bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of artificial neural network and physiologically based biopharmaceutic models in the development of sustained‐release formulations
Authors: Severino Martins Frederico , Borges Luiza , Oliveira do Couto Rene , Schaller Stephan , de Freitas Osvaldo 
Published: August 2023

AbstractModel‐informed drug development is an important area recognized by regulatory authorities and is gaining increasing interest from the generic drug industry. Physiologically based biopharmaceutics modeling (PBBM) is a valuable tool to support drug development and bioequivalence assessments. This study aimed to utilize an artificial neural network (ANN) with a multilayer perceptron (MLP) model to develop a sustained‐release matrix tablet of metformin HCl 500 mg, and to test the likelihood of the prototype formulation being bioequivalent to Glucophage® XR, using PBBM modeling and virtual bioequivalence (vBE). The ANN with MLP model was used to simultaneously optimize 735 formulations to determine the optimal formulation for Glucophage® XR release. The optimized formulation was evaluated and compared to Glucophage® XR using PBBM modeling and vBE. The optimized formulation consisted of 228 mg of hydroxypropyl methylcellulose (HPMC) and 151 mg of PVP, and exhibited an observed release rate of 42% at 1 h, 47% at 2 h, 55% at 4 h, and 58% at 8 h. The PBBM modeling was effective in assessing the bioequivalence of two formulations of metformin, and the vBE evaluation demonstrated the utility and relevance of translational modeling for bioequivalence assessments. The study demonstrated the effectiveness of using PBBM modeling and model‐informed drug development methodologies, such as ANN and MLP, to optimize drug formulations and evaluate bioequivalence. These tools can be utilized by the generic drug industry to support drug development and biopharmaceutics assessments.
Microwave‐assisted solvent‐free synthesis of some novel thiazole‐substituted thiosemicarbazone analogues: antimicrobial and anticancer studies
Authors: Hossan Aisha 
Published: August 2023

AbstractThe increased resistance to antibiotics has compelled researchers to devise novel active compounds targeting multidrug‐resistant pathogenic microorganisms. A series of thiosemicarbazone derivatives was synthesized by reacting thiosemicarbazide with 2‐aryl‐4‐formylthiazole, 2‐aryl‐5‐formyl‐4‐methylthiazole, and/or 5‐acetyl‐2‐aryl‐4‐methylthiazole compounds. These thiosemicarbazone‐based thiazole adducts were evaluated for their inhibitory activities against tuberculosis H37Ra and Bovis BCG mycobacteria. Their cytotoxicity was assessed against two cancer cell lines: colonic carcinoma (HCT‐116) and cervical cancer (HeLa). Notably, these thiosemicarbazones exhibited minimal cytotoxic effects on these cell lines even at their highest concentrations. Furthermore, the prepared thiosemicarbazone derivatives demonstrated significant antimicrobial efficacy against Bacillus subtilis and Staphylococcus aureus (Gram‐positive bacterial pathogens) as well as Escherichia coli and Pseudomonas fluorescens (Gram‐negative bacterial pathogens). While most of the prepared thiosemicarbazone derivatives exhibited moderate activity against Candida albicans (a fungal strain), their performance was notable. The thiosemicarbazone‐based thiazole adducts were also successfully synthesized using a solvent‐free approach under microwave irradiation. Compared with conventional reflux methods, the microwave‐assisted technique yielded high thiazole yields within just 5 min, obviating the need for catalysis. This study signifies significant strides toward the rational design of more potent antimycobacterial agents.
Enhancement of the substrate specificity of D‐amino acid oxidase based on tunnel‐pocket engineering
Authors: Wang Liuyu , Tang Heng , Zhu Hongli , Xue Yaping , Zheng Yuguo 
Published: August 2023

AbstractD‐Amino acid oxidase (DAAO) selectively catalyzes the oxidative deamination of
D‐amino acids, making it one of the most promising routes for synthesizing optically pure
L‐amino acids, including
L‐phosphinothricin (
L‐PPT), a chiral herbicide with significant market potential. However, the native DAAOs that have been reported have low activity against unnatural acid substrate
D‐PPT. Herein, we designed and screened a DAAO from Rhodotorula taiwanensis (RtwDAAO), and improved its catalytic potential toward
D‐PPT through protein engineering. A semirational design approach was employed to create a mutation library based on the tunnel‐pocket engineering. After three rounds of iterative saturation mutagenesis, the optimal variant M3rd‐SHVG was obtained, exhibiting a >2000‐fold increase in relative activity. The kinetic parameters showed that M3rd‐SHVG improved the substrate binding affinity and turnover number. This is the optimal parameter reported so far. Further, molecular dynamics simulation revealed that the M3rd‐SHVG reshapes the tunnel‐pocket and corrects the direction of enzyme–substrate binding, allowing efficiently catalyze unnatural substrates. Our strategy demonstrates that the redesign of tunnel‐pockets is effective in improving the activity and kinetic efficiency of DAAO, which provides a valuable reference for enzymatic catalysis. With the M3rd‐SHVG as biocatalyst, 500 mM D,
L‐PPT was completely converted and the yield reached 98%. The results laid the foundation for further industrial production.
Optimization of a HPLC–UV bioanalytical method using Box–Behnken design to determine the oral pharmacokinetics of neratinib maleate in Wistar rats
Authors: Mahajan Radhika , Ravi Punna Rao , Khan Md Shareef 
Published: August 2023

AbstractThe current research work reports the development and validation of a sensitive, robust and reproducible bioanalytical method for quantifying neratinib maleate in rat plasma. More than 85% of the drug was extracted from the plasma samples by protein precipitation. The method was optimized using Box–Behnken design, a response surface method. The effect of three critical factors, viz., the pH of the buffer (X1), the aqueous phase proportion in the mobile phase (X2) and the mobile phase flow rate (X3), was studied on two response variables, retention time (Y1) and United States Pharmacopoeia (USP) width (Y2). With the highest overall desirability function value of 0.943, the obtained optimized method conditions were: X1 = 2.4 ± 0.1; X2 = 66.7 ml, and X3 = 0.85 ml/min. Under the optimized conditions, the values of Y1 and Y2 for a sample containing 1 ppm of the drug were found to be 14.1 min and 0.50 ± 0.003, respectively. Single‐dose intravenous bolus (7.5 mg/kg) and oral (15 mg/kg) pharmacokinetic studies were performed to determine the absolute bioavailability of the drug. The optimized bioanalytical method was sensitive enough to capture 95% of the drug eliminated from the body. The absolute oral bioavailability of the drug was 49.30%.
Predicting consumer purchase intention on electric cars in India: Mediating role of attitude
Authors: Mukesh  , Narwal Mahabir 
Published: August 2023

AbstractTo reduce emission of greenhouse gases, electric vehicle is a good option. During recent time in India, there is emergence of electric vehicle start‐ups. This paper predicts purchase intention of the consumer on electric cars with mediation role of attitude. A questionnaire was framed to collect the data from all ages with 173 valid samples. SmartPLS 4 and SPSS were used to test hypotheses and research model. The secondary data helped in understanding the concept of electric vehicles and consumer preferences for them. The findings showed that price perception, government support and environmental concern significantly influence consumer attitude on electric cars except relative product advantage and range anxiety. Result shows mediating role of attitude between independent variables (Price perception and environmental concern) and purchase intention. Study highlights the role of relative product advantage, range anxiety, government support, environmental concern, and price perception in electric vehicle (car) adoption but it has limitations that the study were conducted in Haryana state (India). The opinions and perceptions of the respondents may also limit the study. In practical, the market of EVs is continuously growing in India. The present study encourages the different stakeholders to go with plan that actually work. At present, driving electric cars in India is luxury for people due to its high prices. There were very less discussion on consumer perception toward EVs in previous literatures.
An auxiliary development framework for lightweight RPG games based on Unity3D
Authors: Zhang Bo , Shi Huiping , Wang Xinyu 
Published: August 2023

AbstractWith the growing prevalence of virtual reality technology across industries like cinema, video animation, and gaming, game developers must cater to a wider range of players. Game engines serve as middleware, reducing the time spent on coding and improving productivity for creating video games. While mainstream game engines offer a plethora of customization options, certain developers may find themselves limited when it comes to controlling specific aspects of the game. Due to the lack of built‐in functionality in current game engines like Unity and Unreal, the author developed TRPGFramework, a lightweight framework based on Unity3D, to address some of these problems. The game framework consists of two main parts: ZGamework (overall framework) and BGamework (game‐specific framework). To enhance performance, scalability, and code reusability in the game development process, the entity‐component‐system structure is implemented. This approach increases maintainability and makes the code clearer, easier to expand, and debuggable. By creating a simple 2D RPG game for performance testing, we confirmed that the framework significantly improves code reusability and modularity, resulting in faster development time and increased efficiency for interactive applications and games. This framework is particularly useful for creating real‐time combat role‐playing games, which are some of the most complex games available today. Using entity‐component‐system principles, we developed a buff system and unit controller optimized to allow hundreds of intelligent units to fight on the same screen or thousands of non‐intelligent units to fight simultaneously.
Symbiotic Antimicrobial Effects of Cellulose‐Based Bio‐Nanocomposite for Disease Management of Agricultural Crops
Authors: Sharma Chhavi , Singh Dinesh , Srivastava Ritu , Narain Sharma Shailesh 
Published: August 2023

AbstractIn the present work, a bionanocomposite for plant crop protection was prepared by non‐toxic biocompatible & biodegradable nanomaterials (Cellulose & TiO2) to utilize its synergistic effects against antimicrobial pathogens. The commercially available microcrystalline cellulose has been reduced to a nanometric scale regime using acid hydrolysis, while the standard TiO2 nano‐powder of particle size ~20 nm has been used to prepare their nanocomposite (NC). The antibacterial studies via agar well diffusion method demonstrated that after 72 h of incubation, parent nanomaterials Ncell and TiO2 were not showing any activity against phytopathogens X. campestris pv. campestris, and Clavibacter while the nanocomposite's NC's were still effective depicting both bacteriostatic and bactericidal actions. However, the bacterial growth of biocontrol P. fluorescence was not affected by Ncell, TiO2 NPs and NC after 72 h of incubation. The antifungal testing results via poison food agar assay method suggest that the nanocomposite, along with Ncell and TiO2 NPs, exhibited strong inhibition of fungal growth of Phytophthora Spp at 0.125 mg/ml concentration while for F. graminearum, similar effect was observed at 0.25 mg/ml concentration. The nanocomposite has proved its potential by exhibiting longer & stronger synergistic effects against plant pathogens as a good antimicrobial agent for protection of agricultural crops.
Platelet‐derived microvesicles induce intracellular calcium mobilization in human platelets
Authors: Yadav Pooja , Panigrahi Abhishek R. , Beura Samir K. , Singh Sunil K. 
Published: August 2023

AbstractPlatelet‐derived microvesicles (PMVs) represent a significant proportion of microvesicles in circulation and have been linked to various pathophysiological complications. Recent research suggests that PMVs carry significant amounts of cargo that can affect cellular functions by influencing calcium oscillations in target cells. As calcium is involved in multiple cellular processes, including hemostasis and thrombosis, this study aimed to investigate the impact of PMVs on platelet calcium mobilization. The study found that PMVs increase platelet intracellular calcium levels via both intracellular storage and extracellular space in a dose‐dependent manner. The study highlighted the critical role of the dense tubular system, acidic vacuoles, mitochondrial stores, and store‐operated calcium entry (SOCE) in PMV‐mediated calcium release in human platelets. Moreover, the study revealed that PMV‐induced calcium rise in platelets does not occur via sarcoendoplasmic reticulum calcium ATPase, and extracellular calcium addition further increases the calcium level in platelets, demonstrating the involvement of SOCE. These findings provide insights into the platelet stimulation signaling mechanisms and contributes to our understanding of platelet and cell behavior when exposed to PMV‐rich environments.
Enhanced Laccase Activity and Stability as Crosslinked Enzyme Aggregates on Magnetic Copper Ferrite Nanoparticles for Biotechnological Processes
Authors: Escalante Morales Laura Karina , Sengar Prakhar , Dorado Baeza Andrea , Vazquez‐Duhalt Rafael , Chauhan Kanchan 
Published: August 2023

AbstractHighly stable and reusable magnetic crosslinked enzyme aggregates (m‐CLEAS) of laccase are synthesized with simultaneous improved enzymatic activity. Magnetic copper ferrite nanoparticles (CFNPs) were synthesized by solvothermal procedure with an average size of ~8 nm. The nanometric m‐CLEAS were formed by co‐aggregation of enzyme with CFNPs and crosslinked using glutaraldehyde. Different mass ratios of CFNPs:Laccase were assayed (1 : 2, 1 : 3, and 1 : 6), where 1 : 6 resulted in the highest activity recovery (97 %). The m‐CLEAS showed an average size of ~239 nm, ~24 % enzyme immobilization efficiency, and loading as high as 1.75 g of protein per g of support. As expected, m‐CLEAS oxidized the substrate with a higher transformation rate (kcat) and catalytic efficiency (kcat/Km) than the free enzyme. m‐CLEAS showed superior storage and thermostability compared to free enzyme and non‐magnetic CLEAS. In particular, the m‐CLEAS showed ~150 % and ~100 % residual activity after 30 days of storage at 4 °C and room temperature, respectively. Furthermore, m‐CLEAS showed good recyclability, retaining ~78 % and ~54 % laccase activity after 5 and 10 cycles of reuse, respectively. This work highlights the facile and cost‐effective synthesis of nanometric m‐CLEAS with exceptional storage stability and simultaneously improved laccase activity, making them suitable for a range of green industrial processes.
Resource Utilization of Waste Medicine: A Case of Furazolidone Used for Oilfield Water Treatment
Authors: Xu Zhongying , Wang Yefei , Cao Xuewen , Zhu Shidong , Tang Ying 
Published: August 2023

AbstractAs a case study in the practical problem of how to solve the issue of waste medicine more reasonably, furazolidone (FZD) was investigated as an acidizing corrosion inhibitor and bactericide for oilfield water treatment. Gravimetric results indicate that FZD exhibits high inhibitory efficiency under acidic conditions. In addition, the corrosion inhibition performance decreases as the temperature increases. The adsorption of FZD on the surface of steel has been studied, and the experimental results indicate that the material exhibits the characteristics of a Langmuir‐type adsorption isotherm. The thermodynamic results demonstrate that the adsorption behavior of FZD on the steel surface is that of an exothermic, spontaneous, entropy‐decreasing process. Finally, the bactericidal activity of FZD was investigated. This work provides a simple and beneficial way to utilize a particular waste drug.
Mechanistic Investigations of Electrochemical Ethanol Oxidation Reaction by In Situ Raman Spectroscopy
Authors: Xu Jinchang , Wang Zhenyou 
Published: August 2023

AbstractThe Electrochemical Ethanol Oxidation Reaction (EOR) plays a pivotal role in next‐generation energy conversion devices. A clear understanding of the EOR reaction mechanism is critical for rational catalyst design, a task complicated by the numerous reaction intermediates and pathways involved. To this end, in situ Raman spectroscopy has proven invaluable in identifying many such intermediates at the electrode/electrolyte interface under varying applied potentials. Therefore, this technique allows for inference of the reaction mechanism based on the detected Raman signals of intermediates and observed structural changes, positioning in situ Raman spectroscopy as one of the most suitable methods for studying the EOR reaction mechanism. In this short review, with an eye towards future applications, we concentrate on the essential fundamentals of EOR and highlight recent advancements in understanding the EOR mechanism by in situ Raman spectroscopy.
“Click” Chemistry for the Functionalization of Graphene Oxide with Phosphorus Dendrons: Synthesis, Characterization and Preliminary Biological Properties
Authors: Alami Omar , Laurent Régis , Tassé Marine , Coppel Yannick , Bignon Jérôme , El Kazzouli Saïd , Majoral Jean‐Pierre , El Brahmi Nabil , Caminade Anne‐Marie 
Published: August 2023

AbstractTwo families of phosphorhydrazone dendrons having either an azide or an alkyne linked to the core and diverse types of pyridine derivatives as terminal functions have been synthesized and characterized. These dendrons were grafted via click reaction to graphene oxide (GO) functionalized with either alkyne or azide functions, respectively. The resulting modified‐GO and GO‐dendrons materials have been characterized by Fourier Transform Infrared (FTIR), Raman spectroscopy (RS), and Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses. In addition, the free dendrons and the dendrons grafted to GO were tested toward cancerous (HCT116) and non‐cancerous (RPE1) cell lines.
From an Isolable Bismolyl Anion to an Yttrium–Bismolyl Complex with μ‐Bridging Bismuth(I) Centers and Polar Covalent Y‐Bi Bonds
Authors: Pugliese Elizabeth R. , Benner Florian , Demir Selvan 
Published: August 2023

AbstractThe synthesis and first structural characterization of the [K(18‐crown‐6)] bismolyl Bitet (C4Me4Bi) contact ion pair (1) is presented. Notably, according to Natural Resonance Theory calculations, the Bitet anion of 1 features two types of leading mesomeric structures with localized anionic charge and two lone pairs of electrons at the BiI center, as well as delocalized anionic charge in the π‐conjugated C4Bi ring. The lone pairs at Bi enable a unique bridging coordination mode of the bismolyl ligand, as shown for the first rare earth metal bismolyl complex (Cptet2Y)2(μ‐η1‐Bitet)2 (2). The latter results from the salt metathesis reaction of KBitet with Cptet2Y(BPh4) (Cptet=C5Me4H). The Y‐Bi bonding interaction in 2 of 16.6 % covalency at yttrium is remarkably large.
Systeme zur Sauerstoffversorgung
Authors: Imhof Alexander , Kühn Fritz E. 
Published: August 2023

ZusammenfassungDer Mensch kann ohne Nahrung mehrere Wochen überleben, ohne Wasser mehrere Tage aber ohne Sauerstoff nur wenige Minuten. Eine ausreichende Verfügbarkeit von Sauerstoff in der umgebenden Atemluft ist deshalb lebenswichtig. Vor allem in künstlichen Extremlagen wie Bergwerksstollen, Unterseebooten, Tunneln oder in den großen Höhen der Luft‐ und Raumfahrt bedarf es deshalb technischer Lösungen zur Aufrechterhaltung der Sauerstoffversorgung im Regelbetrieb sowie bei Unfällen oder Defekten. Insbesondere die Rolle der dort verwendeten Chemikalien und Verfahren zur Sauerstofffixierung und ‐freisetzung werden beschrieben. Auch die Natur hat faszinierende Wege gefunden, mit dem Element Sauerstoff umzugehen und in scheinbar lebensfeindlichen Orten auf dem Planeten Erde zu nutzen. So werden neben dem anatomischen Aufbau des Atmungsapparats von Säugetieren wie Walen oder von Vögeln auch unterschiedliche Sauerstoff‐Transportproteine im Blut betrachtet.
The impact of degree of internationalization of MNEs on green innovation performance: The moderating role of absorptive capacity and global dynamic management capability
Authors: Zhang Wei , Zhong Xiuli , Li Xue 
Published: August 2023

AbstractWith the increasing attention given to resource scarcity and environmental destruction, growing pressure is imposed upon MNEs (multinational enterprises) by a wide range of stakeholders to exert green innovation. Although an emerging body of research has explored the contributing factors of green innovation, little attention has been paid to the impact of internationalization, especially the different dimensions of internationalization, on green innovation performance. To address this research gap, this research aims to examine the role of both the breadth (geographical range) and depth (intensity) of internationalization on green innovation performance of MNEs, and investigate the moderating roles of MNEs' global dynamic management capability and absorptive capacity. Based on organizational learning theory, this study used secondary data from Chinese listed companies and established econometric models to test the proposed research framework. The results indicated that the breadth of internationalization could enhance MNEs' green innovation performance. Alternatively, the depth of internationalization could inhibit green innovation performance. In addition, the results also revealed that global dynamic managerial and absorptive capacities can both enhance the positive effect between internationalization breadth and green innovation performance while weakening the negative effect of internationalization depth on green innovation performance. This study has implications for strengthening our knowledge of green innovation performance as well as enhancing policy design for sustainable development.