bluuebunny/crossref_metadata_2025 huggingface dataset:
A High-Throughput Small-Angle X-ray Scattering Assay to Determine the Conformational Change of Plasminogen
Authors: Quek Adam J. , Cowieson Nathan P. , Caradoc-Davies Tom T. , Conroy Paul J. , Whisstock James C. , Law Ruby H. P.
Published: September 2023

Plasminogen (Plg) is the inactive form of plasmin (Plm) that exists in two major glycoforms, referred to as glycoforms I and II (GI and GII). In the circulation, Plg assumes an activation-resistant “closed” conformation via interdomain interactions and is mediated by the lysine binding site (LBS) on the kringle (KR) domains. These inter-domain interactions can be readily disrupted when Plg binds to lysine/arginine residues on protein targets or free L-lysine and analogues. This causes Plg to convert into an “open” form, which is crucial for activation by host activators. In this study, we investigated how various ligands affect the kinetics of Plg conformational change using small-angle X-ray scattering (SAXS). We began by examining the open and closed conformations of Plg using size-exclusion chromatography (SEC) coupled with SAXS. Next, we developed a high-throughput (HTP) 96-well SAXS assay to study the conformational change of Plg. This method enables us to determine the Kopen value, which is used to directly compare the effect of different ligands on Plg conformation. Based on our analysis using Plg GII, we have found that the Kopen of ε-aminocaproic acid (EACA) is approximately three times greater than that of tranexamic acid (TXA), which is widely recognized as a highly effective ligand. We demonstrated further that Plg undergoes a conformational change when it binds to the C-terminal peptides of the inhibitor α2-antiplasmin (α2AP) and receptor Plg–RKT. Our findings suggest that in addition to the C-terminal lysine, internal lysine(s) are also necessary for the formation of open Plg. Finally, we compared the conformational changes of Plg GI and GII directly and found that the closed form of GI, which has an N-linked glycosylation, is less stable. To summarize, we have successfully determined the response of Plg to various ligand/receptor peptides by directly measuring the kinetics of its conformational changes.
Endothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling
Authors: Akhter Mohammad Shohel , Goodwin Julie Elizabeth
Published: September 2023

The endothelium constitutes the innermost lining of the blood vessels and controls blood fluidity, vessel permeability, platelet aggregation, and vascular tone. Endothelial dysfunction plays a key role in initiating a vascular inflammatory cascade and is the pivotal cause of various devastating diseases in multiple organs including the heart, lung, kidney, and brain. Glucocorticoids have traditionally been used to combat vascular inflammation. Endothelial cells express glucocorticoid receptors (GRs), and recent studies have demonstrated that endothelial GR negatively regulates vascular inflammation in different pathological conditions such as sepsis, diabetes, and atherosclerosis. Mechanistically, the anti-inflammatory effects of GR are mediated, in part, through the suppression of Wnt signaling. Moreover, GR modulates the fatty acid oxidation (FAO) pathway in endothelial cells and hence can influence FAO-mediated fibrosis in several organs including the kidneys. This review summarizes the relationship between GR and Wnt signaling in endothelial cells and the effects of the Wnt pathway in different cardiac and renal diseases. Available data suggest that GR plays a significant role in restoring endothelial integrity, and research on endothelial GR–Wnt interactions could facilitate the development of novel therapies for many cardiorenal conditions.
High Recovery Chromatographic Purification of mRNA at Room Temperature and Neutral pH
Authors: Miklavčič Rok , Megušar Polona , Kodermac Špela Meta , Bakalar Blaž , Dolenc Darko , Sekirnik Rok , Štrancar Aleš , Černigoj Urh
Published: September 2023

Messenger RNA (mRNA) is becoming an increasingly important therapeutic modality due to its potential for fast development and platform production. New emerging RNA modalities, such as circular RNA, drive the need for the development of non-affinity purification approaches. Recently, the highly efficient chromatographic purification of mRNA was demonstrated with multimodal monolithic chromatography media (CIM® PrimaS), where efficient mRNA elution was achieved with an ascending pH gradient approach at pH 10.5. Here, we report that a newly developed chromatographic material enables the elution of mRNA at neutral pH and room temperature. This material demonstrates weak anion-exchanging properties and an isoelectric point of 5.3. It enables the baseline separation of mRNA (at least up to 10,000 nucleotides (nt) in size) from parental plasmid DNA (regardless of isoform composition) with both a NaCl gradient and ascending pH gradient approach, while mRNA elution is achieved in a pH range of 5–7. In addition, the basic structure of the novel material is a chromatographic monolith, enabling convection-assisted mass transfer of large RNA molecules to and from the active surface. This facilitates the elution of mRNA in 3–7 column volumes with more than 80% elution recovery and uncompromised integrity. This is demonstrated by the purification of a model mRNA (size 995 nt) from an in vitro transcription reaction mixture. The purified mRNA is stable for at least 34 days, stored in purified H2O at room temperature.
The Essential Role of PCR and PCR Panel Size in Comparison with Urine Culture in Identification of Polymicrobial and Fastidious Organisms in Patients with Complicated Urinary Tract Infections
Authors: Hao Xingpei , Cognetti Marcus , Patel Chiraag , Jean-Charles Nathalie , Tumati Arun , Burch-Smith Rhonda , Holton Mara , Kapoor Deepak A.
Published: September 2023

Complicated urinary tract infections (cUTIs) are difficult to treat, consume substantial resources, and cause increased patient morbidity. Data suggest that cUTI may be caused by polymicrobial and fastidious organisms (PMOs and FOs, respectively); as such, urine culture (UC) may be an unreliable diagnostic tool for detecting cUTIs. We sought to determine the utility of PCR testing for patients presumed to have a cUTI and determine the impact of PCR panel size on organism detection. We reviewed 36,586 specimens from patients with presumptive cUTIs who received both UC and PCR testing. Overall positivity rate for PCR and UC was 52.3% and 33.9%, respectively (p < 0.01). PCR detected more PMO and FO than UC (PMO: 46.2% vs. 3.6%; FO: 31.3% vs. 0.7%, respectively, both p < 0.01). Line-item concordance showed that PCR detected 90.2% of organisms identified by UC whereas UC discovered 31.9% of organisms detected by PCR (p < 0.01). Organism detection increased with expansion in PCR panel size from 5–25 organisms (p < 0.01). Our data show that overall positivity rate and the detection of individual organisms, PMO and FO are significantly with PCR testing and that these advantages are ideally realized with a PCR panel size of 25 or greater.
Fit-for-Purpose Information for Offshore Wind Farming Applications—Part-II: Gap Analysis and Recommendations
Authors: Schulz-Stellenfleth Johannes , Blauw Anouk , Laakso Lauri , Mourre Baptiste , She Jun , Wehde Henning
Published: September 2023

Offshore wind energy installations in coastal areas have grown massively over the last decade. This development comes with a large number of technological, environmental, economic, and scientific challenges, which need to be addressed to make the use of offshore wind energy sustainable. One important component in these optimization activities is suitable information from observations and numerical models. The purpose of this study is to analyze the gaps that exist in the present monitoring systems and their respective integration with models. This paper is the second part of two manuscripts and uses results from the first part about the requirements for different application fields. The present solutions to provide measurements for the required information products are described for several European countries with growing offshore wind operations. The gaps are then identified and discussed in different contexts, like technology evolution, trans-European monitoring and modeling initiatives, legal aspects, and cooperation between industry and science. The monitoring gaps are further quantified in terms of missing observed quantities, spatial coverage, accuracy, and continuity. Strategies to fill the gaps are discussed, and respective recommendations are provided. The study shows that there are significant information deficiencies that need to be addressed to ensure the economical and environmentally friendly growth of the offshore wind farm sector. It was also found that many of these gaps are related to insufficient information about connectivities, e.g., concerning the interactions of wind farms from different countries or the coupling between physical and biological processes.
Time–Frequency Analysis of Nonlinear Dynamics of an Aquaculture Cage Array in Waves
Authors: Zhu Liu , Cheng Yuan , Wang Jinfang , Zhu Hongyu , Xu Zhijing
Published: September 2023

The nonlinear dynamic response of an aquaculture cage array caused by wave-frequency and low-frequency excitations coupled with the nonlinearity of the mooring and the netting system is a complicated problem. So far, this problem still has not been completely understood. To address this issue, we consider the nonlinear interaction of an extreme wave with an aquaculture cage array containing 16 net cages in a 2 × 8 configuration. This paper aims to provide insight into understanding the nonlinear dynamics of an aquaculture cage array via time–frequency analysis. Time-domain analysis shows that the cage array exhibits weak nonlinearity in the surge and heave motions. On the contrary, there is strong nonlinearity in the sway motion under 45° and 90° wave attacks. Aside from this, the frequency-domain analysis indicates that nonlinearities exist in all three of these different responses (surge/sway/heave). Particularly, the low-frequency component has a predominant effect on the nonlinearity of the sway motion under 45° and 90° wave attacks. With this understanding, future aquaculture fish farms that contain multiple cages (i.e., cage array) can be potentially designed to withstand severe conditions in the open ocean.
Decoupling CO2 Emissions from Economic Growth in China’s Cities from 2000 to 2020: A Case Study of the Pearl River Delta Agglomeration
Authors: Wang Zhixiong , Li Fuhan , Xie Zihan , Li Qingyin , Zhang Yongli , Dai Meilin
Published: September 2023

As one of the most densely populated, economically developed, and outwardly open urban agglomerations in China, the Pearl River Delta (PRD) urban agglomeration is a key player in achieving China’s carbon peak and carbon neutrality targets. This study analyzes low-emission development by examining the evolutionary patterns of carbon dioxide (CO2) emissions and the decoupling relationship between economic growth and CO2 emissions, using the latest available data from 2000 to 2020. Here are the main findings: (1) We found a significant fluctuation in the decoupling statuses between economic advancements and CO2 emissions within the PRD domain. Predominantly, a weak decoupling scenario was observed, where economic proliferations were paralleled by nearly equivalent increments in CO2 emissions. (2) The growth rate of carbon emissions increased significantly relative to economic expansion during 2015–2020, especially pronounced in cities such as Guangdong, Zhuhai, Foshan, and Dongguan. This delineates the persistent challenges in steering towards a pathway of energy conservation and emission abatement in the region. (3) Furthermore, a differential role of elasticity factors was noted across cities: Guangzhou and Shenzhen witnessed a significant influence of energy-saving elasticity in fostering a decoupling between economic surge and CO2 emissions, whereas in other cities, the emphasis shifted towards emission-reduction elasticity as a more vital determinant. The results of this study are of great significance for guiding policy makers and stakeholders in urban clusters across China and in similar regions globally to achieve low carbon development goals.
Anti-Inflammatory and Antifibrotic Potential of Longidaze in Bleomycin-Induced Pulmonary Fibrosis
Authors: Pakhomova Angelina , Pershina Olga , Bochkov Pavel , Ermakova Natalia , Pan Edgar , Sandrikina Lubov , Dagil Yulia , Kogai Lena , Grimm Wolf-Dieter , Zhukova Mariia , Avdeev Sergey
Published: September 2023

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaze (Bovhyaluronidase Azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaze was administered at different doses by intranasal and intramuscular routes. Histology, hematology, and enzyme-linked immunosorbent assay were used in the study. The use of Longidaze reduced pulmonary fibrosis, as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue, and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaze inhibited the inflammatory response in pulmonary fibrosis, and decreased the levels of IL-6, TNF-α, and hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaze at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaze is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.
Analysis of Compressive Strength of Anhydrite Binder Using Full Factorial Design
Authors: Nizevičienė Dalia , Kybartienė Nora , Jusas Vacius
Published: September 2023

Flue gas desulfurization gypsum (FGD gypsum) is obtained from the desulphurization of combustion gases in fossil fuel power plants. FGD gypsum can be used to produce anhydrite binder. This research is devoted to the investigation of the influence of the calcination temperature of FGD gypsum, the activators K2SO4 and Na2SO4, and their amount on the compressive strength of anhydrite binder during hydration. The obtained results showed that as the calcination temperature increased, the compressive strength of anhydrite binder decreased at its early age (up to 3 days) and increased after 28 days. The compressive strength of the anhydrite binder produced at 800 °C and 500 °C differed more than five times after 28 days. The activators K2SO4 and Na2SO4 had a large effect on the hydration of anhydrite binder at its early age (up to 3 days) in comparison with the anhydrite binder without activators. The presence of the activators of either K2SO4 or K2SO4 almost had no influence on the compressive strength after 28 days. To determine which factor, the calcination temperature of FGD gypsum (500–800 °C), the hydration time (3–28 days) or the amount (0–2%) of the activators K2SO4 and Na2SO4, has the greatest influence on the compressive strength, a 23 full factorial design was applied. Multiple linear regression was used to develop a mathematical model and predict the compressive strength of the anhydrite binder. The statistical analysis showed that the hydration time had the strongest impact on the compressive strength of the anhydrite binder using activators K2SO4 and Na2SO4. The activator K2SO4 had a greater influence on the compressive strength than the activator Na2SO4. The obtained mathematical model can be used to forecast the compressive strength of the anhydrite binder produced from FGD gypsum if the considered factors are within the same limiting values as in the suggested model since the coefficient of determination (R2) was close to 1, and the mean absolute percentage error (MAPE) was less than 10%.
Hybrid Cements and Construction Elements Based on Alkaline Activation with Sodium Sulfates from Fly Ash and Construction and Demolition Waste
Authors: Valencia-Saavedra William , Robayo-Salazar Rafael A. , Mejía de Gutiérrez Ruby
Published: September 2023

This article demonstrates the possibility of producing hybrid cementitious materials (pastes, mortars, concretes, and precast elements) based on fly ash (FA) and construction and demolition wastes (CDW) using alkaline activation technology. Sodium sulfate was used as an activator and fine and coarse aggregates were obtained from CDW residues. An addition of Portland cement (OPC) (10 to 30%) allowed for improvement in the mechanical behavior of the hybrid cements and them to be cured at room temperature (25 °C). The FA and CDW cementitious materials obtained compressive strengths of 37 MPa and 32 MPa, respectively. The compressive strength of FA and CDW alkali-activated concretes at 28 days of curing was 22 MPa and 18 MPa, respectively, which identifies them as structural concretes according to NSR-10 title C in Colombia. The potential use of these concretes was validated by obtaining and classifying precast materials.
Staircase Recognition and Localization Using Convolutional Neural Network (CNN) for Cleaning Robot Application
Authors: Ilyas Muhammad , Lakshmanan Anirudh , Le Anh , Elara Mohan
Published: September 2023

Floor-cleaning robots are primarily designed to clean on a single floor, while multi-floor environments are usually not considered target applications. However, it is more efficient to have an autonomous floor-cleaning robot that can climb stairs and reach the next floors in a multi-floor building. To operate in such environments, the ability of a mobile robot to autonomously traverse staircases is very important. For this operation, staircase detection and localization are essential components for planning the traversal route on staircases. This article describes a deep learning approach using a convolutional neural network (CNN)-based robot operation system (ROS) framework for staircase detection, localization, and maneuvering of the robot to the detected stair. We present a real-time object detection framework to detect staircases in incoming images. We also localize these staircases using a contour detection algorithm to detect the target point: a point close to the center of the first step, and an angle of approach to the target point with respect to the current location of the robot. Experiments are performed with data from images captured on different types of staircases at different viewpoints/angles. The experimental results show that the presented approach can achieve an accuracy of 95% and a recall of 86.81%. A total runtime of 155 ms is taken to identify the presence of a staircase and the detection of the first step in the working environment, as well as being able to locate the target point with an accuracy of ±2 cm, ±1 degree.
Bounds for Toeplitz Determinants and Related Inequalities for a New Subclass of Analytic Functions
Authors: Tang Huo , Gul Ihtesham , Hussain Saqib , Noor Saima
Published: September 2023

In this article, we use the q-derivative operator and the principle of subordination to define a new subclass of analytic functions related to the q-Ruscheweyh operator. Sufficient conditions, sharp bounds for the initial coefficients, a Fekete–Szegö functional and a Toeplitz determinant are investigated for this new class of functions. Additionally, we also present several established consequences derived from our primary findings.
Generalization of Neural Networks on Second-Order Hypercomplex Numbers
Authors: Pavlov Stanislav , Kozlov Dmitry , Bakulin Mikhail , Zuev Aleksandr , Latyshev Andrey , Beliaev Alexander
Published: September 2023

The vast majority of existing neural networks operate by rules set within the algebra of real numbers. However, as theoretical understanding of the fundamentals of neural networks and their practical applications grow stronger, new problems arise, which require going beyond such algebra. Various tasks come to light when the original data naturally have complex-valued formats. This situation is encouraging researchers to explore whether neural networks based on complex numbers can provide benefits over the ones limited to real numbers. Multiple recent works have been dedicated to developing the architecture and building blocks of complex-valued neural networks. In this paper, we generalize models by considering other types of hypercomplex numbers of the second order: dual and double numbers. We developed basic operators for these algebras, such as convolution, activation functions, and batch normalization, and rebuilt several real-valued networks to use them with these new algebras. We developed a general methodology for dual and double-valued gradient calculations based on Wirtinger derivatives for complex-valued functions. For classical computer vision (CIFAR-10, CIFAR-100, SVHN) and signal processing (G2Net, MusicNet) classification problems, our benchmarks show that the transition to the hypercomplex domain can be helpful in reaching higher values of metrics, compared to the original real-valued models.
Metabolite Profile Characterization of Cyanobacterial Strains with Bioactivity on Lipid Metabolism Using In Vivo and In Vitro Approaches
Authors: Ribeiro Tiago , Jónsdóttir Kristín , Hernandez-Bautista Rene , Silva Natália Gonçalves , Sánchez-Astráin Begoña , Samadi Afshin , Eiriksson Finnur F. , Thorsteinsdóttir Margrét , Ussar Siegfried , Urbatzka Ralph
Published: September 2023

Cyanobacteria have demonstrated their therapeutic potential for many human diseases. In this work, cyanobacterial extracts were screened for lipid reducing activity in zebrafish larvae and in fatty-acid-overloaded human hepatocytes, as well as for glucose uptake in human hepatocytes and ucp1 mRNA induction in murine brown adipocytes. A total of 39 cyanobacteria strains were grown and their biomass fractionated, resulting in 117 chemical fractions. Reduction of neutral lipids in zebrafish larvae was observed for 12 fractions and in the human hepatocyte steatosis cell model for five fractions. The induction of ucp1 expression in murine brown adipocytes was observed in six fractions, resulting in a total of 23 bioactive non-toxic fractions. All extracts were analyzed by untargeted UPLC-Q-TOF-MS mass spectrometry followed by multivariate statistical analysis to prioritize bioactive strains. The metabolite profiling led to the identification of two markers with lipid reducing activity in zebrafish larvae. Putative compound identification using mass spectrometry databases identified them as phosphatidic acid and aromatic polyketides derivatives—two compound classes, which were previously associated with effects on metabolic disorders. In summary, we have identified cyanobacterial strains with promising lipid reducing activity, whose bioactive compounds needs to be identified in the future.
Development and Prospective Applications of 3D Membranes as a Sensor for Monitoring and Inducing Tissue Regeneration
Authors: Wu Hanning , Chen Jiawen , Zhao Pengxiang , Liu Mengyu , Xie Fei , Ma Xuemei
Published: September 2023

For decades, tissue regeneration has been a challenging issue in scientific modeling and human practices. Although many conventional therapies are already used to treat burns, muscle injuries, bone defects, and hair follicle injuries, there remains an urgent need for better healing effects in skin, bone, and other unique tissues. Recent advances in three-dimensional (3D) printing and real-time monitoring technologies have enabled the creation of tissue-like membranes and the provision of an appropriate microenvironment. Using tissue engineering methods incorporating 3D printing technologies and biomaterials for the extracellular matrix (ECM) containing scaffolds can be used to construct a precisely distributed artificial membrane. Moreover, advances in smart sensors have facilitated the development of tissue regeneration. Various smart sensors may monitor the recovery of the wound process in different aspects, and some may spontaneously give feedback to the wound sites by releasing biological factors. The combination of the detection of smart sensors and individualized membrane design in the healing process shows enormous potential for wound dressings. Here, we provide an overview of the advantages of 3D printing and conventional therapies in tissue engineering. We also shed light on different types of 3D printing technology, biomaterials, and sensors to describe effective methods for use in skin and other tissue regeneration, highlighting their strengths and limitations. Finally, we highlight the value of 3D bioengineered membranes in various fields, including the modeling of disease, organ-on-a-chip, and drug development.
A Novel Approach for Dry Cutting Inconel 718 in a More Sustainable and Low-Cost Way by Actively and Purposely Utilizing the Built-Up Layer
Authors: Song Xiaoqi , He Weiming , Ihara Tohru
Published: September 2023

Due to its physical and mechanical properties, Inconel 718 remains a difficult-to-cut material and there is an urgent need to develop a more sustainable and low-cost way to machine it. A novel approach for dry cutting Inconel 718 by actively and purposely utilizing the built-up layer (BUL), which can be called the self-protective tool (SPT) method, is proposed and investigated in detail in this paper. Various cutting experiments were carried out using the age-treated Inconel 718 and uncoated cemented carbide tools. The formation condition of the BUL, its formation mechanism, its stability, and its protective effect were examined by measuring the tools after cutting using a scanning electron microscope (SEM) and laser confocal microscopy (LCM). The influences of BUL on the cutting process were investigated using cutting force analysis and surface roughness analysis. The results confirmed that the stability of the BUL is very high, and the BUL can not only significantly protect the tool from wear but also reduce friction at the tool–chip interface and maintain surface roughness. It also revealed that the height of the BUL can play a very important role in its protective effect. Comparative experiments verified the effectiveness and generalizability of the proposed SPT method.
Fabrication of PEG-PLGA Microparticles with Tunable Sizes for Controlled Drug Release Application
Authors: Sagoe Paul Nana Kwame , Velázquez Eduardo José Machado , Espiritusanto Yohely Maria , Gilbert Amelia , Orado Thalma , Wang Qiu , Jain Era
Published: September 2023

Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Although existing techniques for producing polymeric drug carriers offer the possibility of achieving greater production yield across a wide range of sizes, these methods are improbable to precisely tune particle size while upholding uniformity of particle size and morphology, ensuring consistent production yield, maintaining batch-to-batch reproducibility, and improving drug loading capacity. Herein, we developed a novel scalable method for the synthesis of tunable-sized microparticles with improved monodispersity and batch-to-batch reproducibility via the coaxial flow-phase separation technique. The study evaluated the effect of various process parameters on microparticle size and polydispersity, including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution, whereas surfactant concentration had the most substantial impact on the morphology of particles. In addition to synthesizing microparticles of spherical morphology yielding particle sizes in the range of 5–50 µm across different formulations, we were able to also synthesize several microparticles exhibiting different morphologies and particle concentrations as a demonstration of the tunability and scalability of this method. Notably, by adjusting key determining process parameters, it was possible to achieve microparticle sizes in a comparable range (5–7 µm) for different formulations despite varying the concentration of polymer and volume of polymer solution in the organic phase by an order of magnitude. Finally, by the incorporation of fluorescent dyes as model hydrophilic and hydrophobic drugs, we further demonstrated how polymer amount influences drug loading capacity, encapsulation efficiency, and release kinetics of these microparticles of comparable sizes. Our study provides a framework for fabricating both hydrophobic and hydrophilic drug-loaded microparticles and elucidates the interplay between fabrication parameters and the physicochemical properties of microparticles, thereby offering an itinerary for expanding the applicability of this method for producing polymeric microparticles with desirable characteristics for specific drug delivery applications.
Recent Synthetic Advances on the Use of Diazo Compounds Catalyzed by Metalloporphyrins
Authors: Simões Mário M. Q. , Cavaleiro José A. S. , Ferreira Vitor F.
Published: September 2023

Diazo compounds are organic substances that are often used as precursors in organic synthesis like cyclization reactions, olefinations, cyclopropanations, cyclopropenations, rearrangements, and carbene or metallocarbene insertions into C−H, N−H, O−H, S−H, and Si−H bonds. Typically, reactions from diazo compounds are catalyzed by transition metals with various ligands that modulate the capacity and selectivity of the catalyst. These ligands can modify and enhance chemoselectivity in the substrate, regioselectivity and enantioselectivity by reflecting these preferences in the products. Porphyrins have been used as catalysts in several important reactions for organic synthesis and also in several medicinal applications. In the chemistry of diazo compounds, porphyrins are very efficient as catalysts when complexed with low-cost metals (e.g., Fe and Co) and, therefore, in recent years, this has been the subject of significant research. This review will summarize the advances in the studies involving the field of diazo compounds catalyzed by metalloporphyrins (M−Porph, M = Fe, Ru, Os, Co, Rh, Ir) in the last five years to provide a clear overview and possible opportunities for future applications. Also, at the end of this review, the properties of artificial metalloenzymes and hemoproteins as biocatalysts for a broad range of applications, namely those concerning carbene-transfer reactions, will be considered.
Activation of SF5CF3 by the N-Heterocyclic Carbene SIMes
Authors: Herbstritt Domenique , Tomar Pooja , Braun Thomas
Published: September 2023

The greenhouse gas SF5CF3 was photochemically activated with SIMes (1,3-Bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene) to give 1,3-dimesityl-2,2-difluoroimidazolidine (SIMesF2), and 1,3-dimesitylimidazolidine-2-sulfide, as well as the trifluoromethylated carbene derivative 1,3-dimesityl-2-fluoro-2-trifluoromethylimidazolidine. CF3 radicals, as well as SF4, serve presumably as intermediates of the conversions. In addition, the photochemical activation of SF5CF3 was performed in the presence of triphenylphosphine. The formation of triphenyldifluorophosphorane and triphenylphosphine sulfide was observed.
A Review of the Current State of Magnetic Force Microscopy to Unravel the Magnetic Properties of Nanomaterials Applied in Biological Systems and Future Directions for Quantum Technologies
Authors: Winkler Robert , Ciria Miguel , Ahmad Margaret , Plank Harald , Marcuello Carlos
Published: September 2023

Magnetism plays a pivotal role in many biological systems. However, the intensity of the magnetic forces exerted between magnetic bodies is usually low, which demands the development of ultra-sensitivity tools for proper sensing. In this framework, magnetic force microscopy (MFM) offers excellent lateral resolution and the possibility of conducting single-molecule studies like other single-probe microscopy (SPM) techniques. This comprehensive review attempts to describe the paramount importance of magnetic forces for biological applications by highlighting MFM’s main advantages but also intrinsic limitations. While the working principles are described in depth, the article also focuses on novel micro- and nanofabrication procedures for MFM tips, which enhance the magnetic response signal of tested biomaterials compared to commercial nanoprobes. This work also depicts some relevant examples where MFM can quantitatively assess the magnetic performance of nanomaterials involved in biological systems, including magnetotactic bacteria, cryptochrome flavoproteins, and magnetic nanoparticles that can interact with animal tissues. Additionally, the most promising perspectives in this field are highlighted to make the reader aware of upcoming challenges when aiming toward quantum technologies.
Investigation of Perception of Quality of Life and Psychological Burden of Patients Undergoing Hemodialysis—Quality of Life of Hemodialysis Patients
Authors: Rikos Nikos , Kassotaki Anna , Frantzeskaki Chara , Fragiadaki Maria , Mpalaskas Andreas , Vasilopoulos Georgios , Linardakis Manolis
Published: September 2023

Chronic kidney disease (CKD) has a significant impact on the life of patients undergoing chronic periodic hemodialysis. It negatively affects their social, economic and family status, and particularly their psychological well-being. The aim of this study was to investigate the perception of the quality of life (QoL) and psychological burden of patients undergoing hemodialysis. A cross-sectional study was conducted with 63 patients. Τhe majority were men (63.5%), and the mean age of the patients was 66.7 years (±12.9) with 61.9% aged 65–89 years. Data collection was performed in 2021 using the Hospital Anxiety and Depression Scale (HADS) and the Kidney Disease and Quality of Life-Short Form (KDQOL-SF™) research tools, and their relationships were assessed using parametric and non-parametric methods. Moderate to mild levels of Anxiety and Depression were found. Physical and Mental Composite Scores were mild to moderate, with the Mental Composite Score being significantly higher (p < 0.05). Anxiety and Depression were significantly correlated with lower QoL (p < 0.05), while a higher educational level was correlated with lower Depression Symptom Levels and higher QoL for Disease Symptoms, Disease Effects, Physical Functioning, Vitality and Overall Health (p < 0.05). A higher number of years of hemodialysis was correlated with lower levels of Anxiety and higher levels of Quality of Sleep (p < 0.05). Ease of Access to the Hemodialysis Unit was correlated with lower levels of Social Support (p < 0.05). The highest Mental Composite Scores were also correlated with a higher level of education, with patients living in urban areas, and with a higher monthly income (p < 0.05). Patients with moderate or severe levels of Anxiety and Depression had a lower QoL in the Physical and Mental Composite Scores, indicating their dependence on the appropriate medical, nursing and social environment in order to attain higher levels of well-being, leading to the improvement of patients’ health. This study was not registered.
A New Paclitaxel Formulation Based on Secretome Isolated from Mesenchymal Stem Cells Shows a Significant Cytotoxic Effect on Osteosarcoma Cell Lines
Authors: Banche Niclot Alessia Giovanna Santa , Marini Elena , Ferrero Ivana , Barbero Francesco , Rosso Elena , Fenoglio Ivana , Barge Alessandro , Pessina Augusto , Coccè Valentina , Paino Francesca , Mareschi Katia , Fagioli Franca
Published: September 2023

Background: Osteosarcoma (OS) represents a rare cancer with an unfavorable prognosis that needs innovative treatment. The aim was to isolate a secretome from mesenchymal stem cells (MSCs) that are treated with paclitaxel (PTX)-containing microvesicles as a drug delivery system and analyze its cytotoxic effects on OS cell lines (SJSA, MG63, and HOS). Methods: Three batches of secretome (SECR-1, SECR-2, and SECR-3) were produced from three bone marrow (BM) MSCs samples treated for 24 h with 15 µg/mL of PTX or with a standard medium. The viability of the OS cell lines after 5 days of exposure to SECR-1-2-3 (pure and diluted to 1:2 and 1:4) was analyzed with an MTT assay. The same SECR batches were analyzed with high-performance liquid chromatography (HPLC) and with a nanoparticle tracking assay (NTA). Results: A statistically significant decrease in the viability of all OS cell lines was observed after treatment with SECR-PTX 1-2-3 in a dose–response manner. The NTA analyses showed the presence of nanoparticles (NPs) with a mean size comparable to that of extracellular vesicles (EVs). The HPLC analyses detected the presence of PTX in minimal doses in all SECR batches. Conclusions: This proof-of-concept study showed that the conditioned medium isolated from MSCs loaded with PTX had a strong cytotoxic effect on OS cell lines, due to the presence of EV and PTX.
Exploring Carob (Ceratonia siliqua L.): A Comprehensive Assessment of Its Characteristics, Ethnomedicinal Uses, Phytochemical Aspects, and Pharmacological Activities
Authors: Dahmani Widad , Elaouni Nabia , Abousalim Abdelhadi , Akissi Zachée Louis Evariste , Legssyer Abdelkhaleq , Ziyyat Abderrahim , Sahpaz Sevser
Published: September 2023

The carob tree (Ceratonia siliqua L.) is currently considered one of the most valuable fruit and forest trees in various fields and sectors of activity. It is a versatile plant, belonging to the Fabaceae family. It is widely used in traditional medicine to treat many diseases such as diabetes, hypertension, and gastrointestinal disorders, given that all its parts (leaves, flowers, pods, seeds, wood, bark, and roots) are useful and hold value in many areas. Its importance has increased significantly in recent years. Originating from the Middle East, it is recognized for its ecological and industrial significance. Previous studies conducted on Ceratonia siliqua L. have revealed the presence of several compounds, including polyphenols, flavonoids, carbohydrates, minerals, and proteins. The carob tree demonstrates antihypertensive, antidepressant, anti-obesity, and antihyperglycemic activities. This plant is known for its medicinal and therapeutic virtues. Moreover, it is particularly interesting to consider the pharmacological activities of the major phytochemical compounds present in the different extracts of this plant, such as phenolic acids, for example, coumaric and gallic acids, as well as flavonoids such as kaempferol and quercetin. Therefore, this review aims to analyze some aspects of this plant, especially the taxonomy, cytogeography, traditional uses, phytochemical constituents, and pharmacological activities of Ceratonia siliqua L., in addition to its biological properties.
First Report of Hemp Fusarium Wilt Caused by Fusarium oxysporum in Croatia
Authors: Duvnjak Tomislav , Vrandecic Karolina , Sudaric Aleksandra , Cosic Jasenka , Siber Tamara , Matosa Kocar Maja
Published: September 2023

Wilted hemp (Cannabis sativa L.) plants were observed in August 2019 in commercial fields around Osijek, Croatia. Plants and roots with disease symptoms were collected. The single-spored isolates produced septate cottony white to light pink aerial mycelium and purple undersurface on potato dextrose agar (PDA). Smooth and hyaline hyphae were branched and septate. Macroconidia were fusiform to sickle-shaped with foot-shaped basal cells, elongated apical cells and three to five septa. Sequencing of the internal transcribed spacer and the partial elongation factor 1-α gene identified the species as Fusarium oxysporum. Artificial infection fulfills Koch’s postulates, producing plants which show stunted growth and wilt symptoms similar to those observed in the commercial fields. Control seedlings remained symptomless and healthy. To the best of our knowledge, this is the first report of hemp Fusarium wilt causing F. oxysporum in Croatia. Considering that F. oxysporum has been reported in main field crops in Croatia, the presence of this pathogen could cause economically significant hemp production decreases, especially in humid and cold springs and susceptible varieties.
Salvia rosmarinus Spenn. (Lamiaceae) Hydroalcoholic Extract: Phytochemical Analysis, Antioxidant Activity and In Vitro Evaluation of Fatty Acid Accumulation
Authors: Musolino Vincenzo , Macrì Roberta , Cardamone Antonio , Tucci Luigi , Serra Maria , Lupia Carmine , Maurotti Samantha , Mare Rosario , Nucera Saverio , Guarnieri Lorenza , Marrelli Mariangela , Coppoletta Anna Rita , Carresi Cristina , Gliozzi Micaela , Mollace Vincenzo
Published: September 2023

Salvia rosmarinus Spenn. is a native Mediterranean shrub belonging to the Lamiaceae family and is well-known as a flavoring and spicing agent. In addition to its classical use, it has drawn attention because its biological activities, due particularly to the presence of polyphenols, including carnosic acid and rosmarinic acid, and phenolic diterpenes as carnosol. In this study, the aerial part of rosemary was extracted with a hydroalcoholic solution through maceration, followed by ultrasound sonication, to obtain a terpenoids-rich Salvia rosmarinus extract (TRSrE) and a polyphenols-rich Salvia rosmarinus extract (PRSrE). After phytochemical characterization, both extracts were investigated for their antioxidant activity through a classical assay and with electron paramagnetic resonance (EPR) for their DPPH and hydroxyl radicals scavenging. Finally, their potential beneficial effects to reduce lipid accumulation in an in vitro model of NAFLD were evaluated.
Integral Effects of Porosity, Permeability, and Wettability on Oil–Water Displacement in Low-Permeability Sandstone Reservoirs—Insights from X-ray CT-Monitored Core Flooding Experiments
Authors: Wang Zhongnan , Liu Keyu , Zhang Chaoqian , Yan Haijun , Yu Jing , Yu Biao , Liu Jianliang , Jiang Tailiang , Dan Weidong , Hu Caizhi
Published: September 2023

Porosity, permeability, and wettability are crucial factors that affect the oil–water displacement process in reservoirs. Under subsurface conditions, the integral effects of these factors are extremely difficult to document. In this paper, waterflooding experiments were carried out using a core flooding system monitored with X-ray dual-energy CT. The mesoscale, three-dimensional characteristics of water displacing oil were obtained in real time. The integral effects of porosity, permeability, and wettability on the waterflooding in the low-permeability sandstone reservoirs were investigated. It was found that if the reservoir rock is water-wet, then the residual oil saturation decreases gradually with increasing porosity and permeability, showing an increasing waterflooding efficiency. On the contrary, if the reservoir rock is oil-wet, the residual oil saturation gradually increases with improving porosity and permeability, showing a decreasing waterflooding efficiency. The porosity, permeability, and wettability characteristics of reservoirs should be comprehensively evaluated before adopting technical countermeasures of waterflooding or wettability modification during oilfield development. If the porosity and permeability of the reservoir are high, water-wet reservoirs can be directly developed with waterflooding. However, it is better to make wettability modifications first before the waterflooding for oil-wet reservoirs. If the porosity and permeability of the reservoir are poor, direct waterflooding development has a better effect on oil-wet reservoirs compared with the water-wet reservoirs.
Study on Performance Optimization of Water-Rich Grouting Materials Based on Response Surface Methodology
Authors: Li Xiaoping , Han Guoping , Wang Yong , Xu Jie , Du Jie , Yang Bo , Zhang Min , Li Tao , Li Bo
Published: September 2023

The quality of borehole sealing is a key factor affecting the efficiency of gas production. A new water-rich grouting material (RW) with composite coagulant and other additives was prepared in this study to overcome the disadvantages of long setting time and low stone rate of traditional cement materials. When the coagulants A is 4 g and coagulants B is 2 g, the setting time of RW material was reduced by 60.85% and 50.62%, which significantly shortened the setting time of the RW material, respectively. Based on the orthogonal method, 29 groups of comparative experiments were designed to investigate the interaction mechanism between different additives on the performance index of RW, including setting time, water secretion rate, and compressive strength. Quadratic regression equations were fitted using the response surface method. All the correlation coefficients R2 of each response model were greater than 0.97, R2 and R2adj were less than 0.2 through variance analysis, indicating a high correlation between the actual and prediction results. The water–cement ratio had the most significant effect among all factors on setting time, water secretion rate, and compressive strength of the RW material. The scanning electron microscope (SEM) was used to compared the micromorphological characteristics of RW and conventional Portland cement material (PC). The results showed that the hydration products of RW were mostly smack ettringite, calcium silicate hydrate gel, and calcium hydroxide, which interweaved with each other to form a network structure that was denser than the PC material. Furthermore, the interface bonding degree between RW and injected coal was tighter than that of PC, without obvious cracks at the slurry–coal interface. The results indicate that the addition of composite coagulant can significantly accelerate the hydration process of RW material and also enhance the interface strength of injected coal, which is conducive to improving the grouting quality and sealing effect of the extraction borehole.
An Illustrated Haggadah for Sefardi Exiles in Istanbul
Authors: Kogman-Appel Katrin
Published: September 2023

The first illustrated haggadah of the print era was published around 1505 by David and Samuel ibn Nahmias in Istanbul (henceforth “Istanbul Haggadah”). It was embellished with woodcuts that had been commissioned in 1492 in Naples. This paper approaches the Istanbul Haggadah as a cultural product of the early Sefardi Diaspora. A comparative iconographic method reveals idiosyncrasies in relation to the tradition of medieval manuscript haggadot, which are then contextualized within the cultural ambience of the early Sefardi Diaspora in Naples, where Don Isaac Abarbanel played a central role as a spiritual and communal leader. My analysis is based on three types of information and sources: Abarbanel’s post-expulsion writings, among others a commentary on the haggadah; book-historical data on the early phases of printing; and historical information on the lives of the refugees. Most Sefardi printing projects from the post-expulsion years were aimed at meeting the spiritual needs of the community of exiles. The Istanbul Haggadah, and particularly its illustration program, was a fitting compliment to these endeavors.