bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting sphingosine kinase 1 (SK1) enhances oncogene-induced senescence through ceramide synthase 2 (CerS2)-mediated generation of very-long-chain ceramides
Authors: Trayssac Magali , Clarke Christopher J. , Stith Jeffrey L. , Snider Justin M. , Newen Naomi , Gault Christopher R. , Hannun Yusuf A. , Obeid Lina M.
Published: January 2021

Senescence is an antiproliferative mechanism that can suppress tumor development and can be induced by oncogenes such as genes of the Ras family. Although studies have implicated bioactive sphingolipids (SL) in senescence, the specific mechanisms remain unclear. Here, using MCF10A mammary epithelial cells, we demonstrate that oncogenic K-Ras (Kirsten rat sarcoma viral oncogene homolog) is sufficient to induce cell transformation as well as cell senescence—as revealed by increases in the percentage of cells in the G1 phase of the cell cycle, p21WAF1/Cip1/CDKN1A (p21) expression, and senescence-associated β-galactosidase activity (SA-β-gal). Furthermore, oncogenic K-Ras altered SL metabolism, with an increase of long-chain (LC) C18, C20 ceramides (Cer), and very-long-chain (VLC) C22:1, C24 Cer, and an increase of sphingosine kinase 1 (SK1) expression. Since Cer and sphingosine-1-phosphate have been shown to exert opposite effects on cellular senescence, we hypothesized that targeting SK1 could enhance oncogenic K-Ras-induced senescence. Indeed, SK1 downregulation or inhibition enhanced p21 expression and SA-β-gal in cells expressing oncogenic K-Ras and impeded cell growth. Moreover, SK1 knockdown further increased LC and VLC Cer species (C18, C20, C22:1, C24, C24:1, C26:1), especially the ones increased by oncogenic K-Ras. Fumonisin B1 (FB1), an inhibitor of ceramide synthases (CerS), reduced p21 expression induced by oncogenic K-Ras both with and without SK1 knockdown. Functionally, FB1 reversed the growth defect induced by oncogenic K-Ras, confirming the importance of Cer generation in the senescent phenotype. More specifically, downregulation of CerS2 by siRNA blocked the increase of VLC Cer (C24, C24:1, and C26:1) induced by SK1 knockdown and phenocopied the effects of FB1 on p21 expression. Taken together, these data show that targeting SK1 is a potential therapeutic strategy in cancer, enhancing oncogene-induced senescence through an increase of VLC Cer downstream of CerS2.
Role of Sciellin in gallbladder cancer proliferation and formation of neutrophil extracellular traps
Authors: Li Yang , Yuan Ruiyan , Ren Tai , Yang Bo , Miao Huijie , Liu Liguo , Li Yongsheng , Cai Chen , Yang Yang , Hu Yunping , Jiang Chengkai , Xu Qindie , Zhang Yijian , Liu Yingbin
Published: January 2021

Apart from primary tumor development and metastasis, cancer-associated thrombosis is the second cause of cancer death in solid tumor malignancy. However, the mechanistic insight into the development of gallbladder cancer (GBC) and cancer-associated thrombosis remains unclear. This study aimed to investigate the mechanistic role of Sciellin (SCEL) in GBC cell proliferation and the development of venous thromboembolism. The expression level of SCEL was determined by immunohistochemical staining. Roles of SCEL in gallbladder cancer cell were determined by molecular and cell biology methods. SCEL was markedly upregulated in GBC and associated with advanced TNM stages and a poor prognosis. Furthermore, SCEL interacted with EGFR and stabilized EGFR expression that activates downstream PI3K and Akt pathway, leading to cell proliferation. In addition, SCEL induces tumor cell IL-8 production that stimulates the formation of neutrophil extracellular traps (NETs), accelerating thromboembolism. In xenografts, SCEL-expressing GBCs developed larger tumors and thrombosis compared with control cells. The present results indicate that SCEL promotes GBC cell proliferation and induces NET-associated thrombosis, thus serving as a potential therapeutic target.
A triple-drug nanotherapy to target breast cancer cells, cancer stem cells, and tumor vasculature
Authors: El-Sahli Sara , Hua Khang , Sulaiman Andrew , Chambers Jason , Li Li , Farah Eliya , McGarry Sarah , Liu Dan , Zheng Peiyong , Lee Seung-Hwan , Cui Jiefeng , Ekker Marc , Côté Marceline , Alain Tommy , Li Xuguang , D’Costa Vanessa M. , Wang Lisheng , Gadde Suresh
Published: January 2021

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, accounting for the majority of breast cancer-related death. Due to the lack of specific therapeutic targets, chemotherapeutic agents (e.g., paclitaxel) remain the mainstay of systemic treatment, but enrich a subpopulation of cells with tumor-initiating capacity and stem-like characteristics called cancer stem cells (CSCs); thus development of a new and effective strategy for TNBC treatment is an unmet medical need. Cancer nanomedicine has transformed the landscape of cancer drug development, allowing for a high therapeutic index. In this study, we developed a new therapy by co-encapsulating clinically approved drugs, such as paclitaxel, verteporfin, and combretastatin (CA4) in polymer-lipid hybrid nanoparticles (NPs) made of FDA-approved biomaterials. Verteporfin is a drug used in the treatment of macular degeneration and has recently been found to inhibit the Hippo/YAP (Yes-associated protein) pathway, which is known to promote the progression of breast cancer and the development of CSCs. CA4 is a vascular disrupting agent and has been tested in phase II/III of clinical trials. We found that our new three drug-NP not only effectively inhibited TNBC cell viability and cell migration, but also significantly diminished paclitaxel-induced and/or CA4-induced CSC enrichment in TNBC cells, partially through inhibiting the upregulated Hippo/YAP signaling. Combination of verteporfin and CA4 was also more effective in suppressing angiogenesis in an in vivo zebrafish model than single drug alone. The efficacy and application potential of our triple drug-NPs were further assessed by using clinically relevant patient-derived xenograft (PDX) models. Triple drug-NP effectively inhibited the viability of PDX organotypic slide cultures ex vivo and stopped the growth of PDX tumors in vivo. This study developed an approach capable of simultaneously inhibiting bulk cancer cells, CSCs, and angiogenesis.
PLPP/CIN-mediated NF2-serine 10 dephosphorylation regulates F-actin stability and Mdm2 degradation in an activity-dependent manner
Authors: Kim Ji-Eun , Lee Duk-Shin , Kim Tae-Hyun , Park Hana , Kim Min-Ju , Kang Tae-Cheon
Published: January 2021

Neurofibromin 2 (NF2, also known as merlin) is a tumor suppressor protein encoded by the neurofibromatosis type 2 gene NF2. NF2 is also an actin-binding protein that functions in an intrinsic signaling network critical for actin dynamics. Although protein kinase A (PKA)-mediated NF2-serin (S) 10 phosphorylation stabilizes filamentous actin (F-actin), the underlying mechanisms of NF2-S10 dephosphorylation and the role of NF2 in seizures have been elusive. Here, we demonstrate that pyridoxal-5′-phosphate phosphatase/chronophin (PLPP/CIN) dephosphorylated NF2-S10 site as well as cofilin-S3 site. In addition, NF2-S10 dephosphorylation reversely regulated murine double minute-2 (Mdm2) and postsynaptic density 95 (PSD95) degradations in an activity-dependent manner, which increased seizure intensity and its progression in response to kainic acid (KA). In addition, NF2 knockdown facilitated seizure intensity and its progress through F-actin instability independent of cofilin-mediated actin dynamics. Therefore, we suggest that PLPP/CIN may be a potential therapeutic target for epileptogenesis and NF2-associated diseases.
Combined and selective miR-21 silencing and doxorubicin delivery in cancer cells using tailored DNA nanostructures
Authors: Raniolo Sofia , Unida Valeria , Vindigni Giulia , Stolfi Carmine , Iacovelli Federico , Desideri Alessandro , Biocca Silvia
Published: January 2021

MicroRNAs play an important role in tumorigenesis and, among them, miR-21 is found to be aberrantly up-regulated in various tumors. The tumor-associated antigen, folate receptor alpha is a GPI-membrane protein overexpressed in many malignant tumors of epithelial origin, including ovarian and cervical cancers. Covalently bound octahedral DNA nanocages were functionalized with folate molecules and utilized as scaffolds to engineer four sequestering units with a miR-21 complementary sequence for obtaining biocompatible Fol-miR21-NC non-toxic nanostructures, to be able to selectively recognize folate receptor alpha-overexpressing cancer cells and sequester the oncogenic miR-21. qPCR assays showed that Fol-miR21-NCs reduce the miR-21 expression up to 80% in cancer cells in the first 2 days of treatment. Functional assays demonstrated that miR-21 sequestering leads to up-regulation of miR-21 tumor suppressor targets (i.e., PTEN and Pdcd4), reduction in cancer cell migration, reduction in proliferation, and increase in cell death. Fol-miR21-NCs can be efficiently loaded with the chemotherapeutic agent doxorubicin. Co-delivery of anti-miR-21 and doxorubicin showed additive cytotoxic effects on tumor cells, paving the way for their use as selective nucleic acid drugs.
Liver fibrosis-induced muscle atrophy is mediated by elevated levels of circulating TNFα
Authors: Kurosawa Tamaki , Goto Momo , Kaji Noriyuki , Aikiyo Satoshi , Mihara Taiki , Ikemoto-Uezumi Madoka , Toyoda Masashi , Kanazawa Nobuo , Nakazawa Tatsu , Hori Masatoshi , Uezumi Akiyoshi
Published: January 2021

Liver cirrhosis is a critical health problem associated with several complications, including skeletal muscle atrophy, which adversely affects the clinical outcome of patients independent of their liver functions. However, the precise mechanism underlying liver cirrhosis-induced muscle atrophy has not been elucidated. Here we show that serum factor induced by liver fibrosis leads to skeletal muscle atrophy. Using bile duct ligation (BDL) model of liver injury, we induced liver fibrosis in mice and observed subsequent muscle atrophy and weakness. We developed culture system of human primary myotubes that enables an evaluation of the effects of soluble factors on muscle atrophy and found that serum from BDL mice contains atrophy-inducing factors. This atrophy-inducing effect of BDL mouse serum was mitigated upon inhibition of TNFα signalling but not inhibition of myostatin/activin signalling. The BDL mice exhibited significantly up-regulated serum levels of TNFα when compared with the control mice. Furthermore, the mRNA expression levels of Tnf were markedly up-regulated in the fibrotic liver but not in the skeletal muscles of BDL mice. The gene expression analysis of isolated nuclei revealed that Tnf is exclusively expressed in the non-fibrogenic diploid cell population of the fibrotic liver. These findings reveal the mechanism through which circulating TNFα produced in the damaged liver mediates skeletal muscle atrophy. Additionally, this study demonstrated the importance of inter-organ communication that underlies the pathogenesis of liver cirrhosis.
Nogo-A regulates myogenesis via interacting with Filamin-C
Authors: Park SunYoung , Park Ji-Hwan , Kang Un-Beom , Choi Seong-Kyoon , Elfadl Ahmed , Ullah H. M. Arif , Chung Myung-Jin , Son Ji-Yoon , Yun Hyun Ho , Park Jae-Min , Yim Jae-hyuk , Jung Seung-Jun , Kim Sang-Hyup , Choi Young-Chul , Kim Dae-Seong , Shin Jin-Hong , Park Jin-Sung , Hur Keun , Lee Sang-Han , Lee Eun-Joo , Hwang Daehee , Jeong Kyu-Shik
Published: January 2021

Among the three isoforms encoded by Rtn4, Nogo-A has been intensely investigated as a central nervous system inhibitor. Although Nogo-A expression is increased in muscles of patients with amyotrophic lateral sclerosis, its role in muscle homeostasis and regeneration is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in various muscle-related pathological conditions. Nogo−/− mice displayed dystrophic muscle structure, dysregulated muscle regeneration following injury, and altered gene expression involving lipid storage and muscle cell differentiation. We hypothesized that increased Nogo-A levels might regulate muscle regeneration. Differentiating myoblasts exhibited Nogo-A upregulation and silencing Nogo-A abrogated myoblast differentiation. Nogo-A interacted with filamin-C, suggesting a role for Nogo-A in cytoskeletal arrangement during myogenesis. In conclusion, Nogo-A maintains muscle homeostasis and integrity, and pathologically altered Nogo-A expression mediates muscle regeneration, suggesting Nogo-A as a novel target for the treatment of myopathies in clinical settings.
Author Correction: Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction
Authors: Steinhorn Benjamin , Sorrentino Andrea , Badole Sachin , Bogdanova Yulia , Belousov Vsevolod , Michel Thomas
Published: January 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20668-1
Sleep classification from wrist-worn accelerometer data using random forests
Authors: Sundararajan Kalaivani , Georgievska Sonja , te Lindert Bart H. W. , Gehrman Philip R. , Ramautar Jennifer , Mazzotti Diego R. , Sabia Séverine , Weedon Michael N. , van Someren Eus J. W. , Ridder Lars , Wang Jian , van Hees Vincent T.
Published: January 2021

Accurate and low-cost sleep measurement tools are needed in both clinical and epidemiological research. To this end, wearable accelerometers are widely used as they are both low in price and provide reasonably accurate estimates of movement. Techniques to classify sleep from the high-resolution accelerometer data primarily rely on heuristic algorithms. In this paper, we explore the potential of detecting sleep using Random forests. Models were trained using data from three different studies where 134 adult participants (70 with sleep disorder and 64 good healthy sleepers) wore an accelerometer on their wrist during a one-night polysomnography recording in the clinic. The Random forests were able to distinguish sleep-wake states with an F1 score of 73.93% on a previously unseen test set of 24 participants. Detecting when the accelerometer is not worn was also successful using machine learning ($$\hbox {F1-score} > 93.31\%$$

F1-score
>
93.31
%

), and when combined with our sleep detection models on day-time data provide a sleep estimate that is correlated with self-reported habitual nap behaviour ($$\hbox {r}=.60$$

r
=
.
60

). These Random forest models have been made open-source to aid further research. In line with literature, sleep stage classification turned out to be difficult using only accelerometer data.
National trends in cardiovascular health metrics among Iranian adults using results of three cross-sectional STEPwise approaches to surveillance surveys
Authors: Rahmani Fatemeh , Asgari Samaneh , Khalili Davood , Habibi Moeini Ali Siamak , Tohidi Maryam , Azizi Fereidoun , Hadaegh Farzad
Published: January 2021

To examine the trends of 7 cardiovascular health metrics (CVH metrics) incorporate of smoking, physical activity, diet, body mass index (BMI), fasting plasma glucose (FPG), total cholesterol (TC), and blood pressure (BP) level during three cross-sectional STEPwise approaches to surveillance (STEPS), 2007–2016, among Iranian adults. The study population consisted of 19,841 women and 17,243 men, aged 20–65 years. The CVH metrics were categorized as ‘ideal’, ‘intermediate’, and ‘poor’. The sex-stratified weighted prevalence rate of each CVH metrics was reported. The conditional probability of each poor versus combined intermediate and ideal metric was analyzed using logistic regression. In 2016 compared to 2007, the prevalence of poor BP level (20.4% vs. 23.7%), smoking (13.7% vs. 23.8%), TC ≥ 240 mg/dl (2.4% vs. 11.2%) and FPG < 100 mg/dl (75.6% vs. 82.3%) declined, whereas poor physical activity level (49.7% vs. 30%), poor healthy diet score (38.1% vs. 4.1%), BMI levels ≥ 25 kg/m2 (62.8% vs. 57.8%) increased. Despite a high prevalence of obesity among women, it remained constant in women but showed an increasing trend in men; moreover, the trends of low physical activity and current smoking were better for women. Despite some improvement in CVH metrics, < 4% of Iranian adults meet ≥ 6 CVH metrics in 2016; this issue needs intervention at the public health level using a multi-component strategy.
Coronary artery lumen complexity as a new marker for refractory symptoms in patients with vasospastic angina
Authors: Tanaka Atsushi , Taruya Akira , Shibata Kyosuke , Fuse Kota , Katayama Yosuke , Yokoyama Mao , Kashiwagi Manabu , Shingo Ota , Akasaka Takashi , Kato Nobuhiro
Published: January 2021

Refractory angina is an independent predictor of adverse events in patients with vasospastic angina (VSA). The aim of this study was to investigate the relationship between coronary lumen complexity and refractory symptoms in patients with VSA. Seventeen patients with VSA underwent optical coherence tomography. The patients were divided into the refractory VSA group (n = 9) and the stable VSA group (n = 8). A shoreline development index was used to assess the coronary artery lumen complexity. Shear stress was estimated using a computational fluid dynamics model. No difference was observed in the baseline characteristics between the two groups. The refractory VSA group showed the higher shoreline development index (refractory VSA 1.042 [1.017–1.188] vs stable VSA 1.003 [1.006–1.025], p = 0.036), and higher maximum medial thickness (refractory VSA 184 ± 17 μm vs stable VSA 148 ± 31 μm, p = 0.017), and higher maximum shear stress (refractory VSA 14.5 [12.1–18.8] Pa vs stable VSA 5.6 [3.0–10.5] Pa, p = 0.003). The shoreline development index positively correlates with shear stress (R2 = 0.46, P = 0.004). Increased medial thickness of the coronary arteries provokes lumen complexity and high shear stress, which might cause refractory symptoms in patients with VSA. The shoreline index could serve as a marker for irritability of the medial layer of coronary arteries and symptoms.
Environmental biodegradability of recombinant structural protein
Authors: Tachibana Yuya , Darbe Sunita , Hayashi Senri , Kudasheva Alina , Misawa Haruna , Shibata Yuka , Kasuya Ken-ichi
Published: January 2021

Next generation polymers needs to be produced from renewable sources and to be converted into inorganic compounds in the natural environment at the end of life. Recombinant structural protein is a promising alternative to conventional engineering plastics due to its good thermal and mechanical properties, its production from biomass, and its potential for biodegradability. Herein, we measured the thermal and mechanical properties of the recombinant structural protein BP1 and evaluated its biodegradability. Because the thermal degradation occurs above 250 °C and the glass transition temperature is 185 °C, BP1 can be molded into sheets by a manual hot press at 150 °C and 83 MPa. The flexural strength and modulus of BP1 were 115 ± 6 MPa and 7.38 ± 0.03 GPa. These properties are superior to those of commercially available biodegradable polymers. The biodegradability of BP1 was carefully evaluated. BP1 was shown to be efficiently hydrolyzed by some isolated bacterial strains in a dispersed state. Furthermore, it was readily hydrolyzed from the solid state by three isolated proteases. The mineralization was evaluated by the biochemical oxygen demand (BOD)-biodegradation testing with soil inocula. The BOD biodegradability of BP1 was 70.2 ± 6.0 after 33 days.
Modular machine learning for Alzheimer's disease classification from retinal vasculature
Authors: Tian Jianqiao , Smith Glenn , Guo Han , Liu Boya , Pan Zehua , Wang Zijie , Xiong Shuangyu , Fang Ruogu
Published: January 2021

Alzheimer's disease is the leading cause of dementia. The long progression period in Alzheimer's disease provides a possibility for patients to get early treatment by having routine screenings. However, current clinical diagnostic imaging tools do not meet the specific requirements for screening procedures due to high cost and limited availability. In this work, we took the initiative to evaluate the retina, especially the retinal vasculature, as an alternative for conducting screenings for dementia patients caused by Alzheimer's disease. Highly modular machine learning techniques were employed throughout the whole pipeline. Utilizing data from the UK Biobank, the pipeline achieved an average classification accuracy of 82.44%. Besides the high classification accuracy, we also added a saliency analysis to strengthen this pipeline's interpretability. The saliency analysis indicated that within retinal images, small vessels carry more information for diagnosing Alzheimer's diseases, which aligns with related studies.
Impact of improved small-scale livestock farming on human nutrition
Authors: Hossain Md. Emran , Hoque Md. Ahasanul , Giorgi Emanuele , Fournié Guillaume , Das Goutam Buddha , Henning Joerg
Published: January 2021

Micronutrient deficiencies and stunting rates are high in many low-income countries. Increasing and diversifying food intake are often challenging for small-scale farmers in lowland areas as flooding often results in crop losses and drowning of livestock. A cluster-randomised controlled trial was conducted over 12-months in Bangladesh, involving 150 small-scale duck rearing households, including 50 control, and 50 households each in two intervention arms. Interventions focussing on improving duck health and duck nutrition were applied on a village level. Data analysis focussed on assessing the impact of interventions on duck mortality, sales and consumption, and on dietary diversity of household members. Improved duck rearing increased the consumption and the sales of ducks. Household selling more ducks were more likely to purchase and consume milk products, contributing to an improved households’ dietary diversity. Our results suggest that improving duck rearing can provide a suitable and sustainable alternative to maintain and improve dietary diversity of households in flood-prone areas.
Development and validation of a sequential two-step algorithm for the screening of individuals with potential polycythaemia vera
Authors: Piris-Villaespesa Miguel , Álvarez-Larrán Alberto , Saez-Marín Adolfo , Nuñez-Torrón Claudia , Muñoz-Martin Gloria , Sánchez Ricardo , del Castillo Francisco J. , Villarrubia Jesús , Lopez-Jimenez Javier , Martinez-Lopez Joaquin , Garcia-Gutierrez Valentin
Published: January 2021

In 2016, the WHO included haemoglobin values within normal ranges as a diagnostic criterion for Polycythaemia Vera (PV). Since then, concerns have arisen that a large number of patients are undergoing unnecessary screening for PV. To address this issue, we estimated the prevalence of JAK2 p.V617F in individuals with elevated haemoglobin or haematocrit and developed and validated a screening algorithm for PV. A total of 15,366 blood counts performed in seven non-consecutive days were reviewed, of which 1001 were selected for subsequent JAK2 p.V617F mutation screening. Eight (0.8%) new JAK2 p.V617F-mutated cases were detected. From ROC curves, a two-step algorithm was developed based on the optimal cut-off for the detection of the JAK2 p.V617F mutation. The algorithm was prospectively validated in an independent cohort of 15,298 blood counts. A total of 1595 (10.4%) cases met the criterion for haemoglobin or haematocrit, of whom 581 passed to step 2 (3.8% of the total). The JAK2 p.V617F mutation was detected in 7 of the 501 patients tested, which accounts for 0.04% of the total cohort and 0.4% of patients with erythrocytosis. In conclusion, this data show that our two-step algorithm improves the selection of candidates for JAK2 p.V617F testing.
Economic impacts of ambient ozone pollution on wood production in Italy
Authors: Sacchelli Sandro , Carrari Elisa , Paoletti Elena , Anav Alessandro , Hoshika Yasutomo , Sicard Pierre , Screpanti Augusto , Chirici Gherardo , Cocozza Claudia , De Marco Alessandra
Published: January 2021

Worldwide, tropospheric ozone (O3) is a potential threat to wood production, but our understanding of O3 economic impacts on forests is still limited. To overcome this issue, we developed an approach for integrating O3 risk modelling and economic estimates, by using the Italian forests as a case study. Results suggested a significant impact of O3 expressed in terms of stomatal flux with an hourly threshold of uptake (Y = 1 nmol O3 m−2 leaf area s−1 to represent the detoxification capacity of trees), i.e. POD1. In 2005, the annual POD1 averaged over Italy was 20.4 mmol m−2 and the consequent potential damage ranged from 790.90 M€ to 2.85 B€ of capital value (i.e. 255–869 € ha−1, on average) depending on the interest rate. The annual damage ranged from 31.6 to 57.1 M€ (i.e. 10–17 € ha−1 per year, on average). There was also a 1.1% reduction in the profitable forest areas, i.e. with a positive Forest Expectation Value (FEV), with significant declines of the annual national wood production of firewood (− 7.5%), timber pole (− 7.4%), roundwood (− 5.0%) and paper mill (− 4.8%). Results were significantly different in the different Italian regions. We recommend our combined approach for further studies under different economic and phytoclimatic conditions.
Nocturnal blood pressure dip and parapapillary choroidal microvasculature dropout in normal-tension glaucoma
Authors: Shin Joong Won , Jo Youn Hye , Song Min Kyung , Won Hun Jae , Kook Michael S.
Published: January 2021

Choroidal microvasculature dropout (CMvD) implies compromised optic nerve head perfusion in glaucoma patients. However, there are conflicting findings whether office-hour systemic blood pressure (BP) is related to the presence of CMvD. The present study investigated which systemic BP parameters, derived from 24-h ambulatory BP monitoring (ABPM), are associated with CMvD as assessed by optical coherence tomography angiography (OCT-A) in normal-tension glaucoma (NTG). This study included 88 eyes of 88 NTG patients who underwent 24-h ABPM and OCT-A imaging. Various systemic BP parameters associated with the presence of CMvD were evaluated using logistic regression analyses. CMvD was detected in 38 NTG eyes (43.2%). NTG eyes with CMvD had nighttime diastolic BP (DBP) dip of greater magnitude and longer duration than eyes without CMvD. In multivariate logistic regression, worse VF mean deviation (MD) (odds ratio [OR] 0.786; P = 0.001), greater nighttime DBP dip “%” (OR 1.051; P = 0.034), and higher daytime peak IOP (OR 1.459; P = 0.013) were significantly associated with the presence of CMvD. Based on our findings that the eyes with CMvD are closely associated with having nighttime DBP dip, NTG patients with CMvD should be recommended to undergo 24-h ABPM.
Avian intestinal ultrastructure changes provide insight into the pathogenesis of enteric diseases and probiotic mode of action
Authors: Shini Shaniko , Aland R. Claire , Bryden Wayne L.
Published: January 2021

Epithelial damage and loss of barrier integrity occur following intestinal infections in humans and animals. Gut health was evaluated by electron microscopy in an avian model that exposed birds to subclinical necrotic enteritis (NE) and fed them a diet supplemented with the probiotic Bacillus amyloliquefaciens strain H57 (H57). Scanning electron microscopy of ileal mucosa revealed significant villus damage, including focal erosions of epithelial cells and villous atrophy, while transmission electron microscopy demonstrated severe enterocyte damage and loss of cellular integrity in NE-exposed birds. In particular, mitochondria were morphologically altered, appearing irregular in shape or swollen, and containing electron-lucent regions of matrix and damaged cristae. Apical junctional complexes between adjacent enterocytes were significantly shorter, and the adherens junction was saccular, suggesting loss of epithelial integrity in NE birds. Segmented filamentous bacteria attached to villi, which play an important role in intestinal immunity, were more numerous in birds exposed to NE. The results suggest that mitochondrial damage may be an important initiator of NE pathogenesis, while H57 maintains epithelium and improves the integrity of intestinal mucosa. Potential actions of H57 are discussed that further define the mechanisms responsible for probiotic bacteria’s role in maintaining gut health.
Environmental drivers of body size evolution in crocodile-line archosaurs
Authors: Stockdale Maximilian T. , Benton Michael J.
Published: January 2021

Ever since Darwin, biologists have debated the relative roles of
external and internal drivers of large-scale evolution. The distributions and
ecology of living crocodilians are controlled by environmental factors such as
temperature. Crocodilians have a rich history, including amphibious, marine and
terrestrial forms spanning the past 247 Myr. It is uncertain whether their evolution
has been driven by extrinsic factors, such as climate change and mass extinctions,
or intrinsic factors like sexual selection and competition. Using a new phylogeny of
crocodilians and their relatives, we model evolutionary rates using phylogenetic
comparative methods. We find that body size evolution follows a punctuated, variable
rate model of evolution, consistent with environmental drivers of evolution, with
periods of stability interrupted by periods of change. Regression analyses show
warmer environmental temperatures are associated with high evolutionary rates and
large body sizes. We confirm that environmental factors played a significant role in
the evolution of crocodiles.
Development of recyclable magnetic cross-linked enzyme aggregates for the synthesis of high value rare sugar d-tagatose in aqueous phase catalysis
Authors: Rai Shushil Kumar , Kumar Varun , Yadav Sudesh Kumar
Published: January 2021

In this study, a high value rare sugar d-tagatose was synthesized using recyclable magnetic catalysts.
Critical challenges and advances in the carbon nanotube–metal interface for next-generation electronics
Authors: Daneshvar Farhad , Chen Hengxi , Noh Kwanghae , Sue Hung-Jue
Published: January 2021

In this paper the major challenges of CNT–metal systems and a few of their potential applications in future electronics are reviewed.
Functional thiophene-diketopyrrolopyrrole-based polymer derivatives as organic anode materials for lithium-ion batteries
Authors: Xu Zichen , Hou Shengxian , Zhu Zhiyou , Zhou Pengfei , Xue Li , Lin Hongtao , Zhou Jin , Zhuo Shuping
Published: January 2021

Four thiophene-diketopyrrolopyrrole-based polymer derivatives were used as lithium ion battery anode materials. We found that the electrode modified with carbazol and tert-butoxycarbonyl groups (P(C-TDPP-TA)) has the best performance.
Revisiting anodic alumina templates: from fabrication to applications
Authors: Ruiz-Clavijo Alejandra , Caballero-Calero Olga , Martín-González Marisol
Published: January 2021

Review of Porous Anodic Aluminum Oxide (AAO or NAA) membranes: from fabrication, mechanisms, and internal and surface nanostructuration to applications.
Spatial distribution of active sites for plasmon-induced chemical reactions triggered by well-defined plasmon modes
Authors: Minamimoto Hiro , Toda Takahiro , Murakoshi Kei
Published: January 2021

The spatial distribution of plasmon induced electron transfer reactions triggered on higher order plasmon modes was visualized through polymerizations of conductive polymers. Absolute electrochemical potential of generated holes was also clarified.
Highly stretchable and strong poly(butylene maleate) elastomersviametal–ligand interactions
Authors: Chen Tong , Geng Kui , Gao Ying , Xie Zhi-Ning , Guo Zhao-Xia , Xu Jun , Guo Bao-Hua
Published: January 2021

The search for advanced elastomers with simultaneously high strength, high stretchability and reprocessability remains a challenging task.
Fine control of the molecular weight and polymer dispersity via a latent monomeric retarder
Authors: Jia Rui , Tu Yanyan , Glauber Mejia , Huang Zhihao , Xuan Sunting , Zhang Weidong , Zhou Nianchen , Li Xiaohong , Zhang Zhengbiao , Zhu Xiulin
Published: January 2021

A latent monomeric retarder was used for a one-shot polymerization with a defined MW and Đ.
Naked-eye detection of Hg(ii) ions by visible light-induced polymerization initiated by a Hg(ii)-selective photoredox catalyst
Authors: Kim Hyungwook , Jung Young Jae , Lee Jungkyu K.
Published: January 2021

A selective turn-on photoredox catalyst extends the applications of visible light-induced polymerization.
Cobalt mediated N-alkylation of amines by alcohols: role of hydrogen bonding pocket
Authors: Prabha Divya , Pachisia Sanya , Gupta Rajeev
Published: January 2021

Cobalt complexes of amide-based pincers provide a H-bonding pocket that binds a reagent in the vicinity of the metal center. These complexes function as catalysts for the N-alkylation of amines using alcohols via a borrowing hydrogen strategy.
Chemical control of peptide material phase transitions
Authors: Tan Junjun , Zhang Li , Hsieh Ming-Chien , Goodwin Jay T. , Grover Martha A. , Lynn David G.
Published: January 2021

Substrate initiated assembly of a dynamic chemical network.
Ligand-controlled and nanoconfinement-boosted luminescence employing Pt(ii) and Pd(ii) complexes: from color-tunable aggregation-enhanced dual emitters towards self-referenced oxygen reporters
Authors: Maisuls Iván , Wang Cui , Gutierrez Suburu Matias E. , Wilde Sebastian , Daniliuc Constantin-Gabriel , Brünink Dana , Doltsinis Nikos L. , Ostendorp Stefan , Wilde Gerhard , Kösters Jutta , Resch-Genger Ute , Strassert Cristian A.
Published: January 2021

Pt(ii) and Pd(ii) complexes with unprecedented photophysical properties were developed. Encapsulation in nanoparticles boosted their performance while rendering them as self-referenced oxygen sensors.
Paramètres démographiques et économie de l’élevage camelin : une étude au Maroc
Authors: Julien Lionel , Moutik Fatima Ezzahra , Haloui Chaïmae , Huguenin Johann , Sraïri Mohamed Taher
Published: January 2021

Le dromadaire est capable de s’accommoder de l’hostilité du milieu désertique en mettant en valeur la végétation qui y est produite. Ces dernières années, il est l’objet d’un regain d’intérêt, eu égard à la qualité de ses produits et à ses caractéristiques physiologiques qui font de cette espèce l’une des plus aptes à s’adapter au changement climatique. Toutefois, les références sur ses performances zootechniques, et plus particulièrement sur les paramètres démographiques dans les systèmes naturels où il est exploité, demeurent limitées. Cette étude se propose d’analyser une partie des éléments démographiques en appliquant une méthode rétrospective de détermination de ces paramètres sur deux années successives, dans 122 troupeaux localisés dans la zone de M’Hamid El Ghizlane, au centre-est du Maroc. Les résultats ont démontré l’importante variabilité annuelle des paramètres démographiques, impactés par la disponibilité alimentaire des parcours, elle-même déterminée par la pluviométrie et sa répartition dans l’année. Les résultats ont aussi souligné la productivité limitée du dromadaire, ne dépassant pas en moyenne un chamelon viable pour trois chamelles en âge de reproduction. L’étude a révélé un potentiel de production de lait réduit dans un contexte de variabilité prononcée de l’offre alimentaire des parcours et d’éloignement des producteurs par rapport aux centres de consommation. En termes de pratiques d’alimentation, le recours à la complémentation est fréquent, sous forme de rebuts de dattes et d’orge subventionné. Les interventions sanitaires sont rares, du fait du pouvoir d’achat limité des éleveurs. Quant aux productions, elles sont surtout représentées par le croît du troupeau, les ventes de lait étant marginales. Quelques rares éleveurs recourent à la location de mâles pour des activités touristiques. Au final, les résultats confirment d’importantes marges d’amélioration de la productivité de l’élevage du dromadaire, qui demeure pour l’instant essentiellement au service de l’autoconsommation et de la capitalisation. Les marges dégagées ne permettent pas aux familles qui pratiquent cet élevage d’obtenir des revenus suffisants.
Forced Unsteady State Operation of a Catalytic Converter during Cold Start-up for Oxidizing CO Over Pt/γ-Al2O3Catalyst
Authors: Budhi Yogi Wibisono , Putri Ade Kusuma , Nashira Alimatun
Published: January 2021

CO oxidation in the catalytic converter hasn’t showed best performance particularly during cold start-up, since the catalyst is not active during this period. The purpose of this experiment was to develop the forced unsteady state operation procedure of CO oxidation using 0.05%-w Pt/γ-Al2O3and space velocity of 0.406 mmol/s/gram. The catalytic converter was gradually ramped-up, while introducing the feed gas containing CO in the air. The feed gas was modulated following a square wave model with switching time variation at 3, 6, 15, and 30 s and various operation modes. To gain the intrinsic reaction rate, the external mass transfer criterion was determined. Ramping-up the temperature from 50 until 150°C increased the CO conversion with different profiles between steady state and dynamic flow rate. The dynamic system with modulated CO feed flow gave lower light-off temperature and higher average CO conversion than the steady state system which gave light off temperature 115°C and average CO conversion of 48.86%. The switching time of 3 s gave highest average CO conversion during ramping-up, which was 79.35%. Meanwhile the dynamic operation system with modulated feed flow gave higher lightoff temperature and lower average CO conversion than steady state system.
Separation and Recovery of Lithium, Cobalt and Nickel Ion in an Aqueous Phase by Slug Flow
Authors: Hinoue Mikiya , Hirayama Masaki , Muto Akinori
Published: January 2021

Extraction by slug flow gives high mass transfer rate and rapid phase separation than the conventional extraction operation. Therefore, there are many advantages such as the volume of the device becomes small and the solvent drastically reduced. The slug flow extraction is expected as a sophisticated separation process. Especially, these advantages become more prominent in the multistage extraction. In this study, the extraction by the slug flow was applied to mutual separation of lithium, cobalt and nickel ions in the mixed aqueous solution. We succeeded in developing a process with lithium, cobalt, nickel ion purity of 85% or more and recovery rate of 90-95%. Furthermore, it was also confirmed that the flow state of the liquid is influenced by the hydrophobicity (PTFE) and hydrophilicity (glass) of the extraction tube. The overall mass transfer volumetric coefficient is affected by (1) the interface area of the oil phase and aqueous phase, (2) the strength of the circulating flow in each segment of the liquid, and (3) the volume flow ratio of the oil phase and the aqueous phase.
Optimization of Ultrasonic-assisted Extraction of Total Phenolic Compound from Leaves of Chromolaena Odorata L. Using Response Surface Methodology
Authors: Sirijeerachai Guntima , Khunasinkun Suphattra , Boonleau Piyapassara , Oonsivilai Ratchadaporn , Nuchitprasitchai Aroonsri
Published: January 2021

Chromolaena odorata L. or C. odorata is a weed that found in tropical continents . Leaves, roots and flowers of C. odorata have been used as medicinal plants for centuries. Preliminary phytochemical screening showed the chemical composition of its extracts having phenolic compounds such as flavonoids, saponins, tannins and steroids. The total phenolic compounds (TPC) in medicinal plants are acknowledged as biochemical activities such as antiinflammatory, antiviral, antimicrobial, antioxidant agents and etc. This work is interested in antioxidant and antimicrobial activity of an ethanolic extract of C. odorata leaves. Though, many solvents can be used to extract TPC from plants. Ethanol with ultrasound assisted extraction was selected. The response surface methodology coupled with the nonlinear solver were used to find the optimal extraction variables. The Central Composite Design (CCD) was employed as the sampling technique. Three variables are the ratio of ethanol to the dried leaves of C. odorata (X1), aqueous ethanol concentration (X2), and the extraction time (X3). The extraction conditions were fixed at 40 kHz and 60 ˚C. The maximum yield of TPC was 111.77 mg GAE/g dry extract at 57 % v/v of aqueous ethanol concentration, 43 mL of solvent/g of dried sample and 35 minutes extraction time.
Targeted Gene Integration into Nuclear Genome of Microalgae Using Cre/loxPRecombination System
Authors: Shirakawa Kazuki , Kawabe Yoshinori , Huang Guan , Ito Akira , Kamihira Masamichi
Published: January 2021

Genetically modified microalgae have been expected to be a useful tool for bioenergy and recombinant protein production. However, random integration of transgene in the microalgae nuclear genome is susceptible to gene silencing of heterologous gene expression. Here, we attempted to perform targeted gene integration into a pre-determined nuclear genomic site ofChlamydomonas reinhardtiiusing Cre/loxPrecombination system for stable transgene expression. We constructed an expression vector plasmid encoding reporter genes (zeocin resistant gene and green fluorescent protein gene;Zeo-2A-GFP) and mutatedloxPto generate founder cells. A donor vector encodingIFNα-4and paromomycin resistant genes flanked by corresponding mutatedloxPs was constructed and introduced into founder cells together with a Cre expression vector. The optimal ratio of donor vector to Cre expression vector was determined by counting the number of paromomycin resistant colonies. For the established clones, the targeted integration was confirmed by genomic PCR using various specific primer sets. Target genes in the donor vector could be integrated into the expected genomic site ofC. reinhardtiiusing Cre/loxPsystem. RT-PCR revealed thatIFNα-4was expressed in five independent transgenic cell lines tested. This result suggests that Cre-based cell engineering is a promising approach to generate smart microalgae expressing foreign genes.
Production of Influenza Virus Proteins Using Recombinant Insect Cells
Authors: Matsuda Takuya , Tanijima Toshikazu , Masumi-Koizumi Kyoko , Katsuda Tomohisa , Yamaji Hideki
Published: January 2021

Influenza vaccines have long been manufactured in embryonated chicken eggs. This method has some problems such as a long production period (about 6 months) and use of large amounts of infectious pathogens. Recently, the production of recombinant subunit vaccines using the baculovirus–insect cell system has been extensively investigated. In this system, viral immunodominant components can be produced more rapidly and in a larger scale than in the conventional egg-based process. However, continuous production is virtually impossible because infection of recombinant baculovirus results in the death of host insect cells. In the present study, we established stably transformed insect cells that secreted influenza virus-like particles (VLPs) consisting of hemagglutinin (HA), the major protective antigen of influenza A virus, and matrix protein 1 (M1), another structural protein of the virus. Hemagglutination assay and transmission electron microscopy (TEM) suggested that HA produced by recombinant insect cells kept the hemagglutination activity and the morphology of the VLPs was similar to that of wild type influenza virus particles.
Advance Stripper Configuration for Energy-Saving Designs Using Standard Monoethanolamine Absorbent for Post-Combustion Carbon Capture
Authors: Liu Jiain , Chen Ding-Sou
Published: January 2021

In a standard post-combustion carbon capture (PCC) process, the regeneration energy of the CO2 lean solvent dominates the overall energy consumption. The energy reduction achieved by stripper modifications, such as the cold-split bypass, interheated stripper, and integration of both configurations, have been reported in the literature. In the cold-split bypass, the cold rich stream is split to recover the energy contained in the overhead vapor that was directly fed into the condenser in the traditional stripper configuration. The interheated stripper draws the semi-rich solvent from the middle of the stripper and exchanges heat with the hightemperature lean solvent from the reboiler; thereby, the overall column temperature can be raised that favors CO2 desorption along the column. Therefore, the literature reported that the integrated modification, combining the cold-split bypass with the interheated stripper, takes both advantages of above modifications that can further reduce the energy requirement. However, the present work shows that energy-saving effect of integrated process is not as promising as the literature claimed. Once the feed stage of the warm-rich solvent is determined properly, the cold-split process can achieve the similar energy-saving performance as that achieved by the integrated process.
Analysis of Change in the Corporate Sphere of the Czech Republic
Authors: Jambal Tsolmon , Stuchlý Jaroslav
Published: January 2021

This contribution presents research into the changes taking place in companies in the Czech Republic. The aim was to determine whether companies in the Czech Republic are undergoing fundamental changes, what influences are forcing them to change, and whether managers prefer radical changes to incremental improvements. The research was carried out in the form of a questionnaire survey, which consisted of four sections and 60 questions, conducted by teachers and students of VSTE in České Budějovice in 2019. The article analyses the characteristics of the selected statements and examines the interdependencies between the variables, including the dependence on the identified identification variables.
Events as an Effective Marketing Communication Tool
Authors: Vítek Martin
Published: January 2021

A brewery wanted to know how a new beer they were launching would be received by consumers. It was therefore decided to organize an event during which the author of this contribution conducted research. The aim of the research was to find out whether the new product, a low alcohol beer, will attract consumers with its taste, whether its price was set correctly, and whether the targeting and marketing communication tools used were appropriate. The results of the research confirmed that the taste of the new product as well as its price corresponded to the imagination of consumers and that the communication mix was appropriate, but required adjustment to make it even more precise.
Comparative Analysis of the Level of Development of Entrepreneurial Competencies among Students in Russia and the Czech Republic
Authors: Pesha Anastasiya , Shavrovskaya Marina , Caha Zdeněk
Published: January 2021

The role of universities in the development of entrepreneurship is increasing. Within this context, universities are introducing specialized programs and disciplines aimed at developing students’ innovative and entrepreneurial competencies. This article presents the results of a comparative analysis of the level of development of students’ entrepreneurial competencies in Russia and the Czech Republic. To implement the key task, the authors analysed approaches to the classification of entrepreneurial competencies. On the basis of relevance and objectivity, the authors selected the EntreComp classification from 2016, which subsequently formed the basis for the developed methodological tools for the empirical research. The method was tested in three universities in the Russian Federation and one in the Czech Republic. The total number of participants was 436. The results of the analysis of the entrepreneurial competencies revealed significant statistical differences between the respondents from the two countries for 10 out of 15 evaluated competencies. At the same time, 68% of respondents in the Russian Federation and 64% in the Czech Republic were found to have an advanced level of development of one entrepreneurial competence. This fact is indicative of the similarity of the vast majority of the final results for the respondents from both countries and confirms the hypothesis that most students participating in the test did not have a lower than average level of competence development. The results of the study may be of interest to scientists and practitioners who study the assessment and development of entrepreneurial competencies in students and specialists.