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Introduction The emotional freedom technique (EFT) is an acupuncture-based psychotherapy that combines tapping on acupoints with cognitive reframing. EFT has been previously shown to have potential for treating post-traumatic stress disorder (PTSD). However, further clinical evidence and underlying mechanisms of EFT are yet to be fully explored. This proposed clinical trial aims to examine the effect of EFT on patients with PTSD compared with the waitlist (WL) and active controls.Methods and analysis This study was designed as a randomised, assessor-blinded, three-arm clinical MRI study. A total of 120 eligible patients with PTSD will be recruited and randomised into EFT, written exposure therapy (WET) or WL groups. EFT and WET will be applied once a week for 5 weeks. For patients in the WL group, EFT will be performed after 12 weeks. PTSD symptoms, depression, anxiety, somatic symptoms and quality of life will be evaluated. Assessments will be conducted at baseline (week 0), post-treatment (week 6) and follow-up (week 12). Structural and functional brain images and recording videos of facial expressions to emotional stimuli will be obtained before and after treatment. Sixty participants without lifetime traumatic experiences will be enrolled as healthy controls. The primary objective of the study is to compare the change from baseline in the Clinician-Administered PTSD Scale after treatment (week 6) between EFT and WL groups and between EFT and WET groups.Ethics and dissemination Ethical approval was obtained from the Institutional Review Board of the Kyung Hee University Korean Medicine Hospital. The research findings will be shared at national and international conferences and will be published in peer-reviewed journals.Trial registration number Clinical Research Information Service KCT0007360 https://cris.nih.go.kr/cris/search/detailSearch.do/21974.

Abstract Background Gyejibokryeong-hwan (GBH) is an herbal medicine composed of five herbs. It has been widely used to treat gynaecological diseases in traditional East Asian medicine. Recent animal studies suggest antidepressant effects of GBH. In this trial, we explore the efficacy and safety of GBH in patients with major depressive disorder and to identify the optimal dose for the next phase III trial. Methods This trial will enrol 126 patients diagnosed with major depressive disorder and not treated with antidepressants. Participants will be randomised to receive a high or a low dose of GBH or placebo granules. The study drugs will be administered three times a day, for 8 weeks. The 17-item Hamilton Depression Rating Scale (HDRS) will be used to measure the severity of depressive symptoms at weeks 2, 4, 6, 8, and 12. The primary efficacy endpoint is the change from baseline in HDRS-17 total score post-treatment at week 8. Analysis of covariance will be based on the baseline HDRS-17 total score and site as the covariates. Safety assessment will be based on the frequency of adverse events. The severity and causality of the study drug will be assessed. Discussion This study is designed to evaluate the efficacy and safety of GBH granules compared with placebo in patients with major depressive disorder. Trial registration Clinical Research Information Service KCT0004417 . Registered on November 1, 2019 (prospective registration)

Abstract Background Bipolar disorder (BD) has the greatest suicide risk among mental and physical disorders. A recent genome-wide association study (GWAS) of European ancestry (EUR) samples revealed that the genetic etiology of suicide attempt (SA) was not only polygenic but also, in part, diagnosis-specific. The authors aimed to examine whether the polygenic risk score (PRS) for SA derived from that study is associated with SA or repeated attempts in Korean patients with BD. This study also investigated the shared heritability of SA and mental disorders which showed an increased risk of SA and a high genetic correlation with BD. Methods The study participants were 383 patients with BD. The history of SA was assessed on a lifetime basis. PRSs for reference disorders were calculated using the aforementioned GWAS data for SA and the Psychiatric Genomics Consortium data of BD, schizophrenia, major depressive disorder (MDD), and obsessive–compulsive disorder (OCD). Results The PRS for SA was significantly associated with lifetime SA in the current subjects (Nagelkerke’s R2 = 2.73%, odds ratio [OR] = 1.36, p = 0.007). Among other PRSs, only the PRS for OCD was significantly associated with lifetime SA (Nagelkerke’s R2 = 2.72%, OR = 1.36, p = 0.007). The PRS for OCD was higher in multiple attempters than in single attempters (Nagelkerke’s R2 = 4.91%, OR = 1.53, p = 0.043). Conclusion The PRS for SA derived from EUR data was generalized to SA in Korean patients with BD. The PRS for OCD seemed to affect repeated attempts. Genetic studies on suicide could benefit from focusing on specific psychiatric diagnoses and refined sub-phenotypes, as well as from utilizing multiple PRSs for related disorders.

IntroductionHibiscus syriacus L. flower (HSF) is a food ingredient commonly used for tea, and previous animal studies have reported its sleep-promoting effect. This study aims to test the potential of HSF extract as functional food that improves sleep in humans.Methods and analysisEighty participants with sleep disturbances who meet the inclusion/exclusion criteria will be enrolled in this study. Since the effect of HSF extract on sleep is considered to be that of a functional food rather than a medicine, participants with severe insomnia will be excluded from the study. The enrolled participants will be randomly assigned to the HSF extract or placebo groups in a 1:1 ratio. The HSF extract and placebo capsules will look identical, and participants, investigators, and outcome assessors will be blinded to the allocation. Four capsules of HSF extract or placebo will be orally administered 30–60 min before bedtime for 4 weeks. The primary outcome of this study will be the change in the Pittsburgh Sleep Quality Index (PSQI) global score from the baseline after 4 weeks. The subjective and objective changes in the participants’ sleep will be evaluated using the Insomnia Severity Index (ISI), Epworth Sleep Scale (ESS), sleep diary, and polysomnography (PSG). The occurrence of adverse events will be closely monitored.DiscussionThe results of this trial will provide data on the efficacy and safety of HSF extract in enhancing sleep quality. Based on the results, the potential of HSF extract as a functional food that improves sleep in humans will be evaluated, and the findings of the trial will be submitted to the Korean Ministry of Food and Drug Safety for consideration as a new functional ingredient that may help to improve sleep quality.Clinical trial registration: Clinical Research Information Service: KCT0007314; Registered 19 May 2022, https://cris.nih.go.kr/cris/search/detailSearch.do/21497.

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease characterized by the deposition of amyloid-beta (Aβ) peptide and neurofibrillary tangles in the brain. The approved drug for AD has certain limitations such as a short period of cognitive improvement effect; moreover, the development of drug for AD therapeutic single target for Aβ clearance in brain ended in failure. Therefore, diagnosis and treatment of AD using a multi-target strategy according to the modulation of the peripheral system, which is not only limited to the brain, is needed. Traditional herbal medicines can be beneficial for AD based on a holistic theory and personalized treatment according to the time-order progression of AD. This literature review aimed to investigate the effectiveness of herbal medicine therapy based on syndrome differentiation, a unique theory of traditional diagnosis based on the holistic system, for multi-target and multi-time treatment of mild cognitive impairment or AD stage. Possible interdisciplinary biomarkers including transcriptomic and neuroimaging studies by herbal medicine therapy for AD were investigated. In addition, the mechanism by which herbal medicines affect the central nervous system in connection with the peripheral system in an animal model of cognitive impairment was reviewed. Herbal medicine may be a promising therapy for the prevention and treatment of AD through a multi-target and multi-time strategy. This review would contribute to the development of interdisciplinary biomarkers and understanding of the mechanisms of action of herbal medicine in AD.

Perovskite oxides hosting ferroelectricity are particularly important materials for modern technologies. The ferroelectric transition in the well-known oxides BaTiO3 and PbTiO3 is realized by softening of a vibration mode in the cubic perovskite structure. For most perovskite oxides, octahedral-site tilting systems are developed to accommodate the bonding mismatch due to a geometric tolerance factor t = (A-O)/ [√2(B-O)] < 1. In the absence of cations having lone-pair electrons, e.g., Bi3+ and Pb2+, all simple and complex A-site and B-site ordered perovskite oxides with a t < 1 show a variety of tilting systems, and none of them become ferroelectric. The ferroelectric CaMnTi2O6 oxide is, up to now, the only one that breaks this rule. It exhibits a columnar A-site ordering with a pronounced octahedral-site tilting and yet becomes ferroelectric at Tc≈ 650 K. Most importantly, the ferroelectricity at T < Tc is caused by an order-disorder transition instead of a displacive transition; this character may be useful to overcome the critical thickness problem experienced in all proper ferroelectrics. Application of this new ferroelectric material can greatly simplify the structure of microelectronic devices. However, CaMnTi2O6 is a high-pressure phase obtained at 7 GPa and 1200 °C, which limits its application. Here we report a new method to synthesize a gram-level sample of ferroelectric Ca2-xMnxTi2O6, having the same crystal structure as CaMnTi2O6 and a similarly high Curie temperature. The new finding paves the way for the mass production of this important ferroelectric oxide. We have used neutron powder diffraction to identify the origin of the peculiar ferroelectric transition in this double perovskite and to reveal the interplay between magnetic ordering and the ferroelectric displacement at low temperatures. [ABSTRACT FROM AUTHOR]

Rotavirus causes a gastrointestinal tract infection that primarily affects young children. Due to the COVID-19 pandemic, individuals infected with the virus were subjected to quarantine measures, with strong emphases on personal hygiene and social distancing. The present study aimed to evaluate the characteristics of rotaviruses and compare the prevalence of rotavirus infection before and during the COVID-19 pandemic. This nationwide representative study was conducted using data acquired from the National Health Insurance Service between 2010 and 2021. We analyzed the data of patients younger than 12 months old who were diagnosed with rotavirus enteritis between January 2010 and December 2021. During the study period, a total of 34,487 infants younger than 12 months were diagnosed with rotavirus enteritis in South Korea. During the two-year COVID-19 pandemic (2020–2021), the rate of decline was significant (5843 cases in 2010 and 1125 in 2019), and by 2021, the total number of patients was almost negligible, as there are only 18 cases in 2021. A significant increase in the ratio of low birth weight (LBW) infants of inpatient department was observed from 2010 to 2021 (4.86% in 2010; 7.77% in 2019; and 23.08% in 2021), indicating that LBW infants are more vulnerable than infants born with normal weight. Average medical expenses related to rotavirus infections also declined significantly from 3,789,443,998 per year (pre-pandemic) to 808,353,795 per year (pandemic). Overall, personal hygiene and social distancing may play important roles in reducing rotavirus infections. However, further studies are needed to determine whether this decreasing trend persists after quarantine and whether the social life of individuals resumes.

Based on traditional pharmacological applications and partial in vitro data, Cynanchum atratum (CA) is proposed to act on skin whitening. However, its functional evaluation and underlying mechanisms have yet to be identified. This study aimed to examine the anti-melanogenesis activity of CA fraction B (CAFB) on UVB-induced skin hyperpigmentation. Forty C57BL/6j mice were exposed to UVB (100 mJ/cm2, five times/week) for eight weeks. After irradiation, CAFB was applied to the left ear once a day for 8 weeks (the right ear served as an internal control). The results showed that CAFB significantly reduced melanin production in the ear skin, as indicated by the gray value and Mexameter melanin index. In addition, CAFB treatment notably decreased melanin production in α-MSH-stimulated B16F10 melanocytes, along with a significant reduction in tyrosinase activity. Cellular cAMP (cyclic adenosine monophosphate), MITF (microphthalmia-associated transcription factor), and tyrosinase-related protein 1 (TRP1) were also noticeably downregulated by CAFB. In conclusion, CAFB is a promising ingredient for treating skin disorders caused by the overproduction of melanin and its underlying mechanisms involving the modulation of tyrosinase, mainly mediated by the regulation of the cAMP cascade and MITF pathway.

Objective To systematically translate the Fugl-Meyer Assessment (FMA) into a Korean version of the FMA (K-FMA). Methods We translated the original FMA into the Korean version with three translators and a translation committee, which included physiatrists, physical therapists, and occupational therapists. Based on a test-retest method, each of 31 patients with stroke was assessed by two evaluators twice, once on recruitment, and again after a week. Analysis of intra- and inter-rater reliabilities was performed using the intra-class correlation coefficient, whereas validity was analysed using Pearson correlation test along with the Motricity Index (MI), Motor Assessment Scale (MAS), and Berg Balance Scale (BBS). Results The intra- and inter-rater reliabilities were significant for the total score, and good to excellent reliability was noted in all domains except for the joint range of motion of the lower extremity domain of the K-FMA. The MI and MAS scores were significantly correlated with all domains, all with p

Pattern identification (PI) is a diagnostic method used in Traditional East Asian medicine (TEAM) to select appropriate and personalized acupuncture points and herbal medicines for individual patients. Developing a reproducible PI model using clinical information is important as it would reflect the actual clinical setting and improve the effectiveness of TEAM treatment. In this paper, we suggest a novel deep learning-based PI model with feature extraction using a deep autoencoder and k-means clustering through a cross-sectional study of sleep disturbance patient data. The data were obtained from an anonymous electronic survey in the Republic of Korea Army (ROKA) members from August 16, 2021, to September 20, 2021. The survey instrument consisted of six sections: demographics, medical history, military duty, sleep-related assessments (Pittsburgh sleep quality index (PSQI), Berlin questionnaire, and sleeping environment), diet/nutrition-related assessments [dietary habit survey questionnaire and nutrition quotient (NQ)], and gastrointestinal-related assessments [gastrointestinal symptom rating scale (GSRS) and Bristol stool scale]. Principal component analysis (PCA) and a deep autoencoder were used to extract features, which were then clustered using the k-means clustering method. The Calinski-Harabasz index, silhouette coefficient, and within-cluster sum of squares were used for internal cluster validation and the final PSQI, Berlin questionnaire, GSRS, and NQ scores were used for external cluster validation. One-way analysis of variance followed by the Tukey test and chi-squared test were used for between-cluster comparisons. Among 4,869 survey responders, 2,579 patients with sleep disturbances were obtained after filtering using a PSQI score of >5. When comparing clustering performance using raw data and extracted features by PCA and the deep autoencoder, the best feature extraction method for clustering was the deep autoencoder (16 nodes for the first and third hidden layers, and two nodes for the second hidden layer). Our model could cluster three different PI types because the optimal number of clusters was determined to be three via the elbow method. After external cluster validation, three PI types were differentiated by changes in sleep quality, dietary habits, and concomitant gastrointestinal symptoms. This model may be applied to the development of artificial intelligence-based clinical decision support systems through electronic medical records and clinical trial protocols for evaluating the effectiveness of TEAM treatment.

To modify the luminescence properties of Ce3+-doped Y3Al5O12 (YAG) phosphors, they have been coated with a carbon layer by chemical vapor deposition and subsequently heat-treated at high temperature under N2 atmosphere. Luminescence of the carbon coated YAG:Ce3+ phosphors has been investigated as a function of heat-treatment at 1500 and 1650 °C. The 540 nm emission intensity of C@YAG:Ce3+ is the highest when heated at 1650 °C, while a blue emission at 400-420 nm is observed when heated at 1500 °C but not at 1650 °C. It is verified by X-ray diffraction (XRD) that the intriguing luminescence changes are induced by the formation of new phases in C@YAG:Ce3+-1500 °C, which disappear in C@YAG:Ce3+-1650 °C. In order to understand the mechanisms responsible for the enhancement of YAG:Ce3+ emission and the presence of the blue emission observed for C@YAG:Ce3+ -1500 ° C, the samples have been investigated by a combination of several electron microscopy techniques, such as HRTEM, SEM-CL, and SEM-EDS. This local and cross-sectional analysis clearly reveals a gradual transformation of phase and morphology in heated C@YAG:Ce3+ phosphors, which is related to a reaction between C and YAG:Ce3+ in N2 atmosphere. Through reaction between the carbon layer and YAG host materials, the emission colour of the phosphors can be modified from yellow, white, and then back to yellow under UV excitation as a function of heat-treatment in N2 atmosphere. [ABSTRACT FROM AUTHOR]

Electrical characteristics of leakage current paths in vertical-type n-GaN Schottky barrier diodes (SBDs) on free-standing GaN substrates are investigated by using photon emission microscopy (PEM). The PEM mapping shows that the initial failure of the SBD devices at low voltages is due to the leakage current paths from polygonal pits in the GaN epilayers. It is observed that these polygonal pits originate from carbon impurity accumulation to the dislocations with a screw-type component by microstructure analysis. For the SBD without polygonal pits, no initial failure is observed and the first leakage appeals at the edge of electrodes as a result of electric field concentration. The mechanism of leakage at pits is explained in terms of trap assisted tunneling through fitting current-voltage characteristics. [ABSTRACT FROM AUTHOR]

Abstract Background When evaluating the long-term treatment response to mood stabilizers using the Alda scale, mood stabilizer combination therapy is typically considered a confounding factor, and patients receiving combination therapy are excluded from the analysis. However, this may result in bias if those under combination therapy are worse treatment responders. This study aims to explore whether the Alda scale is applicable to patients taking lithium and valproate combination therapy. We compared long-term treatment response in patients receiving monotherapy and combination therapy of the two drugs, and investigated clinical correlates of the responses to each drug. Methods The study subjects consisted of 102 patients with bipolar I (BD-I) or bipolar II (BD-II) disorder who had been undergoing maintenance treatment with lithium and/or valproate for more than 2 years at a single specialized bipolar disorder clinic. Long-term treatment response was measured using the Alda scale and compared among the lithium monotherapy group, the valproate monotherapy group, and the mood stabilizer combination group. Clinical correlates of long-term treatment response were evaluated in lithium users and valproate users separately. Results There were no significant differences in terms of baseline illness characteristics among groups. The combination group showed the worst treatment response for all the response measurements applied. This group also had the higher rate of ‘poor responder’ with a statistically significant difference compared to valproate group. Older age at onset and (hypo)manic episode at onset showed significant positive associations with total Alda score in lithium users, while comorbid anxiety disorders, obsessive–compulsive disorder and mixed episode showed significant negative associations in valproate users. Conclusions The combination group had poorer long-term treatment response but did not show distinct clinical characteristics compared to the monotherapy groups. When exploring the long-term effects of mood stabilizers, excluding patients undergoing combination treatment could result in bias because they may represent a poor response group. The long-term treatment responses of lithium and valproate had different clinical correlates.

We report the photoluminescence (PL) and cathodoluminescence (CL) properties of facecapped [Mo6Xi8La6]2- (X = Cl, Br, I; L = organic or inorganic ligands) cluster units. We show that the emission of Mo6 metal atom clusters depends not only on the nature of X and L ligands bound to the cluster and counter-cations, but also on the excitation source. Seven members of the AxMo6Xi8La6 series (A = Cs+, (n-C4H9)4N+, NH4+) were selected to evaluate the influence of countercations and ligands on de-excitation mechanisms responsible for multicomponent emission of cluster units. This study evaluates the ageing of each member of the series, which is crucial for further energy conversion applications (photovoltaic, lighting, water splitting, etc.). [ABSTRACT FROM AUTHOR]

Neuroinflammation causes various neurological disorders, including depression and neurodegenerative diseases. Therefore, regulation of neuroinflammation is a promising therapeutic strategy for inflammation-related neurological disorders. This study aimed to investigate whether yomogin, isolated from Artemisia iwayomogi, has anti-neuroinflammatory effects. First, we evaluated the effects of yomogin by assessing pro-inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. The results showed that yomogin inhibited the increase in neuroinflammatory factors, including nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-α, and suppressed phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, which participate in the mitogen-activated protein kinase (MAPK) pathway. To confirm these effects in vivo, we measured the activation of astrocyte and microglia in LPS-injected mouse brains. Results showed that yomogin treatment decreased astrocyte and microglia activations. Collectively, these results suggest that yomogin suppresses neuroinflammation by regulating the MAPK pathway and it could be a potential candidate for inflammation-mediated neurological diseases.

Through-Silicon-Vias (TSVs)—10 μm-diameter conducting rods that connect vertically stacked silicon layers—provide three dimensional circuit integration, but introduce strain in the surrounding silicon when thermally cycled. Here, we noninvasively probe strain fields around Cu TSVs in Si(001) using optical second-harmonic generation (SHG) microscopy. Results are compared with micro-Raman spectra of the strained regions. We find that SHG probes strain fields more quickly than Raman spectroscopy, while maintaining comparable sensitivity and spatial resolution, and avoiding the need for spectral analysis. Moreover, SHG is selectively sensitive to axial shear components uiz (i = x, y) of the strain tensor that are often neglected in Raman analysis. Thus, SHG complements Raman spectroscopy. [ABSTRACT FROM AUTHOR]

Objectives: Emerging studies found the potential effects of acupuncture for treating chronic pain and mental disorders, namely, depressive and anxiety disorders. Acupuncture is widely used for treating culture-related anger syndrome, Hwa-byung. This pilot trial aimed to investigate the feasibility of a clinical trial testing acupuncture for the psychosomatic symptoms of Hwa-byung.Methods: A total of 26 patients with Hwa-byung planned to be randomly assigned to the acupuncture or sham acupuncture groups. About 10 treatment sessions were applied over 4 weeks. The 100-mm visual analog scale was used to measure the six major Hwa-byung symptoms: stuffiness in the chest, heat sensations, pushing-up in the chest, feeling a mass in the throat, feelings of unfairness, and hard feelings. The criteria for assessing the success of this pilot trial were defined as improvement in three or more of the six Hwa-byung symptoms after treatment, with an effect size >0.2.Results: A total of 15 patients were finally included and randomly assigned to the acupuncture group (n = 7) or the sham acupuncture group (n = 8). After 10 treatment sessions, the Cohen's d effect sizes for acupuncture compared to sham acupuncture were >0.2 for each one of the six major Hwa-byung symptoms, which met our a priori criteria for success. Also, the effect size for the somatic symptoms of “stuffiness in the chest” was 0.81 (95% CI −0.40, 2.20), referring to a large effect size.Conclusions: Our results suggest that acupuncture treatment would be regarded as an acceptable intervention for a full-scale study of psychosomatic symptoms in patients with Hwa-byung.Trial Registration:cris.nih.go.kr, identifier: KCT0001732.

Background: Huanglian-jie-du (HJD) granule, which is composed of representative “heat-clearing” herbs has been used for Hwa-byung. Hwa-byung is a culture-bound syndrome in Korea, characterized by distinct somatic symptoms such as chest congestion and heat sensation resulting from suppressed anger. We investigated the effect of HJD in patients with Hwa-byung. Methods: Forty-four patients with Hwa-byung were recruited, and HJD or placebo granules were administered orally three times daily for seven days. The two primary outcomes were somatic symptoms, which were measured by Patient Health Questionnaire of physical symptoms (PHQ-15), and insomnia, which was measured by Insomnia Severity Index (ISI) at post-treatment. Results: Between July 10 and October 31, 2017, 44 patients with Hwa-byung (mean age 36.68 years; and 38 female) were randomly assigned to HJD (n = 22) or placebo (n = 22) group. After administration of HJD or placebo granule for seven days, ISI score was lower in the HJD group compared to placebo group at post-treatment (adjusted mean difference -2.56 [95% CI -4.72 to -0.39], p = 0.0208). Meanwhile, there was no difference in PHQ-15 score between HJD group and placebo group at post-treatment (adjusted mean difference -0.50 [95% CI: -3.02–4.02], p = 0.7812). Conclusions: Our results suggest that the administration of HJD granule has a potential to improve insomnia in Hwa-byung patients. Effect of HJD granule for general somatic symptoms in Hwa-byung patients is unclear, and further researches are needed. Trial registration: Clinical Research Information Service, KCT0002379.

Background: Herbal medicine has been used frequently in Korean medicine. We aimed to summarize the relevant regulations for herbal medicine clinical trials and to analyze their current status in the Republic of Korea. Methods: We searched for legislation to find regulations on herbal medicine clinical trials. Additionally, the websites of the Korean Ministry of Food and Drug Safety (KMFDS) and Clinical Research Information Service (CRIS) were searched to investigate the current status of them. Results: To conduct herbal medicine clinical trials for new drugs or previously approved drugs outside of indications, investigational new drug (IND) approval should be obtained from the KMFDS. For clinical trials of herbal medicines that have been used for more than 3 years with 200 cases at the clinical trial institution, nonclinical data can be exempted from IND approval. Total 95 and 108 herbal medicine clinical trials from the KMFDS and CRIS websites were analyzed. The number of clinical trials showed an increasing trend each year, as did KMFDS-regulated clinical trials. Recently, three clinical trials targeting new herbal formulations frequently used in Korean medicine institutions have been approved based on relevant regulations. Conclusion: We confirmed that herbal medicine clinical trials are managed through strict regulations, which can ensure the safe and effective use of herbal medicine. Despite strict regulations, attempts to accumulate evidence through clinical trials for herbal medicine are increasing. High-quality clinical trials should be conducted to develop new drugs that reflect the clinical setting using relevant regulations, evaluate the efficacy and safety of the drugs, and strengthen insurance coverage.

A CFBC (Circulating Fluidized Bed Combustor) boiler for combusted SRF (Solid Refused Fuel) is designed for solid waste combustion and power generation. The boiler consumes about 200 tons/day of SRF and generates 60 ton/h of steam or 10 MWe in electricity. The boiler is designed to burn pelletized waste fuel made of municipal solid waste collected from a town with a population of 400,000. Heat and mass balance calculations over the combustor and at each boiler section were performed and compared between the designed and measured data to analyze the boiler’s performance. After-combustion, the most significant phenomenon in low-density waste-derived fuel combustion in a CFBC boiler was monitored. The heat and mass balance were the most appropriate tools to analyze the boiler performance. The flow rate of spray water at the de-superheater was a reliable indicator to quantify the after-combustion. The design modification of the boiler unit for after-combustion control in the existing boiler was based on the quantification of spray water. The load distribution of the de-superheater decreases from 1.76% to 0.87% in 89% MCR before the installation of the evaporator and 82* % MCR load distribution of each boiler part after installation. The result was effective for the control of after-combustion in the existing boiler.

Exosomes are a type of extracellular vesicles containing mRNA, miRNA, and proteins of origin cells, which can control the characteristics of other cells or surroundings. Despite increasing evidence on oncogenic properties of tumor-derived exosomes, fibrosarcoma-derived exosomes remain largely unrevealed. While the proper extraction and characterization of exosomes is critical in exosomes research, there are various limitations in techniques to measure the size and homogeneity of exosomes. Here, we analyzed exosomes from a fibrosarcoma cell line WEHI-164 compared with a breast cancer cell line MDA-MD-231 as a control. Results from dot blot and western blot analysis demonstrated that GM1 ganglioside, and TSG101, HSC70 and GAPDH proteins were contained in exosomes from the WEHI-164 fibrosarcoma cell line. The existence of tetraspanins such as CD81, CD63 and CD9 was confirmed in the exosomes by ExoView analysis. The results obtained from TEM showed their sphere-like shapes of around 50 to 70 nm in radius. Through DLS, we found out that the mean radius of the exosomes derived from WEHI-164 and MDA-MB-231 cell lines was 94.4 nm and 107.8 nm, respectively, with high homogeneity. When comparing the radius measured by TEM with the radius measured by DLS, it was revealed that the difference between the two methods was about 40 nm. This study has significance in characterizing the molecular properties of exosomes from a fibrosarcoma, which has not been researched much before, and in providing clear evidence that DLS can be used as an efficient, convenient and noninvasive technique to simply check the homogeneity and size of exosomes.

Five types of Escherichia coli strains were obtained and sequenced: colistin-susceptible (CL-S) strains, in vitro induced colistin-resistant (CL-IR) strains, mcr-1-negative colistin-resistant strains from livestock (CL-chrR), mcr-1-positive colistin-resistant strains (CL-mcrR), and mcr-1-transferred transconjugants (TC-mcr). Amino acid alterations of PmrAB, PhoPQ, and EptA were identified, and their mRNA expression was measured. Their growth rate was evaluated, and an in vitro competition assay was performed. Virulence was compared through serum resistance and survival in macrophages and Drosophila melanogaster. CL-IR and CL-chrR strains were colistin-resistant due to amino acid alterations in PmrAB, PhoPQ, or EptA, and their overexpression. All colistin-resistant strains did not show reduced growth rates compared with CL-S strains. CL-IR and CL-chrR strains were less competitive than the susceptible strain, but CL-mcrR strains were not. In addition, TC-mcr strains were also significantly more competitive than their respective parental susceptible strain. CL-IR strains had similar or decreased survival rates in human serum, macrophages, and fruit flies, compared with their parental, susceptible strains. CL-chrR strains were also less virulent than CL-S strains. Although CL-mcrR strains showed similar survival rates in human serum and fruit fly to CL-S strains, the survival rates of TC-mcr strains decreased significantly in human serum, macrophages, and fruit flies, compared with their susceptible recipient strain (J53). Chromosome-mediated, colistin-resistant E. coli strains have a fitness cost, but plasmids bearing mcr-1 do not increase the fitness burden of E. coli. Along with high usage of polymyxins, the no fitness cost of mcr-1-positive strains may facilitate rapid spread of colistin resistance.