bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Platform GPU-Based Implementation of Lattice Boltzmann Method Solver Using ArrayFire Library
Authors: Takáč Michal , Petráš Ivo
Published: July 2021

This paper deals with the design and implementation of cross-platform, D2Q9-BGK and D3Q27-MRT, lattice Boltzmann method solver for 2D and 3D flows developed with ArrayFire library for high-performance computing. The solver leverages ArrayFire’s just-in-time compilation engine for compiling high-level code into optimized kernels for both CUDA and OpenCL GPU backends. We also provide C++ and Rust implementations and show that it is possible to produce fast cross-platform lattice Boltzmann method simulations with minimal code, effectively less than 90 lines of code. An illustrative benchmarks (lid-driven cavity and Kármán vortex street) for single and double precision floating-point simulations on 4 different GPUs are provided.
RKC-B1 Blocks Activation of NF-κB and NLRP3 Signaling Pathways to Suppress Neuroinflammation in LPS-Stimulated Mice
Authors: Liu Man , Yang Ying-Lin , Zhang Shan-Shan , Liu Dong-Ni , Fang Lian-Hua , Du Guan-Hua , Wang Yue-Hua
Published: July 2021

RKC-B1 is a novel fermentation product obtained from the marine micromonospora FIM02-523A. Thus far, there have been few reports about the pharmacological activity of RKC-B1. In our present study, we investigated the anti-neuroinflammatory effects and the possible mechanism of RKC-B1 in LPS-stimulated mice. After treatment with RKC-B1, RNA-seq transcriptome of the cerebral cortex tissue was conducted to find the differentially expressed genes (DEGs). Inflammatory cytokines and proteins were evaluated by ELISA and WB. In RNA-seq analysis, there were 193 genes screened as core genes of RKC-B1 for treatment with neuroinflammation. The significant KEGG enrichment signaling pathways of these core genes were mainly included TNF signaling pathway, IL-17 signaling pathway, NOD-like receptor signaling pathway, NF-κB signaling pathway and others. The corresponding top five KEGG enrichment pathways of three main clusters in PPI network of core genes were closely related to human immune system and immune disease. The results showed that RKC-B1 reduced the levels of pro-inflammatory factors (IL-6, IL-1β, MCP-1, and ICAM-1) and the expression of COX2 in cerebral cortex tissue. Additionally, we found that the anti-neuroinflammation activity of RKC-B1 might be related to suppress activating of NF-κB and NLRP3/cleaved caspase-1 signaling pathways. The current findings suggested that RKC-B1 might be a promising anti-neuroinflammatory agent.
Clinical and Histological Long-Term Follow-Up of De Novo HBV-Infection after Liver Transplantation
Authors: Ossami Saidy Ramin Raul , Eurich Franziska , Postel Maximilian Paul , Dobrindt Eva Maria , Feldkamp Jasper , Schaper Selina Johanna , Pratschke Johann , Globke Brigitta , Eurich Dennis
Published: July 2021

Background and Objectives: Development of hepatitis-B is considered a serious complication after liver transplantation. HBV de novo infection is a rather rare phenomenon, however it deserves attention in the era of donor organ shortage. The aim of the present analysis was to examine its course in liver transplant patients. Materials and Methods: Prevalence of de novo HBV-infections was extracted from our local transplant data base. Analysis focused on the moment of HBV-detection and on the long-term follow-up in terms of biochemical and histological changes over 30 years. Results: 46 patients were identified with the diagnosis of de novo hepatitis B. Median time from liver transplantation to diagnosis was 397 days (7–5505). 39 patients received antiviral therapy. No fibrosis progression could be detected, whereas the grade of inflammation significantly lessened from the moment of HBV detection to the end of histological follow-up over a median of 4344 days (range 123–9490). Patients with a poor virological control demonstrated a significantly poorer overall survival. Conclusions: De novo hepatitis B in liver transplant patients is a condition that can be controlled very well without significant fibrosis progression or graft loss if recognized on time within a regular transplant follow-up schedule.
Using kICS to Reveal Changed Membrane Diffusion of AQP-9 Treated with Drugs
Authors: Kure Jakob L. , Karlsson Thommie , Andersen Camilla B. , Lagerholm B. Christoffer , Loitto Vesa , Magnusson Karl-Eric , Arnspang Eva C.
Published: July 2021

The formation of nanodomains in the plasma membrane are thought to be part of membrane proteins regulation and signaling. Plasma membrane proteins are often investigated by analyzing the lateral mobility. k-space ICS (kICS) is a powerful image correlation spectroscopy (ICS) technique and a valuable supplement to fluorescence correlation spectroscopy (FCS). Here, we study the diffusion of aquaporin-9 (AQP9) in the plasma membrane, and the effect of different membrane and cytoskeleton affecting drugs, and therefore nanodomain perturbing, using kICS. We measured the diffusion coefficient of AQP9 after addition of these drugs using live cell Total Internal Reflection Fluorescence imaging on HEK-293 cells. The actin polymerization inhibitors Cytochalasin D and Latrunculin A do not affect the diffusion coefficient of AQP9. Methyl-β-Cyclodextrin decreases GFP-AQP9 diffusion coefficient in the plasma membrane. Human epidermal growth factor led to an increase in the diffusion coefficient of AQP9. These findings led to the conclusion that kICS can be used to measure diffusion AQP9, and suggests that the AQP9 is not part of nanodomains.
In Silico Identification of Cholesterol Binding Motifs in the Chemokine Receptor CCR3
Authors: van Aalst Evan , Koneri Jotham , Wylie Benjamin J.
Published: July 2021

CC motif chemokine receptor 3 (CCR3) is a Class A G protein-coupled receptor (GPCR) mainly responsible for the cellular trafficking of eosinophils. As such, it plays key roles in inflammatory conditions, such as asthma and arthritis, and the metastasis of many deadly forms of cancer. However, little is known about how CCR3 functionally interacts with its bilayer environment. Here, we investigate cholesterol binding sites in silico through Coarse-Grained Molecular Dynamics (MD) and Pylipid analysis using an extensively validated homology model based on the crystal structure of CCR5. These simulations identified several cholesterol binding sites containing Cholesterol Recognition/Interaction Amino Acid Consensus motif (CRAC) and its inversion CARC motifs in CCR3. One such site, a CARC site in TM1, in conjunction with aliphatic residues in TM7, emerged as a candidate for future investigation based on the cholesterol residency time within the binding pocket. This site forms the core of a cholesterol binding site previously observed in computational studies of CCR2 and CCR5. Most importantly, these cholesterol binding sites are conserved in other chemokine receptors and may provide clues to cholesterol regulation mechanisms in this subfamily of Class A GPCRs.
The Effect of LSP on the Structure Evolution and Self-Heating of ARMCO Iron under Cyclic Loading
Authors: Prokhorov Aleksander , Vshivkov Aleksei , Plekhov Oleg , Kashaev Nikolai , Fomin Fedor , Ozerov Maxim , Zherebtsov Sergey
Published: July 2021

This work is devoted to the experimental investigation of the effect of laser shock peening (LSP) on the thermo-mechanical properties of metals. ARMCO iron was chosen as the model material for the study. Samples were subjected to LSP, and were tested following the procedure of the self-heating (Risitano) technique. To investigate the damage that was induced by heating, the fatigue tests were coupled with infrared thermography measurements. The results of the study showed that the LSP procedure qualitatively changes the temperature evolution in ARMCO iron during cyclic loading. The heating (energy dissipation) of the LSP treated specimen was several times higher than that of the specimen in the initial state. To explain the structural mechanisms of energy dissipation, the microstructure of the specimens was examined using transmission (TEM) and scanning (SEM) electron microscopy, as well as electron backscattering diffraction (EBSD). The results of the structural investigation confirm the qualitative change of defect evolution caused by LSP treatment.
Investigating Global Lipidome Alterations with the Lipid Network Explorer
Authors: Köhler Nikolai , Rose Tim Daniel , Falk Lisa , Pauling Josch Konstantin
Published: July 2021

Lipids play an important role in biological systems and have the potential to serve as biomarkers in medical applications. Advances in lipidomics allow identification of hundreds of lipid species from biological samples. However, a systems biological analysis of the lipidome, by incorporating pathway information remains challenging, leaving lipidomics behind compared to other omics disciplines. An especially uncharted territory is the integration of statistical and network-based approaches for studying global lipidome changes. Here we developed the Lipid Network Explorer (LINEX), a web-tool addressing this gap by providing a way to visualize and analyze functional lipid metabolic networks. It utilizes metabolic rules to match biochemically connected lipids on a species level and combine it with a statistical correlation and testing analysis. Researchers can customize the biochemical rules considered, to their tissue or organism specific analysis and easily share them. We demonstrate the benefits of combining network-based analyses with statistics using publicly available lipidomics data sets. LINEX facilitates a biochemical knowledge-based data analysis for lipidomics. It is availableas a web-application and as a publicly available docker container.
Rapid Identification of Common Secondary Metabolites of Medicinal Herbs Using High-Performance Liquid Chromatography with Evaporative Light Scattering Detector in Extracts
Authors: Ali Kiran , Ali Arslan , Khan Muhammad Noman , Rahman Saeedur , Faizi Shaheen , Ali Muhammad Shaiq , Khalifa Shaden A. M. , El-Seedi Hesham R. , Musharraf Syed Ghulam
Published: July 2021

The discovery and identification of novel natural products of medicinal importance in the herbal medicine industry becomes a challenge. The complexity of this process can be reduced by dereplication strategies. The current study includes a method based on high-performance liquid chromatography (HPLC), using the evaporative light scattering detector (ELSD) to identify the 12 most common secondary metabolites in plant extracts. Twelve compounds including rutin, taxifolin, quercetin, apigenin, kaempferol, betulinic acid, oleanolic acid, betulin, lupeol, stigmasterol, and β-sitosterol were analyzed simultaneously. The polarity of the compounds varied greatly from highly polar (flavonoids) to non-polar (triterpenes and sterols). This method was also tested for HPLC-DAD and HPLC-ESI-MS/MS analysis. Oleanolic acid and ursolic acid could not be separated in HPLC-ELSD analysis but were differentiated using LC-ESI-MS/MS analysis due to different fragment ions. The regression values (R2 > 0.996) showed good linearity in the range of 50–1000 µg/mL for all compounds. The range of LOD and LOQ values were 7.76–38.30 µg/mL and 23.52–116.06 µg/mL, respectively. %RSD and % trueness values of inter and intraday studies were mostly <10%. This method was applied on 10 species of medicinal plants. The dereplication strategy has the potential to facilitate and shorten the identification process of common secondary metabolites in complex plant extracts.
Editorial for the Special Issue on Nanofabrication with Focused Electron/Ion Beam Induced Processing
Authors: Córdoba Rosa
Published: July 2021

Focused electron beam (FEB) and focused ion beam (FIB) technologies have opened novel paths for material science research and technology at the micro and nano scales in recent decades [...]
Gut Dysbiosis during COVID-19 and Potential Effect of Probiotics
Authors: Hung Yuan-Pin , Lee Ching-Chi , Lee Jen-Chieh , Tsai Pei-Jane , Ko Wen-Chien
Published: July 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus of the family Coronaviridae, causes coronavirus disease 2019 (COVID-19), an influenza-like disease that chiefly infects the lungs through respiratory transmission. The spike protein of SARS-CoV-2, a transmembrane protein in its outer portion, targets angiotensin-converting enzyme 2 (ACE2) as the binding receptor for the cell entry. As ACE2 is highly expressed in the gut and pulmonary tissues, SARS-CoV-2 infections frequently result in gastrointestinal inflammation, with presentations ordinarily ranging from intestinal cramps to complications with intestinal perforations. However, the evidence detailing successful therapy for gastrointestinal involvement in COVID-19 patients is currently limited. A significant change in fecal microbiomes, namely dysbiosis, was characterized by the enrichment of opportunistic pathogens and the depletion of beneficial commensals and their crucial association to COVID-19 severity has been evidenced. Oral probiotics had been evidenced to improve gut health in achieving homeostasis by exhibiting their antiviral effects via the gut–lung axis. Although numerous commercial probiotics have been effective against coronavirus, their efficacies in treating COVID-19 patients remain debated. In ClinicalTrials.gov, 19 clinical trials regarding the dietary supplement of probiotics, in terms of Lactobacillus and mixtures of Bifidobacteria and Lactobacillus, for treating COVID-19 cases are ongoing. Accordingly, the preventive or therapeutic role of probiotics for COVID-19 patients can be elucidated in the near future.
Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders
Authors: Quezada Elías , Rodríguez-Enríquez Fernanda , Laguna Reyes , Cutrín Elena , Otero Francisco , Uriarte Eugenio , Viña Dolores
Published: July 2021

Neurodegenerative diseases have a complex nature which highlights the need for multitarget ligands to address the complementary pathways involved in these diseases. Over the last decade, many innovative curcumin-based compounds have been designed and synthesized, searching for new derivatives having anti-amyloidogenic, inhibitory of tau formation, as well as anti-neuroinflammation, antioxidative, and AChE inhibitory activities. Regarding our experience studying 3-substituted coumarins with interesting properties for neurodegenerative diseases, our aim was to synthesize a new series of curcumin–coumarin hybrid analogues and evaluate their activity. Most of the 3-(7-phenyl-3,5-dioxohepta-1,6-dien-1-yl)coumarin derivatives 11–18 resulted in moderated inhibitors of hMAO isoforms and AChE and BuChE activity. Some of them are also capable of scavenger the free radical DPPH. Furthermore, compounds 14 and 16 showed neuroprotective activity against H2O2 in SH-SY5Y cell line. Nanoparticles formulation of these derivatives improved this property increasing the neuroprotective activity to the nanomolar range. Results suggest that by modulating the substitution pattern on both coumarin moiety and phenyl ring, ChE and MAO-targeted derivatives or derivatives with activity in cell-based phenotypic assays can be obtained.
The Effect of Fat Content and Fatty Acids Composition on Color and Textural Properties of Butter
Authors: Pădureţ Sergiu
Published: July 2021

The textural properties of butter are influenced by its fat content and implicitly by the fatty acids composition. The impact of butter’s chemical composition variation was studied in accordance with texture and color properties. From 37 fatty acids examined, only 18 were quantified in the analyzed butter fat samples, and approximately 69.120% were saturated, 25.482% were monounsaturated, and 5.301% were polyunsaturated. The butter samples’ viscosity ranged between 0.24 and 2.12 N, while the adhesiveness ranged between 0.286 to 18.19 N·mm. The principal component analysis (PCA) separated the butter samples based on texture parameters, fatty acids concentration, and fat content, which were in contrast with water content. Of the measured color parameters, the yellowness b* color parameter is a relevant indicator that differentiated the analyzed sample into seven statistical groups; the ANOVA statistics highlighted this difference at a level of p < 0.001.
Inhibitory Activity and Mechanism Investigation of Hypericin as a Novel α-Glucosidase Inhibitor
Authors: Dong Qi , Hu Na , Yue Huilan , Wang Honglun
Published: July 2021

α-glucosidase is a major enzyme that is involved in starch digestion and type 2 diabetes mellitus. In this study, the inhibition of hypericin by α-glucosidase and its mechanism were firstly investigated using enzyme kinetics analysis, real-time interaction analysis between hypericin and α-glucosidase by surface plasmon resonance (SPR), and molecular docking simulation. The results showed that hypericin was a high potential reversible and competitive α-glucosidase inhibitor, with a maximum half inhibitory concentration (IC50) of 4.66 ± 0.27 mg/L. The binding affinities of hypericin with α-glucosidase were assessed using an SPR detection system, which indicated that these were strong and fast, with balances dissociation constant (KD) values of 6.56 × 10−5 M and exhibited a slow dissociation reaction. Analysis by molecular docking further revealed that hydrophobic forces are generated by interactions between hypericin and amino acid residues Arg-315 and Tyr-316. In addition, hydrogen bonding occurred between hypericin and α-glucosidase amino acid residues Lys-156, Ser-157, Gly-160, Ser-240, His-280, Asp-242, and Asp-307. The structure and micro-environment of α-glucosidase enzymes were altered, which led to a decrease in α-glucosidase activity. This research identified that hypericin, an anthracene ketone compound, could be a novel α-glucosidase inhibitor and further applied to the development of potential anti-diabetic drugs.
A Study of the Interaction, Morphology, and Structure in Trypsin-Epigallocatechin-3-Gallate Complexes
Authors: Liu Jiayin , Ghanizadeh Hossein , Li Xinmao , Han Zhengyuan , Qiu Youwen , Zhang Yao , Chen Xiuling , Wang Aoxue
Published: July 2021

Understanding the interaction between proteins and polyphenols is of significance to food industries. The aim of this research was to investigate the mode of aggregation for trypsin-EGCG (Epigallocatechin-3-gallate) complexes. For this, the complex was characterized by fluorescence spectroscopy, circular dichroism (CD) spectra, small-angel X-ray scattering (SAXS), and atomic force microscope (AFM) techniques. The results showed that the fluorescence intensity of trypsin-EGCG complexes decreased with increasing the concentration of EGCG, indicating that the interaction between trypsin and EGCG resulted in changes in the microenvironment around fluorescent amino acid residues. The results of CD analysis showed conformational changes in trypsin after binding with EGCG. The results from SAXS analysis showed that the addition of EGCG results in the formation of aggregates of trypsin-EGCG complexes, and increasing the concentration of EGCG resulted in larger aggregates. AFM images showed that the trypsin-EGCG complex formed aggregates of irregular ellipsoidal shapes with the size of about 200 × 400 × 200 nm, with EGCG interconnecting the trypsin particles. Overall, according to these results, it was concluded that the large aggregates of trypsin-EGCG complexes are formed from several small aggregates that are interconnected. The results of this study shed some light on the interaction between digestive enzymes and EGCG.
Non-Saccharomyces as Biotools to Control the Production of Off-Flavors in Wines
Authors: Morata Antonio , Loira Iris , González Carmen , Escott Carlos
Published: July 2021

Off-flavors produced by undesirable microbial spoilage are a major concern in wineries, as they affect wine quality. This situation is worse in warm areas affected by global warming because of the resulting higher pHs in wines. Natural biotechnologies can aid in effectively controlling these processes, while reducing the use of chemical preservatives such as SO2. Bioacidification reduces the development of spoilage yeasts and bacteria, but also increases the amount of molecular SO2, which allows for lower total levels. The use of non-Saccharomyces yeasts, such as Lachancea thermotolerans, results in effective acidification through the production of lactic acid from sugars. Furthermore, high lactic acid contents (>4 g/L) inhibit lactic acid bacteria and have some effect on Brettanomyces. Additionally, the use of yeasts with hydroxycinnamate decarboxylase (HCDC) activity can be useful to promote the fermentative formation of stable vinylphenolic pyranoanthocyanins, reducing the amount of ethylphenol precursors. This biotechnology increases the amount of stable pigments and simultaneously prevents the formation of high contents of ethylphenols, even when the wine is contaminated by Brettanomyces.
Testing Strategies of the In Vitro Micronucleus Assay for the Genotoxicity Assessment of Nanomaterials in BEAS-2B Cells
Authors: Cervena Tereza , Rossnerova Andrea , Zavodna Tana , Sikorova Jitka , Vrbova Kristyna , Milcova Alena , Topinka Jan , Rossner Pavel
Published: July 2021

The evaluation of the frequency of micronuclei (MN) is a broadly utilised approach in in vitro toxicity testing. Nevertheless, the specific properties of nanomaterials (NMs) give rise to concerns regarding the optimal methodological variants of the MN assay. In bronchial epithelial cells (BEAS-2B), we tested the genotoxicity of five types of NMs (TiO2: NM101, NM103; SiO2: NM200; Ag: NM300K, NM302) using four variants of MN protocols, differing in the time of exposure and the application of cytochalasin-B combined with the simultaneous and delayed co-treatment with NMs. Using transmission electron microscopy, we evaluated the impact of cytochalasin-B on the transport of NMs into the cells. To assess the behaviour of NMs in a culture media for individual testing conditions, we used dynamic light scattering measurement. The presence of NMs in the cells, their intracellular aggregation and dispersion properties were comparable when tests with or without cytochalasin-B were performed. The genotoxic potential of various TiO2 and Ag particles differed (NM101 < NM103 and NM302 < NM300K, respectively). The application of cytochalasin-B tended to increase the percentage of aberrant cells. In conclusion, the comparison of the testing strategies revealed that the level of DNA damage induced by NMs is affected by the selected methodological approach. This fact should be considered in the interpretation of the results of genotoxicity tests.
Hybrid Films Based on Bilayer Graphene and Single-Walled Carbon Nanotubes: Simulation of Atomic Structure and Study of Electrically Conductive Properties
Authors: Slepchenkov Michael M. , Barkov Pavel V. , Glukhova Olga E.
Published: July 2021

One of the urgent problems of materials science is the search for the optimal combination of graphene modifications and carbon nanotubes (CNTs) for the formation of layered hybrid material with specified physical properties. High electrical conductivity and stability are one of the main optimality criteria for a graphene/CNT hybrid structure. This paper presents results of a theoretical and computational study of the peculiarities of the atomic structure and the regularities of current flow in hybrid films based on single-walled carbon nanotubes (SWCNTs) with a diameter of 1.2 nm and bilayer zigzag graphene nanoribbons, where the layers are shifted relative to the other. It is found that the maximum stresses on atoms of hybrid film do not exceed ~0.46 GPa for all considered topological models. It is shown that the electrical conductivity anisotropy takes place in graphene/SWCNT hybrid films at a graphene nanoribbon width of 4 hexagons. In the direction along the extended edge of the graphene nanoribbon, the electrical resistance of graphene/SWCNT hybrid film reaches ~125 kOhm; in the direction along the nanotube axis, the electrical resistance is about 16 kOhm. The prospects for the use of graphene/SWCNT hybrid films in electronics are predicted based on the obtained results.
Low-Cost 400 Gbps DR4 Silicon Photonics Transmitter for Short-Reach Datacenter Application
Authors: Zhu Haike , Anderson Sean , Karfelt Nick , Jiang Lingjun , Li Yunchu , Boeck Robert , Yamazaki Hiroyuki , Wang Meng , Kankipati Raju , Grzybowski Richard
Published: July 2021

Targeting high-speed, low-cost, short-reach intra-datacenter connections, we designed and tested an integrated silicon photonic circuit as a transmitter engine. This engine can be packaged into an optical transceiver module which meets the QSFP-DD Form Factor, together with other electrical/optical components. We first present the design and performance of a high-speed silicon modulator, which had a 3-dB EO bandwidth of >40 GHz and an ER of >5 dB. We then incorporated the engine onto a test board and injected a 53.125 Gbaud PAM4 signal. Clear eye patterns were observed at the receiver with TDECQ ~3 dB for all four lanes.
Treating Traumatic Brain Injuries with Electroceuticals: Implications for the Neuroanatomy of Consciousness
Authors: Aburas Jihad , Aziz Areej , Butt Maryam , Leschinsky Angela , Pierce Marsha L.
Published: July 2021

According to the Centers for Disease Control and Prevention (CDC), traumatic brain injury (TBI) is the leading cause of loss of consciousness, long-term disability, and death in children and young adults (age 1 to 44). Currently, there are no United States Food and Drug Administration (FDA) approved pharmacological treatments for post-TBI regeneration and recovery, particularly related to permanent disability and level of consciousness. In some cases, long-term disorders of consciousness (DoC) exist, including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) characterized by the exhibition of reflexive behaviors only or a minimally conscious state (MCS) with few purposeful movements and reflexive behaviors. Electroceuticals, including non-invasive brain stimulation (NIBS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS) have proved efficacious in some patients with TBI and DoC. In this review, we examine how electroceuticals have improved our understanding of the neuroanatomy of consciousness. However, the level of improvements in general arousal or basic bodily and visual pursuit that constitute clinically meaningful recovery on the Coma Recovery Scale-Revised (CRS-R) remain undefined. Nevertheless, these advancements demonstrate the importance of the vagal nerve, thalamus, reticular activating system, and cortico-striatal-thalamic-cortical loop in the process of consciousness recovery.
A Fit-for-Purpose Nutrient Profiling Model to Underpin Food and Nutrition Policies in South Africa
Authors: Frank Tamryn , Thow Anne-Marie , Ng Shu Wen , Ostrowski Jessica , Bopape Makoma , Swart Elizabeth C.
Published: July 2021

South Africa (SA) is facing a rising prevalence of obesity and diet-related chronic diseases. The government is seeking to develop effective, evidence-based policy measures to address this. A well-designed, fit-for-purpose nutrient profiling model (NPM) can aid policy development. The aim of this study was to develop a fit-for-purpose NPM in SA. Steps included: (1) determining the purpose and target population; (2) selecting appropriate nutrients and other food components to include; (3) selecting a suitable NPM type, criteria and base; and (4) selecting appropriate numbers and thresholds. As part of the evaluation, the nutritional composition of packaged foods containing nutritional information (n = 6747) in the SA food supply chain was analyzed, a literature review was undertaken and various NPMs were evaluated. Our findings indicated that it is most appropriate to adapt an NPM and underpin regulation with a restrictive NPM that limits unhealthy food components. The Chile 2019 NPM was identified as suitable to adapt, and total sugar, saturated fat, sodium and non-sugar sweetener were identified as appropriate to restrict. This NPM has the potential to underpin restrictive policies, such as front-of-package labelling and child-directed marketing regulations in SA. These policies will support the fight against obesity and NCDs in the country.
Diet and Leukocyte Telomere Length in a Population with Extended Longevity: The Costa Rican Longevity and Healthy Aging Study (CRELES)
Authors: Ruiz-Narváez Edward A. , Baylin Ana , Azofeifa Jorge , Leal Alejandro , Rosero-Bixby Luis
Published: July 2021

Elderly Costa Ricans have lower mortality rates compared to their counterparts from developed countries. Reasons for this survival advantage are not completely known. In the present study, we aimed to identify dietary factors associated with leukocyte telomere length (LTL), a marker of biologic aging, in the elderly population of Costa Rica. We conducted prospective analysis in 909 participants aged 60+ years from the Costa Rican Longevity and Healthy Aging Study (CRELES). We used a food frequency questionnaire to assess usual diet. We calculated dietary patterns using Principal Component Analysis (PCA). We used generalized linear models to examine the association of dietary patterns and food groups with leukocyte telomere length. We found two major dietary patterns explaining 9.15% and 7.18% of the total variation of food intake, respectively. The first dietary pattern, which represents a traditional Costa Rican rice and beans pattern, was more frequent in rural parts of the country and was positively associated with baseline LTL: β (95% CI) = 42.0 base-pairs (bp) (9.9 bp, 74.1 bp) per one-unit increase of the traditional dietary pattern. In analysis of individual food groups, intake of grains was positively associated with baseline LTL: β (95% CI) = 43.6 bp (13.9 bp, 73.3 bp) per one-serving/day increase of consumption of grains. Our results suggest that dietary factors, in particular a traditional food pattern, are associated with telomere length and may contribute to the extended longevity of elderly Costa Ricans.
Palmitoleoylethanolamide Is an Efficient Anti-Obesity Endogenous Compound: Comparison with Oleylethanolamide in Diet-Induced Obesity
Authors: Tovar Rubén , Gavito Ana Luisa , Vargas Antonio , Soverchia Laura , Hernandez-Folgado Laura , Jagerovic Nadine , Baixeras Elena , Ciccocioppo Roberto , Rodríguez de Fonseca Fernando , Decara Juan
Published: July 2021

Obesity is currently a major epidemic in the developed world. However, we lack a wide range of effective pharmacological treatments and therapies against obesity, and those approved are not devoid of adverse effects. Dietary components such as palmitoleic acid have been proposed to improve metabolic disbalance in obesity, although the mechanisms involved are not well understood. Both palmitoleic acid (POA) and oleic acid (OA) can be transformed in N-acylethanolamines (NAEs), mediating the effects of dietary POA and OA. To test this hypothesis, here, we study the effects on food intake and body weight gain of palmitoleylethanolamide (POEA) and the OA-derived NAE analogue, oleoylethanolamide (OEA), in Sprague–Dawley rats with a hypercaloric cafeteria diet (HFD). Plasma biochemical metabolites, inflammatory mediators, and lipogenesis-associated liver protein expression were also measured. The results indicate that POEA is able to improve health status in diet-induced obesity, decreasing weight, liver steatosis, inflammation, and dyslipemia. The action of POEA was found to be almost identical to that of OEA, which is an activator of the nuclear peroxisome proliferator receptor alpha (PPARα), and it is structurally related to POEA. These results suggest that the dietary administration of either POA or POEA might be considered as nutritional intervention as complementary treatment for complicated obesity in humans.
Plasma Free Fatty Acid Concentration as a Modifiable Risk Factor for Metabolic Disease
Authors: Henderson Gregory C.
Published: July 2021

Plasma free fatty acid (FFA) concentration is elevated in obesity, insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and related comorbidities such as cardiovascular disease (CVD). Furthermore, experimentally manipulating plasma FFA in the laboratory setting modulates metabolic markers of these disease processes. In this article, evidence is presented indicating that plasma FFA is a disease risk factor. Elevations of plasma FFA can promote ectopic lipid deposition, IR, as well as vascular and cardiac dysfunction. Typically, elevated plasma FFA results from accelerated adipose tissue lipolysis, caused by a high adipose tissue mass, adrenal hormones, or other physiological stressors. Reducing an individual’s postabsorptive and postprandial plasma FFA concentration is expected to improve health. Lifestyle change could provide a significant opportunity for plasma FFA reduction. Various factors can impact plasma FFA concentration, such as chronic restriction of dietary energy intake and weight loss, as well as exercise, sleep quality and quantity, and cigarette smoking. In this review, consideration is given to multiple factors which lead to plasma FFA elevation and subsequent disruption of metabolic health. From considering a variety of medical conditions and lifestyle factors, it becomes clear that plasma FFA concentration is a modifiable risk factor for metabolic disease.
Physiological Functions of Threonine in Animals: Beyond Nutrition Metabolism
Authors: Tang Qi , Tan Peng , Ma Ning , Ma Xi
Published: July 2021

Threonine (Thr), an essential amino acid for animals and the limiting amino acid in swine and poultry diets, which plays a vital role in the modulation of nutritional metabolism, macromolecular biosynthesis, and gut homeostasis. Current evidence supports that the supplementation of Thr leads to benefits in terms of energy metabolism. Threonine is not only an important component of gastrointestinal mucin, but also acts as a nutritional modulator that influences the intestinal immune system via complex signaling networks, particularly mitogen-activated protein kinase (MAPK) and the target of the rapamycin (TOR) signal pathway. Threonine is also recognized as an indispensable nutrient for cell growth and proliferation. Hence, optimization of Thr requirement may exert a favorable impact on the factors linked to health and diseases in animals. This review focuses on the latest reports of Thr in metabolic pathways and nutritional regulation, as well as the relationship between Thr and relevant physiological functions.
Allium-Derived Compound Propyl Propane Thiosulfonate (PTSO) Attenuates Metabolic Alterations in Mice Fed a High-Fat Diet through Its Anti-Inflammatory and Prebiotic Properties
Authors: Vezza Teresa , Garrido-Mesa José , Diez-Echave Patricia , Hidalgo-García Laura , Ruiz-Malagón Antonio J. , García Federico , Sánchez Manuel , Toral Marta , Romero Miguel , Duarte Juan , Guillamón Enrique , Baños Arjona Alberto , Moron Rocío , Galvez Julio , Rodríguez-Nogales Alba , Rodríguez-Cabezas María Elena
Published: July 2021

Background: Propyl propane thiosulfonate (PTSO) is an organosulfur compound from Allium spp. that has shown interesting antimicrobial properties and immunomodulatory effects in different experimental models. In this sense, our aim was to evaluate its effect on an experimental model of obesity, focusing on inflammatory and metabolic markers and the gut microbiota. Methods and results: Mice were fed a high-fat diet and orally treated with different doses of PTSO (0.1, 0.5 and 1 mg/kg/day) for 5 weeks. PTSO lessened the weight gain and improved the plasma markers associated with glucose and lipid metabolisms. PTSO also attenuated obesity-associated systemic inflammation, reducing the immune cell infiltration and, thus, the expression of pro-inflammatory cytokines in adipose and hepatic tissues (Il-1ẞ, Il-6, Tnf-α, Mcp-1, Jnk-1, Jnk-2, Leptin, Leptin R, Adiponectin, Ampk, Ppar-α, Ppar-γ, Glut-4 and Tlr-4) and improving the expression of different key elements for gut barrier integrity (Muc-2, Muc-3, Occludin, Zo-1 and Tff-3). Additionally, these effects were connected to a regulation of the gut microbiome, which was altered by the high-fat diet. Conclusion: Allium-derived PTSO can be considered a potential new tool for the treatment of metabolic syndrome.
Clinical and Immunological Efficacy of Mangosteen and Propolis Extracted Complex in Patients with Gingivitis: A Multi-Centered Randomized Controlled Clinical Trial
Authors: Park Jin-Young , Ko Kyung-A , Lee Ji-Yeong , Oh Jae-Woon , Lim Hyun-Chang , Lee Dong-Woon , Choi Seong-Ho , Cha Jae-Kook
Published: July 2021

Background: Mangosteen and propolis extracts (MAEC) have been potential therapeutic agents known to exhibit powerful antioxidant and anti-inflammatory properties. The aim of the current study was to evaluate the clinical and immunological efficacy of MAEC as well as safety and patient-reported outcomes (PROMs) on gingivitis and incipient periodontitis. Methods: This study was performed on 104 patients diagnosed with gingivitis or incipient periodontitis. At baseline, the participants were randomly allocated to either the test group, with daily intake of a single capsule containing 194 mg of MAEC for eight weeks, or control group, with placebo. Clinical periodontal evaluation and immunological parameters from saliva and gingival sulcular fluid were assessed at baseline, four, and eight weeks. Individual PROMs were assessed by OHIP-14 questionnaires. Results: There was a significant difference of modified gingival index at four and eight weeks between the test and control groups. In the test group, crevicular interleukin (IL)-6 was reduced, and the salivary matrix metalloproteinase (MMP)-9 was increased after eight weeks. PROMs were improved up to four weeks compared to placebo. Conclusion: Oral administration of MAEC would have a potential to reduce gingival inflammation clinically and immunologically in the patients with gingivitis and incipient periodontitis.
Is School Gardening Combined with Physical Activity Intervention Effective for Improving Childhood Obesity? A Systematic Review and Meta-Analysis
Authors: Qi Yufei , Hamzah Sareena Hanim , Gu Erya , Wang Haonan , Xi Yue , Sun Minghui , Rong Siyu , Lin Qian
Published: July 2021

School gardening activities (SGA) combined with physical activities (PA) may improve childhood dietary intake and prevent overweight and obesity. This study aims to evaluate the effect of SGA combined with PA on children’s dietary intake and anthropometric outcomes. We searched studies containing randomized controlled trials up to January 2021 in Web of Science, PubMed, Cochrane Library, and the EBSCO database on this topic for children aged 7 to 12 years. Fourteen studies met the requirements for meta-analysis (n = 9187). We found that SGA has no obvious effect on improving children’s BMI (WMD = −0.49; p = 0.085; I2 = 86.3%), BMI z-score (WMD = −0.12; p = 0.235; I2 = 63.0%), and WC (WMD = −0.98; p = 0.05; I2 = 72.9%). SGA can effectively improve children’s FVs (WMD = 0.59, p = 0.003, I2 = 95.3%). SGA combined with PA can significantly increase children’s FVs but cannot greatly improve weight status. Although more studies on this topic are needed to prove the effectiveness of this method, the results of our review show that both SGA and SGA combined with PA has a modest but positive impact of reducing BMI and WC outcomes but can significantly increase children’s FVs.
Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review
Authors: Pietkiewicz Dagmara , Klupczynska-Gabryszak Agnieszka , Plewa Szymon , Misiura Magdalena , Horala Agnieszka , Miltyk Wojciech , Nowak-Markwitz Ewa , Kokot Zenon J. , Matysiak Jan
Published: July 2021

Gynecological and breast cancers still remain a significant health problem worldwide. Diagnostic methods are not sensitive and specific enough to detect the disease at an early stage. During carcinogenesis and tumor progression, the cellular need for DNA and protein synthesis increases leading to changes in the levels of amino acids. An important role of amino acids in many biological pathways, including biosynthesis of proteins, nucleic acids, enzymes, etc., which serve as an energy source and maintain redox balance, has been highlighted in many research articles. The aim of this review is a detailed analysis of the literature on metabolomic studies of gynecology and breast cancers with particular emphasis on alterations in free amino acid profiles. The work includes a brief overview of the metabolomic methodology and types of biological samples used in the studies. Special attention was paid to the possible role of selected amino acids in the carcinogenesis, especially proline and amino acids related to its metabolism. There is a clear need for further research and multiple external validation studies to establish the role of amino acid profiling in diagnosing gynecological and breast cancers.
GALAD Score Detects Early-Stage Hepatocellular Carcinoma in a European Cohort of Chronic Hepatitis B and C Patients
Authors: Schotten Clemens , Ostertag Bastian , Sowa Jan-Peter , Manka Paul , Bechmann Lars P. , Hilgard Gudrun , Marquardt Claudio , Wichert Marc , Toyoda Hidenori , Lange Christian M. , Canbay Ali , Johnson Philip , Wedemeyer Heiner , Best Jan
Published: July 2021

Despite vaccination programs and direct antiviral treatments, the incidence of virus-related hepatocellular carcinoma (HCC) remains high, while ultrasound-based detection rates for early-stage HCC is continuously low. To address this insufficiency, we set out to characterize whether the GALAD score, which incorporates gender, age, and serum levels of AFP, AFP isoform L3 (AFP-L3), and des-gamma-carboxy-prothrombin (DCP), can improve early-stage HCC detection in a Caucasian HBV/HCV cohort. In a retrospective German single-center study, 182 patients with HBV, 223 with HCV and 168 with other etiology (OE) of chronic liver disease (CLD) were enrolled. HCC was confirmed in 52 HBV, 84 HCV and 60 OE CLD patients. The diagnostic performance of the single biomarkers in HCC detection was compared to the GALAD model. At initial diagnosis, most patients were at (very) early BCLC 0 (n = 14/7%) or A (n = 56/29%) or intermediate stage BCLC B (n = 93/47%) HCC in all three subgroups. In the BCLC 0/A cohort, GALAD exhibited an AUC of 0.94 discriminating HCC from non-HCC, surpassing AFP (AUC 0.86), AFP-L3 (AUC 0.83) and DCP (AUC 0.83). In the HBV population, GALAD achieved an AUC of 0.96, in HCV an AUC of 0.98 and in OE an AUC of 0.99, clearly superior to the biomarkers alone. Furthermore, in HCV patients GALAD showed a significantly higher specificity (89%) versus AFP (64%) alone. In chronic viral hepatitis, the GALAD model showed superior performance in detection of early-stage HCC, while exhibiting higher specificity in HCV patients compared to AFP alone. We conclude that the GALAD score shows potential for HCC surveillance in Caucasian HBV/HCV patients.
Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues
Authors: Gatti Milo , Turrini Eleonora , Raschi Emanuel , Sestili Piero , Fimognari Carmela
Published: July 2021

We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID-19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti-inflammatory and anti-viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID-19 in hospitalized patients ≥ 2 years old who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. By July 2021, the European Medicines Agency is also expected to issue the opinion on whether or not to extend its use in hospitalised patients from 10 years of age who require supplemental oxygen. Ruxolitinib, approved for myelofibrosis, was prescribed in patients with COVID-19 within an open-label Emergency Expanded Access Plan. This review will address key milestones in the discovery and use of JAK inhibitors in COVID-19, from artificial intelligence to current clinical evidence, including real world experience, and critically appraise emerging safety issues, namely infections, thrombosis, and liver injury. An outlook to ongoing studies (clinicaltrials.gov) and unpublished pharmacovigilance data is also offered.
GMP-Compliant Radiosynthesis of [18F]GP1, a Novel PET Tracer for the Detection of Thrombi
Authors: Hugenberg Verena , Zerna Marion , Berndt Mathias , Zabel Reinhard , Preuss Rainer , Rolfsmeier Dirk , Wegener Janet , Fox Henrik , Kassner Astrid , Milting Hendrik , Koglin Norman , Stephens Andrew W. , Gummert Jan F. , Burchert Wolfgang , Deutsch Marcus-André
Published: July 2021

Thrombus formation and thromboembolic events play important roles in various cardiovascular pathologies. The key receptor involved in platelet aggregation is the fibrinogen receptor glycoprotein IIb/IIIa. [18F]GP1, a derivative of the GPIIb/IIIa antagonist elarofiban, is a specific 18F-labeled small-molecule radiotracer that binds with high affinity to GPIIb/IIIa receptors of activated platelets. An improved, robust and fully automated radiosynthesis of [18F]GP1 has been developed. [18F]GP1 has been synthesized with decay corrected radiochemical yields of 38 ± 6%, with a radiochemical concentration up to 1900 MBq/mL, molar activities of 952–9428 GBq/µmol and a radio-chemical purity >98%. After determination of the optimal reaction conditions, in particular for HPLC separation, adaption of the reaction conditions to PET center requirements, validation of the manufacturing process and the quality control methods, the synthesis of [18F]GP1 was successfully implemented to GMP standards and was available for clinical application. We describe the GMP-compliant synthesis of the novel radiotracer [18F]GP1. Moreover, we provide some proof-of-concept examples for clinical application in the cardiovascular field. PET/CT with the novel small-molecular radiotracer [18F]GP1 may serve as a novel highly sensitive tool for visualizing active platelet aggregation at the molecular level.
Mesenchymal Stromal Cells Perspective: New Potential Therapeutic for the Treatment of Neurological Diseases
Authors: Mukai Takeo , Sei Kenshi , Nagamura-Inoue Tokiko
Published: July 2021

Several studies have shown that mesenchymal stromal/stem cells (MSCs) exert their neuroprotective and neurorestorative efficacy via the secretion of neurotrophic factors. Based on these studies, many clinical trials using MSCs for the treatment of neurological disorders have been conducted, and results regarding their feasibility and efficacy have been reported. The present review aims to highlight the characteristics and basic research regarding the role of MSCs in neurological disease and to discuss the recent progress in clinical trials using MSCs to treat various neurological disorders.