bluuebunny/crossref_metadata_2025 huggingface dataset:
Sagan Dalya Tea, a New “Old” Probable Adaptogenic Drug: Metabolic Characterization and Bioactivity Potentials of Rhododendron adamsii Leaves
Authors: Olennikov Daniil N. , Nikolaev Vyacheslav M. , Chirikova Nadezhda K.
Published: May 2021

Adams’ rhododendron (Rhododendron adamsii Rehder) or Sagan Dalya tea is a famous Siberian evergreen medical plant of the Ericaceae family used in traditional medicines of Buryats, Yakuts, and Mongols as a tonic, stimulant, and adaptogenic drug. The high popularity of R. adamsii coupled with poor scientific knowledge prompted the addressing of gaps related to metabolic and biomedical data of Sagan Dalya tea. The application of solid-phase extraction and liquid chromatography-mass spectrometric techniques for the metabolomic study of R. adamsii leaf extracts resulted in the identification of more than 170 compounds, including carbohydrates, organic acids, simple phenol glycosides, triterpene glycosides, flavonoids, prenylated phenols, benzoic acid derivatives, hydroxycinnamates, dihydrochalcones, catechins, and procyanidins, most of which were identified for the first time in the plant. Extended surveys of the seasonal content of all detected compounds prove that specific metabolite variations reflect the bioactivity of R. adamsii extracts. Regarding in vitro methods, the expressed antioxidant potential of R. adamsii extracts was investigated via radical-scavenging, nitric oxide scavenging, and ferrous (II) ion chelating assays. The animal-based swimming to exhaustion test demonstrates the stimulating influence of R. adamsii extract on physical performance and endurance, concluding that the drug could act as an adaptogen. Thus, Sagan Dalya tea (R. adamsii) has confirmed its “old” application as a tonic remedy and requires further precise study as a novel adaptogenic plant.
Mapping the Intramolecular Communications among Different Glutamate Dehydrogenase States Using Molecular Dynamics
Authors: Basith Shaherin , Manavalan Balachandran , Shin Tae Hwan , Lee Gwang
Published: May 2021

Glutamate dehydrogenase (GDH) is a ubiquitous enzyme that catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate. It acts as an important branch-point enzyme between carbon and nitrogen metabolisms. Due to the multifaceted roles of GDH in cancer, hyperinsulinism/hyperammonemia, and central nervous system development and pathologies, tight control of its activity is necessitated. To date, several GDH structures have been solved in its closed form; however, intrinsic structural information in its open and apo forms are still deficient. Moreover, the allosteric communications and conformational changes taking place in the three different GDH states are not well studied. To mitigate these drawbacks, we applied unbiased molecular dynamic simulations (MD) and network analysis to three different GDH states i.e., apo, active, and inactive forms, for investigating their modulatory mechanisms. In this paper, based on MD and network analysis, crucial residues important for signal transduction, conformational changes, and maps of information flow among the different GDH states were elucidated. Moreover, with the recent findings of allosteric modulators, an allosteric wiring illustration of GDH intramolecular signal transductions would be of paramount importance to obtain the process of this enzyme regulation. The structural insights gained from this study will pave way for large-scale screening of GDH regulators and could support researchers in the design and development of new and potent GDH ligands.
Occlusion of the Superior Mesenteric Artery in Rats Reversed by Collateral Pathways Activation: Gastric Pentadecapeptide BPC 157 Therapy Counteracts Multiple Organ Dysfunction Syndrome; Intracranial, Portal, and Caval Hypertension; and Aortal Hypotension
Authors: Knezevic Mario , Gojkovic Slaven , Krezic Ivan , Zizek Helena , Malekinusic Dominik , Vrdoljak Borna , Vranes Hrvoje , Knezevic Tamara , Barisic Ivan , Horvat Pavlov Katarina , Drmic Domagoj , Staroveski Miro , Djuzel Antonija , Rajkovic Zoran , Kolak Toni , Kocman Ivica , Lovric Eva , Milavic Marija , Sikiric Suncana , Tvrdeic Ante , Patrlj Leonardo , Strbe Sanja , Kokot Antonio , Boban Blagaic Alenka , Skrtic Anita , Seiwerth Sven , Sikiric Predrag
Published: May 2021

Gastric pentadecapeptide BPC 157 therapy counteracts multiple organ dysfunction syndrome in rats, which have permanent occlusion of the superior mesenteric artery close to the abdominal aorta. Previously, when confronted with major vessel occlusion, its effect would rapidly activate collateral vessel pathways and resolve major venous occlusion syndromes (Pringle maneuver ischemia, reperfusion, Budd–Chiari syndrome) in rats. This would overwhelm superior mesenteric artery permanent occlusion, and result in local, peripheral, and central disturbances. Methods: Assessments, for 30 min (gross recording, angiography, ECG, pressure, microscopy, biochemistry, and oxidative stress), included the portal hypertension, caval hypertension, and aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis; ECG disturbances; MDA-tissue increase; and multiple organ lesions and disturbances, including the heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus). BPC 157 therapy (/kg, abdominal bath) (10 µg, 10 ng) was given for a 1-min ligation time. Results: BPC 157 rapidly recruits collateral vessels (inferior anterior pancreaticoduodenal artery and inferior mesenteric artery) that circumvent occlusion and ascertains blood flow distant from the occlusion in the superior mesenteric artery. Portal and caval hypertension, aortal hypotension, and, centrally, superior sagittal sinus hypertension were attenuated or eliminated, and ECG disturbances markedly mitigated. BPC 157 therapy almost annihilated venous and arterial thrombosis. Multiple organ lesions and disturbances (i.e., heart, lung, liver, and gastrointestinal tract, in particular, as well as brain) were largely attenuated. Conclusions: Rats with superior mesenteric artery occlusion may additionally undergo BPC 157 therapy as full counteraction of vascular occlusion-induced multiple organ dysfunction syndrome.
SR-B1, a Key Receptor Involved in the Progression of Cardiovascular Disease: A Perspective from Mice and Human Genetic Studies
Authors: Gracia-Rubio Irene , Martín César , Civeira Fernando , Cenarro Ana
Published: May 2021

High plasma level of low-density lipoprotein (LDL) is the main driver of the initiation and progression of cardiovascular disease (CVD). Nevertheless, high-density lipoprotein (HDL) is considered an anti-atherogenic lipoprotein due to its role in reverse cholesterol transport and its ability to receive cholesterol that effluxes from macrophages in the artery wall. The scavenger receptor B class type 1 (SR-B1) was identified as the high-affinity HDL receptor, which facilitates the selective uptake of cholesterol ester (CE) into the liver via HDL and is also implicated in the plasma clearance of LDL, very low-density lipoprotein (VLDL) and lipoprotein(a) (Lp(a)). Thus, SR-B1 is a multifunctional receptor that plays a main role in the metabolism of different lipoproteins. The aim of this review is to highlight the association between SR-B1 and CVD risk through mice and human genetic studies.
Evolving Treatment of Advanced Hepatocellular Carcinoma in the Asia–Pacific Region: A Review and Multidisciplinary Expert Opinion
Authors: Ogasawara Sadahisa , Choo Su-Pin , Li Jiang-Tao , Yoo Changhoon , Wang Bruce , Lee Dee , Chow Pierce K. H.
Published: May 2021

Hepatocellular carcinoma (HCC) is the fourth most common driver of cancer-related death globally, with an estimated 72% of cases in Asia. For more than a decade, first-line systemic treatments for advanced or unresectable HCC were limited to the multi-targeted kinase inhibitors sorafenib and, more recently, lenvatinib. Now, treatment options have expanded to include immunotherapy, as exemplified by the immune checkpoint inhibitor (ICI) atezolizumab combined with the antiangiogenic agent bevacizumab. Additional combinations of ICIs with kinase inhibitors, other ICIs, or antiangiogenic agents are under investigation, further supporting the new era of immunotherapy for first-line treatment of advanced or unresectable HCC. We describe this evolving landscape and provide expert opinion on therapeutic best practices in the Asia–Pacific region, where different costs of, and patient access to, treatment are a challenge. With the combination of atezolizumab plus bevacizumab likely to become the clinical standard of care, optimising treatment sequence and ensuring patient access to newer therapies remain priorities. Cost containment and treatment sequencing may be facilitated by characterisation of predictive positive and negative biomarkers. With these considerations in mind, this review and expert opinion focused on advanced HCC in the Asia–Pacific region offers perspectives of multiple stakeholders, including physicians, payer systems, and patients.
International Multi-Site Initiative to Develop an MRI-Inclusive Nomogram for Side-Specific Prediction of Extraprostatic Extension of Prostate Cancer
Authors: Wibmer Andreas G. , Kattan Michael W. , Alessandrino Francesco , Baur Alexander D. J. , Boesen Lars , Franco Felipe Boschini , Bonekamp David , Campa Riccardo , Cash Hannes , Catalá Violeta , Crouzet Sebastien , Dinnoo Sounil , Eastham James , Fennessy Fiona M. , Ghabili Kamyar , Hohenfellner Markus , Levi Angelique W. , Ji Xinge , Løgager Vibeke , Margolis Daniel J. , Moldovan Paul C. , Panebianco Valeria , Penzkofer Tobias , Puech Philippe , Radtke Jan Philipp , Rouvière Olivier , Schlemmer Heinz-Peter , Sprenkle Preston C. , Tempany Clare M. , Vilanova Joan C. , Weinreb Jeffrey , Hricak Hedvig , Shukla-Dave Amita
Published: May 2021

Background: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data. Methods: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens. The performance of the statistical model was evaluated by bootstrap resampling and cross validation and compared with the performance of benchmark models that do not incorporate MRI findings. Results: Data from 840 patients were analyzed; pathologic EPE was found in 320/840 (31.8%). The nomogram model included patient age, prostate-specific antigen density, side-specific biopsy data (i.e., Gleason grade group, percent positive cores, tumor extent), and side-specific MRI features (i.e., presence of a PI-RADSv2 4 or 5 lesion, level of suspicion for EPE, length of capsular contact). The area under the receiver operating characteristic curve of the new, MRI-inclusive model (0.828, 95% confidence limits: 0.805, 0.852) was significantly higher than that of any of the benchmark models (p < 0.001 for all). Conclusions: In an international, multi-site study, we developed an MRI-inclusive nomogram for the side-specific prediction of EPE of prostate cancer that demonstrated significantly greater accuracy than clinical benchmark models.
Improved Tumor-Targeting with Peptidomimetic Analogs of Minigastrin 177Lu-PP-F11N
Authors: Grob Nathalie M. , Schibli Roger , Béhé Martin , Mindt Thomas L.
Published: May 2021

The cholecystokinin-2 receptor (CCK2R) is an attractive target in nuclear medicine due to its overexpression by different tumors. Several radiolabeled peptidic ligands targeting the CCK2R have been investigated in the past; however, their low stability against proteases can limit their uptake in tumors and metastases. Substitution of single or multiple amide bonds with metabolically stable 1,4-disubstituted 1,2,3-triazoles as amide bond bioisosteres proved a promising strategy for improving the tumor-targeting properties of a truncated analog of minigastrin. In this study, we applied the previously studied structural modifications to improve the pharmacokinetic and pharmacodynamic properties of PP-F11N, a minigastrin analog currently in clinical trials. Novel minigastrins (NMGs) as analogs of PP-F11N with one or two amide bonds substituted by 1,2,3-triazoles were synthesized, radiolabeled with 177Lu3+, and subjected to full evaluation in vitro (cell internalization, receptor affinity, stability in blood plasma) and in vivo (stability, biodistribution, SPECT/CT imaging). NMGs with triazoles inserted between the amino acids DGlu10-Ala11 and/or Tyr12-Gly13 showed a significantly increased cellular uptake and affinity toward the CCK2R in vitro. Resistance against the metabolic degradation of the NMGs was comparable to those of the clinical candidate PP-F11N. Imaging by SPECT/CT and biodistribution studies demonstrated a higher uptake in CCK2R-positive tumors but also in the CCK2R-positive stomach. The peptidomimetic compounds showed a slow tumor washout and high tumor-to-kidney ratios. The structural modifications led to the identification of analogs with promising properties for progression to clinical applications in the diagnosis and therapy of CCK2R-positive neoplasms.
Comprehensive Plasma Metabolomic Profile of Patients with Advanced Neuroendocrine Tumors (NETs). Diagnostic and Biological Relevance
Authors: Soldevilla Beatriz , López-López Angeles , Lens-Pardo Alberto , Carretero-Puche Carlos , Lopez-Gonzalvez Angeles , La Salvia Anna , Gil-Calderon Beatriz , Riesco-Martinez Maria C. , Espinosa-Olarte Paula , Sarmentero Jacinto , Rubio-Cuesta Beatriz , Rincón Raúl , Barbas Coral , Garcia-Carbonero Rocio
Published: May 2021

Purpose: High-throughput “-omic” technologies have enabled the detailed analysis of metabolic networks in several cancers, but NETs have not been explored to date. We aim to assess the metabolomic profile of NET patients to understand metabolic deregulation in these tumors and identify novel biomarkers with clinical potential. Methods: Plasma samples from 77 NETs and 68 controls were profiled by GC−MS, CE−MS and LC−MS untargeted metabolomics. OPLS-DA was performed to evaluate metabolomic differences. Related pathways were explored using Metaboanalyst 4.0. Finally, ROC and OPLS-DA analyses were performed to select metabolites with biomarker potential. Results: We identified 155 differential compounds between NETs and controls. We have detected an increase of bile acids, sugars, oxidized lipids and oxidized products from arachidonic acid and a decrease of carnitine levels in NETs. MPA/MSEA identified 32 enriched metabolic pathways in NETs related with the TCA cycle and amino acid metabolism. Finally, OPLS-DA and ROC analysis revealed 48 metabolites with diagnostic potential. Conclusions: This study provides, for the first time, a comprehensive metabolic profile of NET patients and identifies a distinctive metabolic signature in plasma of potential clinical use. A reduced set of metabolites of high diagnostic accuracy has been identified. Additionally, new enriched metabolic pathways annotated may open innovative avenues of clinical research.
Optimal Allocation of Large-Capacity Distributed Generation with the Volt/Var Control Capability Using Particle Swarm Optimization
Authors: Lee Donghyeon , Son Seungwan , Kim Insu
Published: May 2021

Widespread interest in environmental issues is growing. Many studies have examined the effect of distributed generation (DG) from renewable energy resources on the electric power grid. For example, various studies efficiently connect growing DG to the current electric power grid. Accordingly, the objective of this study is to present an algorithm that determines DG location and capacity. For this purpose, this study combines particle swarm optimization (PSO) and the Volt/Var control (VVC) of DG while regulating the voltage magnitude within the allowable variation (e.g., ±5%). For practical optimization, the PSO algorithm is enhanced by applying load profile data (e.g., 24-h data). The objective function (OF) in the proposed PSO method considers voltage variations, line losses, and economic aspects of deploying large-capacity DG (e.g., installation costs) to transmission networks. The case studies validate the proposed method (i.e., optimal allocation of DG with the capability of VVC with PSO) by applying the proposed OF to the PSO that finds the optimal DG capacity and location in various scenarios (e.g., the IEEE 14- and 30-bus test feeders). This study then uses VVC to compare the voltage profile, loss, and installation cost improved by DG to a grid without DG.
Nuclear Hydrogen Production: Modeling and Preliminary Optimization of a Helical Tube Heat Exchanger
Authors: Bolfo Lorenzo , Devia Francesco , Lomonaco Guglielmo
Published: May 2021

Hydrogen production is a topical issue in an energy scenario where decarbonization is a priority, especially with reference to the transport sector that has a great weight on global emissions. Starting from this consideration, GIF (Generation-IV International Forum) investigated the possibility to produce hydrogen by nuclear energy. The “classic” strategy is based on the use of nuclear as energy source for the electrolysis; but on the medium-long term, a more sustainable and smart approach could be founded on the use of thermochemical processes (e.g., I-S) that require a direct coupling of a chemical plant to a nuclear reactor. In order to develop this strategy, it is mandatory to design and optimize all the key components involved in this complex plant. In this study, we developed the 3D-CAD and CFD models of the intermediate heat exchanger (IHX) installed in the Japanese HTTR nuclear power plant. This component is extremely important for both the safety of the two plants and the stability of the whole hydrogen production plant. Initially, our model (developed by AutoCAD 3D and implemented in Star CCM+) was validated on the basis of experimental data available in literature; then, an initial optimization of the IHX testing innovative materials, such as Alloy 617 and ODS–MA754, and a different primary coolant (supercritical CO2) was performed.
Non-Parametric Computational Measures for the Analysis of Resource Productivity
Authors: Bampatsou Christina , Halkos George
Published: May 2021

In this study, we assumed that 28 European countries (Decision Making Units (DMUs)) aimed to accomplish higher economic outputs, using fewer resources and producing fewer emissions in the form of environmental degradation. In this context, we studied the drivers of total factor productivity change (TFPCH) in DMUs, associated with either managerial capabilities (efficiency change (EC)) or innovations (technical change (TC)) in resource-saving production methods, before and after the integration of CO2 (carbon dioxide) emissions as an additional variable (undesirable output) in the initial model of one output (gross domestic product (GDP)) and five inputs (labor, capital, energy, domestic material consumption and recycled municipal waste). The primary focus of this study is to identify best practices that policymakers can adopt as they attempt to reduce productivity loss. Our results highlight the weak areas of individual countries and seem to indicate the action that should be taken to improve their productivity by taking into consideration the main driving force behind productivity and technical efficiency change. Our findings reveal that an effective use of technological developments is determined as important strategic information for ensuring managerial performance.
Machine Learning Techniques for Energy Efficiency and Anomaly Detection in Hybrid Wireless Sensor Networks
Authors: Mittal Mohit , de Prado Rocío Pérez , Kawai Yukiko , Nakajima Shinsuke , Muñoz-Expósito José E.
Published: May 2021

Wireless sensor networks (WSNs) are among the most popular wireless technologies for sensor communication purposes nowadays. Usually, WSNs are developed for specific applications, either monitoring purposes or tracking purposes, for indoor or outdoor environments, where limited battery power is a main challenge. To overcome this problem, many routing protocols have been proposed through the last few years. Nevertheless, the extension of the network lifetime in consideration of the sensors capacities remains an open issue. In this paper, to achieve more efficient and reliable protocols according to current application scenarios, two well-known energy efficient protocols, i.e., Low-Energy Adaptive Clustering hierarchy (LEACH) and Energy–Efficient Sensor Routing (EESR), are redesigned considering neural networks. Specifically, to improve results in terms of energy efficiency, a Levenberg–Marquardt neural network (LMNN) is integrated. Furthermore, in order to improve the performance, a sub-cluster LEACH-derived protocol is also proposed. Simulation results show that the Sub-LEACH with LMNN outperformed its competitors in energy efficiency. In addition, the end-to-end delay was evaluated, and Sub-LEACH protocol proved to be the best among existing strategies. Moreover, an intrusion detection system (IDS) has been proposed for anomaly detection based on the support vector machine (SVM) approach for optimal feature selection. Results showed a 96.15% accuracy—again outperforming existing IDS models. Therefore, satisfactory results in terms of energy efficiency, end-to-end delay and anomaly detection analysis were attained.
Estimating VAIA Windstorm Damaged Forest Area in Italy Using Time Series Sentinel-2 Imagery and Continuous Change Detection Algorithms
Authors: Giannetti Francesca , Pecchi Matteo , Travaglini Davide , Francini Saverio , D’Amico Giovanni , Vangi Elia , Cocozza Claudia , Chirici Gherardo
Published: May 2021

Mapping forest disturbances is an essential component of forest monitoring systems both to support local decisions and for international reporting. Between the 28 and 29 October 2018, the VAIA storm hit the Northeast regions of Italy with wind gusts exceeding 200 km h−1. The forests in these regions have been seriously damaged. Over 490 Municipalities in six administrative Regions in Northern Italy registered forest damages caused by VAIA, that destroyed or intensely damaged forest stands spread over an area of 67,000 km2. The present work tested the use of two continuous change detection algorithms, i.e., the Bayesian estimator of abrupt change, seasonal change, and trend (BEAST) and the continuous change detection and classification (CCDC) to map and estimate forest windstorm damage area using a normalized burned ration (NBR) time series calculated on three years Sentinel-2 (S2) images collection (i.e., January 2017–October 2019). We analyzed the accuracy of the maps and the damaged forest area using a probability-based stratified estimation within 12 months after the storm with an independent validation dataset. The results showed that close to the storm (i.e., 1 to 6 months November 2018–March 2019) it is not possible to obtain accurate results independently of the algorithm used, while accurate results were observed between 7 and 12 months from the storm (i.e., May 2019–October 2019) in terms of Standard Error (SE), percentage SE (SE%), overall accuracy (OA), producer accuracy (PA), user accuracy (UA), and gmean for both BEAST and CCDC (SE < 3725.3 ha, SE% < 9.69, OA > 89.7, PA and UA > 0.87, gmean > 0.83).
Variations in Soil Enzyme Activities and Microbial Communities along an Altitudinal Gradient on the Eastern Qinghai–Tibetan Plateau
Authors: Fan Shiyu , Sun Hui , Yang Jiyuan , Qin Jihong , Shen Danjie , Chen Yuexi
Published: May 2021

The Qinghai–Tibetan Plateau is the highest plateau in the world and is sensitive to climate change. The dynamics of soil enzyme activities and microbial communities are good indicators of alpine biochemical processes during warming. We collected topsoil (0–10 cm) and subsoil (10–20 cm) samples at altitudes of 3200–4000 m; determined the activities of β-1,4-glucosidase (BG), cellobiohydrolase (CBH), β-1,4-N-acetyl-glucosaminidase (NAG) and acid phosphomonoesterase (PME); and performed Illumina 16S rRNA high-throughput sequencing. We found that the soil carbon (total organic carbon and dissolved organic carbon) and nitrogen (total nitrogen and dissolved organic nitrogen) fluctuated with altitude in both the topsoil and subsoil, whereas the dissolved phosphorus continuously decreased with the increasing altitude. BG and CBH decreased from 3200 to 3600 m and increased from 3800 to 4000 m, with the lowest levels occurring at 3600 m (topsoil) and 3800 m (subsoil). NAG and PME showed similar fluctuations with altitude, with the highest levels occurring at 3400 m and 4000 m in both the topsoil and subsoil. Generally, the altitudes from 3600 to 3800 m were an ecological transition belt where most of the nutrients and enzyme activities reached their lowest levels. All of the alpine soils shared similar dominant phyla, including Proteobacteria (32.7%), Acidobacteria (30.2%), Actinobacteria (7.7%), Bacteroidetes (4.4%), Planctomycetes (2.9%), Firmicutes (2.3%), Gemmatimonadetes (2.0%), Chloroflexi, (1.2%) and Nitrospirae (1.2%); Gemmatimonadetes and Verrucomicrobia were significantly affected by soil depth and Planctomycetes, Firmicutes, Gemmatimonadetes, Nitrospirae, Latescibacteria and Armatimonadetes were significantly affected by altitude. In addition, nutrient availability, enzyme activity and microbial diversity were higher in the topsoil than in the subsoil, and they had more significant correlations in the subsoil than in the topsoil. Our results provide useful insights into the close linkages between soil nutrient cycling and microbial activities on the eastern Qinghai–Tibetan Plateau, and are of great significance for further assessing the long-term impact of environmental changes in the alpine ecosystems.
Amorphophallus konjac: A Novel Alternative Flour on Gluten-Free Bread
Authors: Laignier Fernanda , Akutsu Rita de Cássia Coelho de Almeida , Maldonade Iriani Rodrigues , Bertoldo Pacheco Maria Teresa , Silva Vera Sônia Nunes , Mendonça Marcio Antônio , Zandonadi Renata Puppin , Raposo António , Botelho Raquel Braz Assunção
Published: May 2021

The demand for gluten-free products is rising, but their production with similar quality as their gluten counterparts is challenging. This study aimed to develop gluten-free bread samples using different concentrations of Amorphophallus konjac flour (0%, 12.5%, 25%, 37.5%, and 50% of the total flour content) and to evaluate their nutritional and physicochemical properties. Proteins, lipids, carbohydrates, moisture, ash content, fibers, resistant starch, firmness, specific volume, and color were evaluated using official methods. Protein varied from 2.95% to 4.94%, the energy value from 347.93 to 133.55 kcal/100 g, dietary fiber from 8.19 to 17.90%, and resistant starch from 0.67% to 0.75% on wet basis. The addition of konjac flour positively influenced the specific volume. Higher concentrations of konjac flour in the formulations led to lower calories of the bread due to the significant addition of water to the dough. The bread samples with konjac showed high fiber content due to the composition of the flour. They had lower levels of carbohydrates, which can positively influence the glycemic index. Konjac flour provided dough mold, growth, and better texture for gluten-free bread. The best formulations were prepared in concentrations up to 37.5% konjac. The 50% konjac bread showed slightly reduced specific volume and pale color.
Yeast Particle Encapsulation of Scaffolded Terpene Compounds for Controlled Terpene Release
Authors: Soto Ernesto R. , Rus Florentina , Li Hanchen , Garceau Carli , Chicca Jeffrey , Elfawal Mostafa , Gazzola David , Nielsen Martin K. , Urban Joseph F. , Aroian Raffi V. , Ostroff Gary R.
Published: May 2021

Terpenes are naturally occurring compounds produced by plants that are of great commercial interest in the food, agricultural, cosmetic, and pharmaceutical industries due to their broad spectra of antibacterial, antifungal, anthelmintic, membrane permeation enhancement, and antioxidant biological activities. Applications of terpenes are often limited by their volatility and the need for surfactants or alcohols to produce stable, soluble (non-precipitated) products. Yeast particles (YPs) are hollow, porous microspheres that have been used for the encapsulation of terpenes (YP terpenes) by passive diffusion of terpenes through the porous YP cell walls. We here report the development of a second generation YP encapsulated terpene technology that incorporates the stimuli-responsive control of terpene release using biodegradable pro-terpene compounds (YP pro-terpenes). YP terpenes and YP pro-terpenes were both produced, in which high levels of carvacrol, eugenol, thymol and geraniol were encapsulated. The YP pro-terpenes show higher encapsulation stability than YP terpenes due to pro-terpenes being non-volatile solids at room temperature and stable in suspensions at neutral pH. YP pro-terpenes and YP terpenes were evaluated for biological activity in antibacterial, antifungal and anthelmintic assays. The YP pro-terpenes retained the full biological activity of the parent terpene compound.
Physicochemical and Rheological Characterization of Different Low Molecular Weight Gellan Gum Products and Derived Ionotropic Crosslinked Hydrogels
Authors: Fiorica Calogero , Biscari Giuseppina , Palumbo Fabio Salvatore , Pitarresi Giovanna , Martorana Annalisa , Giammona Gaetano
Published: May 2021

A series of four different low molecular weight gellan gum products was obtained by alkaline hydrolysis with the aim to investigate the impact of the molecular weight on the rheological properties of the polysaccharide aqueous dispersions and on the physicochemical characteristics of derived ionotropic crosslinked hydrogels. In particular, thermo-rheological analysis was conducted on aqueous dispersions to study the influence of molecular weight on the thermogelation properties typical of the native polysaccharide while strain sweep experiments were conducted to establish if aqueous dispersion shows a viscoelastic behavior. The effect of different Ca2+ on the rheological properties of hydrogels were studied. Furthermore, ionotropic crosslinked hydrogels were analyzed in terms of morphology on the dried state and swelling behavior, while their viscoelastic properties were studied by means of rheological analysis conducted in frequency sweep regime after different time points of incubation in phosphate buffer at pH 7.4. Release experiments conducted using fluorescein isothiocyanate labelled dextran as a model diffusion agent and was performed to investigate the possibility of using the low molecular weight GG-derived hydrogels as an active molecule-releasing device. Finally, the cytocompatibility of hydrolysis products was investigated, as well as the capacity of hydrogels to encapsulate viable MC3T3-E1 preosteoblastic cells.
miR-21-5p Regulates the Proliferation and Differentiation of Skeletal Muscle Satellite Cells by Targeting KLF3 in Chicken
Authors: Zhang Donghao , Ran Jinshan , Li Jingjing , Yu Chunlin , Cui Zhifu , Amevor Felix Kwame , Wang Yan , Jiang Xiaosong , Qiu Mohan , Du Huarui , Zhu Qing , Yang Chaowu , Liu Yiping
Published: May 2021

The proliferation and differentiation of skeletal muscle satellite cells (SMSCs) play an important role in the development of skeletal muscle. Our previous sequencing data showed that miR-21-5p is one of the most abundant miRNAs in chicken skeletal muscle. Therefore, in this study, the spatiotemporal expression of miR-21-5p and its effects on skeletal muscle development of chickens were explored using in vitro cultured SMSCs as a model. The results in this study showed that miR-21-5p was highly expressed in the skeletal muscle of chickens. The overexpression of miR-21-5p promoted the proliferation of SMSCs as evidenced by increased cell viability, increased cell number in the proliferative phase, and increased mRNA and protein expression of proliferation markers including PCNA, CDK2, and CCND1. Moreover, it was revealed that miR-21-5p promotes the formation of myotubes by modulating the expression of myogenic markers including MyoG, MyoD, and MyHC, whereas knockdown of miR-21-5p showed the opposite result. Gene prediction and dual fluorescence analysis confirmed that KLF3 was one of the direct target genes of miR-21-5p. We confirmed that, contrary to the function of miR-21-5p, KLF3 plays a negative role in the proliferation and differentiation of SMSCs. Si-KLF3 promotes cell number and proliferation activity, as well as the cell differentiation processes. Our results demonstrated that miR-21-5p promotes the proliferation and differentiation of SMSCs by targeting KLF3. Collectively, the results obtained in this study laid a foundation for exploring the mechanism through which miR-21-5p regulates SMSCs.
Are Cyanobacteria an Ancestor of Chloroplasts or Just One of the Gene Donors for Plants and Algae?
Authors: Sato Naoki
Published: May 2021

Chloroplasts of plants and algae are currently believed to originate from a cyanobacterial endosymbiont, mainly based on the shared proteins involved in the oxygenic photosynthesis and gene expression system. The phylogenetic relationship between the chloroplast and cyanobacterial genomes was important evidence for the notion that chloroplasts originated from cyanobacterial endosymbiosis. However, studies in the post-genomic era revealed that various substances (glycolipids, peptidoglycan, etc.) shared by cyanobacteria and chloroplasts are synthesized by different pathways or phylogenetically unrelated enzymes. Membranes and genomes are essential components of a cell (or an organelle), but the origins of these turned out to be different. Besides, phylogenetic trees of chloroplast-encoded genes suggest an alternative possibility that chloroplast genes could be acquired from at least three different lineages of cyanobacteria. We have to seriously examine that the chloroplast genome might be chimeric due to various independent gene flows from cyanobacteria. Chloroplast formation could be more complex than a single event of cyanobacterial endosymbiosis. I present the “host-directed chloroplast formation” hypothesis, in which the eukaryotic host cell that had acquired glycolipid synthesis genes as an adaptation to phosphate limitation facilitated chloroplast formation by providing glycolipid-based membranes (pre-adaptation). The origins of the membranes and the genome could be different, and the origin of the genome could be complex.
Evaluation of the Risk of Anxiety and/or Depression during Confinement Due to COVID-19 in Central Spain
Authors: Cárdaba-García Rosa M , Pérez Pérez Lucia , Niño Martín Virtudes , Cárdaba-García Inés , Durantez-Fernández Carlos , Olea Elena
Published: May 2021

(1) Background: The confinement of the population in response to the COVID-19 pandemic was related to an increased risk of suffering from anxiety and/or depression in previous studies with other populations. (2) Methods: descriptive study using surveys (Goldberg Anxiety and Depression Scale) with 808 participants over 18 years of age between 14 and 20 of May 2020 during the confinement due to the SARS-CoV-2 virus in Spain. (3) Results: 63% of the participants were at risk of suffering from anxiety and 64.9% were at risk of depression. Variables reaching statistical significance were: age (t anxiety = −0.139 and t depression = −0.153), gender (t anxiety = −4.152 and t depression = −4.178), marital status (anxiety F = 2.893 and depression F = 3.011), symptoms compatible with COVID-19 (t anxiety = −4.177 and t depression = −3.791), previous need for psychological help (t anxiety = −5.385 and t depression = −7.136) and need for such help at the time of the study (t anxiety = −9.144 and depression = −10.995). In addition, we generated two regression models that estimate the risk of anxiety and depression. (4) Conclusions: more than half of the participants were at risk of suffering from anxiety and/or depression, confirming the negative effect of confinement on the population.
Anaemia in Children and Adolescents: A Bibliometric Analysis of BRICS Countries (1990–2020)
Authors: Awe Olushina Olawale , Dogbey Dennis Makafui , Sewpaul Ronel , Sekgala Derrick , Dukhi Natisha
Published: May 2021

Background/objectives: Brazil, Russia, India China and South Africa have prioritized cooperation regarding health, including malnutrition. Anaemia in children, adolescents and women of reproductive age has been on the increase in these countries, placing a huge strain on healthcare systems. This study aimed to map the scientific perspective and research publications on anaemia in children and adolescents in the BRICS countries. Methods: Bibliometric analyses were employed to map scientific publications related to anaemia in children and adolescents in BRICS countries using VOSviewer software. Research documents from 1990 to 2020 were imported from PubMed. Descriptive statistics was used to analyse trends in research publications, authorship and keywords over the 30-year period. Findings: BRICS countries accounted for 15% of all publications on the subject within the last three decades. While India had the highest number of publications, China had the author with the highest number of research publications and co-authorship links. Of all article types, India had the highest number of letters, while China and South Africa published the highest number of RCT/clinical trial and review articles, respectively. Conclusion: The review of all scientific studies on anaemia in BRICS nations for the past 30 years revealed gaps in research collaborations on anaemia between authors in BRICS nations. However, collaborative research projects may contribute to building a shared base of evidence, innovations, data and methodologies for a more comprehensive understanding of the risks and vulnerabilities of child and adolescent anaemia. This will aid in the development and evaluation of interventions and policies to alleviate anaemia and nutrient deficiencies.
Pregnancy and COVID-19 Pandemic Perception in Malaysia: A Cross-Sectional Study
Authors: Syed Anwar Aly Sharifah Aminah , Abdul Rahman Rahana , Sharip Shalisah , Shah Shamsul Azhar , Abdullah Mahdy Zaleha , Kalok Aida
Published: May 2021

Pregnant women are susceptible to COVID-19 complications due to gestation-related physiological changes. We aimed to evaluate the level of maternal knowledge, perception, and practice during the pandemic. A cross-sectional study was conducted during the Malaysian Movement Control Order (MCO) between April and June 2020. A self-administered electronic questionnaire that included the knowledge and practice domains was distributed. A newly designed set of questions was used to evaluate (1) women’s perception of MCO and (2) maternal experience, which was subdivided into clinical care provision and maternal anxiety. The survey response rate was 93% with the final number for analysis of 415. The majority of women (95%) demonstrated an adequate level of knowledge on COVID-19, whilst 99% had a good practice. We found that tertiary education (p < 0.001), employment status (p = 0.03), higher household income (p < 0.001), and multiple sources of information (p < 0.001) were independent predictors of adequate maternal knowledge on COVID-19. Women with adequate knowledge also reported a more positive perception of MCO (p < 0.001) and better obstetric care experience (p = 0.037), as did those of Malay ethnicity. Younger (p < 0.001) and nulliparous (p = 0.01) women demonstrated greater anxiety levels. The majority of our women reported good practice and adequate knowledge, which contributed to a positive perception of MCO and better maternal obstetric experience. First-time mothers may benefit from extra support and reassurance during the pandemic to alleviate maternal anxiety.
Assessment of the Toxicity of Quantum Dots through Biliometric Analysis
Authors: Zhong Lishi , Zhang Lili , Li Yimeng , Liang Xue , Kong Lu , Shen Xiaobing , Wu Tianshu
Published: May 2021

Along with the rapid development of nanotechnology, the biosafety of quantum dots (QDs), a widely used kind of nanoparticles, has grabbed the attentions of researchers, because QDs have excellent and unique optical properties that other commonly used nanoparticles, like walled carbon nanotubes, do not have. The understanding of the toxicity of QDs is an important premise for their application in wider fields, including biology and medicine. This study sought to analyze scientific publications on the toxicity of QDs and to construct a bibliometric model for qualitative and quantitative evaluation of these publications over the past decade, which visually presented the status quo and future development trend on the toxicological study of QDs. A search for data using the triple blind method revealed that, as of 31 December 2018, there were 5269 papers published on the toxicity of QDs. RSC ADVANCES (5-year IF, 3.096) ranked first in the number of publications. China had the largest number of publications (2233) and the highest H-index (119), but the United States was still the leading country with regards to the quality of the research. LIU Y (106 publications) published the most papers, while Hardman R (304 co-citations) had the most co-citations. The keyword “walled carbon nanotube” ranked first in the research frontier. The findings not only determine a development trend of the toxicological study of QDs, but also identify further research directions in this field.
Phenolic Profiles of Red Wine Relate to Vascular Endothelial Benefits Mediated by SIRT1 and SIRT6
Authors: D’Onofrio Nunzia , Martino Elisa , Chianese Giuseppina , Coppola Francesca , Picariello Luigi , Moio Luigi , Balestrieri Maria Luisa , Gambuti Angelita , Forino Martino
Published: May 2021

Dietary phenolic compounds possess potent bioactivity against inflammatory pathways of chronic inflammatory conditions, such as type 2 diabetes. Here, the phenolic profile and bioactivity of Italian red wines Gaglioppo, Magliocco, and Nerello Mascalese were characterized. NMR, HPLC/UV-Vis and spectrophotometric characterization showed that Magliocco was the richest wine in monomeric anthocyanins (two-fold), catechins, and low molecular weight phenolics (LMWP). A positive correlation was observed between the polyphenolic content and antioxidant capacity (p < 0.05), with Magliocco displaying the highest antioxidant capacity (p < 0.01). In vitro evidence on the endothelial cell models of insulin resistance and hyperglycemia showed the ability of Magliocco to reduce reactive oxygen species (ROS) (p < 0.01) and cytokine release (p < 0.01) and to upregulate SIRT1 and SIRT6 (p < 0.01). On the whole, the results indicated that the quantitative and qualitative phenolic profiles of red wines influence their in vitro beneficial effects on oxidative and proinflammatory milieu in endothelial cells, showing a positive modulation of SIRT1 and SIRT6, both implied in vascular aging.
Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake
Authors: Aviñó Anna , Clua Anna , Bleda Maria José , Eritja Ramon , Fàbrega Carme
Published: May 2021

Conjugation of small molecules such as lipids or receptor ligands to anti-cancer drugs has been used to improve their pharmacological properties. In this work, we studied the biological effects of several small-molecule enhancers into a short oligonucleotide made of five floxuridine units. Specifically, we studied adding cholesterol, palmitic acid, polyethyleneglycol (PEG 1000), folic acid and triantennary N-acetylgalactosamine (GalNAc) as potential enhancers of cellular uptake. As expected, all these molecules increased the internalization efficiency with different degrees depending on the cell line. The conjugates showed antiproliferative activity due to their metabolic activation by nuclease degradation generating floxuridine monophosphate. The cytotoxicity and apoptosis assays showed an increase in the anti-cancer activity of the conjugates related to the floxuridine oligomer, but this effect did not correlate with the internalization results. Palmitic and folic acid conjugates provide the highest antiproliferative activity without having the highest internalization results. On the contrary, cholesterol oligomers that were the best-internalized oligomers had poor antiproliferative activity, even worse than the unmodified floxuridine oligomer. Especially relevant is the effect induced by palmitic and folic acid derivatives generating the most active drugs. These results are of special interest for delivering other therapeutic oligonucleotides.
Neurotrophins as Key Regulators of Cell Metabolism: Implications for Cholesterol Homeostasis
Authors: Colardo Mayra , Martella Noemi , Pensabene Daniele , Siteni Silvia , Di Bartolomeo Sabrina , Pallottini Valentina , Segatto Marco
Published: May 2021

Neurotrophins constitute a family of growth factors initially characterized as predominant mediators of nervous system development, neuronal survival, regeneration and plasticity. Their biological activity is promoted by the binding of two different types of receptors, leading to the generation of multiple and variegated signaling cascades in the target cells. Increasing evidence indicates that neurotrophins are also emerging as crucial regulators of metabolic processes in both neuronal and non-neuronal cells. In this context, it has been reported that neurotrophins affect redox balance, autophagy, glucose homeostasis and energy expenditure. Additionally, the trophic support provided by these secreted factors may involve the regulation of cholesterol metabolism. In this review, we examine the neurotrophins’ signaling pathways and their effects on metabolism by critically discussing the most up-to-date information. In particular, we gather experimental evidence demonstrating the impact of these growth factors on cholesterol metabolism.
Update in Biomolecular and Genetic Bases of Bicuspid Aortopathy
Authors: Junco-Vicente Alejandro , del Río-García Álvaro , Martín María , Rodríguez Isabel
Published: May 2021

Bicuspid aortic valve (BAV) associated with aortopathy is the most common congenital heart disease in the general population. Far from being a simple harmless valve malformation, it can be a complex and heterogeneous disease and a source of chronic and acute pathology (early valvular disease, aneurysm, dissection). In the previous years, intense research has been carried out to find out and understand its mechanisms, but the pathophysiology of the disease is still not fully understood and many questions remain open. Recent studies have discovered several genetic mutations involved in the development of valvular and aortic malformations, but still cannot explain more than 5–10% of cases. Other studies have also focused on molecular alterations and cellular processes (TGF-β pathway, microRNAs, degradation of the extracellular matrix, metalloproteinases, etc.), being a field in constant search and development, looking for a therapeutic target to prevent the development of the disease. Increased knowledge about this multifaceted disorder, derived from both basic and clinical research, may influence the diagnosis, follow-up, prognosis, and therapies of affected patients in the near future. This review focuses on the latest and outstanding developments on the molecular and genetic investigations of the bicuspid aortopathy.