bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of CrossFit Training on Physical Fitness of Kickboxers
Authors: Ambroży Tadeusz , Rydzik Łukasz , Kwiatkowski Amadeusz , Spieszny Michał , Ambroży Dorota , Rejman Aneta , Koteja Agnieszka , Jaszczur-Nowicki Jarosław , Duda Henryk , Czarny Wojciech
Published: April 2022

Background: Kickboxing is a combat sport that is complex in technique, tactics, and movement structure, and requires an adequate level of motor skills as a foundation for activities during competitions. General physical fitness, defined as the effect of the externalization of motor skills, is the basis for athletic training regardless of the sport. The aim of this study was to determine the effect of modified training based on the principles of CrossFit on the development of general physical fitness in a group of kickboxers compared to a control group. Methods: The study was experimental in nature and was conducted in a group of 60 kickboxers, divided into experimental and control groups. Participants were selected by purposive sampling, and the criteria were training experience, sports skill level (minimum class 1 athletes), and consent to participate in the experiment. The intervention in the study group involved the introduction of CrossFit-based training into a conventional kickboxing training program. General and special physical fitness of the athletes were diagnosed. Results: Statistically significant differences were found in general fitness in terms of abdominal strength (p < 0.001), pull-ups (p < 0.001), dynamometric measurement of handgrip force (p < 0.001) (kg), clap push-ups (p < 0.001), standing long jump (p < 0.001), shuttle run (p < 0.001), sit-and-reach (p < 0.001), and tapping (p < 0.001). Furthermore, changes in special fitness were also demonstrated for the special kickboxing fitness test (SKFT) (p < 0.02), the total number of punches (p < 0.001), punching speed (p < 0.001), and hip turning speed (p < 0.001). There was also a correlation between characteristics of general fitness and special fitness (p < 0.001). Conclusions: The experimental training program based on the principles of CrossFit training had a positive effect on the general and special kickboxing physical fitness.
Biometal Dyshomeostasis in Olfactory Mucosa of Alzheimer’s Disease Patients
Authors: Lampinen Riikka , Górová Veronika , Avesani Simone , Liddell Jeffrey R. , Penttilä Elina , Závodná Táňa , Krejčík Zdeněk , Lehtola Juha-Matti , Saari Toni , Kalapudas Juho , Hannonen Sanna , Löppönen Heikki , Topinka Jan , Koivisto Anne M. , White Anthony R. , Giugno Rosalba , Kanninen Katja M.
Published: April 2022

Olfactory function, orchestrated by the cells of the olfactory mucosa at the rooftop of the nasal cavity, is disturbed early in the pathogenesis of Alzheimer’s disease (AD). Biometals including zinc and calcium are known to be important for sense of smell and to be altered in the brains of AD patients. Little is known about elemental homeostasis in the AD patient olfactory mucosa. Here we aimed to assess whether the disease-related alterations to biometal homeostasis observed in the brain are also reflected in the olfactory mucosa. We applied RNA sequencing to discover gene expression changes related to metals in olfactory mucosal cells of cognitively healthy controls, individuals with mild cognitive impairment and AD patients, and performed analysis of the elemental content to determine metal levels. Results demonstrate that the levels of zinc, calcium and sodium are increased in the AD olfactory mucosa concomitantly with alterations to 17 genes related to metal-ion binding or metal-related function of the protein product. A significant elevation in alpha-2-macroglobulin, a known metal-binding biomarker correlated with brain disease burden, was observed on the gene and protein levels in the olfactory mucosa cells of AD patients. These data demonstrate that the olfactory mucosa cells derived from AD patients recapitulate certain impairments of biometal homeostasis observed in the brains of patients.
Clinical and Molecular Insights of Radiation-Induced Breast Sarcomas: Is There Hope on the Horizon for Effective Treatment of This Aggressive Disease?
Authors: Kokkali Stefania , Moreno Jose Duran , Klijanienko Jerzy , Theocharis Stamatios
Published: April 2022

Radiation-induced breast sarcomas (RIBS) are rare entities representing <1% of all primary breast malignancies, limiting most reports to small retrospective case series. They constitute a heterogeneous group of neoplasms, with high-grade angiosarcoma being the most common subtype. Other sarcoma histotypes, such as undifferentiated pleomorphic sarcoma and leiomyosarcoma, can also be identified. Radiation-induced breast angiosarcoma (RIBA) has an incidence of approximately 0.1% after breast-conserving therapy and arises mainly from the dermis of the irradiated breast. MYC gene amplification is highly indicative of secondary breast angiosarcomas. Their clinical presentation often mimics benign port-radiation lesions, leading to a delay in diagnosis and a lost window of opportunity for cure. Surgery with negative margins is the mainstay of treatment of localized RIBS. In the case of angiosarcoma, technical difficulties, including multifocality, infiltrative margins, and difficulty in assessing tumor margins, render surgical treatment quite challenging. A limited number of studies showed that adjuvant radiation therapy reduces local recurrences; therefore, it is proposed by many groups for large, high-grade tumors. Chemotherapy has been evaluated retrospectively in a small subset of patients, with some evidence supporting its use in angiosarcoma patients. Approximately half of patients with RIBA will show local recurrence. In the advanced setting, different therapeutic options are discussed in the review, including chemotherapy, antiangiogenic therapy, and immunotherapy, whereas the need for further research on molecular therapeutic targets is pointed out.
Structural Comparison of Sulfonamide-Based Derivatives That Can Improve Anti-Coagulation Properties of Metformin
Authors: Zajda Agnieszka , Sikora Joanna , Huttunen Kristiina M. , Markowicz-Piasecka Magdalena
Published: April 2022

Due to its high efficiency, good safety profile, and potential cardio-protective properties, metformin, a dimethyl biguanide, is the first-line medication in antihyperglycemic treatment for type 2 diabetic patients. The aim of our present study was to assess the effects of eight new sulfonamide-based derivatives of metformin on selected plasma parameters and vascular hemostasis, as well as on endothelial and smooth muscle cell function. The compounds with an alkyl chain (1–3), trifluoromethyl substituent (4), or acetyl group (5) significantly elevated glucose utilization in human umbilical endothelial cells (HUVECs), similarly to metformin. Our novel findings showed that metformin analogues 1–3 presented the most beneficial properties because of their greatest safety profile in the WST-1 cell viability assay, which was also proved in the further HUVEC integrity studies using RTCA DP. Compounds 1–3 did not affect either HUVEC or aortal smooth muscle cell (AoSMC) viability up to 3.0 mM. Importantly, these compounds beneficially affected some of the coagulation parameters, including factor X and antithrombin III activity. In contrast to the above-mentioned metformin analogues, derivatives 4 and 5 exerted more profound anticoagulation effects; however, they were also more cytotoxic towards HUVECs, as IC50 values were 1.0–1.5 mM. In conclusion, the chemical modification of a metformin scaffold into sulfonamides possessing alkyl substituents results in the formation of novel derivatives with potential bi-directional activity including anti-hyperglycemic properties and highly desirable anti-coagulant activity.
Deficiency of Thyroid Hormone Reduces Voltage-Gated Na+ Currents as Well as Expression of Na+/K+-ATPase in the Mouse Hippocampus
Authors: Sundaram Sivaraj Mohana , Marx Romy , Lesslich Heiko M. , Dietzel Irmgard D.
Published: April 2022

Mice lacking functional thyroid follicular cells, Pax8−/− mice, die early postnatally, making them suitable models for extreme hypothyroidism. We have previously obtained evidence in postnatal rat neurons, that a down-regulation of Na+-current density could explain the reduced excitability of the nervous system in hypothyroidism. If such a mechanism underlies the development of coma and death in severe hypothyroidism, Pax8−/− mice should show deficits in the expression of Na+ currents and potentially also in the expression of Na+/K+-ATPases, which are necessary to maintain low intracellular Na+ levels. We thus compared Na+ current densities in postnatal mice using the patch-clamp technique in the whole-cell configuration as well as the expression of three alpha and two beta-subunits of the Na+/K+-ATPase in wild type versus Pax8−/− mice. Whereas the Na+ current density in hippocampal neurons from wild type mice was upregulated within the first postnatal week, the Na+ current density remained at a very low level in hippocampal neurons from Pax8−/− mice. Pax8−/− mice also showed significantly decreased protein expression levels of the catalytic α1 and α3 subunits of the Na+/K+-ATPase as well as decreased levels of the β2 isoform, with no changes in the α2 and β1 subunits.
Type XX Collagen Is Elevated in Circulation of Patients with Solid Tumors
Authors: Thorlacius-Ussing Jeppe , Jensen Christina , Madsen Emilie A. , Nissen Neel I. , Manon-Jensen Tina , Chen Inna M. , Johansen Julia S. , Diab Hadi M. H. , Jørgensen Lars N. , Karsdal Morten A. , Willumsen Nicholas
Published: April 2022

In the tumor microenvironment, the extracellular matrix (ECM) has been recognized as an important part of cancer development. The dominant ECM proteins are the 28 types of collagens, each with a unique function in tissue architecture. Type XX collagen, however, is poorly characterized, and little is known about its involvement in cancer. We developed an ELISA quantifying type XX collagen, named PRO-C20, using a monoclonal antibody raised against the C-terminus. PRO-C20 and PRO-C1, an ELISA targeting the N-terminal pro-peptide of type I collagen, was measured in sera of 219 patients with various solid cancer types and compared to sera levels of 33 healthy controls. PRO-C20 was subsequently measured in a separate cohort comprising 36 patients with pancreatic ductal adenocarcinoma (PDAC) and compared to 20 healthy controls and 11 patients with chronic pancreatitis. PRO-C20 was significantly elevated in all cancers tested: bladder, breast, colorectal, head and neck, kidney, lung, melanoma, ovarian, pancreatic, prostate, and stomach cancer (p < 0.01–p < 0.0001). PRO-C1 was only elevated in patients with ovarian cancer. PRO-C20 could discriminate between patients and healthy controls with AUROC values ranging from 0.76 to 0.92. Elevated levels were confirmed in a separate cohort of patients with PDAC (p < 0.0001). High PRO-C20 levels (above 2.57 nM) were predictive of poor survival after adjusting for the presence of metastasis, age, and sex (HR: 4.25, 95% CI: 1.52–11.9, p-value: 0.006). Circulating type XX collagen is elevated in sera of patients with various types of cancer and has prognostic value in PDAC. If validated, PRO-C20 may be a novel biomarker for patients with solid tumors and can help understand the ECM biology of cancer.
Soil Aggregate Stability in Salt-Affected Vineyards: Depth-Wise Variability Analysis
Authors: Bless Aplena E. S. , Colin François , Crabit Armand , Follain Stéphane
Published: April 2022

Soil aggregate stability is an ideal integrative soil quality indicator, but little is known about the relevance of such an indicator with soil depth for salt-affected soils. The objective of this study was to determine soil aggregate stability and identify preponderant aggregation factors, both in topsoil and subsoil horizons in salt-affected conditions. We conducted field investigations by describing soil profiles in pedological pits and by collecting soil samples from different field units. Soils were sampled within different soil horizon types, from superficial tilled organo-mineral horizons to mineral horizons. For all soil samples, we determined the mean weight diameter (MWD) as an indicator of soil aggregate stability and also determined associated physical and chemical properties in some samples. The measured MWD value from 0.28 mm to 1.10 mm could be categorised as unstable, with MWD values and variability decreasing drastically from the topsoil to the deepest mineral horizons. Analysis of MWD in relation to physical and chemical properties suggested that the variability in the MWD value of A-horizons was influenced by both clay fraction abundance and soil organic carbon (SOC) content and the nature of the agricultural practices, while at deeper B-horizons, the decrease in SOC content and the variability in other soil properties with soil depth could be used to explain the overall low aggregate stability. In this study, investigations of soil pits coupled with measurements of soil aggregate stability indicated that it could be possible to restore soil structure quality by limiting deep soil profile compaction in order to improve salt leaching and exportation.
Agent-Based Recommendation in E-Learning Environment Using Knowledge Discovery and Machine Learning Approaches
Authors: Shahbazi Zeinab , Byun Yung-Cheol
Published: April 2022

E-learning is a popular area in terms of learning from social media websites in various terms and contents for every group of people in this world with different knowledge backgrounds and jobs. E-learning sites help users such as students, business workers, instructors, and those searching for different educational institutions. Excluding the benefits of this system, there are various challenges that the users face in online platforms. One of the important challenges is the true information and right content based on these resources, search results and quality. This research proposes virtual and intelligent agent-based recommendation, which requires users’ profile information and preferences to recommend the proper content and search results based on their search history. We applied Natural Language Processing (NLP) techniques and semantic analysis approaches for the recommendation of course selection to e-learners and tutors. Moreover, machine learning performance analysis applied to improve the user rating results in the e-learning environment. The system automatically learns and analyzes the learner characteristics and processes the learning style through the clustering strategy. Compared with the recent state-of-the-art in this field, the proposed system and the simulation results show the minimizing number of metric errors compared to other works. The achievements of the presented approach are providing a comfortable platform to the user for course selection and recommendations. Similarly, we avoid recommending the same contents and courses. We analyze the user preferences and improving the recommendation system performance to provide highly related content based on the user profile situation. The prediction accuracy of the proposed system is 98% compared to hybrid filtering, self organization systems and ensemble modeling.
Adaptive Intelligent Sliding Mode Control of a Dynamic System with a Long Short-Term Memory Structure
Authors: Liu Lunhaojie , Fu Wen , Bian Xingao , Fei Juntao
Published: April 2022

In this work, a novel fuzzy neural network (NFNN) with a long short-term memory (LSTM) structure was derived and an adaptive sliding mode controller, using NFNN (ASMC-NFNN), was developed for a class of nonlinear systems. Aimed at the unknown uncertainties in nonlinear systems, an NFNN was designed to estimate unknown uncertainties, which combined the advantages of fuzzy systems and neural networks, and also introduced a special LSTM recursive structure. The special three gating units in the LSTM structure enabled it to have selective forgetting and memory mechanisms, which could make full use of historical information, and have a stronger ability to learn and estimate unknown uncertainties than general recurrent neural networks. The Lyapunov stability rule guaranteed the parameter convergence of the neural network and system stability. Finally, research into a simulation of an active power filter system showed that the proposed new algorithm had better static and dynamic properties and robustness compared with a sliding controller that uses a recurrent fuzzy neural network (RFNN).
Intangible ICT and Their Importance within Global Value Chains: An Empirical Analysis Based on Longitudinal Data Regression
Authors: Pekarčík Marek , Ďurčová Júlia , Glova Jozef
Published: April 2022

The rising global importance of global value chains was enabled by developing information and communication technologies, ICT. A correct understanding of ICT roles determines a country’s global competitiveness. The study aims to examine the role of intangible ICT assets in creating domestic and foreign value added in export. Based on a sample of available longitudinal data from the EU-KLEMS database, for the period 2000–2015, 10 EU countries have been selected and analysed. We applied several panel regression models to confirm the important role of ICT capital, specific to intangible ICT, in creating domestic added value in exports and participation in the global value chains. Our results show that intangible ICT assets have a higher impact on the global value chain participation than tangible ICT assets. Moreover, the analysis at the sectoral level reveals a stronger effect of total ICT assets in the case of total business sectors.
Modelling Asymmetric Data by Using the Log-Gamma-Normal Regression Model
Authors: Tovar-Falón Roger , Martínez-Flórez Guillermo , Bolfarine Heleno
Published: April 2022

In this paper, we propose a linear regression model in which the error term follows a log-gamma-normal (LGN) distribution. The assumption of LGN distribution gives flexibility to accommodate skew forms to the left and to the right. Kurtosis greater or smaller than the normal model can also be accommodated. The regression model for censored asymmetric data is also considered (censored LGN model). Parameter estimation is implemented using the maximum likelihood approach and a small simulation study is conducted to evaluate parameter recovery. The main conclusion is that the approach is very much satisfactory for moderate and large sample sizes. Results for two applications of the proposed model to real datasets are provided for illustrative purposes.
Riemann–Hilbert Problem for the Matrix Laguerre Biorthogonal Polynomials: The Matrix Discrete Painlevé IV
Authors: Branquinho Amílcar , Moreno Ana Foulquié , Fradi Assil , Mañas Manuel
Published: April 2022

In this paper, the Riemann–Hilbert problem, with a jump supported on an appropriate curve on the complex plane with a finite endpoint at the origin, is used for the study of the corresponding matrix biorthogonal polynomials associated with Laguerre type matrices of weights—which are constructed in terms of a given matrix Pearson equation. First and second order differential systems for the fundamental matrix, solution of the mentioned Riemann–Hilbert problem, are derived. An explicit and general example is presented to illustrate the theoretical results of the work. The non-Abelian extensions of a family of discrete Painlevé IV equations are discussed.
The Emerging Evidence for a Protective Role of Fucoidan from Laminaria japonica in Chronic Kidney Disease-Triggered Cognitive Dysfunction
Authors: Ma Zhihui , Yang Zhiyou , Feng Xinyue , Deng Jiahang , He Chuantong , Li Rui , Zhao Yuntao , Ge Yuewei , Zhang Yongping , Song Cai , Zhong Saiyi
Published: April 2022

This study aimed to explore the mechanism of fucoidan in chronic kidney disease (CKD)-triggered cognitive dysfunction. The adenine-induced ICR strain CKD mice model was applied, and RNA-Seq was performed for differential gene analysis between aged-CKD and normal mice. As a result, fucoidan (100 and 200 mg kg−1) significantly reversed adenine-induced high expression of urea, uric acid in urine, and creatinine in serum, as well as the novel object recognition memory and spatial memory deficits. RNA sequencing analysis indicated that oxidative and inflammatory signaling were involved in adenine-induced kidney injury and cognitive dysfunction; furthermore, fucoidan inhibited oxidative stress via GSK3β-Nrf2-HO-1 signaling and ameliorated inflammatory response through regulation of microglia/macrophage polarization in the kidney and hippocampus of CKD mice. Additionally, we clarified six hallmarks in the hippocampus and four in the kidney, which were correlated with CKD-triggered cognitive dysfunction. This study provides a theoretical basis for the application of fucoidan in the treatment of CKD-triggered memory deficits.
Self-Healing Silver Nanowires and Reduced Graphene Oxide/Polyurethane Composite Film Based on the Diels–Alder Reaction under Infrared Radiation
Authors: Wang Yi , Zhou Zhimin , Chen Jiali , Li Sixing , Zheng Han , Lu Jiaxin , Wang Shuyue , Zhang Jiahao , Lin Kaiwen , Wang Ke , Wang Yuehui
Published: April 2022

The hybrid composite of silver nanowires (AgNWs) and reduced graphene oxide (RGO) was synthesized in situ by an improved polyol–thermal method. The AgNWs-RGO with mass contents of 5–37 wt% was added into the thermo-reversible Diels–Alder reaction polyurethane (DA-PU) matrix with the AgNWs as the main conductor and the RGO as the auxiliary conductor to prepare self-healing composite conductive films. Further, the electrical conductivity, thermal conductivity, mechanical properties, infrared thermal response, and self-healing property of the composite film under infrared light irradiation were studied. The experimental results demonstrate that the AgNWs-RGO endows the composite film with good electrical and thermal conductivity and infrared thermal response ability, while the mechanical properties of the composite film decrease as the AgNWs-RGO mass content increases. The self-healing efficiency of the composite film is higher than that of the pure DA-PU under infrared light irradiation due to the good infrared photothermal response ability of the AgNWs-RGO. When the mass content of AgNWs-RGO in the composite film was 25 wt%, the AgNWs-RGO showed good dispersion in composite films, and the resistivity, thermal conductivity, and tensile strength of the composite film were 0.544 Ω·m, 0.3039 W·m−1·K−1, and 9.05 MPa, respectively. The infrared photothermal conversion temperature of the composite film is 158.5 °C (3450 lux for 1 min), and the infrared photothermal self-healing efficiency is 118% (3450 lux for 600 s). The AgNWs-RGO also improves the multiple self-healing ability of the composite film. The use of a high mass content of AgNWs-RGO in the composite film is beneficial in obtaining high multiple self-healing efficiencies. The first and the fifth infrared thermal self-healing efficiencies of the composite film with AgNWs-RGO of 35 wt% are 105% and 86%, respectively, and the resistivity of the composite film changes little and still maintains good conductivity.
Study on Stress Corrosion Cracking Behavior of Incoloy825/X65 Bimetallic Composite Pipe Welded Joint in Wet Hydrogen Sulfide Environment
Authors: Wang Bingying , Ouyang Li , Xu Jianxing , Huang Peng , Liu Enyang , Yang Bin
Published: April 2022

The stress corrosion cracking behavior of an Incoloy825/X65 bimetallic composite pipe welded joint in wet hydrogen sulfide (H2S) environment was investigated by means of the creviced bent beam (CBB) test in this study. The microstructure, element distribution and crack propagation behavior of the welded joint were analyzed by optical microscope (OM), scanning electron microscope (SEM), electron dispersive spectroscopy (EDS) and electron backscatter diffraction (EBSD). The results showed that two types of cracks were observed in the Incoloy825/X65 bimetallic composite pipe welded joint in wet H2S environment, they initiated from the notch and the intersection of the three zones (cladding Incoloy825, base X65 and weld), respectively, and propagated along the fusion boundary(FB) and the Type-II-like grain boundary. The mechanisms of the two types of cracks are due to the combination of anodic dissolution, stress and hydrogen. Near the FB, there are high angle grain boundaries, Type-I, Type-II and the Type-II-like grain boundaries, which have high SCC sensitivity. The element distribution in the intersection of the three zones and the crack tip is complex, with element diffusion, Cr loss and large residual strain. All these provide the conditions for cracks initiation and propagation.
Soy Phospholipids Exert a Renoprotective Effect by Inhibiting the Nuclear Factor Kappa B Pathway in Macrophages
Authors: Ohta Satoshi , Asanoma Masashi , Irie Nao , Tachibana Nobuhiko , Kohno Mitsutaka
Published: April 2022

Complications associated with chronic kidney disease (CKD), which involves kidney inflammation, are a major health problem. Soy protein isolate (SPI) reportedly inhibits CKD exacerbation; however, its detailed action mechanism remains obscure. Therefore, the role of the polar lipid component of SPI in suppressing inflammation was investigated. Zucker fatty rats were divided into three groups and fed a diet containing casein, SPI, or casein + SPI ethanol extract (SPIEE) for 16 weeks. The isoflavones and phospholipids of SPIEE were evaluated for their anti-inflammatory effects. Rats in the SPI and casein + SPIEE groups showed reduced levels of the urinary N-acetyl-β-d-glucosaminidase and renal IL-1β mRNA (an inflammatory marker) compared with those in the casein group. In proximal tubular cells, genistein significantly inhibited monocyte chemoattractant protein-1 (MCP-1) expression induced by an IL-1β stimulus. In macrophages, soybean phospholipids suppressed lipopolysaccharide-induced IL-1β gene expression by inhibiting the phosphorylation of inhibitor κB and p65. Phosphatidylinositol (PI) was found to be essential for inhibition of IL-1β expression. SPIEE inhibited the exacerbation of kidney disease. Genistein and soybean phospholipids, especially soybean-specific phospholipids containing PI, effectively inhibited the inflammatory spiral in vitro. Hence, daily soybean intake may be effective for inhibiting chronic inflammation and slowing kidney disease progression.
The Role of Thyroid Hormones on Skeletal Muscle Thermogenesis
Authors: Sawicka-Gutaj Nadia , Erampamoorthy Abikasinee , Zybek-Kocik Ariadna , Kyriacou Angelos , Zgorzalewicz-Stachowiak Małgorzata , Czarnywojtek Agata , Ruchała Marek
Published: April 2022

Nowadays obesity becomes a significant global problem. Hence, recently more and more attention has been paid to substances present in the body that have a significant impact on metabolic processes and thermogenesis, in the context of their potential use in the prevention and treatment of obesity. It is well known that the relationship between thyroid hormones and obesity is multilayered, however recently, more and more information about the possible relation between thyroid hormones and muscle metabolism has been published. The aim of this review is to present the most updated information on the physiological impact of thyroid hormones on muscle tissue, as well as pathological changes related to the occurrence of various types of thyroid disorders, including hypothyroidism, hyperthyroidism and sick euthyroid syndrome. However, the data in humans still remains insufficient, and further studies are needed to fully explore the thyroid-muscle cross-talk.
Safety Assessment of Lactiplantibacillus plantarum TWK10 Based on Whole-Genome Sequencing, Phenotypic, and Oral Toxicity Analysis
Authors: Hsu Han-Yin , Liao Yi-Chu , Lin Shih-Hsuan , Lin Jin-Seng , Lee Chia-Chia , Watanabe Koichi
Published: April 2022

Lactiplantibacillus plantarum TWK10 (TWK10), isolated from Taiwanese pickled cabbage, has been demonstrated to exert beneficial probiotic effects in both mice and humans. Here, we comprehensively assessed the safety of TWK10 using both in vivo and in vitro approaches, including whole-genome sequence analysis, an assessment of hemolytic activity, and performing an antimicrobial susceptibility test, the Ames bacterial reverse mutation assay, the chromosomal aberration test, a rodent peripheral blood micronucleus test, and the 28-day subacute oral toxicity assay. The results showed that there was no significant increase in the incidence of reverse mutations or chromosomal aberrations following exposure to TWK10. Moreover, no significant changes were detected either in the number of reticulocytes or the incidence of micronuclei in ICR mice, and no subacute toxicity was recorded in SD rats at the oral TWK10 dosage of 2000 mg/kg body weight/day repeated for 28 days. Additionally, TWK10 exhibited no hemolytic activity and was susceptible to all the antibiotics tested, except kanamycin. However, no antimicrobial resistance genes, virulence factors, or genes involved in biogenic amine synthesis were found in the genome of TWK10. Our findings demonstrated that TWK10 has high potential of being safe for human consumption as a probiotic.
Computational Analysis and Biological Activities of Oxyresveratrol Analogues, the Putative Cyclooxygenase-2 Inhibitors
Authors: Jongkon Nathjanan , Seaho Boonwiset , Tayana Ngampuk , Prateeptongkum Saisuree , Duangdee Nongnaphat , Jaiyong Panichakorn
Published: April 2022

Polyphenols are a large family of naturally occurring phytochemicals. Herein, oxyresveratrol was isolated from ethanolic crude extracts of Artocarpus lacucha Buch.-Ham., and chemically modified to derive its lipophilic analogues. Biological screening assays showed their inhibitory potency against cyclooxygenase-2 (COX-2) with very low cytotoxicity to the MRC-5 normal cell lines. At the catalytic site of COX-2, docking protocols with ChemPLP, GoldScore and AutoDock scoring functions were carried out to reveal hydrogen bonding interactions with key polar contacts and hydrophobic pi-interactions. For more accurate binding energetics, COX-2/ligand complexes at the binding region were computed in vacuo and implicit aqueous solvation using M06-2X density functional with 6-31G+(d,p) basis set. Our computational results confirmed that dihydrooxyresveratrol (4) is the putative inhibitor of human COX-2 with the highest inhibitory activity (IC50 of 11.50 ± 1.54 µM) among studied non-fluorinated analogues for further lead optimization. Selective substitution of fluorine provides a stronger binding affinity; however, lowering the cytotoxicity of a fluorinated analogue to a normal cell is challenging. The consensus among biological activities, ChemPLP docking score and the binding energies computed at the quantum mechanical level is obviously helpful for identification of oxyresveratrol analogues as a putative anti-inflammatory agent.
Synthesis of Novel C/D Ring Modified Bile Acids
Authors: Landaeta Aponte Roselis A. , Luxenburger Andreas , Cameron Scott A. , Weymouth-Wilson Alex , Furneaux Richard H. , Harris Lawrence D. , Compton Benjamin J.
Published: April 2022

Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro–furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.
The Pharmacological Potential of Adenosine A2A Receptor Antagonists for Treating Parkinson’s Disease
Authors: Mori Akihisa , Chen Jiang-Fan , Uchida Shinichi , Durlach Cecile , King Shelby M. , Jenner Peter
Published: April 2022

The adenosine A2A receptor subtype is recognized as a non-dopaminergic pharmacological target for the treatment of neurodegenerative disorders, notably Parkinson’s disease (PD). The selective A2A receptor antagonist istradefylline is approved in the US and Japan as an adjunctive treatment to levodopa/decarboxylase inhibitors in adults with PD experiencing OFF episodes or a wearing-off phenomenon; however, the full potential of this drug class remains to be explored. In this article, we review the pharmacology of adenosine A2A receptor antagonists from the perspective of the treatment of both motor and non-motor symptoms of PD and their potential for disease modification.
A New Cationic Fluorescent Probe for HSO3− Based on Bisulfite Induced Aggregation Self-Assembly
Authors: Zhang Xing , Su Shao-Yuan , Chen Xuan-Ting , Shen Ling-Yi , Zhang Qi-Long , Ni Xin-Long , Xu Hong , Wang Zhi-Yong , Redshaw Carl
Published: April 2022

In comparison with the numerous studies that have centered on developing molecular frameworks for the functionalization of fluorescent materials, less research has addressed the influence of the side chains, despite such appendages contributing significantly to the properties and applications of fluorescent materials. In this work, a new series of cationic fluorescent probes with AIE characteristics have been developed, which exhibit unique sensitivity for charge-diffusion anions, namely HSO3−, via the interactions of ions and the cooperation of the controllable hydrophobicity. The impact of the alkyl chain length attached at the cationic probes suggested that the fluorescent intensity and sensitivity of the probes could be partially enhanced by adjusting their aggregation tendency through the action of the hydrophobic effect under aqueous conditions. DLS and SEM images indicated that different particle sizes and new morphologies of the probes were formed in the anion-recognition-triggered self-assembly process, which could be attributed to the composite effect of electrostatic actions, Van der Waals forces and π-π stacking.
Poly(lactic acid)/Poly(3-hydroxybutyrate) Biocomposites with Differently Treated Cellulose Fibers
Authors: Frone Adriana Nicoleta , Ghiurea Marius , Nicolae Cristian Andi , Gabor Augusta Raluca , Badila Stefania , Panaitescu Denis Mihaela
Published: April 2022

The growing concern about environmental pollution has generated an increased demand for biobased and biodegradable materials intended particularly for the packaging sector. Thus, this study focuses on the effect of two different cellulosic reinforcements and plasticized poly(3-hydroxybutyrate) (PHB) on the properties of poly(lactic acid) (PLA). The cellulose fibers containing lignin (CFw) were isolated from wood waste by mechanical treatment, while the ones without lignin (CF) were obtained from pure cellulose by acid hydrolysis. The biocomposites were prepared by means of a melt compounding-masterbatch technique for the better dispersion of additives. The effect of the presence or absence of lignin and of the size of the cellulosic fibers on the properties of PLA and PLA/PHB was emphasized by using in situ X-ray diffraction, polarized optical microscopy, atomic force microscopy, and mechanical and thermal analyses. An improvement of the mechanical properties of PLA and PLA/PHB was achieved in the presence of CF fibers due to their smaller size, while CFw fibers promoted an increased thermal stability of PLA/PHB, owing to the presence of lignin. The overall thermal and mechanical results show the great potential of using cheap cellulose fibers from wood waste to obtain PLA/PHB-based materials for packaging applications as an alternative to using fossil based materials. In addition, in situ X-ray diffraction analysis over a large temperature range has proven to be a useful technique to better understand changes in the crystal structure of complex biomaterials.
Validation of an LC–MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma
Authors: Schwarz Rico , Richter Anna , Ito Elisabeth R. D. , Murua Escobar Hugo , Junghanß Christian , Hinz Burkhard
Published: April 2022

Silmitasertib (CX-4945) is currently being investigated in clinical trials against various types of cancer. The U.S. Food and Drug Administration (FDA) has already granted orphan drug designation to the compound for the treatment of advanced cholangiocarcinoma, medulloblastoma, and biliary tract cancer. Silmitasertib inhibits the serine/threonine protein kinase CK2, which exerts a proliferation-promoting and anti-apoptotic effect on cancer cells. In view of current and future applications, the measurement of silmitasertib levels in plasma is expected to play an important role in the evaluation of therapeutic and toxic concentrations in cancer patients. In the present work, we therefore present an LC–MS/MS method for the quantification of silmitasertib in human plasma. Using a simple liquid–liquid extraction with ethyl acetate and a mixture of n-hexane and ethyl acetate, this method can be performed in any laboratory with mass spectrometry. The validation was carried out according to the FDA guideline.
Preparation and Characterization of New Electrospun Poly(lactic acid) Nanofiber Antioxidative Active Packaging Films Containing MCM-41 Mesoporous Molecular Sieve Loaded with Phloridzin and Their Application in Strawberry Packaging
Authors: Xie Yuan , Cheng Guiguang , Wu Zhoushan , Shi Shang , Zhao Jinghao , Jiang Lin , Jiang Dengbang , Yuan Mingwei , Wang Yudan , Yuan Minglong
Published: April 2022

Health concerns about food safety have increased in recent years. In order to ensure the safety and increase the shelf-life of food, many methods have been used to slow down the oxidation rate of food fat. In order to solve this problem, a new type of antioxidant-active packaging has emerged. Poly(lactic acid) (PLA) films containing phloridzin adsorbed on to an MCM-41 mesoporous molecular sieve were prepared by electrostatic spinning, using PLA as a film-forming substrate, phloridzin as an antioxidant, and MCM-41 as the adsorption and controlled release carrier. The physical properties of the new films—including microscopic structure, water vapor transmission rate, and fresh-keeping effects, as well as the mechanical, thermal, antioxidant, and antibacterial properties—were studied. When the mass ratio of MCM-41 to phloridzin is 1:2, the nanofiber membrane achieves a 53.61% free-radical scavenging rate and better antibacterial performance (85.22%) due to the high content of phloridzin (30.54%). Additionally, when the mass ratio of the molecular sieve to phloridzin is 1:2 and 3:4 (with the best antibacterial performance of 89.30%), the films significantly delay lipid oxidation in the strawberry packaging, allowing the fresh-keeping time to be extended to up to 21 days before mildew appears. In this study, an MCM-41 mesoporous molecular sieve was used to load phloridzin for the first time. The packaging film with phloridzin, MCM-41, and poly(lactic acid) were used as the raw materials and electrospinning technology was used to prepare the packaging film with antioxidant activity. The packaging film was used for the first time in the packaging of strawberries.
Nano-Composite Filler of Heteropolyacid-Imidazole Modified Mesoporous Silica for High Temperature PEMFC at Low Humidity
Authors: Lee Gicheon , Kim Jinsol , Park Jungho , Jeon Yukwon , Park Jinwon , Shul Yong-Gun
Published: April 2022

Nano-composite filler has received attention for the application to high temperature and low humidity polymer electrolyte membrane (PEM) in fuel cell systems. Heteropolyacids (HPAs) are one of the most attractive materials because of their conductive and thermally stable properties, but have practical limitations due to their high solubility. We investigated the stabilization of HPA on imidazole modified mesoporous silica as a nano-composite filler. The role of mesoporous silica as a support for imidazole and the distribution of chemically bonded HPA on the surface were both confirmed through physical and chemical analysis. The developed nano-composite was utilized to a PEM as a proton conducting filler, cast with commercial AquivionTM solution. Changing the HPA: imidazole ratio and HPA wt%, the composite membrane of Im10/PWA6/Si-MCM-41 (PWA 10 wt%) resulted in higher proton conductivity compared to the non-modified membrane at all operation conditions, especially at high temperature (140 °C) and low relative humidity (RH 10%), with values of 0.3530 and 0.0241 S/m, respectively. A single cell test at H2/Air also showed the effect of adding the nano-composite filler at a wide range of temperatures, which outperformed a single cell with a pristine membrane even at an extremely low humidity condition.
A Robust Silicone Rubber Strip-Based Triboelectric Nanogenerator for Vibration Energy Harvesting and Multi-Functional Self-Powered Sensing
Authors: Du Taili , Ge Bin , Mtui Anaeli Elibariki , Zhao Cong , Dong Fangyang , Zou Yongjiu , Wang Hao , Sun Peiting , Xu Minyi
Published: April 2022

Vibration is a common phenomenon in various fields which can not only indicate the working condition of the installation, but also serve as an energy source if it is efficiently harvested. In this work, a robust silicone rubber strip-based triboelectric nanogenerator (SRS-TENG) for vibration energy harvesting and multi-functional self-powered sensing is proposed and systematically investigated. The SRS-TENG consists of a silicone rubber strip and two aluminum electrode layers supported by polylactic acid (PLA), and acts as a sustainable power source and vibration frequency, amplitude and acceleration sensor as well. The soft contact between the aluminum electrode and silicone rubber strip makes it robust and stable even after 14 days. It can be applied in ranges of vibration frequencies from 5 to 90 Hz, and amplitudes from 0.5 to 9 mm, which shows it has advantages in broadband vibration. Additionally, it can achieve lower startup limits due to its soft structure and being able to work in multi-mode. The output power density of the SRS-TENG can reach 94.95 W/m3, matching a resistance of 250 MΩ, and it can light up more than 100 LEDs and power a commercial temperature sensor after charging capacitors. In addition, the vibration amplitude can be successfully detected and displayed on a human–machine interface. Moreover, the frequency beyond a specific limit can be distinguished by the SRS-TENG as well. Therefore, the SRS-TENG can be utilized as an in situ power source for distributed sensor nodes and a multifunctional self-powered vibration sensor in many scenarios.
The Association between Lead Exposure and Bone Mineral Density in Childhood and Adolescence: Results from NHANES 1999–2006 and 2011–2018
Authors: Li Tao , Xie Yixuan , Wang Liang , Huang Guimin , Cheng Yijing , Hou Dongqing , Liu Wenqian , Zhang Tong , Liu Junting
Published: April 2022

There are few studies on lead’s effect on bone mineral density (BMD) in childhood. In this study, we examined the association between lead exposure and BMD among 13,951 children and adolescents aged 8–19 years from NHANES 1999–2006 and 2011–2018. The whole blood lead levels (BLLs) were used as lead exposure biomarkers, and total BMD, subtotal BMD, lumbar spine BMD and limb BMD were used as outcome variables. The survey weighted multivariable generalized additive models (GAMs) with smoothing terms were used to explore the association between blood lead levels and BMDs, adjusted for age, sex, race/ethnicity, height, weight, family-income-to-poverty ratio and blood cadmium. Subgroup analyses stratified by sex and bony sites were further performed. We found an N-shaped curve association between BLLs and total BMD, subtotal BMD and limb BMD for males and females, whereas the association between BLLs and lumbar spine BMD was only significantly negative for females. The findings suggested that lead exposure had different effects on BMD of different bony sites (highly cortical or trabecular regions) in childhood and adolescence and had different effects on the same bone among different ages population and/or at different levels.
Fermented Foods, Health and the Gut Microbiome
Authors: Leeuwendaal Natasha K. , Stanton Catherine , O’Toole Paul W. , Beresford Tom P.
Published: April 2022

Fermented foods have been a part of human diet for almost 10,000 years, and their level of diversity in the 21st century is substantial. The health benefits of fermented foods have been intensively investigated; identification of bioactive peptides and microbial metabolites in fermented foods that can positively affect human health has consolidated this interest. Each fermented food typically hosts a distinct population of microorganisms. Once ingested, nutrients and microorganisms from fermented foods may survive to interact with the gut microbiome, which can now be resolved at the species and strain level by metagenomics. Transient or long-term colonization of the gut by fermented food strains or impacts of fermented foods on indigenous gut microbes can therefore be determined. This review considers the primary food fermentation pathways and microorganisms involved, the potential health benefits, and the ability of these foodstuffs to impact the gut microbiome once ingested either through compounds produced during the fermentation process or through interactions with microorganisms from the fermented food that are capable of surviving in the gastro-intestinal transit. This review clearly shows that fermented foods can affect the gut microbiome in both the short and long term, and should be considered an important element of the human diet.
Metabolic Syndrome and High-Obesity-Related Indices Are Associated with Poor Cognitive Function in a Large Taiwanese Population Study Older than 60 Years
Authors: Huang Szu-Han , Chen Szu-Chia , Geng Jiun-Hung , Wu Da-Wei , Li Chien-Hsun
Published: April 2022

Metabolic syndrome (MetS) is prevalent in Taiwan; however, the association between MetS and cognitive function is unclear. The aim of this study was to explore the associations between MetS, its components, and obesity-related indices with cognitive function in a large Taiwanese cohort. We enrolled a total of 28,486 participants who completed the Mini-Mental State Examination (MMSE) questionnaire, which was used to evaluate cognitive function. MetS was defined according to the NCEP-ATP III guidelines and modified criteria for Asians. Ten obesity-related indices were also evaluated: body mass index (BMI), abdominal volume index (AVI), body adiposity index (BAI), waist–hip ratio (WHR), a body shape index (ABSI), lipid accumulation product, waist-to-height ratio (WHtR), conicity index (CI), body roundness index (BRI), and triglyceride glucose index. The prevalence of MetS and its components (except for hypertriglyceridemia) and the number of MetS components increased while the cognitive impairment worsened (from MMSE ≥ 24, 18–23 to 0–17). In addition, increases in all obesity-related index values were associated with a decline in cognitive function (from MMSE ≥ 24, 18–23 to 0–17, ANOVA p < 0.001). Multivariable analysis showed that MetS (p = 0.002), abdominal obesity (p < 0.001), low high-density lipoprotein cholesterol (p = 0.004), and hyperglycemia (p = 0.012) were significantly associated with a low MMSE score. Further, participants with high BMI (p = 0.001), WHR (p < 0.001), WHtR (p < 0.001), BRI (p < 0.001), CI (p < 0.001), BAI (p < 0.001), AVI (p < 0.001), and ABSI (p < 0.001) values were significantly associated with a low MMSE score. Our results show that MetS and its components (except for hypertriglyceridemia and high blood pressure) may lead to cognitive impairment, and that high values of obesity-related indices were associated with poor cognitive function.