bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal Exposure to Preeclampsia and Long-Term Ophthalmic Morbidity of the Offspring
Authors: Kedar Sade Eliel , Wainstock Tamar , Tsumi Erez , Sheiner Eyal
Published: April 2020

The aim of this population-based study was to evaluate whether prenatal exposure to preeclampsia poses a risk for long-term ophthalmic morbidity. A population-based cohort analysis compared the risk of long-term ophthalmic morbidity among children who were prenatally exposed to preeclampsia and those who were not. The study population was composed of children who were born between the years 1991 and 2014 at a single tertiary medical center. Total ophthalmic hospitalization and time-to-event were both evaluated. A Kaplan–Meier survival curve was conducted to compare cumulative ophthalmic hospitalization incidence based on the severity of preeclampsia. Confounders were controlled using a Cox regression model. A total of 242,342 deliveries met the inclusion criteria, of which 7279 (3%) were diagnosed with mild preeclampsia and 2222 (0.92%) with severe preeclampsia or eclampsia. A significant association was found between severe preeclampsia or eclampsia and the risk of long-term vascular-associated ophthalmic morbidity in the offspring (no preeclampsia 0.3%, mild preeclampsia 0.2% and severe preeclampsia or eclampsia 0.5%, p = 0.008). This association persisted after controlling for maternal age and ethnicity (adjusted hazard ratio (HR) 1.861, 95% CI 1.051–3.295). In conclusion, within our population, prenatal exposure to severe preeclampsia or eclampsia was found to be a risk factor for long-term vascular-associated ophthalmic morbidity in the offspring.
Revisiting Inflammatory Bowel Disease: Pathology, Treatments, Challenges and Emerging Therapeutics Including Drug Leads from Natural Products
Authors: Yeshi Karma , Ruscher Roland , Hunter Luke , Daly Norelle L. , Loukas Alex , Wangchuk Phurpa
Published: April 2020

Inflammatory bowel disease (IBD) is a chronic and life-long disease characterized by gastrointestinal tract inflammation. It is caused by the interplay of the host’s genetic predisposition and immune responses, and various environmental factors. Despite many treatment options, there is no cure for IBD. The increasing incidence and prevalence of IBD and lack of effective long-term treatment options have resulted in a substantial economic burden to the healthcare system worldwide. Biologics targeting inflammatory cytokines initiated a shift from symptomatic control towards objective treatment goals such as mucosal healing. There are seven monoclonal antibody therapies excluding their biosimilars approved by the US Food and Drug Administration for induction and maintenance of clinical remission in IBD. Adverse side effects associated with almost all currently available drugs, especially biologics, is the main challenge in IBD management. Natural products have significant potential as therapeutic agents with an increasing role in health care. Given that natural products display great structural diversity and are relatively easy to modify chemically, they represent ideal scaffolds upon which to generate novel therapeutics. This review focuses on the pathology, currently available treatment options for IBD and associated challenges, and the roles played by natural products in health care. It discusses these natural products within the current biodiscovery research agenda, including the applications of drug discovery techniques and the search for next-generation drugs to treat a plethora of inflammatory diseases, with a major focus on IBD.
The Effect of a Virtual Reality-Based Intervention Program on Cognition in Older Adults with Mild Cognitive Impairment: A Randomized Control Trial
Authors: Thapa Ngeemasara , Park Hye Jin , Yang Ja-Gyeong , Son Haeun , Jang Minwoo , Lee Jihyeon , Kang Seung Wan , Park Kyung Won , Park Hyuntae
Published: April 2020

This study aimed to investigate the association between a virtual reality (VR) intervention program and cognitive, brain and physical functions in high-risk older adults. In a randomized controlled trial, we enrolled 68 individuals with mild cognitive impairment (MCI). The MCI diagnosis was based on medical evaluations through a clinical interview conducted by a dementia specialist. Cognitive assessments were performed by neuropsychologists according to standardized methods, including the Mini-Mental State Examination (MMSE) and frontal cognitive function: trail making test (TMT) A & B, and symbol digit substitute test (SDST). Resting state electroencephalogram (EEG) was measured in eyes open and eyes closed conditions for 5 minutes each, with a 19-channel wireless EEG device. The VR intervention program (3 times/week, 100 min each session) comprised four types of VR game-based content to improve the attention, memory and processing speed. Analysis of the subjects for group–time interactions revealed that the intervention group exhibited a significantly improved executive function and brain function at the resting state. Additionally, gait speed and mobility were also significantly improved between and after the follow-up. The VR-based training program improved cognitive and physical function in patients with MCI relative to controls. Encouraging patients to perform VR and game-based training may be beneficial to prevent cognitive decline.
Current Concepts on the Reno-Protective Effects of Phosphodiesterase 5 Inhibitors in Acute Kidney Injury: Systematic Search and Review
Authors: Georgiadis Georgios , Zisis Ioannis-Erineos , Docea Anca Oana , Tsarouhas Konstantinos , Fragkiadoulaki Irene , Mavridis Charalampos , Karavitakis Markos , Stratakis Stavros , Stylianou Kostas , Tsitsimpikou Christina , Calina Daniela , Sofikitis Nikolaos , Tsatsakis Aristidis , Mamoulakis Charalampos
Published: April 2020

Acute kidney injury (AKI) is associated with increased morbidity, prolonged hospitalization, and mortality, especially in high risk patients. Phosphodiesterase 5 inhibitors (PDE5Is), currently available as first-line therapy of erectile dysfunction in humans, have shown a beneficial potential of reno-protection through various reno-protective mechanisms. The aim of this work is to provide a comprehensive overview of the available literature on the reno-protective properties of PDE5Is in the various forms of AKI. Medline was systematically searched from 1946 to November 2019 to detect all relevant animal and human studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 83 studies were included for qualitative synthesis. Sildenafil is the most widely investigated compound (42 studies), followed by tadalafil (20 studies), icariin (10 studies), vardenafil (7 studies), zaprinast (4 studies), and udenafil (2 studies). Even though data are limited, especially in humans with inconclusive or negative results of only two clinically relevant studies available at present, the results of animal studies are promising. The reno-protective action of PDE5Is was evident in the vast majority of studies, independently of the AKI type and the agent applied. PDE5Is appear to improve the renal functional/histopathological alternations of AKI through various mechanisms, mainly by affecting regional hemodynamics, cell expression, and mitochondrial response to oxidative stress and inflammation.
Salivary Gland Dysfunction, Protein Glycooxidation and Nitrosative Stress in Children with Chronic Kidney Disease
Authors: Maciejczyk Mateusz , Szulimowska Julita , Taranta-Janusz Katarzyna , Wasilewska Anna , Zalewska Anna
Published: April 2020

This study is the first to evaluate protein glycooxidation products, lipid oxidative damage and nitrosative stress in non-stimulated (NWS) and stimulated whole saliva (SWS) of children with chronic kidney disease (CKD) divided into two subgroups: normal salivary secretion (n = 18) and hyposalivation (NWS flow < 0.2 mL min−1; n = 12). Hyposalivation was observed in all patients with severe renal failure (4–5 stage CKD), while saliva secretion > 0.2 mL/min in children with mild-moderate CKD (1–3 stage) and controls. Salivary amylase activity and total protein content were significantly lower in CKD children with hyposalivation compared to CKD patients with normal saliva secretion and control group. The fluorescence of protein glycooxidation products (kynurenine, N-formylkynurenine, advanced glycation end products), the content of oxidative damage to lipids (4-hydroxynonneal, 8-isoprostanes) and nitrosative stress (peroxynitrite, nitrotyrosine) were significantly higher in NWS, SWS, and plasma of CKD children with hyposalivation compared to patients with normal salivary secretion and healthy controls. In CKD group, salivary oxidation products correlated negatively with salivary flow rate, α-amylase activity and total protein content; however, salivary oxidation products do not reflect their plasma level. In conclusion, children with CKD suffer from salivary gland dysfunction. Oxidation of salivary proteins and lipids increases with CKD progression and deterioration of salivary gland function.
Compliance of Atrial Fibrillation Treatment with the Atrial Fibrillation Better Care (ABC) Pathway Improves the Clinical Outcomes in the Middle East Population: A Report from the Gulf Survey of Atrial Fibrillation Events (SAFE) Registry
Authors: Gumprecht Jakub , Domek Magdalena , Proietti Marco , Li Yan-Guang , Asaad Nidal , Rashed Wafa , Alsheikh-Ali Alawi , Zubaid Mohammad , Lip Gregory Y. H.
Published: April 2020

Atrial fibrillation (AF) is associated with substantially increased risk of cardiovascular events and overall mortality. The Atrial fibrillation Better Care (A—Avoid stroke, B—Better symptom management, C—Cardiovascular and comorbidity risk management) pathway provides a simple and comprehensive approach for integrated AF therapy. This study’s goals were to evaluate the ABC pathway compliance and determine the main gaps in AF management in the Middle East population, and to assess the impact of ABC pathway adherence on the all-cause mortality and composite outcome in AF patients. 2021 patients (mean age 57; 52% male) from the Gulf SAFE registry were studied. We evaluated: A—appropriate implementation of OACs according to CHA2DS2-VASc score; B—symptom control according to European Heart Rhythm Association (EHRA) symptom scale; C—proper cardiovascular comorbidities management. The primary endpoints were the composite cardiovascular outcome (ischemic stroke or systemic embolism, all-cause death and cardiovascular hospitalization) and all-cause mortality. One-hundred and sixty-eight (8.3%) patients were optimally managed according to adherence with the ABC pathway. Over the one-year follow up (FU), there were 578 composite outcome events and 224 deaths. Patients managed with integrated care had significantly lower rates for the composite outcome and mortality comparing to non-ABC group (20.8% vs. 29.3%, p = 0.02 and 7.3% vs. 13.1%, p = 0.033, respectively). On multivariable analysis, ABC compliance was independently associated with reduced risk of composite outcome (HR 0.53; 95% CI 0.36–0.8, p = 0.002) and death (HR 0.46; 95% CI 0.25–0.86, p = 0.015). Integrated ABC pathway adherent care resulted in the reduced composite outcome and all-cause mortality in AF patients from Middle East, highlighting the necessity of promoting comprehensive holistic and integrated care management of AF.
Features of Earthquake-Induced Seabed Liquefaction and Mitigation Strategies of Novel Marine Structures
Authors: Huang Yu , Han Xu
Published: April 2020

With the accelerated development of marine engineering, a growing number of marine structures are being constructed (e.g., seabed pipelines, drilling platforms, oil platforms, wind turbines). However, seismic field investigations over recent decades have shown that many marine structures were damaged or destroyed due to liquefaction. Seismic liquefaction in marine engineering can have huge financial repercussions as well as a devastating effect on the marine environment, which merits our great attention. As the effects of seawater and the gas component in the seabed layers are not negligible, the seabed soil layers are more prone to liquefaction than onshore soil layers, and the liquefied area may be larger than when liquefaction occurs on land. To mitigate the impact of liquefaction events on marine engineering structures, some novel liquefaction-resistant marine structures have been proposed in recent years. This paper reviews the features of earthquake-induced liquefaction and the mitigation strategies for marine structures to meet the future requirements of marine engineering.
Coastal Phytoplankton Pigments Composition in Three Tropical Estuaries of Indonesia
Authors: Damar Ario , Colijn Franciscus , Hesse Karl-Juergen , Kurniawan Fery
Published: April 2020

In this study, the composition and distribution of phytoplankton pigments and its relation to nutrients and light was investigated, and an elaboration of using it as a proxy for phytoplankton group composition followed, in different nutrient-level tropical bays of Indonesia. Phytoplankton pigment analysis by using High Performance Liquid Chromatographer (HPLC) resulted in a set of pigments of chlorophyll-a (Chl-a), chlorophyll-b (Chl-b), chlorophyll-c (Chl-c), lutein, zeaxanthin, fucoxanthin, peridinin, diadinoxanthin, and ß-carotene. Linear multi regression and multivariate principal component analysis (PCA) showed that algae pigments correlate positively with nutrients and are not significantly correlated with underwater light and water transparency, suggesting important roles of nutrients for phytoplankton development in tropical estuaries. There were differences in total algae pigment concentration between bays (p < 0.005), showing that the eutrophic system of Jakarta Bay was the highest (mean of 10.55 μg L−1), Lampung Bay was the second highest (mean of 3.37 μg L−1), and the lowest were the oligotrophic waters of Semangka Bay (mean of 0.80 μg L−1). At all bays studied, high nutrient sites, which were located in the river mouths and inner part of the bay, were always characterized by high phytoplankton pigment concentration. Pigment composition had a high correlation with phytoplankton composition: diatoms with fucoxanthin, dinoflagellates with peridinin and Chl-c, and Chlorophyceae with Chl-b and lutein. This conformity suggests that algae pigments can be used as a biomarker for phytoplankton group determination along with microscopic species identification.
CFD Simulation of Ship Seakeeping Performance and Slamming Loads in Bi-Directional Cross Wave
Authors: Jiao Jialong , Huang Songxing
Published: April 2020

Accurate prediction of ship seakeeping performance in complex ocean environment is a fundamental requirement for ship design and actual operation in seaways. In this paper, an unsteady Reynolds-averaged Navier–Stokes (RANS) computational fluid dynamics (CFD) solver with overset grid technique was applied to estimate the seakeeping performance of an S175 containership operating in bi-directional cross waves. The cross wave is reproduced by linear superposition of two orthogonal regular waves in a rectangle numerical wave tank. The ship nonlinear motion responses, bow slamming loads, and green water on deck induced by cross wave with different control parameters such as wave length and wave heading angle are systemically analyzed. The results demonstrate that both vertical and transverse motion responses, as well as slamming pressure of ship induced by cross wave, can be quite large, and they are quite different from those in regular wave. Therefore, ship navigational safety when suffering cross waves should be further concerned.
Landslide Mapping and Susceptibility Assessment Using Geospatial Analysis and Earth Observation Data
Authors: Psomiadis Emmanouil , Papazachariou Andreas , Soulis Konstantinos , Alexiou Despoina-Simoni , Charalampopoulos Ioannis
Published: April 2020

The western part of Crete Island has undergone serious landslide events in the past. The intense rainfalls that took place in the September 2018 to February 2019 period provoked extensive landslide events at the northern part of Chania prefecture, along the motorway A90. Geospatial analysis methods and earth observation data were utilized to investigate the impact of the various physical and anthropogenic factors on landslides and to evaluate landslide susceptibility. The landslide inventory map was created based on literature, aerial photo analysis, satellite images, and field surveys. A very high-resolution Digital Elevation Model (DEM) and land cover map was produced from a dense point cloud and Earth Observation data (Landsat 8), accordingly. Sentinel-2 data were used for the detection of the recent landslide events and offered suitable information for two of them. Eight triggering factors were selected and manipulated in a GIS-based environment. A semi-quantitative method of Analytical Hierarchy Process (AHP) and Weighted Linear Combination (WLC) was applied to evaluate the landslide susceptibility index (LSI) both for Chania prefecture and the motorway A90 in Chania. The validation of the two LSI maps provided accurate results and, in addition, several susceptible points with high landslide hazards along the motorway A90 were detected.
On Hybrid Contractions in the Context of Quasi-Metric Spaces
Authors: Fulga Andreea , Karapınar Erdal , Petruşel Gabriela
Published: April 2020

In this manuscript, we will investigate the existence of fixed points for mappings that satisfy some hybrid type contraction conditions in the setting of quasi-metric spaces. We provide examples to assure the validity of the given results. The results of this paper generalize several known theorems in the recent literature.
Chitosan-Gentamicin Conjugate Hydrogel Promoting Skin Scald Repair
Authors: Yan Tingting , Kong Songzhi , Ouyang Qianqian , Li Chengpeng , Hou Tingting , Chen Yu , Li Sidong
Published: April 2020

Our earlier research indicated that chitosan-gentamicin conjugate (CS-GT) possesses superior antimicrobial activity and good water solubility. To develop CS-GT-based scald dressings, the antibacterial properties of CS-GT were further studied, and the biosafety of CS-GT and the healing mechanism of CS-GT hydrogel was systematically explored in this article. It was found that cell viability shows a declined inclination with the prolonged culture time and the increased concentration of CS-GT. After three day’s culture, the cell viability could still remain at 79.72% when CS-GT concentration was as high as 1000 μg/mL. On the other hand, the hemolysis rate of CS-GT was lower than 5% when its concentration is 800 μg/mL. Therefore CS-GT has good cytocompatibility and hemocompatibility. A wound-healing experiment has shown that the skin healing rate of CS-GT hydrogel was the highest at 99.61%, followed by the positive control (wet burn ointment) 94.98%, GT hydrogel 87.50%, and matrix 77.39%. The blank control group, however, possessed the lowest healing rate of 75.45%. Further analysis indicated that CS-GT hydrogel could promote the synthesis of total protein (TP) in skin granulation tissue, resulting in the enhanced hydroxyproline (HYP) content, which facilitated collagen fibrogenesis, reduced cytokine expression in an inflammatory response, and, ultimately, accelerated wound healing. To sum up, CS-GT hydrogel is a promising scald dressing.
Transport Properties and Mechanical Features of Sulfonated Polyether Ether Ketone/Organosilica Layered Materials Nanocomposite Membranes for Fuel Cell Applications
Authors: Simari Cataldo , Enotiadis Apostolos , Nicotera Isabella
Published: April 2020

In this work, we study the preparation of new sulfonated polyether ether ketone (sPEEK) nanocomposite membranes, containing highly ionic silica layered nanoadditives, as a low cost and efficient proton exchange membranes for fuel cell applications. To achieve the best compromise among mechanical strength, dimensional stability and proton conductivity, sPEEK polymers with different sulfonation degree (DS) were examined. Silica nanoplatelets, decorated with a plethora of sulfonic acid groups, were synthesized through the one-step process, and composite membranes at 1, 3 and 5 wt% of filler loadings were prepared by a simple casting procedure. The presence of ionic layered additives improves the mechanical strength, the water retention capacity and the transport properties remarkably. The nanocomposite membrane with 5% wt of nanoadditive exhibited an improvement of tensile strength almost 160% (68.32 MPa,) with respect to pristine sPEEK and a ten-times higher rate of proton conductivity (12.8 mS cm−1) under very harsh operative conditions (i.e., 90 °C and 30% RH), compared to a filler-free membrane. These findings represent a significant advance as a polymer electrolyte or a fuel cell application.
The Manufacture of Synthetic Rutile by Solvent Extraction of Tri-Alkyl Phosphine Oxide from HCl Leaching Solution of Soda-Roasted Ilmenite Ore
Authors: Joo Sung-Ho , Shin Dong Ju , Lee Dongseok , Kang Jungshin , Kim Min-seuk , Jeon Hoseok , Park Jin-Tae , Shin Shun Myung
Published: April 2020

To manufacture TiO2, a high-purity synthetic rutile, the recovery of Ti was investigated using a hydro-metallurgical process. Using a feed solution containing 32050 mg/L Ti, 110 mg/L Si, 88 mg/L Nb, 2614 mg/L Fe, and 130 mg/L Zr, solvent-extraction experiments were conducted with alkyl phosphine oxide in conjunction with diluents such as kerosene and xylene. The results showed that the extraction mechanism of both diluents was very similar to slope analysis, which had a value of 1.9; however, the extraction equilibrium constant value of organic–metallic species in xylene as a diluent was lower than in kerosene as a diluent. This result affected the stripping efficiency of Ti in particular; therefore, xylene was selected as a diluent. To recover Ti ion from a leaching solution, a series of experiments was conducted, such as the McCabe–Thiele method and countercurrent simulation test for extraction and stripping of Ti. As a result, Ti and impurities such as Fe and Zr were extracted to 99.9% from Si and Nb under optimal conditions using countercurrent four-stage extraction, with 1 M Cyanex 923 at a ratio of organic phase/ aqueous phase=3. In the stripping test, Ti was selectively stripped to 90.1% from Fe and Zr in the organic phase by 1 M HCl. The obtained powder, which was hydrolyzed from an impurity-free solution, was analyzed to a purity of 99.9% by inductively coupled plasma. The TiO2, which has a spherical shape and a diameter of approximately 2 µm according to SEM, was evident by XRD.
Metabolic Effects of Bovine Milk Oligosaccharides on Selected Commensals of the Infant Microbiome—Commensalism and Postbiotic Effects
Authors: Jakobsen Louise M. A. , Maldonado-Gómez Maria X. , Sundekilde Ulrik K. , Andersen Henrik J. , Nielsen Dennis S. , Bertram Hanne C.
Published: April 2020

Oligosaccharides from human or bovine milk selectively stimulate growth or metabolism of bacteria associated with the lower gastrointestinal tract of infants. Results from complex infant-type co-cultures point toward a possible synergistic effect of combining bovine milk oligosaccharides (BMO) and lactose (LAC) on enhancing the metabolism of Bifidobacterium longum subsp. longum and inhibition of Clostridium perfringens. We examine the interaction between B. longum subsp. longum and the commensal Parabacteroides distasonis, by culturing them in mono- and co-culture with different carbohydrates available. To understand the interaction between BMO and lactose on B. longum subsp. longum and test the potential postbiotic effect on C. perfringens growth and/or metabolic activity, we inoculated C. perfringens into fresh media and compared the metabolic changes to C. perfringens in cell-free supernatant from B. longum subsp. longum fermented media. In co-culture, B. longum subsp. longum benefits from P. distasonis (commensalism), especially in a lactose-rich environment. Furthermore, B. longum subsp. longum fermentation of BMO + LAC impaired C. perfringens’ ability to utilize BMO as a carbon source (potential postbiotic effect).
Identification of Metabolic Alterations in Breast Cancer Using Mass Spectrometry-Based Metabolomic Analysis
Authors: Fan Sili , Shahid Muhammad , Jin Peng , Asher Arash , Kim Jayoung
Published: April 2020

Breast cancer (BC) is a major global health issue and remains the second leading cause of cancer-related death in women, contributing to approximately 41,760 deaths annually. BC is caused by a combination of genetic and environmental factors. Although various molecular diagnostic tools have been developed to improve diagnosis of BC in the clinical setting, better detection tools for earlier diagnosis can improve survival rates. Given that altered metabolism is a characteristic feature of BC, we aimed to understand the comparative metabolic differences between BC and healthy controls. Metabolomics, the study of metabolism, can provide incredible insight and create useful tools for identifying potential BC biomarkers. In this study, we applied two analytical mass spectrometry (MS) platforms, including hydrophilic interaction chromatography (HILIC) and gas chromatography (GC), to generate BC-associated metabolic profiles using breast tissue from BC patients. These metabolites were further analyzed to identify differentially expressed metabolites in BC and their associated metabolic networks. Additionally, Chemical Similarity Enrichment Analysis (ChemRICH), MetaMapp, and Metabolite Set Enrichment Analysis (MSEA) identified significantly enriched clusters and networks in BC tissues. Since metabolomic signatures hold significant promise in the clinical setting, more effort should be placed on validating potential BC biomarkers based on identifying altered metabolomes.
Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain
Authors: Swann Jonathan R. , Spitzer Sonia O. , Diaz Heijtz Rochellys
Published: April 2020

The gut microbiome is recognized to exert a wide-ranging influence on host health and disease, including brain development and behavior. Commensal bacteria can produce bioactive molecules that enter the circulation and impact host physiology and homeostasis. However, little is known about the potential for these metabolites to cross the blood–brain barrier and enter the developing brain under normal physiological conditions. In this study, we used a liquid chromatography–mass spectrometry-based metabolomic approach to characterize the developmental profiles of microbial-derived metabolites in the forebrains of mice across three key postnatal developmental stages, co-occurring with the maturation of the gut microbiota. We demonstrate that direct metabolites of the gut microbiome (e.g., imidazole propionate) or products of the combinatorial metabolism between the microbiome and host (e.g., 3-indoxyl-sulfate, trimethylamine-N-oxide, and phenylacetylglycine) are present in the forebrains of mice as early as the neonatal period and remain into adulthood. These findings demonstrate that microbial-associated molecules can cross the BBB either in their detected form or as precursor molecules that undergo further processing in the brain. These chemical messengers are able to bind receptors known to be expressed in the brain. Alterations in the gut microbiome may therefore influence neurodevelopmental trajectories via the regulation of these microbial-associated metabolites.
An LC–MS Assay to Measure Superoxide Radicals and Hydrogen Peroxide in the Blood System
Authors: Tsamesidis Ioannis , Egwu Chinedu O. , Pério Pierre , Augereau Jean-Michel , Benoit-Vical Françoise , Reybier Karine
Published: April 2020

Red blood cells are constantly exposed to reactive species under physiological or pathological conditions or during administration of xenobiotics. Regardless of the source, its accurate quantification is paramount in the area of theragnostics, which had been elusive up until now. Even if there are a lot of approaches to evaluate the oxidative stress, very sensitive methods are missing for the blood system. We therefore sought to apply a highly sensitive approach, by liquid chromatography coupled to mass spectrometry (UPLC–MS), for the quantification of reactive species such as superoxide radical and hydrogen peroxide using dihydroethidium (DHE) and coumarin boronic acid (CBA) probes respectively through the detection of 2-hydroxyethidium (2OH-E+) and 7-hydroxycoumarin (COH). The use of the high-resolution mass spectrometry associated to UPLC ensured a selective detection of superoxide and hydrogen peroxide in the blood system under diverse conditions such as oxidized red blood cells (RBCs), untreated and treated parasitized RBCs. Moreover, this technique allowed the determination of reactive species in human plasma. This protocol provides a huge opportunity for in-depth study of several pathological conditions vis-a-vis their treatment in modern medicine.
Profiling of Chlorogenic Acids from Bidens pilosa and Differentiation of Closely Related Positional Isomers with the Aid of UHPLC-QTOF-MS/MS-Based In-Source Collision-Induced Dissociation
Authors: Ramabulana Anza-Tshilidzi , Steenkamp Paul , Madala Ntakadzeni , Dubery Ian A.
Published: April 2020

Bidens pilosa is an edible herb from the Asteraceae family which is traditionally consumed as a leafy vegetable. B. pilosa has many bioactivities owing to its diverse phytochemicals, which include aliphatics, terpenoids, tannins, alkaloids, hydroxycinnamic acid (HCA) derivatives and other phenylpropanoids. The later include compounds such as chlorogenic acids (CGAs), which are produced as either regio- or geometrical isomers. To profile the CGA composition of B. pilosa, methanol extracts from tissues, callus and cell suspensions were utilized for liquid chromatography coupled to mass spectrometric detection (UHPLC-QTOF-MS/MS). An optimized in-source collision-induced dissociation (ISCID) method capable of discriminating between closely related HCA derivatives of quinic acids, based on MS-based fragmentation patterns, was applied. Careful control of collision energies resulted in fragment patterns similar to MS2 and MS3 fragmentation, obtainable by a typical ion trap MSn approach. For the first time, an ISCID approach was shown to efficiently discriminate between positional isomers of chlorogenic acids containing two different cinnamoyl moieties, such as a mixed di-ester of feruloyl-caffeoylquinic acid (m/z 529) and coumaroyl-caffeoylquinic acid (m/z 499). The results indicate that tissues and cell cultures of B. pilosa contained a combined total of 30 mono-, di-, and tri-substituted chlorogenic acids with positional isomers dominating the composition thereof. In addition, the tartaric acid esters, caftaric- and chicoric acids were also identified. Profiling revealed that these HCA derivatives were differentially distributed across tissues types and cell culture lines derived from leaf and stem explants.
Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics
Authors: Hochstetter Axel
Published: April 2020

In the last three decades, microfluidics and its applications have been on an exponential rise, including approaches to isolate rare cells and diagnose diseases on the single-cell level. The techniques mentioned herein have already had significant impacts in our lives, from in-the-field diagnosis of disease and parasitic infections, through home fertility tests, to uncovering the interactions between SARS-CoV-2 and their host cells. This review gives an overview of the field in general and the most notable developments of the last five years, in three parts: 1. What can we detect? 2. Which detection technologies are used in which setting? 3. How do these techniques work? Finally, this review discusses potentials, shortfalls, and an outlook on future developments, especially in respect to the funding landscape and the field-application of these chips.
Lipocalin2 Induced by Bacterial Flagellin Protects Mice against Cyclophosphamide Mediated Neutropenic Sepsis
Authors: Lim Daejin , Kim Hee Kyung , Jeong Jae-Ho , Jung Yoon Seok , Lee Shee Eun , Jang Hee-Chang , Jung Sook-In , Choi Hueng-Sik , Rhee Joon Haeng , Lee Sung-Gwon , Park Chungoo , Song Miryoung , Choy Hyon E.
Published: April 2020

Neutropenic sepsis is a fatal consequence of chemotherapy, and septic complications are the principal cause of mortality. Chemotherapy-induced neutropenia leads to the formation of microscopic ulcers in the gastrointestinal epithelium that function as a portal of entry for intraluminal bacteria, which translocate across the intestinal mucosal barrier and gain access to systemic sites, causing septicemia. A cyclophosphamide-induced mouse model was developed to mimic the pathophysiologic sequence of events that occurs in patients with neutropenic sepsis. The TLR5 agonist bacterial flagellin derived from Vibrio vulnificus extended the survival of cyclophosphamide-treated mice by reducing the bacterial load in internal organs. The protective effect of flagellin was mediated by the antimicrobial protein lipocalin 2 (Lcn2), which is induced by TLR5-NF-κB activation in hepatocytes. Lcn2 sequestered iron from infecting bacteria, particularly siderophore enterobactin-dependent members of the Enterobacteriaceae family, thereby limiting their proliferation. Lcn2 should be considered for the treatment of neutropenic sepsis and gastrointestinal damage during chemotherapy to prevent or minimize the adverse effects of cancer chemotherapy.
Microbial Screening Based on the Mizoroki–Heck Reaction Permits Exploration of Hydroxyhexylitaconic-Acid-Producing Fungi in Soils
Authors: Sano Mei , Yada Ryoki , Nomura Yusuke , Kusukawa Takahiro , Ando Hiroshi , Matsumoto Keiji , Wada Kazuhito , Tanaka Tomonari , Ohara Hitomi , Aso Yuji
Published: April 2020

Recently, we developed a unique microbial screening method based on the Mizoroki–Heck reaction for itaconic acid (IA)-producing fungi. This method revealed that 37 out of 240 fungal strains isolated from soils produce vinyl compounds, including IA. In this study, we further characterized these compounds in order to verify that the screening method permits the isolation of fungi that produce other vinyl compounds, excluding IA. HPLC analysis showed that 11 out of 37 isolated strains produced IA, similar to Aspergillus terreus S12-1. Surprisingly, the other 8 isolated strains produced two vinyl compounds with HPLC retention times different from that of IA. From these strains, the vinyl compounds of Aspergillus niger S17-5 were characterized. Mass spectrometric and NMR analyses showed that they were identical to 8-hydroxyhexylitaconic acid (8-HHIA) and 9-HHIA. This finding showed that 8-HHIA- and 9-HHIA-producing fungi, as well as IA-producing fungi, are ubiquitously found in soils. Neither 8-HHIA nor 9-HHIA showed antibacterial or anti-inflammatory activities. Interestingly, 8-HHIA and 9-HHIA showed cytotoxicity against the human cervical cancer cell line (HeLa) and human diploid cell line (MRC-5), and MRC-5 only, respectively, compared to IA at the same concentration. This study indicates that the screening method could easily discover fungi producing 8-HHIA and 9-HHIA in soils.
Molecular Identification of Borrelia afzelii from Ticks Parasitizing Domestic and Wild Animals in South Korea
Authors: Seo Min-Goo , Kwon Oh-Deog , Kwak Dongmi
Published: April 2020

Lyme borreliosis is one of the most prevalent tick-borne infectious zoonotic diseases caused by spirochetes of the Borrelia burgdorferi sensu lato group. The present study assessed the risk factors and prevalence of Lyme borreliosis in ticks parasitizing domestic and wild animals. A total of 589 ticks (329 tick pools) collected from animals were identified as Haemaphysalis longicornis, (85.7%), H. flava (10.0%), and Ixodes nipponensis (4.3%) using morphological and molecular methods in South Korea. In this study, the 5S–23S gene sequences of B. afzelii (6/329, 1.8%) were detected in ticks taken from mammals, including ticks from horses (2/147 pools, 1.4%), wild boar (1/19 pools, 5.3%), native Korean goats (NKG, 2/34 pools, 5.9%), and Korean water deer (1/129 pools, 0.8%). Unfortunately, ospA, pyrG, and flagellin genes were not able to be amplified in the present study. To our knowledge, our results are the first inclusive data available for B. afzelii circulation in several tick species taken from NKG, horses, and wild boar in South Korea. We believe that the current findings extend our knowledge of the distribution and possible vector spectrum of Borrelia spp. We recommend continuous evaluation of the potential public health threat posed by Borrelia infected ticks.
Slatecalculation—A Practical Tool for Deriving Norm Minerals in the Lowest-Grade Metamorphic Pelites and Roof Slates
Authors: Wagner Hans Wolfgang , Jung Dieter , Wagner Jean-Frank , Wagner Matthias Patrick
Published: April 2020

Roof and wall slates are fine-grained rocks with slaty cleavage, and it is often difficult to determine their mineral composition. A new norm mineral calculation called slatecalculation allows the determination of a virtual mineral composition based on full chemical analysis, including the amounts of carbon dioxide (CO2), carbon (C), and sulfur (S). Derived norm minerals include feldspars, carbonates, micas, hydro-micas, chlorites, ore-minerals, and quartz. The mineral components of the slate are assessed with superior accuracy compared to the petrographic analysis based on the European Standard EN 12326. The inevitable methodical inaccuracies in the calculations are limited and transparent. In the present paper, slates, shales, and phyllites from worldwide occurrences were examined. This also gives an overview of the rocks used for discontinuous roofing and external cladding.
Effects of Step-Wise Acid Leaching with HCl on Synthesis of Zeolitic Materials from Paper Sludge Ash
Authors: Wajima Takaaki
Published: April 2020

Incinerated ash with a relatively high Ca content, paper sludge ash, was converted to zeolitic materials with high cation-exchange capacities (CECs) by aging at 80 °C in NaOH solution via step-wise acid leaching with HCl to reduce the ash Ca content. The extraction of Ca, Mg, Si, and Al from the ash into the acid solutions during leaching and the products obtained from the leached ash by reaction with an alkali were examined. The contents of Ca and Mg in the ash were more easily extracted from the ash than those of Si and Al in the initial leaching. The leachant pH decreased with increasing numbers of leaching steps, and the amounts of Si, Al, and Ca extracted from the ash increased as a result of the dissolution of gehlenite (Ca2Al2SiO7), one of the main minerals in the ash. Zeolites A and P were synthesized from the leached ashes, and hydroxysodalite was synthesized from the raw ash. With increasing numbers of leaching steps of the ash, the obtained product contained lower released Ca, whereas the product contained higher released Na and has higher CEC, depending on the zeolite phases in the product. The product with the highest CEC was synthesized from third-leached ash, and its CEC was 1.5 mmol/g, which is about four times higher than that of the raw ash (0.4 mmol/g).
Framework for Monitoring and Control of the Production of Calcined Kaolin
Authors: Guatame-Garcia Adriana , Buxton Mike
Published: April 2020

In response to the growing demand for sustainable products and services, the kaolin calcination industry is developing practices that optimise the use of resources. The main challenges include more efficient use of raw materials and a reduction in the energy consumed by the calcination furnace. An opportunity to achieve this lies in the optimisation of the calcination process. This can be done by giving real-time feedback on the quality parameters of the generated calcined kaolin. This study proposes the use of infrared spectroscopy as a monitoring technique to determine the chemical properties of the calcined kaolin product. The basis of the monitoring system is the measurement of the kaolin soluble alumina content as one of the most important quality parameters; this property is an indicator of the over- or under-use of raw materials and energy during the calcination process and can advise the operations regarding the optimisation of the working conditions of the furnace. The implementation of an infrared-based monitoring system would lead to increased efficiency in the production of calcined kaolin.
Hematite Nanoparticles from Unexpected Reaction of Ferrihydrite with Concentrated Acids for Biomedical Applications
Authors: Lunin Afanasy V. , Lizunova Anna A. , Mochalova Elizaveta N. , Yakovtseva Maria N. , Cherkasov Vladimir R. , Nikitin Maxim P. , Kolychev Eugene L.
Published: April 2020

The development of synthetic ways to fabricate nanosized materials with a well-defined shape, narrow-sized distribution, and high stability is of great importance to a rapidly developing area of nanotechnology. Here, we report an unusual reaction between amorphous two-line ferrihydrite and concentrated sulfuric or other mineral and organic acids. Instead of the expected dissolution, we observed the formation of new narrow-distributed brick-red nanoparticles (NPs) of hematite. Different acids produce similar nanoparticles according to scanning (SEM) and transmission electron microscopy (TEM), selected area electron diffraction (SAED), X-ray diffraction (XRD), infrared spectroscopy (FTIR), and energy-dispersive X-ray spectroscopy (EDX). The reaction demonstrates new possibilities for the synthesis of acid-resistant iron oxide nanoparticles and shows a novel pathway for the reaction of iron hydroxide with concentrated acids. The biomedical potential of the fabricated nanoparticles is demonstrated by the functionalization of the particles with polymers, fluorescent labels, and antibodies. Three different applications are demonstrated: i) specific targeting of the red blood cells, e.g., for red blood cell (RBC)-hitchhiking; ii) cancer cell targeting in vitro; iii) infrared ex vivo bioimaging. This novel synthesis route may be useful for the development of iron oxide materials for such specificity-demanding applications such as nanosensors, imaging, and therapy.
N-Acetylation of Amines in Continuous-Flow with Acetonitrile—No Need for Hazardous and Toxic Carboxylic Acid Derivatives
Authors: Orsy György , Fülöp Ferenc , Mándity István M.
Published: April 2020

A continuous-flow acetylation reaction was developed, applying cheap and safe reagent, acetonitrile as acetylation agent and alumina as catalyst. The method developed utilizes milder reagent than those used conventionally. The reaction was tested on various aromatic and aliphatic amines with good conversion. The catalyst showed excellent reusability and a scale-up was also carried out. Furthermore, a drug substance (paracetamol) was also synthesized with good conversion and yield.
Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy
Authors: Feldmann Daniel P. , Heyza Joshua , Zimmermann Christoph M. , Patrick Steve M. , Merkel Olivia M.
Published: April 2020

Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an alternative to small molecule inhibitors, small interfering RNA (siRNA) has often been described to be more efficient in interrupting protein–protein interactions. The goal of this study was therefore to determine whether biocompatible nanoparticles consisting of an amphiphilic triblock copolymer (polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG)) and carrying siRNA targeted to ERCC1 and XPF made by microfluidic assembly are capable of efficient gene silencing and able to sensitize lung cancer cells to cisplatin. First, we show that our PEI-PCL-PEG micelleplexes carrying ERCC1 and XPF siRNA efficiently knocked down ERCC1/XPF protein expression to the same extent as the standard siRNA transfection reagent, Lipofectamine. Second, we show that our siRNA-carrying nanoparticles enhanced platinum sensitivity in a p53 wildtype model of non-small cell lung cancer in vitro. Our results suggest that nanoparticle-mediated targeting of ERCC1/XPF is feasible and could represent a novel therapeutic strategy for targeting ERCC1/XPF in vivo.
Plant In Vitro Systems as a Sustainable Source of Active Ingredients for Cosmeceutical Application
Authors: Marchev Andrey S. , Georgiev Milen I.
Published: April 2020

Cosmeceuticals are hybrids between cosmetics and pharmaceuticals which are being designed for a dual purpose: (1) To provide desired esthetical effects and (2) simultaneously treat dermatological conditions. The increased demand for natural remedies and the trends to use natural and safe ingredients resulted in intensive cultivation of medicinal plants. However, in many cases the whole process of plant cultivation, complex extraction procedure, and purification of the targeted molecules are not economically feasible. Therefore, the desired production of natural cosmetic products in sustainable and controllable fashion in the last years led to the intensive utilization of plant cell culture technology. The present review aims to highlight examples of biosynthesis of active ingredients derived through plant in vitro systems with potential cosmeceutical application. The exploitation of different type of extracts used in a possible cosmeceutical formulation, as well as, their activity tested in in vitro/in vivo models is thoroughly discussed. Furthermore, opportunities to manipulate the biosynthetic pathway, hence engineering the biosynthesis of some secondary metabolites, such as anthocyanins, have been highlighted.
Antioxidant Sulfated Polysaccharide from Edible Red Seaweed Gracilaria birdiae is an Inhibitor of Calcium Oxalate Crystal Formation
Authors: Oliveira Leticia Castelo Branco Peroba , Queiroz Moacir Fernandes , Fidelis Gabriel Pereira , Melo Karoline Rachel Teodosio , Câmara Rafael Barros Gomes , Alves Monique Gabriela Chagas Faustino , Costa Leandro Silva , Teixeira Dárlio Inácio Alves , Melo-Silveira Raniere Fagundes , Rocha Hugo Alexandre Oliveira
Published: April 2020

The genus Gracilaria synthesizes sulfated polysaccharides (SPs). Many of these SPs, including those synthesized by the edible seaweed Gracilaria birdiae, have not yet been adequately investigated for their use as potential pharmaceutical compounds. Previous studies have demonstrated the immunomodulatory effects of sulfated galactans from G. birdiae. In this study, a galactan (GB) was extracted from G. birdiae and evaluated by cell proliferation and antioxidant tests. GB showed no radical hydroxyl (OH) and superoxide (O2−) scavenging ability. However, GB was able to donate electrons in two further different assays and presented iron- and copper-chelating activity. Urolithiasis affects approximately 10% of the world’s population and is strongly associated with calcium oxalate (CaOx) crystals. No efficient compound is currently available for the treatment of this disease. GB appeared to interact with and stabilize calcium oxalate dihydrate crystals, leading to the modification of their morphology, size, and surface charge. These crystals then acquired the same characteristics as those found in healthy individuals. In addition, GB showed no cytotoxic effect against human kidney cells (HEK-293). Taken together, our current findings highlight the potential application of GB as an antiurolithic agent.