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2. Manipulation of the Global Regulator

Author

Bo, Yuan, Nancy P, Keller, Berl R, Oakley, Jason E, Stajich, and Clay C C, Wang

Subjects
Emodin, Aspergillus, Glucose, Ribonucleoproteins, Multigene Family, CRISPR-Cas Systems, Polyketide Synthases
Abstract

Genome sequencing of filamentous fungi has demonstrated that most secondary metabolite biosynthetic gene clusters (BGCs) are silent under standard laboratory conditions. In this work, we have established an in vitro CRISPR-Cas9 system in

Published
2023

9. [Advances in the classification and treatment of isolated superior mesenteric artery dissection]

Author

C C, Wang, Y D, Sun, X L, Wei, Z P, Jing, and Z Q, Zhao

Abstract

Isolated superior mesenteric artery dissection (ISMAD) has attracted more and more clinicians' attention in recent years. Patients onset of ISMAD often present with abdominal pain. The misdiagnosis or miss diagnosis is common because of the non-specific symptoms and signs, which even can endanger lives in serious cases. Imaging classification is of great significance for diagnosis and treatment of ISMAD. The Sakamoto classification and the Yun classification are two classical classified methods. However, with the further study of ISMAD, various new classifications emerge. Conservative treatment was once considered as the preferred. As the rapid development of endovascular therapy and the great progress of new devices, stenting therapy can significantly improve symptoms and achieve satisfactory long-term effects, and be even expected to become the preferred method for clinical therapy of ISMAD. However, the long-term effects of endovascular therapy still need a large number of follow-up data, and complications after stent implantation can't be ignored.近年来，孤立性肠系膜上动脉夹层被越来越多的临床医师关注。患者发病时常表现为腹痛，其症状、体征无特异性，易被误诊、漏诊，严重时可危及患者生命。影像学分型对该疾病的诊断和指导治疗有着重要意义，Sakamoto分型和Yun分型是两种经典的分型方式。随着对该病了解的不断深入，各种新分型不断出现，各有千秋。保守治疗曾被认为是孤立性肠系膜上动脉夹层的首选治疗方式，但随着血管腔内治疗的迅速发展和新器械的不断出现，支架成形术后患者症状改善明显，中长期效果满意，有望成为该疾病的首选治疗方法。然而，腔内治疗的远期效果仍需大样本随访资料支持，支架植入后并发症同样不可忽视。.

Published
2023

11. Mirror-plane disorder in a nickel chloride Schiff base complex: a suitable case study for crystallographic instruction

Author

Hsuan Chang, Wen-Ching Chen, Jiun-Shian Shen, Tiow-Gan Ong, Vincent C.-C. Wang, and Glenn P. A. Yap

Subjects
Inorganic Chemistry, Nickel, Materials Chemistry, Hydrogen Bonding, Physical and Theoretical Chemistry, Crystallography, X-Ray, Condensed Matter Physics, Schiff Bases
Abstract

The nickel chloride complex of the Schiff base N 2,N 2′-propanediylbis(2,3-butanedione-2-imine-3-oxime), namely, chlorido(3,9-dimethylundeca-3,8-diene-2,10-dione 10-oxime 2-oximato-κ4 N,N′,N′′,N′′′)nickel(II), [NiCl(C11H19N4O2)], at 100 K crystallizes in the orthorhombic space group Cmce. The structure exhibits mirror disorder of the main molecule that is not present in the bromide analogue. The relatively small number of unique reflections in the data set and the disorder imposed by the crystallographic mirror plane present a challenging educational case study.

Published
2022

15. Conversion of Polyethylenes into Fungal Secondary Metabolites

Author

Chris Rabot, Yuhao Chen, Swati Bijlani, Yi‐Ming Chiang, C. Elizabeth Oakley, Berl R. Oakley, Travis J. Williams, and Clay C. C. Wang

Subjects
General Chemistry, General Medicine, Catalysis
Abstract

Waste plastics represent major environmental and economic burdens due to their ubiquity, slow breakdown rates, and inadequacy of current recycling routes. Polyethylenes are particularly problematic, because they lack robust recycling approaches despite being the most abundant plastics in use today. We report a novel chemical and biological approach for the rapid conversion of polyethylenes into structurally complex and pharmacologically active compounds. We present conditions for aerobic, catalytic digestion of polyethylenes collected from post-consumer and oceanic waste streams, creating carboxylic diacids that can then be used as a carbon source by the fungus Aspergillus nidulans. As a proof of principle, we have engineered strains of A. nidulans to synthesize the fungal secondary metabolites asperbenzaldehyde, citreoviridin, and mutilin when grown on these digestion products. This hybrid approach considerably expands the range of products to which polyethylenes can be upcycled.

Published
2022

16. [Application of the concept of precision obesity metabolic surgery in laparoscopic Roux-en-Y gastric bypass]

Author

Y, Yang, W H, Chen, Z Y, Dong, and C C, Wang

Subjects
Treatment Outcome, Diabetes Mellitus, Type 2, Artificial Intelligence, Weight Loss, Gastric Bypass, Bariatric Surgery, Humans, Laparoscopy, Obesity, Obesity, Morbid
Abstract

Due to the complexity and heterogeneity of obesity, the diagnosis and treatment of obesity vary greatly. Five to 10 percent of body weight can be lost through lifestyle modifications, nutritional and behavioral counseling, and the use of approved weight reduction medicines for obesity and diabetes; however, these non-surgical treatments are not effective for all patients. Compared to medical therapy, bariatric surgery is associated with higher rates of type 2 diabetes remission, lower mortality from vascular complications, and long-term, sustained weight loss. With the advent of precision medicine in surgical therapy, bariatric surgeons' fundamental understanding of laparoscopic Roux-en-Y gastric bypass surgery has evolved in recent years. The objective of surgery has shifted from short-term weight loss to the safe and successful long-term management of patient weight and comorbidities. In laparoscopic Roux-en-Y gastric bypass surgery, the concept of precision bariatric and metabolic surgery is mainly reflected in three aspects: accurate preoperative assessment, precise intraoperative operation, and comprehensive postoperative management. A new direction for the future development of precision laparoscopic Roux-en-Y gastric bypass surgery and obesity metabolic surgery is to formulate precise and individualized surgical treatment plans for patients and to use artificial intelligence and big data technology to improve the standardization of specialist data.由于肥胖本身的复杂性和异质性，导致肥胖症的诊疗方法个体化差异较大。通过改变生活方式和饮食结构、采用行为疗法以及使用已经批准的减肥药物治疗肥胖和糖尿病患者，可以实现5%~10%的体质量减轻，但并非所有患者都可以通过这些非手术的治疗手段获益。与药物治疗相比，减重代谢手术有更高的2型糖尿病缓解率和更低的血管并发症病死率并且可以长期持续减轻体质量。近些年来，随着精准医学在外科治疗中的发展，减重外科医生对腹腔镜Roux-en-Y胃旁路手术的核心理念也发生了改变。手术目的从强调短期体质量大幅下降转变为安全有效地长期控制患者的体质量和并发症。在腹腔镜Roux-en-Y胃旁路手术中，精准减重代谢外科理念主要体现在3个方面：术前的精准评估、术中的精细操作和术后的综合管理。为患者制定精准、个体化的手术治疗方案，同时利用人工智能和大数据技术，提高专科数据的标准化是精准腹腔镜Roux-en-Y胃旁路手术和减重代谢外科未来发展的新方向。.

Published
2022

17. [Effects of bariatric surgery on sex hormones in male patients with obesity]

Author

S J, Luo, J X, Zheng, Y T, Chen, Z W, Xie, Z S, Yang, G J, Chen, C C, Wang, and Z Y, Dong

Subjects
Adult, Male, Estradiol, Bariatric Surgery, Luteinizing Hormone, Body Mass Index, Prolactin, Young Adult, Diabetes Mellitus, Type 2, Weight Loss, Humans, Testosterone, Obesity, Follicle Stimulating Hormone, Progesterone, Retrospective Studies
Published
2022

18. The real-world effectiveness and safety of edoxaban treatment in 27,333 Global ETNA-AF programme patients with and without a history of heart failure

Author

J Siller-Matula, M Unverdorben, C C Wang, Y Koretsune, L Pecen, A Borrow, C Chen, P Kirchhof, and R De Caterina

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background Heart failure (HF) occurs in approximately 26% of patients with atrial fibrillation (AF). Real-world data of oral anticoagulation with edoxaban in AF patients with HF history are limited. Purpose To compare edoxaban effectiveness and safety in AF patients with or without HF history. Methods The Global ETNA-AF programme (EU: NCT02944019, Japan: UMIN000017011, South Korea/Taiwan: NCT02951039) integrates data from multiple prospective, observational, noninterventional regional studies of AF patients receiving edoxaban for stroke prevention. This snapshot analysis summarises baseline characteristics and 2-year annualised rates of all-cause death, cardiovascular (CV) death, stroke (haemorrhagic, ischaemic, any), and bleeding (major bleeding [MB], major gastrointestinal [GI] bleeding, intracranial haemorrhage [ICH], clinically relevant nonmajor bleeding [CRNMB], and any bleeding) in patients with or without HF history. Univariate Cox regression models assessed clinical outcomes. Results Data from 27,333 patients (5258 with HF history) from Europe, Japan, South Korea, and Taiwan were analysed. Patients with HF history were significantly older and had lower mean body weight and creatinine clearance (P Conclusions In AF patients receiving edoxaban, the rates of MB, major GI bleeding, and CV or all-cause death were higher when comparing those with versus without HF history. The higher incidence of MB and major GI bleeding in patients with HF history did not lead to proportionally higher fatal bleeding rates among all-cause deaths. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo

Published
2022

19. Real-world effectiveness and safety of edoxaban in patients with and without a history of ischaemic stroke: results from the ETNA-AF programme

Author

R De Caterina, M Unverdorben, B C Lee, T Yamashita, W S Lin, C C Wang, L Pecen, A Borrow, C Chen, and P Kirchhof

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background Atrial fibrillation (AF) patients with a history of ischaemic stroke (IS) have a higher risk for recurrent IS events and were largely excluded from the pivotal, randomised, controlled phase 3 trials on oral anticoagulants. Thus, the effectiveness and safety of edoxaban in these patients need to be studied in a real-world setting. Purpose To compare edoxaban real-world effectiveness and safety in AF patients with or without an IS history. Methods The Global ETNA-AF programme (EU: NCT02944019, Japan: UMIN000017011, South Korea/Taiwan: NCT02951039) integrates data from multiple prospective, observational, noninterventional regional studies of AF patients receiving edoxaban for stroke prevention. This snapshot analysis summarises baseline characteristics with medical history and 2-year annualised rates of all-cause death, cardiovascular (CV) death, stroke (haemorrhagic, ischaemic, any), and bleeding (including major bleeding [MB], major gastrointestinal [GI] bleeding, intracranial haemorrhage [ICH], clinically relevant nonmajor bleeding [CRNMB], and any bleeding) in patients with or without IS history. Results Data from 27,333 patients (3215 with prior IS and 24,118 without) from Europe, Japan, South Korea, and Taiwan were analysed. Patients with IS history were significantly older, more likely ≥75 years of age, and had a lower mean body weight and creatinine clearance (P Conclusions Patients with AF who have a history of IS are more likely elderly; have histories of MB, ICH, and TIA; and have high baseline stroke and bleeding risk scores. Patients with IS history receiving edoxaban have a considerably higher likelihood of experiencing IS or TIA, whereas the risk of experiencing any bleeding event (with the exception of ICH) is only modestly higher than in those without IS history. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo

Published
2022

20. Two-year effectiveness and safety outcomes in 27,333 edoxaban-treated patients with and without a history of major bleeding from the Global ETNA-AF programme

Author

V Russo, C C Wang, M Unverdorben, T Yamashita, L Pecen, A Borrow, C Chen, P Kirchhof, and R De Caterina

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background Atrial fibrillation patients with a history of major bleeding (MB) are at high risk of future bleeding events; this history was an exclusion criterion in pivotal phase 3 trials of anticoagulation for stroke prevention. Real-world edoxaban effectiveness and safety in patients with a history of MB were analysed from the global ETNA programme. Purpose To compare edoxaban effectiveness and safety in AF patients with or without an MB history. Methods The Global ETNA-AF programme (EU: NCT02944019, Japan: UMIN000017011, South Korea/Taiwan: NCT02951039) integrates data from multiple prospective, observational, noninterventional regional studies of AF patients treated with edoxaban for stroke prevention. This snapshot analysis summarises global baseline characteristics and 2-year annualised rates of all-cause death, cardiovascular death, stroke (haemorrhagic, ischaemic, any), and bleeding (including MB, major gastrointestinal bleeding [MGIB], intracranial haemorrhage [ICH], clinically relevant nonmajor bleeding, and any bleeding) in patients with or without MB history. Results Data from 27,333 patients (479 with MB history and 26,854 without) from Europe, Japan, South Korea, and Taiwan were analysed. Patients with MB history were significantly older (P Conclusions Patients with AF receiving edoxaban and who have a history of MB are more likely elderly, male, and have comorbidities, including HF. These patients are also more susceptible to any adverse cardiovascular event. ICH event rates were not higher in patients with prior ICH than those with non-ICH major bleedings, whereas history of MGIB was associated with a high risk of MGIB recurrence. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo

Published
2022

21. [Research advances on the function of skin touch receptor Merkel cells]

Author

H P, Yuan, Y Y, Ding, Y X, Zheng, Y J, Zhang, X, Liu, C, Rui, C C, Wang, and Y, Xiao

Subjects
Touch, Animals, Mechanotransduction, Cellular, Ion Channels, Merkel Cells, Skin
Abstract

The reconstruction of tactile function during the repair of skin damage caused by factors including burns is inseparable from the functional regeneration of tactile receptor Merkel cells. Merkel cells mainly exist in the basal layer of the epidermis and are closely connected with nerves to form Merkel cell-nerve complexes, which play an important role in biological organisms. A large number of studies have shown that Merkel cells conduct precise transmission of mechanical force stimuli through the mechanically gated ion channels PIEZO2, and perform the function of tactile receptors. In this paper, we discussed the characteristics of Merkel cells and analyzed the different subgroups that may possibly exist in this type of cells and their functions, at the same time, we investigated the animal model research of touch-related diseases and the clinical diseases related to touch, revealing the importance of Merkel cell function research.在由烧伤等因素导致的皮肤损伤修复过程中，触觉功能的重建离不开触觉感受器默克尔细胞的功能再生。默克尔细胞主要存在于表皮基底层，与神经紧密相连形成默克尔细胞-神经复合体，在生物机体内发挥重要作用。大量研究表明默克尔细胞通过机械门控离子通道PIEZO2对机械力刺激进行精确传导，行使触觉感受器的功能。该文通过论述默克尔细胞的特征，分析该类细胞可能存在的不同亚群及其功能，同时调研了触觉相关疾病的动物模型研究和触觉相关的临床疾病，揭示了默克尔细胞功能研究的重要性。.

Published
2022

22. [Occurrence of gastric cancer after laparoscopic Roux-en-Y gastric bypass: a systematic review]

Author

S L, Dong, Y L, Liang, C C, Wang, and Z Y, Dong

Subjects
Esophageal Neoplasms, Stomach Neoplasms, Gastric Bypass, Humans, Laparoscopy, Obesity, Obesity, Morbid
Abstract

Laparoscopic Roux-en-Y gastric bypass (RYGB) is an important obesity surgery. The risk of remnant gastric cancer after RYGB for obesity is gaining growing attention from bariatric surgeons and patients with obesity. This systematic review included articles from major databases internationally and domestically that specifically described the remnant gastric cancer after RYGB intervention, a total of 21 cases was subsequently analyzed. The average median time from post-operative RYGB to diagnosis of gastric cancer was 11 years (1-28 years), the duration of gastric cancer symptoms lasted 7 days to 6 years, abdominal pain is the most common (71.4%), especially in the upper abdomen (33.3%), followed by nausea and vomiting (33.3%), over-weight loss (33.3%), and abdominal bloating (28.6%), etc. Neoplasm location was reported to occur in the antrum or the pre-pyloric region (71.4%), with adenocarcinoma being the most common tumor histology observed (71.4%), tumor stage III-IV as the most diagnosed, 38.1% of tumor were deemed to be unresectable, 52.4% of the patients performed subtotal gastrectomy and lymphadenectomy. In addition, a global article investigating the occurrence of esophageal gastric cancer after RYGB in 64 cases revealed the common preoperative medical history include smoking habits (37.5%), alcohol issues (14.0%), GERD (86.0%), presence with Barret esophagus (10.9%), patients that has other malignant tumor medical history (6.3%), first-degree relatives (6.3%), or other family members with gastric esophagus cancer family history. Although the incidence of gastric cancer after RYGB is rare, the increasing prevalence of gastric cancer development is one of great concern. A rise in clinical cases of patients treated with RYGB presents a target for future studies. Risk of gastric cancer after RYGB should be evaluated and considered in high-risk cases.腹腔镜Roux-en-Y胃旁路术（RYGB）是重要的减重术式之一。RYGB与残胃癌发生风险之间的关系，越来越受到减重外科医生以及肥胖症人群的关注。本文系统分析国内外主要医学数据平台与RYGB术后发生胃癌相关的文献发现，21例RYGB胃旁路术后相关胃癌的患者从接受RYGB到诊断为肿瘤的中位时间为11（1~28）年，症状的持续时间为7 d至6年，其中最常见的症状是腹痛（71.4%），尤其是上腹部（33.3%），其次为恶心和呕吐（33.3%）、体质量过度减轻（33.3%）以及腹胀（28.6%）等。肿瘤多位于胃窦或幽门（71.4%），腺癌是最常见的肿瘤组织类型（71.4%），以Ⅲ~Ⅳ期为主，38.1%的患者肿瘤无法完全切除，52.4%患者接受了胃次全切除术和淋巴结切除术。关于RYGB术后发生胃癌的术前病史，一项有关64例食管胃癌患者的全球性报道发现，常见术前病史包括抽烟（37.5%）、饮酒史（14.0%）、胃食管反流病症状（86.0%）、存在Barrett食管（10.9%）、有其他恶性肿瘤的个人病史（6.3%）、一级亲属（6.3%）或其他家族成员（1.6%）有胃食管恶性肿瘤的家族史。虽然RYGB术后胃癌的发生很少见，但随着越来越多的患者采用RYGB来治疗肥胖及其代谢病，需警惕高危患者术后发生肿瘤的风险。.

Published
2022

23. The International Space Station Environment Triggers Molecular Responses in Aspergillus niger

Author

Adriana Blachowicz, Jillian Romsdahl, Abby J. Chiang, Sawyer Masonjones, Markus Kalkum, Jason E. Stajich, Tamas Torok, Clay C. C. Wang, and Kasthuri Venkateswaran

Subjects
Microbiology (medical), Microbiology
Abstract

Due to immense phenotypic plasticity and adaptability, Aspergillus niger is a cosmopolitan fungus that thrives in versatile environments, including the International Space Station (ISS). This is the first report of genomic, proteomic, and metabolomic alterations observed in A. niger strain JSC-093350089 grown in a controlled experiment aboard the ISS. Whole-genome sequencing (WGS) revealed that ISS conditions, including microgravity and enhanced irradiation, triggered non-synonymous point mutations in specific regions, chromosomes VIII and XII of the JSC-093350089 genome when compared to the ground-grown control. Proteome analysis showed altered abundance of proteins involved in carbohydrate metabolism, stress response, and cellular amino acid and protein catabolic processes following growth aboard the ISS. Metabolome analysis further confirmed that space conditions altered molecular suite of ISS-grown A. niger JSC-093350089. After regrowing both strains on Earth, production of antioxidant—Pyranonigrin A was significantly induced in the ISS-flown, but not the ground control strain. In summary, the microgravity and enhanced irradiation triggered unique molecular responses in the A. niger JSC-093350089 suggesting adaptive responses.

Published
2022

27. Recurrent umbilical varix rupture with hemoperitoneum: a case report and review of literature

Author

W. S. Yu, M. H. Chang, H. L. Lee, Y. T. Lee, M. C. Tsai, and C. C. Wang

Subjects
Adult, Male, Varicose Veins, Carcinoma, Hepatocellular, Rupture, Spontaneous, Hemoperitoneum, Liver Neoplasms, Gastroenterology, Humans, General Medicine
Abstract

Background Non-traumatic hemoperitoneum was a rare event with the risk of sudden death. Spontaneous rupture of hepatocellular carcinoma is the most intuitive diagnosis when hemoperitoneum occurs in cirrhotic patients who are not regularly followed up. However, other etiologies of hemoperitoneum, such as intra-abdominal varix rupture, should be kept in mind. Case presentation A 44-year-old man with alcoholic liver cirrhosis, Child–Pugh B was sent to our emergency department (ED) because of recurrent abdominal pain and hypovolemic shock. He had similar symptoms one month ago and was diagnosed as hepatocellular carcinoma (HCC) rupture with hemoperitoneum, therefore he underwent trans-arterial embolization (TAE). However, the follow-up magnetic resonance imaging (MRI) showed less possibility of hepatocellular carcinoma. Contrast enhanced abdominal computed tomography (CT) showed possible umbilical vein contrast agent extravasation. Exploratory laparotomy confirmed the diagnosis of rupture umbilical varix with hemoperitoneum. Conclusion Although umbilical varix rupture is a rare cause of hemoperitoneum, it should be kept in mind in cirrhotic patients with unexplained hemoperitoneum.

Published
2022

28. An Aspergillus nidulans Platform for the Complete Cluster Refactoring and Total Biosynthesis of Fungal Natural Products

Author

Green Ahn, Shu-Lin Chang, Tzu-Shyang Lin, Yi-Ming Chiang, and Clay C. C. Wang

Subjects
Asperfuranone, biology, Chemistry, technology, industry, and agriculture, Biomedical Engineering, Total synthesis, General Medicine, respiratory system, biology.organism_classification, computer.software_genre, Biochemistry, Genetics and Molecular Biology (miscellaneous), chemistry.chemical_compound, Biochemistry, Biosynthesis, Code refactoring, Aspergillus nidulans, Heterologous expression, Pleuromutilin, Gene, computer, health care economics and organizations
Abstract

Fungal natural products (NPs) comprise a vast number of bioactive molecules with diverse activities, and among them are many important drugs. However, the yields of fungal NPs from native producers are usually low, and total synthesis of structurally complex NPs is challenging. As such, downstream derivatization and optimization of lead fungal NPs can be impeded by the high cost of obtaining sufficient starting material. In recent years, reconstitution of NP biosynthetic pathways in heterologous hosts has become an attractive alternative approach to produce complex NPs. Here, we present an efficient, cloning-free strategy for the cluster refactoring and total biosynthesis of fungal NPs in Aspergillus nidulans. Our platform places our genes of interest (GOIs) under the regulation of the robust asperfuranone afo biosynthesis gene machinery, allowing for their concerted activation upon induction. We demonstrated the utility of our system by creating strains that can synthesize high-value NPs, citreoviridin (1), mutilin (2), and pleuromutilin (3), with good to high yield and purity. This platform can be used not only for producing NPs of interests (i.e., total biosynthesis) but also for elucidating cryptic biosynthesis pathways.

Published
2020

33. Genomic Characterization of Potential Plant Growth-Promoting Features of Sphingomonas Strains Isolated from the International Space Station

Author

Jonathan Lombardino, Swati Bijlani, Nitin K. Singh, Jason M. Wood, Richard Barker, Simon Gilroy, Clay C. C. Wang, and Kasthuri Venkateswaran

Subjects
Microbiology (medical), Infectious Diseases, General Immunology and Microbiology, Ecology, Physiology, Genetics, Cell Biology
Abstract

Sphingomonas is ubiquitous in nature, including the anthropogenically contaminated extreme environments. Members of the Sphingomonas genus have been identified as potential candidates for space biomining beyond earth.

Published
2022

34. Genomic Characterization of Potential Plant Growth-Promoting Features of

Author

Jonathan, Lombardino, Swati, Bijlani, Nitin K, Singh, Jason M, Wood, Richard, Barker, Simon, Gilroy, Clay C C, Wang, and Kasthuri, Venkateswaran

Subjects
plant growth promotion, Indoleacetic Acids, Whole Genome Sequencing, Plant Development, Genomics, Sphingomonas, International Space Station, phytohormones, Plant Growth Regulators, RNA, Ribosomal, 16S, Metagenome, Metagenomics, Spacecraft, Phylogeny, Research Article
Abstract

In an ongoing microbial tracking investigation of the International Space Station (ISS), several Sphingomonas strains were isolated. Based on the 16S rRNA gene sequence, phylogenetic analysis identified the ISS strains as Sphingomonas sanguinis (n = 2) and one strain isolated from the Kennedy Space Center cleanroom (used to assemble various Mars mission spacecraft components) as Sphingomonas paucimobilis. Metagenomic sequence analyses of different ISS locations identified 23 Sphingomonas species. An abundance of shotgun metagenomic reads were detected for S. sanguinis in the location from where the ISS strains were isolated. A complete metagenome-assembled genome was generated from the shotgun reads metagenome, and its comparison with the whole-genome sequences (WGS) of the ISS S. sanguinis isolates revealed that they were highly similar. In addition to the phylogeny, the WGS of these Sphingomonas strains were compared with the WGS of the type strains to elucidate genes that can potentially aid in plant growth promotion. Furthermore, the WGS comparison of these strains with the well-characterized Sphingomonas sp. LK11, an arid desert strain, identified several genes responsible for the production of phytohormones and for stress tolerance. Production of one of the phytohormones, indole-3-acetic acid, was further confirmed in the ISS strains using liquid chromatography-mass spectrometry. Pathways associated with phosphate uptake, metabolism, and solubilization in soil were conserved across all the S. sanguinis and S. paucimobilis strains tested. Furthermore, genes thought to promote plant resistance to abiotic stress, including heat/cold shock response, heavy metal resistance, and oxidative and osmotic stress resistance, appear to be present in these space-related S. sanguinis and S. paucimobilis strains. Characterizing these biotechnologically important microorganisms found on the ISS and harnessing their key features will aid in the development of self-sustainable long-term space missions in the future. IMPORTANCE Sphingomonas is ubiquitous in nature, including the anthropogenically contaminated extreme environments. Members of the Sphingomonas genus have been identified as potential candidates for space biomining beyond earth. This study describes the isolation and identification of Sphingomonas members from the ISS, which are capable of producing the phytohormone indole-3-acetic acid. Microbial production of phytohormones will help future in situ studies, grow plants beyond low earth orbit, and establish self-sustainable life support systems. Beyond phytohormone production, stable genomic elements of abiotic stress resistance, heavy metal resistance, and oxidative and osmotic stress resistance were identified, rendering the ISS Sphingomonas isolate a strong candidate for biotechnology-related applications.

Published
2022

36. Natural products development under epigenetic modulation in fungi

Author

Fang Rong Chang, Chi-Ying Li, Attila Hunyadi, Clay C. C. Wang, Yang Chang Wu, and Yu-Ming Chung

Subjects
0106 biological sciences, chemistry.chemical_classification, Plant Science, Computational biology, Biology, 01 natural sciences, DNA methyltransferase, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Clinical therapy, Enzyme, chemistry, Histone deacetylase, Epigenetics, Natural Product Research, Gene, High potential, 010606 plant biology & botany, Biotechnology
Abstract

Natural products derived from microorganisms play a key role in the discovery and development of drug candidates. Several drugs have originated from secondary metabolites or their derivatives from microorganisms in clinical therapy, such as penicillin, cyclosporine, and lovastatin. Application of epigenetic methodology on modulation and stimulation of secondary metabolites from fungi provides a practical way to investigate fungal natural products. Addition of enzyme inhibitors such as histone deacetylase (HDAC) or DNA methyltransferase (DNMT) inhibitors to activate silent biosynthetic gene clusters result in the potential for generating a variety of secondary metabolites with novel skeletons and diversity of stereochemistry, as well as unprecedented heterocyclic rings. After triggering the epigenetic modifiers, some species were affected and produced several uncovered secondary metabolites. Although this strategy has been successfully carried out for few reports, the results of this research field have demonstrated high potential for engineering the secondary metabolites from fungi. By utilizing the above strategy, modulation and characterization of the secondary metabolites from fungi make them able to generate several novel or bioactive natural products that will provide sources for discovering new candidates. Furthermore, the epigenetic modulation technique integrated with pharmacological assays for further investigation becomes a promising avenue for improvement of natural products research and development. This review summarizes the progression and development of epigenetic manipulation in fungal natural product research.

Published
2020

37. Effect of grain boundary precipitation on corrosion of heating-aging treated Al-4.47Zn-2.13Mg-1.20Cu alloy

Author

J.C. Huang, Zijun Zhao, Xu Wang, C. C. Wang, M. Wu, Diyao Zhang, and Xinyi Liu

Subjects
lcsh:TN1-997, Materials science, Diffusion, Alloy, Precipitation, 02 engineering and technology, engineering.material, Electrochemistry, 01 natural sciences, Corrosion, Biomaterials, Intergranular corrosion, 0103 physical sciences, lcsh:Mining engineering. Metallurgy, Heating-aging treatment, 010302 applied physics, Precipitation (chemistry), Metallurgy, Metals and Alloys, Al–Zn–Mg–Cu wrought alloy, 021001 nanoscience & nanotechnology, Surfaces, Coatings and Films, Transmission electron microscopy, Ceramics and Composites, engineering, Grain boundary, 0210 nano-technology
Abstract

To thoroughly explore the relationship between precipitation and corrosion in a precipitation-strengthened Al-4.47Zn-2.13Mg-1.20Cu (wt%) wrought alloy plate after a nonisothermal aging (NIA) treatment, specifically, a heating-aging treatment (HAT), electrochemical testing and transmission electron microscopy (TEM) were conducted in the present work. The H(5) process exhibited excellent corrosion resistance with a low corrosion current density (icorr) and a high corrosion potential (Ecorr) compared to those for the T6 treatment. After the HAT, the precipitates at the grain boundaries (GBs) gradually became intermittent with a narrow precipitate-free zone (PFZ), effectively preventing GBs precipitates from anodic dissolution. The HAT enabled the rapid diffusion and enrichment of Cu at the GBs and reduced the potential difference between the grain boundary and matrix, thereby decreasing the intergranular corrosion (IGC) susceptibility. Moreover, the time spent for a HAT can be decreased by approximately 70% in comparison with that for a T6 treatment. The current results indicate that NIAs could improve the mechanical properties and production efficiency with a decreased energy consumption.

Published
2020

38. Genomic Characterization of the Titan-like Cell Producing

Author

Swati, Bijlani, Ceth, Parker, Nitin K, Singh, Maria A, Sierra, Jonathan, Foox, Clay C C, Wang, Christopher E, Mason, and Kasthuri, Venkateswaran

Abstract

Multiple strains of a novel yeast belonging to genus

Published
2021

40. [Mixed tall cell variant and cribriform morular variant of papillary thyroid carcinoma: report of a case]

Author

C C, Wang, R X, Cao, B B, Jiang, and X H, Liu

Subjects
Thyroid Cancer, Papillary, Humans, Thyroid Neoplasms, Carcinoma, Papillary
Abstract

混合高细胞-筛状桑葚亚型（TCV-CMV）是甲状腺乳头状癌（PTC）罕见亚型。仔细的细胞学、组织学观察及特异的免疫组织化学染色有助于作出正确诊断。高细胞亚型PTC（TCV-PTC）是侵袭性亚型之一，术前及术中准确诊断有助于手术方案的合理选择及预后判断。筛状桑葚亚型PTC（CMV-PTC）有独特的病理、免疫组织化学及分子特征，也是遗传性甲状腺癌的典型亚型，可提示临床医师进行结肠镜检查、遗传咨询和家庭成员筛选。CMV-PTC多数预后较好，当出现不良预后指征时，警惕其复发及转移可能。.

Published
2021

41. Measurement of differential tt¯ production cross sections in the full kinematic range using lepton+jets events from proton-proton collisions at s=13 TeV

Author

Aliaksandr Litomin, Andrew Askew, Aliakbar Ebrahimi, Nicholas Haubrich, Rachel Yohay, Giancarlo Mantovani, J. K. Lim, F. Simonetto, I. Gonzalez Caballero, Shabnam Jabeen, T. Aushev, Parker Gardner, Dmytro Kovalskyi, V. Kutzner, Ram Krishna Dewanjee, Frank Chlebana, L. V. Kardapoltsev, K. Gill, Amitabh Lath, Giovanni Organtini, Paolo Lariccia, A. Baden, Alexandre Zabi, Alessia Saggio, M. Barrio Luna, Cilicia Uzziel Perez, Paolo Spagnolo, P. Gras, Ivan Ovtin, Gyorgy Vesztergombi, Kenneth Long, Frank Jm Geurts, Xuli Yan, B. V. Sathia Narayanan, Claudio Quaranta, Dan Quach, Lindsey Gray, David Petyt, Smarajit Karmakar, Elizabeth Locci, Arnaud Steen, Thomas Reitenspiess, R. F. Von Cube, Riccardo Andrea Manzoni, M. H. Schmitt, Uttiya Sarkar, M. A. Shah, F. Pandolfi, Alicia Calderon, Derek James Cranshaw, Alberto Belloni, Tariq Aziz, David Krofcheck, S. Tkaczyk, David Stuart, Alice Mignerey, A. Benecke, Andrius Juodagalvis, Inna Makarenko, Victor Shang, Fabio Iemmi, Sebastian Wieland, Teruki Kamon, Dmitry Elumakhov, Piet Verwilligen, Guillaume Bourgatte, Malte Backhaus, Evgueni Vlasov, Daniel Savoiu, Y. J. Mao, Chiara Mariotti, Marco Monteno, Boaz Klima, S. Fonseca De Souza, J. F. de Trocóniz, G. G. Hanson, Kenneth Osterberg, Ohannes Kamer Köseyan, Attilio Santocchia, Jean Fay, Fanbo Meng, P. Lenzi, S. V. Afanasiev, Marko Dragicevic, Weinan Si, Mikko Lotti, Georgios Anagnostou, Maxwell Chertok, R. Mulargia, Ulrich Heintz, M. Kovac, Bjorn Burkle, Grigory Pivovarov, S. Slabospitskii, Gianny Mestdach, E. Eskut, Federico Siviero, Pavel Parygin, J. S. Kim, Michael Tytgat, Kaori Maeshima, Martin Erdmann, G. Correia Silva, Seema Bahinipati, Sushrut Karmarkar, Andrew Buccilli, Runyu Bi, Robin Erbacher, Alessio Boletti, Senta Greene, C. Baldenegro Barrera, Chayanit Asawatangtrakuldee, Rogelio Reyes-Almanza, V. Avati, Marc Huwiler, Daniele Spiga, Philip Keicher, Vladimir Epshteyn, Angelo Giacomo Zecchinelli, Junquan Tao, O. Kukral, Francesca Romana Cavallo, George Karathanasis, S. B. Oh, Alexander Malakhov, O. Davignon, Kerstin Borras, Diana Seitova, Giacomo Fedi, J. Alexander, G. M. Bilei, Pawan Kumar Netrakanti, Gabriel Madigan, Angela Giraldi, G. P. Van Onsem, Metin Yalvac, Stephan Lammel, Andrew Wisecarver, Daniel Noonan, S. Mukherjee, Danek Kotlinski, Jordan Martins, M. Alhusseini, A. Melo, G. S. Chahal, Catherine Schiber, W. Jang, Dylan Teague, Tengizi Toriashvili, Tamer Elkafrawy, Markus Spanring, A. B. Meyer, N. De Filippis, Alessandro Calandri, Qianying Guo, O. Hlushchenko, Mitchell Wayne, Karol Bunkowski, A.-M. Lyon, Kurtis F Johnson, Günter Flügge, Greg P Heath, Danyyl Brzhechko, M. Naimuddin, R. Granier de Cassagnac, Maxime Gouzevitch, Christoph Schäfer, Alexander Grohsjean, Benjamin Bordy Tannenwald, Salim Cerci, O. Cerri, Lev Uvarov, Z. Tsamalaidze, Rajdeep Mohan Chatterjee, C. Fernandez Madrazo, Tiziano Rovelli, Alberto Ruiz-Jimeno, Tanvi Wamorkar, Taha Beyrouthy, Robert Clare, Lucas Torterotot, Patrizia Azzi, Prabhat Ranjan Pujahari, Q. Wang, Jingyan Li, Urs Langenegger, Kevin Black, Gabriel Ramirez-Sanchez, Georgy Antchev, B. C. Choudhary, Dirk Krücker, Gianluca Cerminara, Nhan Viet Tran, Mohammad Abrar Wadud, Yao Yao, O. Gonzalez Lopez, J. Wang, Brendan Regnery, Zhibo Wu, Natasa Raicevic, Liliana Teodorescu, Michele Bianco, Patricia McBride, J. C. Williams, Krzysztof Doroba, Dylan Rankin, Andrew Brinkerhoff, Animesh Datta, Thomas Ferguson, Gianni Zumerle, Klaas Padeken, Peter Meiring, Eshwen Bhal, Jose Flix, E. Meschi, James John Brooke, Georg Auzinger, Sadia Khalil, S. Van Putte, Ali Awais, Didar Dobur, Vyacheslav Valuev, S. Goy Lopez, K. B. Lee, Kadir Ocalan, Maria Agnese Ciocci, Ioanna Papavergou, David Sperka, Wolfram Erdmann, Thomas Hebbeker, Paul Lecoq, Ren-Yuan Zhu, Wolfgang Waltenberger, L. Hay, Alexis Kalogeropoulos, Olivér Surányi, Pascal Vanlaer, Richard Breedon, Stefan Grünendahl, Martina Malberti, Diogo Bastos, C. Oropeza Barrera, P. Busson, Kyungwook Nam, S. M. Spanier, Robert Schöfbeck, Olena Karacheban, Abraham Tishelman-Charny, V. Milosevic, Shubham Pandey, Wei Shi, O. Rieger, Thomas Klijnsma, W. S. Hou, Nadezda Chernyavskaya, Nathaniel Odell, J. Berenguer Antequera, Pritam Kalbhor, Crisostomo Sciacca, Baokai Wang, M. Dordevic, A. De Roeck, Katerina Lipka, Martin Kirakosyan, Anup Kumar Sikdar, Gerry Bauer, A.N. Kozyrev, Cheng-Chieh Peng, S. Mersi, Patrick Bryant, David Colling, Amina Zghiche, Samuel May, Emily MacDonald, Paul Sheldon, M. Aldaya Martin, Jindrich Lidrych, Harvey B Newman, J. D. Tapia Takaki, V. Matveev, Juska Pekkanen, Sa. Jain, A. Penzo, Fabrice Couderc, J. Thieman, Philip Harris, D. Matos Figueiredo, K. Ehataht, A. J. Campbell, A. David, Ksenia Shchelina, Steffie Ann Thayil, Andrew Gilbert, Santiago Folgueras, Ridhi Chawla, V. K. Muraleedharan Nair Bindhu, Bugra Bilin, Christoph Garbers, Muhammad Ansar Iqbal, Luc Pape, Simone Scarfi, David Saltzberg, Kati Lassila-Perini, Dongjoon Song, Petra Merkel, William Arthur Nash, Arnab Laha, Khawla Jaffel, Si Xie, Jean-Charles Fontaine, Anton Dimitrov, Vinicius Massami Mikuni, Balazs Ujvari, Moritz Guthoff, Luciano Di Fiore, Didier Contardo, Reham Aly, K. Vellidis, E. Di Marco, Gaël Touquet, Jeremi Niedziela, Werner Lustermann, Andromachi Tsirou, Clément Grimault, A. Kayis Topaksu, H. A. Salazar Ibarguen, Maria Savina, Rohith Saradhy, M Nickel, Maciej Malawski, Debarati Roy, Teresa Rodrigo, Robert Stone, A. Starodumov, Frank Jensen, Sinan Sagir, Nicolaus Kratochwil, Anton Karneyeu, Ugo Gasparini, A. Di Pilato, James Strait, Meenakshi Narain, J. León Holgado, Leonardo Giannini, Kinga Anna Wozniak, Norbert Neumeister, Kai Wei, Stephen Sanders, Nicholas Wardle, Corrinne Mills, Tao Huang, Viktor Savrin, Cristina Fernandez Bedoya, Isabel Pedraza, D. J. Hofman, M. Vander Donckt, Dave M. Newbold, Jochen Schieck, N. Redaelli, Paolo Azzurri, Giacomo Bruno, Ian Mcalister, Antonio Cassese, Anna Tsatsos, T. A. Gómez Espinosa, Carlos Erice, Simone Calzaferri, K. S. Lee, Sudha Ahuja, R. Taus, Austin Townsend, M. Della Negra, S. Sharma, Joshua Hiltbrand, Maria Isabel Josa, M. Tadel, Eva Halkiadakis, SeongMoo Yang, Frank Glege, Debabrata Bhowmik, Conor Henderson, A. Hervé, Christina Snyder, H. Becerril Gonzalez, Konstantin Matchev, J. J. Hollar, Igor Bayshev, Vasken Hagopian, Xavier Coubez, G. M. Dallavalle, Egidio Longo, Hideki Okawa, Bhargav Madhusudan Joshi, Georgios Krintiras, Anna Stakia, Sébastien Wertz, Savvas Kyriacou, Raghav Kansal, Salvatore Rappoccio, L. Kreczko, Loukas Gouskos, Maksim Azarkin, J. Alcaraz Maestre, Krisztián Farkas, Isa Dumanoglu, Y. Gershtein, Zeynep Demiragli, Marina Kolosova, Nicolo Cartiglia, Chiara Amendola, A. Di Florio, Yalcin Guler, A. De Wit, Frans Meijers, Stephen Trembath-Reichert, Hessamoddin Kaveh, Sascha Pascal Liechti, Edward Scott, Gregor Kasieczka, Adel Terkulov, Neha Rawal, Y. Chao, L. S. Durkin, A. Samalan, Gianni Masetti, Natalia Lychkovskaya, Sam Harper, A. Gurtu, Timo Peltola, Y. Wang, Carlo Rovelli, Wagner Carvalho, Silvio Donato, Vladimir Palichik, A. K. Virdi, Sourabh Dube, C. S. Moon, Caglar Zorbilmez, P. C. Tiwari, Kathryn Coldham, Vladimir Karjavine, Antoine Lesauvage, Geetanjali Chaudhary, Georgios Bakas, F. Vazquez Valencia, Abhirami Harilal, Zhen Lin, Alexander Nikitenko, Jasvinder A. Singh, M. Rahmani, Dipanwita Dutta, S. Wunsch, Emrah Tiras, Caleb Fangmeier, D. W. Kim, Ryan White, Martin Delcourt, Francesco Fallavollita, Simon Fayer, Julie Managan Hogan, Sridhara Dasu, Nicolas Stylianou, Alexey Volkov, Bolek Wyslouch, Mehmet Kaya, S. Ha, Intae Yu, Adish Vartak, Anna Elliott-Peisert, Vuko Brigljevic, Lucia Silvestris, David Taylor, L. Zhang, S. Sanchez Cruz, Lucas Corcodilos, Andrea Massironi, Shane Breeze, Iban Jose Cabrillo, Tribeni Mishra, Charalambos Nicolaou, M. Mendizabal Morentin, Jingyu Luo, Daniele Bonacorsi, Brian L Winer, Sercan Sen, D. P. Stickland, Leonardo Lunerti, M. Bharti, V. Sola, A. Escalante Del Valle, A. Rose, Emilien Chapon, M. R. Di Domenico, Claudia Pistone, Dong Yu, H. El Mamouni, Vittorio Raoul Tavolaro, I. O. Atakisi, W. E. Johns, Sándor Lökös, H. El Faham, Alexey A. Petrov, Elham Khazaie, K. De Leo, Shuichi Kunori, Ilia Zhizhin, Sandeep Bhowmik, Amandeep Kaur Kalsi, M. Magherini, Roger Wolf, Antonin Kveton, Mauro Menichelli, Tamás Álmos Vámi, A. Da Rold, Roland Horisberger, Michele Arneodo, Garvita Agarwal, Alexei Raspereza, G. B. Yu, Giorgio Apollinari, Christoph Heidecker, Xudong Lyu, Kristian Harder, Francesco Navarria, Amandeep Singh Bakshi, Aurélien Carle, Peicho Petkov, Douja Darej, J. Prisciandaro, Harry Cheung, Stepan Obraztsov, Fotios Ptochos, Zhen Hu, W. Haj Ahmad, Zoltan Laszlo Trocsanyi, D. Del Re, Jeremy Andrea, P. Bloch, Mehmet Özgür Sahin, Donato Creanza, Vincent Lemaitre, K. Wichmann, P. Kyberd, S. N. White, Joshuha Thomas-Wilsker, J. A. Murillo Quijada, Maria Spiropulu, Redwan Habibullah, Valerie Scheurer, Kajari Mazumdar, Christian Dorfer, Morris Swartz, Josry Metwally, Aran Garcia-Bellido, Nils Faltermann, Hans Rykaczewski, Vladyslav Danilov, Hong Ni, W. T. Ford, P. J. Fernández Manteca, Ka Tung Lau, Umberto Dosselli, Gage Dezoort, M. Gola, Michael Revering, Leonid Didukh, S. Luo, Brieuc Francois, Furkan Dolek, Franco Ligabue, P. N. Y. David, Matthew Herndon, Julia Velkovska, Christopher George Tully, Halil Saka, D. Cutts, Ugur Kiminsu, Kelci Mohrman, Luca Guzzi, Davide Fiorina, Pierluigi Zotto, Martin Wolf, V. N. Ivanchenko, K. J. R. Cormier, M. Tornago, G. Maggi, Giuseppe Barbagli, Salvatore Nuzzo, Martina Vit, Sh. Jain, Lorenzo Bianchini, Martti Raidal, Vasilije Perovic, Mei-li Holmberg, Thomas James, Sevgi Tekten, Jovan Milosevic, Apostolos Panagiotou, Benjamin Kilminster, Hyun-Soo Kim, Benjamin Fischer, Ricardo Lopez-Fernandez, K. M. Ecklund, A. Canepa, Rui Zou, Anastasia Grebenyuk, Maksym Titov, Federico Ferri, Artur Apresyan, Marc Besancon, C. Chen, Dinyar Rabady, Jan Steggemann, Wolfram Dietrich Zeuner, Christopher West, Jonas Roemer, T. Boccali, Maurizio Pierini, Priyanka Kumari, David Cussans, S. K. Park, Peter Robmann, Ralf Ulrich, Tiziano Camporesi, L. Brigliadori, Shivali Malhotra, Brent Stone, Isabel Ojalvo, Youn Roh, Douglas Berry, Barry Blumenfeld, Igor Azhgirey, T. V. Dimova, Samuel Baxter, Salvatore Buontempo, Frank Golf, Robert Hirosky, F. Wang, A. Pérez-Calero Yzquierdo, Márton Bartók, Nicolas Chanon, S. Lo Meo, Alexx Perloff, Alexander Belyaev, W. Snoeys, Michael Benjamin Andrews, Stephanie Brandt, R. Mankel, Wolfgang Lohmann, Simone Paoletti, Abhijith Gandrakota, Giulio Mandorli, C. Mcgrady, Anne-Marie Magnan, Leszek Grzanka, Achille Petrilli, Greg Landsberg, J. Zhang, Manjit Kaur, Sitong An, S. Bansal, Louise Skinnari, Hannu Siikonen, Sheng Wang, M. I. Asghar, Alexander Toropin, P. K. Behera, Paul Baillon, Andrea Carlo Marini, Duong Nguyen, Ilknur Hos, Johann Rauser, Alexander Tapper, Anna Colaleo, Milos Vojinovic, Yildiray Komurcu, Pierluigi Bortignon, Guido Tonelli, Yasser Maghrbi, Zeljko Antunovic, Andrej Saibel, Antonello Pellecchia, Christine Mclean, M. Choi, Shirin Chenarani, M. M. Obertino, Jozsef Molnar, Y. Ban, Bennett Marsh, Nicola Minafra, Johannes Schulz, Geonhee Oh, Marcus Hohlmann, Roger Rusack, F. X. Yumiceva, Tielige Mengke, Juliette Alimena, Paul Asmuss, Nan Lu, Dennis Schwarz, Ekaterina Kuznetsova, Hevjin Yarar, Diwakar Vats, I. J. Watson, Mattia Lizzo, Silvia Maselli, Ioannis Papadopoulos, Unki Yang, David Seith, R. Frühwirth, K. W. Bell, E. A. De Wolf, P. G. Mercadante, Prasant Kumar Rout, Jean-Louis Faure, Z. Y. You, J. Almond, Laurits Tani, Liam Wezenbeek, Yuta Takahashi, A Dodonova, Sioni Summers, James Bueghly, Matthew Nguyen, V. Rodríguez Bouza, E. Gurpinar Guler, J. W. Berryhill, Matthias Schnepf, Robin Aggleton, M. Barroso Ferreira Filho, L. J. Gutay, V. E. Blinov, Grace Cummings, Camelia Mironov, A. A. Savin, Rudy Ceccarelli, Benedikt Vormwald, Gillian Kopp, Daniel Rosenzweig, Hans-Christian Kaestli, A. H. Merrit, Irene Dutta, Shawn Zaleski, Neil Schroeder, Sumit Keshri, J. L. Dulemba, G. Boudoul, M. Fernandez, S. Somalwar, Pedrame Bargassa, Bekhzod S Yuldashev, Vyacheslav Krutelyov, Maria Florencia Canelli, Deborah Pinna, Altan Cakir, Cecilia Elena Gerber, Riccardo Paramatti, Andrea Giammanco, Francesco Fienga, Rishi Patel, Y. D. Oh, Fabrizio Palla, R. Demina, Michael Pitt, Gilvan Alves, M. Pelliccioni, C. Foudas, G. L. Pinna Angioni, Marco Pieri, Cesar Augusto Bernardes, Miranda Bryson, Vinzenz Stampf, Konstantinos Kousouris, Arne Reimers, Joshua Bendavid, M. Vanden Bemden, Nicanor Colino, Y. Chen, Patrick Asenov, A. Roy, M. Weber, Aruna Nayak, J. H. Yoo, P. Martinez Ruiz del Arbol, James Dolen, Konstantinos Manolopoulos, Yeonju Go, W. A. T. Wan Abdullah, Yongjae Lee, Jason Gilmore, C. Collard, Freya Blekman, David Michael Morse, L. Layer, G. Hamel de Monchenault, Aditee Rane, B. Jayatilaka, Ettore Focardi, Marco Paganoni, Emanuela Barberis, J. N. Butler, Mikkel B. Johnson, Mia Tosi, J. Bonilla, A. Sanchez, L. Romero, Prashant Shukla, Efe Yigitbasi, A. Bocci, Jay Dittmann, Nikolay Voytishin, K. H. M. Kwok, Kira Burt, Simon Christoph Schuler, János Karancsi, Marijus Ambrozas, Anna Teresa Meneguzzo, James Sheplock, Z. Chen, Dmitry Sosnov, D. Horvath, Robert Bainbridge, Gobinda Majumder, Alain Givernaud, H. Rejeb Sfar, Jane Nachtman, Sergio F Novaes, Kevin Burkett, Morgan Lethuillier, Yasar Onel, Eleni Erodotou, Amedeo Staiano, Ignacio Redondo, Dylan Lutton, Yurii Maravin, Vladimir Gavrilov, H. Sert, Anterpreet Kaur, Don Lincoln, Li Yuan, Nancy Marinelli, De Hua Zhu, Samet Lezki, J. S. Conway, Gervasio Gomez, A. Delgado Peris, Marta Cremonesi, Hulin Wang, K. Wong, Yen-Jie Lee, A. Ahmad, Louis Lyons, W. De Boer, Jory Sonneveld, Simon Kwan, Michael Dittmar, Joona Havukainen, Alessandro Cardini, P. Das, Diego Beghin, Maria Toms, E. De La Cruz-Burelo, Oleg Teryaev, I. Babounikau, A. Ranieri, Izzeddin Suat Donertas, Livia Soffi, Jacob Linacre, Christopher Seez, Bernard Ille, Ali Mohammadi, Matthew Kilpatrick, Dinko Ferencek, Atanu Modak, Marco Cipriani, Peter Elmer, M. K. Jayananda, Marcella Diemoz, Mikhail Dubinin, Wei Li, Giovanni Petrucciani, Suzanne Rosenzweig, Tobias Kramer, Ketino Kaadze, Evgueni Tcherniaev, K. A. Ulmer, Vitalii Okhotnikov, Petar Adzic, Charis Kleio Koraka, R. S. P. Mueller, Muhammad Gul, P. Van Mulders, Hugues Lattaud, Z. Ye, E. W. Vaandering, André Rosowsky, Andrew Ivanov, Siarhei Shulha, H. Aarup Petersen, V. Re, David Zou, Finn Feindt, Suat Ozkorucuklu, John Strologas, J. Fernandez Menendez, Paolo Gunnellini, Wei Xie, Rainer Wallny, Andrey Korytov, Nairit Sur, P. Chang, Helen F. Heath, Plamen Iaydjiev, Michael Lukasik, Mauro Donegà, Pierluigi Paolucci, R. M. Harris, V. Papadimitriou, Y. Kang, S. Sarkar, Salavat Abdullin, Tommaso Tedeschi, Jona Motta, Daniel Robert Marlow, Tahir Javaid, M. Lazarovits, Luigi Calligaris, Eduardo De Moraes Gregores, Michael Oshiro, I. R. Tomalin, M. J. Costa, Tyler Lam, Nadja Strobbe, Jean-Laurent Agram, G. Paspalaki, Steven F. Maier, Dimitrios Karasavvas, Francesco Setti, Igor Volobouev, I. Dremin, Sergio P. Ratti, P. D. Dauncey, A. Castro, J. R. González Fernández, Hongbo Liao, Aleko Khukhunaishvili, Manfred Jeitler, S. Lowette, D. H. Kim, Owen Baron, Vivekanand Jha, Steve Schnetzer, Renato Campanini, Oliver Pooth, Prafulla Saha, C. S. Rogan, Werner Sun, Santeri Laurila, Stefano Marcellini, Alexandra Tews, Spandan Mondal, A. C. Le Bihan, Sandor Czellar, Alexei Safonov, Christian Dziwok, Juliet Ritchie Patterson, Mikhail Kirsanov, G. De Lentdecker, R. Cousins, B. De La Cruz, Samuel Higginbotham, R. M. Brown, Salvatore Costa, J. Puerta Pelayo, Indara Suarez, Scarlet Norberg, Devdatta Majumder, Leonardo Cristella, Joao Varela, Aristotelis Kyriakis, Piero Giorgio Verdini, Ivan Amos Cali, A. Carvalho Antunes De Oliveira, Rosamaria Venditti, Leander Litov, Jean-Pierre Merlo, Michele Gallinaro, Yves Sirois, Chiara Aime, Salvatore My, Giovanni Franzoni, Hyonsan Seo, Rachael Bucci, Y. Musienko, Joseph Reichert, C. Martin Perez, P. H. Butler, Tommaso Isidori, Niels Dupont, Roland Koppenhöfer, Zuhal Seyma Demiroglu, Felipe Ramirez, Berkan Kaynak, Melissa Quinnan, Vladimir Korenkov, D. Pérez Adán, C. 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Madrid, Francesca Maria Addesa, Ian Laflotte, A. Vagnerini, S. Kaur, Marius Metzler, Marc Osherson, Roy Montalvo, Thomas Bergauer, A. Vorobyev, Livio Fanò, A. Bragagnolo, John Lawrence, Stefaan Tavernier, Sarah Freed, Andrea Perrotta, Timothy Koeth, Jan Krolikowski, Luiz Mundim, C.-E. Wulz, Duccio Abbaneo, Matteo Bonanomi, Kamal Lamichhane, S. M. Silva Do Amaral, Christophe Ochando, P. Rebello Teles, Leonard Spiegel, Najaf Amin, A. Braghieri, Erik Butz, Oleksandr Viazlo, Y. I. Skovpen, Giulia Sorrentino, Kamuran Dilsiz, Francesco Santanastasio, Stoyan Stoynev, Semra Turkcapar, Linda Finco, Francesco Romeo, Robert Klanner, Paolo Giacomelli, Sergey Polikarpov, Helio Nogima, U. Joshi, S. Nandan, A. De Iorio, G. W. Wilson, Pietro Vischia, W. H. Smith, Seyed Mohsen Etesami, M. Presilla, Elif Asli Yetkin, Dmitry Eliseev, Francisco Matorras, S. Banerjee, T. L. Cheng, Mary Hadley, Jan Kieseler, Laurent Forthomme, Giulia Negro, A. 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Savoy-Navarro, Alexander Pauls, J. W. Gary, Paolo Rumerio, Simone Gennai, Jeremy Mans, C. Ramón Álvarez, D. E. Pellett, Patrick Jarry, Marius Teroerde, Laurent Pétré, Konstantinos Theofilatos, P. Kontaxakis, Manuel Giffels, Guo-Ming Chen, Mohammad Hassan Hassanshahi, Arabella Martelli, Muhammad Ahmad, N. Bin Norjoharuddeen, Helena Bialkowska, Niki Saoulidou, Mia Liu, Nur Zulaiha Jomhari, Vivian O'Dell, Charlotte Cooke, Ernesto Migliore, Hans-Jürgen Simonis, Todd Adams, Andrew Wightman, Wit Busza, Jacobo Konigsberg, J. F. Benitez, Georgia Karapostoli, Bryan Cardwell, Florian Joel J Bury, Meena Meena, Alexander Fröhlich, Davide Valsecchi, Christine Nielsen, D. A. Sanz Becerra, R. Salvatico, J. A. Nash, Elisabetta Gallo, Tomas Kello, Kenneth Bloom, Henri Petrow, M. C. Fouz, Lukas Lechner, Andreas Nürnberg, Prasanna Siddireddy, H. Brandao Malbouisson, T. Geralis, Mateusz Zarucki, Antoni Shtipliyski, G. Quast, Emery Nibigira, A. Khan, Erich Schmitz, Lutz Feld, Shaun Hogan, V. P. 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Petrushanko, Giuseppe Benedetto Cerati, Barbara Clerbaux, Rishabh Uniyal, Giuseppe Latino, Dylan Apparu, Alessandro Giassi, F. Gasparini, John Paul Chou, Brian Paul Padley, M. R. Adams, Sotiroulla Konstantinou, T. R. Fernandez Perez Tomei, F. De Guio, Daniel Abercrombie, J. Piedra Gomez, Irene Zoi, Gregory Iles, Cristina Tuve, Stefanos Leontsinis, R. G. Kellogg, M. Guchait, Alexis Pompili, Ang Li, K. Pedro, Muhammad Imran Malik Awan, Jennifer Ngadiuba, Giovanna Selvaggi, Yongbin Feng, Y. D. Kim, Henning Flacher, J. Wanczyk, Wolfgang Adam, A. Álvarez Fernández, R. Kumar Verma, Nikolaos Manthos, Michael Krohn, Kun Shi, Lorenzo Vigilante, Martin Grunewald, Oleg Prokofyev, Alp Akpinar, M. B. Tonjes, Serguei Ganjour, Danilo Meuser, Darien Wood, A. J. Hart, Marc Dünser, Jyothsna Rani Komaragiri, Janek Bechtel, Konstantin Shchablo, Claudio Caputo, J. Pata, Nicholas John Hadley, Y. Zhang, Jehad Mousa, Yangyang Cheng, Bennett Greenberg, Manfred Paulini, A. Rizzi, Maral Alyari, A. 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Dinardo, Alexi Mestvirishvili, Sema Zahid, Dominic Stafford, Sergei Gleyzer, Ying An, Massimo Casarsa, Steve Nahn, Wren Vetens, Marco Meschini, Andrea Venturi, M. Khakzad, Rino Castaldi, Paolo Capiluppi, Frigyes Nemes, James Rohlf, Carlos Avila, J. Seixas, Etiennette Auffray, J. Park, S. K. Kim, Mariarosaria D'Alfonso, Zoltan Szillasi, Jussi Viinikainen, D. R. Muller, A. Yagil, Negin Shafiei, Ian Reed, Jaana Kristiina Heikkilä, Nikitas Loukas, Huilin Qu, Andrey Uzunian, Alice Bean, Rachel Bartek, Marco Peruzzi, Usama Hussain, Owen Rosser Long, A. Popov, M. Csanad, Margaret Eminizer, Nicola Amapane, R. Sharma, Andrea Piccinelli, Andreas Nowack, B. Schneider, Koushik Mandal, S. Belforte, Nabarun Dev, Johan Borg, A. Bermúdez Martínez, Michael Reichmann, J. S. Wilson, Y. Haddad, J. H. Kim, Anton Babaev, Eric Adams, Dennis Noll, M. Nunez Ornelas, A. Schmidt, C. Campagnari, P. C. Bhat, Fabrizio Ferro, Jared Sturdy, Thomas Ferbel, David Gabriel Monk, J. 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Mota Amarilo, Marco Zanetti, Pietro Govoni, Samila Muthumuni, Tae Jeong Kim, Samuel Webb, Emmanouil Vourliotis, Michael Murray, Jakob Salfeld-Nebgen, Louis Moureaux, Sebastian Wiedenbeck, R. Lander, Nazar Bartosik, W. Van Doninck, Christos Roskas, Maria Cepeda, Sergio Cittolin, Jorgen D'Hondt, Francesco Ivone, C. A. Carrillo Montoya, Zoltan Gecse, Davide Piccolo, Tim Ziemons, T. Mitchell, Matthias Komm, Nadeesha Wickramage, Q. Ingram, L. Valencia Palomo, E. Fontanesi, Lisa Benato, L. I. Estevez Banos, Randy Ruchti, Joe Incandela, Luca Cadamuro, Daniel Pitzl, M. León Coello, Valentina Mariani, Paolo Montagna, J. Madhusudanan Sreekala, Othmane Bouhali, Milan Stojanovic, H. Zhang, David Mason, Ivan Shvetsov, Z Warner, Igor Golutvin, Serguei Volkov, Luigi Moroni, Luca Lista, Pei-rong Yu, C. C. Wang, A. Das, He He, Á. Navarro Tobar, Attila Racz, Roberta Arcidiacono, Dhanush Anil Hangal, Anatoli Pashenkov, Avto Kharchilava, Mikhail Ignatenko, G. Martinez, Merve Ince, J. P. Fernández Ramos, S. Gianì, Andrew Evans, Fengwangdong Zhang, Markus Merschmeyer, Ozlem Kaya, Sevil Salur, W. L. Aldá Júnior, Daniele Fasanella, B. McMaster, Ddc Wickramarathna, Dietrich Liko, Tapio Lampén, Andre Frankenthal, Mykhailo Dalchenko, Christian Veelken, Yu. Andreev, Markus Klute, Mario Galanti, Joel Goldstein, Milena Misheva, Robert Lee, Silvano Tosi, Norraphat Srimanobhas, Cécile Caillol, Dermot Moran, Ryan Heller, Daniel Treille, Kelvin Mei, S. R. Dugad, D. De Jesus Damiao, Sebastian Wuchterl, Evan Ranken, Tamas Novak, Ibrahim Soner Zorbakir, A. M. Vargas Hernandez, T. Susa, Cristina Botta, Jonathon Langford, Viesturs Veckalns, Dario Bisello, Pascal Paganini, R. Walsh, Jonas Rembser, S. Zhang, D. Soldi, S. Sánchez Navas, Jose Chinellato, Richard Cavanaugh, Ruchi Chudasama, Marco Rovere, Mariana Shopova, Marco Toliman Lucchini, Mauricio Thiel, Ilya Gorbunov, Tobias Pook, Peter Timothy Cox, Torben Lange, Michael Mulhearn, Monika Mittal, Jie Xiao, Jeroen Hegeman, Sang Il Pak, Anatoli Zarubin, Federica Maria Simone, S. Seif El Nasr-storey, Dimitri Bourilkov, Vassili Kachanov, S. W. Cho, Andrew Whitbeck, and Viktor Veszpremi

Subjects
Physics, Nuclear physics, Range (particle radiation), Proton, 010308 nuclear & particles physics, 0103 physical sciences, Kinematics, 010303 astronomy & astrophysics, 01 natural sciences, Differential (mathematics), Lepton
Published
2021

42. Temporal trend of clinical events in patients with atrial fibrillation on edoxaban therapy: results from the non-interventional global ETNA-AF program

Author

Takanori Yamashita, Cathy Chen, Y.-H Kim, Ladislav Pecen, Paulus Kirchhof, R. De Caterina, P.E. Reimitz, Leon Dinshaw, Doralisa Morrone, Yukihiro Koretsune, W Jiang, Martin Unverdorben, and C.-C Wang

Subjects
medicine.medical_specialty, Clinical events, business.industry, Atrial fibrillation, medicine.disease, chemistry.chemical_compound, chemistry, Edoxaban, Internal medicine, Non interventional, Cardiology, medicine, In patient, Cardiology and Cardiovascular Medicine, business
Abstract

Background Patients with atrial fibrillation (AF) who initiated vitamin K antagonist (VKA) were at highest risk of stroke and bleeding in the first few months of therapy. Understanding of the temporal trend of clinical events in AF patients on non-VKA oral anticoagulant (NOAC) therapy should aid therapeutic decisions. Purpose To evaluate the temporal trend of clinical events in AF patients receiving edoxaban in routine clinical practice in the Global ETNA-AF program. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program evaluating the safety and effectiveness of edoxaban in patients from European and Asian countries. Thromboembolic, bleeding and death events were analysed separately for the 1st and 2nd year of the follow-up period, using a time-to-first-event estimation of cumulative incidence and annual rate via Kaplan-Meier method. Results A total of 27,617 patients were included in this analysis, 48.6% from Europe and 51.4% from Japan, Korea, and Taiwan. Baseline characteristics were consistent with typical AF population in real world studies (Table 1). Approximately 83% of patients received the recommended edoxaban dose. Annualized rates of ischaemic stroke and major bleeding (ISTH) were lower in the 2nd year than in the 1st year: ischaemic stroke 0.59% (95% CI, 0.50–0.70) vs 0.86% (95% CI, 0.75–0.98), p=0.015; major bleeding 0.87% (95% CI, 0.75–1.00) vs 1.15% (95% CI, 1.02–1.29), p=0.036. The trend toward lower rates of ischaemic stroke and major bleeding in the 2nd year was consistent across regions. All-cause mortality increased slightly from the 1st year to the 2nd year, which was not statistically significant and was not driven by cardiovascular (CV) mortality (Table 2). Conclusion In routine clinical practice in the Global ETNA-AF program, major bleeding and ischaemic stroke rates in >27,000 patients on edoxaban therapy declined from 1st year to 2nd year. Further analyses will investigate whether such trend is influenced by selection for healthier patients over time. Longer follow-up is needed to better understand long-term trends. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Table 1. Baseline characteristicsTable 2. Annualised clinical event rates

Published
2021

43. Edoxaban treatment in real-world practice is highly concordant with ESC atrial fibrillation guidelines: results from the non-interventional global ETNA-AF program

Author

D Morrone, C Chen, L Dinshaw, W Jiang, Y.-H Kim, P Kirchhof, Y Koretsune, L Pecen, P.-E Reimitz, C.-C Wang, T Yamashita, M Unverdorben, and R De Caterina

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background The ESC atrial fibrillation management guidelines recommend a risk-based approach to oral anticoagulant (OAC) therapy. How clinical practice aligns with these recommendations is of interest. Purpose To analyse real world data from Global ETNA-AF program in patient groups stratified by stroke and bleeding risk scores according to ESC guidelines. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program evaluating the safety and effectiveness of edoxaban in patients from European and Asian countries. Baseline characteristics and clinical event data at 2-year follow-up were analysed in 4 subgroups defined by CHA2DS2-VASc score (≥3 for female / ≥2 for male [OAC recommended] vs 2 for female / 1 for male [OAC should be considered]) and HAS-BLED score (≥3 [Bleeding risk high] vs Results Of 27,616 patients included in this analysis, 23,152 (83.8%) were in the “OAC recommended” category and 3,539 (12.8%) were in the “OAC should be considered” category. Only 3.3% of patients did not meet ESC guideline criteria for OAC initiation. Among patients with high bleeding risk, 98% were in the “OAC recommended” category. A similar distribution was observed across regions (Table 2). The recommended edoxaban dose was used in the vast majority (>80%) of patients across all risk stratification subgroups. In the “OAC recommended” category, patients with high bleeding risk had higher rates of thromboembolic, bleeding, and death events than those with low bleeding risk. Conclusion Data from routine clinical practice in Global ETNA-AF demonstrate high concordance of edoxaban treatment with ESC guidelines. Edoxaban dose is consistent with label recommendation in the vast majority (>80%) of patients. Clinical event rates were generally low across all risk groups, including acceptable bleeding rates in anticoagulated patients with high bleeding risk. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Table 1. Subgroups as per ESC guidelinesTable 2. Patient characteristics & events

Published
2021

44. Building Information Modelling Implementation in the Design Stage of Chinese Prefabrication Construction

Author

M Wang, C C Wang, S Sepasgozar, and S Zlatanova

Subjects
General Medicine, General Chemistry
Abstract

Prefabrication construction has gained popularity in the construction industry during the last few years. Due to the complexity of prefabrication design, building information modelling (BIM) is adopted in the design stage to improve efficiency and accuracy. Many previous studies have examined the adoption of BIM in the design stage and explored the current practice of BIM adoption in prefabrication construction, however fewer first-hand investigations are made on assessing the adoption of BIM. This study aims to identify the opportunities and challenges of utilizing BIM technology in the design stage of prefabrication construction from the perspective of designers. A semi-structured interview was conducted for qualitative data collection and the data are analysed by thematic analysis. A total of eight designers from Chinese prefabrication construction projects were interviewed. The research identified 8 opportunities and 15 challenges of BIM adoption in prefabrication construction. The top four challenges are: (1) inaccurate prefabrication production drawings generated by BIM software, (2) late adoption of BIM in the design stage, (3) lack of communication platform for different designers, and (4) lack of sharing the updated design model among designers, manufacturers, and onsite engineers. These findings provide directions for improving BIM adoption in the design of prefabrication construction.

Published
2022

46. The sexual spore pigment asperthecin is required for normal ascospore production and protection from UV light in Aspergillus nidulans

Author

Yi-Ming Chiang, Philipp Wiemann, Claudio Greco, Jonathan M. Palmer, Daniel L. Lindner, Clay C. C. Wang, and Nancy P. Keller

Subjects
Ultraviolet Rays, Mutant, Ascospore, Anthraquinones, Bioengineering, Polyketide, Applied Microbiology and Biotechnology, Aspergillus nidulans, Article, Microbiology, Conidium, Fungal Proteins, Pigment, Gene Expression Regulation, Fungal, Gene cluster, UV protection, Gene, biology, Pigmentation, fungi, Fungi, Spores, Fungal, Cleistothecia, biology.organism_classification, Spore, visual_art, visual_art.visual_art_medium, Biotechnology
Abstract

Many fungi develop both asexual and sexual spores that serve as propagules for dissemination and/or recombination of genetic traits. Asexual spores are often heavily pigmented and this pigmentation provides protection from UV light. However, little is known about any purpose pigmentation that may serve for sexual spores. The model Ascomycete Aspergillus nidulans produces both green pigmented asexual spores (conidia) and red pigmented sexual spores (ascospores). Here we find that the previously characterized red pigment, asperthecin, is the A. nidulans ascospore pigment. The asperthecin biosynthetic gene cluster is composed of three genes: aptA, aptB, and aptC, where deletion of either aptA (encoding a polyketide synthase) or aptB (encoding a thioesterase) yields small, mishappen hyaline ascospores; while deletion of aptC (encoding a monooxygenase) yields morphologically normal but purple ascospores. ∆aptA and ∆aptB but not ∆aptC or wild type ascospores are extremely sensitive to UV light. We find that two historical ascospore color mutants, clA6 and clB1, possess mutations in aptA and aptB sequences, respectively.

Published
2021

47. Highly transparent conductive ZnO films prepared by reactive RF sputtering with Zn/ZnO composite target

Author

C. C. Wang, B.L. Zhu, Jianfang Wu, T. Xie, and Shi Xinwei

Subjects
Materials science, Composite number, General Chemistry, Substrate (electronics), Sputter deposition, Volumetric flow rate, Stress (mechanics), Crystallinity, symbols.namesake, Chemical engineering, Sputtering, symbols, General Materials Science, Raman spectroscopy
Abstract

Using Zn/ZnO composite target, ZnO films were prepared by RF magnetron sputtering under Ar, Ar + O2 and Ar + H2 atmospheres and substrate temperatures of 150 and 300 °C. The effects of gas (O2 or H2) flow rate and substrate temperature on the thickness, preferred orientation, crystallinity, stress, transparent conductive properties, electrically conductive stability in air, Eg and Raman spectrum of the films were investigated. The results show that the film prepared in Ar atmosphere exhibits poor transparent conductive properties and conductive stability. Substrate temperature of 300 °C is advantageous to prepare ZnO films with (002) preferred orientation, high crystallinity, low compressive stress and good transparent conductive properties under Ar + O2 atmosphere. Under Ar + H2 atmosphere, ZnO films with low compressive stress and better transparent conductive properties can be obtained at substrate temperature of 150 °C. The related mechanisms for the effect of gas flow rate and substrate temperature on structure and properties of ZnO films are discussed.

Published
2021

48. The Efficacy of Herbal Supplement

Author

Eliza L Y, Wong, Annie W L, Cheung, C J, Haines, C C, Wang, Chun-Kwok, Wong, Karl W K, Tsim, William K F, Cheng, and Ping-Chung, Leung

Abstract

This study aimed to further explore the efficacy and safety ofA third clinical trial to determine the clinical efficacy of high-dose DBT for a period of 12 weeks was carried out. The standard Menopause-Specific Quality of Life (MENQOL) assessment chart was used for the evaluation. Safety was defined as an absence of direct estrogenic effects, serum inflammatory cytokines. Notably, interleukin IL-6, IL-8 and tumor necrosis factor TNF-α, known to be directly related to estrogenic reactions in menopause studies, were monitored.The third clinical trial indicated an overall improvement in the four domains of MENQOL, offering further proof of the efficacy of DBT demonstrated in the two previous trials. The serial checks of the three cytokines related to estrogen activities did not show either upward or downward trends. The haphazard behavior reactions of the three cytokines offered indirect indications that DBT improved the MENQOL independently from estrogen activities.The three clinical trials using DBT to relieve menopausal syndrome have offered solid evidence for its efficacy. The uncertainty regarding whether the "phytoestrogen" contained in DBT had bioactivities similar to estrogen was alleviated through the confirmation that no strict estrogenic bioactivities were observed. The issue of safety was further clarified via laboratory platform studies on DBT, which not only showed the lack of similarity with estrogen actions but also confirmed the value of combining the two herbs in the classic formula.

Published
2021

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