bluuebunny/crossref_metadata_2025 huggingface dataset:
More Bone with Less Minerals? The Effects of Dietary Phosphorus on the Post-Cranial Skeleton in Zebrafish
Authors: Cotti Silvia , Huysseune Ann , Koppe Wolfgang , Rücklin Martin , Marone Federica , Wölfel Eva M. , Fiedler Imke A. K. , Busse Björn , Forlino Antonella , Witten P. Eckhard
Published: July 2020

Dietary phosphorus (P) is essential for bone mineralisation in vertebrates. P deficiency can cause growth retardation, osteomalacia and bone deformities, both in teleosts and in mammals. Conversely, excess P supply can trigger soft tissue calcification and bone hypermineralisation. This study uses a wide range of complementary techniques (X-rays, histology, TEM, synchrotron X-ray tomographic microscopy, nanoindentation) to describe in detail the effects of dietary P on the zebrafish skeleton, after two months of administering three different diets: 0.5% (low P, LP), 1.0% (regular P, RP), and 1.5% (high P, HP) total P content. LP zebrafish display growth retardation and hypomineralised bones, albeit without deformities. LP zebrafish increase production of non-mineralised bone matrix, and osteoblasts have enlarged endoplasmic reticulum cisternae, indicative for increased collagen synthesis. The HP diet promotes growth, high mineralisation, and stiffness but causes vertebral centra fusions. Structure and arrangement of bone matrix collagen fibres are not influenced by dietary P in all three groups. In conclusion, low dietary P content stimulates the formation of non-mineralised bone without inducing malformations. This indicates that bone formation and mineralisation are uncoupled. In contrast, high dietary P content promotes mineralisation and vertebral body fusions. This new zebrafish model is a useful tool to understand the mechanisms underlying osteomalacia and abnormal mineralisation, due to underlying variations in dietary P levels.
Insect Physical Control: Electric Field-Based Pest Management Approach
Authors: Toyoda Hideyoshi
Published: July 2020

The Special Issue ‘Insect physical control: electric field-based pest management approach’ was launched to showcase valuable new research on pest control using applied electrostatic engineering. Some phenomena generated in static and dynamic electric fields can be used to build new devices to capture or kill target insects using an attractive force or a force striking insects entering an electric field. This research field is new, and there are few researchers currently working within it. Consequently, this editorial introduces the history and general principles of electric field generation. I then discuss future directions for this field.
The Hidden Burden of Severe Asthma: From Patient Perspective to New Opportunities for Clinicians
Authors: Scichilone Nicola , Barnes Peter John , Battaglia Salvatore , Benfante Alida , Brown Robert , Canonica Giorgio Walter , Caramori Gaetano , Cazzola Mario , Centanni Stefano , Cianferoni Antonella , Corsico Angelo , De Carlo Giuseppe , Di Marco Fabiano , Gaga Mina , Hawrylowicz Catherine , Heffler Enrico , Matera Maria Gabriella , Matucci Andrea , Paggiaro Pierluigi , Papi Alberto , Popov Todor , Rogliani Paola , Santus Pierachille , Solidoro Paolo , Togias Alkis , Boulet Louis-Philippe
Published: July 2020

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the “International Course on Severe Asthma” that took place in Palermo, Italy, on May 10–11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient’s needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach.
Concurrent Disorder Management Guidelines. Systematic Review
Authors: Hakobyan Syune , Vazirian Sara , Lee-Cheong Stephen , Krausz Michael , Honer William G. , Schutz Christian G.
Published: July 2020

Concurrent disorder refers to a diverse set of combinations of substance use disorders and mental disorders simultaneously in need of treatment. Concurrent disorders are underdiagnosed, undertreated, and more complex to manage, practicing the best recommendations can support better outcomes. The purpose of this work is to systematically assess the quality of the current concurrent disorders’ clinical recommendation management guidelines. Literature searches were performed by two independent authors in electronic databases, web, and gray literature. The inclusion criteria were English language clinical management guidelines for adult concurrent disorders between 2000 and 2020. The initial search resulted in 8841 hits. A total of 24 guidelines were identified and assessed with the standardized guidelines assessment tool: AGREE II (Appraisal of Guidelines for Research and Evaluation). Most guidelines had acceptable standards, however, only the NICE guidelines had all detailed information on all AGREE II Domains. Guidelines generally supported combinations of treatments for individual disorders with a very small evidence base for concurrent disorders, and they provided little recommendation for further structuring of the field, such as level of complexity or staging, or evaluating different models of treatment integration.
Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals
Authors: Molina-Carrión Silvia , Brochado-Kith Óscar , González-García Juan , Berenguer Juan , Díez Cristina , Llop Elba , Hontañón Victor , Ibañez-Samaniego Luis , Montes Maria Luisa , Resino Salvador , Fernández-Rodríguez Amanda , Jiménez-Sousa María Ángeles
Published: July 2020

Introduction: Human immunodeficiency virus (HIV) infection and cirrhosis are associated with a senescent phenotype that decreases telomere length. We evaluated the impact of hepatitis C virus (HCV) elimination on telomere length in patients with advanced HCV-related cirrhosis after sustained virological response (SVR), with all-oral direct-acting antiviral agents (DAAs). Methods: Prospective study of 60 HIV/HCV-coinfected and 30 HCV-monoinfected patients with advanced HCV cirrhosis (liver decompensation or liver stiffness measurement (LSM) ≥ 25 kPa, hepatic liver pressure gradient (HVPG) ≥ 10 mmHg, or Child–Pugh–Turcotte (CPT) ≥ 7). The relative telomere length (RTL) was quantified by real-time multiplex PCR (MMqPCR) on peripheral blood mononuclear cells at baseline and 48 weeks after HCV treatment. Generalized linear models (GLMs) adjusted for the most relevant clinical and epidemiological variables and mixed GLMs were used. Results: In comparison with HCV-monoinfected patients, HIV/HCV-coinfected patients were younger (p < 0.001), had lower body mass index (BMI) (p = 0.002), and had been exposed less frequently to interferons (p = 0.011). In addition, they were more frequently men (p = 0.011), smokers (p = 0.005), prior intravenous drug users (IVDUs) (p < 0.001), and alcohol abusers (p = 0.005). RTL was significantly lower in HIV/HCV-coinfected patients than in HCV-monoinfected patients, both at baseline (p < 0.001), and at the end of follow-up (p = 0.032). A significant RTL increase over time was found only for HIV/HCV-coinfected patients (p < 0.001), especially in those patients with compensated cirrhosis (p < 0.001). Conclusion: HCV eradication with all-oral DAAs was associated with an increase in telomere length in HIV/HCV-coinfected patients with advanced cirrhosis, particularly in compensated patients. This finding suggests that HCV clearance may have implications in age-related conditions in this population group.
Impact of Women Obesity and Obesity Severity on Live Birth Rate after In Vitro Fertilization
Authors: Brunet Cécile , Aouinti Safa , Huguet Fanchon , Macioce Valérie , Ranisavljevic Noémie , Gala Anna , Avignon Antoine , Mura Thibault , Sultan Ariane
Published: July 2020

Access to in vitro fertilization (IVF) for obese women varies across centers, and the impact of obesity on IVF outcomes is widely discussed. We assessed the impact of obesity and its severity on live birth rate (LBR) after IVF. We included women treated for IVF in our center. Data were prospectively collected in the BabySentryTM software. LBR per cycle and cumulative LBR including all attempts of the couple were calculated, considering transfer of both fresh and frozen embryos. Of 1588 included women (2379 controlled ovarian stimulations), 70.2%, 19.5%, 7.9%, and 2.4% were normal-weight, overweight, class I obesity, and class II/III obesity, respectively. For each cycle, LBR did not differ according to BMI category. Adjusted odds ratios (95% confidence intervals) for obtaining a live birth at the first cycle were 1.11 (0.78–1.58) for overweight, 1.17 (0.70–1.95) for class I obese, and 1.05 (0.48–2.31) for class II/III obese women, as compared with normal-weight women. Similarly, no significant associations were found at cycles 2, 3, and 4. Cumulative LBR increased with the number of cycles, independently of the BMI class (p log-rank = 0.91). After adjustment, obesity status did not impact significantly the miscarriage rate, regardless of the cycle. In conclusion, neither women obesity nor its severity impacted the cumulative LBR after IVF.
The Reality of Patient-Reported Outcomes of Health-Related Quality of Life in an Italian Cohort of Patients with Inflammatory Bowel Disease: Results from a Cross-Sectional Study
Authors: Larussa Tiziana , Flauti Danilo , Abenavoli Ludovico , Boccuto Luigi , Suraci Evelina , Marasco Raffaella , Imeneo Maria , Luzza Francesco
Published: July 2020

Inflammatory bowel disease (IBD) has a negative impact on patients’ physical and psychological well-being, social performance, and working capacity, thereby worsening their health-related quality of life (HRQoL). Clinicians should take care of the patients’ global health, including the psychological, social, and emotional spheres. We aimed to investigate the reality of patient-reported outcomes of HRQoL in a series of IBD patients. Consecutive Crohn´s disease (CD) and ulcerative colitis (UC) patients in clinical remission were recruited. The survey consisted of the Short Inflammatory Bowel Disease Questionnaire (S-IBDQ), the Hospital Anxiety and Depression Scale (HADS), the Brief Illness Perception Questionnaire (B-IPQ), and a questionnaire dealing with impact of IBD on patients’ lives. Demographic and clinical characteristics were recorded. Of 202 participants (29% CD and 71% UC; 54% male; median age 48 years; mean disease duration 14 ± 11 years), 52% had poor HRQoL, 45% anxiety/depression, and 35% sleep disturbance and a high perception of disease (mean score 42.8 ± 14.3). In the multivariate analysis, a low HRQoL was rather associated with UC than CD (p = 0.037), IBD surgery (p = 0.010), disease duration (p = 0.01), sleep disturbance (p = 0.014), anxiety/depression (p = 0.042), and high illness perception (p = 0.006). IBD affected working performance and social activities in 62% and 74% of patients, respectively. Satisfaction regarding quality of care, biologics, and surgery approach were claimed in 73%, 69%, and 76% of patients, respectively. Although 84% of patients trusted their gastroenterologist, only 66% of them discussed IBD impact on HRQoL during visit. In a series of IBD patients in remission, the low HRQoL was significantly associated with surgery, disease duration, sleep disturbance, anxiety/depression, and high illness perception. Even though patients were satisfied with the quality of their care, it appears that clinicians should pay more attention to patients’ emotional status.
MicroRNA-199b Deregulation Shows a Strong SET-Independent Prognostic Value in Early-Stage Colorectal Cancer
Authors: Cristóbal Ion , Rubio Jaime , Torrejón Blanca , Santos Andrea , Caramés Cristina , Luque Melani , Sanz-Álvarez Marta , Alonso Ruth , Zazo Sandra , Madoz-Gúrpide Juan , Rojo Federico , García-Foncillas Jesús
Published: July 2020

The endogenous PP2A inhibitor SET Nuclear Proto-Oncogene (SET) has been reported to play oncogenic roles and determines poor outcomes in colorectal cancer (CRC). Our group previously showed that miR-199b is deregulated in metastatic CRC, and reduced the cell viability and enhanced the sensitivity of CRC cells to standard induction chemotherapy drugs, mainly through direct negative SET regulation. Clinically, miR-199b downregulation was identified as the molecular mechanism responsible for SET overexpression in around half of metastatic CRC patients. However, the potential clinical value of miR-199b in early-stage CRC remains totally unknown. Thus, here we explored the expression levels of this microRNA in a cohort of 171 early-stage CRC patients using real-time polymerase chain reactions. MiR-199b downregulation was found in 21.6% of cases (37 out of 171) and was significantly associated with those patients with a worse Eastern Cooperative Oncology Group (ECOG) status (p = 0.045). Moreover, miR-199b downregulation predicted shorter overall (p < 0.001) and progression-free survival (p = 0.015). As expected, we next immunohistochemically analyzed SET, observing that it was significantly associated with miR-199b in our cohort. However, multivariate analyses showed that miR-199b was an independent biomarker of poor outcomes in early-stage CRC with a predictive value stronger than SET. In conclusion, our results highlight the potential clinical usefulness of miR-199b and suggest that it could represent a novel molecular target in this disease.
The Impact of Korean Medicine Treatment on the Incidence of Parkinson’s Disease in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study in South Korea
Authors: Noh Hyeonseok , Jang Jeongju , Kwon Seungwon , Cho Seung-Yeon , Jung Woo-Sang , Moon Sang-Kwan , Park Jung-Mi , Ko Chang-Nam , Kim Ho , Park Seong-Uk
Published: July 2020

We aimed to investigate the association between Korean medicine (KM) treatment and the risk of Parkinson’s Disease (PD) in patients with inflammatory bowel disease (IBD) in South Korea. This study analyzed data from the National Health Insurance Service-Senior cohort in South Korea. The 1816 IBD patients enrolled in the analysis comprised 411 who received only conventional treatment (monotherapy group) and 1405 who received both conventional and KM treatments (integrative therapy group). The risk of PD in patients with IBD was significantly lower in the integrative therapy group than in the monotherapy group after adjusting for confounding variables (adjusted hazard ratio (HR), 0.56; 95% confidence interval (CI) = 0.34–0.92). In the mild Charlson Comorbidity Index (CCI) group, the risk of PD in patients with IBD in the integrative therapy group was 0.39 times lower (adjusted HR, 95% CI = 0.20–0.77) than that in the monotherapy group. However, there was no significant difference in the risk of PD in patients with IBD between the integrative therapy and monotherapy groups among individuals with severe CCI (adjusted HR, 0.90; 95% CI = 0.41−1.96). IBD patients are at a decreased risk of PD when they receive integrative therapy. KM treatment may prevent PD in IBD patients.
Neurologic Safety of Etomidate-Based Sedation during Upper Endoscopy in Patients with Liver Cirrhosis Compared with Propofol: A Double-Blind, Randomized Controlled Trial
Authors: Jung Jang Han , Hyun Bomi , Lee Jin , Koh Dong Hee , Kim Jung Hee , Park Se Woo
Published: July 2020

(1) Background: Although etomidate-based sedation is an effective and safe protocol in endoscopic procedures, there is a lack of evidence regarding the safety of etomidate in patients with liver cirrhosis (LC). This study aimed to compare the neurologic safety and efficacy of etomidate and propofol for endoscopic sedation in patients with LC. (2) Methods: From December 2017 to December 2019, consecutive cirrhotic patients who underwent sedative endoscopy using either etomidate or propofol were randomly recruited. The primary endpoint was the number connection test (NCT), and the secondary endpoints included factors for the safety of sedatives during endoscopy. (3) Results: 63 patients were enrolled in each of the etomidate and propofol groups. The NCT times were significantly lower in the etomidate group than in the propofol group. Furthermore, severe or very severe degree of encephalopathy was higher in the propofol group but was not significantly different. Pharmacological properties and the overall incidence of respiratory and cardiovascular events did not differ significantly between the groups. (4) Conclusion: Etomidate-based sedation exacerbates neither subclinical nor overt hepatic encephalopathy. It guarantees efficacies similar to those of propofol regarding rapid sedation, fast recovery, and early discharge, with no increased risk of adverse respiratory or cardiovascular events in patients with LC.
Improvement of the Full-Range Equation for Wave Boundary Layer Thickness
Authors: Tanaka Hitoshi , Tinh Nguyen Xuan , Sana Ahmad
Published: July 2020

In order to improve the accuracy of the original full-range equation for wave boundary layer thickness, with special reference to increasing its applicability to tsunami-scale waves, a theoretical investigation is carried out to derive a dimensionless expression which is valid under both smooth and rough turbulent regimes. A coefficient in the equation is determined through a comparison with k-ω  model computation results for tsunami-waves along with laboratory scale oscillatory flow experiments. Thus, the improved full-range equation for wave boundary layer thickness enables us to cover a wide range of wave periods from wind-wave to tsunami.
3D-Printed Drug Delivery Systems: The Effects of Drug Incorporation Methods on Their Release and Antibacterial Efficiency
Authors: Shaqour Bahaa , Reigada Inés , Górecka Żaneta , Choińska Emilia , Verleije Bart , Beyers Koen , Święszkowski Wojciech , Fallarero Adyary , Cos Paul
Published: July 2020

Additive manufacturing technologies have been widely used in the medical field. More specifically, fused filament fabrication (FFF) 3D-printing technology has been thoroughly investigated to produce drug delivery systems. Recently, few researchers have explored the possibility of directly 3D printing such systems without the need for producing a filament which is usually the feedstock material for the printer. This was possible via direct feeding of a mixture consisting of the carrier polymer and the required drug. However, as this direct feeding approach shows limited homogenizing abilities, it is vital to investigate the effect of the pre-mixing step on the quality of the 3D printed products. Our study investigates the two commonly used mixing approaches—solvent casting and powder mixing. For this purpose, polycaprolactone (PCL) was used as the main polymer under investigation and gentamicin sulfate (GS) was selected as a reference. The produced systems’ efficacy was investigated for bacterial and biofilm prevention. Our data show that the solvent casting approach offers improved drug distribution within the polymeric matrix, as was observed from micro-computed topography and scanning electron microscopy visualization. Moreover, this approach shows a higher drug release rate and thus improved antibacterial efficacy. However, there were no differences among the tested approaches in terms of thermal and mechanical properties.
Experimental Study on the Permeability of SAP Modified Concrete
Authors: Guo Yaohua , Zhang Puyang , Ding Hongyan , Le Conghuan
Published: July 2020

To study the permeability of superabsorbent polymer (SAP) modified concrete and the effect of internal pore characteristics on the permeability of concrete specimens, the results of the water penetration under pressure test, the mercury intrusion porosimetry (MIP) test, and scanning electron microscopy (SEM) of SAP concrete were obtained and analyzed. The research shows that the addition of an appropriate amount of SAP can effectively improve the anti-permeability performance of concrete. After adding 0.2~0.6% SAP of cement quality to concrete, the penetration height value was reduced by 35~45%, the porosity was increased by 21–95%, and the tortuosity is increased by 14–15%, and all indicators show regular changes with the increase in SAP usage. Adding SAP to concrete changes the internal connection state of concrete, thereby further improving its impermeability by reducing the capillary pressure and changing the shape of the pores. The liquid permeation resistance is increased by the “threshold effect” inside concrete; this “threshold effect” is caused by the addition of SAP.
Estimation of the Adhesion Interface Performance in Aluminum-PLA Joints by Thermographic Monitoring of the Material Extrusion Process
Authors: Bechtel Stephan , Meisberger Mirko , Klein Samuel , Heib Tobias , Quirin Steven , Herrmann Hans-Georg
Published: July 2020

Using additive manufacturing to generate a polymer–metal structure offers the potential to achieve a complex customized polymer structure joined to a metal base of high stiffness and strength. A tool to evaluate the generated interface during the process is of fundamental interest, as the sequential deposition of the polymer as well as temperature gradients within the substrate lead to local variations in adhesion depending on the local processing conditions. On preheated aluminum substrates, 0.3 and 0.6 mm high traces of polylactic acid (PLA) were deposited. Based on differential scanning calorimetry (DSC) and rheometry measurements, the substrate temperature was varied in between 150 and 200 °C to identify an optimized manufacturing process. Decreasing the layer height and increasing the substrate temperature promoted wetting and improved the adhesion interface performance as measured in a single lap shear test (up to 7 MPa). Thermographic monitoring was conducted at an angle of 25° with respect to the substrate surface and allowed a thermal evaluation of the process at any position on the substrate. Based on the thermographic information acquired during the first second after extrusion and the preset shape of the polymer trace, the resulting wetting and shear strength were estimated.
New Concepts in Intuitionistic Fuzzy Graph with Application in Water Supplier Systems
Authors: Shao Zehui , Kosari Saeed , Rashmanlou Hossein , Shoaib Muhammad
Published: July 2020

In recent years, the concept of domination has been the backbone of research activities in graph theory. The application of graphic domination has become widespread in different areas to solve human-life issues, including social media theories, radio channels, commuter train transportation, earth measurement, internet transportation systems, and pharmacy. The purpose of this paper was to generalize the idea of bondage set (BS) and non-bondage set (NBS), bondage number α(G), and non-bondage number αk(G), respectively, in the intuitionistic fuzzy graph (IFG). The BS is based on a strong arc (SA) in the fuzzy graph (FG). In this research, a new definition of SA in connection with the strength of connectivity in IFGs was applied. Additionally, the BS, α(G), NBS, and αk(G) concepts were presented in IFGs. Three different examples were described to show the informative development procedure by applying the idea to IFGs. Considering the examples, some results were developed. Also, the applications were utilized in water supply systems. The present study was conducted to make daily life more useful and productive.
Multiple New Paralytic Shellfish Toxin Vectors in Offshore North Sea Benthos, a Deep Secret Exposed
Authors: Dean Karl J. , Hatfield Robert G. , Lee Vanessa , Alexander Ryan P. , Lewis Adam M. , Maskrey Benjamin H. , Teixeira Alves Mickael , Hatton Benjamin , Coates Lewis N. , Capuzzo Elisa , Ellis Jim R. , Turner Andrew D.
Published: July 2020

In early 2018, a large easterly storm hit the East Anglian coast of the UK, colloquially known as the ‘Beast from the East’, which also resulted in mass strandings of benthic organisms. There were subsequent instances of dogs consuming such organisms, leading to illness and, in some cases, fatalities. Epidemiological investigations identified paralytic shellfish toxins (PSTs) as the cause, with toxins present in a range of species and concentrations exceeding 14,000 µg STX eq./kg in the sunstar Crossaster papposus. This study sought to better elucidate the geographic spread of any toxicity and identify any key organisms of concern. During the summers of 2018 and 2019, various species of benthic invertebrates were collected from demersal trawl surveys conducted across a variety of locations in the North Sea. An analysis of the benthic epifauna using two independent PST testing methods identified a ‘hot spot’ of toxic organisms in the Southern Bight, with a mean toxicity of 449 µg STX eq./kg. PSTs were quantified in sea chervil (Alcyonidium diaphanum), the first known detection in the phylum bryozoan, as well as eleven other new vectors (>50 µg STX eq./kg), namely the opisthobranch Scaphander lignarius, the starfish Anseropoda placenta, Asterias rubens, Luidia ciliaris, Astropecten irregularis and Stichastrella rosea, the brittlestar Ophiura ophiura, the crustaceans Atelecyclus rotundatus and Munida rugosa, the sea mouse Aphrodita aculeata, and the sea urchin Psammechinus miliaris. The two species that showed consistently high PST concentrations were C. papposus and A. diaphanum. Two toxic profiles were identified, with one dominated by dcSTX (decarbamoylsaxitoxin) associated with the majority of samples across the whole sampling region. The second profile occurred only in North-Eastern England and consisted of mostly STX (Saxitoxin) and GTX2 (gonyautoxin 2). Consequently, this study highlights widespread and variable levels of PSTs in the marine benthos, together with the first evidence for toxicity in a large number of new species. These findings highlight impacts to ‘One Health’, with the unexpected sources of toxins potentially creating risks to animal, human and environmental health, with further work required to assess the severity and geographical/temporal extent of these impacts.
Mass Spectrometry-Based Metabolomics Combined with Quantitative Analysis of the Microalgal Diatom (Chaetoceros calcitrans)
Authors: Azizan Awanis , Maulidiani M. , R. Rudiyanto , Shaari Khozirah , Ismail Intan Safinar , Nagao Norio , Abas Faridah
Published: July 2020

Although many metabolomics studies of higher land plant species have been conducted, similar studies of lower nonland plant species, which include microalgae, are still developing. The present study represents an attempt to characterize the metabolic profile of a microalgal diatom Chaetoceros calcitrans, by applying high-resolution mass spectrometry detection, via Q-ExactiveTM Plus Orbitrap mass spectrometry. The results showed that 54 metabolites of various classes were tentatively identified. Experimentally, the chloroform and acetone extracts were clearly distinguished from other solvent extracts in chemometric regression analysis using PLS, showing the differences in the C. calcitrans metabolome between the groups. In addition, specific metabolites were evaluated, which supported the finding of antioxidant and anti-inflammatory activities. This study also provides data on the quantitative analysis of four carotenoids based on the identification results. Therefore, these findings could serve as a reliable tool for identifying and quantifying the metabolome that could reflect the metabolic activities of C. calcitrans.
The κ-Carbides in Low-Density Fe-Mn-Al-C Steels: A Review on Their Structure, Precipitation and Deformation Mechanism
Authors: Chen Peng , Li Xiaowu , Yi Hongliang
Published: July 2020

Fe-Mn-Al-C steels exhibit an outstanding combination of strength and ductility, and the addition of aluminum drastically reduces the density of steels. The low density also offers the advantage of lightweight structures compared with other alloys in practical applications. The addition of aluminum leads to an increased probability of κ-carbide precipitation, which would significantly affect the mechanical properties. This paper aims to review the κ-carbide in Fe-Mn-Al-C steels, including the structure, elastic and magnetic properties of κ-carbide, the precipitation mechanism of κ-carbide involving thermodynamic equilibrium, and the operative deformation mechanism of κ-carbide that governs the mechanical properties. It is hoped that such a comprehensive summarization of the knowledge of κ-carbide will be beneficial for the further development of low-density Fe-Mn-Al-C steels.
Probiotics for the Treatment of Overweight and Obesity in Humans—A Review of Clinical Trials
Authors: Wiciński Michał , Gębalski Jakub , Gołębiewski Jakub , Malinowski Bartosz
Published: July 2020

The World Health Organization (WHO) reports that 400 million people are obese, and over 1.6 billion adults are overweight worldwide. Annually, over 2.8 million people die from obesity-related diseases. The incidence of overweight and obesity is steadily increasing, and this phenomenon is referred to as a 21st-century pandemic. The main reason for this phenomenon is an easy access to high-energy, processed foods, and a low-activity lifestyle. These changes lead to an energy imbalance and, as a consequence, to the development of body fat. Weight gain contributes to the development of heart diseases, skeletal system disorders, metabolic disorders such as diabetes, and certain types of cancer. In recent years, there have been many works linking obesity with intestinal microbiota. Experiments on germ-free animals (GFs) have provided much evidence for the contribution of bacteria to obesity. The composition of the gut microbiota (GM) changes in obese people. These changes affect the degree of energy obtained from food, the composition and secretory functions of adipose tissue, carbohydrate, and lipid metabolism in the liver, and the activity of centers in the brain. The study aimed to present the current state of knowledge about the role of intestinal microbiota in the development of obesity and the impact of supplementation with probiotic bacteria on the health of overweight and obese patients.
Sugar Production from Hybrid Poplar Sawdust: Optimization of Enzymatic Hydrolysis and Wet Explosion Pretreatment
Authors: Biswas Rajib , Teller Philip J. , Khan Muhammad U. , Ahring Birgitte K.
Published: July 2020

Wet explosion pretreatment of hybrid poplar sawdust (PSD) for the production of fermentable sugar was carried out in the pilot-scale. The effects of pretreatment conditions, such as temperature (170–190 °C), oxygen dosage (0.5–7.5% of dry matter (DM), w/w), residence time (10–30 min), on cellulose and hemicellulose digestibility after enzymatic hydrolysis were ascertained with a central composite design of the experiment. Further, enzymatic hydrolysis was optimized in terms of temperature, pH, and a mixture of CTec2 and HTec2 enzymes (Novozymes). Predictive modeling showed that cellulose and hemicellulose digestibility of 75.1% and 83.1%, respectively, could be achieved with a pretreatment at 177 °C with 7.5% O2 and a retention time of 30 min. An increased cellulose digestibility of 87.1% ± 0.1 could be achieved by pretreating at 190 °C; however, the hemicellulose yield would be significantly reduced. It was evident that more severe conditions were required for maximal cellulose digestibility than that of hemicellulose digestibility and that an optimal sugar yield demanded a set of conditions, which overall resulted in the maximum sugar yield.
Identification and Characterization of a Novel N- and O-Glycosyltransferase from Saccharopolyspora erythraea
Authors: Gutacker Fabienne , Schmidt-Bohli Yvonne-Isolde , Strobel Tina , Qiu Danye , Jessen Henning , Paululat Thomas , Bechthold Andreas
Published: July 2020

Glycosyltransferases are important enzymes which are often used as tools to generate novel natural products. In this study, we describe the identification and characterization of an inverting N- and O-glycosyltransferase from Saccharopolyspora erythraea NRRL2338. When feeding experiments with 1,4-diaminoanthraquinone in Saccharopolyspora erythraea were performed, the formation of new compounds (U3G and U3DG) was observed by HPLC-MS. Structure elucidation by NMR revealed that U3G consists of two compounds, N1-α-glucosyl-1,4-diaminoanthraquinone and N1-β-glucosyl-1,4-diaminoanthraquinone. Based on UV and MS data, U3DG is a N1,N4-diglucosyl-1,4-diaminoanthraquinone. In order to find the responsible glycosyltransferase, gene deletion experiments were performed and we identified the glycosyltransferase Sace_3599, which belongs to the CAZy family 1. When Streptomyces albus J1074, containing the dTDP-d-glucose synthase gene oleS and the plasmid pUWL-A-sace_3599, was used as host, U3 was converted to the same compounds. Protein production in Escherichia coli and purification of Sace_3599 was carried out. The enzyme showed glycosyl hydrolase activity and was able to produce mono- and di-N-glycosylated products in vitro. When UDP-α-d-glucose was used as a sugar donor, U3 was stereoselective converted to N1-β-glucosyl-1,4-diaminoanthraquinone and N1,N4-diglucosyl-1,4-diaminoanthraquinone. The use of 1,4-dihydroxyanthraquinone as a substrate in in vitro experiments also led to the formation of mono-glucosylated and di-glucosylated products, but in lower amounts. Overall, we identified and characterized a novel glycosyltransferase which shows glycohydrolase activity and the ability to glycosylate “drug like” structures forming N- and O-glycosidic bonds.
Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics
Authors: Meléndez-Martínez David , Plenge-Tellechea Luis Fernando , Gatica-Colima Ana , Cruz-Pérez Martha Sandra , Aguilar-Yáñez José Manuel , Licona-Cassani Cuauhtémoc
Published: July 2020

Chronic wounds are a major health problem that cause millions of dollars in expenses every year. Among all the treatments used, active wound treatments such as enzymatic treatments represent a cheaper and specific option with a fast growth category in the market. In particular, bacterial and plant proteases have been employed due to their homology to human proteases, which drive the normal wound healing process. However, the use of these proteases has demonstrated results with low reproducibility. Therefore, alternative sources of proteases such as snake venom have been proposed. Here, we performed a functional mining of proteases from rattlesnakes (Crotalus ornatus, C. molossus nigrescens, C. scutulatus, and C. atrox) due to their high protease predominance and similarity to native proteases. To characterize Crotalus spp. Proteases, we performed different protease assays to measure and confirm the presence of metalloproteases and serine proteases, such as the universal protease assay and zymography, using several substrates such as gelatin, casein, hemoglobin, L-TAME, fibrinogen, and fibrin. We found that all our venom extracts degraded casein, gelatin, L-TAME, fibrinogen, and fibrin, but not hemoglobin. Crotalus ornatus and C. m. nigrescens extracts were the most proteolytic venoms among the samples. Particularly, C. ornatus predominantly possessed low molecular weight proteases (P-I metalloproteases). Our results demonstrated the presence of metalloproteases capable of degrading gelatin (a collagen derivative) and fibrin clots, whereas serine proteases were capable of degrading fibrinogen-generating fibrin clots, mimicking thrombin activity. Moreover, we demonstrated that Crotalus spp. are a valuable source of proteases that can aid chronic wound-healing treatments.
The Mineral Profile of Polish Beers by Fast Sequential Multielement HR CS FAAS Analysis and Its Correlation with Total Phenolic Content and Antioxidant Activity by Chemometric Methods
Authors: Zambrzycka-Szelewa Elżbieta , Nalewajko-Sieliwoniuk Edyta , Zaremba Mariusz , Bajguz Andrzej , Godlewska-Żyłkiewicz Beata
Published: July 2020

Beer is the most common alcoholic beverage worldwide, and is an excellent source of macro- and microelements, as well as phenolic compounds. In this study, a fast method for the determination of Na, K, Mg, Ca, Fe, Mn, and Cu in beer was developed using flame atomic absorption spectrometry. The precision of this method was between 0.8 and 8.0% (as the relative standard deviation (RSD)), and limits of detections were in the range of 0.45 (Mn)–94 µg/L (Na). Among the macroelements tested in the beer samples, K was found at the highest concentration, whereas Na was found at the lowest concentration level. Beer also turned out to be a good source of Mg and K. The total phenolic content (TPC) was determined by the Folin–Ciocalteu method, while the antioxidant activity was estimated by the ABTS method. The results show remarkable variations in the mineral content, TPC, and antioxidant activity across the beer types and brands. Moreover, the relations between the type, color, refraction index, antioxidant activity, extract, alcohol, mineral, and the total phenolic contents were investigated using the factor analysis of mixed data (FAMD) combined with hierarchical clustering on principal components (HCPC).
Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)
Authors: Mohd Sakeh Nurshafika , Md Razip Nurliyana Najwa , Mohd Ma’in Farah Idayu , Abdul Bahari Mohammad Nazri , Latif Naimah , Akhtar Muhammad Nadeem , Balia Yusof Zetty Norhana , Ahmad Syahida
Published: July 2020

Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
Multilayer Gold-Silver Bimetallic Nanostructures to Enhance SERS Detection of Drugs
Authors: Gambucci Marta , Cambiotti Elena , Sassi Paola , Latterini Loredana
Published: July 2020

Surface-enhanced Raman scattering (SERS) is a widely used technique for drug detection due to high sensitivity and molecular specificity. The applicability and selectivity of SERS in the detection of specific drug molecules can be improved by gathering information on the specific interactions occurring between the molecule and the metal surface. In this work, multilayer gold-silver bimetallic nanorods (Au@Ag@AuNRs) have been prepared and used as platforms for SERS detection of specific drugs (namely promethazine, piroxicam, furosemide and diclofenac). The analysis of SERS spectra provided accurate information on the molecular location upon binding and gave some insight into molecule-surface interactions and selectivity in drug detection through SERS.
The Secret Lives of Fluorescent Membrane Probes as Revealed by Molecular Dynamics Simulations
Authors: Filipe Hugo A. L. , Moreno Maria João , Loura Luís M. S.
Published: July 2020

Fluorescent probes have been employed for more than half a century to study the structure and dynamics of model and biological membranes, using spectroscopic and/or microscopic experimental approaches. While their utilization has led to tremendous progress in our knowledge of membrane biophysics and physiology, in some respects the behavior of bilayer-inserted membrane probes has long remained inscrutable. The location, orientation and interaction of fluorophores with lipid and/or water molecules are often not well known, and they are crucial for understanding what the probe is actually reporting. Moreover, because the probe is an extraneous inclusion, it may perturb the properties of the host membrane system, altering the very properties it is supposed to measure. For these reasons, the need for independent methodologies to assess the behavior of bilayer-inserted fluorescence probes has been recognized for a long time. Because of recent improvements in computational tools, molecular dynamics (MD) simulations have become a popular means of obtaining this important information. The present review addresses MD studies of all major classes of fluorescent membrane probes, focusing in the period between 2011 and 2020, during which such work has undergone a dramatic surge in both the number of studies and the variety of probes and properties accessed.
Effect of Distance from Catalytic Synergy Group to Iron Porphyrin Center on Activity of G-Quadruplex/Hemin DNAzyme
Authors: Qiu Dehui , Mo Jingang , Liu Yuan , Zhang Jiangyan , Cheng Yongqiang , Zhang Xiaobo
Published: July 2020

G-quadruplex/Hemin (G4/Hemin) complex has been widely used in biocatalysis and analytical applications. Meanwhile, compared with natural proteinous enzyme, its low catalytic activity is still limiting its applications. Even though several methods have been developed to enhance the peroxidation efficiency, the important core of the G4 design based enhancement mechanism is still indistinct. Here, we focus the mechanism study on the two most important microdomains: the iron porphyrin center and the catalytic synergy group within the 3′ flanking. These microdomains not only provide the pocket for the combination of substrate, but also offer the axial coordination for the accelerated formation of Compound I (catalytic intermediate). In order to obtain a more suitable space layout to further accelerate the catalytic process, we have used the bases within the 3′ flanking to precisely regulate the distance between microdomains. Finally, the position-dependent effect on catalytic enhancement is observed. When dC is positioned at the second-position of 3′ flanking, the newly obtained DNAzyme achieves an order of magnitude improvement compared to parent G4/Hemin in catalytic activity. The results highlight the influence of the distance between the catalytic synergy group and iron porphyrin center on the activity of DNAzyme, and provide insightful information for the design of highly active DNAzymes.
Antinociceptive and Cytotoxic Activity of Opioid Peptides with Hydrazone and Hydrazide Moieties at the C-Terminus
Authors: Dyniewicz Jolanta , Lipiński Piotr F. J. , Kosson Piotr , Bochyńska-Czyż Marta , Matalińska Joanna , Misicka Aleksandra
Published: July 2020

In the present contribution, we analyze the influence that C-terminal extension of short opioid peptide sequences by organic fragments has on receptor affinity, in vivo analgesic activity, and antimelanoma properties. The considered fragments were based on either N-acylhydrazone (NAH) or N′-acylhydrazide motifs combined with the 3,5-bis(trifluoromethyl)phenyl moiety. Eleven novel compounds were synthesized and subject to biological evaluation. The analyzed compounds exhibit a diversified range of affinities for the µ opioid receptor (MOR), rather low δ opioid receptor (DOR) affinities, and no appreciable neurokinin-1 receptor binding. In three out of four pairs, N-acylhydrazone-based derivatives bind MOR better than their N’-acylhydrazide counterparts. The best of the novel derivatives have similar low nanomolar MOR binding affinity as the reference opioids, such as morphine and biphalin. The obtained order of MOR affinities was compared to the results of molecular docking. In vivo, four tested compounds turned out to be relatively strong analgesics. Finally, the NAH-based analogues reduce the number of melanoma cells in cell culture, while their N′-acylhydrazide counterparts do not. The antimelanoma properties are roughly correlated to the lipophilicity of the compounds.
Ion-Pair Interaction and Hydrogen Bonds as Main Features of Protein Thermostability in Mutated T1 Recombinant Lipase Originating from Geobacillus zalihae
Authors: Ishak Siti Nor Hasmah , Kamarudin Nor Hafizah Ahmad , Ali Mohd Shukuri Mohamad , Leow Adam Thean Chor , Rahman Raja Noor Zaliha Raja Abd.
Published: July 2020

A comparative structure analysis between space- and an Earth-grown T1 recombinant lipase from Geobacillus zalihae had shown changes in the formation of hydrogen bonds and ion-pair interactions. Using the space-grown T1 lipase validated structure having incorporated said interactions, the recombinant T1 lipase was re-engineered to determine the changes brought by these interactions to the structure and stability of lipase. To understand the effects of mutation on T1 recombinant lipase, five mutants were developed from the structure of space-grown T1 lipase and biochemically characterized. The results demonstrate an increase in melting temperature up to 77.4 °C and 76.0 °C in E226D and D43E, respectively. Moreover, the mutated lipases D43E and E226D had additional hydrogen bonds and ion-pair interactions in their structures due to the improvement of stability, as observed in a longer half-life and an increased melting temperature. The biophysical study revealed differences in β-Sheet percentage between less stable (T118N) and other mutants. As a conclusion, the comparative analysis of the tertiary structure and specific residues associated with ion-pair interactions and hydrogen bonds could be significant in revealing the thermostability of an enzyme with industrial importance.
Apoferritin and Apoferritin-Capped Metal Nanoparticles Inhibit Arginine Kinase of Trypanosoma brucei
Authors: Adeyemi Oluyomi Stephen , Arowolo Afolake T. , Hetta Helal F. , Al-Rejaie Salim , Rotimi Damilare , Batiha Gaber El-Saber
Published: July 2020

The aim of this study was to explore the inhibitory potential of apoferritin or apoferritin-capped metal nanoparticles (silver, gold and platinum) against Trypanosomabrucei arginine kinase. The arginine kinase activity was determined in the presence and absence of apoferritin or apoferritin-capped metal nanoparticles. In addition, kinetic parameters and relative inhibition of enzyme activity were estimated. Apoferritin or apoferritin-capped metal nanoparticles’ interaction with arginine kinase of T. brucei led to a >70% reduction in the enzyme activity. Further analysis to determine kinetic parameters suggests a mixed inhibition by apoferritin or apoferritin-nanoparticles, with a decrease in Vmax. Furthermore, the Km of the enzyme increased for both ATP and L-arginine substrates. Meantime, the inhibition constant (Ki) values for the apoferritin and apoferritin-nanoparticle interaction were in the submicromolar concentration ranging between 0.062 to 0.168 nM and 0.001 to 0.057 nM, respectively, for both substrates (i.e., L-arginine and ATP). Further kinetic analyses are warranted to aid the development of these nanoparticles as selective therapeutics. Also, more studies are required to elucidate the binding properties of these nanoparticles to arginine kinase of T. brucei.