bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Health-Related Behavior Interventions on Physical Activity-Related Injuries in Junior Middle School Students
Authors: Tang Dongchun , Cai Weicong , Yang Wenda , Chen Shangmin , Li Liping
Published: March 2022

The objective of this study was to determine the effectiveness of an intervention program based on Health-Related Behavior Theory (HRBT) in reducing physical activity-related injuries (PARIs) occurrence and individual risk-taking behaviors, as well as improving PA-related behaviors. A total of 1044 students from six junior middle schools in Shantou city were included and divided randomly into an intervention group (n = 550) and a control group (n = 494), respectively. The intervention group followed a prescribed PARIs intervention program based on HRBT, and the control group performed a common health education program, consisting of seven sessions and lasting seven months from May to November 2018. After the intervention, both groups showed a significantly lower prevalence of PARIs (intervention group: from 25.45% to 10.91%, control group: from 29.76% to 11.74%, both p < 0.05), but no significant between-group differences could be observed in the post-intervention PARIs prevalence (p > 0.05). Compared with the control group, students in the intervention group had a higher improvement in PA-related behaviors and a lower score of risk-taking behaviors (both p < 0.05). Thus, it could be concluded that the HRBT intervention program had a positive effect on PA-related and risk-taking behaviors in junior middle school students, though its effectiveness in reducing the occurrence of PARIs was not significant.
An Attention-Based Multi-Representational Fusion Method for Social-Media-Based Text Classification
Authors: Liu Jing , Wang Xiaoying , Tan Yan , Huang Lihua , Wang Yue
Published: March 2022

There exist various text-classification tasks using user-generated contents (UGC) on social media in the big data era. In view of advantages and disadvantages of feature-engineering-based machine-learning models and deep-learning models, we argue that fusing handcrafted-text representation via feature engineering and data-driven deep-text representations extracted by performing deep-learning methods is conducive to enhancing text-classification capability. Given the characteristics of different deep neural networks, their complementary effect needs to be investigated. Moreover, contributions of these representations need to be adaptively learned when it comes to addressing different tasks or predicting different samples. Therefore, in this paper, we propose a novel fused deep-neural-network architecture with a hierarchical attention mechanism for text classification with social media data. Specifically, in the context that handcraft features are available, we employ the attention mechanism to adaptively fuse totally data-driven-text representation and handcrafted representation. For the generation of the data-driven-text representation, we propose a data-driven encoder that fuses text representations derived from three deep-learning methods with the attention mechanism, to adaptively select discriminative representation and explore their complementary effect. To verify the effectiveness of our approach, we performed two text-classification tasks, i.e., identifying adverse drug reaction (ADR)-relevant tweets from social media and identifying comparative-relevant reviews from an E-commerce platform. Experimental results demonstrate that our approach outperforms other baselines.
Transitioning from Multichannel to Omnichannel Customer Experience in Service-Based Companies: Challenges and Coping Strategies
Authors: Gerea Carmen , Herskovic Valeria
Published: March 2022

Omnichannel as a strategy has long been associated with retailing, but service-based organizations have been increasingly embracing it with the help of digital technologies. Moving from a multichannel to an omnichannel service-based organization is a challenge per se; we aim to add to the discussion an understanding from a customer experience (CX) management point of view. Our goals are to (1) understand the key factors to unlock omnichannel capabilities, (2) identify the challenges of becoming an omnichannel service-based organization, and (3) propose a set of strategies to overcome them. We interviewed practitioners in key roles in traditional industries such as banking, insurance, and telecommunications. Based on the findings, we introduce and validate a conceptual framework, which includes enablers, challenges, drivers, and contextual factors, for the transition process from a multichannel to an omnichannel customer-experience-oriented organization.
Fabrication and Characterization of Highly Efficient As-Synthesized WO3/Graphitic-C3N4 Nanocomposite for Photocatalytic Degradation of Organic Compounds
Authors: Hussien Mai S. A. , Bouzidi Abdelfatteh , Abd-Rabboh Hisham S. M. , Yahia Ibrahim S. , Zahran Heba Y. , Abdel-wahab Mohamed Sh. , Alharbi Walaa , Awwad Nasser S. , Ibrahim Medhat A.
Published: March 2022

The incorporation of tungsten trioxide (WO3) by various concentrations of graphitic carbon nitride (g-C3N4) was successfully studied. X-ray diffraction (XRD), Scanning Electron Microscope (SEM), and Diffused Reflectance UV-Vis techniques were applied to investigate morphological and microstructure analysis, diffused reflectance optical properties, and photocatalysis measurements of WO3/g-C3N4 photocatalyst composite organic compounds. The photocatalytic activity of incorporating WO3 into g-C3N4 composite organic compounds was evaluated by the photodegradation of both Methylene Blue (MB) dye and phenol under visible-light irradiation. Due to the high purity of the studied heterojunction composite series, no observed diffraction peaks appeared when incorporating WO3 into g-C3N4 composite organic compounds. The particle size of the prepared composite organic compound photocatalysts revealed no evident influence through the increase in WO3 atoms from the SEM characteristic. The direct and indirect bandgap were recorded for different mole ratios of WO3/g-C3N4, and indicated no apparent impact on bandgap energy with increasing WO3 content in the composite photocatalyst. The composite photocatalysts’ properties better understand their photocatalytic activity degradations. The pseudo-first-order reaction constants (K) can be calculated by examining the kinetic photocatalytic activity.
Many-Scale Investigations of the Deformation Behavior of Polycrystalline Composites: I—Machine Learning Applied for Image Segmentation
Authors: Schneider Yanling , Prabhu Vighnesh , Höss Kai , Wasserbäch Werner , Schmauder Siegfried , Zhou Zhangjian
Published: March 2022

Our work investigates the polycrystalline composite deformation behavior through multiscale simulations with experimental data at hand. Since deformation mechanisms on the micro-level link the ones on the macro-level and the nanoscale, it is preferable to perform micromechanical finite element simulations based on real microstructures. The image segmentation is a necessary step for the meshing. Our 2D EBSD images contain at least a few hundred grains. Machine learning (ML) was adopted to automatically identify subregions, i.e., individual grains, to improve local feature extraction efficiency and accuracy. Denoising in preprocessing and postprocessing before and after ML, respectively, is beneficial in high quality feature identification. The ML algorithms used were self-developed with the usage of inherent code packages (Python). The performances of the three supervised ML models—decision tree, random forest, and support vector machine—are compared herein; the latter two achieved accuracies of up to 99.8%. Calculations took about 0.5 h from the original input dataset (EBSD image) to the final output (segmented image) running on a personal computer (CPU: 3.6 GHz). For a realizable manual pixel sortation, the original image was firstly scaled from the initial resolution 10802 pixels down to 3002. After ML, some manual work was necessary due to the remaining noises to achieve the final image status ready for meshing. The ML process, including this manual work time, improved efficiency by a factor of about 24 compared to a purely manual process. Simultaneously, ML minimized the geometrical deviation between the identified and original features, since it used the original resolution. For serial work, the time efficiency would be enhanced multiplicatively.
Compounding a High-Permittivity Thermoplastic Material and Its Applicability in Manufacturing of Microwave Photonic Crystals
Authors: Mazzei Capote Gerardo Andres , Montoya-Ospina Maria Camila , Liu Zijie , Mattei Michael Sabatini , Liu Boyuan , Delgado Aidan P. , Yu Zongfu , Goldsmith Randall H. , Osswald Tim Andreas
Published: March 2022

Additive Manufacturing (AM) techniques allow the production of complex geometries unattainable through other traditional technologies. This advantage lends itself well to rapidly iterating and improving upon the design of microwave photonic crystals, which are structures with intricate, repeating features. The issue tackled by this work involves compounding a high-permittivity material that can be used to produce 3D microwave photonic structures using polymer extrusion-based AM techniques. This material was acrylonitrile butadiene styrene (ABS)-based and used barium titanate (BaTiO3) ceramic as the high-permittivity component of the composite and involved the use of a surfactant and a plasticizer to facilitate processing. Initial small amounts of the material were compounded using an internal batch mixer and studied using polymer thermal analysis techniques, such as thermogravimetric analysis, rheometry, and differential scanning calorimetry to determine the proper processing conditions. The production of the material was then scaled up using a twin-screw extruder system, producing homogeneous pellets. Finally, the thermoplastic composite was used with a screw-based, material extrusion additive manufacturing technique to produce a slab for measuring the relative permittivity of the material, as well as a preliminary 3D photonic crystal. The real part of the permittivity was measured to be 12.85 (loss tangent = 0.046) in the range of 10 to 12 GHz, representing the highest permittivity ever demonstrated for a thermoplastic AM composite at microwave frequencies.
Tensile Properties and Microstructure Evolutions of Low-Density Duplex Fe–12Mn–7Al–0.2C–0.6Si Steel
Authors: Liu Shuai , Ge Yinlei , Liu Huanyou , Liu Junyu , Feng Yunli , Chen Chen , Zhang Fucheng
Published: March 2022

An austenite-ferrite duplex low-density steel (Fe–12Mn–7Al–0.2C–0.6Si, wt%) was designed and fabricated by cold rolling and annealing at different temperatures. The tensile properties, microstructure evolution, deformation mechanism and stacking fault energy (SFE) of the steel were systemically investigated at ambient temperature. Results show two phases of fine equiaxed austenite and coarse band-like δ-ferrite in the microstructure of the steel. With increasing annealing temperature, the yield and tensile strengths decrease while the total elongation increases. At initial strains, the deformation is mainly concentrated in the fine austenite and grain boundaries of the coarse δ-ferrite, and the interior of the coarse δ-ferrite gradually deforms with further increase in the strain to 0.3. No twinning-induced plasticity (TWIP) or transformation-induced plasticity (TRIP) occurred during the tensile deformation. Considering element segregation and two-phase proportion, the chemical composition of austenite was measured more precisely. The SFE of the austenite is 39.7 mJ/m2, and the critical stress required to produce deformation twins is significantly higher than the maximum flow stress of the steel.
Mesoscopic Fluid-Particle Flow and Vortex Structural Transmission in a Submerged Entry Nozzle of Continuous Caster
Authors: Zhao Peng , Piao Rongxun , Zou Zongshu
Published: March 2022

Understanding the essence of the flow oscillations within a submerged-entry nozzle (SEN) is essential to control flow patterns in the continuous casting mold and consequently increase the superficial quality of steel products. A numerical study of the mesoscopic fluid-particle flow in a bifurcated pool-type SEN under steady operating conditions is conducted using the lattice Boltzmann method (LBM) coupled with the large eddy simulation (LES) model. The accuracy of the model has been verified by comparing vortex structures and simulated velocities with published experimental values. The LBM modeling is also verified by comparing the “stair-step” jet patterns observed in the experiment. The geometrical parameters and operational conditions of physical experiments are reproduced in the simulations. By comparing the time-averaged velocities of Reynolds-averaged Navier–Stokes equations (RANS) with LBM models, transient mesoscopic fluid-particles and related vortex structures can be better reproduced within the SEN. The visualization of internal flow within the SEN is illustrated through the mass-less Discrete Phase Model (DPM) model. The trajectories show that the LBM–LES–DPM coupled model is good at predicting the transient vortical flow within the SEN. A large vortex is found inside the exit port and continuously changes in shape and size therein. The monitoring points and lines within the SEN are selected to illustrate the velocity variations and effective viscosity, which can reflect the oscillating characteristics even under stable operating conditions without changes at the exit from the SEN. Furthermore, the formation, development, diffusion, and dissipation of the vortex structures from the exit port of the SEN are also investigated using the Q criteria. The comparison of the power spectrum with high-frequency components along the exit port indicates that the flow oscillations must originate from within the SEN and are intensified in the exit port. The mesoscopic LBM model can replicate the fluid-particle flow and vortex structure transmission as well as their turbulence effects inside the SEN in detail.
Effects of Graphene Oxide and Crumb Rubber on the Fresh Properties of Self-Compacting Engineered Cementitious Composite Using Response Surface Methodology
Authors: Abdulkadir Isyaka , Mohammed Bashar S. , Ali Montasir Osman Ahmed , Liew M. S.
Published: March 2022

Graphene oxide-modified rubberized engineered cementitious composite (GO-RECC) is attracting the attention of researchers because of the reported benefits of the GO and crumb rubber (CR) on the strength and deformation properties of the composite. While it is well established that GO negatively affects the workability of cementitious composites, its influence on the attainment of the desired self-compacting (SC) properties of ECC has not yet been thoroughly investigated, especially when combined with crumb rubber (CR). In addition, to simplify the number of trial mixes involved in designing SC-GO-RECC, there is a need to develop and optimize the process using Design of Experiment (DOE) methods. Hence, this research aims to investigate and model using response surface methodology (RSM), the combined effects of the GO and CR on the SC properties of ECC through the determination of T500, slump flow, V-funnel, and L-box ratio of the SC-GORECC as the responses, following the European Federation of National Associations Representing for Concrete (EFNARC) 2005 specifications. The input factors considered were the GO by wt.% of cement (0.02, 0.04, 0.06, and 0.08) and CR as a replacement of fine aggregate by volume (5, 10, and 15%). The results showed that increasing the percentages of GO and CR affected the fresh properties of the SC-GORECC adversely. However, all mixes have T500 of 2.4 to 5.2 s, slump flow of 645 to 800 mm, V-funnel time of 7.1 to 12.3 s, and L-box ratio (H2/H1) of 0.8 to 0.98, which are all within acceptable limits specified by EFNARC 2005. The developed response prediction models were well fitted with R2 values ranging from 91 to 99%. Through the optimization process, optimal values of GO and CR were found to be 0.067% and 6.8%, respectively, at a desirability value of 1.0.
Anti-Hair Loss Effect of Adenosine Is Exerted by cAMP Mediated Wnt/β-Catenin Pathway Stimulation via Modulation of Gsk3β Activity in Cultured Human Dermal Papilla Cells
Authors: Kim Jaeyoon , Shin Jae Young , Choi Yun-Ho , Kang Nae Gyu , Lee Sanghwa
Published: March 2022

In the present study, we investigated the molecular mechanisms of adenosine for its hair growth promoting effect. Adenosine stimulated the Wnt/β-catenin pathway by modulating the activity of Gsk3β in cultured human dermal papilla cells. It also activated adenosine receptor signaling, increasing intracellular cAMP level, and subsequently stimulating the cAMP mediated cellular energy metabolism. The phosphorylation of CREB, mTOR, and GSK3β was increased. Furthermore, the expression of β-catenin target genes such as Axin2, Lef1, and growth factors (bFGF, FGF7, IGF-1) was also enhanced. The inhibitor study data conducted in Wnt reporter cells and in cultured human dermal papilla cells demonstrated that adenosine stimulates Wnt/β-catenin signaling through the activation of the adenosine receptor and Gsk3β plays a critical role in transmitting the signals from the adenosine receptor to β-catenin, possibly via the Gαs/cAMP/PKA/mTOR signaling cascade.
Structural Insights into the Design of Synthetic Nanobody Libraries
Authors: Valdés-Tresanco Mario S. , Molina-Zapata Andrea , Pose Alaín González , Moreno Ernesto
Published: March 2022

Single domain antibodies from camelids, or nanobodies, are a unique class of antibody fragments with several advantageous characteristics: small monomeric size, high stability and solubility and easy tailoring for multiple applications. Nanobodies are gaining increasing acceptance as diagnostic tools and promising therapeutic agents in cancer and other diseases. While most nanobodies are obtained from immunized animals of the camelid family, a few synthetic nanobody libraries constructed in recent years have shown the capability of generating high quality nanobodies in terms of affinity and stability. Since this synthetic approach has important advantages over the use of animals, the recent advances are indeed encouraging. Here we review over a dozen synthetic nanobody libraries reported so far and discuss the different approaches followed in their construction and validation, with an emphasis on framework and hypervariable loop design as critical issues defining their potential as high-class nanobody sources.
Isolation and Structural Elucidation of Compounds from Pleiocarpa bicarpellata and Their In Vitro Antiprotozoal Activity
Authors: Sevik Kilicaslan Ozlem , Cretton Sylvian , Quirós-Guerrero Luis , Bella Merveilles A. , Kaiser Marcel , Mäser Pascal , Ndongo Joseph T. , Cuendet Muriel
Published: March 2022

Species of the genus Pleiocarpa are used in traditional medicine against fever and malaria. The present study focuses on the isolation and identification of bioactive compounds from P. bicarpellata extracts, and the evaluation of their antiprotozoal activity. Fractionation and isolation combined to LC-HRMS/MS-based dereplication provided 16 compounds: seven indole alkaloids, four indoline alkaloids, two secoiridoid glycosides, two iridoid glycosides, and one phenolic glucoside. One of the quaternary indole alkaloids (7) and one indoline alkaloid (15) have never been reported before. Their structures were elucidated by analysis of spectroscopic data, including 1D and 2D NMR experiments, UV, IR, and HRESIMS data. The absolute configurations were determined by comparison of the experimental and calculated ECD data. The extracts and isolated compounds were evaluated for their antiprotozoal activity towards Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum, as well as for their cytotoxicity against rat skeletal myoblast L6 cells. The dichloromethane/methanol (1:1) root extract showed strong activity against P. falciparum (IC50 value of 3.5 µg/mL). Among the compounds isolated, tubotaiwine (13) displayed the most significant antiplasmodial activity with an IC50 value of 8.5 µM and a selectivity index of 23.4. Therefore, P. bicarpallata extract can be considered as a source of indole alkaloids with antiplasmodial activity.
Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance
Authors: Leonardo-Sousa Carlota , Carvalho Andreia Neves , Guedes Romina A. , Fernandes Pedro M. P. , Aniceto Natália , Salvador Jorge A. R. , Gama Maria João , Guedes Rita C.
Published: March 2022

Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literature. In this review, we discuss the development of proteasome inhibitors and the mechanisms of innate and acquired resistance to their activity—a major challenge in preclinical and clinical therapeutics. An improved understanding of these mechanisms is crucial to guiding the design of new and more effective drugs to tackle these devastating diseases. In addition, we provide a comprehensive overview of proteasome inhibitors used in combination with other chemotherapeutic agents, as this is a key strategy to combat resistance.
Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety
Authors: Bui Hue Thi Buu , Nguyen Phuong Hong , Pham Quan Minh , Tran Hoa Phuong , Tran De Quang , Jung Hosun , Hong Quang Vinh , Nguyen Quoc Cuong , Nguyen Quy Phu , Le Hieu Trong , Yang Su-Geun
Published: March 2022

Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures. Five compounds exhibited antiproliferative activity with IC50 values of 3.4–37.8 µM. Compound 8 with a 2-mercaptoquinazolinone cap moiety displayed the highest antiproliferative efficacy against MCF-7 cells. For the HDAC6 target selectivity study, compound 8 displayed an IC50 value of 2.3 µM, which is 29.3 times higher than those of HDAC3, HDAC4, HDAC8, and HDAC11. Western blot assay proved that compound 8 strongly inhibited tubulin acetylation, a substrate of HDAC6. Compound 8 also displayed stronger inhibition activity against HDAC11 than the control drug Belinostat. The inhibitory mechanism of action of compound 8 on HDAC enzymes was then explored using molecular docking study. The data revealed a high binding affinity (−7.92 kcal/mol) of compound 8 toward HDAC6. In addition, dock pose analysis also proved that compound 8 might serve as a potent inhibitor of HDAC11.
The Theoretical and Experimental Investigation of the Fluorinated Palladium β-Diketonate Derivatives: Structure and Physicochemical Properties
Authors: Dorovskikh Svetlana I. , Tryakhov Denis E. , Klyamer Darya D. , Sukhikh Alexander S. , Mirzaeva Irina V. , Morozova Natalia B. , Basova Tamara V.
Published: March 2022

To search for new suitable Pd precursors for MOCVD/ALD processes, the extended series of fluorinated palladium complexes [Pd(CH3CXCHCO(R))2] with β-diketone [tfa−1,1,1-trifluoro-2,4-pentanedionato (1); pfpa−5,5,6,6,6-pentafluoro-2,4-hexanedionato (3); hfba−5,5,6,6,7,7,7-heptafluoro-2,4-heptanedionato (5)] and β-iminoketone [i-tfa−1,1,1-trifluoro-2-imino-4-pentanonato (2); i-pfpa−5,5,6,6,6-pentafluoro-2-imino-4-hexanonato (4); i-hfba-5,5,6,6,7,7,7-heptafluoro-2-imino-4-heptanonato (6)] ligands were synthesized with 70–80% yields and characterized by a set of experimental (SXRD, XRD, IR, NMR spectroscopy, TG) and theoretical (DFT, Hirshfeld surface analysis) methods. Solutions of Pd β-diketonates contained both cis and trans isomers, while only trans isomers were detected in the solutions of Pd β-iminoketonates. The molecules 2–6 and new polymorphs of complexes 3 and 5 were arranged preferentially in stacks, and the distance between molecules in the stack generally increased with elongation of the fluorine chain in ligands. The H…F contacts were the main ones involved in the formation of packages of molecules 1–2, and C…F, F…F, NH…F contacts appeared in the structures of complexes 4–6. The stability of complexes and their polymorphs in the crystal phases were estimated from DFT calculations. The TG data showed that the volatility differences between Pd β-iminoketonates and Pd β-diketonates were minimized with the elongation of the fluorine chain in the ligands.
A Rapid LC-MS/MS-PRM Assay for Serologic Quantification of Sialylated O-HPX Glycoforms in Patients with Liver Fibrosis
Authors: Panigrahi Aswini , Benicky Julius , Wei Renhuizi , Ahn Jaeil , Goldman Radoslav , Sanda Miloslav
Published: March 2022

Development of high throughput robust methods is a prerequisite for a successful clinical use of LC-MS/MS assays. In earlier studies, we reported that nLC-MS/MS measurement of the O-glycoforms of HPX is an indicator of liver fibrosis. In this study, we show that a microflow LC-MS/MS method using a single column setup for capture of the analytes, desalting, fast gradient elution, and on-line mass spectrometry measurements, is robust, substantially faster, and even more sensitive than our nLC setup. We demonstrate applicability of the workflow on the quantification of the O-HPX glycoforms in unfractionated serum samples of control and liver disease patients. The assay requires microliter volumes of serum samples, and the platform is amenable to one hundred sample injections per day, providing a valuable tool for biomarker validation and screening studies.
Effects of Abelmoschus manihot Flower Extract on Enhancing Sexual Arousal and Reproductive Performance in Zebrafish
Authors: Chang Chi-Chang , Houng Jer-Yiing , Peng Wei-Hao , Yeh Tien-Wei , Wang Yun-Ya , Chen Ya-Ling , Chang Tzu-Hsien , Hung Wei-Chin , Yu Teng-Hung
Published: March 2022

The flower of Abelmoschus manihot L. is mainly used for the treatment of chronic kidney diseases, and has been reported to have bioactivities such as antioxidant, anti-inflammatory, antiviral, and antidepressant activities. This study used wild-type adult zebrafish as an animal model to elucidate the potential bioactivity of A. manihot flower ethanol extract (AME) in enhancing their sexual and reproductive functions. Zebrafish were fed AME twice a day at doses of 0.2%, 1%, and 10% for 28 days, and were then given the normal feed for an additional 14 days. The hormone 17-β estradiol was used as the positive control. Sexual behavioral parameters such as the number of times males chased female fish, the production of fertilized eggs, and the hatching rate of the fertilized eggs were recorded at days 0.33, 7, 14, 21, 28, and 42. The expression levels of sex-related genes—including lhcgr, ar, cyp19a1a, and cyp19a1b—were also examined. The results showed that the chasing number, fertilized egg production, and hatching rate were all increased with the increase in the AME treatment dose and treatment time. After feeding with 1% and 10% AME for 28 days, the chasing number in the treated group as compared to the control group increased by 1.52 times and 1.64 times, respectively; the yield of fertilized eggs increased by 1.59 times and 2.31 times, respectively; and the hatching rate increased by 1.26 times and 1.69 times, respectively. All three parameters exhibited strong linear correlations with one another (p < 0.001). The expression of all four genes was also upregulated with increasing AME dose and treatment duration. When feeding with 0.2%, 1%, and 10% AME for 28 days, the four sex-related genes were upregulated at ranges of 1.79–2.08-fold, 2.74–3.73-fold, and 3.30–4.66-fold, respectively. Furthermore, the effect of AME was persistent, as the promotion effect continued after the treatment was stopped for at least two weeks. The present findings suggest that AME can enhance the endocrine system and may improve libido and reproductive performance in zebrafish.
Anti-Cancer Activity of Buthus occitanus Venom on Hepatocellular Carcinoma in 3D Cell Culture
Authors: Lafnoune Ayoub , Lee Su-Yeon , Heo Jin-Yeong , Daoudi Khadija , Darkaoui Bouchra , Chakir Salma , Cadi Rachida , Mounaji Khadija , Shum David , Seo Haeng-Ran , Oukkache Naoual
Published: March 2022

Hepatocellular carcinoma (HCC) is the most dominant primary liver cancer, which can be caused by chronic hepatitis virus infections and other environmental factors. Resection, liver transplantation, and local ablation are only a few of the highly effective and curative procedures presently accessible. However, other complementary treatments can reduce cancer treatment side effects. In this present work, we evaluated the activity of Moroccan scorpion venom Buthus occitanus and its fractions obtained by chromatography gel filtration against HCC cells using a 3D cell culture model. The venom was fractionated by gel filtration chromatography, each fraction and the crude venom was tested on normal hepatocytes (Fa2N-4 cells). Additionally, the fractions and the crude venom were tested on MCTSs (multicellular tumor spheroids), and this latter was generated by cultivate Huh7.5 cancer cell line with WI38 cells, LX2 cells, and human endothelial cells (HUVEC). Our results indicate that Buthus occitanus venom toxin has no cytotoxic effects on normal hepatocytes. Moreover, it is reported that F3 fraction could significantly inhibit the MCTS cells. Other Protein Separation Techniques (High-performance liquid chromatography) are needed in order to identify the most active molecule.
Rhodamine 101 Conjugates of Triterpenoic Amides Are of Comparable Cytotoxicity as Their Rhodamine B Analogs
Authors: Heise Niels V. , Major Daniel , Hoenke Sophie , Kozubek Marie , Serbian Immo , Csuk René
Published: March 2022

Pentacyclic triterpenoic acids (betulinic, oleanolic, ursolic, and platanic acid) were selected and subjected to acetylation followed by the formation of amides derived from either piperazine or homopiperazine. These amides were coupled with either rhodamine B or rhodamine 101. All of these compounds were screened for their cytotoxic activity in SRB assays. As a result, the cytotoxicity of the parent acids was low but increased slightly upon their acetylation while a significant increase in cytotoxicity was observed for piperazinyl and homopiperazinyl amides. A tremendous improvement in cytotoxicity was observed; however, for the rhodamine B and rhodamine 101 conjugates, and compound 27, an ursolic acid derived homopiperazinyl amide holding a rhodamine 101 residue showed an EC50 = 0.05 µM for A2780 ovarian cancer cells while being less cytotoxic for non-malignant fibroblasts. To date, the rhodamine 101 derivatives presented here are the first examples of triterpene derivatives holding a rhodamine residue different from rhodamine B.
Metabolomic Profiling Reveals Protective Effects and Mechanisms of Sea Buckthorn Sterol against Carbon Tetrachloride-Induced Acute Liver Injury in Rats
Authors: Sheng Changting , Guo Yang , Ma Jing , Hong Eun-Kyung , Zhang Benyin , Yang Yongjing , Zhang Xiaofeng , Zhang Dejun
Published: March 2022

The present study was designed to examine the efficacy and protection mechanisms of sea buckthorn sterol (SBS) against acute liver injury induced by carbon tetrachloride (CCl4) in rats. Five-week-old male Sprague-Dawley (SD) rats were divided into six groups and fed with saline (Group BG), 50% CCl4 (Group MG), or bifendate 200 mg/kg (Group DDB), or treated with low-dose (Group LD), medium-dose (Group MD), or high-dose (Group HD) SBS. This study, for the first time, observed the protection of SBS against CCl4-induced liver injury in rats and its underlying mechanisms. Investigation of enzyme activities showed that SBS-fed rats exhibited a significant alleviation of inflammatory lesions, as evidenced by the decrease in cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and gamma-glutamyl transpeptidase (γ-GT). In addition, compared to the MG group, the increased indices (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and total protein (TP)) of lipid peroxidation and decreased malondialdehyde (MDA) in liver tissues of SBS-treated groups showed the anti-lipid peroxidation effects of SBS. Using the wide range of targeted technologies and a combination of means (UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis), the addition of SBS was found to restore the expression of metabolic pathways (e.g., L-malic acid, N-acetyl-aspartic acid, N-acetyl-l-alanine, etc.) in rats, which means that the metabolic damage induced by CCl4 was alleviated. Furthermore, transcriptomics was employed to analyze and compare gene expression levels of different groups. It showed that the expressions of genes (Cyp1a1, Noct, and TUBB6) related to liver injury were regulated by SBS. In conclusion, SBS exhibited protective effects against CCl4-induced liver injury in rats. The liver protection mechanism of SBS is probably related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of the inflammatory response.
Curcumin: A Promising Tool to Develop Preventive and Therapeutic Strategies against Non-Communicable Diseases, Still Requiring Verification by Sound Clinical Trials
Authors: Masella Roberta , Cirulli Francesca
Published: March 2022

Curcumin is a pleiotropic compound found in the rhizome of Curcuma longa (turmeric) [...]
Special Issue “Dietary (Poly)Phenols and Health”
Authors: Mladěnka Přemysl
Published: March 2022

Interest in understanding the mechanisms of the positive effects of dietary phenolic and polyphenolic compounds on human health has markedly increased in recent years [...]
Free Zinc as a Predictive Marker for COVID-19 Mortality Risk
Authors: Maares Maria , Hackler Julian , Haupt Alessia , Heller Raban Arved , Bachmann Manuel , Diegmann Joachim , Moghaddam Arash , Schomburg Lutz , Haase Hajo
Published: March 2022

Free zinc is considered to be the exchangeable and biological active form of zinc in serum, and is discussed to be a suitable biomarker for alterations in body zinc homeostasis and related diseases. Given that coronavirus disease 2019 (COVID-19) is characterized by a marked decrease in total serum zinc, and clinical data indicate that zinc status impacts the susceptibility and severity of the infection, we hypothesized that free zinc in serum might be altered in response to SARS-CoV-2 infection and may reflect disease severity. To test this hypothesis, free zinc concentrations in serum samples of survivors and nonsurvivors of COVID-19 were analyzed by fluorometric microassay. Similar to the reported total serum zinc deficit measured by total reflection X-ray fluorescence, free serum zinc in COVID-19 patients was considerably lower than that in control subjects, and surviving patients displayed significantly higher levels of free zinc than those of nonsurvivors (mean ± SD; 0.4 ± 0.2 nM vs. 0.2 ± 0.1 nM; p = 0.0004). In contrast to recovering total zinc concentrations (r = 0.706, p < 0.001) or the declining copper–zinc ratio (r = −0.646; p < 0.001), free zinc concentrations remained unaltered with time in COVID-19 nonsurvivors. Free serum zinc concentrations were particularly low in male as compared to female patients (mean ± SD; 0.4 ± 0.2 nM vs. 0.2 ± 0.1 nM; p = 0.0003). This is of particular interest, as the male sex is described as a risk factor for severe COVID-19. Overall, results indicate that depressed free serum zinc levels are associated with increased risk of death in COVID-19, suggesting that free zinc may serve as a novel prognostic marker for the severity and course of COVID-19.
The Influence of Ketone Bodies on Circadian Processes Regarding Appetite, Sleep and Hormone Release: A Systematic Review of the Literature
Authors: Masi Davide , Spoltore Maria Elena , Rossetti Rebecca , Watanabe Mikiko , Tozzi Rossella , Caputi Alessandra , Risi Renata , Balena Angela , Gandini Orietta , Mariani Stefania , Spera Giovanni , Gnessi Lucio , Lubrano Carla
Published: March 2022

Chrononutrition is an emerging branch of chronobiology focusing on the profound interactions between biological rhythms and metabolism. This framework suggests that, just like all biological processes, even nutrition follows a circadian pattern. Recent findings elucidated the metabolic roles of circadian clocks in the regulation of both hormone release and the daily feeding–fasting cycle. Apart from serving as energy fuel, ketone bodies play pivotal roles as signaling mediators and drivers of gene transcription, promoting food anticipation and loss of appetite. Herein we provide a comprehensive review of the literature on the effects of the ketogenic diets on biological processes that follow circadian rhythms, among them appetite, sleep, and endocrine function.
Inverse Association of Plasma Vanadium Concentrations with Gestational Diabetes Mellitus
Authors: Li Xiaoqin , Zhu Yalun , Yin Jiawei , Li Ben , Li Peiyun , Cao Benfeng , Wang Qiang , Xu Jian , Liu Liegang
Published: March 2022

Vanadium compounds were identified to be beneficial for the control of glucose homeostasis. We aimed to explore the association of plasma vanadium (V) with gestational diabetes mellitus (GDM). We performed a case-control study including 252 newly diagnosed GDM cases and 252 controls matched by age, parity, and gestational age. Fasting blood samples were collected from each participant at GDM screening (≥24 weeks of gestation). The plasma concentrations of V were determined utilizing inductively coupled plasma mass spectrometry. Plasma V levels were significantly lower in the GDM group than those in the control group (p < 0.001). The adjusted OR (95% CI) of GDM comparing the highest V tertile with the lowest tertile was 0.35 (0.20–0.61). According to the cubic spline model, the relation between plasma V and odds of GDM was potentially nonlinear (p < 0.001). Moreover, plasma V was negatively correlated with 1-h post-glucose load, 2-h post-glucose load, and lipid metabolism indices (all p < 0.05). The present study indicates an inverse association of plasma V with GDM. Further prospective cohort studies are required to validate our results.
Nutrition for Brain Development
Authors: Mohajeri M. Hasan
Published: March 2022

This Special Issue focuses on the fundamental role of nutrition in brain development [...]
Bifidobacterium Species Colonization in Infancy: A Global Cross-Sectional Comparison by Population History of Breastfeeding
Authors: Taft Diana H. , Lewis Zachery T. , Nguyen Nhu , Ho Steve , Masarweh Chad , Dunne-Castagna Vanessa , Tancredi Daniel J. , Huda M. Nazmul , Stephensen Charles B. , Hinde Katie , von Mutius Erika , Kirjavainen Pirkka V. , Dalphin Jean-Charles , Lauener Roger , Riedler Josef , Smilowitz Jennifer T. , German J. Bruce , Morrow Ardythe L. , Mills David A.
Published: March 2022

Bifidobacterium species are beneficial and dominant members of the breastfed infant gut microbiome; however, their health benefits are partially species-dependent. Here, we characterize the species and subspecies of Bifidobacterium in breastfed infants around the world to consider the potential impact of a historic dietary shift on the disappearance of B. longum subsp. infantis in some populations. Across populations, three distinct patterns of Bifidobacterium colonization emerged: (1) The dominance of Bifidobacterium longum subspecies infantis, (2) prevalent Bifidobacterium of multiple species, and (3) the frequent absence of any Bifidobacterium. These patterns appear related to a country’s history of breastfeeding, with infants in countries with historically high rates of long-duration breastfeeding more likely to be colonized by B. longum subspecies infantis compared with infants in countries with histories of shorter-duration breastfeeding. In addition, the timing of infant colonization with B. longum subsp. infantis is consistent with horizontal transmission of this subspecies, rather than the vertical transmission previously reported for other Bifidobacterium species. These findings highlight the need to consider historical and cultural influences on the prevalence of gut commensals and the need to understand epidemiological transmission patterns of Bifidobacterium and other major commensals.
Is There an Academic Bias against Low-Energy Sweeteners?
Authors: Mela David J.
Published: March 2022

This perspective considers evidence of a common academic bias against low-energy sweeteners (LES). The core proposition is that this bias is manifested in research and reporting focused on generating and placing a negative spin on LES, largely through selective citation, interpretation and reporting. The evidence centres on three inter-related points, which together may generate a misleading impression of the balance of evidence: (1) basic and mechanistic research on LES perpetuates “explanations” for unsubstantiated adverse effects of LES; (2) the literature on LES—particularly narrative reviews and commentaries—continually reprises hypotheses of adverse effects without acknowledging where these hypotheses have been rigorously tested and rejected; and (3) negative interpretations of the effects of LES largely rely upon selectively emphasising lower-quality research whilst ignoring or dismissing higher-quality evidence. The expert community should consider these issues in assuring scientific integrity and balance in the academic discourse on LES, and how this is translated into messages for public health and consumers.
Association between the Phytochemical Index and Overweight/Obesity: A Meta-Analysis
Authors: Wei Chaojie , Liu Liping , Liu Renli , Dai Wenwen , Cui Weiwei , Li Dong
Published: March 2022

Some studies suggest that a higher phytochemical index (PI) is associated with a lower risk of overweight/obesity. This meta-analysis is performed to summarize published studies on the relationship of PI and the risk of overweight/obesity. We searched on PubMed, Cochrane Library and Web of Science from the inception dates to February 2022. The random-effect model was used based on heterogeneity. Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was evaluated using Begg’s and Egger’s tests. The dose–response relationship was assessed using a restricted cubic spline model. Nine studies were included in the meta-analysis, with a total of 100,753 participants. The meta-analysis showed that the phytochemical index was associated with a decreased risk of overweight/obesity. The pooled OR (95% CI) was 0.81 (0.74–0.90). The findings from dose–response analysis showed a nonlinear association between the phytochemical index and the risk of overweight/obesity. The results of the meta-regression showed that gender and area were significant covariates influencing the heterogeneity between studies. There was no publication bias in the meta-analysis of this study. In conclusion, although this meta-analysis indicates that a high phytochemical index is associated with a reduced risk of overweight/obesity, all the studies included in this meta-analysis were cross-sectional studies with high heterogeneity. As such, more data from randomized controlled trials are required to confirm the efficacy of PI in evaluating the risk of overweight/obesity.
Modulation of Paracellular-like Drug Transport across an Artificial Biomimetic Barrier by Osmotic Stress-Induced Liposome Shrinking
Authors: Eriksen Jonas Borregaard , Barakat Hesham , Luppi Barbara , Brandl Martin , Bauer-Brandl Annette
Published: March 2022

Various types of artificial biomimetic barriers are widely utilized as in vitro tools to predict the passive “transcellular” transport of drug compounds. The current study investigated if the sandwich barrier PermeaPad®, which is composed of tightly packed phospholipid vesicles enclosed between two support sheets, contributes to a transport mechanism that is paracellular-like, representing one of the alternative pathways of passive transport in vivo, primarily of relevance for hydrophilic drug compounds. To this end, we pretreated the commercial PermeaPad® barrier with NaCl solutions of either high or low osmolality prior to permeation experiments on reversed Franz cell setups with hydrophilic model compounds calcein and acyclovir and hydrophobic model compounds hydrocortisone and celecoxib. Our starting hypothesis was that the liposomes formed in the barrier during the hydration step should either shrink or swell upon contact with test media (drug solutions) due to osmotic pressure difference as compared to the pretreatment solutions. Apparent permeabilities for calcein and acyclovir across the PermeaPad® barrier were found to increase approximately 2.0 and 1.7 fold, respectively, upon hypo-osmotic pretreatment (soaking in hypotonic medium, while the permeation of hydrocortisone and celecoxib remained unchanged. A control experiment with lipid-free barriers (support sheets) indicated that the permeation of all the compounds was virtually unchanged upon hypo-osmotic pretreatment. In conclusion, soaking PermeaPad® in a medium of lower osmotic pressure than that used during the permeation study appears to induce the osmotic shrinking of the lipid vesicles in the barrier, leaving wider water channels between the vesicles and, thus, allowing hydrophilic compounds to pass the barrier in a paracellular-like manner.
Modernising Orodispersible Film Characterisation to Improve Palatability and Acceptability Using a Toolbox of Techniques
Authors: Desai Neel , Masen Marc , Cann Philippa , Hanson Ben , Tuleu Catherine , Orlu Mine
Published: March 2022

Orodispersible films (ODFs) have been widely used in paediatric, geriatric and dysphagic patients due to ease of administration and precise and flexible dose adjustments. ODF fabrication has seen significant advancements with the move towards more technologically advanced production methods. The acceptability of ODFs is dependent upon film composition and process of formation, which affects disintegration, taste, texture and mouthfeel. There is currently a lack of testing to accurately assess ODFs for these important acceptability sensory perceptions. This study produced four ODFs formed of polyvinyl alcohol and sodium carboxymethylcellulose using 3D printing. These were assessed using three in vitro methods: Petri dish and oral cavity model (OCM) methods for disintegration and bio-tribology for disintegration and oral perception. Increasing polymer molecular weight (MW) exponentially increased disintegration time in the Petri dish and OCM methods. Higher MW films adhered to the OCM upper palate. Bio-tribology analysis showed that films of higher MW disintegrated quickest and had lower coefficient of friction, perhaps demonstrating good oral perception but also stickiness, with higher viscosity. These techniques, part of a toolbox, may enable formulators to design, test and reformulate ODFs that both disintegrate rapidly and may be better perceived when consumed, improving overall treatment acceptability.