bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Pulmonary Aspergillosis Situation among Post Tuberculosis Patients in Vietnam: An Observational Study
Authors: Nguyen Ngoc Thi Bich , Le Ngoc Huy , Nguyen Nhung Viet , Dinh Luong Van , Nguyen Hung Van , Nguyen Huyen Thi , Denning David W.
Published: June 2021

This study provides a brief view of chronic pulmonary aspergillosis (CPA) in the post-tuberculosis treatment community in Vietnam, a high burden tuberculosis (TB) country. In three months in late 2019, 70 post-TB patients managed at Vietnam National Lung Hospital were enrolled. Of these, 38 (54.3%) had CPA. The male/female ratio was 3/1 (28 males and ten females). CPA patients had a mean age of 59 ± 2.3 years (95%CI 54.4–63.6). The mean Body mass index (BMI) was 19.0 ± 0.5 (18.0–20.0) and 16 of 38 (42.1%) patients had concurrent diseases, the most common of which were chronic obstructive pulmonary disease (COPD) and diabetes. Twenty-six patients (68.4%) developed hemoptysis, 21 (55.3%) breathlessness, and weight loss was seen in 30 (78.9%). Anaemia was seen in 15 (39.5%) and 27 of 38 (71.1%) patients had an elevated C-reactive protein (CRP). The most common radiological findings were multiple cavities (52.6%) and pleural thickening (42.7%), followed by aspergilloma (29.0%) and non-specific infiltrates. There were five of 38 patients (13.2%) with a cavity containing a fungal ball on the chest X-ray, but when the high resolution computed tomography (HRCT) was examined, the number of patients with fungal balls rose to 11 (28.9%). Overall, 34 of 38 (89.5%) cases had an elevated Aspergillus IgG with an optical density ≥ 1, and in 2 cases, it was 0.9–1.0 (5%), borderline positive. In nine patients (23.7%) Aspergillus fumigatus was cultured from sputum. CPA is an under-recognised problem in Vietnam and other high burden TB countries, requiring a different diagnostic approach and treatment and careful management. HRCT and Aspergillus IgG serum test are recommended as initial diagnostic tools for CPA diagnosis.
Improving an Urban Cellular Automata Model Based on Auto-Calibrated and Trend-Adjusted Neighborhood
Authors: Pan Xinhao , Wang Zichen , Huang Miao , Liu Zhifeng
Published: June 2021

Accurately simulating urban expansion is of great significance for promoting sustainable urban development. The calculation of neighborhood effects is an important factor that affects the accuracy of urban expansion models. The purpose of this study is to improve the calculation of neighborhood effects in an urban expansion model, i.e., the land-use scenario dynamics-urban (LUSD-urban) model, by integrating the trend-adjusted neighborhood algorithm and the automatic rule detection procedure. Taking eight sample cities in China as examples, we evaluated the accuracies of the original model and the improved model. We found that the improved model can increase the accuracy of simulated urban expansion in terms of both the degree of spatial matching and the similarity of urban form. The increase of accuracy can be attributed to such integration comprehensively considers the effects of historical urban expansion trends and the influences of neighborhoods at different scales. Therefore, the improved model in this study can be widely used to simulate the process of urban expansion in different regions.
The Sh(e)aring Economy. Debates on the Law on Takings
Authors: Sheffi Nofar
Published: June 2021

Rethinking ‘sharing’ and the relationship between ‘sharing’ and ‘jurisdiction’, this meander proceeds in three parts. It begins with a journey to and through the forests of the nineteenth-century Rhineland, rereading Marx’s journalistic reports on debates in the Sixth Rhine Province Assembly about proposed amendments to forest regulation (including an extension of the definition of ‘wood theft’ to include the gathering of fallen wood) as a reflection on the making of law by legal bodies. From the forests of the Rhineland, the paper journeys to the forests of England, retracing the common story about the development, by legal bodies, of the body of common law principles applicable to ‘innkeeping’. Traveling to and through the ‘concrete jungles’ of the United States of America, the paper concludes with a reflection on Airbnb’s common story of creation as well as debates about the legality of Airbnb, Airbnb-ing, and ‘sharing’.
Consequences and Resolution of Transcription–Replication Conflicts
Authors: Lalonde Maxime , Trauner Manuel , Werner Marcel , Hamperl Stephan
Published: June 2021

Transcription–replication conflicts occur when the two critical cellular machineries responsible for gene expression and genome duplication collide with each other on the same genomic location. Although both prokaryotic and eukaryotic cells have evolved multiple mechanisms to coordinate these processes on individual chromosomes, it is now clear that conflicts can arise due to aberrant transcription regulation and premature proliferation, leading to DNA replication stress and genomic instability. As both are considered hallmarks of aging and human diseases such as cancer, understanding the cellular consequences of conflicts is of paramount importance. In this article, we summarize our current knowledge on where and when collisions occur and how these encounters affect the genome and chromatin landscape of cells. Finally, we conclude with the different cellular pathways and multiple mechanisms that cells have put in place at conflict sites to ensure the resolution of conflicts and accurate genome duplication.
The Effect of Vibration Mixing on the Mechanical Properties of Steel Fiber Concrete with Different Mix Ratios
Authors: Zhang Chunyu , Sun Yikai , Xu Jianguo , Wang Bo
Published: June 2021

This work addresses how vibration stirring, steel-fiber volume ratio, and matrix strength affect the mechanical properties of steel-fiber-reinforced concrete. The goal of the work is to improve the homogeneity of steel-fiber-reinforced concrete, which is done by comparing the mechanical properties of steel-fiber-reinforced concrete fabricated by ordinary stirring with that fabricated by vibration stirring. The results show that the mechanical properties of steel-fiber-reinforced concrete produced by vibration mixing are better than those produced by ordinary mixing. The general trend is that the mechanical properties of steel-fiber concrete have a linear relationship with the matrix strength and the volume ratio of steel fiber. The best mechanical properties are obtained for a steel-fiber volume ratio of less than 1%. We have also established calculation models for the mechanical performance index of vibration, mixing steel-fiber concrete based on the test results. Microscopic studies show that vibration stirring optimizes the microstructure of the transition zone between the concrete interface and the slurry, and improves the homogeneity of the steel-fiber-reinforced concrete, and enhances the adhesion between the mixture components.
Infinitely Smooth Polyharmonic RBF Collocation Method for Numerical Solution of Elliptic PDEs
Authors: Liu Chih-Yu , Ku Cheng-Yu , Hong Li-Dan , Hsu Shih-Meng
Published: June 2021

In this article, a novel infinitely smooth polyharmonic radial basis function (PRBF) collocation method for solving elliptic partial differential equations (PDEs) is presented. The PRBF with natural logarithm is a piecewise smooth function in the conventional radial basis function collocation method for solving governing equations. We converted the piecewise smooth PRBF into an infinitely smooth PRBF using source points collocated outside the domain to ensure that the radial distance was always greater than zero to avoid the singularity of the conventional PRBF. Accordingly, the PRBF and its derivatives in the governing PDEs were always continuous. The seismic wave propagation problem, groundwater flow problem, unsaturated flow problem, and groundwater contamination problem were investigated to reveal the robustness of the proposed PRBF. Comparisons of the conventional PRBF with the proposed method were carried out as well. The results illustrate that the proposed approach could provide more accurate solutions for solving PDEs than the conventional PRBF, even with the optimal order. Furthermore, we also demonstrated that techniques designed to deal with the singularity in the original piecewise smooth PRBF are no longer required.
AFM Study of Nanoscale Membrane Perturbation Induced by Antimicrobial Lipopeptide C14 KYR
Authors: Nasompag Sawinee , Siritongsuk Pawinee , Thammawithan Saengrawee , Srichaiyapol Oranee , Prangkio Panchika , Camesano Terri A. , Sinthuvanich Chomdao , Patramanon Rina
Published: June 2021

Lipopeptides have been extensively studied as potential antimicrobial agents. In this study, we focused on the C14-KYR lipopeptide, a modified version of the KYR tripeptide with myristic acid at the N-terminus. Here, membrane perturbation of live E. coli treated with the parent KYR and C14-KYR peptides was compared at the nanoscale level using AFM imaging. AFM analyses, including average cellular roughness and force spectroscopy, revealed the severe surface disruption mechanism of C14-KYR. A loss of surface roughness and changes in topographic features included membrane shrinkage, periplasmic membrane separation from the cell wall, and cytosolic leakage. Additional evidence from synchrotron radiation FTIR microspectroscopy (SR-FTIR) revealed a marked structural change in the membrane component after lipopeptide attack. The average roughness of the E. coli cell before and after treatment with C14-KYR was 129.2 ± 51.4 and 223.5 ± 14.1 nm, respectively. The average rupture force of the cell treated with C14-KYR was 0.16 nN, four times higher than that of the untreated cell. Our study demonstrates that the mechanistic effect of the lipopeptide against bacterial cells can be quantified through surface imaging and adhesion force using AFM.
CO2 Absorption Using Hollow Fiber Membrane Contactors: Introducing pH Swing Absorption (pHSA) to Overcome Purity Limitation
Authors: Chavan Sayali Ramdas , Perré Patrick , Pozzobon Victor , Lemaire Julien
Published: June 2021

Recently, membrane contactors have gained more popularity in the field of CO2 removal; however, achieving high purity and competitive recovery for poor soluble gas (H2, N2, or CH4) remains elusive. Hence, a novel process for CO2 removal from a mixture of gases using hollow fiber membrane contactors is investigated theoretically and experimentally. A theoretical model is constructed to show that the dissolved residual CO2 hinders the capacity of the absorbent when it is regenerated. This model, backed up by experimental investigation, proves that achieving a purity > 99% without consuming excessive chemicals or energy remains challenging in a closed-loop system. As a solution, a novel strategy is proposed: the pH Swing Absorption which consists of manipulating the acido–basic equilibrium of CO2 in the absorption and desorption stages by injecting moderate acid and base amount. It aims at decreasing CO2 residual content in the regenerated absorbent, by converting CO2 into its ionic counterparts (HCO3− or CO32−) before absorption and improving CO2 degassing before desorption. Therefore, this strategy unlocks the theoretical limitation due to equilibrium with CO2 residual content in the absorbent and increases considerably the maximum achievable purity. Results also show the dependency of the performance on operating conditions such as total gas pressure and liquid flowrate. For N2/CO2 mixture, this process achieved a nitrogen purity of 99.97% with a N2 recovery rate of 94.13%. Similarly, for H2/CO2 mixture, a maximum H2 purity of 99.96% and recovery rate of 93.96% was obtained using this process. Moreover, the proposed patented process could potentially reduce energy or chemicals consumption.
Transport Reagents through the Pore Structure of a Membrane Catalyst under Isothermal and Non-Isothermal Conditions
Authors: Gavrilova Natalia , Gubin Sergey , Myachina Maria , Skudin Valery
Published: June 2021

The article presents the results of an experimental comparison of methane transport in the pore structure of a membrane catalyst under isothermal and non-isothermal Knudsen diffusion conditions. It is shown that under the conditions of non-isothermal Knudsen diffusion in the pore structure of the membrane catalyst, there is a coupling of dry reforming of the methane (DRM) and gas transport, which leads to the intensification of this process. The reasons for the intensification are changes in the mechanism of gas transport, an increase in the rate of mass transfer, and changes in the mechanism of some stages of the DRM. The specific rate constant of the methane dissociation reaction on a membrane catalyst turned out to be an order of magnitude (40 times) higher than this value on a traditional (powder) catalyst.
Reconstitution of Functional Integrin αIIbβ3 and Its Activation in Plasma Membrane-Mimetic Lipid Environments
Authors: Janke Una , Mitlehner Alexandra , Weide Aileen , Gutmann Theresia , Delcea Mihaela
Published: June 2021

The study of the platelet receptor integrin αIIbβ3 in a membrane-mimetic environment without interfering signalling pathways is crucial to understand protein structure and dynamics. Our understanding of this receptor and its sequential activation steps has been tremendously progressing using structural and reconstitution approaches in model membranes, such as liposomes or supported-lipid bilayers. For most αIIbβ3 reconstitution approaches, saturated short-chain lipids have been used, which is not reflecting the native platelet cell membrane composition. We report here on the reconstitution of label-free full-length αIIbβ3 in liposomes containing cholesterol, sphingomyelin, and unsaturated phosphatidylcholine mimicking the plasma membrane that formed supported-lipid bilayers for quartz-crystal microbalance with dissipation (QCM-D) experiments. We demonstrate the relevance of the lipid environment and its resulting physicochemical properties on integrin reconstitution efficiency and its conformational dynamics. We present here an approach to investigate αIIbβ3 in a biomimetic membrane system as a useful platform do dissect disease-relevant integrin mutations and effects on ligand binding in a lipid-specific context, which might be applicable for drug screening.
Crystallization and Hardness Change of the Ti-Based Bulk Metallic Glass Manufactured by a Laser Powder Bed Fusion Process
Authors: Jang Ji-Hoon , Kim Hyung-Guin , Kim Hwi-Jun , Lee Dong-Geun
Published: June 2021

Ti-2.5Zr-5.0Hf-37.5Cu-7.5Ni-1.0Si-5.0Sn (at.%) BMG has been successfully manufactured in amorphous powder with a size of about 25 μm (D50). Using this amorphous powder, a Ti-based BMG was manufactured by an additive manufacturing process based on a laser powder bed fusion (LPBF) technique. In 3D printing processes using amorphous powders, it is necessary and important to understand the crystallization behavior due to the difference in energy density applied to the powders. An LPBF process has been carried out with various energy density conditions to minimize the inner defects and identify the sound mechanical properties of 3D-printed BMG parts. At the lowest energy density condition (3.0 J/mm3), the most pores were generated. Even if the same energy density (3.0 J/mm3) was applied, the rapid laser movement caused many pores to form inside the material. The relatively sound 3D-printed Ti-based BMG was successfully fabricated with a size of about 5 mm × 5 mm × 3 mm. Peaks at 41° and 44° showing crystallization were observed in all conditions. The higher the laser power was, the greater each peak intensity and the more crystallization (CuTi, Ti3Cu4, etc.) was present in the BMG, and the higher the scan speed, the more the internal defects were found.
Potential Metabolic Biomarkers in Adult Asthmatics
Authors: Sim Soyoon , Choi Youngwoo , Park Hae-Sim
Published: June 2021

Asthma is the most common chronic airway inflammation, with multiple phenotypes caused by complicated interactions of genetic, epigenetic, and environmental factors. To date, various determinants have been suggested for asthma pathogenesis by a new technology termed omics, including genomics, transcriptomics, proteomics, and metabolomics. In particular, the systematic analysis of all metabolites in a biological system, such as carbohydrates, amino acids, and lipids, has helped identify a novel pathway related to complex diseases. These metabolites are involved in the regulation of hypermethylation, response to hypoxia, and immune reactions in the pathogenesis of asthma. Among them, lipid metabolism has been suggested to be related to lung dysfunction in mild-to-moderate asthma. Sphingolipid metabolites are an important mediator contributing to airway inflammation in obese asthma and aspirin-exacerbated respiratory disease. Although how these molecular variants impact the disease has not been completely determined, identification of new causative factors may possibly lead to more-personalized and precise pathway-specific approaches for better diagnosis and treatment of asthma. In this review, perspectives of metabolites related to asthma and clinical implications have been highlighted according to various phenotypes.
Simultaneous Trapping of Two Types of Particles with Focused Elegant Third-Order Hermite–Gaussian Beams
Authors: Su Jingjing , Li Nan , Mou Jiapeng , Liu Yishi , Chen Xingfan , Hu Huizhu
Published: June 2021

The focusing properties of elegant third-order Hermite–Gaussian beams (TH3GBs) and the radiation forces exerted on dielectric spherical particles produced by such beams in the Rayleigh scattering regime have been theoretically studied. Numerical results indicate that the elegant TH3GBs can be used to simultaneously trap and manipulate nanosized dielectric spheres with refractive indexes lower than the surrounding medium at the focus and those with refractive indexes larger than the surrounding medium in the focal vicinity. Furthermore, by changing the radius of the beam waist, the transverse trapping range and stiffness at the focal plane can be changed.
Structural Design of Vascular Stents: A Review
Authors: Pan Chen , Han Yafeng , Lu Jiping
Published: June 2021

Percutaneous Coronary Intervention (PCI) is currently the most conventional and effective method for clinically treating cardiovascular diseases such as atherosclerosis. Stent implantation, as one of the ways of PCI in the treatment of coronary artery diseases, has become a hot spot in scientific research with more and more patients suffering from cardiovascular diseases. However, vascular stent implanted into vessels of patients often causes complications such as In-Stent Restenosis (ISR). The vascular stent is one of the sophisticated medical devices, a reasonable structure of stent can effectively reduce the complications. In this paper, we introduce the evolution, performance evaluation standards, delivery and deployment, and manufacturing methods of vascular stents. Based on a large number of literature pieces, this paper focuses on designing structures of vascular stents in terms of “bridge (or link)” type, representative volume unit (RVE)/representative unit cell (RUC), and patient-specific stent. Finally, this paper gives an outlook on the future development of designing vascular stents.
A Kalman Filter-Based Kernelized Correlation Filter Algorithm for Pose Measurement of a Micro-Robot
Authors: Zhang Heng , Zhan Hongwu , Zhang Libin , Xu Fang , Ding Xinbin
Published: June 2021

This paper proposes a moving-target tracking algorithm that measures the pose of a micro-robot with high precision and high speed using the Kalman filter-based kernelized correlation filter (K2CF) algorithm. The adaptive Kalman filter can predict the state of linearly and nonlinearly fast-moving targets. The kernelized correlation filter algorithm then accurately detects the positions of the moving targets and uses the detection results to modify the moving states of the targets. This paper verifies the performance of the algorithm on a monocular vision measurement platform and using a pose measurement method. The K2CF algorithm was embedded in the micro-robot’s attitude measurement system, and the tracking performances of three different trackers were compared under different motion conditions. Our tracker improved the positioning accuracy and maintained real-time operation. In a comparison study of K2CF and many other algorithms on Object Tracking Benchmark-50 and Object Tracking Benchmark-100 video sequences, the K2CF algorithm achieved the highest accuracy. In the 400 mm × 300 mm field of view, when the target radius is about 3 mm and the inter-frame acceleration displacement does not exceed 5.6 mm, the root-mean-square error of position and attitude angle can satisfy the precision requirements of the system.
Escherichia coli Causing Recurrent Urinary Tract Infections: Comparison to Non-Recurrent Isolates and Genomic Adaptation in Recurrent Infections
Authors: Nielsen Karen Leth , Stegger Marc , Kiil Kristoffer , Lilje Berit , Ejrnæs Karen , Leihof Rikke Fleron , Skjøt-Rasmussen Line , Godfrey Paul , Monsen Tor , Ferry Sven , Hammerum Anette M. , Frimodt-Møller Niels
Published: June 2021

Recurrent urinary tract infection (rUTI) remains a major problem for many women and therefore the pursuit for genomic and phenotypic traits which could define rUTI has been ongoing. The present study applied a genomic approach to investigate recurrent urinary tract infections by comparative analyses of recurrent and non-recurrent Escherichia coli isolates from general practice. From whole-genome sequencing data, phylogenetic clustering and genomic traits were studied on a collection of isolates which caused recurrent infection compared to non-recurrent isolates. In addition, genomic variation between the 1st and following infection was studied on a subset of the isolates. Evidence of limited adaptation between the recurrent infections based on single nucleotide polymorphism analyses with a range of 0–13 non-synonymous single nucleotide polymorphisms (SNPs) between the paired isolates. This included an overrepresentation of SNPs in metabolism genes. We identified several genes which were more common in rUTI isolates, including nine fimbrial genes, however, not significantly after false-discovery rate. Finally, the results show that recurrent isolates of the present dataset are not distinctive by variation in the core genome, and thus, did not cluster distinct from non-rUTI isolates in a SNP phylogeny.
Hydrogen Peroxide Ammonium Citrate Extraction: Mineral Decomposition and Preliminary Waste Rock Characterization
Authors: Karlsson Teemu , Räisänen Marja Liisa , Myöhänen Timo , Alakangas Lena , Lehtonen Marja , Kauppila Päivi
Published: June 2021

A commonly-used method in ore exploration is hydrogen peroxide ammonium citrate (HA) extraction, which has not typically been used in waste rock characterization. In this study, the sulfide specificity and leaching of other minerals in HA extraction was evaluated and its performance was compared with the aqua regia (AR) extraction for preliminary assessment of harmful element mobility. Samples collected from several different mine sites in Finland were utilized. The waste rock sample S contents ranged from 0.3% to 5.3%, and sums of the AR extractable elements As, Cd, Co, Cu, Ni and Zn range from 120 to 8040 mg/kg. The drainage types ranged from acid high-metal to neutral low-metal, with pH’s of 3.3–7.7. Mineralogical changes that took place in the HA solution were investigated by the field emission scanning electron microscope (FE-SEM) equipped with an energy-dispersive X-ray spectroscopy analyzer (EDS) and X-ray diffraction (XRD) methods. Results of the study showed that the HA extraction appears to be a more specific method for sulfide decomposition compared with AR extraction. Sulfide minerals, especially base metal sulfides pentlandite, chalcopyrite and sphalerite, decomposed efficiently in HA extraction. However, the Fe-sulfides pyrrhotite and pyrite only decomposed incompletely. The study showed that the HA extraction results can be used in the preliminary prediction of element mobility. Based on the results, the elevated As, Cd, Co, Cu, Ni, S and Zn leachability in the HA extraction appears to predict elevated drainage concentrations. If the HA-extractable sum of As, Cd, Co, Cu, Ni and Zn is >750 mg/kg, there is an increased risk of high-metal (>1000 µg/L) drainage. Therefore, the HA extraction data, e.g., produced during ore exploration, can be utilized to preliminary screen the risks of sulfide related element mobilities from waste rock material.
The Synthesis of Organoclays Based on Clay Minerals with Different Structural Expansion Capacities
Authors: Perelomov Leonid , Mandzhieva Saglara , Minkina Tatiana , Atroshchenko Yury , Perelomova Irina , Bauer Tatiana , Pinsky David , Barakhov Anatoly
Published: June 2021

An important goal in environmental research for industrial activity and sites is the investigation and development of effective adsorbents for chemical pollutants that are widespread, inexpensive, unharmful to the environment, and have the required adsorption selectivity. Organoclays are adsorption materials that can be obtained by modifying clays and clay minerals with various organic compounds through intercalation and surface grafting. Organoclays have important practical applications as adsorbents of a wide range of organic pollutants and some inorganic contaminants. The traditional raw materials for the synthesis of organoclays are phyllosilicates with the expanding structural cell of the smectite group, such as montmorillonite. Moreover, other phyllosilicates and inosilicates are used to synthesize organoclay to a limited extent. The purpose of this review was to analyze the possibility of using minerals of other groups with different abilities to expand the structure and structural charge for the adsorption of chemical environmental pollutants. The structural characteristics of various groups of phyllosilicates and chain minerals that affect their ability to modify organic surfactants and the adsorption properties of prepared organoclays were reviewed.
Methanolic Extract of Piper sarmentosum Attenuates Obesity and Hyperlipidemia in Fructose-Induced Metabolic Syndrome Rats
Authors: Kumar Sivanesan Raja , Mohd Ramli Elvy Suhana , Abdul Nasir Nurul Alimah , Mohd Ismail Nafeeza , Mohd Fahami Nur Azlina
Published: June 2021

Obesity and hyperlipidemia are metabolic dysregulations that arise from poor lifestyle and unhealthy dietary intakes. These co-morbidity conditions are risk factors for vascular diseases. Piper sarmentosum (PS) is a nutritious plant that has been shown to pose various phytochemicals and pharmacological actions. This study aimed to investigate the effect of PS on obesity and hyperlipidemia in an animal model. Forty male Wistar rats were randomly divided into five experimental groups. The groups were as follows: UG—Untreated group; CTRL—control; FDW—olive oil + 20% fructose; FDW-PS—PS (125 mg/kg) + 20% fructose; FDW-NGN—naringin (100 mg/kg) + 20% fructose. Fructose drinking water was administered daily for 12 weeks ad libitum to induce metabolic abnormality. Treatment was administered at week 8 for four weeks via oral gavage. The rats were sacrificed with anesthesia at the end of the experimental period. Blood, liver, and visceral fat were collected for further analysis. The consumption of 20% fructose water by Wistar rats for eight weeks displayed a tremendous increment in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, leptin, and reduced the levels of HDL and adiponectin as well as adipocyte hypertrophy. Following the treatment period, FDW-PS and FDW-NGN showed a significant reduction in body weight, fat mass, percentage fat, LDL, TG, TC, HMG-CoA reductase, and leptin with an increment in the levels of HDL and adiponectin compared to the FDW group. FDW-PS and FDW-NGN also showed adipocyte hypotrophy compared to the FDW group. In conclusion, oral administration of 125 mg/kg PS methanolic extract to fructose-induced obese rats led to significant amelioration of obesity and hyperlipidemia through suppressing the adipocytes and inhibiting HMG-CoA reductase. PS has the potential to be used as an alternative or adjunct therapy for obesity and hyperlipidemia.
Bioaccessibility and Cellular Uptake of Carotenoids Extracted from Bactris gasipaes Fruit: Differences between Conventional and Ionic Liquid-Mediated Extraction
Authors: de Souza Mesquita Leonardo M. , Murador Daniella Carisa , Neves Bruna Vitória , Braga Anna Rafaela Cavalcante , Pisani Luciana Pellegrini , de Rosso Veridiana Vera
Published: June 2021

Currently, on an industrial scale, synthetic colorants are used in many fields, as well as those extracted with conventional organic solvents (COSs), leading to several environmental issues. Therefore, we developed a sustainable extraction and purification method mediated by ionic liquids (IL), which is considered an alternative high-performance replacement for COSs. Carotenoids are natural pigments with low bioaccessibility (BCT) and bioavailability (BV) but with huge importance to health. To investigate if the BCT and cellular uptake of the carotenoids are modified by the extraction method, we conducted a comparison assay between both extraction procedures (IL vs. COS). For this, we used the Amazonian fruit Bactris gasipaes, a rich source of pro-vitamin A carotenoids, to obtain the extract, which was emulsified and subjected to an in vitro digestion model followed by the Caco-2 cell absorption assay. The bioaccessibility of carotenoids using IL was better than those using COS (33.25%, and 26.84%, respectively). The cellular uptake of the carotenoids extracted with IL was 1.4-fold higher than those extracted using COS. Thus, IL may be a feasible alternative as extraction solvent in the food industry, replacing COS, since, in this study, no IL was present in the final extract.
Neuroprotective Activities of Crossyne flava Bulbs and Amaryllidaceae Alkaloids: Implications for Parkinson’s Disease
Authors: Omoruyi Sylvester I. , Ibrakaw Abobaker S. , Ekpo Okobi E. , Boatwright James S. , Cupido Christopher N. , Hussein Ahmed A.
Published: June 2021

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and affects approximately 6.3 million people worldwide. To date, the treatment of PD remains a challenge, as available treatment options are known to be associated with serious side effects; hence, the search for new treatment strategies is critical. Extracts from the Amaryllidaceae plant family as well as their alkaloids have been reported to have neuroprotective potentials. This study, therefore, investigated the biological activities of Crossyne flava and its isolated alkaloids in an in vitro MPP+ (1-methyl-4-phenylpyridinium) PD model using SH-SY5Y cells. The effects of the total extract as well as the four compounds isolated from Crossyne flava (i.e., pancratinine B (1), bufanidrine (2), buphanisine (3), and epibuphanisine (4)) were evaluated for cell viability, neuroprotection, levels of reactive oxygen species (ROS), adenosine triphosphate activity (ATP), and caspase 3/7 activity in SH-SY5Y cells. The results obtained showed that pre-treatment with both the extract and the isolated compounds was effective in protecting the SH-SY5Y cells from MPP+-induced neurotoxicity and inhibited ROS generation, ATP depletion as well as apoptosis induction in the SH-SY5Y cells. The results of this study show that the Amaryllidaceae plant family may be a source of novel compounds for the treatment of neurodegenerative diseases, which validates the reported traditional uses.
A Call for a Change in Policy Regarding the Necessity for SDE Tests to Validate the Veracity of the Outcome of Enantioselective Syntheses, the Inherent Chiral State of Natural Products, and Other Cases Involving Enantioenriched Samples
Authors: Han Jianlin , Dembinski Roman , Soloshonok Vadim A. , Klika Karel D.
Published: June 2021

We wish to draw attention to an important issue concerning scientific practice with regard to enhancing the quality of publications in Molecules (as well as for other journals) [...]
Supramolecular Chemistry: Host–Guest Molecular Complexes
Authors: Khan Sadaf Bashir , Lee Shern-Long
Published: June 2021

In recent times, researchers have emphasized practical approaches for capturing coordinated and selective guest entrap. The physisorbed nanoporous supramolecular complexes have been widely used to restrain various guest species on compact supporting surfaces. The host–guest (HG) interactions in two-dimensional (2D) permeable porous linkages are growing expeditiously due to their future applications in biocatalysis, separation technology, or nanoscale patterning. The different crystal-like nanoporous network has been acquired to enclose and trap guest molecules of various dimensions and contours. The host centers have been lumped together via noncovalent interactions (such as hydrogen bonds, van der Waals (vdW) interactions, or coordinate bonds). In this review article, we enlighten and elucidate recent progress in HG chemistry, explored via scanning tunneling microscopy (STM). We summarize the synthesis, design, and characterization of typical HG structural design examined on various substrates, under ambient surroundings at the liquid-solid (LS) interface, or during ultrahigh vacuum (UHV). We emphasize isoreticular complexes, vibrant HG coordination, or hosts functional cavities responsive to the applied stimulus. Finally, we critically discuss the significant challenges in advancing this developing electrochemical field.
Assessment of Antidiabetic Activity of the Shikonin by Allosteric Inhibition of Protein-Tyrosine Phosphatase 1B (PTP1B) Using State of Art: An In Silico and In Vitro Tactics
Authors: Saeed Mohd , Shoaib Ambreen , Tasleem Munazzah , Alabdallah Nadiyah M. , Alam Md Jahoor , Asmar Zeina El , Jamal Qazi Mohammad Sajid , Bardakci Fevzi , Alqahtani Saad S. , Ansari Irfan Ahmad , Badraoui Riadh
Published: June 2021

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin’s in silico interaction with protein tyrosine phosphate 1B, as well as it’s in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule’s module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.
Chemical Variations among Shengmaisan-Based TCM Patent Drugs by Ultra-High Performance Liquid Chromatography Coupled with Hybrid Quadrupole Orbitrap Mass Spectrometry
Authors: Xu Lulu , Shang Zhanpeng , Tian Yungang , Xiong Ming , Nijat Dilaram , Wang Yuan , Qiao Xue , Ye Min
Published: June 2021

Shengmaisan (SMS) is a famous traditional Chinese medicine (TCM) formula to treat coronary heart diseases. It has been developed into several TCM patent drugs to meet the demands of different patients. In this study, a research strategy was proposed to reveal the chemical variations among four SMS-based patent drugs, including Shengmai Oral Solution (Shengmaiyin, SMY), Shengmai Capsule (Shengmai Jiaonang, SMJN), Yiqi Fumai Injection (YQFMI), and Yiqi Fumai Capsule (Yiqi Fumai Jiaonang, YQJN). Firstly, 227 compounds were tentatively identified using an Orbitrap-MS in the full scan/dd-MS2 mode. Secondly, untargeted metabolomics analysis suggested that ginsenosides, steroidal saponins, and lignans were the main types of differential compounds for the four patent drugs. Finally, the contents of 25 compounds were simultaneously determined in 30 batches of samples in the parallel reaction monitoring (PRM) mode. Partial least squares discriminant analysis (PLS-DA) revealed the contents of ginsenosides Re, Rg1, Rb1, Ro, and Rg3, and schisandrin showed the highest intergroup variations. These compounds were chemical markers to differentiate the SMS-based patent drugs.
In Silico Approach Using Free Software to Optimize the Antiproliferative Activity and Predict the Potential Mechanism of Action of Pyrrolizine-Based Schiff Bases
Authors: Almalki Faisal A. , Abdalla Ashraf N. , Shawky Ahmed M. , El Hassab Mahmoud A. , Gouda Ahmed M.
Published: June 2021

In the current study, a simple in silico approach using free software was used with the experimental studies to optimize the antiproliferative activity and predict the potential mechanism of action of pyrrolizine-based Schiff bases. A compound library of 288 Schiff bases was designed based on compound 10, and a pharmacophore search was performed. Structural analysis of the top scoring hits and a docking study were used to select the best derivatives for the synthesis. Chemical synthesis and structural elucidation of compounds 16a–h were discussed. The antiproliferative activity of 16a–h was evaluated against three cancer (MCF7, A2780 and HT29, IC50 = 0.01–40.50 μM) and one normal MRC5 (IC50 = 1.27–24.06 μM) cell lines using the MTT assay. The results revealed the highest antiproliferative activity against MCF7 cells for 16g (IC50 = 0.01 μM) with an exceptionally high selectivity index of (SI = 578). Cell cycle analysis of MCF7 cells treated with compound 16g revealed a cell cycle arrest at the G2/M phase. In addition, compound 16g induced a dose-dependent increase in apoptotic events in MCF7 cells compared to the control. In silico target prediction of compound 16g showed six potential targets that could mediate these activities. Molecular docking analysis of compound 16g revealed high binding affinities toward COX-2, MAP P38α, EGFR, and CDK2. The results of the MD simulation revealed low RMSD values and high negative binding free energies for the two complexes formed between compound 16g with EGFR, and CDK2, while COX-2 was in the third order. These results highlighted a great potentiality for 16g to inhibit both CDK2 and EGFR. Taken together, the results mentioned above highlighted compound 16g as a potential anticancer agent.
Subcritical Water Extraction of Natural Products
Authors: Cheng Yan , Xue Fumin , Yu Shuai , Du Shichao , Yang Yu
Published: June 2021

Subcritical water refers to high-temperature and high-pressure water. A unique and useful characteristic of subcritical water is that its polarity can be dramatically decreased with increasing temperature. Therefore, subcritical water can behave similar to methanol or ethanol. This makes subcritical water a green extraction fluid used for a variety of organic species. This review focuses on the subcritical water extraction (SBWE) of natural products. The extracted materials include medicinal and seasoning herbs, vegetables, fruits, food by-products, algae, shrubs, tea leaves, grains, and seeds. A wide range of natural products such as alkaloids, carbohydrates, essential oil, flavonoids, glycosides, lignans, organic acids, polyphenolics, quinones, steroids, and terpenes have been extracted using subcritical water. Various SBWE systems and their advantages and drawbacks have also been discussed in this review. In addition, we have reviewed co-solvents including ethanol, methanol, salts, and ionic liquids used to assist SBWE. Other extraction techniques such as microwave and sonication combined with SBWE are also covered in this review. It is very clear that temperature has the most significant effect on SBWE efficiency, and thus, it can be optimized. The optimal temperature ranges from 130 to 240 °C for extracting the natural products mentioned above. This review can help readers learn more about the SBWE technology, especially for readers with an interest in the field of green extraction of natural products. The major advantage of SBWE of natural products is that water is nontoxic, and therefore, it is more suitable for the extraction of herbs, vegetables, and fruits. Another advantage is that no liquid waste disposal is required after SBWE. Compared with organic solvents, subcritical water not only has advantages in ecology, economy, and safety, but also its density, ion product, and dielectric constant can be adjusted by temperature. These tunable properties allow subcritical water to carry out class selective extractions such as extracting polar compounds at lower temperatures and less polar ingredients at higher temperatures. SBWE can mimic the traditional herbal decoction for preparing herbal medication and with higher extraction efficiency. Since SBWE employs high-temperature and high-pressure, great caution is needed for safe operation. Another challenge for application of SBWE is potential organic degradation under high temperature conditions. We highly recommend conducting analyte stability checks when carrying out SBWE. For analytes with poor SBWE efficiency, a small number of organic modifiers such as ethanol, surfactants, or ionic liquids may be added.
Niclosamide Is Active In Vitro against Mycetoma Pathogens
Authors: Mahmoud Abdelhalim B. , Abd Algaffar Shereen , van de Sande Wendy , Khalid Sami , Kaiser Marcel , Mäser Pascal
Published: June 2021

Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamidein particular, as drug repurposing candidates for mycetoma.
Streptomyces griseus KJ623766: A Natural Producer of Two Anthracycline Cytotoxic Metabolites β- and γ-Rhodomycinone
Authors: Zaid Ahmed S. Abu , Aleissawy Ahmed E. , Yahia Ibrahim S. , Yassien Mahmoud A. , Hassouna Nadia A. , Aboshanab Khaled M.
Published: June 2021

Background: This study aimed to produce, purify, structurally elucidate, and explore the biological activities of metabolites produced by Streptomyces (S.) griseus isolate KJ623766, a recovered soil bacterium previously screened in our lab that showed promising cytotoxic activities against various cancer cell lines. Methods: Production of cytotoxic metabolites from S. griseus isolate KJ623766 was carried out in a 14L laboratory fermenter under specified optimum conditions. Using a 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide assay, the cytotoxic activity of the ethyl acetate extract against Caco2 and Hela cancer cell lines was determined. Bioassay-guided fractionation of the ethyl acetate extract using different chromatographic techniques was used for cytotoxic metabolite purification. Chemical structures of the purified metabolites were identified using mass, 1D, and 2D NMR spectroscopic analysis. Results: Bioassay-guided fractionation of the ethyl acetate extract led to the purification of two cytotoxic metabolites, R1 and R2, of reproducible amounts of 5 and 1.5 mg/L, respectively. The structures of R1 and R2 metabolites were identified as β- and γ-rhodomycinone with CD50 of 6.3, 9.45, 64.8 and 9.11, 9.35, 67.3 µg/mL against Caco2, Hela and Vero cell lines, respectively. Values were comparable to those of the positive control doxorubicin. Conclusions: This is the first report about the production of β- and γ-rhodomycinone, two important scaffolds for synthesis of anticancer drugs, from S. griseus.
Resveratrol Butyrate Esters Inhibit Obesity Caused by Perinatal Exposure to Bisphenol A in Female Offspring Rats
Authors: Shih Ming-Kuei , Tain You-Lin , Chen Yu-Wei , Hsu Wei-Hsuan , Yeh Yao-Tsung , Chang Sam K. C. , Liao Jin-Xian , Hou Chih-Yao
Published: June 2021

Resveratrol butyrate esters (RBE) are derivatives of resveratrol (RSV) and butyric acid and exhibit biological activity similar to that of RSV but with higher bioavailability. The aim of this study was designed as an animal experiment to explore the effects of RBE on the serum biochemistry, and fat deposits in the offspring rats exposed to bisphenol A (BPA), along with the growth and decline of gut microbiota. We constructed an animal model of perinatal Bisphenol A (BPA) exposure to observe the effects of RBE supplementation on obesity, blood lipids, and intestinal microbiota in female offspring rats. Perinatal exposure to BPA led to weight gain, lipid accumulation, high levels of blood lipids, and deterioration of intestinal microbiota in female offspring rats. RBE supplementation reduced the weight gain and lipid accumulation caused by BPA, optimised the levels of blood lipids, significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio, and increased and decreased the abundance of S24-7 and Lactobacillus, respectively. The analysis of faecal short-chain fatty acid (SCFA) levels revealed that BPA exposure increased the faecal concentration of acetate, which could be reduced via RBE supplementation. However, the faecal concentrations of propionate and butyrate were not only significantly lower than that of acetate, but also did not significantly change in response to BPA exposure or RBE supplementation. Hence, RBE can suppress BPA-induced obesity in female offspring rats, and it demonstrates excellent modulatory activity on intestinal microbiota, with potential applications in perinatological research.