related angiogenesis. [ABSTRACT FROM AUTHOR]

Accurate origin determination of seafood is crucial for consumer trust and safety. This study was performed to develop a machine learning-based single-nucleotide polymorphism (SNP) analysis technique to determine the origin of Acetes species in salted small-shrimp products. Mitochondrial DNA (COI and 16S rRNA) analysis revealed genetic variations among species and origins. Eight candidate SNPs were identified, six of which were developed into markers for genotyping analysis. Using the developed markers, an SNP array was created and SNP data from salted small-shrimp samples were obtained. Machine learning analysis using a supervised learning algorithm achieved 100% accuracy in classifying the origin of Acetes based on SNP data. This method offers a reliable method for regulatory bodies to combat food fraud and ensure product integrity. The approach can be further improved by expanding the data set to encompass a wider range of species and origins. This study highlights the potential of SNP analysis and machine learning for ensuring seafood authenticity and promoting sustainable practices.

Purpose: This study aimed to analyze interventions for bereaved families and evaluate their effectiveness, with the ultimate goal of supporting evidence-based nursing for bereaved families., Methods: Research trends were identified based on a search of domestic databases from January 2000 to December 2022, and a meta-analysis was conducted on interventions for bereaved families. Forty-five papers were selected, and information was extracted on participants, research design, and interventions. A meta-analysis of seven papers was performed, and the effect size was calculated., Results: Fourteen papers dealt with interventions for middle-aged women who had lost their spouses, 20 used qualitative research methods, and 20 were on art therapy programs. Thirty studies had fewer than 10 participants, and most interventions had 60~120 minutes per session and 9~16 sessions in total. There were seven randomized controlled trials, and all studies included in the quality evaluation showed a low risk of bias. Four papers measured grief as an outcome, and the effect size was -1.9577 (95% CI -2.9206 to -0.9947), indicating that the treatment significantly decreased grief (P<0.001). Six papers measured depression as an outcome, and the effect size was -1.6775 (95% CI -2.1835 to -1.1716), showing that the treatment significantly decreased depression (P<0.001)., Conclusion: Intervention programs for bereaved families were shown to be effective in relieving grief and depression. However, programs should be developed that target middle-aged men who have lost their spouses and children who have lost their parents. Randomized controlled trials should also be conducted on interventions to reduce grief and depression., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by Korean Society for Hospice and Palliative Care.)

Time-restricted feeding (TRF) has been shown to improve the disordered metabolic and immunologic functions associated with obesity, however little is known about its post-effects after the cessation of TRF practice. In the current study, we determined how long the effects of TRF persist, and whether the effects are tissue-dependent. There were four groups of mice in this study: overweight and obese mice were randomized into (1) TRF group (TRF for 6 weeks), (2) post-TRF group (TRF for 4 weeks and later ad libitum), (3) continuous ad libitum of high-fat diet (HFD-AL), and (4) the lean control-fed low-fat diet ad libitum. Blood, liver, and adipose tissues were collected to measure the metabolic, inflammatory, and immune cell parameters. The results showed that TRF withdrawal quickly led to increased body weight/adiposity and reversed fasting blood glucose. However, fasting insulin and insulin resistance index HOMA-IR remained lower in the post-TRF than in the HFD-AL group. In addition, TRF-induced reduction in blood monocytes waned in the post-TRF group, but the TRF effects on mRNA levels of proinflammatory immune cells (macrophages Adgre1 and Itgax ) and cytokine ( Tnf ) in adipose tissue remained lower in the post-TRF group than in the HFD-AL group. Furthermore, the TRF group was protected from the down-regulation of Pparg mRNA expression in adipose tissue, which was also observed in the post-TRF group to a lesser extent. The post-TRF animals displayed liver mass similar to those in the TRF group, but the TRF effects on the mRNA of inflammation markers in the liver vanished completely. Together, these results indicate that, although the lasting effects of TRF may differ by tissues and genes, the impact of TRF on adipose tissue inflammation and immune cell infiltration could last a couple of weeks, which may, in part, contribute to the maintenance of insulin sensitivity even after the cessation of TRF.

Time-restricted feeding (TRF) has emerged as a promising dietary approach in improving metabolic parameters associated with obesity, but its effect on immune cells under obesogenic condition is poorly understood. We conducted this study to determine whether TRF exerts its therapeutic benefit over obesity-induced myeloid cell production by analyzing hematopoietic stem and progenitor cells in bone marrow (BM) and immune cell profile in circulation. Male C57BL/6 mice were fed a low-fat diet (LFD) or high-fat diet (HFD) ad libitum for 6 weeks and later a subgroup of HFD mice was switched to a daily 10 h-TRF schedule for another 6 weeks. Mice on HFD ad libitum for 12 weeks had prominent monocytosis and neutrophilia, associated with expansion of BM myeloid progenitors, such as multipotent progenitors, pre-granulocyte/macrophage progenitors, and granulocyte/macrophage progenitors. TRF intervention in overweight and obese mice diminished these changes to a level similar to those seen in mice fed LFD. While having no effect on BM progenitor cell proliferation, TRF reduced expression of Cebpa , a transcription factor required for myeloid differentiation. These results indicate that TRF intervention may help maintain immune cell homeostasis in BM and circulation during obesity, which may in part contribute to health benefits associated with TRF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflicted of interest., (Copyright © 2022 Kim, Lee, Lee, Nah, Yun, Wu and Pae.)

The purpose of this study was to provide basic data on health by examining the effect of HINT-eight on the physical activity of middle-aged Korean women using secondary data from the 2019 KNHANES. The subjects were 1,428 middle-aged women aged 45-64. Multiple regression was performed to verify the relationship between physical activity and HINT-eight. Following confirmation of the association between HINT-eight and physical activity, it was found that the subdomains of QOL, such as stair climbing, vitality, work, sleeping, and happiness, were connected to physical activity. Stair climbing positively affected physical activity, education level, and grip strength and negatively affected age. Pain positively affected education level and grip strength and negatively affected age. Vitality positively affected physical activity, monthly household income, and grip strength. Working positively affected education level, monthly household income, and grip strength and negatively affected age. Depression positively affected monthly household income. Memory and sleep positively affected education level and negative effect on age. Happiness positively affected physical activity and monthly household income. In this study, physical activity was found to have an effect on various factors of QOL. Physical activity in middle age is an important influencing factor on the QOL in old age; to improve the QOL in older adult, it is necessary to make efforts to improve physical activity in middle age., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Myung-Nam Lee et al.)

(1) Background: During the coronavirus disease 2019 (COVID-19) pandemic, the prevalence of obesity or severe obesity has increased worldwide to the point that it has even been referred to as a new disease. However, the impacts of the pandemic on obesity or severe obesity remain unclear, thus requiring a thorough examination of the leading factors of obesity and severe obesity during this time. (2) Methods: The required dataset for this study was extracted from the eighth (2019-2020) Korea National Health and Nutrition Examination Survey (KNHNES). The survey's data for 2019 and 2020 were analyzed to confirm the leading factors of obesity and severe obesity before and after the outbreak of COVID-19. The samples were weighted, and the data were analyzed using multiple logistic regression. (3) Results: In 2020, the prevalence of obesity and severe obesity in the Korean adult population aged 19 and over, compared with the normal weight group, showed significant increases of 2.5% and 1.4%, respectively, compared with those rates in 2019 ( p < 0.05). The main variables affecting the obesity prevalence in Korean adults aged 19 and over in 2020 were gender, age, sitting time per day, and walking time per day, and the factors affecting severe obesity were gender and age. Meanwhile, the daily energy intake variable had no impact on the prevalence of obesity and severe obesity. (4) Conclusions: These findings will serve as a basis to help the present management directions and treatment approaches for individuals with obesity or severe obesity in the post-COVID-19 era.

Purpose: The purpose of this study was to confirm the factor structure of the McGill Quality of Life Questionnaire-Revised (MQOL-R) in the context of Korean culture and to verify its reliability and validity., Methods: The participants comprised terminal cancer patients aged 25 or older, and data from 164 participants were analyzed. The study was conducted in the following order translation, expert review, reverse translation, preliminary investigation and interviews, and completion of the final version. Confirmatory factor analysis was applied to evaluate the validity of the instrument, and the Beck Depression Inventory, Korean version (K-BDI) was applied to confirm the criterion validity of the MQOL-R Korean version. The Cronbach's alpha coefficient, representing internal consistency, was measured to evaluate reliability., Results: Cronbach's alpha for all 14 questions was 0.862. The model fit indices for confirmatory factor analysis were within the acceptance criteria. The factor loadings of all four factors were over 0.50, and convergent validity and discriminant validity were confirmed. Regarding criterion validity, a negative correlation was found between the four factors of MQOL-R Korean version and the K-BDI., Conclusion: The MQOL-R Korean version, the reliability and validity of which were verified in this study, is a 15-item tool consisting of 14 items dealing with four physical, psychological, existential, and social factors and a single item evaluating the overall quality of life. The MQOL-R Korean version is an instrument that can more concisely and effectively measure the quality of life of patients with life-threatening diseases., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2022 by Korean Society for Hospice and Palliative Care.)

Purpose: This study aimed to describe nurses' perceived needs and barriers to pediatric palliative care (PPC)., Methods: Mixed methods with an embedded design were applied. An online survey was conducted for nurses who participated in the End-of-Life Nursing Education Consortium- Pediatric Palliative Care (ELNEC-PPC) train-the-trainer program, of whom 63 responded. Quantitative data were collected with a survey questionnaire developed through the Delphi method. The 47 items for needs and 15 items for barriers to PPC were analyzed with descriptive statistics. Qualitative data were collected through open- ended questions and analyzed with topic modeling techniques., Results: The mean scores of most subdomains of the PPC needs were 3.5 or higher out of 4, and those of PPC barriers ranged from 3.22 to 3.56, indicating the items in the questionnaire developed in this study properly reflect each factor. The needs for PPC were divided into 4 categories "children and adolescents," "families," "PPC management system," and "community-based PPC." Meanwhile, PPC barriers were divided into 3 categories "healthcare delivery system," "healthcare provider," and "client." The keywords derived from the topic modeling were perception, palliative, children, and education for necessities and lack, perception, medical care, professional care providers, service, and system for barriers to PPC., Conclusion: In this study, by using mixed-methods, items of nurses' perceived needs and barriers to PPC were identified, categorized, and weighted, and their meanings were explored. For the stable establishment of PPC, the priority should be given to improving perceptions of PPC, establishing an appropriate system, and training professional care providers., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2022 by Korean Society for Hospice and Palliative Care.)

Background: The use of mouse bone marrow mesenchymal stem cells (mBMSCs) represents a promising strategy for performing preclinical studies in the field of cell-based regenerative medicine; however, mBMSCs obtained via conventional isolation methods have two drawbacks, i.e., (i) they are heterogeneous due to frequent macrophage contamination, and (ii) they require long-term culturing for expansion., Methods: In the present study, we report a novel strategy to generate highly pure mBMSCs using liposomal clodronate. This approach is based on the properties of the two cell populations, i.e., BMSCs (to adhere to the plasticware in culture dishes) and macrophages (to phagocytose liposomes)., Results: Liposomal clodronate added during the first passage of whole bone marrow culture was selectively engulfed by macrophages in the heterogeneous cell population, resulting in their effective elimination without affecting the MSCs. This method allowed the generation of numerous high-purity Sca-1 + CD44 + F4/80 - mBMSCs (> 95%) with just one passaging. Comparative studies with mBMSCs obtained using conventional methods revealed that the mBMSCs obtained in the present study had remarkably improved experimental utilities, as demonstrated by in vitro multilineage differentiation and in vivo ectopic bone formation assays., Conclusion: Our newly developed method, which enables the isolation of mBMSCs using simple and convenient protocol, will aid preclinical studies based on the use of MSCs., (© 2021. The Author(s).)

Mitochondrial quality control (MQC) consists of multiple processes: the prevention of mitochondrial oxidative damage, the elimination of damaged mitochondria via mitophagy and mitochondrial fusion and fission. Several studies proved that MQC impairment causes a plethora of pathological conditions including cardiovascular diseases. However, the precise molecular mechanism by which MQC reverses mitochondrial dysfunction, especially in the heart, is unclear. The mitochondria-specific peroxidase Peroxiredoxin 3 (Prdx3) plays a protective role against mitochondrial dysfunction by removing mitochondrial reactive oxygen species. Therefore, we investigated whether Prdx3-deficiency directly leads to heart failure via mitochondrial dysfunction. Fifty-two-week-old Prdx3-deficient mice exhibited cardiac hypertrophy and dysfunction with giant and damaged mitochondria. Mitophagy was markedly suppressed in the hearts of Prdx3-deficient mice compared to the findings in wild-type and Pink1-deficient mice despite the increased mitochondrial damage induced by Prdx3 deficiency. Under conditions inducing mitophagy, we identified that the damaged mitochondrial accumulation of PINK1 was completely inhibited by the ablation of Prdx3. We propose that Prdx3 interacts with the N-terminus of PINK1, thereby protecting PINK1 from proteolytic cleavage in damaged mitochondria undergoing mitophagy. Our results provide evidence of a direct association between MQC dysfunction and cardiac function. The dual function of Prdx3 in mitophagy regulation and mitochondrial oxidative stress elimination further clarifies the mechanism of MQC in vivo and thereby provides new insights into developing a therapeutic strategy for mitochondria-related cardiovascular diseases such as heart failure., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Topoisomerase IIIβ (Top3β), the only dual-activity topoisomerase in mammals that can change topology of both DNA and RNA, is known to be associated with neurodevelopment and mental dysfunction in humans. However, there is no report showing clear associations of Top3β with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3β on neuro-behavior using newly generated Top3β deficient ( Top3β -/- ) mice. We found that Top3β -/- mice showed decreased anxiety and depression-like behaviors. The lack of Top3β was also associated with changes in circadian rhythm. In addition, a clear expression of Top3β was demonstrated in the central nervous system of mice. Positron emission tomography/computed tomography (PET/CT) analysis revealed significantly altered connectivity between many brain regions in Top3β -/- mice, including the connectivity between the olfactory bulb and the cerebellum, the connectivity between the amygdala and the olfactory bulb, and the connectivity between the globus pallidus and the optic nerve. These connectivity alterations in brain regions are known to be linked to neurodevelopmental as well as psychiatric and behavioral disorders in humans. Therefore, we conclude that Top3β is essential for normal brain function and behavior in mice and that Top3β could be an interesting target to study neuropsychiatric disorders in humans.

An ethanol extract (Pd-EE) of Pinus densiflora Siebold and Zucc was derived from the branches of pine trees. According to the Donguibogam, pine resin has the effects of lowering the fever, reducing pain, and killing worms. The purpose of this study is to investigate whether Pd-EE has anti-inflammatory effects. During in vitro trials, NO production, as well as changes in the mRNA levels of inflammation-related genes and the phosphorylation levels of related proteins, were confirmed in RAW264.7 cells activated with lipopolysaccharide depending on the presence or absence of Pd-EE treatment. The activities of transcription factors were checked in HEK293T cells transfected with adapter molecules in the inflammatory pathway. The anti-inflammatory efficacy of Pd-EE was also estimated in vivo with acute gastritis and acute lung injury models. LC-MS analysis was conducted to identify the components of Pd-EE. This extract reduced the production of NO and the mRNA expression levels of iNOS, COX-2, and IL-6 in RAW264.7 cells. In addition, protein expression levels of p50 and p65 and phosphorylation levels of FRA1 were decreased. In the luciferase assay, the activities of NF-κB and AP-1 were lowered. In acute gastritis and acute lung injury models, Pd-EE suppressed inflammation, resulting in alleviated damage.

Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) is the major acetyltransferase, with 40-50% of all mammalian proteins being potential substrates. However, the overall role of amino-terminal acetylation on a whole-organism level is poorly understood, particularly in mammals. Male mice lacking Naa10 show no globally apparent in vivo amino-terminal acetylation impairment and do not exhibit complete embryonic lethality. Rather Naa10 nulls display increased neonatal lethality, and the majority of surviving undersized mutants exhibit a combination of hydrocephaly, cardiac defects, homeotic anterior transformation, piebaldism, and urogenital anomalies. Naa12 is a previously unannotated Naa10 -like paralog with NAT activity that genetically compensates for Naa10 . Mice deficient for Naa12 have no apparent phenotype, whereas mice deficient for Naa10 and Naa12 display embryonic lethality. The discovery of Naa12 adds to the currently known machinery involved in amino-terminal acetylation in mice., Competing Interests: HK, ML, MD, SS, LG, TP, NM, RR, DB, AG, MF, JC, AS, SL, AI, EM, SS, SJ, SJ, SJ, SC, TK, HK, CL, TR, TA, RM, GO, GL No competing interests declared, (© 2021, Kweon et al.)

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

Background: The delivery of recombinant human bone morphogenetic protein 2 (rhBMP2) by using various carriers has been used to successfully induce bone formation in many animal models. However, the effect of multiple administration of rhBMP2 on bone formation and BMP2 antibody production has not been determined. Our aim was to examine the bone formation activity of rhBMP2 and serum levels of anti-BMP2 antibodies following the repeated administration of rhBMP2 in mice., Methods: Absorbable collagen sponges or polyphosphazene hydrogels containing rhBMP2 were subcutaneously implanted or injected into one side on the back of six-week-old C57BL/6 mice. Three or 4 weeks later, the same amount of rhBMP2 was administered again with the same carrier into the subcutaneous regions on the other side of the back or into calvarial defects. The effects of a single administration of rhBMP2 on the osteoinductive ability in the ectopic model were compared with those of repeated administrations. In vivo ectopic or orthotopic bone formation was evaluated using microradiography and histological analyses. Serum concentrations of anti-rhBMP2 antibodies were measured by ELISAs., Results: Re-administration of the same amount of rhBMP2 into the subcutaneous area showed a comparable production of ectopic bone as after the first administration. The bone forming ability of repeated rhBMP2 administrations was equal to that of single rhBMP2 administration. The administration of rhBMP2 into calvarial defects, following the first subcutaneous administration of rhBMP2 on the back, completely recovered the defect area with newly regenerated bone within 3 weeks. Repeated administration of rhBMP2 at 4-week intervals did not significantly alter the serum levels of anti-BMP2 antibodies and did not induce any inflammatory response. The serum obtained from rhBMP2-exposed mice had no effect on the ability of rhBMP2 to induce osteogenic gene expressions in MC3T3-E1., Conclusion: We suggest that the osteoinductive ability of rhBMP2 is not compromised by repeated administrations. Thus, rhBMP2 can be repeatedly used for bone regeneration at various sites within a short duration.

Background: Bystander-initiated cardiopulmonary resuscitation (CPR) and the use of automated external defibrillation (AED) is pivotal in the community chain of survival, but little is known regarding the bystander experience of performing CPR and AED, and their psychological infl uence from the incidents in the Asian community. This qualitative study was conducted to explore the experiences of lay rescuers who had performed CPR and AED in public locations in Taiwan., Methods: Lay rescuers who had provided initial CPR and defi brillation with AED in public locations across Taiwan in 2015 were selectively recruited from Taiwan Public AED Registry for a semi-structured interview., Results: Nine participants were included in the study, and event-to-interview duration was within 1 year (n = 4) and 1-2 years (n = 5). The major fi ndings from the study were: (1) the lay rescuers possessed helping traits and high motivation; (2) the lay rescuers reported certain aspects of rescue reality that differed much from prior training and expectations, including diffi culty in the depth of chest compression, and uncertainties in real emergency situations; (3) the lay rescuers gained positive personal fulfi llment in sharing their experience and receiving positive feedback from others, and were willing to help next time, although they experienced a short-term negative psychological impact from the event., Conclusions: This study provides valuable information on strategies to increase layperson CPR rates and effectiveness in CPR training. Measures should be taken to increase layperson's confi dence and situation awareness, reduce training-reality discrepancy, build up a support system to avoid negative psychological effects, and prepare lay rescuers for the next resuscitation., Competing Interests: None., (Copyright © 2020 by Taiwan Society of Emergency Medicine & Ainosco Press. All Rights Reserved.)

With the global pandemic of the coronavirus disease, virtual reality simulation (vSim) has emerged as a simulation educational method. The purpose of this study is to examine the learning effects of vSim by comparing three different educational modalities of nursing care for children with asthma. A quasi-experimental design with three different teaching methods, vSim, high-fidelity simulation (HFS), and vSim with HFS, were used in the study. The group using vSim with HFS showed the highest scores in knowledge, confidence in practice, and performance compared to groups using vSim or HFS alone. Simulation practice using vSim combined with HFS could be an effective educational method for nursing students.

Background: Macrophages produce many inflammation-associated molecules, released by matrix metalloproteinases, such as adhesion molecules, and cytokines, as well, which play a crucial role in atherosclerosis. In this context, we investigated the relationship between Ninjurin-1 (Ninj1 [nerve injury-induced protein]), a novel matrix metalloproteinase 9 substrate, expression, and atherosclerosis progression., Methods: Ninj1 expression and atherosclerosis progression were assessed in atherosclerotic aortic tissue and serum samples from patients with coronary artery disease and healthy controls, and atheroprone apolipoprotein e-deficient ( Apoe -/- ) and wild-type mice, as well. Apoe -/- mice lacking systemic Ninj1 expression ( Ninj1 -/- Apoe -/- ) were generated to assess the functional effects of Ninj1. Bone marrow transplantation was also used to generate low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice that lack Ninj1 specifically in bone marrow-derived cells. Mice were fed a Western diet for 5 to 23 weeks, and atherosclerotic lesions were investigated. The anti-inflammatory role of Ninj1 was verified by treating macrophages and mice with the peptides Ninj1 1 -56 (ML56) and Ninj1 26 -37 (PN12), which mimic the soluble form of Ninj1 (sNinj1)., Results: Our in vivo results conclusively showed a correlation between Ninj1 expression in aortic macrophages and the extent of human and mouse atherosclerotic lesions. Ninj1 -deficient macrophages promoted proinflammatory gene expression by activating mitogen-activated protein kinase and inhibiting the phosphoinositide 3-kinase/Akt signaling pathway. Whole-body and bone marrow-specific Ninj1 deficiencies significantly increased monocyte recruitment and macrophage accumulation in atherosclerotic lesions through elevated macrophage-mediated inflammation. Macrophage Ninj1 was directly cleaved by matrix metalloproteinase 9 to generate a soluble form that exhibited antiatherosclerotic effects, as assessed in vitro and in vivo. Treatment with the sNinj1-mimetic peptides, ML56 and PN12, reduced proinflammatory gene expression in human and mouse classically activated macrophages, thereby attenuating monocyte transendothelial migration. Moreover, continuous administration of mPN12 alleviated atherosclerosis by inhibiting the enhanced monocyte recruitment and inflammation characteristics of this disorder in mice, regardless of the presence of Ninj1., Conclusions: Ninj1 is a novel matrix metalloproteinase 9 substrate in macrophages, and sNinj1 is a secreted atheroprotective protein that regulates macrophage inflammation and monocyte recruitment in atherosclerosis. Moreover, sNinj1-mediated anti-inflammatory effects are conserved in human macrophages and likely contribute to human atherosclerosis.

Background: Macrophage-stimulating protein (MSP; also known as macrophage stimulating 1 and hepatocyte growth factor-like protein) has been shown to play a crucial role in calcium homeostasis and skeletal mineralization in zebrafish. However, the precise role of MSP in osteoblasts has not been elucidated. In this study, we investigated the effect of MSP on osteoblast differentiation of pre-osteoblast cells., Methods: Osteoblast differentiation upon MSP treatment was evaluated by analyzing the osteogenic gene expression, alkaline phosphatase (ALP) activity, and mineralized nodule formation. To assess changes in the MSP-RON signaling pathway, knockdown of Ron gene was performed using siRNA and pharmacological inhibitor treatment., Results: Expression of the tyrosine kinase receptor RON, a receptor of MSP, was found to be significantly increased during osteoblast differentiation. MSP treatment significantly upregulated the expression of osteogenic marker genes and remarkably increased ALP activity and mineralized nodule formation. Conversely, knockdown of Ron significantly attenuated the expression of osteogenic marker genes and ALP activity that were induced upon MSP treatment. Mechanistically, MSP treatment significantly enhanced the phosphorylation of extracellular signal-regulated kinase (ERK); however, additional treatment with the selective ERK inhibitor PD98059 attenuated the effect of MSP on osteoblast differentiation., Conclusions: Altogether, these results indicate that the MSP-RON axis is involved in promoting osteoblast differentiation via activation of the ERK signaling pathway.

Aims: This study explores the effects of various genetic polymorphisms in candidate genes on thiopurine metabolism and toxicity in adult patients with Crohn's disease in Korea., Methods: A total of 131 adult patients with Crohn's disease receiving thiopurine treatment were included. The TPMT and NUDT15 genes and an additional 116 genetic polymorphisms (in 40 genes and 3 intergenic locations) were screened for genotyping. Among the polymorphisms screened, 91 genetic polymorphisms (in 34 genes and 3 intergenic locations) in addition to TPMT and NUDT15 genotypes were included for statistical analyses to investigate their effects on thiopurine metabolites and adverse outcomes (leukopenia, hepatotoxicity, gastrointestinal intolerance, skin rash and alopecia)., Results: The median duration of thiopurine treatment was 47.0 months (range 6.0-153.4 months). Patient sex, maintenance dose of thiopurine, and use of anti-tumour necrosis factor agents were associated with thiopurine metabolite concentrations (P < .05). In the univariate analysis, the TPMT genotype was associated with 6-thioguanine level (P < .05), although the significance of this did not remain in multivariate analysis. Genetic polymorphisms in the ATIC (rs3821353 and rs16853834), IMPDH2 (rs11706052) and ITPA (rs6139036) genes were associated with thiopurine metabolism (P < .05). Genetic polymorphisms in the ABCC5 (rs8180093) and NUDT15 genotypes were associated with leukopenia (P < .05)., Conclusion: The results of this study may help clinicians to understand the effects of other various polymorphisms in addition to TPMT and NUDP15 in thiopurine metabolism for management of Crohn's disease patients., (© 2020 The British Pharmacological Society.)

Purpose: This study aimed to describe the meaning of spiritual care as perceived by nursing students., Methods: This study used a descriptive research design, and the participants were 126 fourth-year nursing students from three nursing colleges. Data were collected from August to September 2019, and were analyzed using the content analysis method., Results: Four themes of spiritual care with 15 sub-themes were extracted from the content analysis 1) "promoting spiritual well-being" (sub-themes "providing religious help", "caring for the patient as a spiritual being", and "presupposing human dignity regardless of religion"); 2) "taking place in actual nursing practice" (representative sub-themes "considering the perspective of the patient", "reducing suffering"); 3) "caring for the multifaceted needs of human beings" (representative sub-themes "providing physical, mental, and spiritual care", "caring for both the mental and physical health of the patient"), and 4) "growing together" (sub-themes "positively affecting patient well-being", "beginning with the nurse's self-transcendence")., Conclusion: These results suggest that nursing students consider spiritual care to be a highly positive and practical form of nursing care. However, because few students have been exposed to religion and spirituality, more systematic training should be provided., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2020 by Korean Society for Hospice and Palliative Care.)

Takifugu rubripes is more expensive than other species of the genus because of its high protein content and special flavor. However, it is easily confused with imported T. chinensis and T. pseudommus because they have similar morphological characteristics. We identified single nucleotide polymorphism (SNP) markers of T. rubripes by genotyping-by-sequencing (GBS) and evaluated their ability to distinguish among T. rubripes, T. chinensis, and T. pseudommus. In all, 18 polymorphic SNPs were subjected to phylogenetic analyses of the three Takifugu species. Additionally, we subjected a second set of samples to Sanger sequencing to verify that the polymorphic SNPs could be used to evaluate the genetic variation among the three Takifugu species. A phylogenetic tree that included the analyzed sequence of set A, which is referred to as the reference sequence, and a validation sequence of set B with 18 SNPs were produced. Based on this phylogenetic tree and STRUCTURE analyses, T. rubripes, T. chinensis and T. pseudommus have low genetic variation and should be considered the same gene pool. Our findings suggest that further studies are needed to estimate the genetic association of the three Takifugu species., Competing Interests: No authors have competing interests.

The CUE domain-containing 2 (CUEDC2) protein plays critical roles in many biological processes, such as the cell cycle, inflammation, and tumorigenesis. However, whether CUEDC2 is involved in osteoblast differentiation and plays a role in bone regeneration remains unknown. This study investigated the role of CUEDC2 in osteogenesis and its underlying molecular mechanisms. We found that CUEDC2 is expressed in bone tissues. The expression of CUEDC2 decreased during bone development and BMP2-induced osteoblast differentiation. The overexpression of CUEDC2 suppressed the osteogenic differentiation of precursor cells, while the knockdown of CUEDC2 showed the opposite effect. In vivo studies showed that the overexpression of CUEDC2 decreased bone parameters (bone volume, bone area, and bone mineral density) during ectopic bone formation, whereas its knockdown increased bone volume and the reconstruction percentage of critical-size calvarial defects. We found that CUEDC2 affects STAT3 activation by regulating SOCS3 protein stability. Treatment with a chemical inhibitor of STAT3 abolished the promoting effect of CUEDC2 silencing on osteoblast differentiation. Together, we suggest that CUEDC2 functions as a key regulator of osteoblast differentiation and bone formation by targeting the SOCS3-STAT3 pathway. CUEDC2 manipulation could serve as a therapeutic strategy for controlling bone disease and regeneration.

The primary cilium acts as a sensory organelle with diverse receptors and ion channels to detect extracellular cues and regulate cellular functions, including cell migration. The migration of mesenchymal stem cells (MSCs) to bone remodeling sites is important for bone homeostasis. Recently, we have suggested that osteopontin (OPN) is a significant chemoattractant in MSC migration to bone remodeling sites. The objective of this study was to determine whether the primary cilium acts as a chemoattractant sensory unit to detect OPN cues and control MSC migration. We found that the loss of primary cilium induced by silencing of IFT88 reduced OPN-induced migration of MSCs. The effect of IFT88 silencing on cellular attachment, spreading, and proliferation was negligible. The loss of primary cilium did not affect the level of integrinβ1 or CD44, two known receptors for OPN. Interestingly, CD44 was localized to the primary cilium by OPN stimulus. Knockdown of IFT88 or CD44 dysregulated OPN-induced signaling activation and abolished OPN-induced Cdc42 activation. Our findings suggest that the primary cilium acts as a chemoattractant sensor for OPN to regulate MSC migration by controlling not only CD44-mediated OPN signaling, but also Cdc42-mediated actin cytoskeleton rearrangement., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

The Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS)⋅tRNA Pyl pair can be used to incorporate non-canonical amino acids (ncAAs) into proteins at installed amber stop codons. Although engineering of the PylRS active site generates diverse binding pockets, the substrate ranges are found similar in charging lysine and phenylalanine analogs. To expand the diversity of the ncAA side chains that can be incorporated via the PylRS⋅tRNA Pyl pair, exploring remote interactions beyond the active site is an emerging approach in expanding the genetic code research. In this work, remote interactions between tRNA Pyl , the tRNA binding domain of PylRS, and/or an introduced non-structured linker between the N- and C-terminus of PylRS were studied. The substrate range of the PylRS⋅tRNA Pyl pair was visualized by producing sfGFP-UAG gene products, which also indicated amber suppression efficiencies and substrate specificity. The unstructured loop linking the N-terminal and C-terminal domains (CTDs) of PylRS has been suggested to regulate the interaction between PylRS and tRNA Pyl . In exploring the detailed role of the loop region, different lengths of the linker were inserted into the junction between the N-terminal and the C-terminal domains of PylRS to unearth the impact on remote effects. Our findings suggest that the insertion of a moderate-length linker tunes the interface between PylRS and tRNA Pyl and subsequently leads to improved suppression efficiencies. The suppression activity and the substrate specificity of PylRS were altered by introducing three mutations at or near the N-terminal domain of PylRS (N-PylRS). Using a N-PylRS⋅tRNA Pyl pair, three ncAA substrates, two S -benzyl cysteine and a histidine analog, were incorporated into the protein site specifically., (Copyright © 2020 Jiang, Lee, Tsou, Chang, Tseng, Chen, Li and Wang.)

CD137, a potent costimulatory receptor for CD8 + T cells, is expressed in various non-T cells, but little is known about its regulatory functions in these cells. In this study, we show that CD137 signaling, specifically in intestinal CD11b - CD103 + dendritic cells (DCs), restricts acute colitis progression. Mechanistically, CD137 engagement activates TAK1 and subsequently stimulates the AMPK-PGC-1α axis to enhance expression of the Aldh1a2 gene encoding the retinoic acid (RA) metabolizing enzyme RALDH2. RA can act on CD11b + CD103 - DCs and induce SOCS3 expression, which, in turn, suppresses p38MAPK activation and interleukin-23 (IL-23) production. Administration of RA in DC-specific CD137 -/- mice represses IL-23-producing CD11b + CD103 - DCs and T H 17 cells, indicating that RA is a major inhibitory effector molecule against intestinal CD11b + CD103 - DCs. Additionally, the therapeutic effect of the anti-CD137 antibody is abrogated in DC-specific CD137 -/- mice. Taken together, our results define a mechanism of paracrine immunoregulation operating between adjacent DC subsets in the intestine., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiac regeneration with adult stem-cell (ASC) therapy is a promising field to address advanced cardiovascular diseases. In addition, extracellular vesicles (EVs) from ASCs have been implicated in acting as paracrine factors to improve cardiac functions in ASC therapy. In our work, we isolated human cardiac mesenchymal stromal cells (h-CMSCs) by means of three-dimensional organ culture (3D culture) during ex vivo expansion of cardiac tissue, to compare the functional efficacy with human bone-marrow derived mesenchymal stem cells (h-BM-MSCs), one of the actively studied ASCs. We characterized the h-CMSCs as CD90low, c-kit negative , CD105 positive phenotype and these cells express NANOG, SOX2, and GATA4. To identify the more effective type of EVs for angiogenesis among the different sources of ASCs, we isolated EVs which were derived from CMSCs with either normoxic or hypoxic condition and BM-MSCs. Our in vitro tube-formation results demonstrated that the angiogenic effects of EVs from hypoxia-treated CMSCs (CMSC-Hpx EVs) were greater than the well-known effects of EVs from BM-MSCs (BM-MSC EVs), and these were even comparable to human vascular endothelial growth factor (hVEGF), a potent angiogenic factor. Therefore, we present here that CD90 low c-kit negative CD105 positive CMSCs under hypoxic conditions secrete functionally superior EVs for in vitro angiogenesis. Our findings will allow more insights on understanding myocardial repair. [BMB Reports 2020; 53(2): 118-123].

The injection and mixing of contaminant mass into the fuel in inertial confinement fusion (ICF) implosions is a primary factor preventing ignition. ICF experiments have recently achieved an alpha-heating regime, in which fusion self-heating is the dominant source of yield, by reducing the susceptibility of implosions to instabilities that inject this mass. We report the results of unique separated reactants implosion experiments studying pre-mixed contaminant as well as detailed high-resolution three-dimensional simulations that are in good agreement with experiments. At conditions relevant to mixing regions in high-yield implosions, we observe persistent chunks of contaminant that do not achieve thermal equilibrium with the fuel throughout the burn phase. The assumption of thermal equilibrium is made in nearly all computational ICF modeling and methods used to infer levels of contaminant from experiments. We estimate that these methods may underestimate the amount of contaminant by a factor of two or more.

A Caucasian woman aged 58 years with history of asthma and surgically repaired congenital diaphragmatic hernia presented to the emergency department (ED) with persistent cough, pleuritic chest pain, shortness of breath, in spite of recent treatment for influenza A virus. On physical examination, a large bulge was protruding from her left posterior thorax. She was found to have a large abnormal radiographic lucency on lateral chest X-ray posterior to the thoracic cavity, confirmed with chest CT to represent a large lung herniation in between the left seventh and eighth ribs. The patient was evaluated by a thoracic surgeon and offered surgical repair but ultimately decided on conservative management which to date has been ineffective., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The health condition of old age is affected by various factors such as economic level, disease condition, and nutrition. With the aging population in Korea, the ratio of single-person households increased rapidly. Research on the health status and nutrition of the elderly in the single-person household is very insufficient. In this study, we compared the health and nutritional status of the elderly by the household type., Methods: Data from the 2013 to 2014 Korea National Health and Nutrition Examination Survey were used. A total of 2,730 patients were classified into 2 groups (single-person, with family), and general, chronic disease, health behavior, nutrient intake, and food insecurity status were compared by the statistical analysis., Results: Single-person households had a low economic and educational level and a higher percentage of women. In addition, obesity, hypertension, dyslipidemia, stroke, myocardial infarction disease rate was significantly higher. Sing-person households answered that their subjective health status was bad, and their quality of life was low. As a result of analysis of the quality of the diet in the single-person, the intake of protein, calcium, iron, vitamin B2, niacin, and vitamin C was significantly lower. In particular, the intake of calcium was the most insufficient. Food insecurity has also been observed, including the inability to consume diverse and sufficient foods due to economic difficulties., Conclusions: More attention should be paid to the health of single-person households in elderly population and various policies should be prepared., Competing Interests: No potential conflict of interest relevant to this article was reported.

While genetic variants are known to be associated with overall gene abundance in stimulated immune cells, less is known about their effects on alternative isoform usage. By analyzing RNA-seq profiles of monocyte-derived dendritic cells from 243 individuals, we uncovered thousands of unannotated isoforms synthesized in response to influenza infection and type 1 interferon stimulation. We identified more than a thousand quantitative trait loci (QTLs) associated with alternate isoform usage (isoQTLs), many of which are independent of expression QTLs (eQTLs) for the same gene. Compared with eQTLs, isoQTLs are enriched for splice sites and untranslated regions, but depleted of sequences upstream of annotated transcription start sites. Both eQTLs and isoQTLs explain a significant proportion of the disease heritability attributed to common genetic variants. At the ERAP2 locus, we shed light on the function of the gene and how two frequent, highly differentiated haplotypes with intermediate frequencies could be maintained by balancing selection. At baseline and following type 1 interferon stimulation, the major haplotype is associated with low ERAP2 expression caused by nonsense-mediated decay, while the minor haplotype, known to increase Crohn's disease risk, is associated with high ERAP2 expression. In response to influenza infection, we found two uncharacterized isoforms expressed from the major haplotype, likely the result of multiple perfectly linked variants affecting the transcription and splicing at the locus. Thus, genetic variants at a single locus could modulate independent gene regulatory processes in innate immune responses and, in the case of ERAP2 , may confer a historical fitness advantage in response to virus., (© 2018 Ye et al.; Published by Cold Spring Harbor Laboratory Press.)

Evidence is presented demonstrating that alfalfa cultivars in the United States could be widely infected with cryptic virus of the genus Alphapartitivirus. The nucleotide sequences of several U.S. isolates were obtained. The biological significance or negative effects of the virus on alfalfa are unknown and require further investigation.

Supplementation of mesenchymal stem cells (MSCs) at sites of bone resorption is required for bone homeostasis because of the non-proliferation and short lifespan properties of the osteoblasts. Calcium ions (Ca 2+ ) are released from the bone surfaces during osteoclast-mediated bone resorption. However, how elevated extracellular Ca 2+ concentrations would alter MSCs behavior in the proximal sites of bone resorption is largely unknown. In this study, we investigated the effect of extracellular Ca 2+ on MSCs phenotype depending on Ca 2+ concentrations. We found that the elevated extracellular Ca 2+ promoted cell proliferation and matrix mineralization of MSCs. In addition, MSCs induced the expression and secretion of osteopontin (OPN), which enhanced MSCs migration under the elevated extracellular Ca 2+ conditions. We developed in vitro osteoclast-mediated bone resorption conditions using mouse calvaria bone slices and demonstrated Ca 2+ is released from bone resorption surfaces. We also showed that the MSCs phenotype, including cell proliferation and migration, changed when the cells were treated with a bone resorption-conditioned medium. These findings suggest that the dynamic changes in Ca 2+ concentrations in the microenvironments of bone remodeling surfaces modulate MSCs phenotype and thereby contribute to bone regeneration.

N-α-acetyltransferase 10 (NAA10) is a subunit of N α -terminal protein acetyltransferase that plays a role in many biological processes. Among the six N-α-acetyltransferases (NATs) in eukaryotes, the biological significance of the N-terminal acetyl-activity of Naa10 has been the most studied. Recent findings in a few species, including humans, indicate that loss of N-terminal acetylation by NAA10 is associated with developmental defects. However, very little is known about the role of NAA10, and more research is required in relation to the developmental process. This review summarizes recent studies to understand the function of NAA10 in the development of multicellular organisms.

Background: JAK2 V617F is the most common mutation in myeloproliferative neoplasms (MPNs) and is a major diagnostic criterion. Mutation quantification is useful for classifying patients with MPN into subgroups and for prognostic prediction. Droplet digital PCR (ddPCR) can provide accurate and reproducible quantitative analysis of DNA. This study was designed to verify the correlation of ddPCR with pyrosequencing results in the diagnosis of MPN and to investigate clinical implications of the mutational burden., Methods: Peripheral blood or bone marrow samples were obtained from 56 patients newly diagnosed with MPN or previously diagnosed with MPN but not yet indicated for JAK2 inhibitor treatment between 2012 and 2016. The JAK2 V617F mutation was detected by pyrosequencing as a diagnostic work-up. The same samples were used for ddPCR to determine the correlation between assays and establish a detection sensitivity cut-off. Clinical and hematologic aspects were reviewed., Results: Forty-two (75%) and 46 (82.1%) patients were positive for JAK2 V617F by pyrosequencing and ddPCR, respectively. The mean mutated allele frequency at diagnosis was 37.5±30.1% and was 40.7±31.2% with ddPCR, representing a strong correlation (r=0.9712, P<0.001). Follow-up samples were available for 12 patients, including eight that were JAK2 V617F-positive. Of these, mutational burden reduction after treatment was observed in six patients (75%), consistent with trends of hematologic improvement., Conclusions: Quantitative analysis of the JAK2 V617F mutation using ddPCR was highly correlated with pyrosequencing data and may reflect the clinical response to treatment., Competing Interests: The authors have no conflicts of interest to declare., (© The Korean Society for Laboratory Medicine)

Oxidative stress activates macroautophagy/autophagy and contributes to atherogenesis via lipophagic flux, a form of lipid removal by autophagy. However, it is not known exactly how endogenous antioxidant enzymes are involved in lipophagic flux. Here, we demonstrate that the antioxidant PRDX1 (peroxiredoxin 1) has a crucial role in the maintenance of lipophagic flux in macrophages. PRDX1 is more highly expressed than other antioxidant enzymes in monocytes and macrophages. We determined that Prdx1 deficiency induced excessive oxidative stress and impaired maintenance of autophagic flux in macrophages. Prdx1-deficient macrophages had higher intracellular cholesterol mass and lower cholesterol efflux compared with wild type. This perturbation in cholesterol homeostasis was due to impaired lipophagic cholesterol hydrolysis caused by excessive oxidative stress, resulting in the inhibition of free cholesterol formation and the reduction of NR1H3 (nuclear receptor subfamily 1, group H, member 3) activity. Notably, impairment of both lipophagic flux and cholesterol efflux was restored by the 2-Cys PRDX-mimics ebselen and gliotoxin. Consistent with this observation, apoe -/- mice transplanted with bone marrow from prdx1 -/- apoe -/- mice had increased plaque formation compared with apoe -/- BM-transplanted recipients. This study reveals that PRDX1 is crucial to regulating lipophagic flux and maintaining macrophage cholesterol homeostasis against oxidative stress. We suggest that PRDX1-dependent control of oxidative stress may provide a strategy for treating atherosclerosis and autophagy-related human diseases.

Insulin resistance causes type 2 diabetes; therefore, increasing insulin sensitivity is a therapeutic approach against type 2 diabetes. Activating AMP-activated protein kinase (AMPK) is an effective approach for treating diabetes, and reduced insulin receptor substrate-1 (IRS-1) protein levels have been suggested as a molecular mechanism causing insulin resistance. Thus, dual targeting of AMPK and IRS-1 might provide an ideal way to treat diabetes. We found that 15,16-dihydrotanshinone I (DHTS), as a C1-Ten protein tyrosine phosphatase inhibitor, increased IRS-1 stability, improved glucose tolerance and reduced muscle atrophy. Identification of DHTS as a C1-Ten inhibitor revealed a new function of C1-Ten in AMPK inhibition, possibly through regulation of IRS-1. These findings suggest that C1-Ten inhibition by DHTS could provide a novel therapeutic strategy for insulin resistance-associated metabolic syndrome through dual targeting of IRS-1 and AMPK.

Bacterial stem blight caused by Pseudomonas syringae pv. syringae is a common disease of alfalfa (Medicago sativa L). Little is known about host-pathogen interactions and host defense mechanisms. Here, individual resistant and susceptible plants were selected from cultivars Maverick and ZG9830 and used for transcript profiling at 24 and 72 hours after inoculation (hai) with the isolate PssALF3. Bioinformatic analysis revealed a number of differentially expressed genes (DEGs) in resistant and susceptible genotypes. Although resistant plants from each cultivar produced a hypersensitive response, transcriptome analyses indicated that they respond differently at the molecular level. The number of DEGs was higher in resistant plants of ZG9830 at 24 hai than in Maverick, suggesting that ZG9830 plants had a more rapid effector triggered immune response. Unique up-regulated genes in resistant ZG9830 plants included genes encoding putative nematode resistance HSPRO2-like proteins, orthologs for the rice Xa21 and soybean Rpg1-b resistance genes, and TIR-containing R genes lacking both NBS and LRR domains. The suite of R genes up-regulated in resistant Maverick plants had an over-representation of R genes in the CC-NBS-LRR family including two genes for atypical CCR domains and a putative ortholog of the Arabidopsis RPM1 gene. Resistance in both cultivars appears to be mediated primarily by WRKY family transcription factors and expression of genes involved in protein phosphorylation, regulation of transcription, defense response including synthesis of isoflavonoids, and oxidation-reduction processes. These results will further the identification of mechanisms involved in resistance to facilitate selection of parent populations and development of commercial varieties.

Epidermal growth factor-like repeats and discoidin I-like domain 3 (Edil3) is an extracellular matrix protein containing an Arg-Gly-Asp (RGD) motif that binds integrin. Recently, Edil3 has been implicated in various biological processes, including angiogenesis and cellular differentiation. It can inhibit inflammatory bone destruction. The objective of this study was to explore the role of Edil3 in osteoblast differentiation and its underlying molecular mechanisms. In wild-type mice, high expression levels of Edil3 mRNA were observed in isolated calvaria and tibia/femur bones. Immunohistochemical analysis showed that Edil3 protein was localized along periosteum and calcified regions surrounding bone tissues. When murine calvaria-derived MC3T3-E1 cells were cultured in osteogenic medium containing 50 μg/ml ascorbic acid and 5 mM β-glycerophosphate, Edil3 mRNA and protein expression levels were increased. Treatment with Edil3 protein in growth media increased expression levels of alkaline phosphatase and osteocalcin gene and phosphorylation level of extracellular signal-regulated kinase (ERK). Edil3 treatment with osteogenic medium induced mineralization. Treatment with a neutralizing antibody against α5β1 and MEK inhibitor U0126 inhibited Edil3-enhanced osteogenic marker gene expression and mineral deposition. Edil3 increased protein expression levels of transcription factor runt-related transcription factor2 (Runx2). Edil3-induced Runx2 protein expression was suppressed by pretreatment with U0126. Taken together, these results suggest that Edil3 may stimulate osteoblast differentiation and matrix mineralization by increasing expression of Runx2 through α5β1 integrin /ERK pathway.

Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests.

Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2017 Korean Endocrine Society.)