bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular Economy of Cultural Heritage—Possibility to Create a New Tourism Product through Adaptive Reuse
Authors: Rudan Elena
Published: March 2023

Cultural heritage is a particularly significant resource in creating tourism. When a local community recognizes its cultural heritage (small historic towns, buildings, castles, and forts), it is possible to create new value to meet the needs of tourists, using the principles of a circular economy. Adapting, reusing and restoring heritage sites can contribute to the revitalization of the local economy by creating jobs (increased employment), increased spending, economic development, etc. Adaptive reuse, as one of the principles of a circular economy, represents how the circular economy can pave the way to create new tourism products. The three basic principles of sustainable waste management are reduce, reuse, and recycle (3R). This paper tackles the reuse principle by analyzing case studies involving the application of a circular economy to cultural heritage in the Kvarner tourism destination (Croatia) in the context of reusing resources to create a sustainable destination. The goal is to determine to what extent the reuse of heritage sites makes them useful for the local community, and for tourists to stay in the destination. The research showed positive examples in the Kvarner tourism destination, primarily of a cultural tourism nature and that were achieved in the last ten years; however, the conclusion is that this is still insufficient. By aggregating knowledge and research results, the paper emphasizes the importance of applying the concept of the circular economy to cultural heritage in tourism destinations, with special emphasis on the role of all stakeholders in creating sustainable heritage tourism (local self-government, destination management, local population, and entrepreneurship).
Numerical Modeling of Kinetic Features and Stability Analysis of Jinpingzi Landslide
Authors: Huang Jiaxuan , Du Weichao , Xie Mowen
Published: March 2023

The kinetic features of a slow-moving landslide situated above the Wudongde hydropower station were analyzed using particle flow code 3D (PFC3D) software. This research was based on geological investigations, remote sensing interpretation, and digital elevation models to build the structure of the Jinpingzi landslide. Finite element analysis (FEM) was used to determine the sliding surface. Strength reduction theory (SRT) and particle flow code coupling were used to invert the macro-strength parameters into micro-strength parameters. Finally, the slope failure process was simulated. Meanwhile, the displacement vector angle (DVA) and velocity were used for stability analysis. The simulation results of the kinetic features of slow-moving landslides show that the initial stage begins with accelerated movement, followed by constant-velocity movement and instability failure. The larger the reduction coefficient is, the shorter the duration of each stage is. A two-parameter instability criterion is proposed based on velocity, DVA, and reduction coefficient. Using this criterion, the critical velocity was 200 mm/s, and the critical DVA was 28.15°. The analysis results agree with the actual field monitoring results and motion process. This work confirms that the PFC3D modeling method is suitable for simulating the motion features of landslides.
Paraffin-Multilayer Graphene Composite for Thermal Management in Electronics
Authors: Balan Adriana Elena , AL-Sharea Ali , Lavasani Esmaeil Jalali , Tanasa Eugenia , Voinea Sanda , Dobrica Bogdan , Stamatin Ioan
Published: March 2023

Multilayer graphene–paraffin composites with different contents of graphene (0–10 wt.%) were prepared using an ultra-high shear mixer. The aim is to improve the heat transfer in paraffin wax, which will lead to more-efficient thermal buffering in electronic applications. The multi-layer graphenes obtained by supercritical fluid exfoliation of graphite in alcohol were investigated by Raman spectroscopy, scanning electron microscopy and atomic force microscopy. Interesting morphological features were found to be related to the intercalation of paraffins between the multilayer graphene flakes. Thermal properties were also investigated in terms of phase change transition temperatures, latent heat by differential scanning calorimetry and thermal conductivity. It was found that the addition of graphene resulted in a slight decrease in energy storage capacity but a 150% improvement in thermal conductivity at the highest graphene loading level. This phase-change material is then used as a thermal heat sink for an embedded electronic processor. The temperature of the processor during the execution of a pre-defined programme was used as a performance indicator. The use of materials with multilayer graphene contents of more than 5 wt.% was found to reduce the processor operating temperature by up to 20%. This indicates that the use of such composite materials can significantly improve the performance of processors.
The Influence of Cellulose Nanocrystal Characteristics on Regenerative Silk Composite Fiber Properties
Authors: Kim Hak Jeon , Lee Won Jun
Published: March 2023

Cellulose nanocrystals (CNCs), obtained from natural resources, possess great potential as a bioderived reinforcement for natural-fiber-reinforced composites (NFRPs) due to their superior crystallinity and high aspect ratio. To elucidate the specific parameters of CNCs that significantly affect their mechanical performance, various CNCs were investigated to fabricate high-performance nanocomposite fibers together with regenerated silk fibroin (RSF). We confirmed that the high aspect ratio (~9) of the CNCs was the critical factor to increase the tensile strength and stiffness rather than the crystallinity. At a 1 vol% of CNCs, the strength and stiffness reached ~300 MPa and 10.5 GPa, respectively, which was attributed not only to a stable dispersion but also to alignment. This approach has the potential to evaluate the parameters of natural reinforcement and may also be useful in constructing high-performance NFRPs.
Metallic Coatings through Additive Manufacturing: A Review
Authors: Mohanty Shalini , Gokuldoss Prashanth Konda
Published: March 2023

Metallic additive manufacturing is expeditiously gaining attention in advanced industries for manufacturing intricate structures for customized applications. However, the inadequate surface quality has inspired the inception of metallic coatings through additive manufacturing methods. This work presents a brief review of the different genres of metallic coatings adapted by industries through additive manufacturing technologies. The methodologies are classified according to the type of allied energies used in the process, such as direct energy deposition, binder jetting, powder bed fusion, hot spray coatings, sheet lamination, etc. Each method is described in detail and supported by relevant literature. The paper also includes the needs, applications, and challenges involved in each process.
Alginate-Based Hydrogels and Scaffolds for Biomedical Applications
Authors: Tomić Simonida Lj. , Babić Radić Marija M. , Vuković Jovana S. , Filipović Vuk V. , Nikodinovic-Runic Jasmina , Vukomanović Marija
Published: March 2023

Alginate is a natural polymer of marine origin and, due to its exceptional properties, has great importance as an essential component for the preparation of hydrogels and scaffolds for biomedical applications. The design of biologically interactive hydrogels and scaffolds with advanced, expected and required properties are one of the key issues for successful outcomes in the healing of injured tissues. This review paper presents the multifunctional biomedical applications of alginate-based hydrogels and scaffolds in selected areas, highlighting the key effect of alginate and its influence on the essential properties of the selected biomedical applications. The first part covers scientific achievements for alginate in dermal tissue regeneration, drug delivery systems, cancer treatment, and antimicrobials. The second part is dedicated to our scientific results obtained for the research opus of hydrogel materials for scaffolds based on alginate in synergy with different materials (polymers and bioactive agents). Alginate has proved to be an exceptional polymer for combining with other naturally occurring and synthetic polymers, as well as loading bioactive therapeutic agents to achieve dermal, controlled drug delivery, cancer treatment, and antimicrobial purposes. Our research was based on combinations of alginate with gelatin, 2-hydroxyethyl methacrylate, apatite, graphene oxide and iron(III) oxide, as well as curcumin and resveratrol as bioactive agents. Important features of the prepared scaffolds, such as morphology, porosity, absorption capacity, hydrophilicity, mechanical properties, in vitro degradation, and in vitro and in vivo biocompatibility, have shown favorable properties for the aforementioned applications, and alginate has been an important link in achieving these properties. Alginate, as a component of these systems, proved to be an indispensable factor and played an excellent “role” in the optimal adjustment of the tested properties. This study provides valuable data and information for researchers and demonstrates the importance of the role of alginate as a biomaterial in the design of hydrogels and scaffolds that are powerful medical “tools” for biomedical applications.
Co2CrAl Heuslerene: Mechanical, Thermodynamic and Electronic Properties
Authors: Boochani Arash , Asshabi Moein , Khodadadi Jabbar , Sartipi Elmira , Jamal Morteza , Sabbagzadeh Jamshid , Shahrokhi Masoud , Amiri Malieheh , Yari Arash , Solaymani Shahram , Sari Amir hossein , Jalali-Asadabadi Saeid
Published: March 2023

This work investigates the ground state’s stability of the bulk and three Heuslerene Co2CrAl compounds, named as α, β, and γ phases, by density functional theory (DFT) with the generalized gradient approximation (GGA), GGA+U, and GGA+U+mBJ approximations. The results demonstrate the ground state stability of all mentioned cases since they pass the thermodynamic, elastic, and phonon stability tests. All three structures are more stable in the ferromagnetic phase than the antiferromagnetic phase. In the β phase, Young’s and Shear’s moduli were 73.97 GPa and 24.83 GPa, respectively. The thermodynamic diagram has shown existence of the accessible region, which indicates the possibility of making this structure. For all three structures, the phonon branches in the symmetry paths are positive, which represent the complete dynamic stability of these compositions in the presence of mechanical stresses and thermal vibrations. According to the electronic calculations, the bulk phase of Co2CrAl is a half-metal with 3μB magnetic moment and 100% spin polarization at the Fermi level. Furthermore, all imposed approximations approve that α and γ Heuslerenes are metal for both spin directions, while the GGA+U+mBJ approximation indicates that β phase is a ferromagnetic half-metal of 1μB magnetic moment. Based on the electron density diagrams, the highest (lowest) amount of electron density is created on the α (β) phase surface.
A New Bending Force Formula for the V-Die Bending Process
Authors: Doungmarda Kongkiet , Thipprakmas Sutasn
Published: March 2023

The V-die bending force is an important parameter in respect of press machine capacity selection, but it has not been the focus of previous research. Furthermore, while the various modified formulas proposed in previous research were calculated using V-die bending theory, they are insufficient for predicting the actual V-die bending force. Based on the actual V-die bending mechanism, a new V-die bending force formula is proposed in this study, in which bending is generated not only in the bending allowance zone but also on the legs next to the bending allowance zone. Therefore, the bending force in these zones must be carefully considered. The finite element method (FEM) was used as an effective technique to clearly determine the actual V-die bending mechanism and to modify and develop a new V-die bending force formula. Laboratory experiments were carried out to validate the FEM simulation results as well as to confirm the accuracy of the proposed new V-die bending force formula. Two types of workpiece material, aluminum AA1100-O (JIS) and medium carbon-steel sheet-grade SPCC (JIS), were used as test materials. The results clearly show that the new V-die bending force formula offers more accuracy in V-die bending force prediction than predictions based on past formulas. The error in the V-die bending forces predicted using the new formula was approximately 5% compared with those of the experimental works.
Integrative Analysis of Metabolome and Transcriptome Reveals Molecular Insight into Metabolomic Variations during Hawthorn Fruit Development
Authors: Wang Yan , Hao Ruixin , Guo Rongkun , Nong Huilan , Qin Yu , Dong Ningguang
Published: March 2023

Hawthorn (Crataegus pinnatifida var. major), a cultivated fruit tree, is native and unique to China. Its fruits have high nutritional, health, and medicinal values. However, the development and ripening process of hawthorns is accompanied by dramatic changes in flavor, aroma, and bioactive phytochemicals, which are the fundamental factors that contribute to the potential health benefits and establishment of fruit quality. Therefore, an exploration of the dynamic changes in metabolites and their regulatory networks during the development of hawthorn fruits can elucidate the formation mechanisms of active substances in hawthorn fruits. In this study, we used a broad targeted metabolomics approach to identify and analyze the dynamics of metabolites in hawthorn fruits at five developmental stages. The results revealed 998 primary and secondary metabolites that were classified into 15 categories. The accumulation levels of most sugars increased during fruit development and then accelerated at the fruit ripening stage. The accumulation levels of a few organic acids (e.g., citric acid, isocitric acid, and quinic acid) continuously increased. Many organic acids exhibited significant decreasing trends. Among the 561 secondary metabolites detected, 189 were phenolic acids and 199 were flavonoids. The levels of many flavonoids were significantly reduced at later stages of fruit development; in contrast, the levels of two anthocyanins significantly increased during fruit ripening. Correlation analysis revealed that there is a certain correlation within and between primary as well as secondary metabolites during fruit development. Furthermore, the integration of metabolomic and transcriptomic data in this study revealed that changes in the expression of some differentially expressed genes (DEGs) were associated with the accumulation of metabolites such as sugars, organic acids, and flavonoids, e.g., the upregulated expression levels of CS (citrate synthase) genes were consistent with the continued accumulation of citric acid. Overall, this study demonstrates the metabolic changes that occur during the development of hawthorn fruit, explores the molecular mechanisms that underlie metabolite changes during fruit development, and lays a strong theoretical foundation for the improvement of hawthorn fruit quality and the development of functional components.
K8sSim: A Simulation Tool for Kubernetes Schedulers and Its Applications in Scheduling Algorithm Optimization
Authors: Wen Shilin , Han Rui , Qiu Ke , Ma Xiaoxin , Li Zeqing , Deng Hongjie , Liu Chi Harold
Published: March 2023

In recent years, Kubernetes (K8s) has become a dominant resource management and scheduling system in the cloud. In practical scenarios, short-running cloud workloads are usually scheduled through different scheduling algorithms provided by Kubernetes. For example, artificial intelligence (AI) workloads are scheduled through different Volcano scheduling algorithms, such as GANG_MRP, GANG_LRP, and GANG_BRA. One key challenge is that the selection of scheduling algorithms has considerable impacts on job performance results. However, it takes a prohibitively long time to select the optimal algorithm because applying one algorithm in one single job may take a few minutes to complete. This poses the urgent requirement of a simulator that can quickly evaluate the performance impacts of different algorithms, while also considering scheduling-related factors, such as cluster resources, job structures and scheduler configurations. In this paper, we design and implement a Kubernetes simulator called K8sSim, which incorporates typical Kubernetes and Volcano scheduling algorithms for both generic and AI workloads, and provides an accurate simulation of their scheduling process in real clusters. We use real cluster traces from Alibaba to evaluate the effectiveness of K8sSim, and the evaluation results show that (i) compared to the real cluster, K8sSim can accurately evaluate the performance of different scheduling algorithms with similar CloseRate (a novel metric we define to intuitively show the simulation accuracy), and (ii) it can also quickly obtain the scheduling results of different scheduling algorithms by accelerating the scheduling time by an average of 38.56×.
Editorial for the Special Issue on Advances in Optoelectronic Devices
Authors: Yi Zichuan , Zhang Hu , Jiang Mouhua , Wang Jiashuai
Published: March 2023

Optoelectronic devices are fabricated based on an optoelectronic conversion effect, which is a developing research field of modern optoelectronic technology and microelectronics technology [...]
Zircon Concentrate Enrichment by Dry Magnetic Separation and Centrifugal Air Separation
Authors: Sachkov Victor Ivanovich , Nefedov Roman Andreevich , Medvedev Rodion Olegovych , Amelichkin Ivan Vyacheslavovich , Sachkova Anna Sergeevna , Shcherbakov Pavel Sergeevich , Solovyev Vladislav Sergeevich , Leonov Daniil Igorevich , Biryukov Danil Aleksandrovich
Published: March 2023

The possibility of enrichment and radioactivity reduction of zirconium concentrate obtained at the Obukhovsky mining and processing plant, located in the North Kazakhstan region, was investigated. The zircon concentrate was enriched and deactivated by dry magnetic separation and centrifugal air separation. The elements distribution over the grain surface of the obtained fractions was studied and the particle size distribution was determined by energy dispersive X-ray spectroscopy. The characteristics of the initial zircon concentrate were determined. The average particle size was 70 µm, the bulk density was 2.21 g/cm3, the true density was 4.05 g/cm3, the activity was 10.3 ± 0.6 kBq/kg, and the ZrO2 content was 44.85 wt.%. Dry magnetic separation was carried out at a magnetic induction value of 1.3 T in the separator working area and a feed rate of 5 g/min. Centrifugal air separation was carried out using a rotary classifier at rotor speeds of 3000, 980, and 600 rpm, consuming 2000 Nm3 of air per hour and a concentrate flow of 20 kg/h. The scheme of zircon concentrate processing to produce three final products was proposed. The first is the zircon concentrate having a low activity (ZrO2 content = 55.4 wt.%, P = 5.8 ± 0.6 kBq/kg). The second is the titanium-containing fraction having a low zirconium content (ZrO2 content = 17.7 wt.%, P = 14.2 ± 0.6 kBq/kg). The third is the concentrate having a considerable zirconium content and high activity (ZrO2 content = 23.5 wt.%, P = 12.8 ± 0.6 kBq/kg).
Target-Based Anticancer Indole Derivatives for the Development of Anti-Glioblastoma Agents
Authors: Salerno Silvia , Barresi Elisabetta , Baglini Emma , Poggetti Valeria , Da Settimo Federico , Taliani Sabrina
Published: March 2023

Glioblastoma (GBM) is the most aggressive and frequent primary brain tumor, with a poor prognosis and the highest mortality rate. Currently, GBM therapy consists of surgical resection of the tumor, radiotherapy, and adjuvant chemotherapy with temozolomide. Consistently, there are poor treatment options and only modest anticancer efficacy is achieved; therefore, there is still a need for the development of new effective therapies for GBM. Indole is considered one of the most privileged scaffolds in heterocyclic chemistry, so it may serve as an effective probe for the development of new drug candidates against challenging diseases, including GBM. This review analyzes the therapeutic benefit and clinical development of novel indole-based derivatives investigated as promising anti-GBM agents. The existing indole-based compounds which are in the pre-clinical and clinical stages of development against GBM are reported, with particular reference to the most recent advances between 2013 and 2022. The main mechanisms of action underlying their anti-GBM efficacy, such as protein kinase, tubulin and p53 pathway inhibition, are also discussed. The final goal is to pave the way for medicinal chemists in the future design and development of novel effective indole-based anti-GBM agents.
Gastrodin and Gastrodigenin Improve Energy Metabolism Disorders and Mitochondrial Dysfunction to Antagonize Vascular Dementia
Authors: Wu Sha , Huang Rong , Zhang Ruiqin , Xiao Chuang , Wang Lueli , Luo Min , Song Na , Zhang Jie , Yang Fang , Liu Xuan , Yang Weimin
Published: March 2023

Vascular dementia (VD) is the second most common dementia syndrome worldwide, and effective treatments are lacking. Gastrodia elata Blume (GEB) has been used in traditional Chinese herbal medicine for centuries to treat cognitive impairment, ischemic stroke, epilepsy, and dizziness. Gastrodin (p-hydroxymethylphenyl-b-D-glucopyranoside, Gas) and Gastrodigenin (p-hydroxybenzyl alcohol, HBA) are the main bioactive components of GEB. This study explored the effects of Gas and HBA on cognitive dysfunction in VD and their possible molecular mechanisms. The VD model was established by bilateral common carotid artery ligation (2-vessel occlusion, 2-VO) combined with an intraperitoneal injection of sodium nitroprusside solution. One week after modeling, Gas (25 and 50 mg/kg, i.g.) and HBA (25 and 50 mg/kg, i.g.) were administered orally for four weeks, and the efficacy was evaluated. A Morris water maze test and passive avoidance test were used to observe their cognitive function, and H&E staining and Nissl staining were used to observe the neuronal morphological changes; the expressions of Aβ1-42 and p-tau396 were detected by immunohistochemistry, and the changes in energy metabolism in the brain tissue of VD rats were analyzed by targeted quantitative metabolomics. Finally, a Hippocampus XF analyzer measured mitochondrial respiration in H2O2-treated HT-22 cells. Our study showed that Gas and HBA attenuated learning memory dysfunction and neuronal damage and reduced the accumulation of Aβ1-42, P-Tau396, and P-Tau217 proteins in the brain tissue. Furthermore, Gas and HBA improved energy metabolism disorders in rats, involving metabolic pathways such as glycolysis, tricarboxylic acid cycle, and the pentose phosphate pathway, and reducing oxidative damage-induced cellular mitochondrial dysfunction. The above results indicated that Gas and HBA may exert neuroprotective effects on VD by regulating energy metabolism and mitochondrial function.
Integrative Analysis of the Transcriptome and Metabolome Reveals the Developmental Mechanisms and Metabolite Biosynthesis of the Tuberous Roots of Tetrastigma hemsleyanum
Authors: Hang Suni , Xu Pan , Zhu Sheng , Ye Min , Chen Cuiting , Wu Xiaojun , Liang Weiqing , Pu Jinbao
Published: March 2023

The tuberous root of Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) is a traditional Chinese medicine with a wide range of clinical applications. However, the scarcity of its wild resources, its low yield, and the variable quality that results from its artificial cultivation leads to expensive market prices that are not conducive to the further industrial development of T. hemsleyanum. In this study, transcriptomic and non-targeted metabolomic analyses were integrated to explore the underlying molecular mechanisms and metabolite biosynthesis that occur during its root development. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were predominantly enriched for processes associated with flavonoid and phenylpropanoid biosynthesis, starch and sucrose metabolism, and plant hormone signal transduction. Genes related to lignin were downregulated in tuberous roots (TRs), resulting in a decrease in lignification and the downregulation of metabolites related to flavonoids and phenylpropanoid biosynthesis. In addition, the expression levels of starch- and sucrose-related genes were upregulated in TRs. The root development of SYQ is also related to IAA, GA, ABA, and JA signaling pathways. Collectively, this study lays the foundation for analyzing the root development and quality-modulating mechanisms employed by T. hemsleyanum; this will be beneficial in conducting molecular-assisted breeding and controlling its secondary metabolite production.
Synthesis of Cerium Oxide Nanoparticles in a Bacterial Nanocellulose Matrix and the Study of Their Oxidizing and Reducing Properties
Authors: Melnikova Nina , Malygina Darina , Korokin Vitaly , Al-Azzawi Hayder , Zdorova Daria , Mokshin Evgeniy , Liyaskina Elena , Kurgaeva Irina , Revin Victor
Published: March 2023

A soft synthesis of nanoceria with non-stoichiometric composition (33% Ce3+/67% Ce4+) named CeO2 NPs in bacterial cellulose (BC) matrix in the form of aerogel and hydrogel with controlled CeO2 NPs content was proposed. The advantage of CeO2 NPs synthesis in BC is the use of systemic antacid API–trisamine as a precursor, which did not destruct cellulose at room temperature and enabled a reduction in the duration of synthesis and the number of washes. Moreover, this method resulted in the subsequent uniform distribution of CeO2 NPs in the BC matrix due to cerium (III) nitrate sorption in the BC matrix. CeO2 NPs (0.1–50.0%) in the BC matrix had a fluorite structure with a size of 3–5 nm; the specific surface area of the composites was 233.728 m2/g. CeO2 NPs in the BC-CeO2 NPs composite demonstrated SOD-like activity in the processes of oxidation and reduction of cytochrome c (cyt c3+/cyt c2+), as well as epinephrine to inhibit its auto-oxidation in aqueous solutions by 33–63% relative to the control. In vitro experiments on rat blood showed a decrease in the MDA level and an increase in the activity of antioxidant defense enzymes–SOD by 24% and G6PDH by 2.0–2.5 times. Therefore, BC-CeO2 NPs can be proposed for wound healing as antioxidant material.
Preparation, Characterization and Evaluation of Flavonolignan Silymarin Effervescent Floating Matrix Tablets for Enhanced Oral Bioavailability
Authors: Ahmad Sher , Khan Jamshaid Ali , Kausar Tabassum Naheed , Mahnashi Mater H. , Alasiri Ali , Alqahtani Abdulsalam A. , Alqahtani Thamer S. , Walbi Ismail A. , Alshehri Osama M. , Elnoubi Osman A. , Mahmood Fawad , Sadiq Abdul
Published: March 2023

The convenient and highly compliant route for the delivery of active pharmaceutical ingredients is the tablet. A versatile platform of tablets is available for the delivery of therapeutic agents to the gastrointestinal tract. This study aimed to prepare gastro retentive drug delivery floating tablets of silymarin to improve its oral bioavailability and solubility. Hydroxypropyl methylcellulose (HPMCK4M and HPMCK15), Carbopol 934p and sodium bicarbonate were used as a matrix, floating enhancer and gas generating agent, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, in vitro drug release, in vivo floating behavior and in vivo pharmacokinetics. The drug–polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infrared (FTIR). The floating lag time of the formulation was within the prescribed limit (<2 min). The formulation showed good matrix integrity and retarded the release of drug for >12 h. The dissolution can be described by zero-order kinetics (r2 = 0.979), with anomalous diffusion as the release mechanism (n = 0.65). An in vivo pharmacokinetic study showed that Cmax and AUC were increased by up to two times in comparison with the conventional dosage form. An in vivo imaging study showed that the tablet was present in the stomach for 12 h. It can be concluded from this study that the combined matrix system containing hydrophobic and hydrophilic polymers min imized the burst release of the drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only a hydrophilic matrix. An in vivo pharmacokinetic study elaborated that the bioavailability and solubility of silymarin were improved with an increased mean residence time.
Adsorption and Removal of Cr6+, Cu2+, Pb2+, and Zn2+ from Aqueous Solution by Magnetic Nano-Chitosan
Authors: He Yuran , Zhang Panqing , Wang Lijun
Published: March 2023

Magnetic nano-chitosan (MNC) was prepared and characterized. The kinetics, thermodynamics, and influencing factors of the adsorption of Cr6+, Cu2+, Pb2+, and Zn2+, as well as their competitive adsorption onto MNC in aqueous solution, were studied. The results showed that the adsorption kinetics and thermodynamics of Cr6+, Cu2+, Pb2+, and Zn2+ were well described by the pseudo-second-order kinetic model and Langmuir isothermal adsorption model, indicating that the adsorption was mainly chemical adsorption and endothermic. Increasing the dosage of MNC, the equilibrium adsorption capacity (qe) of Cr6+, Cu2+, Pb2+, and Zn2+ decreased; their removal rate (η) increased. With the increase in the solution’s pH, the qe and η of Cr6+ first increased and then decreased; the qe and η of Cu2+, Pb2+, and Zn2+ increased. With the increase in the metal ion initial concentration, the qe increased; the η of Cr6+, Cu2+, and Zn2+ decreased, while the η of Pb2+ increased first and then decreased. Temperature had a weak influence on the qe of Cr6+ and Pb2+, while it had a strong influence on Cu2+ and Zn2+, the qe and η were greater when the temperature was higher, and the adsorption was spontaneous and endothermic. The qe and η of Cu2+, Pb2+, and Zn2+ decreased in the presence of co-existing ions. The influences among metal ions existed in a binary and ternary ion system. The current study’s results provide a theoretical support for the simultaneous treatment of harmful metal ions in wastewater by MNC.
Assessment of In Silico and In Vitro Selpercatinib Metabolic Stability in Human Liver Microsomes Using a Validated LC-MS/MS Method
Authors: Attwa Mohamed W. , AlRabiah Haitham , Mostafa Gamal A.E. , Bakheit Ahmed H. , Kadi Adnan A.
Published: March 2023

Selpercatinib (SLP; brand name Retevmo®) is a selective and potent RE arranged during transfection (RET) inhibitor. On 21 September 2022, the FDA granted regular approval to SLP (Retevmo, Eli Lilly, and Company). It is considered the only and first RET inhibitor for adults with metastatic or locally advanced solid tumors with RET gene fusion. In the current experiment, a highly specific, sensitive, and fast liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantifying SLP in human liver microsomes (HLMs) was developed and applied to the metabolic stability evaluation of SLP. The LC-MS/MS method was validated following the bioanalytical methodology validation guidelines outlined by the FDA (linearity, selectivity, matrix effect, accuracy, precision, carryover, and extraction recovery). SLP was detected by a triple quadrupole detector (TQD) using a positive ESI source and multiple reaction monitoring (MRM) mode for mass spectrometric analysis and estimation of analytes ions. The IS-normalized matrix effect and extraction recovery were acceptable according to the FDA guidelines for the bioanalysis of SLP. The SLP calibration standards were linear from 1 to 3000 ng/mL HLMs matrix, with a regression equation (y = 1.7298x + 3.62941) and coefficient of variation (r2 = 0.9949). The intra-batch and inter-batch precision and accuracy of the developed LC-MS/MS method were −6.56–5.22% and 5.08–3.15%, respectively. SLP and filgotinib (FLG) (internal standard; IS) were chromatographically separated using a Luna 3 µm PFP (2) stationary phase (150 × 4.6 mm) with an isocratic mobile phase at 23 ± 1 °C. The limit of quantification (LOQ) was 0.78 ng/mL, revealing the LC-MS/MS method sensitivity. The intrinsic clearance and in vitro t1/2 (metabolic stability) of SLP in the HLMs matrix were 34 mL/min/kg and 23.82 min, respectively, which proposed an intermediate metabolic clearance rate of SLP, confirming the great value of this type of kinetic experiment for more accurate metabolic stability predictions. The literature review approved that the established LC-MS/MS method is the first developed and reported method for quantifying SLP metabolic stability.
Why Do These Yeasts Smell So Good? Volatile Organic Compounds (VOCs) Produced by Malassezia Species in the Exponential and Stationary Growth Phases
Authors: Rios-Navarro Andrea , Gonzalez Mabel , Carazzone Chiara , Celis Ramírez Adriana Marcela
Published: March 2023

Malassezia synthesizes and releases volatile organic compounds (VOCs), small molecules that allow them to carry out interaction processes. These lipid-dependent yeasts belong to the human skin mycobiota and are related to dermatological diseases. However, knowledge about VOC production and its function is lacking. This study aimed to determine the volatile profiles of Malassezia globosa, Malassezia restricta, and Malassezia sympodialis in the exponential and stationary growth phases. The compounds were separated and characterized in each growth phase through headspace solid-phase microextraction (HS-SPME) and gas chromatography–mass spectrometry (GC–MS). We found a total of 54 compounds, 40 annotated. Most of the compounds identified belong to alcohols and polyols, fatty alcohols, alkanes, and unsaturated aliphatic hydrocarbons. Unsupervised and supervised statistical multivariate analyses demonstrated that the volatile profiles of Malassezia differed between species and growth phases, with M. globosa being the species with the highest quantity of VOCs. Some Malassezia volatiles, such as butan-1-ol, 2-methylbutan-1-ol, 3-methylbutan-1-ol, and 2-methylpropan-1-ol, associated with biological interactions were also detected. All three species show at least one unique compound, suggesting a unique metabolism. The ecological functions of the compounds detected in each species and growth phase remain to be studied. They could interact with other microorganisms or be an important clue in understanding the pathogenic role of these yeasts.
Phage Display-Derived Peptides and Antibodies for Bacterial Infectious Diseases Therapy and Diagnosis
Authors: Zhao Hui , Nie Dan , Hu Yue , Chen Zhou , Hou Zheng , Li Mingkai , Xue Xiaoyan
Published: March 2023

The emergence of antibiotic-resistant-bacteria is a serious public health threat, which prompts us to speed up the discovery of novel antibacterial agents. Phage display technology has great potential to screen peptides or antibodies with high binding capacities for a wide range of targets. This property is significant in the rapid search for new antibacterial agents for the control of bacterial resistance. In this paper, we not only summarized the recent progress of phage display for the discovery of novel therapeutic agents, identification of action sites of bacterial target proteins, and rapid detection of different pathogens, but also discussed several problems of this technology that must be solved. Breakthrough in these problems may further promote the development and application of phage display technology in the biomedical field in the future.
Deciphering Complex Interactions in Bioactive Lipid Signaling
Authors: Maccarrone Mauro
Published: March 2023

Lipids are usually viewed as metabolic fuel and structural membrane components. Yet, in recent years, different families of lipids able to act as authentic messengers between cells and/or intracellularly have been discovered. Such lipid signals have been shown to exert their biological activity via specific receptors that, by triggering distinct signal transduction pathways, regulate manifold pathophysiological processes in our body. Here, endogenous bioactive lipids produced from arachidonic acid (AA) and other poly-unsaturated fatty acids will be presented, in order to put into better perspective the relevance of their mutual interactions for health and disease conditions. To this end, metabolism and signal transduction pathways of classical eicosanoids, endocannabinoids and specialized pro-resolving mediators will be described, and the intersections and commonalities of their metabolic enzymes and binding receptors will be discussed. Moreover, the interactions of AA-derived signals with other bioactive lipids such as shingosine-1-phosphate and steroid hormones will be addressed.
The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice
Authors: Zanikov Timur , Gerasymchuk Marta , Ghasemi Gojani Esmaeel , Robinson Gregory Ian , Asghari Shima , Groves Alyssa , Haselhorst Lucie , Nandakumar Sanjana , Stahl Cora , Cameron Mackenzie , Li Dongping , Rodriguez-Juarez Rocio , Snelling Alexandra , Hudson Darryl , Fiselier Anna , Kovalchuk Olga , Kovalchuk Igor
Published: March 2023

Inflammation is an organism’s biological defense mechanism. Acute and chronic inflammation of the body triggers the production of pro- and anti-inflammatory pathways that can affect the content of cytokines in the brain and thus cause brain inflammation. Disorders such as depression and posttraumatic stress disorder (PTSD) are often associated with elevated inflammation. Recently, positive and promising clinical results of psilocybin for the treatment of depression and PTSD were reported. Thus, we decided to test whether psilocybin alone or in combination with eugenol, an anti-inflammatory and antioxidant agent, would prevent the increase in or decrease the content of cytokines in the brain of C57BL/6J mice injected with lipopolysaccharides (LPS). Two experiments were performed, one with pre-treatment of mice through gavage with psilocybin (0.88 mg/kg), eugenol (17.6 mg/kg), or combinations of psilocybin and eugenol (1:10, 1:20, or 1:50), followed by intraperitoneal injection of LPS, and the second, post-treatment, with initial injection with LPS, followed by treatment with psilocybin, eugenol, or their combination. Brain tissues were collected, and cytokines were analyzed by qRT-PCR, Western blot, and ELISA. Data were analyzed with a one-way ANOVA followed by Tukey’s post hoc test or with multiple unpaired t-tests. LPS upregulated mRNA expression of COX-2, TNF-α, IL-1β, and IL-6. All pre-treatments decreased the expression of COX-2 and TNF-α, with psilocybin alone and in 1:50 combination, with eugenol being the most effective. In the post-treatment, all combinations of psilocybin and eugenol were effective in reducing inflammation, with the 1:50 ratio displaying the most prominent results in reducing the mRNA content of tested cytokines. Western blot analysis confirmed the effect on COX-2 and IL-1β proteins. Finally, the ELISA showed that post-treatment with psilocybin + eugenol (1:50) demonstrated the best results, decreasing the expression of multiple markers including IL-6 and IL-8. This demonstrates the anti-inflammatory effects of a combination of psilocybin and eugenol in the brain of animals with systemically induced inflammation.
Optimization of the Extraction of Antioxidant Compounds from Roselle Hibiscus Calyxes (Hibiscus sabdariffa), as a Source of Nutraceutical Beverages
Authors: Villalobos-Vega María José , Rodríguez-Rodríguez Gerardo , Armijo-Montes Orlando , Jiménez-Bonilla Pablo , Álvarez-Valverde Víctor
Published: March 2023

Secondary metabolites from Hibiscus sabdariffa have been used to prevent different diseases. Roselle Hibiscus is known for being rich in phenolic bioactive compounds. The extraction conditions are directly related to the chemical composition and then to the overall bioactivity of the extract. In this study, a Box-Behnken experimental design has been used to optimize the antioxidant activity, considering four variables: ethanol:water ratio, temperature, extraction time, and solvent:solid ratio. The experiment comprises 27 experiments and 3 repetitions at the central point. The results are described by surface response analysis and a second-degree polynomial equation. The model explains 87% of the variation in the response. The maximum antioxidant activity is yielded when 1% solids are extracted in 35.5% ethanol at 60 °C for 33 min. Finally, a nutritional functional supplement of 495 µmol Trolox Equivalent (TE) antioxidant capacity was prepared with the optimized extract.
Identification of Sildenafil Compound in Selected Drugs Using X-ray Study and Thermal Analysis
Authors: Jendrzejewska Izabela , Goryczka Tomasz , Pietrasik Ewa , Klimontko Joanna , Jampilek Josef
Published: March 2023

Twelve drugs containing sildenafil compounds (sildenafil citrate and sildenafil base) were examined using X-ray studies and thermal analysis. According to the manufacturer’s information, the presence of sildenafil was confirmed in all investigated drugs. The positions of diffraction lines (value of 2θ angle) agree with the patterns presented in the ICDD database, Release 2018 (ICDD—International Centre of Diffraction Data). The difference expresses the agreement in the position of the diffraction line between the tested substance and the standard. A good agreement is when this difference is less than 0.2°. The values of interplanar distances dhkl are also compatible with the ICDD database. It indicated that the drug examined was genuine. Because all drugs are mixtures of different substances (API and excipients), the various diffraction line intensities were detected in all observed X-ray images for the tested drugs. The intensity of the diffraction line depends on many factors, like the amount of substance, coexisting phases, and mass absorption coefficient of the mixture. The thermal analysis confirmed the results obtained by the X-ray study. On DSC curves, the endothermic peaks for sildenafil compounds were observed. The determined melting points of sildenafil compounds corresponded to the values available in the literature. The results gathered by connecting two methods, X-ray study and thermal analysis, can help identify irregularities that may exist in pharmaceutical specimens, e.g., distinguishing genuine from counterfeit products, the presence of a correct polymorph, a lack of active substance, an inaccurate amount of the active substance, or excipients in the tested drug.
Chemical Evaluation, Phytotoxic Potential, and In Silico Study of Essential Oils from Leaves of Guatteria schomburgkiana Mart. and Xylopia frutescens Aubl. (Annonaceae) from the Brazilian Amazon
Authors: de Moraes Ângelo Antônio Barbosa , Cascaes Márcia Moraes , do Nascimento Lidiane Diniz , de Jesus Pereira Franco Celeste , Ferreira Oberdan Oliveira , Anjos Tainá Oliveira dos , Karakoti Himani , Kumar Ravendra , da Silva Souza-Filho Antônio Pedro , de Oliveira Mozaniel Santana , Andrade Eloisa Helena de Aguiar
Published: March 2023

The essential oils (EOs) of Guatteria schomburgkiana (Gsch) and Xylopia frutescens (Xfru) (Annonaceae) were obtained by hydrodistillation, and their chemical composition was evaluated by gas chromatography-mass spectrometry (GC/MS). Herbicide activity was measured by analyzing the seed germination percentage and root and hypocotyl elongation of two invasive species: Mimosa pudica and Senna obtusifolia. The highest yield was obtained for the EO of Xfru (1.06%). The chemical composition of Gsch was characterized by the presence of the oxygenated sesquiterpenes spathulenol (22.40%) and caryophyllene oxide (14.70%). Regarding the EO of Xfru, the hydrocarbon monoterpenes α-pinene (35.73%) and β-pinene (18.90%) were the components identified with the highest concentrations. The germination of seeds of S. obtusifolia (13.33 ± 5.77%) showed higher resistance than that of seeds of M. pudica (86.67 ± 5.77%). S. obtusifolia was also more sensitive to the EO of Xfru in terms of radicle (55.22 ± 2.72%) and hypocotyl (71.12 ± 3.80%) elongation, while M. pudica showed greater sensitivity to the EO of Gsch. To screen the herbicidal activity, the molecular docking study of the major and potent compounds was performed against 4-hydroxyphenylpyruvate dioxygenase (HPPD) protein. Results showed good binding affinities and attributed the strongest inhibitory activity to δ-cadinene for the target protein. This work contributes to the study of the herbicidal properties of the EOs of species of Annonaceae from the Amazon region.
Sustainable Microfabrication Enhancement of Graphene Nanoplatelet-Reinforced Biomedical Alumina Ceramic Matrix Nanocomposites
Authors: Nasr Mustafa M. , Anwar Saqib , Al-Samhan Ali M. , Alqahtani Khaled N. , Dabwan Abdulmajeed , Alhaag Mohammed H.
Published: March 2023

Studies about adding graphene reinforcement to improve the microfabrication performance of alumina (Al2O3) ceramic materials are still too rare and incomplete to satisfy sustainable manufacturing requirements. Therefore, this study aims to develop a detailed understanding of the effect of graphene reinforcement to enhance the laser micromachining performance of Al2O3-based nanocomposites. To achieve this, high-density Al2O3 nanocomposite specimens were fabricated with 0 wt.%, 0.5 wt.%, 1 wt.%, 1.5 wt.%, and 2.5 wt.% graphene nanoplatelets (GNPs) using a high-frequency induction heating process. The specimens were subjected to laser micromachining. Afterward, the effects of the GNP contents on the ablation depth/width, surface morphology, surface roughness, and material removal rate were studied. The results indicate that the micro-fabrication performance of the nanocomposites was significantly affected by the GNP content. All nanocomposites exhibited improvement in the ablation depth and material removal rate compared to the base Al2O3 (0 wt.% GNP). For instance, at a higher scanning speed, the ablation depth was increased by a factor of 10 times for the GNP-reinforced specimens compared to the base Al2O3 nanocomposites. In addition, the MRRs were increased by 2134%, 2391%, 2915%, and 2427% for the 0.5 wt.%, 1 wt.%, 1.5 wt.%, and 2.5 wt.% GNP/Al2O3 nanocomposites, respectively, compared to the base Al2O3 specimens. Likewise, the surface roughness and surface morphology were considerably improved for all GNP/Al2O3 nanocomposite specimens compared to the base Al2O3. This is because the GNP reinforcement reduced the ablation threshold and increased the material removal efficiency by increasing the optical absorbance and thermal conductivity and reducing the grain size of the Al2O3 nanocomposites. Among the GNP/Al2O3 nanocomposites, the 0.5 wt.% and 1 wt.% GNP specimens showed superior performance with minimum defects in most laser micromachining conditions. Overall, the results show that the GNP-reinforced Al2O3 nanocomposites can be machined with high quality and a high production rate using a basic fiber laser system (20 Watts) with very low power consumption. This study shows huge potential for adding graphene to alumina ceramic-based materials to improve their machinability.