bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Quasi-Newton Acceleration for Fluid-Structure Interaction
Authors: Davis Kyle , Schulte Miriam , Uekermann Benjamin
Published: May 2022

We propose two enhancements of quasi-Newton methods used to accelerate coupling iterations for partitioned fluid-structure interaction. Quasi-Newton methods have been established as flexible, yet robust, efficient and accurate coupling methods of multi-physics simulations in general. The coupling library preCICE provides several variants, the so-called IQN-ILS method being the most commonly used. It uses input and output differences of the coupled solvers collected in previous iterations and time steps to approximate Newton iterations. To make quasi-Newton methods both applicable for parallel coupling (where these differences contain data from different physical fields) and to provide a robust approach for re-using information, a combination of information filtering and scaling for the different physical fields is typically required. This leads to good convergence, but increases the cost per iteration. We propose two new approaches—pre-scaling weight monitoring and a new, so-called QR3 filter, to substantially improve runtime while not affecting convergence quality. We evaluate these for a variety of fluid-structure interaction examples. Results show that we achieve drastic speedups for the pure quasi-Newton update steps. In the future, we intend to apply the methods also to volume-coupled scenarios, where these gains can be decisive for the feasibility of the coupling approach.
Molecularly Imprinting Microfiltration Membranes Able to Absorb Diethyl Phthalate from Water
Authors: Smolinska-Kempisty Katarzyna , Wolska Joanna , Bryjak Marek
Published: May 2022

In this study, polypropylene porous membranes with an average pore size of 1.25 µm were modified by barrier discharge plasma. Next, molecularly imprinted layers with an imprint of diethyl phthalate (DEP) ware grafted of their surface. In order to optimize the composition of the modifying mixture various solvents, the ratios of functional monomers and the cross-linking monomer as well as various amounts of phthalate were verified. It was shown that the most effective membranes were obtained during polymerization in n-octane with the participation of functional monomers in the ratio 3:7 and the amount of phthalate 7 wt.%. The membranes were tested in the filtration process as well as static and dynamic sorption. In all of these processes, the imprinted membranes showed better properties than those without the imprint. The diethyl phthalate retention coefficient was 36.12% for membranes with a grafting yield of 1.916 mg/cm2. On the other hand, DEP static sorption for the imprinted membranes was 3.87 µmol/g higher than for non-imprinted membranes. Also, in the process of dynamic sorption higher values were observed for membranes with the imprint (DSMIM, 4.12 µmol/g; DSNIM, 1.18 µmol/g). The membranes were also tested under real conditions. In the process of filtration of tap water contaminated with phthalate, the presence of imprints in the membrane structure resulted in more than three times higher sorption values (3.09 µmol/g) than in the case of non-imprinted membranes (1.12 µmol/g).
Jarosites: Formation, Structure, Reactivity and Environmental
Authors: Cruells Montserrat , Roca Antoni
Published: May 2022

Jarosite, beudantite and alunite are members of the alunite supergroup. Minerals like those have been detected in different environments on Earth. These jarosite-type compounds are common in acid rock drainage environments and acid sulfate soils, resulting from the weathering of sulfide ores; they are also present in bioleaching systems because they are found in cultures of iron-oxidizing microorganisms. Jarosite is also generated in hydrometallurgical circuits, mainly in zinc hydrometallurgy. These minerals can be used to immobilize different elements such as arsenic and lead, among others. Jarosite and alunite have also been detected on the surface of Mars; the presence of jarosite and alunite and other sulfates provides evidence for the existence of water on Mars. In this work, an exhaustive review of the natural formation, synthesis, structure, thermodynamics, and reactivity of jarosite, beudantite and alunite are included. The capacity of jarosites for the immobilization of the elements, such as lead and arsenic, and information about studies related to jarosite formation on Mars are also included.
Crystallization Kinetics of Hypo, Hyper and Eutectic Ni–Nb Glassy Alloys
Authors: Mendoza Laura Esmeralda , Hernández José Manuel , González José Gonzalo , Orgaz Emilio , Lozada Octavio , Figueroa Ignacio Alejandro
Published: May 2022

This study presents the thermal and kinetic behavior of Ni58.5Nb41.5, Ni59.5Nb40.5, and Ni60.5Nb39.5 binary glassy alloys. The alloys ingots were obtained through an electric arc furnace and the ribbons using the melt-spinning technique at two different wheel speeds, 8 and 25 m/s. The non-isothermal study was carried out by means of Differential Scanning Calorimetry (DSC) at five different heating rates: 12.5, 15, 17.5, 20, and 22.5 K/min. X-ray Diffraction (XRD) analysis showed a fully glassy phase for all ribbons for all compositions. For both wheel speeds, the ribbons with higher Nb content were significantly thinner than those with less content. The activation energies were calculated from the Kissinger method, showing the tendency Ep1>Ex1>Eg, where Ep1, Ex and Eg denote the activation energies of first peak temperature, the first crystallization onset and glass transition, respectively. The Flynn–Wall–Ozawa model displayed a close correlation with heating rates, ribbon thicknesses, and composition. The Nb content enhanced the glassy stability since the activation energy required for crystallization increased at higher Nb concentrations.
Unusual Lipid Components of Legionella gormanii Membranes
Authors: Chmiel Elżbieta , Galuska Christina E. , Koper Piotr , Kowalczyk Bożena , Urbanik-Sypniewska Teresa , Palusińska-Szysz Marta , Fuchs Beate
Published: May 2022

Legionella spp. cause Legionnaires’ disease with pneumonia as the predominant clinical symptom. L. gormanii is the second most prevalent causative agent of community-acquired pneumonia after L. pneumophila. The study aimed to characterize the lipidome of L. gormanii membranes and the importance of these analyses in bacterial chemotaxonomy. Lipidomic analyses based on ultra-high performance liquid chromatography-mass spectrometry allowed the detection of individual molecular species of a wide range of L. gormanii membrane lipids contained in the outer (OM) and inner membranes (IM). The lipid profile comprised glycerolipids (triglycerides, diglycerides), phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, cardiolipin), and sphingolipids (ceramides, hexosylceramides). The most abundant lipid fraction in the IM and OM were phospholipids. The lipidomic analysis showed that two independent phosphatidylcholine (PC) synthesis pathways operating in L. gormanii: the PE-methylation (PmtA) pathway and the PC synthase (Pcs) pathway. Comparison of the molecular profile of PC species contained in the lipids of L. gormanii membranes cultured on the medium, with and without exogenous choline, showed quantitative differences in the PC pool. An unusual feature of the L. gormanii lipids was the presence of ceramides and hexosylceramides, which are typical components of eukaryotic cells and a very small group of bacteria. To the best of our knowledge, this is the first report of the occurrence of ceramides in Legionella bacteria.
Wafer-Level Self-Packaging Design and Fabrication of MEMS Capacitive Pressure Sensors
Authors: Wan Yuanjie , Li Zhiwei , Huang Zile , Hu Baofa , Lv Wenlong , Zhang Chunquan , San Haisheng , Zhang Shaoda
Published: May 2022

This paper reports a MEMS capacitive pressure sensor (CPS) based on the operating principle of touch mode. The CPS was designed and fabricated using wafer-level self-packaged MEMS processes. The variable capacitance sensing structure was vacuum-sealed in a cavity using the Si–glass anodic bonding technique, and the embedded Al feedthrough lines at the Si–glass interface were used to realize the electrical connections between the parallel plate electrodes and the electrode pads through Al vias. The optimal design of the CPS structure was performed to trade-off the performance and reliability using finite element simulation. The CPS based on a circular-shaped diaphragm with a radius of 2000 µm and a thickness of 40 µm exhibits good comprehensive performance with a sensitivity of 52.3 pF/MPa and a nonlinearity of 2.7%FS in the pressure range of 100–500 kPa when the ambient temperature is less than 50 °C.
Growth of Laser-Induced Microbubbles inside Capillary Tubes Affected by Gathered Light-Absorbing Particles
Authors: He Jia-Wen , Wang Hao-Dong , Li Bo-Wei , Bai Wen , Chen Dong , Zhong Min-Cheng
Published: May 2022

Microbubbles have important applications in optofluidics. The generation and growth of microbubbles is a complicated process in microfluidic channels. In this paper, we use a laser to irradiate light-absorbing particles to generate microbubbles in capillary tubes and investigate the factors affecting microbubble size. The results show that the key factor is the total area of the light-absorbing particles gathered at the microbubble bottom. The larger the area of the particles at bottom, the larger the size of the microbubbles. Furthermore, the area is related to capillary tube diameter. The larger the diameter of the capillary tube, the more particles gathered at the bottom of the microbubbles. Numerical simulations show that the Marangoni convection is stronger in a capillary tube with a larger diameter, which can gather more particles than that in a capillary tube with a smaller diameter. The calculations show that the particles in contact with the microbubbles will be in a stable position due to the surface tension force.
Study on Dynamic and Static Performance of a Micro Digital Hydraulic Valve
Authors: Yang Meisheng
Published: May 2022

Previous researchers mostly carried out simulation research and scattered experimental research on the static and dynamic characteristics of the digital valve, but did not form a systematic and in-depth study on the characteristics of the valve. Based on expounding the basic principles and functions of the valve and the test system, this paper carries out the test research under various variables for three kinds of static characteristics, including pressure differential-flow characteristics, signal-pressure characteristics, and signal-flow characteristics. The optimal control frequency of the valve is obtained from the comprehensive consideration of linear interval, linearity, and hysteresis. Three methods are systematically used to deeply study the dynamic characteristics, and the influencing factors of test results under various test conditions are analyzed. Through the research of this paper, it can provide relevant performance parameters for taking the digital valve as the system control element in the next step, and lay the foundation for the accurate control of the system.
Electron Radiation Effects of Grain-Boundary Evolution on Polycrystalline Silicon in MEMS
Authors: Wang Lei , Liu Haiyun , Liu Xing
Published: May 2022

A specimen observed with a transmission electron microscope (TEM) was processed by focused ion beam (FIB) from a surface-micromachined polycrystalline silicon MEMS structure. Electron irradiation and in situ observation were performed on a selected grain boundary in the specimen. The grain boundary was observed and located by using lattice-oriented selective TEM photography. An evolution progress of amorphization of small silicon grain within the grain boundary and recrystallization of amorphous silicon were observed. A silicon grain turned into several smaller bar grains within the grain boundary. The mechanism of grain-boundary evolution inducing a change of conductivity of polycrystalline silicon has been revealed. The conductivity of polycrystalline silicon influenced by electron irradiation could be attributed to the change of grain boundary.
THz MEMS Switch Design
Authors: Feng Yukang , Tsao Han-yu , Barker N. Scott
Published: May 2022

In this work, an mm-wave/THz MEMS switch design process is presented. The challenges and solutions associated with the switch electrical design, modeling, fabrication, and test are explored and discussed. To investigate the feasibility of this design process, the switches are designed on both silicon and fused quartz substrate and then tested in the 140–750 GHz frequency range. The measurement fits design expectations and simulation well. At 750 GHz the measurement results from switches on both substrates have an ON state insertion loss of less than 3 dB and an OFF state isolation larger than 12 dB.
Modeling and Control of a Wheeled Biped Robot
Authors: Cui Zemin , Xin Yaxian , Liu Shuyun , Rong Xuewen , Li Yibin
Published: May 2022

It is difficult to realize the stable control of a wheeled biped robot (WBR), as it is an underactuated nonlinear system. To improve the balance and dynamic locomotion capabilities of a WBR, a decoupled control framework is proposed. First, the WBR is decoupled into a variable-length wheeled inverted pendulum and a five-link multi-rigid body system. Then, for the above two simplified models, a time-varying linear quadratic regulator and a model predictive controller are designed, respectively. In addition, in order to improve the accuracy of the feedback information of the robot, the Kalman filter is used to optimally estimate the system state. The control framework can enable the WBR to realize changing height, resisting external disturbances, velocity tracking and jumping. The results obtained by simulations and physical experiments verify the effectiveness of the framework.
Phosphate-Solubilizing Bacteria Isolated from Phosphate Solid Sludge and Their Ability to Solubilize Three Inorganic Phosphate Forms: Calcium, Iron, and Aluminum Phosphates
Authors: Aliyat Fatima Zahra , Maldani Mohamed , El Guilli Mohammed , Nassiri Laila , Ibijbijen Jamal
Published: May 2022

Biofertilizers are a key component of organic agriculture. Bacterial biofertilizers enhance plant growth through a variety of mechanisms, including soil compound mobilization and phosphate solubilizing bacteria (PSB), which convert insoluble phosphorus to plant-available forms. This specificity of PSB allows them to be used as biofertilizers in order to increase P availability, which is an immobile element in the soil. The objective of our study is to assess the capacity of PSB strains isolated from phosphate solid sludge to solubilize three forms of inorganic phosphates: tricalcium phosphate (Ca3(PO4)2), aluminum phosphate (AlPO4), and iron phosphate (FePO4), in order to select efficient solubilization strains and use them as biofertilizers in any type of soil, either acidic or calcareous soil. Nine strains were selected and they were evaluated for their ability to dissolve phosphate in the National Botanical Research Institute’s Phosphate (NBRIP) medium with each form of phosphate (Ca3(PO4)2, AlPO4, and FePO4) as the sole source of phosphorus. The phosphate solubilizing activity was assessed by the vanadate-molybdate method. All the strains tested showed significantly (p ≤ 0.05) the ability to solubilize the three different forms of phosphates, with a variation between strains, and all strains solubilized Ca3(PO4)2 more than FePO4 and AlPO4.
The Outer Membrane Proteins and Their Synergy Triggered the Protective Effects against Pathogenic Escherichia coli
Authors: Pen Guihong , Yang Na , Teng Da , Hao Ya , Mao Ruoyu , Wang Jianhua
Published: May 2022

Colibacillosis caused by pathogenic Escherichia coli (E. coli) is one of the most serious infectious diseases, causing an extensive burden on animal husbandry and the human healthcare system. Vaccination is one of the ideal ways to prevent E. coli infection. In this work, recombinant outer membrane protein A (rOmpA), outer membrane protein C (rOmpC) and BamA (rBamA) from E. coli O78 (CVCC CAU0768) were expressed in a prokaryotic expression system with the concentration of 1–2 mg/mL after purification. Considerable immune responses could be triggered in mice that were immunized with these recombinant proteins, high antibody titers, high total IgG level and various antibody isotypes were detected in antisera after booster immunizations. Moreover, mice immunized with several recombinant proteins in combination showed a higher survival rate with the challenge of homologous strain E. coli O78 and a more significant cross-protection effect against heterologous strain E. coli O157:H7 (CICC 21530) in vivo than those of immunized alone. The antisera from immunized mice showed high affinity to multiple strains of Escherichia, Shigella and Salmonella in vitro, indicating that recombinant outer membrane proteins from E. coli O78 had the potential to be developed into universal antigenic substances against not only E. coli but also a variety of Gram-negative bacteria. rOmpA was considered as the most immunogenic protein in this work and the combination of different proteins could further enhance the immune response of immunized mice, which provided the reference for the construction of novel antigens with higher efficiency.
Study on the Controlling Factors of Li-Bearing Pegmatite Intrusions for Mineral Exploration, Uljin, South Korea
Authors: Oh Il-Hwan , Yang Seok-Jun , Heo Chul-Ho , Lee Jae-Ho , Kim Eui-Jun , Cho Seong-Jun
Published: May 2022

Recently, the demand for lithium (Li) as an energy storage element has increased, owing to the rapid increase in the number of electric vehicles. To meet this demand, Li exploration has become increasingly important. The Boam deposit is located in the Uljin area of eastern South Korea, where several rare-element pegmatites (0.24% Li) intrude the Precambrian Janggun Limestone Formation. In this study, we performed petrographical and geometrical analyses of the rare-element pegmatites recognized in the vicinity of the Boam deposit, through which the Li-mineralization process was identified and the factors controlling intrusion studied. Our results are summarized as follows: (1) the pegmatites exhibit regional and internal zoning based on their mineral assemblages; (2) Li mineralization is restricted to pegmatites; (3) the geometry and distribution of the pegmatites are strongly controlled by fracture, bed contact, and post-intrusive deformation; and (4) exploration should be concentrated in the ENE–WSW-trending zone of the upper part of the Janggun Limestone Formation. These results provide valuable understanding to guide the development of strategies for early-stage mineral exploration in the Uljin area.
Response of Living Benthic Foraminifera to Anthropogenic Pollution and Metal Concentrations in Saronikos Gulf (Greece, Eastern Mediterranean)
Authors: Dimiza Margarita D. , Triantaphyllou Maria V. , Portela Mélanie , Koukousioura Olga , Karageorgis Aristomenis P.
Published: May 2022

The Saronikos Gulf, including the industrial zone of Elefsis Bay, is subjected to a variety of urban and industrial impacts that significantly contribute to environmental degradation. Benthic foraminifera comprise a significant component of meiobenthic communities and they are widely used as reliable indicators for the determination of the natural environmental and anthropogenic impact in shallow coastal systems. The present study analyses the living benthic foraminifera composition and its relation to environmental parameters such as grain size, organic carbon content, and heavy metal concentrations, from the surficial sediment layer collected in the Elefsis Bay and the Inner Saronikos Gulf in February 2016. Canonical correspondence analysis and Spearman’s rho correlation show that the foraminiferal species composition is significantly influenced by the increase of organic carbon and Cu, Pb, Zn content. In particular, a relatively low diversity fauna dominated by the stress-tolerant species Ammonia tepida, Bulimina elongata, Bulimina marginata, and Nonionella turgida occurs in the restricted environment of the Elefsis Bay, demonstrating the negative environmental impact caused by the relatively elevated organic carbon and heavy metal contents.
Pilot Scale Validation of a Chemical Process for Uranium, Cesium, and Mercury Recovery from Cemented Radioactive Wastes
Authors: Reynier Nicolas , Courchesne Maxime , Anderson Javed , Williams Kevin , Schinnour Kyle
Published: May 2022

The medical isotope (Mo-99) production at Chalk River Laboratory involves the dissolution of irradiated isotope targets prior to the extraction of Mo-99. This process generates a waste that is cemented in 5-gallon containers and transferred to a waste-management facility for intermediate storage. Over the past decades, a large number of five-gallon containers of cemented radioactive waste (CRW) were produced, and Canadian Nuclear Laboratories (CNL) must develop a process to convert this material to a permanent waste form. Research has been undertaken to develop an innovative method for the recovery of U, Hg, and Cs from surrogate cemented radioactive waste (SCRW). This paper presents the pilot scale validation of the operating parameters prior to the demonstration scale testing. Leaching tests at the pilot scale were conducted with 5 kg of SCRW to validate the main operating parameters and evaluate the reuse of the leaching solution. The mean solubilization yields obtained at the pilot scale were 81.9 ± 8.3% for Cs, 99.0 ± 1% for U, and 94.9 ± 4.5% for Hg. Columns with 100 g of KNiFC-PAN and 250 g of Lewatit TP214 allow for the separation of Cs and Hg from 60 L of leaching solution without U loss. Flow rates of 12.5 BV/h and 25 BV/h were suitable to achieve 99% separation of Hg and Cs, respectively. For the Hg resin, the capacity reached 23.4 mg/g, and the capacity for the Cs resin reached 0.79 mg/g. The pilot scale U extraction results showed that the U adsorption is selective, with a breakthrough at 36 BV (capacity for U of 3.70 mg/g). Uranium elution with 1 M Na2CO3 exceeded 99%, and subsequent precipitation with NaOH achieved 99% recovery. SEM data confirmed the high purity of the U solids produced as sodium di-uranate.
Supersaturation-Based Drug Delivery Systems: Strategy for Bioavailability Enhancement of Poorly Water-Soluble Drugs
Authors: Sharma Arvind , Arora Kanika , Mohapatra Harapriya , Sindhu Rakesh K. , Bulzan Madalin , Cavalu Simona , Paneshar Gulsheen , Elansary Hosam O. , El-Sabrout Ahmed M. , Mahmoud Eman A. , Alaklabi Abdullah
Published: May 2022

At present, the majority of APIs synthesized today remain challenging tasks for formulation development. Many technologies are being utilized or explored for enhancing solubility, such as chemical modification, novel drug delivery systems (microemulsions, nanoparticles, liposomes, etc.), salt formation, and many more. One promising avenue attaining attention presently is supersaturated drug delivery systems. When exposed to gastrointestinal fluids, drug concentration exceeds equilibrium solubility and a supersaturation state is maintained long enough to be absorbed, enhancing bioavailability. In this review, the latest developments in supersaturated drug delivery systems are addressed in depth.
Zinc and Copper Ions Induce Aggregation of Human β-Crystallins
Authors: Ramirez-Bello Vanesa , Martinez-Seoane Javier , Fernández-Silva Arline , Amero Carlos
Published: May 2022

Cataracts are defined as the clouding of the lens due to the formation of insoluble protein aggregates. Metal ions exposure has been recognized as a risk factor in the cataract formation process. The γ and β crystallins are members of a larger family and share several structural features. Several studies have shown that copper and zinc ions induce the formation of γ-crystallins aggregates. However, the interaction of metal ions with β-crystallins, some of the most abundant crystallins in the lens, has not been explored until now. Here, we evaluate the effect of Cu(II) and Zn(II) ions on the aggregation of HβA1, as a representative of the acidic form, and HβB2, as a representative of the basic β-crystallins. We used several biophysical techniques and computational methods to show that Cu(II) and Zn(II) induce aggregation following different pathways. Both metal ions destabilize the proteins and impact protein folding. Copper induced a small conformational change in HβA1, leading to high-molecular-weight light-scattering aggregates, while zinc is more aggressive towards HβB2 and induces a larger conformational change. Our work provides information on the mechanisms of metal-induced aggregation of β-crystallins.
Ultra-Thin Wrinkled Carbon Sheet as an Anode Material of High-Power-Density Potassium-Ion Batteries
Authors: Cheng Boshi , Li Xing , Pan Linhai , Xu Hongqiang , Duan Haojie , Wu Qian , Yin Bo , He Haiyong
Published: May 2022

Although K+ is readily inserted into graphite, the volume expansion of graphite of up to 60% upon the formation of KC8, together with its slow diffusion kinetics, prevent graphite from being used as an anode for potassium-ion batteries (PIBs). Soft carbon with low crystallinity and an incompact carbon structure can overcome these shortcomings of graphite. Here, ultra-thin two-dimensional (2D) wrinkled soft carbon sheets (USCs) are demonstrated to have high specific capacity, excellent rate capability, and outstanding reversibility. The wrinkles themselves prevent the dense stacking of micron-sized sheets and provide sufficient space to accommodate the volume change of USCs during the insertion/extraction of K+. The ultra-thin property reduces strain during the formation of K-C compounds, and further maintains structural stability. The wrinkles and heteroatoms also introduce abundant edge defects that can provide more active sites and shorten the K+ migration distance, improving reaction kinetics. The optimized USC20−1 electrode exhibits a reversible capacity of 151 mAh g−1 even at 6400 mA g−1, and excellent cyclic stability up to 2500 cycles at 1000 mA g−1. Such comprehensive electrochemical performance will accelerate the adoption of PIBs in electrical energy applications.
Allosteric Binding of MDMA to the Human Serotonin Transporter (hSERT) via Ensemble Binding Space Analysis with ΔG Calculations, Induced Fit Docking and Monte Carlo Simulations
Authors: Islas Ángel A. , Scior Thomas
Published: May 2022

Despite the recent promising results of MDMA (3,4-methylenedioxy-methamphetamine) as a psychotherapeutic agent and its history of misuse, little is known about its molecular mode of action. MDMA enhances monoaminergic neurotransmission in the brain and its valuable psychoactive effects are associated to a dual action on the 5-HT transporter (SERT). This drug inhibits the reuptake of 5-HT (serotonin) and reverses its flow, acting as a substrate for the SERT, which possesses a central binding site (S1) for antidepressants as well as an allosteric (S2) one. Previously, we characterized the spatial binding requirements for MDMA at S1. Here, we propose a structure-based mechanistic model of MDMA occupation and translocation across both binding sites, applying ensemble binding space analyses, electrostatic complementarity, and Monte Carlo energy perturbation theory. Computed results were correlated with experimental data (r = 0.93 and 0.86 for S1 and S2, respectively). Simulations on all hSERT available structures with Gibbs free energy estimations (ΔG) revealed a favourable and pervasive dual binding mode for MDMA at S2, i.e., adopting either a 5-HT or an escitalopram-like orientation. Intermediate ligand conformations were identified within the allosteric site and between the two sites, outlining an internalization pathway for MDMA. Among the strongest and more frequent interactions were salt bridges with Glu494 and Asp328, a H-bond with Thr497, a π-π with Phe556, and a cation-π with Arg104. Similitudes and differences with the allosteric binding of 5-HT and antidepressants suggest that MDMA may have a distinctive chemotype. Thus, our models may provide a framework for future virtual screening studies and pharmaceutical design and to develop hSERT allosteric compounds with a unique psychoactive MDMA-like profile.
Antioxidant, Antimicrobial, and Metabolomic Characterization of Blanched Pomegranate Peel Extracts: Effect of Cultivar
Authors: Magangana Tandokazi Pamela , Makunga Nokwanda P. , Fawole Olaniyi Amos , Stander Maria A. , Opara Umezuruike Linus
Published: May 2022

Hot water blanching at 80 °C for 3 min can be used as a novel pre-treatment step in pomegranate peel to preserve the integrity of the phytochemical content within the peel extracts by lowering or inactivating enzymes such as polyphenol (PPO) oxidase and peroxidase (POD) that are responsible for the break-down of phytochemicals within the peel. The aim of this study was to investigate the effect of hot water blanching pre-treatment on yield, bioactive compounds, antioxidants, enzyme inactivation, and antibacterial activity of ‘Wonderful’, ‘Acco’, and ‘Herskawitz’ pomegranate peel extracts. We used a variety of spectrophotometric-based assays and liquid chromatography mass spectrometry (LC-MS)-based approach to characterize and quantify metabolites within the peel extracts. Blanching significantly (p < 0.05) reduced PPO activity in all peel extracts, with the highest PPO reduction in ‘Herskawitz’ peel extracts at 0.25 U/mL. Furthermore, higher antioxidant activity in ‘Herskawitz’ blanched peel extracts using 2,2-diphenyl-1-picryl hydrazyl (DPPH) antioxidant activity, ferric ion reducing antioxidant power (FRAP), and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging activity at 567.78 ± 9.47 µmol Trolox/g DM, 800.05 ± 1.60 µmol Trolox/g DM, and 915.27 ± 0.61 µmol Trolox/g DM, respectively, was noted. ‘Herskawitz’ blanched peel extracts were recorded with the lowest minimum inhibitory concentration (MIC) value of 80 µg/mL for Gram-positive Bacillus subtilis and Gram-negative Klebsiella pneumoniae bacteria strains. A total of 30 metabolites were present in ‘Acco’ and ‘Herskawitz’ peel extracts and were tentatively identified after LC-MS profiling. This study demonstrates that blanched peel extracts from ‘Herskawitz’ cultivar have great potential for commercial use in value-added products in the nutraceutical, cosmeceutical, and pharmacological industries.
Multi-Element Analysis and Origin Discrimination of Panax notoginseng Based on Inductively Coupled Plasma Tandem Mass Spectrometry (ICP-MS/MS)
Authors: Ji Chao , Liu Jinyu , Zhang Qin , Li Juan , Wu Zhiqiang , Wang Xingyu , Xie Yuxin , Zhao Jiangchao , Shi Rui , Ma Xing , Khan Mohammad Rizwan , Busquets Rosa , He Xiahong , Zhu Youyong , Zhu Shusheng , Zheng Wenjie
Published: May 2022

Panax notoginseng is an important functional health product, and has been used worldwide because of a wide range of pharmacological activities, of which the taproot is the main edible or medicinal part. However, the technologies for origin discrimination still need to be further studied. In this study, an ICP-MS/MS method for the accurate determination of 49 elements was established, whereby the instrumental detection limits (LODs) were between 0.0003 and 7.716 mg/kg, whereas the quantification limits (LOQs) were between 0.0011 and 25.7202 mg/kg, recovery of the method was in the range of 85.82% to 104.98%, and the relative standard deviations (RSDs) were lower than 10%. Based on the content of multi-element in P. notoginseng (total of 89 mixed samples), the discriminant models of origins and cultivation models were accurately determined by the neural networks (prediction accuracy was 0.9259 and area under ROC curve was 0.9750) and the support vector machine algorithm (both 1.0000), respectively. The discriminant models established in this study could be used to support transparency and traceability of supply chains of P. notoginseng and thus avoid the fraud of geographic identification.
Role of Intracellular Iron in Switching Apoptosis to Ferroptosis to Target Therapy-Resistant Cancer Stem Cells
Authors: Pandrangi Santhi Latha , Chittineedi Prasanthi , Chalumuri Sphoorthi Shree , Meena Avtar Singh , Neira Mosquera Juan Alejandro , Sánchez Llaguno Sungey Naynee , Pamuru Ramachandra Reddy , Mohiddin Gooty Jaffer , Mohammad Arifullah
Published: May 2022

Iron is a crucial element required for the proper functioning of the body. For instance, hemoglobin is the vital component in the blood that delivers oxygen to various parts of the body. The heme protein present in hemoglobin comprises iron in the form of a ferrous state which regulates oxygen delivery. Excess iron in the body is stored as ferritin and would be utilized under iron-deficient conditions. Surprisingly, cancer cells as well as cancer stem cells have elevated ferritin levels suggesting that iron plays a vital role in protecting these cells. However, apart from the cytoprotective role iron also has the potential to induce cell death via ferroptosis which is a non-apoptotic cell death dependent on iron reserves. Apoptosis a caspase-dependent cell death mechanism is effective on cancer cells however little is known about its impact on cancer stem cell death. This paper focuses on the molecular characteristics of apoptosis and ferroptosis and the importance of switching to ferroptosis to target cancer stem cells death thereby preventing cancer relapse. To the best of our knowledge, this is the first review to demonstrate the importance of intracellular iron in regulating the switching of tumor cells and therapy resistant CSCs from apoptosis to ferroptosis.
Construction of Enzyme-Responsive Micelles Based on Theranostic Zwitterionic Conjugated Bottlebrush Copolymers with Brush-on-Brush Architecture for Cell Imaging and Anticancer Drug Delivery
Authors: Liu Fangjun , Wang Dun , Wang Jiaqi , Ma Liwei , Yu Cuiyun , Wei Hua
Published: May 2022

Bottlebrush copolymers with different chemical structures and compositions as well as diverse architectures represent an important kind of material for various applications, such as biomedical devices. To our knowledge, zwitterionic conjugated bottlebrush copolymers integrating fluorescence imaging and tumor microenvironment-specific responsiveness for efficient intracellular drug release have been rarely reported, likely because of the lack of an efficient synthetic approach. For this purpose, in this study, we reported the successful preparation of well-defined theranostic zwitterionic bottlebrush copolymers with unique brush-on-brush architecture. Specifically, the bottlebrush copolymers were composed of a fluorescent backbone of polyfluorene derivate (PFONPN) possessing the fluorescence resonance energy transfer with doxorubicin (DOX), primary brushes of poly(2-hydroxyethyl methacrylate) (PHEMA), and secondary graft brushes of an enzyme-degradable polytyrosine (PTyr) block as well as a zwitterionic poly(oligo (ethylene glycol) monomethyl ether methacrylate-co-sulfobetaine methacrylate) (P(OEGMA-co-SBMA)) chain with super hydrophilicity and highly antifouling ability via elegant integration of Suzuki coupling, NCA ROP and ATRP techniques. Notably, the resulting bottlebrush copolymer, PFONPN9-g-(PHEMA15-g-(PTyr16-b-P(OEGMA6-co-SBMA6)2)) (P2) with a lower MW ratio of the hydrophobic side chains of PTyr and hydrophilic side chains of P(OEGMA-co-SBMA) could self-assemble into stabilized unimolecular micelles in an aqueous phase. The resulting unimolecular micelles showed a fluorescence quantum yield of 3.9% that is mainly affected by the pendant phenol groups of PTyr side chains and a drug-loading content (DLC) of approximately 15.4% and entrapment efficiency (EE) of 90.6% for DOX, higher than the other micelle analogs, because of the efficient supramolecular interactions of π–π stacking between the PTyr blocks and drug molecules, as well as the moderate hydrophilic chain length. The fluorescence of the PFONPN backbone enables fluorescence resonance energy transfer (FRET) with DOX and visualization of intracellular trafficking of the theranostic micelles. Most importantly, the drug-loaded micelles showed accelerated drug release in the presence of proteinase K because of the enzyme-triggered degradation of PTyr blocks and subsequent deshielding of P(OEGMA-co-SBMA) corona for micelle destruction. Taken together, we developed an efficient approach for the synthesis of enzyme-responsive theranostic zwitterionic conjugated bottlebrush copolymers with a brush-on-brush architecture, and the resulting theranostic micelles with high DLC and tumor microenvironment-specific responsiveness represent a novel nanoplatform for simultaneous cell image and drug delivery.
Detection of Ovine or Bovine Milk Components in Commercial Camel Milk Powder Using a PCR-Based Method
Authors: Wu Xiaoyun , Na Qin , Hao Shiqi , Ji Rimutu , Ming Liang
Published: May 2022

Food ingredient adulteration, especially the adulteration of milk and dairy products, is one of the important issues of food safety. The large price difference between camel milk powder, ovine, and bovine milk powder may be an incentive for the incorporation of ovine and bovine derived foods in camel milk products. This study evaluated the use of ordinary PCR and real-time PCR for the detection of camel milk powder adulteration based on the presence of ovine and bovine milk components. DNA was extracted from camel, ovine, and bovine milk powder using a deep-processed product column DNA extraction kit. The quality of the extracted DNA was detected by amplifying the target sequence from the mitochondrial Cytb gene, and the extracted DNA was used for the identification of milk powder based on PCR analysis. In addition, PCR-based methods (both ordinary PCR and real-time PCR) were used to detect laboratory adulteration models of milk powder using primers targeting mitochondrial genes. The results show that the ordinary PCR method had better sensitivity and could qualitatively detect ovine and bovine milk components in the range of 1% to 100% in camel milk powder. The commercial camel milk powder was used to verify the practicability of this method. The real-time PCR normalization system has a good exponential correlation (R2 = 0.9822 and 0.9923) between ovine or bovine content and Ct ratio (specific/internal reference gene) and allows for the quantitative determination of ovine or bovine milk contents in adulterated camel milk powder samples. Accuracy was effectively validated using simulated adulterated samples, with recoveries ranging from 80% to 110% with a coefficient of variation of less than 7%, exhibiting sufficient parameters of trueness. The ordinary PCR qualitative detection and real-time PCR quantitative detection method established in this study proved to be a specific, sensitive, and effective technology, which is expected to be used for market detection.
Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells
Authors: Gado Francesca , Ferrisi Rebecca , Di Somma Sarah , Napolitano Fabiana , Mohamed Kawthar A. , Stevenson Lesley A. , Rapposelli Simona , Saccomanni Giuseppe , Portella Giuseppe , Pertwee Roger G. , Laprairie Robert B. , Malfitano Anna Maria , Manera Clementina
Published: May 2022

1,8-naphthyridine-3-carboxamide structures were previously identified as a promising scaffold from which to obtain CB2R agonists with anticancer and anti-inflammatory activity. This work describes the synthesis and functional characterization of new 1,8-naphthyridin-2(1H)-one-3-carboxamides with high affinity and selectivity for CB2R. The new compounds were able to pharmacologically modulate the cAMP response without modulating CB2R-dependent β-arrestin2 recruitment. These structures were also evaluated for their anti-cancer activity against SH-SY5Y and SK-N-BE cells. They were able to reduce the cell viability of both neuroblastoma cancer cell lines with micromolar potency (IC50 of FG158a = 11.8 μM and FG160a = 13.2 μM in SH-SY5Y cells) by a CB2R-mediated mechanism. Finally, in SH-SY5Y cells one of the newly synthesized compounds, FG158a, was able to modulate ERK1/2 expression by a CB2R-mediated effect, thus suggesting that this signaling pathway might be involved in its potential anti-cancer effect.
Identifying Protein Features and Pathways Responsible for Toxicity Using Machine Learning and Tox21: Implications for Predictive Toxicology
Authors: Moukheiber Lama , Mangione William , Moukheiber Mira , Maleki Saeed , Falls Zackary , Gao Mingchen , Samudrala Ram
Published: May 2022

Humans are exposed to numerous compounds daily, some of which have adverse effects on health. Computational approaches for modeling toxicological data in conjunction with machine learning algorithms have gained popularity over the last few years. Machine learning approaches have been used to predict toxicity-related biological activities using chemical structure descriptors. However, toxicity-related proteomic features have not been fully investigated. In this study, we construct a computational pipeline using machine learning models for predicting the most important protein features responsible for the toxicity of compounds taken from the Tox21 dataset that is implemented within the multiscale Computational Analysis of Novel Drug Opportunities (CANDO) therapeutic discovery platform. Tox21 is a highly imbalanced dataset consisting of twelve in vitro assays, seven from the nuclear receptor (NR) signaling pathway and five from the stress response (SR) pathway, for more than 10,000 compounds. For the machine learning model, we employed a random forest with the combination of Synthetic Minority Oversampling Technique (SMOTE) and the Edited Nearest Neighbor (ENN) method (SMOTE+ENN), which is a resampling method to balance the activity class distribution. Within the NR and SR pathways, the activity of the aryl hydrocarbon receptor (NR-AhR) and the mitochondrial membrane potential (SR-MMP) were two of the top-performing twelve toxicity endpoints with AUCROCs of 0.90 and 0.92, respectively. The top extracted features for evaluating compound toxicity were analyzed for enrichment to highlight the implicated biological pathways and proteins. We validated our enrichment results for the activity of the AhR using a thorough literature search. Our case study showed that the selected enriched pathways and proteins from our computational pipeline are not only correlated with AhR toxicity but also form a cascading upstream/downstream arrangement. Our work elucidates significant relationships between protein and compound interactions computed using CANDO and the associated biological pathways to which the proteins belong for twelve toxicity endpoints. This novel study uses machine learning not only to predict and understand toxicity but also elucidates therapeutic mechanisms at a proteomic level for a variety of toxicity endpoints.
Adaptive Laboratory Evolution of Halomonas bluephagenesis Enhances Acetate Tolerance and Utilization to Produce Poly(3-hydroxybutyrate)
Authors: Zhang Jing , Jin Biao , Fu Jing , Wang Zhiwen , Chen Tao
Published: May 2022

Acetate is a promising economical and sustainable carbon source for bioproduction, but it is also a known cell-growth inhibitor. In this study, adaptive laboratory evolution (ALE) with acetate as selective pressure was applied to Halomonas bluephagenesis TD1.0, a fast-growing and contamination-resistant halophilic bacterium that naturally accumulates poly(3-hydroxybutyrate) (PHB). After 71 transfers, the evolved strain, B71, was isolated, which not only showed better fitness (in terms of tolerance and utilization rate) to high concentrations of acetate but also produced a higher PHB titer compared with the parental strain TD1.0. Subsequently, overexpression of acetyl-CoA synthetase (ACS) in B71 resulted in a further increase in acetate utilization but a decrease in PHB production. Through whole-genome resequencing, it was speculated that genetic mutations (single-nucleotide variation (SNV) in phaB, mdh, and the upstream of OmpA, and insertion of TolA) in B71 might contribute to its improved acetate adaptability and PHB production. Finally, in a 5 L bioreactor with intermittent feeding of acetic acid, B71 was able to produce 49.79 g/L PHB and 70.01 g/L dry cell mass, which were 147.2% and 82.32% higher than those of TD1.0, respectively. These results highlight that ALE provides a reliable method to harness H. bluephagenesis to metabolize acetate for the production of PHB or other high-value chemicals more efficiently.
Extraction, Encapsulation into Lipid Vesicular Systems, and Biological Activity of Rosa canina L. Bioactive Compounds for Dermocosmetic Use
Authors: Sallustio Valentina , Chiocchio Ilaria , Mandrone Manuela , Cirrincione Marco , Protti Michele , Farruggia Giovanna , Abruzzo Angela , Luppi Barbara , Bigucci Federica , Mercolini Laura , Poli Ferruccio , Cerchiara Teresa
Published: May 2022

Valorization of wild plants to obtain botanical ingredients could be a strategy for sustainable production of cosmetics. This study aimed to select the rosehip extract containing the greatest amounts of bioactive compounds and to encapsulate it in vesicular systems capable of protecting their own antioxidant activity. Chemical analysis of Rosa canina L. extracts was performed by LC-DAD-MS/MS and 1H-NMR and vitamins, phenolic compounds, sugars, and organic acids were detected as the main compounds of the extracts. Liposomes, prepared by the film hydration method, together with hyalurosomes and ethosomes, obtained by the ethanol injection method, were characterized in terms of vesicle size, polydispersity index, entrapment efficiency, zeta potential, in vitro release and biocompatibility on WS1 fibroblasts. Among all types of vesicular systems, ethosomes proved to be the most promising nanocarriers showing nanometric size (196 ± 1 nm), narrow polydispersity (0.20 ± 0.02), good entrapment efficiency (92.30 ± 0.02%), and negative zeta potential (−37.36 ± 0.55 mV). Moreover, ethosomes showed good stability over time, a slow release of polyphenols compared with free extract, and they were not cytotoxic. In conclusion, ethosomes could be innovative carriers for the encapsulation of rosehip extract.
A Flexible TENG Based on Micro-Structure Film for Speed Skating Techniques Monitoring and Biomechanical Energy Harvesting
Authors: Lu Zhuo , Jia Changjun , Yang Xu , Zhu Yongsheng , Sun Fengxin , Zhao Tianming , Zhang Shouwei , Mao Yupeng
Published: May 2022

Wearable motion-monitoring systems have been widely used in recent years. However, the battery energy storage problem of traditional wearable devices limits the development of human sports training applications. In this paper, a self-powered and portable micro-structure triboelectric nanogenerator (MS-TENG) has been made. It consists of micro-structure polydimethylsiloxane (PDMS) film, fluorinated ethylene propylene (FEP) film, and lithium chloride polyacrylamide (LiCl-PAAM) hydrogel. Through the micro-structure, the voltage of the MS-TENG can be improved by 7 times. The MS-TENG provides outstanding sensing properties: maximum output voltage of 74 V, angular sensitivity of 1.016 V/degree, high signal-to-noise ratio, and excellent long-term service stability. We used it to monitor the running skills of speed skaters. It can also store the biomechanical energy which is generated in the process of speed skating through capacitors. It demonstrates capability of sensor to power electronic calculator and electronic watch. In addition, as a flexible electrode hydrogel, it can readily stretch over 1300%, which can help improve the service life and work stability of MS-TENG. Therefore, MS-TENG has great application potential in human sports training monitoring and big data analysis.