bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of the Reverse Martensite-to-Austenite Transformation in a Metastable Austenitic Stainless Steel
Authors: Panov Dmitrii , Kudryavtsev Egor , Chernichenko Ruslan , Smirnov Aleksandr , Stepanov Nikita , Simonov Yuri , Zherebtsov Sergey , Salishchev Gennady
Published: April 2021

The martensite-to-austenite reversion mechanisms under continuous heating and annealing of metastable austenitic stainless steel subjected to cold swaging were studied. The reversion-temperature-time diagram was constructed using high-resolution dilatometry. The diagram revealed a sequence of martensitic and diffusional reversion and recrystallization. Martensitic and diffusional reversion might be separated by using the heating rate of >10 °C/s. The reversion started via the martensitic mechanism, and the diffusional mechanism developed during subsequent heating. However, both mechanisms enhance simultaneously during continuous heating at slow heating rates (<10 °C/s). At higher temperatures, recrystallization occurred. Post-mortem microstructure analysis has allowed classifying the reverse annealing modes into low- (500–650 °C), medium- (~700 °C), and high-temperature (~800 °C) regimes. During low-temperature annealing, the development of the phase reversion, recovery, recrystallization, and carbide precipitation was characterized by both a high amount of new austenite grains and restriction of their growth that resulted in the formation of an ultrafine grain structure with an average grain size of 100–200 nm. Medium-temperature annealing was associated with the formation of almost a fully recrystallized austenitic structure, but the lamellar regions were still detected. Austenitic grain growth and dissolution of carbide particles were enhanced during high-temperature annealing.
FepiM: A Novel Inverse Piecewise Method to Determine Isothermal Flow Curves for Hot Working
Authors: Vuppala Aditya , Krämer Alexander , Lohmar Johannes , Hirt Gerhard
Published: April 2021

In forming simulations, flow curves are cardinal inputs to predict features, such as forming forces and material flow. The laboratory-scale experiments to determine them, like compression or tensile tests, are affected by deformation heating, restricting direct flow curve determination. In principle, the current analytical and inverse methods determine flow curves from these tests, but while the analytical methods assume a simplified temperature profile, the inverse methods require a closed-form flow curve equation, which mostly cannot capture complex material behavior like multiple recrystallization cycles. Therefore, the inverse piecewise flow curve determination method “FepiM” previously developed and published by the current authors is extended by introducing a two-step procedure to obtain isothermal flow curves at elevated temperatures and different strain rates. Thereby, the flow curve is represented as tabular data instead of an equation to reproduce complex flow curve shapes while also compensating the effect of inhomogeneous temperature profiles on the flow stress. First, a flow curve at the highest temperature is determined. In the second step, using this first flow curve as a reference, the flow curves at lower temperatures are obtained via interpolation. Flow curves from conventional compression tests for aluminum and copper in the temperature range of 20–500 °C are predicted, and it is shown that these flow curves can reproduce the experimental forces with a maximum deviation of less than 1%. Therefore, the proposed new piecewise method accurately predicts isothermal flow curves for compression tests, and the method could be further extended to highly inhomogeneous methods in the future.
Photonic Crystal Fiber SPR Liquid Sensor Based on Elliptical Detective Channel
Authors: Yan Xin , Wang Yao , Cheng Tonglei , Li Shuguang
Published: April 2021

This paper proposes a Photonic Crystal Fiber (PCF) refractive index sensor model based on the surface plasmon resonance effect. The proposed PCF model also uses the full vector finite element method to transfer the structure under the anisotropic Perfect Matching Layer (PML) boundary condition. Numerical calculations were carried out on the sensor characteristics. The calculation results show that the elliptical air hole on the left side of the PCF core is coated with a gold-nano film which serves as a Surface Plasmon Resonance (SPR) sensing channel to detect the refractive index of liquid materials. Compared with other structures, the resonant peak generated by the excited SPR effect from the elliptical sensing channel has a high sensitivity to the change of the refractive index of the liquid to be measured. With the help of this attribute, it is relatively easy to adjust the sensitivity. The refractive index range of this structure is within 1.43–1.49 and the sensitivity is up to 12,719.97 nm·RIU−1. The linearity is good; R2 = 0.99927, which is very suitable for liquid sensing.
Compact Elliptical UWB Antenna for Underwater Wireless Communications
Authors: Alhawari Adam R. H. , Majeed Sama F. , Saeidi Tale , Mumtaz Sajid , Alghamdi Hisham , Hindi Ayman Taher , Almawgani Abdulkarem H. M. , Imran Muhammad Ali , Abbasi Qammer H.
Published: April 2021

The increasing needs of free licensed frequency bands like Industrial, Scientific, and Medical (ISM), Wireless Local Area Network (WLAN), and 5G for underwater communications required more bandwidth (BW) with higher data transferring rate. Microwaves produce a higher transferring rate of data, and their associated devices are smaller in comparison with sonar and ultrasonic. Thus, transceivers should have broad BW to cover more of a frequency band, especially from ultra-wideband (UWB) systems, which show potential outcomes. However, previous designs of similar work for underwater communications were very complicated, uneasy to fabricate, and large. Therefore, to overcome these shortcomings, a novel compact elliptical UWB antenna is designed to resonate from 1.3 to 7.2 GHz. It is invented from a polytetrafluoroethylene (PTFE) layer with a dielectric constant of 2.55 mm and a thickness of 0.8 mm. The proposed antenna shows higher gain and radiation efficiency and stability throughout the working band when compared to recent similarly reported designs, even at a smaller size. The characteristics of the functioning antenna are investigated through fluid mediums of fresh-water, seawater, distilled water, and Debye model water. Later, its channel capacity, bit rate error, and data rate are evaluated. The results demonstrated that the antenna offers compact, easier fabrication with better UWB characteristics for underwater 5G communications.
β-Sitosterol Circumvents Obesity Induced Inflammation and Insulin Resistance by down-Regulating IKKβ/NF-κB and JNK Signaling Pathway in Adipocytes of Type 2 Diabetic Rats
Authors: Jayaraman Selvaraj , Devarajan Nalini , Rajagopal Ponnulakshmi , Babu Shyamaladevi , Ganesan Senthil Kumar , Veeraraghavan Vishnu Priya , Palanisamy Chella Perumal , Cui Bo , Periyasamy Vijayalakshmi , Chandrasekar Kirubhanand
Published: April 2021

β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKβ/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway.
Protein O-Fucosyltransferase 1 Undergoes Interdomain Flexibility in Solution
Authors: Lira-Navarrete Erandi , Pallarés María Carmen , Castello Fabio , Ruedas-Rama Maria J. , Orte Angel , Lostao Anabel , Hurtado-Guerrero Ramón
Published: April 2021

Protein O-fucosyltransferase 1 (PoFUT1) is a GT-B fold enzyme that fucosylates proteins containing EGF-like repeats. GT-B glycosyltransferases have shown a remarkable grade of plasticity adopting closed and open conformations as a way of tuning their catalytic cycle, a feature that has not been observed for PoFUT1. Here, we analyzed Caenorhabditis elegans PoFUT1 (CePoFUT1) conformational behavior in solution by atomic force microscopy (AFM) and single-molecule fluorescence resonance energy transfer (SMF-FRET). Our results show that this enzyme is very flexible and adopts mainly compact conformations and to a lesser extend a highly dynamic population that oscillates between compact and highly extended conformations. Overall, our experiments illustrate the inherent complexity of CePoFUT1 dynamics, which might play a role during its catalytic cycle.
Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles
Authors: Gaglio Salvatore Calogero , Donini Marta , Denbaes Piyachat Evelyn , Dusi Stefano , Perduca Massimiliano
Published: April 2021

Oxyresveratrol, a stilbene extracted from the plant Artocarpus lakoocha Roxb., has been reported to provide a considerable anti-inflammatory activity. Since the mechanisms of this therapeutic action have been poorly clarified, we investigated whether oxyresveratrol affects the release of the pro-inflammatory cytokines IL-12, IL-6, and TNF-α by human dendritic cells (DCs). We found that oxyresveratrol did not elicit per se the release of these cytokines, but inhibited their secretion induced upon DC stimulation with R848 (Resiquimod), a well-known immune cell activator engaging receptors recognizing RNA viruses. We then investigated whether the inclusion of oxyresveratrol into nanoparticles promoting its ingestion by DCs could favor its effects on cytokine release. For this purpose we synthesized and characterized poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and we assessed their effects on DCs. We found that bare PLGA nanoparticles did not affect cytokine secretion by resting DCs, but increased IL-12, IL-6, and TNF-α secretion by R848-stimulated DCs, an event known as “priming effect”. We then loaded PLGA nanoparticles with oxyresveratrol and we observed that oxyresveratrol-bearing particles did not stimulate the cytokine release by resting DCs and inhibited the PLGA-dependent enhancement of IL-12, IL-6, and TNF-α secretion by R848-stimulated DCs. The results herein reported indicate that oxyresveratrol suppresses the cytokine production by activated DCs, thus representing a good anti-inflammatory and immune-suppressive agent. Moreover, its inclusion into PLGA nanoparticles mitigates the pro-inflammatory effects due to cooperation between nanoparticles and R848 in cytokine release. Therefore, oxyresveratrol can be able to contrast the synergistic effects of nanoparticles with microorganisms that could be present in the patient tissues, therefore overcoming a condition unfavorable to the use of some nanoparticles in biological systems.
Central Activation of Alpha7 Nicotinic Signaling Attenuates LPS-Induced Neuroinflammation and Sickness Behavior in Adult but Not in Aged Animals
Authors: Navarro Elisa , Norden Diana M. , Trojanowski Paige J. , Godbout Jonathan P. , López Manuela G.
Published: April 2021

We previously reported that lipopolysaccharide (LPS) challenge caused microglial-mediated neuroinflammation and sickness behavior that was amplified in aged mice. As α7 nAChRs are implicated in the “Cholinergic anti-inflammatory pathway”, we aimed to determine how α7 nAChR stimulation modulates microglial phenotype in an LPS-induced neuroinflammation model in adult and aged mice. For this, BALB/c mice were injected intraperitoneally with LPS (0.33 mg/kg) and treated with the α7 nAChR agonist PNU282987, using different administration protocols. LPS challenge reduced body weight and induced lethargy and social withdrawal in adult mice. Peripheral (intraperitoneal) co-administration of the α7 nAChR agonist PNU282987 with LPS, attenuated body weight loss and sickness behavior associated with LPS challenge in adult mice, and reduced microglial activation with suppression of IL-1β and TNFα mRNA levels. Furthermore, central (intracerebroventricular) administration of the α7 nAChR agonist, even 2 h after LPS injection, attenuated the decrease in social exploratory behavior and microglial activation induced by peripheral administration of LPS, although this recovery was not achieved if activation of α7 nAChRs was performed peripherally. Finally, we observed that the positive results of central activation of α7 nAChRs were lost in aged mice. In conclusion, we provide evidence that stimulation of α7 nAChR signaling reduces microglial activation in an in vivo LPS-based model, but this cholinergic-dependent regulation seems to be dysfunctional in microglia of aged mice.
Intrinsically Disordered Proteins as Regulators of Transient Biological Processes and as Untapped Drug Targets
Authors: Hosoya Yusuke , Ohkanda Junko
Published: April 2021

Intrinsically disordered proteins (IDPs) are critical players in the dynamic control of diverse cellular processes, and provide potential new drug targets because their dysregulation is closely related to many diseases. This review focuses on several medicinal studies that have identified low-molecular-weight inhibitors of IDPs. In addition, clinically relevant liquid–liquid phase separations—which critically involve both intermolecular interactions between IDPs and their posttranslational modification—are analyzed to understand the potential of IDPs as new drug targets.
Analytical Problems with Preparation of Paraspinal Tissues from Patients with Spinal Fusion for Analysis of Titanium
Authors: Sawicki Jan , Danielewicz Anna , Wójciak Magdalena , Latalski Michał , Skalska-Kamińska Agnieszka , Tyszczuk-Rotko Katarzyna , Sowa Ireneusz
Published: April 2021

Preparation of paraspinal tissue of patients with implants for elemental analysis is a challenge because it contains titanium in the ionic form, as well as metallic debris. Most literature reports focus on dissolving the tissue, but the impact of digestion conditions on metallic debris of Ti has not been investigated. In our work, various digestion conditions, including systems, compositions of oxidising mixture, and time, were tested aiming (i) to digest the tissue without digestion of metallic titanium to quantify soluble Ti and (ii) to digest metallic titanium debris to asses total Ti content in tissue. The experiments were performed in a closed mode using a microwave-assisted system and a carbon heating block. Our study revealed that total digestion of titanium was impossible in the tested conditions and the maximal level of digested titanium was below 70%. The mineralisation with the use of concentrated nitric acid was optimal to prepare paraspinal samples to analyse the soluble titanium form because metallic titanium passivated and did not migrate to the solution. The elaborated conditions were applied to determine titanium ion in the periimplant tissue of patients with three different titanium-based surgical systems, including traditional growing rod (TGR), guided growth systems (GGS), and vertical expandable prosthesis titanium rib (VEPTR).
Mono- and Binuclear Copper(II) and Nickel(II) Complexes with the 3,6-Bis(picolylamino)-1,2,4,5-Tetrazine Ligand
Authors: Stetsiuk Oleh , El-Ghayoury Abdelkrim , Lloret Francesc , Julve Miguel , Avarvari Narcis
Published: April 2021

Four new compounds of formulas [Cu(hfac)2(L)] (1), [Ni(hfac)2(L)] (2), [{Cu(hfac)2}2(µ-L)]·2CH3OH (3) and [{Ni(hfac)2}2(µ-L)]·2CH3CN (4) [Hhfac = hexafluoroacetylacetone and L = 3,6-bis(picolylamino)-1,2,4,5-tetrazine] have been prepared and their structures determined by X-ray diffraction on single crystals. Compounds 1 and 2 are isostructural mononuclear complexes where the metal ions [copper(II) (1) and nickel(II) (2)] are six-coordinated in distorted octahedral MN2O4 surroundings which are built by two bidentate hfac ligands plus another bidentate L molecule. This last ligand coordinates to the metal ions through the nitrogen atoms of the picolylamine fragment. Compounds 3 and 4 are centrosymmetric homodinuclear compounds where two bidentate hfac units are the bidentate capping ligands at each metal center and a bis-bidentate L molecule acts as a bridge. The values of the intramolecular metal···metal separation are 7.97 (3) and 7.82 Å (4). Static (dc) magnetic susceptibility measurements were carried out for polycrystalline samples 1–4 in the temperature range 1.9–300 K. Curie law behaviors were observed for 1 and 2, the downturn of χMT in the low temperature region for 2 being due to the zero-field splitting of the nickel(II) ion. Very weak [J = −0.247(2) cm−1] and relatively weak intramolecular antiferromagnetic interactions [J = −4.86(2) cm−1] occurred in 3 and 4, respectively (the spin Hamiltonian being defined as H = −JS1·S2). Simple symmetry considerations about the overlap between the magnetic orbitals across the extended bis-bidentate L bridge in 3 and 4 account for their magnetic properties.
Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB1/CB2 Receptor Interaction
Authors: Asproni Battistina , Murineddu Gabriele , Corona Paola , Pinna Gérard A.
Published: April 2021

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB1 and/or CB2 receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB1 antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB1 or CB2 receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.
Two Sides to One Story—Aroma Chemical and Sensory Signature of Lugana and Verdicchio Wines
Authors: Slaghenaufi Davide , Luzzini Giovanni , Samaniego Solis Jessica , Forte Filippo , Ugliano Maurizio
Published: April 2021

Lugana and Verdicchio are two Italian white wines with a Protected Designation of Origin (PDO) label. These two wine types are produced in different regions using the same grape variety. The aim of this work is to investigate the existence of volatile chemical markers that could help to elucidate differences between Lugana and Verdicchio wines both at chemical and sensory levels. Thirteen commercial wine samples were analyzed by Gas Chromatography-Mass Spectrometry (GC-MS), and 76 volatile compounds were identified and quantified. Verdicchio and Lugana had been differentiated on the basis of 19 free and glycosidically bound compounds belonging to the chemical classes of terpenes, benzenoids, higher alcohols, C6 alcohols and norisoprenoids. Samples were assessed by means of a sorting task sensory analysis, resulting in two clusters formed. These results suggested the existence of 2 product types with specific sensory spaces that can be related, to a good extend, to Verdicchio and Lugana wines. Cluster 1 was composed of six wines, 4 of which were Lugana, while Cluster 2 was formed of 7 wines, 5 of which were Verdicchio. The first cluster was described as “fruity”, and “fresh/minty”, while the second as “fermentative” and “spicy”. An attempt was made to relate analytical and sensory data, the results showed that damascenone and the sum of 3 of esters the ethyl hexanoate, ethyl octanoate and isoamyl acetate, was characterizing Cluster 1. These results highlighted the primary importance of geographical origin to the volatile composition and perceived aroma of Lugana and Verdicchio wines.
Fabrication of Graphene Based Durable Intelligent Personal Protective Clothing for Conventional and Non-Conventional Chemical Threats
Authors: Jin Youngho , Ka Dongwon , Jang Seongon , Heo Deokjae , Seo Jin Ah , Jung Hyunsook , Jeong Keunhong , Lee Sangmin
Published: April 2021

Conventional or non-conventional chemical threat is gaining huge attention due to its unpredictable and mass destructive effects. Typical military protective suits have drawbacks such as high weight, bulky structure, and unpredictable lifetime. A durable, light, and scalable graphene e-fabric was fabricated from CVD-grown graphene by a simple co-lamination method. The sheet resistance was below 1 kΩ/sq over the wide surface area even after 1000 bending cycles. A graphene triboelectric nanogenerator showed the peak VOC of 68 V and the peak ICC of 14.4 μA and 1 μF capacitor was charged successfully in less than 1 s. A wearable chemical sensor was also fabricated and showed a sensitivity up to 53% for nerve chemical warfare agents (GD). DFT calculations were conducted to unveil the fundamental mechanisms underlying the graphene e-fabric sensor. Additionally, protection against chemical warfare agents was tested, and a design concept of graphene-based intelligent protective clothing has been proposed.
Dimensional Roadmap for Maximizing the Piezoelectrical Response of ZnO Nanowire-Based Transducers: Impact of Growth Method
Authors: Lopez Garcia Andrés Jenaro Lopez , Mouis Mireille , Consonni Vincent , Ardila Gustavo
Published: April 2021

ZnO nanowires are excellent candidates for energy harvesters, mechanical sensors, piezotronic and piezophototronic devices. The key parameters governing the general performance of the integrated devices include the dimensions of the ZnO nanowires used, their doping level, and surface trap density. However, although the method used to grow these nanowires has a strong impact on these parameters, its influence on the performance of the devices has been neither elucidated nor optimized yet. In this paper, we implement numerical simulations based on the finite element method combining the mechanical, piezoelectric, and semiconducting characteristic of the devices to reveal the influence of the growth method of ZnO nanowires. The electrical response of vertically integrated piezoelectric nanogenerators (VING) based on ZnO nanowire arrays operating in compression mode is investigated in detail. The properties of ZnO nanowires grown by the most widely used methods are taken into account on the basis of a thorough and comprehensive analysis of the experimental data found in the literature. Our results show that the performance of VING devices should be drastically affected by growth method. Important optimization guidelines are found. In particular, the optimal nanowire radius that would lead to best device performance is deduced for each growth method.
Association of Vitamin D Receptor and Vitamin D-Binding Protein Polymorphisms with Familial Breast Cancer Prognosis in a Mono-Institutional Cohort
Authors: Aristarco Valentina , Johansson Harriet , Gandini Sara , Macis Debora , Zanzottera Cristina , Tolva Gianluca , Feroce Irene , Accornero Chiara , Bonanni Bernardo , Guerrieri-Gonzaga Aliana , Serrano Davide
Published: April 2021

Low 25-hydroxyvitamin D (25OHD) has been associated with an increased cancer incidence and poorer prognosis. Single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) and vitamin D binding protein (GC gene) may interfere with vitamin D activity. This study assesses the role of VDR and GC SNPs on breast cancer (BC) recurrence and survival in a cohort of patients with a family history of breast cancer, without the pathogenic variant for BRCA1 and BRCA2. A consecutive series of patients who underwent genetic testing were genotyped for VDR and GC genes. Specifically, ApaI, FokI, TaqI, BsmI and rs2282679, rs4588, rs7041 SNPs were determined. A total of 368 wild type (WT) patients with BC were analyzed for VDR and GC SNPs. The GC rs2282679 minor allele was significantly associated with luminal subtype of the primary tumor compared to Her2+/TN breast cancer (p = 0.007). Multivariate Cox models showed that BmsI and TaqI are significantly associated with BC outcome. Patients with the major alleles showed more than 30% lower hazard of relapse (BsmI p = 0.02 and TaqI p = 0.03). Our study supports the evidence for a pivotal role of 25OHD metabolism in BC. GC SNPs may influence the hormone tumor responsiveness and VDR may affect tumor prognosis.
Diet and Nutrition for Hepatitis
Authors: Himoto Takashi
Published: April 2021

The impairment of liver function frequently causes various type of malnutrition, as the liver is one of the most important organs involved in maintaining nutritional homeostasis [...]
The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer
Authors: Adinew Getinet M. , Taka Equar , Mendonca Patricia , Messeha Samia S. , Soliman Karam F. A.
Published: April 2021

Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.
Endocannabinoids and the Gut-Brain Control of Food Intake and Obesity
Authors: DiPatrizio Nicholas V.
Published: April 2021

Gut-brain signaling controls food intake and energy homeostasis, and its activity is thought to be dysregulated in obesity. We will explore new studies that suggest the endocannabinoid (eCB) system in the upper gastrointestinal tract plays an important role in controlling gut-brain neurotransmission carried by the vagus nerve and the intake of palatable food and other reinforcers. A focus will be on studies that reveal both indirect and direct interactions between eCB signaling and vagal afferent neurons. These investigations identify (i) an indirect mechanism that controls nutrient-induced release of peptides from the gut epithelium that directly interact with corresponding receptors on vagal afferent neurons, and (ii) a direct mechanism via interactions between eCBs and cannabinoid receptors expressed on vagal afferent neurons. Moreover, the impact of diet-induced obesity on these pathways will be considered.
Resting Energy Expenditure Is Not Altered in Children and Adolescents with Obesity. Effect of Age and Gender and Association with Serum Leptin Levels
Authors: Zapata J. Karina , Catalán Victoria , Rodríguez Amaia , Ramírez Beatriz , Silva Camilo , Escalada Javier , Salvador Javier , Calamita Giuseppe , Azcona-Sanjulian M. Cristina , Frühbeck Gema , Gómez-Ambrosi Javier
Published: April 2021

In children and adolescents, obesity does not seem to depend on a reduction of resting energy expenditure (REE). Moreover, in this young population, the interactions between either age and obesity or between age and gender, or the role of leptin on REE are not clearly understood. To compare the levels of REE in children and adolescents we studied 181 Caucasian individuals (62% girls) classified on the basis of age- and sex-specific body mass index (BMI) percentile as healthy weight (n = 50), with overweight (n = 34), or with obesity (n = 97) and in different age groups: 8–10 (n = 38), 11–13 (n = 50), and 14–17 years (n = 93). REE was measured by indirect calorimetry and body composition by air displacement plethysmography. Statistically significant differences in REE/fat-free mass (FFM) regarding obesity or gender were not observed. Absolute REE increases with age (p < 0.001), but REE/FFM decreases (p < 0.001) and there is an interaction between gender and age (p < 0.001) on absolute REE showing that the age-related increase is more marked in boys than in girls, in line with a higher FFM. Interestingly, the effect of obesity on absolute REE is not observed in the 8–10 year-old group, in which serum leptin concentrations correlate with the REE/FFM (r = 0.48; p = 0.011). In conclusion, REE/FFM is not affected by obesity or gender, while the effect of age on absolute REE is gender-dependent and leptin may influence the REE/FFM in 8–10 year-olds.
Relationships of Dietary Factors with Obesity, Hypertension, and Diabetes by Regional Type among Single-Person Households in Korea
Authors: Lee Kyung Won , Shin Dayeon
Published: April 2021

This study aims to investigate whether dietary factors are differentially associated with metabolic abnormalities by regional type among single-person households in Korea. A total of 685,327 Korean adults aged ≥19 years who participated in the household and individual surveys of the Korea Community Health Survey 2015–2017 are included in the analysis. The regions are divided into three categories: metropolitan areas, mid-sized cities, and rural areas. Using multivariable logistic regressions, the adjusted odds ratios and 95% confidence intervals for metabolic abnormalities are estimated by regional type after adjusting for covariates. Among the total study population, 12.21% occupy single-person households, and 47.5%, 25.1%, and 27.4% of those single-person households are in rural areas, mid-sized cities, and metropolitan areas, respectively. Compared with single-person households in rural areas, those in mid-sized and metropolitan cities tend to be more familiar with and frequently refer to nutrition labels, skip breakfast, and experience food insecurity. Regional differences are found in the associations of dietary factors and behavior with obesity, hypertension, and diabetes. The use of nutritional fact labels is associated with obesity and hypertension in single-person households in rural areas, and the degree of association between food insecurity and diabetes is highest among single-person households in metropolitan areas. Our findings suggest that policies for improving unhealthy dietary factors by regional type are needed to reduce regional health disparities among single-person households in Korea.
Significance of Levocarnitine Treatment in Dialysis Patients
Authors: Takashima Hiroyuki , Maruyama Takashi , Abe Masanori
Published: April 2021

Carnitine is a naturally occurring amino acid derivative that is involved in the transport of long-chain fatty acids to the mitochondrial matrix. There, these substrates undergo β-oxidation, producing energy. The major sources of carnitine are dietary intake, although carnitine is also endogenously synthesized in the liver and kidney. However, in patients on dialysis, serum carnitine levels progressively fall due to restricted dietary intake and deprivation of endogenous synthesis in the kidney. Furthermore, serum-free carnitine is removed by hemodialysis treatment because the molecular weight of carnitine is small (161 Da) and its protein binding rates are very low. Therefore, the dialysis procedure is a major cause of carnitine deficiency in patients undergoing hemodialysis. This deficiency may contribute to several clinical disorders in such patients. Symptoms of dialysis-related carnitine deficiency include erythropoiesis-stimulating agent-resistant anemia, myopathy, muscle weakness, and intradialytic muscle cramps and hypotension. However, levocarnitine administration might replenish the free carnitine and help to increase carnitine levels in muscle. This article reviews the previous research into levocarnitine therapy in patients on maintenance dialysis for the treatment of renal anemia, cardiac dysfunction, dyslipidemia, and muscle and dialytic symptoms, and it examines the efficacy of the therapeutic approach and related issues.
Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes: Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants
Authors: Pastorino Silvia , Bishop Tom , Sharp Stephen J. , Pearce Matthew , Akbaraly Tasnime , Barbieri Natalia B. , Bes-Rastrollo Maira , Beulens Joline W. J. , Chen Zhengming , Du Huaidong , Duncan Bruce B. , Goto Atsushi , Härkänen Tommi , Hashemian Maryam , Kromhout Daan , Järvinen Ritva , Kivimaki Mika , Knekt Paul , Lin Xu , Lund Eiliv , Magliano Dianna J. , Malekzadeh Reza , Martínez-González Miguel Ángel , O’Donoghue Gráinne , O’Gorman Donal , Poustchi Hossein , Rylander Charlotta , Sawada Norie , Shaw Jonathan E. , Schmidt Maria , Soedamah-Muthu Sabita S. , Sun Liang , Wen Wanqing , Wolk Alicja , Shu Xiao-Ou , Zheng Wei , Wareham Nicholas J. , Forouhi Nita G.
Published: April 2021

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction (p = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01–1.03, I2 = 61%) for total fish, 1.04 (1.01–1.07, I2 = 46%) for fatty fish, and 1.02 (1.00–1.04, I2 = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02–1.04, I2 = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.
Occurrence, Antimicrobial Resistance, and Molecular Characterization of Campylobacter spp. in Intensive Pig Production in South Africa
Authors: Sithole Viwe , Amoako Daniel Gyamfi , Abia Akebe Luther King , Perrett Keith , Bester Linda A. , Essack Sabiha Y.
Published: April 2021

Campylobacter spp. are among the leading foodborne pathogens, causing campylobacteriosis, a zoonotic infection that results in bacterial gastroenteritis and diarrheal disease in animals and humans. This study investigated the molecular epidemiology of antibiotic-resistant Campylobacter spp. isolated across the farm-to-fork-continuum in an intensive pig production system in South Africa. Following ethical approval, samples were collected over sixteen weeks from selected critical points (farm, transport, abattoir, and retail) using a farm-to-fork sampling approach according to WHO-AGISAR guidelines. Overall, 520 samples were investigated for the presence of Campylobacter spp., which were putatively identified using selective media with identity and speciation confirmed by polymerase chain reaction (PCR) of specific genes. Resistance profiles were ascertained by the Kirby–Bauer disk diffusion method. Antibiotic resistance and virulence genes were identified using PCR and DNA sequencing. Clonal relatedness was determined using ERIC-PCR. Altogether, 378/520 (72.7%) samples were positive for Campylobacter spp., with Campylobacter coli being the predominant species (73.3%), followed by Campylobacter jejuni (17.7%); 8.9% of the isolates were classified as “other spp”. Relatively high resistance was observed in C. coli and C. jejuni to erythromycin (89% and 99%), streptomycin (87% and 93%), tetracycline (82% and 96%), ampicillin (69% and 85%), and ciprofloxacin (53% and 67%), respectively. Multidrug resistance (MDR) was noted in 330 of the 378 (87.3%) isolates. The antibiotic resistance genes observed were tetO (74.6%), blaOXA-61 (2.9%), and cmeB (11.1%), accounting for the resistance to tetracycline and ampicillin. The membrane efflux pump (cmeB), conferring resistance to multiple antibiotics, was also detected in most resistant isolates. Chromosomal mutations in gyrA (Thr-86-Ile) and 23S rRNA (A2075G and A2074C) genes, conferring quinolone and erythromycin resistance, respectively, were also found. Of the virulence genes tested, ciaB, dnaJ, pldA, cdtA, cdtB, cdtC, and cadF were detected in 48.6%, 61.1%, 17.4%, 67.4%, 19.3%, 51%, and 5% of all Campylobacter isolates, respectively. Clonal analysis revealed that isolates along the continuum were highly diverse, with isolates from the same sampling points belonging to the same major ERIC-types. The study showed relatively high resistance to antibiotics commonly used in intensive pig production in South Africa with some evidence, albeit minimal, of transmission across the farm-to-fork continuum. This, together with the virulence profiles present in Campylobacter spp., presents a challenge to food safety and a potential risk to human health, necessitating routine surveillance, antibiotic stewardship, and comprehensive biosecurity in intensive pig production.
Neonatal and Pediatric Emergency Room Visits in a Tertiary Center during the COVID-19 Pandemic in Italy
Authors: Silvagni Davide , Baggio Laura , Lo Tartaro Meragliotta Patrizia , Soloni Pietro , La Fauci Giovanna , Bovo Chiara , Ielo Stefania , Biban Paolo
Published: April 2021

The COVID-19 pandemic is affecting healthcare services worldwide. We investigated the impact of a strict lockdown policy on the characteristics of neonatal and pediatric attendances to our pediatric emergency department (PED). The clinical features of PED visits in March–April 2020 (COVID-19) and March–April 2019 (non-COVID-19) were analyzed. During the COVID-19 lockdown period, visits reduced by 67%, from 3159 to 1039. Neonatal access decreased from 78 to 59, mainly due to fewer pathological conditions, with a complete disappearance of respiratory infections. On the other hand, minor neonatal clinical conditions rose from 44 (56.4%) to 48 (81.4%), mostly due to feeding-related issues. Communicable diseases, particularly respiratory infections and gastroenteritis, dropped from 1552 (49.1%) to 288 (27.7%). Accident-related visits also decreased during COVID-19, from 535 (16.9%) to 309 (29.7%), becoming the most common cause of PED access. Hospital admissions reduced from 266 to 109, while PICU (pediatric intensive care unit) admissions decreased from 27 to 11, with a comparable rate of 10.1% in both periods. The lockdown due to COVID-19 had a substantial impact on our PED visits, which markedly decreased, mainly due to fewer respiratory infections. Unexpectedly, neonatal visits for minor conditions did not decline, but rather slightly increased. Among the children admitted to the PICU, none had respiratory disease.
Exstrophy-Epispadias Complex Variants: A Hybrid Case
Authors: Ganarin Alba , Corroppolo Michele , Mazzero Giosuè , Revetria Clara , Beretta Fabio , Ciardini Enrico
Published: April 2021

The term exstrophy-epispadias complex refers to a group of midline defects ranging from epispadias to cloacal exstrophy. Bladder exstrophy is the most frequent malformation of this spectrum and it can present as a classical or a variant form. We report a case of a hybrid bladder exstrophy variant having some characteristics of both a duplicate bladder exstrophy and a superior vesical fistula.
Aryl Urea Based Scaffolds for Multitarget Drug Discovery in Anticancer Immunotherapies
Authors: Martín-Beltrán Celia , Gil-Edo Raquel , Hernández-Ribelles Germán , Agut Raül , Marí-Mezquita Pilar , Carda Miguel , Falomir Eva
Published: April 2021

Twenty-one styryl and phenethyl aryl ureas have been synthetized and biologically evaluated as multitarget inhibitors of Vascular endothelial growth factor receptor-2 VEGFR-2 and programmed death-ligand-1 (PD-L1) proteins in order to overcome resistance phenomena offered by cancer. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, MCF-7, HeLa and A549), on the endothelial cell line human microvascular endothelial cells (HMEC)-1 and on the non-tumor cell line human embryonic kidney cells (HEK)-293 has been determined. Some derivatives were evaluated for their antiangiogenic properties such as their ability to inhibit microvessel formation using HMEC-1 or their effect on VEGFR-2 in both cancer and endothelial cell lines. In addition, the immunomodulator action of a number of selected compounds was also studied on PD-L1 and c-Myc proteins. Compounds 16 and 23 (Z) and (E)-styryl p-bromophenyl urea, respectively, showed better results than sorafenib in down-regulation of VEGFR-2 and also improved the effect of the anti-PD-L1 compound BMS-8 on both targets, PD-L1 and c-Myc proteins.
Development of a Colorimetric Tool for SARS-CoV-2 and Other Respiratory Viruses Detection Using Sialic Acid Fabricated Gold Nanoparticles
Authors: Alfassam Haya A. , Nassar Majed S. , Almusaynid Manal M. , Khalifah Bashayer A. , Alshahrani Abdullah S. , Almughem Fahad A. , Alshehri Abdullah A. , Alawad Majed O. , Massadeh Salam , Alaamery Manal , Aldeailej Ibrahim M. , Alamri Aref A. , Binjomah Abdulwahab Z. , Tawfik Essam A.
Published: April 2021

Sialic acid that presents on the surface of lung epithelial cells is considered as one of the main binding targets for many respiratory viruses, including influenza and the current coronavirus (SARS-CoV-2) through the viral surface protein hemagglutinin. Gold nanoparticles (Au NPs) are extensively used in the diagnostic field owing to a phenomenon known as ‘surface plasmonic resonance’ in which the scattered light is absorbed by these NPs and can be detected via UV-Vis spectrophotometry. Consequently, sialic acid conjugated Au NPs (SA-Au NPs) were utilized for their plasmonic effect against SARS-CoV-2, influenza B virus, and Middle-East respiratory syndrome-related coronavirus (MERS) in patients’ swab samples. The SA-Au NPs system was prepared by a one-pot synthesis method, through which the NPs solution color changed from pale yellow to dark red wine color, indicting its successful preparation. In addition, the SA-Au NPs had an average particle size of 30 ± 1 nm, negative zeta potential (−30 ± 0.3 mV), and a UV absorbance of 525 nm. These NPs have proven their ability to change the color of the NPs solutions and patients’ swabs that contain SARS-CoV-2, influenza B, and MERS viruses, suggesting a rapid and straightforward detection tool that would reduce the spread of these viral infections and accelerate the therapeutic intervention.
Preparation and Preliminary Evaluation of Neurotensin Radiolabelled with 68Ga and 177Lu as Potential Theranostic Agent for Colon Cancer
Authors: Leonte Radu Anton , Chilug Livia Elena , Șerban Radu , Mustăciosu Cosmin , Raicu Alina , Manda Gina , Niculae Dana
Published: April 2021

The neurotensin is a tridecapeptide involved in the proliferation of colon cancer, the overexpression of neurotensin receptors occurring at an early stage development of many tumours. Targeting neurotensin receptors by using the same biological active molecule is an effective approach for both imaging quantification and treatment. The present work aimed to demonstrate the ability of radiolabelled neurotensin to specifically target colon cancer cells, and substantiate its usefulness in targeted imaging and radiotherapy, depending on the emission of the coupled radioisotope. Syntheses of 68Ga–DOTA–NT and 177Lu–DOTA–NT were developed to obtain a level of quality suitable for preclinical use with consistent high synthesis yields. Radiochemical purity meets the pharmaceutical requirements, and it is maintained 4 h for 68Ga–DOTA–NT and 48 h for 177Lu–DOTA–NT. Extensive in vitro studies were conducted to assess the uptake and retention of 68Ga–DOTA–NT, the amount of non-specific binding of neurotensin and the effect of 177Lu–DOTA–NT on HT–29 cells. In vivo biodistribution of 68Ga–DOTA–NT revealed significant uptake at the tumour site, along with fast clearance evidenced by decreasing activity in kidneys and blood after 60 min p.i. 177Lu–DOTA–NT exhibited similar uptake in the tumour, but also a significant uptake at 14 days p.i. in the bone marrow was reported. These results successfully demonstrated the potential of neurotensin to deliver imaging/therapeutic 68Ga/177Lu radioisotopes pair, but also the need for further evaluation of the possible radiotoxicity effects on the liver, kidneys or bone marrow.