bluuebunny/crossref_metadata_2025 huggingface dataset:
A Combination of Metabolomics and Machine Learning Results in the Identification of a New Cyst Nematode Hatching Factor
Authors: Vlaar Lieke E. , Thiombiano Benjamin , Abedini Davar , Schilder Mario , Yang Yuting , Dong Lemeng
Published: June 2022

Potato Cyst Nematodes (PCNs) are an economically important pest for potato growers. A crucial event in the life cycle of the nematode is hatching, after which the juvenile will move toward the host root and infect it. The hatching of PCNs is induced by known and unknown compounds in the root exudates of host plant species, called hatching factors (HFs, induce hatching independently), such as solanoeclepin A (solA), or hatching stimulants (HSs, enhance hatching activity of HFs). Unraveling the identity of unknown HSs and HFs and their natural variation is important for the selection of cultivars that produce low amounts of HFs and HSs, thus contributing to more sustainable agriculture. In this study, we used a new approach aimed at the identification of new HFs and HSs for PCNs in potato. Hereto, root exudates of a series of different potato cultivars were analyzed for their PCN hatch-inducing activity and their solA content. The exudates were also analyzed using untargeted metabolomics, and subsequently the data were integrated using machine learning, specifically random forest feature selection, and Pearson’s correlation testing. As expected, solA highly correlates with hatching. Furthermore, this resulted in the discovery of a number of metabolite features present in the root exudate that correlate with hatching and solA content, and one of these is a compound of m/z 526.18 that predicts hatching even better than solA with both data methods. This compound’s involvement in hatch stimulation was confirmed by the fractionation of three representative root exudates and hatching assays with the resulting fractions. Moreover, the compound shares mass fragmentation similarity with solA, and we therefore assume it has a similar structure. With this work, we show that potato likely produces a solA analogue, and we contribute to unraveling the hatch-inducing cocktail exuded by plant roots.
Correction: Rigamonti et al. The Role of Aspartate Transaminase to Platelet Ratio Index (APRI) for the Prediction of Non-Alcoholic Fatty Liver Disease (NAFLD) in Severely Obese Children and Adolescents. Metabolites 2022, 12, 155
Authors: Rigamonti Antonello E. , Bondesan Adele , Rondinelli Eugenia , Cella Silvano G. , Sartorio Alessandro
Published: June 2022

In the original publication [...]
Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification
Authors: Buyse Chloe , Joudiou Nicolas , Warscotte Aude , Richiardone Elena , Mignion Lionel , Corbet Cyril , Gallez Bernard
Published: June 2022

Extracellular acidification has been shown to be an important characteristic of invasive tumors, as it promotes invasion and migration but also resistance to treatments. Targeting transporters involved in the regulation of tumor pH constitutes a promising anti-tumor approach, as it would disrupt cellular pH homeostasis and negatively impact tumor growth. In this study, we evaluated the impact of syrosingopine, an inhibitor of MCT1 and MCT4, as a modulator of tumor metabolism and extracellular acidification in human breast cancer (MDA-MB-231) and pharyngeal squamous cell carcinoma (FaDu) cell models. In both models in vitro, we observed that exposure to syrosingopine led to a decrease in the extracellular acidification rate, intracellular pH, glucose consumption, lactate secretion and tumor cell proliferation with an increase in the number of late apoptotic/necrotic cells. However, in vivo experiments using the MDA-MB-231 model treated with a daily injection of syrosingopine did not reveal any significant change in extracellular pH (pHe) (as measured using CEST-MRI) or primary tumor growth. Overall, our study suggests that targeting MCT could lead to profound changes in tumor cell metabolism and proliferation, and it warrants further research to identify candidates without off-target effects.
A Precise Closed-Loop Controlled ZnO Nanowire Resonator Operating at Room Temperature
Authors: Cai Xianfa , Xu Lizhong
Published: June 2022

To realize the real-time measurement of masses of nanoparticles, virus molecules, organic macromolecules, and gas molecules, and to analyze their physical and chemical properties, a ZnO nanowire (NW) resonator operating at room temperature with an ultrahigh resonant frequency, real-time detection, and high precision was designed and developed in this study. The machining method is simple and easy to integrate into an integrated circuit. A closed-loop detection system based on a phase-locked loop (PLL) and frequency modulation technology (FM) was used to perform closed-loop testing of electromagnetically excited ZnO NW. The first-order resonance frequency of the resonator was 10.358 MHz, the quality factor Q value was about 600, the frequency fluctuation value fRMS was about 300 Hz, and the FM range could reach 200 kHz. The equivalent circuit model of the resonator was established, the parasitic parameters during the test were obtained, and the frequency accuracy and phase noise of the resonator were analyzed and tested. The experimental results show that the closed-loop system can automatically control the resonator in a wide range of frequency bands, with good tracking performance of the resonant frequency, small frequency fluctuation, and low phase noise level.
Effect of Grain Structure and Ni/Au-UBM Layer on Electromigration-Induced Failure Mechanism in Sn-3.0Ag-0.5Cu Solder Joints
Authors: Zhang Yuanxiang , Zhang Jicheng , Wang Yong , Fang Yike
Published: June 2022

The development of advanced electronic devices leads to highly miniaturized interconnect circuits (ICs), which significantly increases the electromigration (EM) phenomenon of solder and circuits due to higher current density. The electromigration of solder joints under high current density has become a severe reliability concern in terms of microelectronic product reliability. The microstructure of the solder plays an important role in the electromigration induced degradation. In this study, Sn-3.0Ag-0.5Cu solder bumps with Ni/Au under bump metallization (UBM) layer were fabricated and electromigration acceleration tests were conducted under current density of 1.4 × 104 A/cm2 and 120 °C to investigate the effect of grain structure and Ni/Au-UBM layer on EM-induced failure. Grain structures of solder bumps were determined by utilizing the Electron Backscatter Diffraction (EBSD) technique, and single-crystal solder, single-crystal dominated solder, and polycrystalline solder are observed in different test samples. According to the Scanning Electron Microscope (SEM) images, it is observed that the Ni/Au-UBM layer of the Cu pad can inhibit atom diffusion between solder bump and Cu pad, which reduces the consumption of Cu pad but causes a large void and crack at the interface. The EM lifetime of single crystal solder bumps is lower than that of polycrystalline solder bumps when the c-axis of single crystal solder bumps is perpendicular to the electron flow direction. Additionally, the single crystal structure will increase the brittleness of the solder bump, and cracks are easily generated and expanded under the stress caused by the mismatch of thermal expansion coefficients between the solder bump and Ni/Au-UBM layer near Cu pad. Polycrystalline solder bumps with a higher misorientation angle (15–55°) have a higher atom diffusion rate, which will result in the acceleration of the EM-induced failure.
Average Power Handling Capability of Corrugated Slow-Wave Transmission Lines
Authors: Zheng Zehao , Tang Min , Zhang Haochi , Mao Junfa
Published: June 2022

In this article, the average power handling capability (APHC) of corrugated slow-wave transmission lines (SWTLs) is investigated. Firstly, the attenuation constants of conductor and dielectric are extracted by the multiline method. Secondly, the thermal resistance of corrugated SWTLs is analyzed based on the constant-angle model. To deal with the non-uniform corrugated structure of SWTLs, the concept of average heat-spreading width (AHSW) is introduced. Finally, the APHC of the corrugated SWTL is calculated using the attenuation constant and the thermal resistance. In addition, the APHC considering the temperature-dependent resistivity of metal conductor is also presented. For validation, the APHCs of SWTLs with different geometric parameters are evaluated. The results agree well with those obtained by the commercial software.
Evaluation of Commercial Concentration Methods for Microscopic Diagnosis of Protozoa and Helminths in Human Stool Samples in a Non-Endemic Area
Authors: Autier Brice , Gangneux Jean-Pierre , Robert-Gangneux Florence
Published: June 2022

The diagnosis of intestinal parasitic infections still widely relies on microscopic examination of stools and requires reliable reagents and staff expertise. The ParaFlo® assays (Eurobio Ingen) are ready-to-use concentration methods for parasite egg detection, and they could improve reagent traceability and ease of manipulation. Ninety-three stool samples were analyzed with the ParaFlo® concentration methods and then compared with routine microscopic methods for protozoa and helminth detection: seventy-eight were analyzed with ParaFlo® Bailenger and in-house Thebault or Bailenger concentrations, and fifty-five were analyzed with ParaFlo®DC and the in-house merthiolate-formalin diphasic concentration (DC) method. Fully concordant results were obtained for 75%, 70%, and 69% of samples when comparing ParaFlo® DC and in-house DC, ParaFlo® Bailenger and in-house Bailenger, and ParaFlo® Bailenger and Thebault, respectively. The performances of the ParaFlo® assays did not differ statistically from that obtained with their in-house counterparts (Bailenger and DC) for the detection of protozoa, but ParaFlo® Bailenger performed significantly poorer than the Thebault method (p < 0.001). No statistical differences were observed between the commercial and in-house methods for helminth detection. These marketed concentration methods could be used in routine if combined with other techniques for protozoa detection.
Plant Growth-Promoting Microorganism Pseudarthrobacter sp. NIBRBAC000502770 Enhances the Growth and Flavonoid Content of Geum aleppicum
Authors: Ham Seung Hee , Yoon A Ra , Oh Hyun Eui , Park Yoo Gyeong
Published: June 2022

Plant growth-promoting rhizobacteria are known to enhance the growth and antioxidant activity of several plants. However, the effects of such rhizobacteria on Geum aleppicum, a plant with pharmacological potential in Korea are unknown. In this study, we investigated the effects of Pseudarthrobacter sp. NIBRBAC000502770 treatment (100 mL/pot, every two weeks for 55 days), in the form of culture medium, 100−fold diluted culture, culture supernatant, and pelleted cells resuspended in water, on the growth, antibacterial activity and flavonoid content of G. aleppicum. The NIBRBAC000502770 strain showed high indole-3-acetic acid (IAA) content of 461.81 μg∙mL−1. The dry weight of the roots was significantly higher in the supernatant, diluted culture, and pellet-treated plants compared to that in the control plants. Additionally, the plant height, root length, leaf length, leaf width, chlorophyll content, biomass, and dry weight of the shoot were highest in the pellet-treated plants. Further, methanol extracts of pellet-treated plants showed significantly high flavonoid content compared to that in the control plants (28 mg∙g−1 vs. 7.5 mg∙g−1) and exhibited strong antibacterial activity against Gram-positive and negative bacteria. These results demonstrate the beneficial effects of Pseudarthrobacter sp. NIBRBAC000502770 on the growth and flavonoid content of G. aleppicum.
Bentonite Powder XRD Quantitative Analysis Using Rietveld Refinement: Revisiting and Updating Bulk Semiquantitative Mineralogical Compositions
Authors: Cuevas Jaime , Cabrera Miguel Ángel , Fernández Carlos , Mota-Heredia Carlos , Fernández Raúl , Torres Elena , Turrero María Jesús , Ruiz Ana Isabel
Published: June 2022

Bentonite is a claystone formed by a complex mineralogical mixture, composed of montmorillonite, illite, and accessory minerals like quartz, cristobalite, feldspars, carbonates, and minor amounts of iron oxy-hydroxides. Bentonite presents complexity at various scales: (1): a single mineral may present different chemical composition within the same quarry (e.g., feldspars solid solutions); (2): montmorillonite presents variability in the cation-exchange distribution while illite may be presented as mixed-layer with smectite sheets; and (3): hardness and crystal size are larger in accessory minerals than in clay minerals, preventing uniform grinding of bentonite. The FEBEX bentonite used is originally from Almería (Spain), and it is a predominantly calcium, magnesium, and sodium bentonite. This Spanish FEBEX bentonite has been hydrothermally altered at laboratory scale for 7–14 years. A thermal gradient was generated by heating a disk of pressed iron powder, simulating the metal waste canister, in contact with the compacted bentonite sample. Hydration was forced from the opposite direction. XRD recorded patterns were very similar. In order to minimize the bias of XRD semi-quantitative determination methods, Rietveld refinement was performed using BGMN software and different structural models. Confidence in the quantification of the main phases allows us to convincingly detect other subtle changes such as the presence of calcite in the hydration front, right at the interface between the saturated and unsaturated bentonite, or the presence of goethite, and not hematite, in the saturated bentonite, near the source of hydration. Smectite component was 72 ± 3% and the refinement was consistent with the presence of ~10% illite, comparable with previous characterizations.
Chemotaxonomic Identification of Key Taste and Nutritional Components in ‘Shushanggan Apricot’ Fruits by Widely Targeted Metabolomics
Authors: Cui Bei , Liu Shu-Ming , Zheng Tao
Published: June 2022

The chemotypic and the content variation in taste substances and nutrients in ‘Shushanggan apricot’ fruits were detected by UPLC-MS/MS. A total of 592 compounds were identified, of which sucrose contributed mainly to the sweet taste and malic acid and citric acid were important organic acids affecting sweet–sour taste. γ-linolenic acid, α-linolenic acid and linoleic acid were the dominant free fatty acids, and neochlorogenic acid and chlorogenic acid were the predominant phenolic acids. Fruit taste was positively correlated with sucrose and negatively correlated with malic acid and citric acid. The differential metabolites were significantly enriched in the biosynthesis of amino acids and 2-oxocarboxylic acid metabolism pathways, regulating the sugar and organic acid biosynthesis. Taste and nutrient differences could be revealed by variations in composition and abundance of carbohydrates, organic acids and amino acids. The purpose of this study was to provide a comprehensive chemical characterization of taste and nutrient compounds in ‘Shushanggan apricot’ fruits.
Applications of Titanium Dioxide Nanostructure in Stomatology
Authors: Liu Shuang , Chen Xingzhu , Yu Mingyue , Li Jianing , Liu Jinyao , Xie Zunxuan , Gao Fengxiang , Liu Yuyan
Published: June 2022

Breakthroughs in the field of nanotechnology, especially in nanochemistry and nanofabrication technologies, have been attracting much attention, and various nanomaterials have recently been developed for biomedical applications. Among these nanomaterials, nanoscale titanium dioxide (nano-TiO2) has been widely valued in stomatology due to the fact of its excellent biocompatibility, antibacterial activity, and photocatalytic activity as well as its potential use for applications such as dental implant surface modification, tissue engineering and regenerative medicine, drug delivery carrier, dental material additives, and oral tumor diagnosis and treatment. However, the biosafety of nano-TiO2 is controversial and has become a key constraint in the development of nano-TiO2 applications in stomatology. Therefore, in this review, we summarize recent research regarding the applications of nano-TiO2 in stomatology, with an emphasis on its performance characteristics in different fields, and evaluations of the biological security of nano-TiO2 applications. In addition, we discuss the challenges, prospects, and future research directions regarding applications of nano-TiO2 in stomatology that are significant and worthy of further exploration.
Supercritical CO2 Extract from Microalga Tetradesmus obliquus: The Effect of High-Pressure Pre-Treatment
Authors: Vladić Jelena , Jerković Igor , Radman Sanja , Molnar Jazić Jelena , Ferreira Alice , Maletić Snežana , Gouveia Luisa
Published: June 2022

High-pressure pre-treatment followed by supercritical carbon dioxide (ScCO2) extraction (300 bar, 40 °C) was applied for the attainment of the lipophilic fraction of microalga Tetradesmus obliquus. The chemical profile of supercritical extracts of T. obliquus was analyzed by ultra-high-performance liquid chromatography–high-resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Moreover, the impact of ScCO2 on the microbiological and metal profile of the biomass was monitored. The application of the pre-treatment increased the extraction yield approximately three-fold compared to the control. In the obtained extracts (control and pre-treated extracts), the identified components belonged to triacylglyceroles, fatty acid derivatives, diacylglycerophosphocholines and diacylglycerophosphoserines, pigments, terpenes, and steroids. Triacylglycerols (65%) were the most dominant group of compounds in the control extract. The pre-treatment decreased the percentage of triacylglycerols to 2%, while the abundance of fatty acid derivatives was significantly increased (82%). In addition, the pre-treatment led to an increase in the percentages of carotenoids, terpenoids, and steroids. Furthermore, it was determined that ScCO2 extraction reduced the number of microorganisms in the biomass. Considering its microbiological and metal profiles, the biomass after ScCO2 can potentially be used as a safe and important source of organic compounds.
Novel α-Aminophosphonates and α-Aminophosphonic Acids: Synthesis, Molecular Docking and Evaluation of Antifungal Activity against Scedosporium Species
Authors: Cordero-Díaz Anthonny , Robledo-Leal Efren , Hernández-Fernández Eugenio , Hernández-Núñez Emanuel , Elizondo-Zertuche Mariana , López-Cortina Susana T.
Published: June 2022

The Scedosporium genus is an emerging pathogen with worldwide prevalence and high mortality rates that gives multidrug resistance to antifungals; therefore, pharmacological alternatives must be sought for the treatment of diseases caused by this fungus. In the present project, six new α-aminophosphates were synthesized by the Kabachnik–Fields multicomponent reaction by vortex agitation, and six new monohydrolyzed α-aminophosphonic acids were synthesized by an alkaline hydrolysis reaction. Antifungal activity was evaluated using the agar diffusion method as an initial screening to determine the most active compound compared to voriconazole; then it was evaluated against 23 strains of the genus Scedosporium following the M38-A2 protocol from CLSI (activity range: 648.76–700 µg/mL). Results showed that compound 5f exhibited the highest antifungal activity according to the agar diffusion method (≤1 mg/mL). Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay and it was shown that compound 5f exhibits a lower toxicity in comparison to voriconazole at the same concentration (1000 µM). A docking study was conducted afterwards, showing that the possible mechanism of action of the compound is through the inhibition of allosteric 14-α-demethylase. Taking these results as a basis, 5f is presented as a compound with attractive properties for further studies.
Modulated Fluorescence in LB Films Based on DADQs—A Potential Sensing Surface?
Authors: Szablewski Marek , Thompson Richard L. , Pålsson Lars-Olof
Published: June 2022

Novel fluorescent Langmuir-Blodgett (LB) films have been constructed from three different amphiphilic dicynaoquinodimethanes (DADQs). The DADQs varied in functional group structure, which had an impact on the LB film structure and the fluorescence properties. As the fluorescence of DADQs competes with non-radiative decay (conformational change), the packing and/or free volume in the LB film will influence the average fluorescence lifetime and integrated intensity. The pristine (blank) LB films were then exposed to a selection of non-fluorescent target analytes (some with environmental relevance) and the fluorescence was measured and analyzed relative to the pristine LB film. Exposure of the LB films to selected target analytes results in a modulation of the fluorescence, both with respect to average fluorescence lifetime and integrated intensity. The modulation of the fluorescence is different for different DADQ LB films and can be attributed to restricted non-radiative decays or charge transfer reactions between target analyte and DADQ LB film. The response from the DADQ LB films shows that these systems can be developed into sensing surfaces based on fluorescence measurements.
A Capillary Electrophoresis-Based Method for the Measurement of Hydroxychloroquine and Its Active Metabolite Desethyl Hydroxychloroquine in Whole Blood in Patients with Rheumatoid Arthritis
Authors: Sotgia Salvatore , Zinellu Angelo , Mundula Nicola , Mangoni Arduino A. , Carru Ciriaco , Erre Gian Luca
Published: June 2022

A capillary electrophoresis method was developed to detect and measure hydroxychloroquine (HCQ) and its active metabolite desethyl hydroxychloroquine (DHCQ) in whole blood in patients with rheumatoid arthritis. The best separation in terms of peak area reproducibility, migration time, peak shape, and resolution of adjacent peaks was obtained in a 60 cm, 75 µm i.d. uncoated fused-silica capillary using a background electrolyte mixture of an aqueous 55 mmol/L TRIS solution brought to pH 2.6 with phosphoric acid and methanol (85:15) and a voltage and a temperature of separation of 20 kV and 30 °C, respectively. Analytes were separated in less than 12 min, with excellent linearity (R2 ≥ 0.999) in the concentration range of 0.5–8 µmol/L. The recovery of analytes spiked in whole blood was 99–101% for HCQ and 98–99% for DHCQ. Analysis of five samples from patients with rheumatoid arthritis receiving HCQ 400 mg daily yielded mean steady-state concentrations of 2.27 ± 1.61 and 1.54 ± 0.55 μmol/L for HCQ and DHCQ, respectively, with a HCQ to DHCQ ratio of 1.40 ± 0.77.
Phytochemical Composition of Commiphora Oleogum Resins and Their Cytotoxicity against Skin Cancer Cells
Authors: Ulrich Judith , Stiltz Svenja , St-Gelais Alexis , El Gaafary Menna , Simmet Thomas , Syrovets Tatiana , Schmiech Michael
Published: June 2022

Oleogum resins of the genus Commiphora have been used in traditional medicines for centuries. More than 200 Commiphora species exhibit highly variable phytochemical compositions. A novel highly selective, sensitive, accurate HPLC-MS/MS method was developed and validated to quantify five characteristic phytosteroids and furanosesquiterpenoids, namely (E)-guggulsterone, (Z)-guggulsterone, curzerenone, furanoeudesma-1,3-diene, and myrrhone. The resulting contents and additionally GC analysis were used to classify and differentiate Commiphora oleogum resins of the species C. myrrha, C. erythraea, C. mukul, C. holtziana, C. confusa, and C. kua, as well as unspecified resins. Interestingly, a Commiphora sample from Ogaden, Ethiopia, comprised 446 ng/mg guggulsterones presumed to be unique to C. mukul from the Indian subcontinent. However, Commiphora from Ogaden differed considerably from C. mukul in respect to guggulsterones isomer’s ratio. Moreover, the cytotoxicity of Commiphora extracts, essential oils, botanical drugs containing Commiphora, and pure compounds against the epidermoid carcinoma A431, malignant melanoma RPMI-7951 and SK-MEL-28 cells was investigated in vitro. Thereby, especially C. mukul extract and C. myrrha essential oil exhibited high cytotoxicity against skin cancer cells with IC50 of 2.9–10.9 µg/mL, but were less toxic to normal keratinocytes. In summary, Commiphora oleogum resins and its phytochemicals warrant further investigation aiming at chemotaxonomical classification as well as application in skin cancer treatment.
The Effect of Chronic Exposure of Graphene Nanoplates on the Viability and Motility of A549 Cells
Authors: Šestáková Blanka , Schröterová Ladislava , Bezrouk Aleš , Čížková Dana , Elkalaf Moustafa , Havelek Radim , Rudolf Emil , Králová Věra
Published: June 2022

Graphene and its derivatives are popular nanomaterials used worldwide in many technical fields and biomedical applications. Due to such massive use, their anticipated accumulation in the environment is inevitable, with a largely unknown chronic influence on living organisms. Although repeatedly tested in chronic in vivo studies, long-term cell culture experiments that explain the biological response to these nanomaterials are still scarce. In this study, we sought to evaluate the biological responses of established model A549 tumor cells exposed to a non-toxic dose of pristine graphene for eight weeks. Our results demonstrate that the viability of the A549 cells exposed to the tested graphene did not change as well as the rate of their growth and proliferation despite nanoplatelet accumulation inside the cells. In addition, while the enzymatic activity of mitochondrial dehydrogenases moderately increased in exposed cells, their overall mitochondrial damage along with energy production changes was also not detected. Conversely, chronic accumulation of graphene nanoplates in exposed cells was detected, as evidenced by electron microscopy associated with impaired cellular motility.
A Novel Two-Stage Heat Treatment with Medium-Temperature Aging Influence on Microstructure, Al3(Sc, Zr) Nanoprecipitation, and Application Properties, Enhancing Selective Laser Melting of Al–Mg–Sc–Zr Alloy
Authors: Zhao Jun-Ren , Lee Liang-Yan , Chang Kai-Chieh , Hung Fei-Yi
Published: June 2022

Al–Mg–Sc–Zr alloy fabricated through selective laser melting (SLM) is an additive manufacturing alloy with promising industrial potential. In this study, as-printed specimens were subjected to either single-stage or two-stage heat treatment processes to investigate the effect of temperature from room temperature to high temperature on the specimens’ tensile and fatigue properties to establish a reliable reference for aerospace applications. The tensile test results indicated that the heat treatment contributed to determine the properties of the nanoprecipitate Al3(Sc, Zr) with a strengthening phase, improving tensile strength. Moreover, the dynamics strain aging (DSA) effect vanished as temperature increased. It is noteworthy that the nanoprecipitation was distributed at the boundary of the melting pool after single-stage heat treatment with the highest tensile properties in all tests. In addition, the microstructure observed after the two-stage heat treatment indicated a melting pool interface decomposition, and the nanoprecipitation was homogeneously scattered over the Al matrix, increasing strength and further delaying fatigue crack transmission. Those features build a high-fatigue-resistance foundation. TEM analysis also confirmed the promotion of Sc thermal diffusion and an Al3(Sc, Zr) precipitation transformation mechanism under two-stage heat treatment, corresponding to aforementioned inferences. The SLM Al–Mg–Sc–Zr alloy with two-stage heat treatment brings about balance between tensile properties and fatigue resistance, providing new insight into additive manufacturing with Al alloys.
Serum Phytosterols Are Not Associated with Inflammatory Markers in Two Cross-Sectional, Swiss Population-Based Studies (The CoLaus|PsyCoLaus Study)
Authors: Stanasila Laura , Marques-Vidal Pedro
Published: June 2022

Background: The association between inflammation and dietary sterols remains poorly assessed at the population level. Aims: To assess the possible association between serum levels of various phytosterols (PS) and inflammatory markers. Methods: Serum levels of six PS (campesterol, campestanol, stigmasterol, sitosterol, sitostanol, brassicasterol), four cholesterol synthesis markers (lathosterol, lanosterol, desmosterol, dihydroxylanosterol) and one cholesterol absorption marker (cholestanol) were measured together with levels of CRP, IL-6 and TNF-α in two cross-sectional surveys of a population-based, prospective study. Results: CRP levels were negatively associated with levels of cholestanol and of sterols of plant origin, although some associations were not statistically significant. CRP levels were positively associated with cholesterol synthesis markers in the first but not in the second follow-up. IL-6 levels were negatively associated with cholestanol in both follow-ups. No associations between IL-6 levels and PS were found in the first follow-up, while significant negative associations with campesterol, sitosterol, brassicasterol, sitostanol and campesterol:TC ratio were found in the second follow-up. TNF-α levels were negatively associated with cholestanol in both follow-ups. These associations did not withstand adjusting for sex, age, BMI and statin administration. Conclusions: In a population-based study, PS serum levels were not significantly associated with inflammatory markers.
The Effects of an Intensive Rehabilitation Program on the Nutritional and Functional Status of Post-COVID-19 Pneumonia Patients
Authors: Sousa-Catita Diogo , Godinho Catarina , Mascarenhas Paulo , Quaresma Filipa , Fonseca Jorge
Published: June 2022

Most hospitalized COVID-19 pneumonia patients are older adults and/or have nutrition-related issues. Many are bedridden in intensive care units (ICU), a well-documented cause of malnutrition, muscle wasting, and functional impairment. Objectives: To assess the effectiveness of an intensive rehabilitation program over the nutritional/functional status of patients recovering from COVID-19 pneumonia. Post-COVID-19 pneumonia patients underwent a 30-day intensive interdisciplinary rehabilitation program including a personalized nutritional intervention designed to achieve a minimum intake of 30 kcal/kg/day and 1 g protein/kg/day. The nutritional and functional status was assessed in each patient at three different moments. Each assessment included Body Mass Index (BMI), Mid Upper Arm Circumference (MUAC), Mid Arm Muscle Circumference (MAMC), Tricipital Skinfold (TSF), Hand Grip Strength (HGS), and Mini Nutritional Assessment (MNA®). The study included 118 patients, with ages in the range 41–90 years old. BMI increased linearly over time (0.642 units, F-test = 26.458, p < 0.001). MUAC (0.322 units, F-test = 0.515, p = 0.474) and MAMC status (F-test = 1.089, p = 0.299) improved slightly, whereas TSF decreased (F-test = 1.885, p = 0.172), but all these arm anthropometry trends did not show significant variations, while HGS (4.131 units, F-test = 82.540, p < 0.001) and MNA® (1.483 units, F-test = 217.726, p < 0.001) reported a meaningful improvement. Post-COVID-19 pneumonia patients presented malnutrition and functional impairment. An interdisciplinary rehabilitation program, including personalized nutritional intervention, was effective for post-hospital COVID-19 pneumonia nutritional/functional rehabilitation.
Diet Is a Stronger Covariate than Exercise in Determining Gut Microbial Richness and Diversity
Authors: Yun Eon-Joo , Imdad Saba , Jang Junho , Park Jinhan , So Byunghun , Kim Jin-Hee , Kang Chounghun
Published: June 2022

Obesity is a common metabolic disorder caused by a sedentary lifestyle, and a high-fat and a high-glucose diet in the form of fast foods. High-fat diet-induced obesity is a major cause of diabetes and cardiovascular diseases, whereas exercise and physical activity can ameliorate these disorders. Moreover, exercise and the gut microbiota are known to be interconnected, since exercise can increase the gut microbial diversity and contribute to the beneficial health effects. In this context, we analyzed the effect of diet and exercise on the gut microbiota of mice, by next-generation sequencing of the bacterial V4 region of 16S rRNA. Briefly, mice were divided into four groups: chow-diet (CD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise-only (EX). The mice underwent treadmill exercise and diet intervention for 8 weeks, followed by the collection of their feces and DNA extraction for sequencing. The data were analyzed using the QIIME 2 bioinformatics platform and R software to assess their gut microbial composition, richness, and diversity. The Bacteroidetes to Firmicutes ratio was found to be decreased manifold in the HFD and HFX groups compared to the CD and EX groups. The gut microbial richness was comparatively lower in the HFD and HFX groups and higher in the CD and EX groups (ACE, Chao1, and observed OTUs). However, the Shannon alpha diversity index was higher in the HFD and HFX groups than in the CD and EX groups. The beta diversity based on Jaccard, Bray–Curtis, and weighted UniFrac distance metrics was significant among the groups, as measured by PERMANOVA. Paraprevotella, Desulfovibrio, and Lactococcus were the differentially abundant/present genera based on the intervention groups and in addition to these three bacteria, Butyricimonas and Desulfovibrio C21c20 were differentially abundant/present based on diet. Hence, diet significantly contributed to the majority of the changes in the gut microbiota.
Mediterranean Diet and Physical Activity as Healthy Lifestyles for Human Health
Authors: Bonofiglio Daniela
Published: June 2022

Health status is influenced by several factors, such as proper dietary pattern and regular physical activity (PA), which are crucial elements of lifestyle in terms of the prevention and treatment of metabolic and chronic diseases in all stages of life and particularly during childhood and adolescence [...]
Impact of Dietary Fructose and High Salt Diet: Are Preclinical Studies Relevant to Asian Societies?
Authors: Khor Ban Hock , Komnenov Dragana , Rossi Noreen F.
Published: June 2022

Fructose consumption, especially in food additives and sugar-sweetened beverages, has gained increasing attention due to its potential association with obesity and metabolic syndrome. The relationship between fructose and a high-salt diet, leading to hypertension and other deleterious cardiovascular parameters, has also become more evident, especially in preclinical studies. However, these studies have been modeled primarily on Western diets. The purpose of this review is to evaluate the dietary habits of individuals from China, Japan, and Korea, in light of the existing preclinical studies, to assess the potential relevance of existing data to East Asian societies. This review is not intended to be exhaustive, but rather to highlight the similarities and differences that should be considered in future preclinical, clinical, and epidemiologic studies regarding the impact of dietary fructose and salt on blood pressure and cardiovascular health worldwide.
Effects of Childhood Nutrition Education from School and Family on Eating Habits of Japanese Adults
Authors: Kuwahara Mizuki , Eum Wonsub
Published: June 2022

Since the Basic Law of Shokuiku (nutrition education) was established in 2005, the Japanese government has been promoting nutrition education among children to encourage better eating habits. This study analyzes the 2019 survey data on people’s attitudes towards nutrition education, in order to elucidate the relationship between the results of nutrition education, attitude towards nutrition education and proper eating habits, and the experience of nutrition education. The results reveal that people who received nutrition education at elementary school and middle school tend to have a more positive attitude towards nutrition education. In addition, family conversation on foods during elementary school years has a positive effect on nutritionally balanced eating behavior.
The Untapped Potential of Ginsenosides and American Ginseng Berry in Promoting Mental Health via the Gut–Brain Axis
Authors: St-Laurent Tristan , Hammami Riadh
Published: June 2022

Despite the popularity of the ginseng (Panax) root in health research and on the market, the ginseng berry’s potential remains relatively unexplored. Implementing ginseng berry cultivations and designing berry-derived products could improve the accessibility to mental health-promoting nutraceuticals. Indeed, the berry could have a higher concentration of neuroprotective and antidepressant compounds than the root, which has already been the subject of research demonstrating its efficacy in the context of neuroprotection and mental health. In this review, data on the berry’s application in supporting mental health via the gut–brain axis is compiled and discussed.
What Is Anthrax?
Authors: Bower William A. , Hendricks Katherine A. , Vieira Antonio R. , Traxler Rita M. , Weiner Zachary , Lynfield Ruth , Hoffmaster Alex
Published: June 2022

Anthrax has been feared for its high mortality in animals and humans for centuries. The etiologic agent is considered a potentially devastating bioweapon, and since 1876―when Robert Koch demonstrated that Bacillus anthracis caused anthrax―it has been considered the sole cause of the disease. Anthrax is, however, a toxin-mediated disease. The toxins edema toxin and lethal toxin are formed from protein components encoded for by the pXO1 virulence plasmid present in pathogenic B. anthracis strains. However, other members of the Bacillus cereus group, to which B. anthracis belongs, have recently been shown to harbor the pXO1 plasmid and produce anthrax toxins. Infection with these Bacillus cereus group organisms produces a disease clinically similar to anthrax. This suggests that anthrax should be defined by the exotoxins encoded for by the pXO1 plasmid rather than the bacterial species it has historically been associated with, and that the definition of anthrax should be expanded to include disease caused by any member of the B. cereus group containing the toxin-producing pXO1 plasmid or anthrax toxin genes specifically.
A Machine Learning Model for Food Source Attribution of Listeria monocytogenes
Authors: Tanui Collins K. , Benefo Edmund O. , Karanth Shraddha , Pradhan Abani K.
Published: June 2022

Despite its low morbidity, listeriosis has a high mortality rate due to the severity of its clinical manifestations. The source of human listeriosis is often unclear. In this study, we investigate the ability of machine learning to predict the food source from which clinical Listeria monocytogenes isolates originated. Four machine learning classification algorithms were trained on core genome multilocus sequence typing data of 1212 L. monocytogenes isolates from various food sources. The average accuracies of random forest, support vector machine radial kernel, stochastic gradient boosting, and logit boost were found to be 0.72, 0.61, 0.7, and 0.73, respectively. Logit boost showed the best performance and was used in model testing on 154 L. monocytogenes clinical isolates. The model attributed 17.5 % of human clinical cases to dairy, 32.5% to fruits, 14.3% to leafy greens, 9.7% to meat, 4.6% to poultry, and 18.8% to vegetables. The final model also provided us with genetic features that were predictive of specific sources. Thus, this combination of genomic data and machine learning-based models can greatly enhance our ability to track L. monocytogenes from different food sources.
Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective
Authors: Bou-Fakhredin Rayan , De Franceschi Lucia , Motta Irene , Cappellini Maria Domenica , Taher Ali T.
Published: June 2022

A significant amount of attention has recently been devoted to the mechanisms involved in hemoglobin (Hb) switching, as it has previously been established that the induction of fetal hemoglobin (HbF) production in significant amounts can reduce the severity of the clinical course in diseases such as β-thalassemia and sickle cell disease (SCD). While the induction of HbF using lentiviral and genome-editing strategies has been made possible, they present limitations. Meanwhile, progress in the use of pharmacologic agents for HbF induction and the identification of novel HbF-inducing strategies has been made possible as a result of a better understanding of γ-globin regulation. In this review, we will provide an update on all current pharmacological inducer agents of HbF in β-thalassemia and SCD in addition to the ongoing research into other novel, and potentially therapeutic, HbF-inducing agents.
Ultrasound and Nanomedicine for Cancer-Targeted Drug Delivery: Screening, Cellular Mechanisms and Therapeutic Opportunities
Authors: Li Chien-Hsiu , Chang Yu-Chan , Hsiao Michael , Chan Ming-Hsien
Published: June 2022

Cancer is a disease characterized by abnormal cell growth. According to a report published by the World Health Organization (WHO), cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018. It should be noted that ultrasound is already widely used as a diagnostic procedure for detecting tumorigenesis. In addition, ultrasound energy can also be utilized effectively for treating cancer. By filling the interior of lipospheres with gas molecules, these particles can serve both as contrast agents for ultrasonic imaging and as delivery systems for drugs such as microbubbles and nanobubbles. Therefore, this review aims to describe the nanoparticle-assisted drug delivery system and how it can enhance image analysis and biomedicine. The formation characteristics of nanoparticles indicate that they will accumulate at the tumor site upon ultrasonic imaging, in accordance with their modification characteristics. As a result of changing the accumulation of materials, it is possible to examine the results by comparing images of other tumor cell lines. It is also possible to investigate ultrasound images for evidence of cellular effects. In combination with a precision ultrasound imaging system, drug-carrying lipospheres can precisely track tumor tissue and deliver drugs to tumor cells to enhance the ability of this nanocomposite to treat cancer.
A Historical Review of Brain Drug Delivery
Authors: Pardridge William M.
Published: June 2022

The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a drug for syphilis, salvarsan, did not enter the brain, due to the presence of a blood–brain barrier (BBB). Owing to restricted transport across the BBB, FDA-approved drugs for the CNS have been generally limited to lipid-soluble small molecules. Drugs that do not cross the BBB can be re-engineered for transport on endogenous BBB carrier-mediated transport and receptor-mediated transport systems, which were identified during the 1970s–1980s. By the 1990s, a multitude of brain drug delivery technologies emerged, including trans-cranial delivery, CSF delivery, BBB disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, and biologics. The advantages and limitations of each of these brain drug delivery technologies are critically reviewed.
Antioxidative NAC-Loaded Silk Nanoparticles with Opening Mucosal Tight Junctions for Nasal Drug Delivery: An In Vitro and In Vivo Study
Authors: Chung Tze-Wen , Wu Ting-Ya , Siah Zheng-Yu , Liu Der-Zen
Published: June 2022

Using nasal routes to deliver drugs to the brain using multifunctional nanoparticles (NPs) to bypass the blood–brain barrier (BBB) might enhance the delivery efficacy. Anti-oxidative N-Acetyl-L-cysteine (NAC)-loaded silk fibroin (SF/NAC) NPs are produced, characterized and studied as a potential delivery vehicle for NAC delivered to the brain via nasal for both in vitro and in vivo studies. The NPs are not cytotoxic to RPMI 2650 cells, mucosal model cells, at a concentration of 6000 μg/mL. The anti-oxidative activities of SF/NAC NPs are demonstrated by high H2O2 scavenge capacities of the NPs and shown by mitochondrial superoxide (MitoSOX) immunostaining of human mesenchymal stem cells. Tight junctions in RPMI 2650 cells are opened after 30 min of incubation with SF/NAC NPs, which are demonstrated by measuring the decrease in trans-epithelial electrical resistance (TEER) values and discreteness in ZO-1 stains. The cellular uptake of SF/NAC NPs by RPMI 2650 cells is significantly greater than that for SF NPs and increased with increasing incubation time. In an in vivo imaging study (IVIS) using rats shows that the amount of NAC that is delivered to the brain by SF/NAC NPs increased by 1.40–2.60 times and NAC is retained longer in the nasal cavity than NAC solutions in a 2-h study.
Formulated Curcumin Prevents Paclitaxel-Induced Peripheral Neuropathy through Reduction in Neuroinflammation by Modulation of α7 Nicotinic Acetylcholine Receptors
Authors: Caillaud Martial , Thompson Danielle , Toma Wisam , White Alyssa , Mann Jared , Roberts Jane L. , Bigbee John W. , Gewirtz David A. , Damaj M. Imad
Published: June 2022

Paclitaxel is widely used in the treatment of various types of solid malignancies. Paclitaxel-induced peripheral neuropathy (PIPN) is often characterized by burning pain, cold, and mechanical allodynia in patients. Currently, specific pharmacological treatments against PIPN are lacking. Curcumin, a polyphenol of Curcuma longa, shows antioxidant, anti-inflammatory, and neuroprotective effects and has recently shown efficacy in the mitigation of various peripheral neuropathies. Here, we tested, for the first time, the therapeutic effect of 1.5% dietary curcumin and Meriva (a lecithin formulation of curcumin) in preventing the development of PIPN in C57BL/6J mice. Curcumin or Meriva treatment was initiated one week before injection of paclitaxel and continued throughout the study (21 days). Mechanical and cold sensitivity as well as locomotion/motivation were tested by the von Frey, acetone, and wheel-running tests, respectively. Additionally, sensory-nerve-action-potential (SNAP) amplitude by caudal-nerve electrical stimulation, electronic microscopy of the sciatic nerve, and inflammatory-protein quantification in DRG and the spinal cord were measured. Interestingly, a higher concentration of curcumin was observed in the spinal cord with the Meriva diet than the curcumin diet. Our results showed that paclitaxel-induced mechanical hypersensitivity was partially prevented by the curcumin diet but completely prevented by Meriva. Both the urcumin diet and the Meriva diet completely prevented cold hypersensitivity, the reduction in SNAP amplitude and reduced mitochondrial pathology in sciatic nerves observed in paclitaxel-treated mice. Paclitaxel-induced inflammation in the spinal cord was also prevented by the Meriva diet. In addition, an increase in α7 nAChRs mRNA, known for its anti-inflammatory effects, was also observed in the spinal cord with the Meriva diet in paclitaxel-treated mice. The use of the α7 nAChR antagonist and α7 nAChR KO mice showed, for the first time in vivo, that the anti-inflammatory effects of curcumin in peripheral neuropathy were mediated by these receptors. The results presented in this study represent an important advance in the understanding of the mechanism of action of curcumin in vivo. Taken together, our results show the therapeutic potential of curcumin in preventing the development of PIPN and further confirms the role of α7 nAChRs in the anti-inflammatory effects of curcumin.