bluuebunny/crossref_metadata_2025 huggingface dataset:
Clean Electrochemical Synthesis of Pd–Pt Bimetallic Dendrites with High Electrocatalytic Performance for the Oxidation of Formic Acid
Authors: Liu Jie , Li Fangchao , Zhong Cheng , Hu Wenbin
Published: February 2022

Pd–Pt bimetallic catalysts with a dendritic morphology were in situ synthesized on the surface of a carbon paper via the facile and surfactant-free two step electrochemical method. The effects of the frequency and modification time of the periodic square-wave potential (PSWP) on the morphology of the Pd–Pt bimetallic catalysts were investigated. The obtained Pd–Pt bimetallic catalysts with a dendritic morphology displayed an enhanced catalytic activity of 0.77 A mg−1, almost 2.5 times that of the commercial Pd/C catalyst reported in the literature (0.31 A mg−1) in acidic media. The enhanced catalytic activity of the Pd–Pt bimetallic catalysts with a dendritic morphology towards formic acid oxidation reaction (FAOR) was not only attributed to the large number of atomic defects at the edges of dendrites, but also ascribed to the high utilization of active sites resulting from the “clean” electrochemical preparation method. Besides, during chronoamperometric testing, the current density of the dendritic Pd–Pt bimetallic catalysts for a period of 3000 s was 0.08 A mg−1, even four times that of the commercial Pd/C catalyst reported in the literature (about 0.02 A mg−1).
A Novel Method for the Determination of the Lateral Dimensions of 2D Rectangular Flakes
Authors: Papathanasiou Thanasis D. , Tsiantis Andreas , Wang Yanwei
Published: February 2022

We present a novel method for the determination of the lateral dimensions of thin rectangular flakes, as they exist randomly dispersed in flake composites. Knowledge of flake size and shape is essential for the correct prediction of the mechanical, electrical, thermal and barrier properties of flake composites. The required information is the distribution function of lengths of the lines representing the intersection of flakes with a sectioning plane, as seen in cross-sections of composite samples used in optical or electron microscopy or obtained using tomographic imaging techniques. The key observation is that the major peak of the distribution function coincides with the short dimension S of the flake while a secondary peak corresponds to its long dimension W. These observations are explained using Monte-Carlo simulations, as well as deterministic, geometry-based modeling and probability analysis. Since the strength of the secondary peak diminishes with increasing flake aspect ratio r=W/S, we develop two additional methods for the determination of W. The first finds W from the maximum intersection length; this procedure is justified by computing the relevant probability fields through Monte-Carlo simulations. The second method finds r from the average intersection length and is valid in the range 1<r<15. The performance of these techniques is tested and found to be very good using blind experiments in numerically sectioned specimens.
Finite Volume Method Modeling of Heat Transfer in Acoustic Enclosure for Machinery
Authors: Wróbel Jakub , Warzyńska Urszula
Published: February 2022

This paper deals with the problem of heat accumulation in acoustic enclosures. Increased noise levels at production sites or manufacturing lines force the application of acoustic enclosures. Effective noise reduction due to enclosures often comes with the additional thermal insulation of the device, which in many cases causes a strong increase in the device operation temperature. This paper presents the methodology of thermal phenomena numerical modeling based on the potential influence of acoustic enclosures on the increase in device operation temperature. The proposed model consists of an original acoustic enclosure concept design, and the numerical modeling is based on the computational fluid dynamics FVM (finite volume method) conducted in Ansys Fluent. The research comprised a set of simulations at different air flow rates of 52.5 m3/h, 105 m3/h, 210 m3/h and 420 m3/h at the enclosure inlet. The analysis carried out on the basis of flow paths and temperature distribution plots inside the enclosure led to the conclusion that the expected, analytically calculated minimum volumetric flow rate is not sufficient to effectively cool the investigated device to the required temperature of 26 °C, and higher air flow rates should be applied. Simulation results indicated that the numerical tools can be useful in the prediction of the heat exchange process, as well as in the selection of an appropriate source and location of cooling.
Capillary Imbibition in Cementitious Materials: Effect of Salts and Exposure Condition
Authors: De Brabandere Laurena , Alderete Natalia M. , De Belie Nele
Published: February 2022

Concrete structures are often exposed to harsh environmental conditions during their service life. Therefore, the investigation of transport properties and deterioration of concrete in different environments is an important topic. This paper reports the influence of salts (NaCl and Na2SO4) and exposure conditions (ideal laboratory (20 °C, 95% RH), a city and sea environment; including sheltered and exposed conditions) on capillary imbibition in cementitious materials with different water to cement ratios (0.4 and 0.6). First, the pore structure was assessed by water absorption under vacuum, torrent permeability, resistivity, and moisture content. The second part revolves around the capillary imbibition phenomenon with different imbibition liquids (water, NaCl, and Na2SO4). The results showed that, among the studied exposure conditions, sheltered conditions resulted in the largest porosity values and capillary imbibition rates (CIR). The influence of the imbibing liquid on the CIR depends on the w/c of the concrete. The CIR value for samples with a w/c of 0.4 is lower for Na2SO4 as imbibing liquid in comparison to water and NaCl. The sulfates might cause a pore blocking effect leading to a decreased CIR. For concrete with a w/c of 0.6, there was no significant difference between the different imbibition liquids. The influence of the pore blocking effect is probably smaller due to the larger porosity in this case. The findings of this research are important to understand the influence of real-life exposure conditions and therefore the influence of relative humidity, temperature, carbonation, and chloride ingress on the capillary imbibition phenomenon.
Cytotoxic Potential of Denture Adhesives on Human Fibroblasts—In Vitro Study
Authors: Sobolewska Ewa , Makowiecki Piotr , Drozdowska Justyna , Dziuba Ireneusz , Nowicka Alicja , Wyganowska-Świątkowska Marzena , Janiszewska-Olszowska Joanna , Grocholewicz Katarzyna
Published: February 2022

(1) In recent years, there has been a significant increase in the availability of denture adhesives for stabilizing removable dentures. The aim of the present study was to assess the cytotoxicity of three denture adhesives on human fibroblasts. (2) Methods: Three denture adhesives were analyzed. Fibroblast cultures were established for the study and control groups in order to assess the incidence of necrosis and to evaluate the microscopic intracellular alterations induced. Following incubation with (study groups) or without adhesives (control group), trypan blue dye exclusion assay was used to determine the number of viable and/or dead cells. Microscopic specimens were stained with haematoxylin and eosin, scanned, digitally processed and then analyzed by a histopathologist. (3) Results: All three denture adhesives analyzed demonstrated various toxic effects in vitro on human fibroblast: quantitative evaluation—45.87–61.13% reduction of cell viability (p = 0.0001) and slight to moderate cytotoxicity in qualitative evaluation. (4) Conclusions: Denture adhesive creams demonstrated a toxic effect on human fibroblasts in vitro in quantitative and qualitative evaluation. In vivo observations are needed to find out if denture adhesives present a cytotoxic effect in patients.
Smart Warehouse Management System: Architecture, Real-Time Implementation and Prototype Design
Authors: Khan Muhammad Gufran , Huda Noor Ul , Zaman Uzair Khaleeq Uz
Published: February 2022

The world has witnessed the digital transformation and Industry 4.0 technologies in the past decade. Nevertheless, there is still a lack of automation and digitalization in certain areas of the manufacturing industry; in particular, warehouse automation often has challenges in design and successful deployment. The effective management of the warehouse and inventory plays a pivotal role in the supply chain and production. In the literature, different architectures of Warehouse Management Systems (WMSs) and automation techniques have been proposed, but most of those have focused only on particular sections of warehouses and have lacked successful deployment. To achieve the goal of process automation, we propose an Internet-of-Things (IoT)-based architecture for real-time warehouse management by dividing the warehouse into multiple domains. Architecture viewpoints were used to present models based on the context diagram, functional view, and operational view specifically catering to the needs of the stakeholders. In addition, we present a generic IoT-based prototype system that enables efficient data collection and transmission in the proposed architecture. Finally, the developed IoT-based solution was deployed in the warehouse of a textile factory for validation testing, and the results are discussed. A comparison of the key performance parameters such as system resilience, efficiency, and latency rate showed the effectiveness of our proposed IoT-based WMS architecture.
Numerical Investigation of Influence of Fluid Rate, Fluid Viscosity, Perforation Angle and NF on HF Re-Orientation in Heterogeneous Rocks Using UDEC T-W Method
Authors: Zhang Shuai , Xu Jinhai , Chen Liang , Zhang Mingwei , Sasaoka Takashi , Shimada Hideki , He Haiyang
Published: February 2022

Numerical simulation is very useful for understanding the hydraulic fracture (HF) re-orientation mechanism from artificial weaknesses. In this paper, the UDEC T-W (Trigon–Weibull distribution) modeling method is adopted to simulate the hydraulic fracturing process in heterogeneous rocks. First, the reliability of this method is validated against previous laboratory experiments and numerical simulations. Then the effects of fluid rate, fluid viscosity, perforation angle and natural fracture (NF) on the HF re-orientation process in heterogeneous rocks are studied independently. The results show that the HF re-orientation process depends on the combined effect of these factors. The HF re-orientation distance increases significantly, the final HF re-orientation trajectory becomes more complex and the guiding effect of perforation on the HF propagation path is more evident with the increase of fluid rate, fluid viscosity, and perforation angle if the hydraulic fracturing is performed in relatively heterogeneous rocks, while the differential stress is the main influencing factor and is more likely to dictate the HF propagation path if the rocks become relatively homogeneous. However, increasing the fluid viscosity and fluid rate can attenuate the impact of differential stress and can promote HF propagation along the perforation direction. Besides, NFs are also the important factor affecting HF re-orientation and induce secondary HF re-orientation in some cases in heterogeneous rocks.
Research on the Resilient Evolutionary Game of Logistics Service Supply Chain with Government Participation
Authors: Zhang Guangsheng , Wang Xiao , Wang Yanling , Kang Jiayun
Published: February 2022

The resilient strategy of logistics service supply chains with government participation is not only an effective measure for manufacturers and integrators to lower the risks but also an important component of the modern risk management capability of government. From the perspective of risk society, this paper presupposes the existence of emergencies, embeds the “resilient ability” into the logistics service supply chain, establishes a tripartite evolutionary game model among the government, manufacturers, and integrators, and systematically analyzes the strategy selection process under the participation of the government. On this basis, through numerical experiments, this paper examines the supervision sensitivity with different policies on a micro level, investigates the impact incurred by the change in governmental reward and punishment degree, and further complements the research on the complexity of the strategy selection process in reality. The results show that in the short run, regardless of the reward and punishment measure the government chooses, the manufacturers and integrators will choose not to adopt and implement the resilient supply chain strategy, while, in the long run, increasing manufacturers’ initial supervision and implementing relevant reward and punishment measures can guide integrators to choose the strategy. Increasing government integrators’ reward degree and reducing costs can thus promote the enthusiasm of integrators in resilient logistics service supply chains.
The Domatic Partition Problem in Separable Graphs
Authors: Landete Mercedes , Sainz-Pardo José Luis
Published: February 2022

The domatic partition problem consists of partitioning a given graph into a maximum number of disjoint dominating sets. This problem is related with the domatic number problem, which consists of quantifying this maximum number of disjoint dominating sets. Both problems were proved to be NP-complete. In this paper, we present a decomposition algorithm for finding a domatic partition on separable graphs, that is, on graphs with blocks, and as a consequence, its domatic number, highly reducing the computational complexity. Computational results illustrate the benefits of the block decomposition algorithm.
Single-Image Super-Resolution Neural Network via Hybrid Multi-Scale Features
Authors: Huang Wenfeng , Liao Xiangyun , Zhu Lei , Wei Mingqiang , Wang Qiong
Published: February 2022

In this paper, we propose an end-to-end single-image super-resolution neural network by leveraging hybrid multi-scale features of images. Different from most existing convolutional neural network (CNN) based solutions, our proposed network depends on the observation that image features extracted by CNN contain hybrid multi-scale features: both multi-scale local texture features and global structural features. By effectively exploiting these multi-scale and local-global features, our network involves far fewer parameters, leading to a large decrease in memory usage and computation during inference. Our network benefits from three key modules: (1) an efficient and lightweight feature extraction module (EFblock); (2) a hybrid multi-scale feature enhancement module (HMblock); and (3) a reconstruction–restoration module (DRblock). Experiments on five popular benchmarks demonstrate that our super-resolution approach achieves better performance with fewer parameters and less memory consumption, compared to more than 20 SOTAs. In summary, we propose a novel multi-scale super-resolution neural network (HMSF), which is more lightweight, has fewer parameters, and requires less execution time, but has better performance than the state-of-the-art methods. Compared to SOTAs, this method is more practical and better suited to run on constrained devices, such as PCs and mobile devices, without the need for a high-performance server.
Dynamics of a Predator–Prey Model with the Additive Predation in Prey
Authors: Bai Dingyong , Zhang Xiaoxuan
Published: February 2022

In this paper, we consider a predator–prey model, in which the prey’s growth is affected by the additive predation of its potential predators. Due to the additive predation term in prey, the model may exhibit the cases of the strong Allee effect, weak Allee effect and no Allee effect. In each case, the dynamics of global features of the model are investigated. Compared to the well-known Lotka–Volterra type model, the model proposed in this paper exhibits much richer and more complex dynamic behaviors, such as the Allee effect, the sensitivity to the initial conditions caused by the strong Allee effect, the oscillatory behavior and the Hopf and heteroclinic bifurcations. Furthermore, the stability and Hopf bifurcation of the model with the density dependent feedback time delay in prey are investigated. By the normal form method and center manifold theory, the explicit formulas are presented to determine the direction of Hopf bifurcation and the stability and period of Hopf-bifurcating periodic solutions. Theoretical analysis and numerical simulation indicate that the delay may destabilize the model, and cause the Hopf bifurcation not only at the interior equilibrium but also at a boundary equilibrium.
A New Best Proximity Point Result with an Application to Nonlinear Fredholm Integral Equations
Authors: Sahin Hakan
Published: February 2022

In the current paper, we first introduce a new class of contractions via a new notion called p-cyclic contraction mapping by combining the ideas of cyclic contraction mapping and p-contraction mapping. Then, we give a new definition of a cyclically 0-complete pair to weaken the completeness condition on the partial metric spaces. Following that, we prove some best proximity point results for p-cyclic contraction mappings on D∪E where D,E is a cyclically 0-complete pair in the setting of partial metric spaces. Hence, we generalize and unify famous and well-known results in the literature of metric fixed point theory. Additionally, we present some nontrivial examples to compare our results with earlier. Finally, we investigate the sufficient conditions for the existence of a solution to nonlinear Fredholm integral equations by the results in the paper.
Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing
Authors: Bahmad Hisham F. , Demus Timothy , Moubarak Maya M. , Daher Darine , Alvarez Moreno Juan Carlos , Polit Francesca , Lopez Olga , Merhe Ali , Abou-Kheir Wassim , Nieder Alan M. , Poppiti Robert , Omarzai Yumna
Published: February 2022

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical’s mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.
TRPV4 and PIEZO Channels Mediate the Mechanosensing of Chondrocytes to the Biomechanical Microenvironment
Authors: Zhang Min , Meng Nan , Wang Xiaoxiao , Chen Weiyi , Zhang Quanyou
Published: February 2022

Articular cartilage and their chondrocytes are physiologically submitted to diverse types of mechanical cues. Chondrocytes produce and maintain the cartilage by sensing and responding to changing mechanical loads. TRPV4 and PIEZOs, activated by mechanical cues, are important mechanosensing molecules of chondrocytes and have pivotal roles in articular cartilage during health and disease. The objective of this review is to introduce the recent progress indicating that the mechanosensitive ion channels, TRPV4 and PIEZOs, are involved in the chondrocyte sensing of mechanical and inflammatory cues. We present a focus on the important role of TRPV4 and PIEZOs in the mechanotransduction regulating diverse chondrocyte functions in the biomechanical microenvironment. The review synthesizes the most recent advances in our understanding of how mechanical stimuli affect various cellular behaviors and functions through differentially activating TRPV4 and PIEZO ion channels in chondrocyte. Advances in understanding the complex roles of TRPV4/PIEZO-mediated mechanosignaling mechanisms have the potential to recapitulate physiological biomechanical microenvironments and design cell-instructive biomaterials for cartilage tissue engineering.
Study of the Electrical Conductivity of Ion-Exchange Resins and Membranes in Equilibrium Solutions of Inorganic Electrolytes
Authors: Petrov Oleksandr , Iwaszczuk Natalia , Bejanidze Irina , Kharebava Tina , Pohrebennyk Volodymyr , Didmanidze Nato , Nakashidze Nunu
Published: February 2022

The study of the electrical conductivity of ion-exchange membranes in equilibrium electrolyte solutions is of great importance for the theory of membrane processes, in particular for practical electrodialysis. The purpose of the work is to determine the electrical conductivity of industrial ion-exchange membranes MK-40 and MA-40, as well as their basis—granules of a bulk layer of industrial ion exchangers KU-2-8 and EDE-10p, by differential and modified contact methods in electrolyte solutions and the development of a new methodology that will give the values that are closest to the true ones; determination of the dependence of electrical membrane conductivity depending on the type of counterion and concentration equilibrium solution and granules of a bulk layer of ion exchangers on the volume fraction of a dry ion exchanger with different degrees of compaction. It is shown that the dependence of the electrical conductivity of diaphragms on the electrolyte concentration, according to theoretical ideas, disappears under compression. It has been experimentally established that the difference method gives lower values of electrical conductivity in the region of low concentrations. The data obtained by the contact method are in good agreement with the results obtained for compressed diaphragms. The membrane conductivity decreases with increasing ion size.
Joining of Zirconia to Ti6Al4V Using Ag-Cu Sputter-Coated Ti Brazing Filler
Authors: Simões Sónia , Emadinia Omid , Tavares Carlos José , Guedes Aníbal
Published: February 2022

The joining of zirconia (ZrO2) to Ti6Al4V using Ag-Cu sputter-coated Ti brazing filler foil was investigated. Brazing experiments were performed at 900, 950, and 980 °C for 30 min under vacuum. The microstructural features of the brazed interfaces were evaluated by optical microscopy (OM) and by scanning electron microscopy (SEM). The chemical composition of the brazed interfaces was analyzed by energy dispersive X-ray spectroscopy (EDS). Room temperature shear tests and Vickers microhardness tests performed across the interfaces were used to evaluate the mechanical strength of the joints. Multilayered interfaces were produced for all brazing temperatures, consisting essentially in α-Ti + Ti2(Ag, Cu), TiAg. Joining to ZrO2 was promoted by the formation of a hard layer, reaching a maximum of 1715 HV0.01, possibly consisting mainly in α-Ti and Ti oxide(s). Joining to the Ti6Al4V was established by a layer composed of a mixture of α-Ti and Ti2(Ag, Cu). The highest shear strength (152 ± 4 MPa) was obtained for brazing at 980 °C and fracture of joints occurred partially across the interface, throughout the hardest layers formed close to ZrO2, and partially across the ceramic sample.
Alkaloid Profiling, Anti-Enzymatic and Antiproliferative Activity of the Endemic Chilean Amaryllidaceae Phycella cyrtanthoides
Authors: Fernández-Galleguillos Carlos , Romero-Parra Javier , Puerta Adrián , Padrón José M. , Simirgiotis Mario J.
Published: February 2022

This research aims to identify the alkaloid profile and to evaluate the enzyme inhibitory potential and antiproliferative effects of the Amaryllidaceae plant Phycella cyrtanthoides. The alkaloid extracts from bulbs and leaves were analyzed using ultrahigh performance liquid chromatography orbitrap mass spectrometry (UHPLC-Orbitrap-MS) analysis. A total of 70 alkaloids were detected in the P. cyrtanthoides’ extracts. The enzyme inhibition potential against cholinesterases (AChE: acetylcholinesterase, and BChE butyrylcholinesterase) and tyrosinase were studied. Bulbs displayed the best IC50 values against AChE (4.29 ± 0.03 µg/mL) and BChE (18.32 ± 0.03 µg/mL). These results were consistent with docking experiments with selected major compounds in the active sites of enzymes, while no activity was observed against tyrosinase enzyme. Antiproliferative effects were investigated against human cervical (HeLa), lung (A549, SW1573), colon (WiDr), and breast (HBL-100, T-47D) tumor cell lines. Bulbs and leaves were active in all cell lines (GI50 < 2.5 µg/mL). These findings suggest that the endemic Chilean plant P. cyrtanthoides contains diverse types of bioactive alkaloids with antiproliferative activities and inhibitory effects with potential therapeutic applications for neurodegenerative diseases
In Vivo Magnetic Resonance Spectroscopy Methods for Investigating Cardiac Metabolism
Authors: Esmaeili Morteza , Vettukattil Riyas
Published: February 2022

Magnetic resonance spectroscopy (MRS) is a non-invasive and non-ionizing technique, enabling in vivo investigation of cardiac metabolism in normal and diseased hearts. In vivo measurement tools are critical for studying mechanisms that regulate cardiac energy metabolism in disease developments and to assist in early response assessments to novel therapies. For cardiac MRS, proton (1H), phosphorus (31P), and hyperpolarized 13-carbon (13C) provide valuable metabolic information for diagnosis and treatment assessment purposes. Currently, low sensitivity and some technical limitations limit the utility of MRS. An essential step in translating MRS for clinical use involves further technological improvements, particularly in coil design, improving the signal-to-noise ratios, field homogeneity, and optimizing radiofrequency sequences. This review addresses the recent advances in metabolic imaging by MRS from primarily the literature published since 2015.
Inoculation, Growth and Bactericidal Effects of Three Kombucha Cultures
Authors: Jarrell Jill , Walia Namrata , Nemergut Diana , Agadi Amar , Bennett Joan
Published: February 2022

Kombucha, a domesticated consortium of several microorganisms grown on sugared tea, has been valued as a nutritive health aid for over a millennium. In this study, three cultures of kombucha were obtained from diverse sources. Different inoculation methods were compared, and the wet and dry weights of the nascent pellicles were measured when cultured on several carbon sources. In addition, the anti-bacterial properties of the fermented kombucha teas were tested against Escherichia coli and Staphylococcus epidermis. Inoculation with macerated pellicles gave the fastest kombucha growth. The best carbon sources for growth of the nascent kombucha pellicles were sucrose, glucose, and fructose. On maltose, galactose, and lactose, not only did the kombucha pellicles grow poorly but 25% were also contaminated by common airborne molds. Good growth of the kombucha cultures was correlated with low pH of the fermented tea. Antibacterial effects of concentrated fermented teas and vinegar were similar to those of 1 mmol ampicillin against Escherichia coli or 0.01 mmol penicillin against Staphylococcus epidermis. When the pH of concentrated kombucha teas was neutralized, their bactericidal effects were no better than unfermented controls.
From Rest to Growth: Life Collisions of Gordonia polyisoprenivorans 135
Authors: Suzina Nataliya E. , Sorokin Vladimir V. , Polivtseva Valentina N. , Klyueva Violetta V. , Emelyanova Elena V. , Solyanikova Inna P.
Published: February 2022

In the process of evolution, living organisms develop mechanisms for population preservation to survive in unfavorable conditions. Spores and cysts are the most obvious examples of dormant forms in microorganisms. Non-spore-forming bacteria are also capable of surviving in unfavorable conditions, but the patterns of their behavior and adaptive reactions have been studied in less detail compared to spore-forming organisms. The purpose of this work was to study the features of transition from dormancy to active vegetative growth in one of the non-spore-forming bacteria, Gordonia polisoprenivorans 135, which is known as a destructor of such aromatic compounds as benzoate, 3-chlorobenzoate, and phenol. It was shown that G. polyisoprenivorans 135 under unfavorable conditions forms cyst-like cells with increased thermal resistance. Storage for two years does not lead to complete cell death. When the cells were transferred to fresh nutrient medium, visible growth was observed after 3 h. Immobilized cells stored at 4 °C for at least 10 months regenerated their metabolic activity after only 30 min of aeration. A study of the ultrathin organization of resting cells by transmission electron microscopy combined with X-ray microanalysis revealed intracytoplasmic electron-dense spherical membrane ultrastructures with significant similarity to previously described acidocalcisomas. The ability of some resting G. polyisoprenivorans 135 cells in the population to secrete acidocalcisome-like ultrastructures into the extracellular space was also detected. These structures contain predominantly calcium (Ca) and, to a lesser extent, phosphorus (P), and are likely to serve as depots of vital macronutrients to maintain cell viability during resting and provide a quick transition to a metabolically active state under favorable conditions. The study revealed the features of transitions from active growth to dormant state and vice versa of non-spore-forming bacteria G. polyisoprenivorans 135 and the possibility to use them as the basis of biopreparations with a long shelf life.
Bacterial Biofilms Utilize an Underlying Extracellular DNA Matrix Structure That Can Be Targeted for Biofilm Resolution
Authors: Goodman Steven D. , Bakaletz Lauren O.
Published: February 2022

Bacterial biofilms contribute significantly to the antibiotic resistance, pathogenesis, chronicity and recurrence of bacterial infections. Critical to the stability and survival of extant biofilms is the extracellular DNA (eDNA)-dependent matrix which shields the resident bacteria from hostile environments, allows a sessile metabolic state, but also encourages productive interactions with biofilm-inclusive bacteria. Given the importance of the eDNA, approaches to this area of research have been to target not just the eDNA, but also the additional constituent structural components which appear to be widespread. Chief among these is a ubiquitous two-member family of bacterial nucleoid associated proteins (the DNABII proteins) responsible for providing structural integrity to the eDNA and thereby the biofilm. Moreover, this resultant novel eDNA-rich secondary structure can also be targeted for disruption. Here, we provide an overview of both what is known about the eDNA-dependent matrix, as well as the resultant means that have resulted in biofilm resolution. Results obtained to date have been highly supportive of continued development of DNABII-targeted approaches, which is encouraging given the great global need for improved methods to medically manage, or ideally prevent biofilm-dependent infections, which remains a highly prevalent burden worldwide.
Contrasting Modes of Carbonate Precipitation in a Hypersaline Microbial Mat and Their Influence on Biomarker Preservation (Kiritimati, Central Pacific)
Authors: Shen Yan , Suarez-Gonzalez Pablo , Reitner Joachim
Published: February 2022

Microbial mats represented the earliest complex ecosystems on Earth, since fossil mineralized examples (i.e., microbialites) date back to the Archean Eon. Some microbialites contain putative remains of organic matter (OM), however the processes and pathways that lead to the preservation of OM within microbialite minerals are still poorly understood. Here, a multidisciplinary study is presented (including petrographic, mineralogical and organic geochemical analyses), focusing on a modern calcifying mat from a hypersaline lake in the Kiritimati atoll (Central Pacific). The results show that this mat has a complex history, with two main growth phases under hypersaline conditions, separated by an interruption caused by desiccation and/or freshening of the lake. The mineral precipitates of the mat are predominantly aragonitic and two contrasting precipitation modes are observed: the main growth phases of the mat were characterized by the slow formation of irregular micritic particles with micropeloidal textures and subspherical particles, linked to the degradation of the exopolymer (EPS) matrix of the mat; whereas the interruption period was characterized by the rapid development of a thin but laterally continuous crust composed of superposed fibrous aragonite botryoids that entombed their contemporaneous benthic microbial community. These two precipitation modes triggered different preservation pathways for the OM of the mat as the thin crust shows a particular lipid biomarker signature, different from that of other layers and the relatively rapid precipitation of the crust protecting the underlying lipids from degradation, causing them to show a preservation equivalent to that of a modern active microbial community, despite them being >1100 years old. Equivalent thin mineral crusts occur in other microbialite examples and, thus, this study highlights them as excellent targets for the search of well-preserved biomarker signatures in fossil microbialites. Nevertheless, the results of this work warn for extreme caution when interpreting complex microbialite biomarker signatures, advising combined petrographic, mineralogical and geochemical investigations for the different microbialite layers and mineral microfabrics.
Relationship between Apolipoprotein E Genotype and Lipoprotein Profile in Patients with Coronary Heart Disease
Authors: Lin Yahui , Yang Qiong , Liu Zhaohui , Su Baoman , Xu Fen , Li Yang , Kang Jinsuo , Zhou Zhou
Published: February 2022

(1) Background: Apolipoprotein E(ApoE) plays a critical role in lipid transport. The specific allele of APOE being expressed is associated with the development of coronary heart disease (CHD), however the specific mechanisms by which ApoE drives disease are unclear. In this study, we investigated the relationship between APOE allele, lipoprotein metabolome, and CHD severity to provide evidence for the efficacy of clinical cholesterol-lowering therapy; (2) Methods: Blood samples were collected from 360 patients with CHD that were actively being treated with statins. The lipoprotein profile, including particle numbers, particle size, and lipoprotein composition concentrates, was measured by nuclear magnetic resonance (NMR) spectroscopy. The severity of CHD was determined by quantifying coronary angiography results using the Gensini scoring system; (3) Results: We found there was no significant difference in low-density lipoprotein cholesterol (LDL-C) levels among ε2+ (ε2 allele carriers, consisting of ε2/ε2 and ε2/ε3 genotypes), ε3 (consisting of ε3/ε3 and ε2/ε4 genotypes), and ε4+ (ε4 allele carriers, consisting of ε3/ε4 and ε4/ε4 genotypes) participants receiving statin treatment. Compared with the ε3 group, patients with the ε2+ genotype showed lower concentrations of total low-density lipoprotein (LDL), small-LDL, and middle-LDL particles, as well as a larger LDL size, higher very low-density lipoprotein (VLDL) composition concentrates, and higher intermediate density lipoprotein (IDL) composition concentrates. The ε4+ group showed higher concentrations of total LDL, small LDL particles, and LDL compositions with smaller LDL size. The higher level of small LDL concentration was associated with a high Gensini score (B = 0.058, p = 0.024). Compared with the ε3 group, the risk of increased branch lesions in the ε2+ group was lower (OR = 0.416, p = 0.027); (4) Conclusions: The specific allele of APOE being expressed can affect the severity of CHD by altering components of the lipoprotein profile, such as the concentration of small LDL and LDL size.
Fenchone Derivatives as a Novel Class of CB2 Selective Ligands: Design, Synthesis, X-ray Structure and Therapeutic Potential
Authors: Smoum Reem , Haj Christeene , Hirsch Shira , Nemirovski Alina , Yekhtin Zhannah , Bogoslavsky Benny , Bakshi Gaganjyot Kaur , Chourasia Mukesh , Gallily Ruth , Tam Joseph , Mechoulam Raphael
Published: February 2022

A series of novel cannabinoid-type derivatives were synthesized by the coupling of (1S,4R)-(+) and (1R,4S)-(−)-fenchones with various resorcinols/phenols. The fenchone-resorcinol derivatives were fluorinated using Selectfluor and demethylated using sodium ethanethiolate in dimethylformamide (DMF). The absolute configurations of four compounds were determined by X-ray single crystal diffraction. The fenchone-resorcinol analogs possessed high affinity and selectivity for the CB2 cannabinoid receptor. One of the analogues synthesized, 2-(2′,6′-dimethoxy-4′-(2″-methyloctan-2″-yl)phenyl)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol (1d), had a high affinity (Ki = 3.51 nM) and selectivity for the human CB2 receptor (hCB2). In the [35S]GTPγS binding assay, our lead compound was found to be a highly potent and efficacious hCB2 receptor agonist (EC50 = 2.59 nM, E(max) = 89.6%). Two of the fenchone derivatives were found to possess anti-inflammatory and analgesic properties. Molecular-modeling studies elucidated the binding interactions of 1d within the CB2 binding site.
Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways
Authors: Fawzy Michael A. , Maher Sherif A. , El-Rehany Mahmoud A. , Welson Nermeen N. , Albezrah Nisreen K. A. , Batiha Gaber El-Saber , Fathy Moustafa
Published: February 2022

Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition to pantoprazole in treating experimentally induced renal ischemia/reperfusion injury (IRI). One-hundred-and-twenty-eight healthy male Wistar albino rats were included. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were assessed. ELISA was used to estimate the pro-inflammatory cytokines. The expression of Bcl-2 and Bax genes was assessed by quantitative real-time PCR. ERK1/2, JNK1/2, p38, cleaved caspase-3, and NF-κB proteins expressions were estimated using western blot assay. The kidneys were also histopathologically studied. The IRI resulted in impaired cellular functions with increased creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, and IL-1β serum levels, and up-regulated NF-ĸB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it down-regulated the expression of the Bcl-2 gene and upregulated the Bax gene. The treatment with vincamine, in addition to pantoprazole multiple doses, significantly alleviated the biochemical and histopathological changes more than pantoprazole or vincamine alone, whether the dose is single or multiple, declaring their synergistic effect. In conclusion, vincamine with pantoprazole multiple doses mitigated the renal IRI through the inhibition of apoptosis, attenuation of the extracellular signaling pathways through proinflammatory cytokines’ levels, and suppression of the MAPK (ERK1/2, JNK, p38)–NF-κB intracellular signaling pathway.
In Vivo Antistress Effects of Synthetic Flavonoids in Mice: Behavioral and Biochemical Approach
Authors: Ghias Mehreen , Shah Syed Wadood Ali , Al-Joufi Fakhria A. , Shoaib Mohammad , Shah Syed Muhammad Mukarram , Ahmed Muhammad Naeem , Zahoor Muhammad
Published: February 2022

Natural flavonoids, in addition to some of their synthetic derivatives, are recognized for their remarkable medicinal properties. The present study was designed to investigate the in vitro antioxidant and in vivo antistress effect of synthetic flavonoids (flavones and flavonols) in mice, where stress was induced by injecting acetic acid and physically through swimming immobilization. Among the synthesized flavones (F1–F6) and flavonols (OF1–OF6), the mono para substituted methoxy containing F3 and OF3 exhibited maximum scavenging potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) with IC50 of 31.46 ± 1.46 μg/mL and 25.54 ± 1.21 μg/mL, respectively. Minimum antioxidant potential was observed for F6 and OF6 with IC50 values of 174.24 ± 2.71 μg/mL and 122.33 ± 1.98 μg/mL, respectively, in comparison with tocopherol. The ABTS scavenging activity of all the synthesized flavones and flavonols were significantly higher than observed with DPPH assay, indicating their potency as good antioxidants and the effectiveness of ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) assay in evaluating antioxidant potentials of chemical substances. The flavonoids-treated animals showed a significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) reduction in the number of writhes and an increase in swimming endurance time. Stressful conditions changed plasma glucose, cholesterol and triglyceride levels, which were used as markers when evaluating stress in animal models. The level of these markers was nearly brought to normal when pre-treated with flavones and flavonols (10 mg/kg) for fifteen days in experimental animals. These compounds also considerably reduced the levels of lipid peroxidation (TBARS: Thiobarbituric acid reactive substances), which was significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) compared to the control group. A significant rise in the level of catalase and SOD (super oxide dismutase) was also observed in the treated groups. Diazepam (2 mg/kg) was used as the standard drug. Additionally, the flavonoids markedly altered the weight of the adrenal glands, spleen and brain in stress-induced mice. The findings of the study suggest that these flavonoids could be used as a remedy for stress and are capable of ameliorating diverse physiological and biochemical alterations associated with stressful conditions. However, further experiments are needed to confirm the observed potentials in other animal models, especially in those with a closer resemblance to humans. Toxicological evaluations are also equally important.
Computational Drug Repurposing Based on a Recommendation System and Drug–Drug Functional Pathway Similarity
Authors: Shao Mengting , Jiang Leiming , Meng Zhigang , Xu Jianzhen
Published: February 2022

Drug repurposing identifies new clinical indications for existing drugs. It can be used to overcome common problems associated with cancers, such as heterogeneity and resistance to established therapies, by rapidly adapting known drugs for new treatment. In this study, we utilized a recommendation system learning model to prioritize candidate cancer drugs. We designed a drug–drug pathway functional similarity by integrating multiple genetic and epigenetic alterations such as gene expression, copy number variation (CNV), and DNA methylation. When compared with other similarities, such as SMILES chemical structures and drug targets based on the protein–protein interaction network, our approach provided better interpretable models capturing drug response mechanisms. Furthermore, our approach can achieve comparable accuracy when evaluated with other learning models based on large public datasets (CCLE and GDSC). A case study about the Erlotinib and OSI-906 (Linsitinib) indicated that they have a synergistic effect to reduce the growth rate of tumors, which is an alternative targeted therapy option for patients. Taken together, our computational method characterized drug response from the viewpoint of a multi-omics pathway and systematically predicted candidate cancer drugs with similar therapeutic effects.
Monoterpene Indole Alkaloids from the Aerial Parts of Rhazya stricta Induce Cytotoxicity and Apoptosis in Human Adenocarcinoma Cells
Authors: Abdul-Hameed Zainab H. , Bawakid Nahed O. , Alorfi Hajer S. , Sobahi Tariq R. , Alburae Najla Ali , Abdel-Lateff Ahmed , Elbehairi Serag Eldin I. , Alfaifi Mohammad Y. , Alhakamy Nabil A. , Alarif Walied M.
Published: February 2022

Chromatographic investigation of the aerial parts of the Rhazya stricta (Apocynaceae) resulted in the isolation of two new monoterpene indole alkaloids, 6-nor-antirhine-N1-methyl (1) and razyamide (2), along with six known compounds, eburenine (3), epi-rhazyaminine (4), rhazizine (5), 20-epi-sitsirikine (6), antirhine (7), and 16-epi-stemmadenine-N-oxide (8). The chemical structures were established by various spectroscopic experiments. Compounds 1–8 exhibited cytotoxic effects against three cancer cells with IC50 values ranging between 5.1 ± 0.10 and 93.2 ± 9.73 µM against MCF-7; 5.1 ± 0.28 and 290.2 ± 7.50 µM against HepG2, and 3.1 ± 0.17 and 55.7 ± 4.29 µM against HeLa cells. Compound 2 showed the most potent cytotoxic effect against all cancer cell lines (MCF-7, HepG2 and HeLa with IC50 values = 5.1 ± 0.10, 5.1 ± 0.28, and 3.1 ± 0.17 µM, respectively). Furthermore, compound 2 revealed a significant increase in the apoptotic cell population of MCF-7, HepG2, and HeLa cells, with 31.4 ± 0.2%, 29.2 ± 0.5%, and 34.9 ± 0.6%, respectively. Compound 2 decreased the percentage of the phagocytic pathway on HepG2 cells by 15.0 ± 0.1%. These findings can explain the antiproliferative effect of compound 2.
Reproducibility: A Researcher-Centered Definition
Authors: Feger Sebastian Stefan , Woźniak Paweł W.
Published: February 2022

Recent years have introduced major shifts in scientific reporting and publishing. The scientific community, publishers, funding agencies, and the public expect research to adhere to principles of openness, reproducibility, replicability, and repeatability. However, studies have shown that scientists often have neither the right tools nor suitable support at their disposal to meet these modern science challenges. In fact, even the concrete expectations connected to these terms may be unclear and subject to field-specific, organizational, and personal interpretations. Based on a narrative literature review of work that defines characteristics of open science, reproducibility, replicability, and repeatability, as well as a review of recent work on researcher-centered requirements, we find that the bottom-up practices and needs of researchers contrast top-down expectations encoded in terms related to reproducibility and open science. We identify and define reproducibility as a central term that concerns the ease of access to scientific resources, as well as their completeness, to the degree required for efficiently and effectively interacting with scientific work. We hope that this characterization helps to create a mutual understanding across science stakeholders, in turn paving the way for suitable and stimulating environments, fit to address the challenges of modern science reporting and publishing.