bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixing Performance of a Passive Micro-Mixer with Mixing Units Stacked in Cross Flow Direction
Authors: Juraeva Makhsuda , Kang Dong-Jin
Published: December 2021

A new passive micro-mixer with mixing units stacked in the cross flow direction was proposed, and its performance was evaluated numerically. The present micro-mixer consisted of eight mixing units. Each mixing unit had four baffles, and they were arranged alternatively in the cross flow and transverse direction. The mixing units were stacked in four different ways: one step, two step, four step, and eight step stacking. A numerical study was carried out for the Reynolds numbers from 0.5 to 50. The corresponding volume flow rate ranged from 6.33 μL/min to 633 μL/min. The mixing performance was analyzed in terms of the degree of mixing (DOM) and relative mixing energy cost (MEC). The numerical results showed a noticeable enhancement of the mixing performance compared with other micromixers. The mixing enhancement was achieved by two flow characteristics: baffle wall impingement by a stream of high concentration and swirl motion within the mixing unit. The baffle wall impingement by a stream of high concentration was observed throughout all Reynolds numbers. The swirl motion inside the mixing unit was observed in the cross flow direction, and became significant as the Reynolds number increased to larger than about five. The eight step stacking showed the best performance for Reynolds numbers larger than about two, while the two step stacking was better for Reynolds numbers less than about two.
Piezoelectric Hysteresis Modeling of Hybrid Driven Three-Dimensional Elliptical Vibration Aided Cutting System Based on an Improved Flower Pollination Algorithm
Authors: Fu Xifeng , Gong Hong , Lu Mingming , Zhou Jiakang , Lin Jieqiong , Du Yongsheng , Zhou Ruiqi
Published: December 2021

Three-dimensional elliptical vibration assisted cutting technology has been widely used in the past few years. The piezoelectric stack drive structure is an important part of the three-dimensional elliptical vibration aided cutting system. Its piezoelectric hysteresis characteristics affects the final output of the elliptical trajectory. Aiming at this problem, a piezoelectric hysteresis modeling method based on a generalized Bouc–Wen model is presented in this paper. An improved flower pollination algorithm (IFPASO) was used to identify Bouc–Wen model parameters. Standard test result shows that IFPASO has better algorithm performance. The model identification effect experiment proved that the Bouc–Wen model obtained by IFPASO identification, the highest modeling accuracy of the three axial subsystems, can reach 98.86%. Therefore, the model can describe the piezoelectric hysteresis characteristics of the three axial subsystems of the 3D-EVC system effectively and has higher modeling accuracy and fitting accuracy.
The Method of Low-Temperature ICP Etching of InP/InGaAsP Heterostructures in Cl2-Based Plasma for Integrated Optics Applications
Authors: Ishutkin Sergey , Arykov Vadim , Yunusov Igor , Stepanenko Mikhail , Smirnov Vyacheslav , Troyan Pavel , Zhidik Yury
Published: December 2021

Chlorine processes are widely used for the formation of waveguide structures in InP-based optoelectronics. Traditionally, ICP etching of InP in a Cl2-based plasma requires substrate temperatures in the range of 150–200 °C. This condition is mandatory, since during the etching process low-volatility InClx components are formed and at insufficient temperatures are deposited onto substrate, leading to the formation of defects and further impossibility of the formation of waveguide structures. The need to preheat the substrate limits the application of chlorine processes. This paper presents a method of ICP etching an InP/InGaAsP heterostructure in a Cl2/Ar/N2 gas mixture. A feature of the developed method is the cyclic etching of the heterostructure without preliminary heating. The etching process starts at room temperature. In the optimal etching mode, the angle of inclination of the sidewalls of the waveguides reached 88.8° at an etching depth of more than 4.5 μm. At the same time, the surface roughness did not exceed 30 nm. The selectivity of the etching process with respect to the SiNx mask was equal to 9. Using the developed etching method, test integrated waveguide elements were fabricated. The fabricated active integrated waveguide (p-InP epitaxial layers were not removed) with a width of 2 μm demonstrated an optical loss around 11 ± 1.5 dB/cm at 1550 nm. The insertion loss of the developed Y- and MMI-splitters did not exceed 0.8 dB.
Infections in a Tertiary Care Pediatric Center in Southern Poland during the SARS-CoV-2 Pandemic
Authors: Klepacka Joanna , Zakrzewska Zuzanna , Czogała Małgorzata , Chromy-Czoniszwili Adriana , Skoczeń Szymon , Fyderek Krzysztof
Published: December 2021

The worldwide surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic and led governments to control spread of the virus and provide care for the population affected by the infection. Although, in children, COVID-19 is usually asymptomatic or mild (except PIMS), the pandemic affected the whole socioeconomic system and led to the overwhelming of healthcare facilities. We report retrospective observations of the prevalence of various infectious diseases during the SARS-CoV-2 pandemic in a tertiary multidisciplinary pediatric center in Southern Poland. We retrospectively evaluated the impact of the SARS-CoV-2 pandemic on the number of other infections diagnosed in a pediatric tertiary care referral center. Our analysis included the period from the beginning of February to the end of April 2020 (spring pandemic wave), and from the beginning of September to the end of November 2020 (autumn pandemic wave). We compared them to the appropriate periods of 2019. The evaluation included blood, urine, stool and lover respiratory tract cultures as well as virological investigations. Additionally, the costs of antibiotics and antifungal drugs in selected departments were assessed. Our analysis showed considerable reduction in the majority of common infections except for influenza A and B. The microbiological data correspond with economical summary of antibiotic costs, which were significantly lower during the pandemic. One exception was the number of positive blood cultures, which increased even though the overall number of tests was lower. A general reduction of the number of infections diagnosed in children could result from the implemented preventative measures associated with the pandemic and the generally increased awareness of the risk of infection among parents and guardians. The treatment of the most serious diseases continued as it did before the pandemic. To our knowledge, this study is the first attempt to assess the impact of the COVID-19 pandemic on the prevalence of infections in a large pediatric center. Further research on the impact of the COVID-19 pandemic on the healthcare systems is necessary.
A Geological-Geophysical Prospecting Model for Deep-Seated Gold Deposits in the Jiaodong Peninsula, China
Authors: Song Mingchun , Xue Guoqiang , Liu Hongbo , Li Yixin , He Chunyan , Wang Hongjun , Wang Bin , Song Yingxin , Li Shiyong
Published: December 2021

The North China Craton is one of China’s major gold-producing areas. Breakthroughs have been continually made in deep prospecting at depths of 500–2000 m in the Jiaodong Peninsula, and geophysical methods have played an important role. Given that the geophysical signals of deep-seated gold deposits are difficult to detect, due to their thick overburden layers, conventional geophysical methods are not suitable for deep prospecting. Therefore, this study upgrades the geological-geophysical prospecting model, which is based on the deep metallogenic model and geophysical method of large exploration depths. Based on the analysis of the metallogenic geological factors of the altered-rock-type gold deposits in the fracture zones of the Jiaodong Peninsula, this study proposes that the gold deposits are controlled by large-scale faults, generally occur near the contact interfaces between the Early Precambrian metamorphic rock series and Mesozoic granitoids, and exhibit a stepped metallogenic model. This model then becomes the prerequisite and basic condition for deep prospecting by geophysical methods. For this reason, the traditional geophysical model, which focuses on the exploration of shallow mineralization anomalies, is transformed into a comprehensive multi-parameter geological-geophysical qualitative prospecting model highlighting the exploration of ore-controlling structural planes. The model adopts various frequency domain methods (e.g., CSAMT, AMT, WFEM), reflection seismology, and other methods to detect the deep geological structure. The characteristics of parameters such as gravity and magnetism, resistivity, polarizability, and the seismic reflection spectrum are applied to identify the ore-controlling fault location and dip angle change, and to estimate the ore-bearing location according to the stepped metallogenic model. The prospecting demonstration of deep-seated gold deposits in the Shuiwangzhuang mining area indicates the effectiveness of the comprehensive model. The comprehensive deep prospecting model effectively solves the problem of deep prospecting of gold deposits controlled by faults, promotes the great breakthrough of deep prospecting in the Jiaodong Peninsula, and provides an important technology demonstration for deep prospecting throughout China.
Preliminary Data on Geochemical Characteristics of Major and Trace Elements in Typical Biominerals: From the Perspective of Human Kidney Stones
Authors: Tian Yu , Han Guilin , Zeng Jie , Zhang Qian , Xu Lifang , Liu Ke , Xiao Chunlei , Ma Lulin , Zhao Ye
Published: December 2021

The chemical composition of biominerals is essential for understanding biomineral formation and is regarded as an attractive subject in bio-mineralogical research on human kidney stones (urinary calculi). In order to obtain more geochemically interpreted data on biogenic minerals, mineralogical compositions and major and trace element concentrations of sixty-six kidney stone samples derived from kidney stone removal surgeries were measured. Infrared spectroscopy results showed that calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) were the two main mineral components of kidney stones. Geochemical results indicated that major and trace element concentrations were present in the following order: Ca > Mg > Na > K > Zn > Fe > Pb > Ba > Cu > Ti > Mo > Cd > Cr. With the exception of Ca, Mg was the second-most abundant element. Zn exhibited higher concentrations relative to other trace elements, which suggests a potential substitution of calcium by metal ions with a similar charge and radius rather than by metals in kidney stone formation. Pb appeared in significantly higher concentrations than in previous studies, which indicates Pb enrichment in the environment. In order to discern multi-element relationships within kidney stones, principal component analysis was applied. Three principal components (PCs, eigenvalues >1) were extracted to explain 64.4% of the total variance. The first component exhibited positively correlated Na-Zn-Cr-Mo-Cd-Pb, while the second component exhibited more positively weighted Mg-K-Ba-Ti. Fe-Cu demonstrated a positive correlation in the third component. This study suggests that Ca exhibits a preference for uptake by oxalates during human urinary stone crystallization, while other alkali metals and alkaline earth metals precipitate with phosphate.
Development of a Multi-Objective Optimization Tool for Screening Designs of Taut Synthetic Mooring Systems to Minimize Mooring Component Cost and Footprint
Authors: West William , Goupee Andrew , Hallowell Spencer , Viselli Anthony
Published: December 2021

As the offshore wind industry develops, more lease sites in the intermediate water depth (50–85 m) are being released to developers. In these water depths floating wind turbines with chain catenary systems and fixed-bottom turbines with jacketed structures become cost prohibitive. As such, industry and researchers have shifted focus to floating turbines with taut or semi-taut synthetic rope mooring systems. In addition to reducing the cost of the mooring systems, synthetic systems can also reduce the footprint compared to a chain catenary system which frees areas around the turbine for other maritime uses such as commercial fishing. Both the mooring systems component cost and footprint are pertinent design criteria that lend themselves naturally to a multi-objective optimization routine. In this paper a new approach for efficiently screening the design space for plausible mooring systems that balance component cost and footprint using a multi-objective genetic algorithm is presented. This method uses a tiered-constraint method to avoid performing computationally expensive time domain simulations of mooring system designs that are infeasible. Performance metrics for assessing the constraints of candidate designs are performed using open-source software such as Mooring Analysis Program (MAP++), OpenFAST and MoorDyn. A case study is presented providing a Pareto-optimal design front for a taut synthetic mooring system of a 6-MW floating offshore wind turbine.
Inhibition of Cytosolic Phospholipase A2α Induces Apoptosis in Multiple Myeloma Cells
Authors: Mahammad Nur , Ashcroft Felicity J. , Feuerherm Astrid J. , Elsaadi Samah , Vandsemb Esten N. , Børset Magne , Johansen Berit
Published: December 2021

Cytosolic phospholipase A2α (cPLA2α) is the rate-limiting enzyme in releasing arachidonic acid and biosynthesis of its derivative eicosanoids. Thus, the catalytic activity of cPLA2α plays an important role in cellular metabolism in healthy as well as cancer cells. There is mounting evidence suggesting that cPLA2α is an interesting target for cancer treatment; however, it is unclear which cancers are most relevant for further investigation. Here we report the relative expression of cPLA2α in a variety of cancers and cancer cell lines using publicly available datasets. The profiling of a panel of cancer cell lines representing different tissue origins suggests that hematological malignancies are particularly sensitive to the growth inhibitory effect of cPLA2α inhibition. Several hematological cancers and cancer cell lines overexpressed cPLA2α, including multiple myeloma. Multiple myeloma is an incurable hematological cancer of plasma cells in the bone marrow with an emerging requirement of therapeutic approaches. We show here that two cPLA2α inhibitors AVX420 and AVX002, significantly and dose-dependently reduced the viability of multiple myeloma cells and induced apoptosis in vitro. Our findings implicate cPLA2α activity in the survival of multiple myeloma cells and support further studies into cPLA2α as a potential target for treating hematological cancers, including multiple myeloma.
Natural Peptides Inducing Cancer Cell Death: Mechanisms and Properties of Specific Candidates for Cancer Therapeutics
Authors: Trinidad-Calderón Plinio A. , Varela-Chinchilla Carlos Daniel , García-Lara Silverio
Published: December 2021

Nowadays, cancer has become the second highest leading cause of death, and it is expected to continue to affect the population in forthcoming years. Additionally, treatment options will become less accessible to the public as cases continue to grow and disease mechanisms expand. Hence, specific candidates with confirmed anticancer effects are required to develop new drugs. Among the novel therapeutic options, proteins are considered a relevant source, given that they have bioactive peptides encrypted within their sequences. These bioactive peptides, which are molecules consisting of 2–50 amino acids, have specific activities when administered, producing anticancer effects. Current databases report the effects of peptides. However, uncertainty is found when their molecular mechanisms are investigated. Furthermore, analyses addressing their interaction networks or their directly implicated mechanisms are needed to elucidate their effects on cancer cells entirely. Therefore, relevant peptides considered as candidates for cancer therapeutics with specific sequences and known anticancer mechanisms were accurately reviewed. Likewise, those features which turn certain peptides into candidates and the mechanisms by which peptides mediate tumor cell death were highlighted. This information will make robust the knowledge of these candidate peptides with recognized mechanisms and enhance their non-toxic capacity in relation to healthy cells and further avoid cell resistance.
Antibiotics and the Nervous System—Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?
Authors: Hurkacz Magdalena , Dobrek Lukasz , Wiela-Hojeńska Anna
Published: December 2021

Antibiotics as antibacterial drugs have saved many lives, but have also become a victim of their own success. Their widespread abuse reduces their anti-infective effectiveness and causes the development of bacterial resistance. Moreover, irrational antibiotic therapy contributes to gastrointestinal dysbiosis, that increases the risk of the development of many diseases, including neurological and psychiatric. One of the potential options for restoring homeostasis is the use of oral antibiotics that are poorly absorbed from the gastrointestinal tract (e.g., rifaximin alfa). Thus, antibiotic therapy may exert neurological or psychiatric adverse drug reactions which are often considered to be overlooked and undervalued issues. Drug-induced neurotoxicity is mostly observed after beta-lactams and quinolones. Penicillin may produce a wide range of neurological dysfunctions, including encephalopathy, behavioral changes, myoclonus or seizures. Their pathomechanism results from the disturbances of gamma-aminobutyric acid-GABA transmission (due to the molecular similarities between the structure of the β-lactam ring and GABA molecule) and impairment of the functioning of benzodiazepine receptors (BZD). However, on the other hand, antibiotics have also been studied for their neuroprotective properties in the treatment of neurodegenerative and neuroinflammatory processes (e.g., Alzheimer’s or Parkinson’s diseases). Antibiotics may, therefore, become promising elements of multi-targeted therapy for these entities.
New Monoterpenoid Indoles with Osteoclast Activities from Gelsemium elegans
Authors: Wei Xin , Guo Rui , Wang Xiao , Liang Jia-Jun , Yu Hao-Fei , Ding Cai-Feng , Feng Ting-Ting , Zhang Li-Yan , Liu Xia , Hu Xin-Yue , Zhou Ying
Published: December 2021

The well-known toxic medicine Gelsemium elegans is widely and historically used to treat bone fracture and skin ulcers by the folk people of China. Two new monoterpenoid indole alkaloids, gelselegandines D and E, together with the known analogue gelegamine A were isolated from G. elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. All isolated compounds were tested for the effects on RANKL-induced osteoclast formation. Interestingly, gelselegandine E and gelegamine A, respectively, showed significant promoting and inhibitory activities on osteoclastogenesis, while gelselegandine D had no activity under the same concentration. This work suggested the different configurations for the carbons near the C-19/20 oxygen rings of the isolated compounds may be the key active groups on osteoclast formation and provided the evidence for the rationality as the traditional treatment for bone-related diseases of G. elegans.
Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets
Authors: Yapasert Rittibet , Khaw-on Patompong , Banjerdpongchai Ratana
Published: December 2021

COVID-19 is the name of the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in 2019. The virus–host-specific interactions, molecular targets on host cell deaths, and the involved signaling are crucial issues, which become potential targets for treatment. Spike protein, angiotensin-converting enzyme 2 (ACE2), cathepsin L-cysteine peptidase, transmembrane protease serine 2 (TMPRSS2), nonstructural protein 1 (Nsp1), open reading frame 7a (ORF7a), viral main protease (3C-like protease (3CLpro) or Mpro), RNA dependent RNA polymerase (RdRp) (Nsp12), non-structural protein 13 (Nsp13) helicase, and papain-like proteinase (PLpro) are molecules associated with SARS-CoV infection and propagation. SARS-CoV-2 can induce host cell death via five kinds of regulated cell death, i.e., apoptosis, necroptosis, pyroptosis, autophagy, and PANoptosis. The mechanisms of these cell deaths are well established and can be disrupted by synthetic small molecules or natural products. There are a variety of compounds proven to play roles in the cell death inhibition, such as pan-caspase inhibitor (z-VAD-fmk) for apoptosis, necrostatin-1 for necroptosis, MCC950, a potent and specific inhibitor of the NLRP3 inflammasome in pyroptosis, and chloroquine/hydroxychloroquine, which can mitigate the corresponding cell death pathways. However, NF-κB signaling is another critical anti-apoptotic or survival route mediated by SARS-CoV-2. Such signaling promotes viral survival, proliferation, and inflammation by inducing the expression of apoptosis inhibitors such as Bcl-2 and XIAP, as well as cytokines, e.g., TNF. As a result, tiny natural compounds functioning as proteasome inhibitors such as celastrol and curcumin can be used to modify NF-κB signaling, providing a responsible method for treating SARS-CoV-2-infected patients. The natural constituents that aid in inhibiting viral infection, progression, and amplification of coronaviruses are also emphasized, which are in the groups of alkaloids, flavonoids, terpenoids, diarylheptanoids, and anthraquinones. Natural constituents derived from medicinal herbs have anti-inflammatory and antiviral properties, as well as inhibitory effects, on the viral life cycle, including viral entry, replication, assembly, and release of COVID-19 virions. The phytochemicals contain a high potential for COVID-19 treatment. As a result, SARS-CoV-2-infected cell death processes and signaling might be of high efficacy for therapeutic targeting effects and yielding encouraging outcomes.
4-Azidocinnoline—Cinnoline-4-amine Pair as a New Fluorogenic and Fluorochromic Environment-Sensitive Probe
Authors: Danilkina Natalia A. , Andrievskaya Ekaterina V. , Vasileva Anna V. , Lyapunova Anna G. , Rumyantsev Andrey M. , Kuzmin Andrey A. , Bessonova Elena A. , Balova Irina A.
Published: December 2021

A new type of fluorogenic and fluorochromic probe based on the reduction of weakly fluorescent 4-azido-6-(4-cyanophenyl)cinnoline to the corresponding fluorescent cinnoline-4-amine was developed. We found that the fluorescence of 6-(4-cyanophenyl)cinnoline-4-amine is strongly affected by the nature of the solvent. The fluorogenic effect for the amine was detected in polar solvents with the strongest fluorescence increase in water. The environment-sensitive fluorogenic properties of cinnoline-4-amine in water were explained as a combination of two types of fluorescence mechanisms: aggregation-induced emission (AIE) and excited state intermolecular proton transfer (ESPT). The suitability of an azide–amine pair as a fluorogenic probe was tested using a HepG2 hepatic cancer cell line with detection by fluorescent microscopy, flow cytometry, and HPLC analysis of cells lysates. The results obtained confirm the possibility of the transformation of the azide to amine in cells and the potential applicability of the discovered fluorogenic and fluorochromic probe for different analytical and biological applications in aqueous medium.
Formation and Physical Stability of Zanthoxylum bungeanum Essential Oil Based Nanoemulsions Co-Stabilized with Tea Saponin and Synthetic Surfactant
Authors: Zeng Liya , Liu Yongchang , Yuan Zhihui , Wang Zhe
Published: December 2021

The purpose of this work was to evaluate the possibility of adding tea saponin (TS) to reduce the synthetic surfactant concentration, and maintain or improve the shelf stability of nanoemulsions. The Zanthoxylum bungeanum essential oil (2.5 wt%) loaded oil-in-water nanoemulsions were co-stabilized by Tween 40 (0.5–2.5 wt%) and TS (0.1–5 wt%). A combination of several analytical techniques, such as dynamic laser scattering, interfacial tension, zeta potential, and transmission electron microscope, were used for the characterization of nanoemulsions. Low levels of TS (0.1–0.5 wt%) with Tween 40 had significant effects on the emulsification, and a nanoemulsion with the smallest droplet diameter of 89.63 ± 0.67 nm was obtained. However, in the presence of high TS concentration (0.5–5 wt%), micelles generated by the non-adsorbed surfactants in the aqueous lead to droplets growth. In addition, the combinations of Tween 40 and TS at the high level (>3.5 wt%) exerted a synergistic effect on stabilizing the nanoemulsions and preventing both Ostwald ripening and coalescence. The negative charged TS endowed the droplets with electrostatic repulsion and steric hinderance appeared to prevent flocculation and coalescence. These results would provide a potential application of natural TS in the preparation and stabilization of nanoemulsions containing essential oil.
The Antioxidant Phytochemical Schisandrin A Promotes Neural Cell Proliferation and Differentiation after Ischemic Brain Injury
Authors: Zong Wentian , Gouda Mostafa , Cai Enli , Wang Ruofeng , Xu Weijie , Wu Yuming , Munekata Paulo E. S. , Lorenzo José M.
Published: December 2021

Schisandrin A (SCH) is a natural bioactive phytonutrient that belongs to the lignan derivatives found in Schisandra chinensis fruit. This study aims to investigate the impact of SCH on promoting neural progenitor cell (NPC) regeneration for avoiding stroke ischemic injury. The promoting effect of SCH on NPCs was evaluated by photothrombotic model, immunofluorescence, cell line culture of NPCs, and Western blot assay. The results showed that neuron-specific class III beta-tubulin (Tuj1) was positive with Map2 positive nerve fibers in the ischemic area after using SCH. In addition, Nestin and SOX2 positive NPCs were significantly (p < 0.05) increased in the penumbra and core. Further analysis identified that SCH can regulate the expression level of cell division control protein 42 (Cdc42). In conclusion, our findings suggest that SCH enhanced NPCs proliferation and differentiation possible by Cdc42 to regulated cytoskeletal rearrangement and polarization of cells, which provides new hope for the late recovery of stroke.
Isoflavone Changes in Immature and Mature Soybeans by Thermal Processing
Authors: Qu Shanshan , Kwon Soon Jae , Duan Shucheng , Lim You Jin , Eom Seok Hyun
Published: December 2021

The isoflavone changes occurring in mature soybeans during food processing have been well studied, but less information is available on the changes in immature soybeans during thermal processing. This study aimed to determine the effect of thermal processing by dry- or wet-heating on the changes in the isoflavone profiles of immature and mature soybeans. In the malonylglycoside forms of isoflavone, their deglycosylation was more severe after wet-heating than after dry-heating regardless of the soybean maturity. The malonyl forms of isoflavones in the immature seeds were drastically degraded after a short wet-heating process. In the acetylglycoside forms of isoflavone, dry-heating produced relatively low amounts of the acetyl types in the immature soybeans compared with those in the mature soybeans. These results were explained by the content of acetyldaidzin being relatively less changed after dry-heating immature soybeans but increasing four to five times in the mature soybeans. More of the other types of acetylglycoside were produced by dry-heating soybeans regardless of their maturity. Acetylgenistin in wet-heating was a key molecule because its content was unchanged in the immature soybeans during processing but increased in the mature soybeans. This determined the total acetylglycoside content after wet-heating. In contrast, most of the acetyl forms of isoflavone were produced after 90 to 120 min of dry-heating regardless of the seed maturity. It can be suggested that the pattern of isoflavone conversion was significantly affected by the innate water content of the seeds, with a lower water content in the mature soybeans leading to the greater production of acetyl isoflavones regardless of the processing method even if only applied for a relatively short time. The results suggested that the isoflavone conversion in the immature soybeans mainly follows the wet-heating process and can be promoted in the application of stronger processing.
Chemical and Bioactive Characterization of the Essential Oils Obtained from Three Mediterranean Plants
Authors: Xavier Virginie , Finimundy Tiane C. , Heleno Sandrina A. , Amaral Joana S. , Calhelha Ricardo C. , Vaz Josiana , Pires Tânia C. S. P. , Mediavilla Irene , Esteban Luis Saúl , Ferreira Isabel C. F. R. , Barros Lillian
Published: December 2021

Cupressus sempervirens L., Juniperus communis L. and Cistus ladanifer L. are Mediterranean arboreal and shrub species that possess essential oils (EO) in their leaves and branches. This study aimed at characterizing the EOs obtained by steam distillation from the three species collected in different locations from Spain (Almazán, Andévalo, Barriomartín, Cerezal, Ermitas and Huéscar). For this purpose, volatiles composition was determined by GC-MS, and different bioactivities were evaluated. The highest content in terpenes was observed in C. sempervirens (Huéscar origin) followed by J. communis (Almazán origin), corresponding to 92% and 91.9% of total compounds, respectively. With exception of C. ladanifer from Cerezal that presented viridiflorol as the most abundant compound, all the three species presented in common the α-pinene as the major compound. The EOs from C. ladanifer showed high antibacterial potential, presenting MIC values from 0.3 to 1.25 mg/mL. Concerning other bioactivities, C. ladanifer EO revealed an oxidation inhibition of 83%, while J. communis showed cytotoxicity in the MCF-7 cell line, and C. sempervirens and C. ladanifer EOs exhibited the highest potential on NCI-H460 cell lines. Nevertheless, some EOs revealed toxicity against non-tumoral cells but generally presented a GI50 value higher than that of the tumor cell lines.
Conjugated Metabolites of Hydroxytyrosol and Tyrosol Contribute to the Maintenance of Nitric Oxide Balance in Human Aortic Endothelial Cells at Physiologically Relevant Concentrations
Authors: Serreli Gabriele , Le Sayec Melanie , Diotallevi Camilla , Teissier Alice , Deiana Monica , Corona Giulia
Published: December 2021

Nitric oxide (NO) is an important signaling molecule involved in many pathophysiological processes. NO mediates vasodilation and blood flow in the arteries, and its action contributes to maintaining vascular homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium. Dietary antioxidants and their metabolites have been found to be directly and/or indirectly involved in the modulation of the intracellular signals that lead to the production of NO. The purpose of this study was to investigate the contribution of conjugated metabolites of hydroxytyrosol (HT) and tyrosol (TYR) to the release of NO at the vascular level, and the related mechanism of action, in comparison to their parental forms. Experiments were performed in human aortic endothelial cells (HAEC) to evaluate the superoxide production, the release of NO and production of cyclic guanosine monophosphate (cGMP), the activation of serine/threonine-protein kinase 1 (Akt1), and the activation state of endothelial nitric oxide synthase (eNOS). It was observed that the tested phenolic compounds enhanced NO and cGMP concentration, inhibiting its depletion caused by superoxide overproduction. Moreover, some of them enhanced the activation of Akt (TYR, HT metabolites) and eNOS (HT, HVA, TYR-S, HT-3S). Overall, the obtained data showed that these compounds promote NO production and availability, suggesting that HT and TYR conjugated metabolites may contribute to the effects of parental extra virgin olive oil (EVOO) phenolics in the prevention of cardiovascular diseases.
Structural and Functional Changes of Reconstituted High-Density Lipoprotein (HDL) by Incorporation of α-synuclein: A Potent Antioxidant and Anti-Glycation Activity of α-synuclein and apoA-I in HDL at High Molar Ratio of α-synuclein
Authors: Cho Kyung-Hyun
Published: December 2021

α-synuclein (α-syn) is a major culprit of Parkinson’s disease (PD), although lipoprotein metabolism is very important in the pathogenesis of PD. α-syn was expressed and purified using the pET30a expression vector from an E. coli expression system to elucidate the physiological effects of α-syn on lipoprotein metabolism. The human α-syn protein (140 amino acids) with His-tag (8 amino acids) was expressed and purified to at least 95% purity. Isoelectric focusing gel electrophoresis showed that the isoelectric point (pI) of α-syn and apoA-I were pI = 4.5 and pI = 6.4, respectively. The lipid-free α-syn showed almost no phospholipid-binding ability, while apoA-I showed rapid binding ability with a half-time (T1/2) = 8 ± 0.7 min. The α-syn and apoA-I could be incorporated into the reconstituted HDL (rHDL, molar ratio 95:5:1:1, palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC):cholesterol:apoA-I:α-syn with the production of larger particles (92 Å) than apoA-I-rHDL (86 and 78 Å) and α-syn-rHDL (65 Å). An rHDL containing both apoA-I and α-syn showed lower α-helicity around 45% with a red shift of the Trp wavelength maximum fluorescence (WMF) from 339 nm, while apoA-I-HDL showed 76% α-helicity and 337 nm of WMF. The denaturation by urea addition showed that the incorporation of α-syn in rHDL caused a larger increase in the WMF than apoA-I-rHDL, suggesting that the destabilization of the secondary structure of apoA-I by the addition of α-syn. On the other hand, the addition of α-syn induced two-times higher resistance to rHDL glycation at apoA-I:α-syn molar ratios of 1:1 and 1:2. Interestingly, low α-syn in rHDL concentrations, molar ratio of 1:0.5 (apoA-I:α-syn), did not prevent glycation with more multimerization of apoA-I. In the lipid-free and lipid-bound state, α-syn showed more potent antioxidant activity than apoA-I against cupric ion-mediated LDL oxidation. On the other hand, microinjection of α-syn (final 2 μM) resulted in 10% less survival of zebrafish embryos than apoA-I. A subcutaneous injection of α-syn (final 34 μM) resulted in less tail fin regeneration than apoA-I. Interestingly, incorporation of α-syn at a low molar ratio (apoA-I:α-syn, 1:0.5) in rHDL resulted destabilization of the secondary structure and impairment of apoA-I functionality via more oxidation and glycation. However, at a higher molar ratio of α-syn in rHDL (apoA-I:α-syn = 1:1 or 1:2) exhibited potent antioxidant and anti-glycation activity without aggregation. In conclusion, there might be a critical concentration of α-syn and apoA-I in HDL-like complex to prevent the aggregation of apoA-I via structural and functional enhancement.
The Effect of Multiplayer Video Games on Incidental and Intentional L2 Vocabulary Learning: The Case of Among Us
Authors: Calvo-Ferrer José Ramón , Belda-Medina Jose
Published: December 2021

Vocabulary learning has been traditionally considered central to second language learning. It may take place either intentionally, by means of deliberate attempts to commit factual information to memory, or incidentally, as a consequence of other cognitive processes involving comprehension. Video games, which have been extensively employed in educational contexts to understand lexical development in foreign languages, foster both exposure to and the production of authentic and meaning-focused vocabulary. An empirical study was conducted to explore the effect of playing an online multiplayer social deduction game (i.e., a game in which players attempt to uncover each other’s hidden role) on incidental and intentional second language (L2) vocabulary learning. Secondary school pre-intermediate English as a Foreign Language (EFL) students (n = 54) took a vocabulary pre-test that identified eight unknown words likely to appear in the video game Among Us. Then, students were randomly assigned to different groups of players and to different learning conditions—within each group, half of the players were given a list of phrases containing such target words, which they were encouraged to meaningfully use in the game by means of written interaction. In doing so, students learnt some target words intentionally and provided contextualized incidental exposure to other players. They took a vocabulary test after two sessions of practice with the game to explore intentional and incidental L2 vocabulary learning gains. The pre- and post-tests suggested, among other results, that players using new L2 words in the game Among Us would retain more vocabulary than players only encountering them, that vocabulary intentionally input helped other users trigger incidental vocabulary learning, and that repetition had a positive effect on L2 vocabulary learning.
Efficient Recovery of Lithium Cobaltate from Spent Lithium-Ion Batteries for Oxygen Evolution Reaction
Authors: Arif Ayesha , Xu Ming , Rashid Jamshaid , Saraj Chaudry Sajed , Li Wei , Akram Bilal , Hu Binbin
Published: December 2021

Owing to technological advancements and the ever-increasing population, the search for renewable energy resources has increased. One such attempt at finding effective renewable energy is recycling of lithium-ion batteries and using the recycled material as an electrocatalyst for the oxygen evolution reaction (OER) step in water splitting reactions. In electrocatalysis, the OER plays a crucial role and several electrocatalysts have been investigated to improve the efficiency of O2 gas evolution. Present research involves the use of citric acid coupled with lemon peel extracts for efficient recovery of lithium cobaltate from waste lithium-ion batteries and subsequent use of the recovered cathode material for OER in water splitting. Optimum recovery was achieved at 90 °C within 3 h of treatment with 1.5 M citric acid and 1.5% extract volume. The consequent electrode materials were calcined at 600, 700 and 800 °C and compared to the untreated waste material calcined at 600 °C for OER activity. The treated material recovered and calcined at 600 °C was the best among all of the samples for OER activity. Its average particle size was estimated to be within the 20–100 nm range and required a low overpotential of 0.55 V vs. RHE for the current density to reach 10 mA/cm2 with a Tafel value of 128 mV/dec.
Molecular and Functional Characterization of Caveolae in Mixed Cultures of Human NT-2 Neurons and Astrocytes
Authors: Sandhu Jagdeep K. , Ribecco-Lutkiewicz Maria , Abulrob Abedelnasser
Published: December 2021

Caveolae are plasma membrane invaginations that are enriched in cholesterol-binding proteins called caveolins. The presence of caveolae and caveolins in mixed cultures of human neurons and glia has not been investigated. Here, we sought to determine the presence of caveolae and caveolins in human NTera-2 (NT2/D1) cells, differentiated with retinoic acid into neuron-like (NT2/N) and astrocyte-like (NT2/A) cells. We found that while caveolin-3 mRNA levels remained relatively constant, caveolin-1 and -2 levels were upregulated in NT2/A and downregulated in NT2/N. No caveolin-1 immunoreactivity was detected in NT2/N. Electron microscopy revealed numerous flask-shaped invaginations (~86–102 nm in diameter) in the plasma membrane of NT2/A and NT2/N cells, while only few were detected in NT2/D1 cells. Immunoelectron microscopy localized caveolin-1 gold particles in the flask-shaped structures on plasmalemma and cytoplasmic vesicles of NT2/A cells. Furthermore, NT2/A endocytosed Alexa 488 conjugated-cholera toxin B subunit (CTX-B) through a caveolae- and clathrin-dependent pathway, whereas NT2/N endocytosed CTX-B through a caveolae-independent pathway. We have established that while NT2/A expressed functional caveolae, the molecular identity of the plasma membrane invaginations in NT2/N is unknown. The expression of caveolin proteins was differentially regulated in these cells. Taken together, our findings support the usefulness of the human NT2 model system to study the role of caveolins in neuron–glia communication, and their involvement in brain health and disease.
Preferential Metabolic Improvement by Intermittent Fasting in People with Elevated Baseline Red Cell Distribution Width: A Secondary Analysis of the WONDERFUL Randomized Controlled Trial
Authors: Horne Benjamin D. , Muhlestein Joseph B. , May Heidi T. , Le Viet T. , Bair Tami L. , Bennett Sterling T. , Knowlton Kirk U. , Anderson Jeffrey L.
Published: December 2021

Red cell distribution width (RDW) predicts cardiovascular outcomes, but it is unstudied with regard to intermittent fasting. In WONDERFUL trial subjects, the effect of the interaction between baseline RDW and intermittent fasting on changes in insulin and other cardiometabolic endpoints and the effect of fasting on changes in RDW were evaluated. The subjects enrolled were aged 21–70 years and were free of statins, anti-diabetes medications, and chronic diseases, and had ≥1 metabolic syndrome feature, as well as elevated low-density lipoprotein cholesterol. Subjects were randomized to 24-h, water-only fasting (twice per week for 4 weeks, once per week for 22 weeks) or 26 weeks of ad libitum eating. Subjects (N = 71; n = 38 intermittent fasting, n = 33 controls) had more substantial changes in insulin in intermittent fasting vs. controls (−3.45 ± 2.27 vs. 0.48 ± 3.55 mIU/L) when baseline RDW size distribution (RDW-SD) was ≥median (42.6 fL) than <median (−1.99 ± 2.80 vs. −1.08 ± 3.40 mIU/L) (p-interaction = 0.039). Results were similar but weaker for glucose, HOMA-IR, and metabolic syndrome score. RDW-SD (intermittent fasting: 1.27 ± 9.6 fL vs. control: −0.37 ± 1.76 fL, p = 0.34) was unchanged by fasting at 26 weeks. Intermittent fasting decreased insulin more in subjects with higher baseline RDW. RDW may identify individuals who derive the most health benefits from intermittent fasting and who have the most cause to adhere to a fasting regimen.
Vitamin D Status in Pediatric and Young Adult Cystic Fibrosis Patients. Are the New Recommendations Effective?
Authors: Mangas-Sánchez Carmen , Garriga-García María , Serrano-Nieto María Juliana , García-Romero Ruth , Álvarez-Beltrán Marina , Crehuá-Gaudiza Elena , Muñoz-Codoceo Rosana , Suárez-Cortina Lucrecia , Vicente-Santamaría Saioa , Martínez-Costa Cecilia , Díaz-Martin Juan José , Bousoño-García Carlos , González-Jiménez David
Published: December 2021

Introduction: In recent years, guidelines for vitamin D supplementation have been updated and prophylactic recommended doses have been increased in patients with cystic fibrosis (CF). Objective: To evaluate safety and efficacy of these new recommendations. Results: Two cohorts of pancreatic insufficient CF patients were compared before (cohort 1: 179 patients) and after (cohort 2: 71 patients) American CF Foundation and European CF Society recommendations were published. Cohort 2 patients received higher Vitamin D doses: 1509 (1306–1711 95% CI) vs 1084 (983–1184 95% CI) IU/Day (p < 0.001), had higher 25 OH vitamin D levels: 30.6 (27.9–33.26 95% CI) vs. 27.4 (25.9–28.8 95% CI) ng/mL (p = 0.028), and had a lower prevalence of insufficient vitamin D levels (<30 ng/mL): 48% vs 65% (p = 0.011). Adjusted by confounding factors, patients in cohort 1 had a higher risk of vitamin D insufficiency: OR 2.23 (1.09–4.57 95% CI) (p = 0.028). Conclusion: After the implementation of new guidelines, CF patients received higher doses of vitamin D and a risk of vitamin D insufficiency decreased. Despite this, almost a third of CF patients still do not reach sufficient serum calcidiol levels.
Consumption of Dairy Products and the Risk of Developing Breast Cancer in Polish Women
Authors: Wajszczyk Bożena , Charzewska Jadwiga , Godlewski Dariusz , Zemła Brunon , Nowakowska Elżbieta , Kozaczka Maciej , Chilimoniuk Małgorzata , Pathak Dorothy R.
Published: December 2021

Lack of consistency in the relationship between dairy products consumption and breast cancer (BC) risk motivated us to evaluate this association in a case-control study of BC among Polish women. The study includes 1699 women 26–79 years of age, 823 BC cases identified in Cancer Registries and 876 randomly selected controls from the national population registry. Using a validated, semiquantitative food frequency questionnaire (FFQ), the consumption of dairy products was collected for a time period of 10–15 years prior to BC diagnosis. We used logistic regression, adjusting for potential confounders, to assess the relationship between total dairy consumption as well as individual dairy groups of milk, cottage cheese and hard cheese and BC risk for premenopausal and postmenopausal women. For total consumption, a significant decrease in BC risk was observed with increased consumption of one serving/week, OR trend = 0.98, 2% decrease in risk, for premenopausal women only. For milk, a significant decrease in BC risk was observed for an increase in consumption of one glass/week, OR trend = 0.95, 5% decrease, in both strata of menopause. In contrast, for hard cheese, a significant increase in the risk of 10% was observed only in premenopausal women, OR trend = 1.10. Cottage cheese consumption significantly reduced BC risk by 20%, OR trend = 0.80, for an increase in one serving/week for postmenopausal women only. Our results show that individual dairy products have a statistically significant but bi-directional relationship with BC risk, which differs for premenopausal and postmenopausal women.
3D-Printed Coating of Extended-Release Matrix Tablets: Effective Tool for Prevention of Alcohol-Induced Dose Dumping Effect
Authors: Skalická Barbora , Matzick Kevin , Komersová Alena , Svoboda Roman , Bartoš Martin , Hromádko Luděk
Published: December 2021

Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances.