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Abstract Nuclear receptors represent a very good family of protein targets for the prevention and treatment of diverse diseases. In this study, we screened natural compounds and their derivatives, and [...]

Summary Two unique evidence that cancer incidence rates in Fiji were unusually low, compared with those of another Pacific islands and that green tea beverage is an acknowledged cancer preventive [...]

Little attention has been paid to the bryophytes as sources for human diet despite the presence of 23,000 species in the world. Some mosses contain Vitamin B1, tocopherols, prostaglandin-like highly unsaturated fatty acids and phenolic compounds. On the other hand, liverworts contain enantiomeric mono-, sesqui- and diterpenoids similar to those found in vascular plants. Additionally, they possess bibenzyls, bis-bibenzyls and polyketides, many of them showing various bioactivity, such as antimicrobial, antiviral, anti-inflammatory, cytotoxicity against cancer cell lines, muscle relaxing, antioxidant and others. In this paper, the structures of phytochemicals from bryophytes and their biological activities are discussed.

As we are now in the process of publishing the thirteenth volume of Phytomedicine, and as the science of natural products including phytomedicines advances, the Editors have agreed on a [...]

Ten years after the foundation of Phytomedicine, a new phase of the journals' development will begin with volume 11 (2004). This event coincides with the transition of Urban & Fischer [...]

Abstract Background In Japan, few community-based approaches have been adopted in health-care professional education, and the appropriate content for such approaches has not been clarified. In establishing community-based education for health-care professionals, clarification of its learning effects is required. A community-based educational program was started in 2009 in the health sciences course at Gunma University, and one of the main elements in this program is conducting classes outside school. The purpose of this study was to investigate using text-analysis methods how the off-campus program affects students. Methods In all, 116 self-assessment worksheets submitted by students after participating in the off-campus classes were decomposed into words. The extracted words were carefully selected from the perspective of contained meaning or content. With the selected terms, the relations to each word were analyzed by means of cluster analysis. Results Cluster analysis was used to select and divide 32 extracted words into four clusters: cluster 1—“actually/direct,” “learn/watch/hear,” “how,” “experience/participation,” “local residents,” “atmosphere in community-based clinical care settings,” “favorable,” “communication/conversation,” and “study”; cluster 2—“work of staff member” and “role”; cluster 3—“interaction/communication,” “understanding,” “feel,” “significant/important/necessity,” and “think”; and cluster 4—“community,” “confusing,” “enjoyable,” “proactive,” “knowledge,” “academic knowledge,” and “class.” Conclusions The students who participated in the program achieved different types of learning through the off-campus classes. They also had a positive impression of the community-based experience and interaction with the local residents, which is considered a favorable outcome. Off-campus programs could be a useful educational approach for students in health sciences.

Abstract Background The mandatory interprofessional education programme at Gunma University was initiated in 1999. This paper is a statistical evaluation of the programme from 1999 to 2007. Methods A questionnaire of 10 items to assess the achievement levels of the programme, which was developed independently of other assessment systems published previously, was distributed, as well as two or three open-ended questions to be answered at the end of each annual module. A multivariate analysis of variance model was used, and the factor analysis of the responses was performed with varimax rotation. Results Over all, 1418 respondents of a possible 1629 students completed the survey, for a total response rate of 87.1%. Cronbach's alpha of 10 items was 0.793, revealing high internal consistency. Our original questionnaire was categorized into four subscales as follows: "Role and responsibilities", "Teamwork and collaboration", "Structure and function of training facilities", and "Professional identity". Students in the Department of Occupational Therapy reached a relatively lower level of achievement. In the replies to the open-ended questions, requests for the participation of the medical students were repeated throughout the evaluation period. Conclusion The present four subscales measure "understanding", and may take into account the development of interprofessional education programmes with clinical training in various facilities. The content and quality of clinical training subjects may be remarkably dependent on training facilities, suggesting the importance of full consultation mechanisms in the local network with the relevant educational institutes for medicine, health care and welfare.

Partial edentulism, characterized by the congenital absence of six or more permanent teeth (oligodontia), excluding the third molars, manifests with variable maxillofacial skeletal morphologies and occlusions, depending on the site and number of missing teeth, complicating treatment planning for occlusion and gain of function. Herein, we describe the case of a patient with seven non-syndromic congenitally missing permanent teeth (four in the maxillary and three in the mandibular dentition, excluding the third molars), who underwent orthodontic treatment, restorative procedures, and long-term follow-up for six years. The patient was an 18-year-old man presenting with a chief complaint of congenital absence of some permanent teeth and dental malalignment on the first visit. The mandibular right central incisor, bilateral mandibular second premolars, bilateral maxillary lateral incisors, and bilateral maxillary canines were congenitally absent, while the deciduous maxillary lateral incisors, maxillary canines, and mandibular second molars were over-retained bilaterally. Since the persisting deciduous teeth were remarkably well preserved, the patient was willing to retain them as far as possible; thus, we chose orthodontic and restorative treatment to preserve the deciduous teeth. Occlusion was established after the initiation of dynamic orthodontic treatment; restorative treatment with resin-based materials was performed for the bilateral maxillary deciduous incisors, bilateral maxillary deciduous canines, and bilateral mandibular second primary molars after bracket removal, and the retention phase of orthodontic treatment was initiated. At present, six years after establishing retention, the patient exhibits a good occlusal relationship. It is difficult to achieve complete space closure using orthodontic treatment alone in cases with six or more congenitally missing permanent teeth. In addition to considerations for age, esthetic issues due to missing permanent teeth, and maxillofacial skeletal morphology, it is necessary to preserve the deciduous teeth as much as possible and ensure multidisciplinary medical cooperation, including the transition to prosthodontic treatment during long-term follow-up., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kunimatsu et al.)

Several large longitudinal studies on myotonic dystrophy type 1 (DM1) patients have revealed that proximal muscles show more gradual muscle weakness than distal muscles and that the progression of muscle weakness might differ between the sexes. However, these longitudinal studies were based on two follow-up time points. The present report aimed to verify the longitudinal characteristics of muscle strength and various movement abilities in a case of DM1 by examining the results of 44 repeated evaluations for approximately two years. A 40-year-old male patient with DM1 could walk independently without any aid. We recorded the longitudinal changes in his muscle strength and movement ability during outpatient rehabilitation. During follow-up, he had a fall and was diagnosed with a right ankle sprain. To evaluate the effects of the fall, we examined his recorded data. He had a significant decrease in right knee extensor muscle strength after the fall, suggesting muscle weakness due to disuse syndrome. Although his right knee extensor muscle strength and walking speed decreased, the timed up-and-go test score was improved, and walking endurance in the 2-minute walk test was maintained. In the present case, there were some motor tasks in which the movement ability was maintained or improved, likely due to the use of compensation by residual function, even when muscle weakness was present. Regular and repeated evaluations of patients with DM1 lead to reveal longitudinal characteristics of their dysfunction and movement ability., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ishibashi et al.)

Research on bryophyte phytochemistry has revealed the presence of different phytochemicals like fatty acids, terpenoids, small phenolic molecules, etc. Small phenolic molecules, i.e., bibenzyls (of two aromatic rings) and bisbibenzyls (four aromatic rings), are unique signature molecules of liverworts. The first bisbibenzyls marchantin A and riccardin A were discovered in two consecutive years, i.e., 1982 and 1983, respectively, by Asakawa and coworkers. Since then, about 70 bisbibenzyls have been reported. These molecules are characterized and identified using different spectroscopic techniques and surveyed for different bioactivity and structure-activity relations. Biochemistry is determined by the season, geography, and environment. In this review, quantitative and qualitative information on bibenzyls and bisbibenzyl compounds and their distribution in different liverworts across, geographies along withtraditional to advanced extraction methods, and characterization techniques are summarized. Also, a comprehensive account of characteristic spectra of different bisbibenzyl compounds, their subtypes, and their basic skeleton patterns are compared. A comprehensive table is provided here for the first time presenting the quantity of bibenzyls, bisbenzyls, and their derivatives found in bryophytes, mentioning the spectroscopic data and mass profiles of the compounds. The significance of these compounds in different bioactivities like antibiotic, antioxidative, antitumor, antivenomous, anti-influenza, insect antifeedant, cytotoxic, and anticancerous activities are surveyed and critically enumerated.

Objective: : To examine activities of daily living (ADL) and physical activity in older adults with heart failure admitted to a rehabilitation ward for subacute musculoskeletal disease., Methods: : This study included patients with musculoskeletal disease (aged ≥75 years) who were admitted to the rehabilitation ward. Data on age, ADL, and time for physical activity (metabolic equivalents [METs]) were collected. Patients were divided into groups with or without heart failure, and the differences were compared using Mann-Whitney U-test., Results: : This study included 84 musculoskeletal patients, including 25 with heart failure. The heart-failure group had similar levels of ADL independence compared to the without-heart-failure group (p=0.28) but had shorter duration of continuous and sustained physical activities and less total time (p<0.01) of light-intensity physical activity or higher., Conclusion: : Older adults with subacute musculoskeletal disease with heart failure do not necessarily require a large amount of physical activity to maintain ADL at the time of discharge. But very low physical activity may increase the risk for developing hospitalization-associated disability. Physical activity in older adults with subacute musculoskeletal disease with heart failure should be monitored separately from ADL.

Estrogen is a steroid hormone that induces skeletal growth and affects endochondral ossification of the long tubular bone growth plate during the growth period. However, the effects of estrogen on endochondral ossification of the mandibular condylar cartilage are unclear. In this study, ovariectomized Wistar/ST rats were used to investigate the longitudinal effects of estrogen on mandibular growth. The rats were administered different doses of estrogen. Longitudinal micro-computed tomographic scanning, histological staining and ELISA on plasma growth hormone were performed to examine the effects of estrogen on mandibular growth. The results showed that mandibular growth was suppressed throughout the growth period by estrogen in a dose-dependent manner. In addition, long-term administration of a high dose of estrogen to the rats resulted in significant increase in growth hormone throughout the growth period, significant circularization of cell nuclei in the proliferative layer, intensely staining cartilage matrix in the subchondral bone, and significant suppression of estrogen receptor (ER) alpha and beta expression in the mandibular cartilage. However, regardless of estrogen concentration, in the posterior part of the mandibular cartilage, ER expression extended to both the hypertrophic and proliferative layers. These results indicate that estrogen suppresses mandibular growth throughout the growth period. Additionally, it influences endochondral ossification via its effect on ERs., Competing Interests: Declarations of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Volatile emissions from 22 bryophyte species from Peninsular Malaysia were collected using a dynamic headspace technique and analyzed by gas chromatography-mass spectrometry (GC-MS). Thirty organic compounds (VOCs) from eight different groups were detected in bryophytes from the montane forest in Cameron Highlands and the lowland dipterocarp forest in Lata Belatan. The headspace of bryophytes in Cameron Highlands was dominated by tetradecane, 2-ethyl-1-hexanol, decanal, pentanoic acid, 2,2,4-trimethyl-3-carboxyisopropyl, isobutyl ester, D-limonene and naphthalene. On the contrary, in the bryophyte headspace of Lata Belatan, naphthalene and tetradecane were dominant compounds. The elevational pattern detected in VOC composition of bryophytes appears to be an evolutionary feature at the family level that needs verification at other sites. The results also confirmed that the VOC composition of bryophytes is species-specific. The roles of VOCs in bryophytes are presented, including plant-plant communication and plant-insect interaction and as an additional taxonomic character in chemotaxonomy.

Idiopathic mandibular condylar resorption (ICR) is a pathological condition characterized by idiopathic resorption of the mandibular condyle, resulting in a decrease in the size and height of the mandibular condyle. The purpose of this study was to characterize the maxillofacial morphology of ICR patients. Subjects were selected from patients that attended our orthodontic clinic between 1991 and 2019. Twenty-five patients were diagnosed with ICR by magnetic resonance imaging; however, growing patients were excluded. In total, 18 patients were finally selected. The control group comprised 18 healthy volunteers. Lateral and frontal cephalograms were also used. The ICR group had significantly more severe skeletal class II malocclusions than the control group, mainly due to retrusion of the mandible. In the ICR group, there was a tendency for a skeletal open bite due to a significantly larger clockwise rotation of the mandible than in the control group. There was no significant difference between the two groups in the inclination of the upper and lower central incisors or protrusion of the upper and lower central incisors and first molars. ICR patients have been suggested to exhibit skeletal open bite and maxillary protrusion with changes in maxillofacial morphology due to abnormal resorption of the mandibular condyle.

Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted molecule with numerous physiologic and pathologic functions, for example, in angiogenesis, hematopoiesis, and tumorigenesis. Although recent studies implicated ANGPTL2 in chronic inflammation in mouse peritoneal macrophages, human ligamentum flavum fibroblasts, and human retinal microvascular endothelial cells, the mechanism underlying ANGPTL2-associated inflammation in chondrocytes remains unclear. Therefore, it was investigated whether ANGPTL2 is expressed in or functions in chondrocytes., Methods: Expression of ANGPTL2 and its receptor, integrin α5β1 were examined over time in ATDC5 cells using real-time RT-PCR (reverse transcription-polymerase chain reaction) analysis. ATDC5 cells were then incubated with or without ANGPTL2 for 3 hours, and expression of the IL-1β, TNF-α, COX-2, aggrecanase (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13 genes were examined using real-time RT-PCR. Additionally, phosphorylation of ERK, JNK, p38, Akt, and NF-κB was examined by western blotting. Furthermore, it was also investigated for the effect of anti-integrin α 5 β 1 antibody on the expression of inflammatory markers and intracellular signaling pathways., Results: ANGPTL2 induced the phosphorylation of all 3 MAPKs, Akt, and NF-κB and dramatically upregulated the expression of inflammation-related factor genes. Inhibiting the activation of integrin α5β1 suppressed these reactions., Conclusion: ANGPTL2 may induce inflammatory factors by stimulating the integrin α5β1/MAPKs, Akt, and NF-κB signaling pathway.

Objective: This study aimed to determine the optimal β value of the relaxation control parameter and the post-smoothing filter in the list-mode dynamic row-action maximum likelihood algorithm (LM-DRAMA) to detect early stage breast cancer with high-resolution dedicated breast positron emission tomography (dbPET) in phantom and clinical studies., Methods: A breast phantom containing four spheres (5, 7.5, 10, and 16 mm in diameter) was filled with 18 F-fluorodeoxyglucose solution (sphere-to-background ratio, 8:1) and scanned on a dbPET scanner. The images were reconstructed using LM-DRAMA with different β values (5, 20, or 100) and Gaussian post-filters (0, 0.78, 1.17, 1.56, 1.95, or 2.34 mm). Other conditions were according to those routinely used (1 iteration and 128 subsets including attenuation and scatter correction). Image quality was evaluated visually and by computing the coefficient of variation of the background (CV BG ), detectability index (DI), and contrast recovery coefficient. Parameters optimized in these phantom studies were applied to 25 clinical data sets. Variabilities for different reconstruction methods in visual scores, the maximum standardized uptake value of breast cancer, and the tumor-to-background uptake ratio were estimated., Results: The reconstruction images of the phantom with higher β values and smaller post-filters yielded higher visual scores for detectability and DI and lower smoothness and CV BG scores. Based on the phantom study, the β values and post-filter were optimized for clinical dbPET images except for β5 and 2.34 mm post-filter. Applying the other reconstructions to clinical studies showed that β100 provided higher quantitative parameter values. The detectability of lesions was similar for β100 and β20 and decreased with larger post-filters. The lesion detection rate was similar for β100 and β20 and decreased with larger post-filter., Conclusion: The relaxation coefficient factor β20 and a 0.78- or 1.17-mm post-filter were optimal for dbPET image reconstruction with balanced spatial resolution and noise. However, they should be selected according to the impact on the dbPET image and the purpose of the examination.

Objectives: To reveal self-rated changes of health status during stay-at-home orders among older adults and to verify whether decrease in frequency of going outdoors during these orders was related to self-rated changes in health status., Method: A self-completed questionnaire for older adults was provided in 2 dayservice facilities and a nursing station. We operationally defined health status with 4 domains (motor function, oral and swallowing function, depression, and social networks) and designed the questionnaire to determine self-rated changes in health status using factor analysis. After factor analysis, regression analyses were conducted. Dependent variable was each factor score (self-rated changes of health status), and independent variable was decrease in frequency of going outdoors., Results: Approximately 80% of participants answered that their health status had "worsened" in motor function (75.0%-87.2%). Moreover, more than 70% of participants answered "worsened" in "Feeling energy" and "Getting together and speaking with friends" (72.3% and 75.7%, respectively). Regression analyses demonstrated that, after adjusting for covariates, the decrease in frequency of going outdoors was related to self-rated changes of motor function and friend network., Conclusion: During stay-at-home orders, older adults felt deterioration in their motor function, in feeling energy, and in their friend network, especially people who had decreased their frequency of going outdoors felt more deterioration in their motor function and in their friend network., Competing Interests: The authors declare no conflict of interest., (2021, JAPANESE PHYSICAL THERAPY ASSOCIATION.)

OPS-2071 is a novel quinolone antibacterial agent characterized by low oral absorption that reduces the risk of adverse events typical of fluoroquinolone class antibiotics. The in vitro and in vivo antibacterial activities of OPS-2071 against Clostridioides difficile were evaluated in comparison to vancomycin and fidaxomicin. OPS-2071 exhibited potent antibacterial activity against 54 clinically isolated C. difficile strains with a MIC of 0.125 μg/ml (MIC 50 ) and 0.5 μg/ml (MIC 90 ), making it more active than vancomycin on a concentration basis (MIC 50 , 2 μg/ml; MIC 90 , 4 μg/ml) and comparable to fidaxomicin (MIC 50 , 0.063 μg/ml; MIC 90 , 8 μg/ml). OPS-2071 showed equally potent antibacterial activity against both hypervirulent and nonhypervirulent strains, while a significant difference in susceptibility to fidaxomicin was observed. Spontaneous resistance to OPS-2071 and vancomycin was not observed; however, resistance to fidaxomicin was observed at 4× MIC. The mutant prevention concentration of OPS-2071 was 16-fold lower than those of fidaxomicin and vancomycin, and the postantibiotic effect of OPS-2071 was longer than those of fidaxomicin and vancomycin. Also, OPS-2071 showed low systemic exposure, with OPS-2071 having 2.9% oral bioavailability at 1 mg/kg in rats. Furthermore, OPS-2071 showed significant in vivo efficacy at 0.0313 mg/kg/day (50% effective doses), 39.0-fold and 52.1-fold lower than those of vancomycin and fidaxomicin, respectively, in a hamster model of C. difficile infection. OPS-2071 has the potential to become a new therapeutic option for treating C. difficile infection., (Copyright © 2021 Oka et al.)

Background and Aim: There are no globally approved, distinguishing criteria enabling the classification of gastric adenomas and intramucosal carcinomas for differential diagnosis of noninvasive neoplasia (NIN)., Methods: Next-generation sequencing of 50 cancer-related genes was undertaken on 68 pathologically diagnosed microdissected gastric neoplasms (25 adenomas, 27 intramucosal carcinomas, and 16 submucosal carcinomas) obtained during endoscopic submucosal dissection. Findings from magnifying endoscopy with narrow-band imaging (M-NBI) of 52 NINs (the 25 adenomas and 27 intramucosal carcinomas) were compared with these data., Results: Among all 68 neoplasms, the most frequently mutated genes were APC (76% in adenoma, 11.1% in intramucosal carcinoma, and 0% in submucosal carcinoma; P  < 0.001) and TP53 in intramucosal and submucosal carcinomas (8% in adenoma, 48.1% in intramucosal carcinoma, and 75% in submucosal carcinoma; P  < 0.001). Dividing the NIN neoplasms into five groups according to their mutational status (A1: APC mutation, A2: APC  + α mutation, B: APC  +  TP53 mutation, C: TP53 mutation, D: no mutation in either APC or TP53 ) resulted in almost identical diagnoses by pathology and M-NBI for groups A1 (12/13, 92%), C (12/13, 92%), and D (16/17, 94%) but not for groups A2 (3/7, 43%) or B (0/2, 0%). This finding implies that NINs with the APC  + α mutation have carcinoma-like endoscopic features despite most being judged as adenomas by pathology., Conclusion: A diagnosis of NINs by pathology or M-NBI in the subset of gastric tumors classified by cancer-related mutations is not completely identical, suggesting the possible additional role of M-NBI in diagnosing NINs. Further studies are needed to confirm this., (© 2021 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

[Purpose] We aimed to investigate the difficulties perceived by physical therapy students during clinical practice, and to identify the associated factors based on the results of our previous interview survey. We collected opinions from these students through a questionnaire survey. Furthermore, we analyzed the relationships between the difficulties perceived by physical therapy students during clinical practice and the students' level of achievement at the end of their clinical practice. [Participants and Methods] The study included 176 students, who had completed comprehensive clinical practice during their fourth year, to rate the difficulties perceived by them on an 11-point scale from 0 to 10. [Results] There were 127 responses. Through exploratory factor analysis, 43 items representing 5 factors were selected: Factor 1, difficulties related to communication of behavioral improvement/relationship building; Factor 2, difficulty obtaining supportive guidance/having appropriate learning environments coordinated; Factor 3, difficulty organizing/expressing clinical reasoning for physical therapy; Factor 4, difficulty learning in the clinical practice environment; and Factor 5, difficulty managing patients/adapting to the environment. [Conclusion] Regardless of the level of achievement at the end of clinical practice, the students strongly perceived "Factor 2: difficulty obtaining supportive guidance/having appropriate learning environments coordinated". The results identified the factors associated with the difficulties perceived by physical therapy students during clinical practice, thereby providing a basis for resolving such difficulties., Competing Interests: The authors declare no conflicts of interest., (2020©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Gas evolution in Li-ion batteries remains a barrier for the implementation of high voltage materials in a pouch cell format; the inflation of the pouch cell is a safety issue that can cause battery failure. In particular, for manganese-based materials employed for fabricating cathodes, the dissolution of Mn 2+ in the electrolyte can accelerate cell degradation, and subsequently gas evolution, of which carbon dioxide (CO 2 ) is a major component. We report on the utilization of a mixture of polymers that can chemically absorb the CO 2 , including the coating of aluminum foils, which serve as trapping sheets, introduced into two Ah pouch cells-based on a LiMnFePO 4 (cathode) and a Li 4 Ti 5 O 12 (anode). The pouch cells with trapping sheets experienced only an 8.0 vol% inflation (2.7 mmol CO 2 per gram of polymers) as opposed to the 40 vol% inflation for the reference sample. Moreover, the cells were cycled for 570 cycles at 1 C and 45 °C before reaching 80% of their retention capacity.

Epstein-Barr virus (EBV) is associated with particular forms of gastric cancer (GC). We previously showed that EBV infection into gastric epithelial cells induced aberrant DNA hypermethylation in promoter regions and silencing of tumor suppressor genes. We here undertook integrated analyses of transcriptome and epigenome alteration during EBV infection in gastric cells, to investigate activation of enhancer regions and related transcription factors (TFs) that could contribute to tumorigenesis. Formaldehyde-assisted isolation of regulatory elements (FAIRE) sequencing (-seq) data revealed 19 992 open chromatin regions in putative H3K4me1 + H3K4me3 - enhancers in EBV-infected MKN7 cells (MKN7&#95;EB), with 10 260 regions showing increase of H3K27ac. Motif analysis showed candidate TFs, eg activating transcription factor 3 (ATF3), to possibly bind to these activated enhancers. ATF3 was considerably upregulated in MKN7&#95;EB due to EBV factors including EBV-determined nuclear antigen 1 (EBNA1), EBV-encoded RNA 1, and latent membrane protein 2A. Expression of mutant EBNA1 decreased copy number of the EBV genome, resulting in relative downregulation of ATF3 expression. Epstein-Barr virus was also infected into normal gastric epithelial cells, GES1, confirming upregulation of ATF3. Chromatin immunoprecipitation-seq analysis on ATF3 binding sites and RNA-seq analysis on ATF3 knocked-down MKN7&#95;EB revealed 96 genes targeted by ATF3-activating enhancers, which are related with cancer hallmarks, eg evading growth suppressors. These 96 ATF3 target genes were significantly upregulated in MKN7&#95;EB compared with MKN7 and significantly downregulated when ATF3 was knocked down in EBV-positive GC cells SNU719 and NCC24. Knockdown of ATF3 in EBV-infected MKN7, SNU719, and NCC24 cells all led to significant decrease of cellular growth through an increase of apoptotic cells. These indicate that enhancer activation though ATF3 might contribute to tumorigenesis of EBV-positive GC., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Lithium titanium oxide (Li 4 Ti 5 O 12 )-based cells are a promising technology for ultra-fast charge-discharge and long life-cycle batteries. However, the surface reactivity of Li 4 Ti 5 O 12 and lack of electronic conductivity still remains problematic. One of the approaches toward mitigating these problems is the use of carbon-coated particles. In this study, we report the development of an economical, eco-friendly, and scalable method of making a homogenous 3D network coating of N-doped carbons. Our method makes it possible, for the first time, to fill the pores of secondary particles with carbons; we reveal that it is possible to cover each primary nanoparticle. This unique approach permits the creation of lithium-ion batteries with outstanding performances during ultra-fast charging (4C and 10C), and demonstrates an excellent ability to inhibit the degradation of cells over time at 1C and 45 °C. Furthermore, using this method, we can eliminate the addition of conductive carbons during electrode preparation, and significantly increase the energy density (by weight) of the anode.

Bryophytes, phylogenetically placed between the algae and pteridophytes, are divided into three classes: mosses, liverworts, and hornworts. Traditional system of medicine throughout the world has been utilizing this group of plants to treat various ailments. One of the outstanding features of these spore forming plants is their chemistry, especially that of the liverworts. Liverworts have yielded a rich array of terpenoids, especially sesqui- and diterpenoids. Many of these compounds are characterized by unprecedented structures, and some have not been found in any other plants, fungi or marine organisms. Among the bryophytes, the chemical constituents of liverworts and their biological activity have been studied in the most detail. In this review the chemistry of the terpenoids found in bryophytes have been presented, and their phytotoxic, antimicrobial, antifungal, cytotoxic, anti-inflammatory, piscicidal, insect repellent, antileishmanial and antitrypanosomal activities., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Aims: The recent advancement of next-generation sequencing (NGS) has enabled the identification of cancer-related somatic aberrations in advanced gastric cancer. However, these remain unclear in early gastric cancers, especially in intramucosal gastric cancers., Patients and Methods: Thirty-one well-differentiated (tub1) intramucosal gastric cancers obtained by endoscopic submucosal dissection (ESD) from 29 patients were analyzed. After precise collection of tumors and non-tumors from formalin-fixed paraffin-embedded tissues using laser-captured microdissection (LCM), target sequencing analysis of 50 cancer-related genes was performed using an Ion-Proton sequencer., Results: The most frequent hotspot mutation was found in TP53 (17 lesions, 54.8%) followed by the Wnt-signaling pathway genes, APC and CTNNB1 (6 lesions, 19.4%). The mutations in TP53 and the Wnt-signaling genes were mutually exclusive (p = 0.004). There was a tendency that H. pylori infection (p = 0.082) and macroscopic protrusion (p = 0.095) was associated with the presence of these mutations. Only 10 lesions (59%) among 17 lesions with proven TP53 mutations were positive for p53 immunostaining demonstrating the superiority of the mutational analysis. In addition, focal gene amplification of ERBB2 (16%) was found frequently in these early stage lesions., Conclusions: Using LCM and NGS, mutations in TP53 and the Wnt-signaling pathway were frequently found and were mutually exclusive in the earliest stage of gastric carcinogenesis.

Background and Aims: Next generation sequencing (NGS) has revealed a great deal about cancer-related somatic changes in esophageal squamous cell neoplasia; however, the changes in the very early stages remain unclear., Results: TP53 (87%) and CDKN2A (20%) hot spot mutations were frequently found in early lesions. TP53 was the most common mutation (LGIN/HGIN, 86%; EP, 83%; LPM, 95%; MM/SM1, 80%), followed by CDKN2A (29%, 28%, 16% and 10%, respectively); the frequency of other mutations increased as the disease advanced ( p < 0.01). Copy number variation analysis revealed copy number aberrations in multiple genes, including PIK3CA amplification (48%). NGS was superior to p53 immunostaining for detecting TP53 mutations (74% vs. 87%); in combination, the two tests improved detectability to 94%. Clinically, smoking was associated with the occurrence of TP53 mutations in these early lesions ( p = 0.049)., Materials and Methods: Fifty-four early esophageal neoplasia lesions from 47 patients treated by endoscopic resection (low-grade intraepithelial neoplasia [LGIN], n = 1; high-grade intraepithelial neoplasia [HGIN] n = 7; invasion limited to epithelium [EP/M1], n = 18; lamina propria mucosae [LPM/M2], n = 19; muscularis mucosae [MM/M3], n = 8; and upper third of the SM [SM1], n = 2) were isolated from formalin-fixed paraffin-embedded tissue specimens by laser-capture microdissection. Target sequencing of 50 cancer-related genes was performed with an Ion Proton sequencer; their association with the clinical characteristics was investigated., Conclusions: Mutations of TP53 and CDKN2A , and PIK3CA amplification were common in early esophageal squamous neoplasia, while other mutations accumulated with disease progression. An understanding of these molecular events might provide a molecular basis for early lesion treatment., Competing Interests: CONFLICTS OF INTEREST None.

Rhododendron dauricum produces daurichromenic acid, an anti-HIV meroterpenoid, via oxidative cyclization of the farnesyl group of grifolic acid. The prenyltransferase (PT) that synthesizes grifolic acid is a farnesyltransferase in plant specialized metabolism. In this study, we demonstrated that the isoprenoid moiety of grifolic acid is derived from the 2- C -methyl-d-erythritol-4-phosphate pathway that takes place in plastids. We explored candidate sequences of plastid-localized PT homologs and identified a cDNA for this PT, RdPT1, which shares moderate sequence similarity with known aromatic PTs. RdPT1 is expressed exclusively in the glandular scales, where daurichromenic acid accumulates. In addition, the gene product was targeted to plastids in plant cells. The recombinant RdPT1 regiospecifically synthesized grifolic acid from orsellinic acid and farnesyl diphosphate, demonstrating that RdPT1 is the farnesyltransferase involved in daurichromenic acid biosynthesis. This enzyme strictly preferred orsellinic acid as a prenyl acceptor, whereas it had a relaxed specificity for prenyl donor structures, also accepting geranyl and geranylgeranyl diphosphates with modest efficiency to synthesize prenyl chain analogs of grifolic acid. Such a broad specificity is a unique catalytic feature of RdPT1 that is not shared among secondary metabolic aromatic PTs in plants. We discuss the unusual substrate preference of RdPT1 using a molecular modeling approach. The biochemical properties as well as the localization of RdPT1 suggest that this enzyme produces meroterpenoids in glandular scales cooperatively with previously identified daurichromenic acid synthase, probably for chemical defense on the surface of R. dauricum plants., (© 2018 American Society of Plant Biologists. All rights reserved.)

Volatile components of seven species of the Bazzanioideae sub-family (Lepidoziaceae) native to New Caledonia, including three endemic species ( Bazzania marginata , Acromastigum caledonicum and A. tenax ), were analyzed by GC-FID-MS in order to index these plants to known or new chemotypes. Detected volatile constituents in studied species were constituted mainly by sesquiterpene, as well as diterpene compounds. All so-established compositions cannot successfully index some of them to known chemotypes but afforded the discovery of new chemotypes such as cuparane/fusicoccane. The major component of B. francana was isolated and characterized as a new zierane-type sesquiterpene called ziera-12(13),10(14)-dien-5-ol ( 23 ). In addition, qualitative intraspecies variations of chemical composition were very important particularly for B. francana which possessed three clearly defined different compositions. We report here also the first phytochemical investigation of Acromastigum species. Moreover, crude diethyl ether extract of B. vitatta afforded a new bis(bibenzyl) called vittatin ( 51 ), for which a putative biosynthesis was suggested.

Background: In the search for novel antidepressive drug candidates, bioguided fractionation of nonpolar constituents present in the oleoresin from ginger rhizomes ( Zingiber officinale Roscoe, Zingiberaceae) was performed. This particular direction of the research was chosen due to the existing reports on the antidepressive properties of ginger total extract. The search for individual metabolites acting as MAO-A inhibitors, which correspond to the apparent effect of the total extract, is the subject of this work., Methods: Hexane extracts from ginger rhizomes were fractionated by using column chromatography (including silica gel impregnated with silver nitrate) and semi-preparative high-performance chromatography. For the activity assessment, an in vitro monoamine oxidase A (MAO-A) inhibition luminescence assay was performed on 10 purified terpenes: 1,8-cineole, α-citronellal, geraniol, β-sesquiphellandrene, γ-terpinen, geranyl acetate, isobornyl acetate, terpinen-4-ol, ( E , E )-α-farnesene, and α-zingiberene., Results: Geraniol and (-)-terpinen-4-ol were found to be the strongest enzyme inhibitors with inhibition of 44.1% and 42.5%, respectively, at a concentration of 125 µg/mL. No differences in the inhibition potential were observed for the different groups of terpenes: sesquiterpenes, monoterpenes, or sesquiterpene alcohols; however, the two most active compounds contained a hydroxyl moiety., Conclusions: Terpene constituents from ginger's extract were found to exhibit moderate inhibitory properties against the MAO-A enzyme in in vitro tests.

Van der Waals heterostructures are comprised of stacked atomically thin two-dimensional crystals and serve as novel materials providing unprecedented properties. However, the random natures in positions and shapes of exfoliated two-dimensional crystals have required the repetitive manual tasks of optical microscopy-based searching and mechanical transferring, thereby severely limiting the complexity of heterostructures. To solve the problem, here we develop a robotic system that searches exfoliated two-dimensional crystals and assembles them into superlattices inside the glovebox. The system can autonomously detect 400 monolayer graphene flakes per hour with a small error rate (<7%) and stack four cycles of the designated two-dimensional crystals per hour with few minutes of human intervention for each stack cycle. The system enabled fabrication of the superlattice consisting of 29 alternating layers of the graphene and the hexagonal boron nitride. This capacity provides a scalable approach for prototyping a variety of van der Waals superlattices.

Background: Excessive mechanical stress causes inflammation and destruction of cartilage and is considered one of the cause of osteoarthritis (OA). Expression of semaphorin 3A (Sema3A), which is an axon guidance molecule, has been confirmed in chondrocytes. However, there are few reports about Sema3A in chondrocytes, and the effects of Sema3A on inflammation in the cartilage are poorly understood. The aim of this study was to examine the role of Sema3A in inflammation caused by high magnitude cyclic tensile strain (CTS)., Methods: Expression of Sema3A and its receptors neuropilin-1 (NRP-1) and plexin-A1 (PLXA1) in ATDC5 cells was examined by Western blot analysis. ATDC5 cells were subjected to CTS of 0.5 Hz, 10% elongation with added Sema3A for 3 h. Gene expression of IL-1 β , TNF- ɑ , COX-2, MMP-3, and MMP-13 was examined by qPCR analysis. Furthermore, the phosphorylation of AKT, ERK, and NF- κ B was detected by Western blot analysis., Results: Added Sema3A inhibited the gene expression of inflammatory cytokines upregulated by CTS in a dose-dependent manner. Addition of Sema3A suppressed the activation of AKT, ERK, and NF- κ B in a dose-dependent manner., Conclusions: Sema3A reduces the gene expression of inflammatory cytokines by downregulating the activation of AKT, ERK, and NF- κ B pathways in ATDC5 cells under CTS.