bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic Effect of Plant Extracts on Endodontic Pathogens Isolated from Teeth with Root Canal Treatment Failure: An In Vitro Study
Authors: Arora Suraj , Saquib Shahabe Abullais , Algarni Youssef A , Kader Mohammed Abdul , Ahmad Irfan , Alshahrani Mohammad Y , Saluja Priyanka , Baba Suheel Manzoor , Abdulla Anshad M. , Bavabeedu Shashit Shetty
Published: May 2021

Background and objectives: This study aimed to evaluate the synergistic antimicrobial activity of extracts obtained from Salvadora persica (Miswak), Commiphora molmol (myrrh) and Azadirachta indica (neem) in combination with commercially available antimicrobial agents: penicillin, tetracycline, ofloxacin and fluconazole on endodontic pathogens such as Enterococcus faecalis, Streptococcus mitis,Actinomyces naeslundii and Candida albicans. Materials and Methods: Microbiological samples from the root canals of the teeth undergoing retreatment were taken using sterile paper points kept at full length in the canal for 30 s. The disc diffusion method was used to check the susceptibility of microbes to the plant extracts and antimicrobials by measuring the diameter of the inhibition zones. Against the microbes, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)/minimum fungicidal concentration (MFC) of the plant extracts were assessed. The fractional inhibitory concentration index (FICI) was used to estimate the synergistic effect of plant extracts combined with antimicrobials against the resistant endodontic microbes. Results: The findings clearly indicate the effectiveness of all the three plant extracts, Commiphora molmol, Azadirachta indica, Salvadora persica, against all the experimental pathogenic microorganisms except for the ineffectiveness of Azadirachta indica, Salvadora persica against Candidaalbicans. Maximum antimicrobial activity was displayed by Azadirachta indica against Enterococcusfaecalis (MIC = 0.09 ± 1.2 mg/mL, MBC = 0.78 ± 1.25 mg/mL) and the minimum antimicrobial activity was displayed by Commiphora molmol against Actinomyces naeslundii (MIC = 12.5 ± 3.25 mg/mL, MBC = 100 ± 3.75 mg/mL). The best synergy was displayed by Commiphora molmol with fluconazole against Candidaalbicans (FICI = 0.45). Conclusions: The current study delineates the variable antimicrobial activity of plant extracts against the experimental endodontic pathogenic microorganisms. Plant extracts in conjunction with various antimicrobials can be valuable aids in combating relatively resistant endodontic microorganisms that have been the cause of worry in recent years, leading to failure even in treatment procedures following all required protocols.
Phage PPPL-1, A New Biological Agent to Control Bacterial Canker Caused by Pseudomonas syringae pv. actinidiae in Kiwifruit
Authors: Song Yu-Rim , Vu Nguyen Trung , Park Jungkum , Hwang In Sun , Jeong Hyeon-Ju , Cho Youn-Sup , Oh Chang-Sik
Published: May 2021

Pseudomonas syringae pv. actinidiae (Psa) is a Gram-negative bacterium that causes bacterial canker disease in kiwifruit. Copper or antibiotics have been used in orchards to control this disease, but the recent emergence of antibiotic-resistant Psa has called for the development of a new control agent. We previously reported that the bacteriophage (or phage) PPPL-1 showed antibacterial activity for both biovar 2 and 3 of Psa. To investigate the possibility of PPPL-1 to control bacterial canker in kiwifruit, we further tested the efficacy of PPPL-1 and its phage cocktail with two other phages on suppressing disease development under greenhouse conditions using 6 weeks old kiwifruit plants. Our results showed that the disease control efficacy of PPPL-1 treatment was statistically similar to those of phage cocktail treatment or AgrimycinTM, which contains streptomycin and oxytetracycline antibiotics as active ingredients. Moreover, PPPL-1 could successfully kill streptomycin-resistant Psa isolates, of which the treatment of BuramycinTM carrying only streptomycin as an active ingredient had no effect in vitro. The phage PPPL-1 was further characterized, and stability assays showed that the phage was stable in the field soil and at low temperature of 0 ± 2 °C. In addition, the phage could be scaled up quickly up to 1010 pfu/mL at 12 h later from initial multiplicity of infection of 0.000005. Our results indicate that PPPL-1 phage is a useful candidate as a biocontrol agent and could be a tool to control the bacterial canker in kiwifruit by Psa infection in the field conditions.
Caffeic Acid Phenethyl Ester Protects Kidney Mitochondria against Ischemia/Reperfusion Induced Injury in an In Vivo Rat Model
Authors: Kamarauskaite Justina , Baniene Rasa , Trumbeckas Darius , Strazdauskas Arvydas , Trumbeckaite Sonata
Published: May 2021

To improve ischemia/reperfusion tolerance, a lot of attention has been focused on natural antioxidants. Caffeic acid phenethyl ester (CAPE), an active component of the resinous exudates of the buds and young leaves of Populus nigra L., Baccharis sarothroides A., etc., and of propolis, possesses unique biological activities such as anti-inflammatory, antioxidant, immunomodulating, and cardioprotective effects, among others. There is a lack of studies showing a link between the antioxidant potential of CAPE and the mechanism of protective action of CAPE at the level of mitochondria, which produces the main energy for the basic functions of the cell. In the kidney, ischemia/reperfusion injury contributes to rapid kidney dysfunction and high mortality rates, and the search for biologically active protective compounds remains very actual. Therefore, the aim of this study was to identify the antioxidant potential of CAPE and to investigate whether CAPE can protect rat kidney mitochondria from in vivo kidney ischemia/reperfusion induced injury. We found that CAPE (1) possesses antioxidant activity (the reducing properties of CAPE are more pronounced than its antiradical properties); CAPE effectively reduces cytochrome c; (2) protects glutamate/malate oxidation and Complex I activity; (3) preserves the mitochondrial outer membrane from damage and from the release of cytochrome c; (4) inhibits reactive oxygen species (ROS) generation in the Complex II (SDH) F site; (5) diminishes ischemia/reperfusion-induced LDH release and protects from necrotic cell death; and (6) has no protective effects on succinate oxidation and on Complex II +III activity, but partially protects Complex II (SDH) from ischemia/reperfusion-induced damage. In summary, our study shows that caffeic acid phenethyl ester protects kidney mitochondrial oxidative phosphorylation and decreases ROS generation at Complex II in an in vivo ischemia/reperfusion model, and shows potential as a therapeutic agent for the development of pharmaceutical preparations against oxidative stress-related diseases.
Biochemical Validation of a Self-Administered Food Frequency Questionnaire to Assess Diet Using Carotenoids and Vitamins E and D in Male Adolescents in Spain
Authors: Notario-Barandiaran Leyre , Navarrete-Muñoz Eva-María , Valera-Gran Desirée , Hernández-Álvarez Elena , Donoso-Navarro Encarnación , González-Palacios Sandra , García-de-la-Hera Manuela , Fernández Mariana F. , Freire Carmen , Vioque Jesús
Published: May 2021

Reliable tools to evaluate diet are needed, particularly in life periods such as adolescence in which a rapid rate of growth and development occurs. We assessed the biochemical validity of a self-administered food frequency questionnaire (FFQ) in a sample of Spanish male adolescents using carotenoids and vitamin E and D data. We analyzed data from 122 male adolescents aged 15–17 years of the INMA-Granada birth cohort study. Adolescents answered a 104-item FFQ and provided a non-fasting blood sample. Mean daily nutrient intakes and serum concentration were estimated for main carotenoids (lutein-zeaxanthin, β-cryptoxanthin, lycopene, α-carotene and β-carotene), vitamins E and D and also for fruit and vegetable intake. Pearson correlation coefficients (r) and the percentage of agreement (same or adjacent quintiles) between serum vitamin concentrations and energy-adjusted intakes were estimated. Statistically significant correlation coefficients were observed for the total carotenoids (r = 0.40) and specific carotenoids, with the highest correlation observed for lutein–zeaxanthin (r = 0.42) and the lowest for β-carotene (0.23). The correlation coefficient between fruit and vegetable intake and serum carotenoids was 0.29 (higher for vegetable intake, r = 0.33 than for fruit intake, r = 0.19). Low correlations were observed for vitamin E and D. The average percentage of agreement for carotenoids was 55.8%, and lower for vitamin E and D (50% and 41%, respectively). The FFQ may be an acceptable tool for dietary assessment among male adolescents in Spain.
Comparison of Antioxidant Properties of Dehydrolutein with Lutein and Zeaxanthin, and their Effects on Cultured Retinal Pigment Epithelial Cells
Authors: Różanowska Małgorzata B. , Czuba-Pelech Barbara , Landrum John T. , Różanowski Bartosz
Published: May 2021

Dehydrolutein accumulates in substantial concentrations in the retina. The aim of this study was to compare antioxidant properties of dehydrolutein with other retinal carotenoids, lutein, and zeaxanthin, and their effects on ARPE-19 cells. The time-resolved detection of characteristic singlet oxygen phosphorescence was used to compare the singlet oxygen quenching rate constants of dehydrolutein, lutein, and zeaxanthin. The effects of these carotenoids on photosensitized oxidation were tested in liposomes, where photo-oxidation was induced by light in the presence of photosensitizers, and monitored by oximetry. To compare the uptake of dehydrolutein, lutein, and zeaxanthin, ARPE-19 cells were incubated with carotenoids for up to 19 days, and carotenoid contents were determined by spectrophotometry in cell extracts. To investigate the effects of carotenoids on photocytotoxicity, cells were exposed to light in the presence of rose bengal or all-trans-retinal. The results demonstrate that the rate constants for singlet oxygen quenching are 0.77 × 1010, 0.55 × 1010, and 1.23 × 1010 M−1s−1 for dehydrolutein, lutein, and zeaxanthin, respectively. Overall, dehydrolutein is similar to lutein or zeaxanthin in the protection of lipids against photosensitized oxidation. ARPE-19 cells accumulate substantial amounts of both zeaxanthin and lutein, but no detectable amounts of dehydrolutein. Cells pre-incubated with carotenoids are equally susceptible to photosensitized damage as cells without carotenoids. Carotenoids provided to cells together with the extracellular photosensitizers offer partial protection against photodamage. In conclusion, the antioxidant properties of dehydrolutein are similar to lutein and zeaxanthin. The mechanism responsible for its lack of accumulation in ARPE-19 cells deserves further investigation.
The Use of Coenzyme Q10 in Cardiovascular Diseases
Authors: Rabanal-Ruiz Yoana , Llanos-González Emilio , Alcain Francisco Javier
Published: May 2021

CoQ10 is an endogenous antioxidant produced in all cells that plays an essential role in energy metabolism and antioxidant protection. CoQ10 distribution is not uniform among different organs, and the highest concentration is observed in the heart, though its levels decrease with age. Advanced age is the major risk factor for cardiovascular disease and endothelial dysfunction triggered by oxidative stress that impairs mitochondrial bioenergetic and reduces NO bioavailability, thus affecting vasodilatation. The rationale of the use of CoQ10 in cardiovascular diseases is that the loss of contractile function due to an energy depletion status in the mitochondria and reduced levels of NO for vasodilatation has been associated with low endogenous CoQ10 levels. Clinical evidence shows that CoQ10 supplementation for prolonged periods is safe, well-tolerated and significantly increases the concentration of CoQ10 in plasma up to 3–5 µg/mL. CoQ10 supplementation reduces oxidative stress and mortality from cardiovascular causes and improves clinical outcome in patients undergoing coronary artery bypass graft surgery, prevents the accumulation of oxLDL in arteries, decreases vascular stiffness and hypertension, improves endothelial dysfunction by reducing the source of ROS in the vascular system and increases the NO levels for vasodilation.
Aqueous Blackcurrant Extract Improves Insulin Sensitivity and Secretion and Modulates the Gut Microbiome in Non-Obese Type 2 Diabetic Rats
Authors: Yang Hye-Jeong , Zhang Ting , Wu Xuan-Gao , Kim Min-Jung , Kim Young-Ho , Yang Eun-Suk , Yoon Yeong-Seok , Park Sunmin
Published: May 2021

This study was undertaken to determine whether aqueous blackcurrant extracts (BC) improve glucose metabolism and gut microbiomes in non-obese type 2 diabetic animals fed a high-fat diet and to identify the mechanism involved. Partially pancreatectomized male Sprague–Dawley rats were provided a high-fat diet containing 0% (control), 0.2% (L-BC; low dosage), 0.6% (M-BC; medium dosage), and 1.8% (H-BC; high dosage) blackcurrant extracts; 0.2% metformin (positive-C); plus 1.8%, 1.6%, 1.2%, 0%, and 1.6% dextrin, specifically indigestible dextrin, daily for 8 weeks. Daily blackcurrant extract intakes were equivalent to 100, 300, and 900 mg/kg body weight (bw). After a 2 g glucose or maltose/kg bw challenge, serum glucose and insulin concentrations during peak and final states were obviously lower in the M-BC and H-BC groups than in the control group (p < 0.05). Intraperitoneal insulin tolerance testing showed that M-BC and H-BC improved insulin resistance. Hepatic triglyceride deposition, TNF-α expression, and malondialdehyde contents were lower in the M-BC and H-BC groups than in the control group. Improvements in insulin resistance in the M-BC and H-BC groups were associated with reduced inflammation and oxidative stress (p < 0.05). Hyperglycemic clamp testing showed that insulin secretion capacity increased in the acute phase (2 to 10 min) in the M-BC and H-BC groups and that insulin sensitivity in the hyperglycemic state was greater in these groups than in the control group (p < 0.05). Pancreatic β-cell mass was greater in the M-BC, H-BC, and positive-C groups than in the control group. Furthermore, β-cell proliferation appeared to be elevated and apoptosis was suppressed in these three groups (p < 0.05). Serum propionate and butyrate concentrations were higher in the M-BC and H-BC groups than in the control group. BC dose-dependently increased α-diversity of the gut microbiota and predicted the enhancement of oxidative phosphorylation-related microbiome genes and downregulation of carbohydrate digestion and absorption-related genes, as determined by PICRUSt2 analysis. In conclusion, BC enhanced insulin sensitivity and glucose-stimulated insulin secretion, which improved glucose homeostasis, and these improvements were associated with an incremental increase of the α-diversity of gut microbiota and suppressed inflammation and oxidative stress.
Protective Measurement—A New Quantum Measurement Paradigm: Detailed Description of the First Realization
Authors: Rebufello Enrico , Piacentini Fabrizio , Avella Alessio , Lussana Rudi , Villa Federica , Tosi Alberto , Gramegna Marco , Brida Giorgio , Cohen Eliahu , Vaidman Lev , Degiovanni Ivo Pietro , Genovese Marco
Published: May 2021

We present a detailed description of the experiment realizing for the first time a protective measurement, a novel measurement protocol which combines weak interactions with a “protection mechanism” preserving the measured state coherence during the whole measurement process. Furthermore, protective measurement allows finding the expectation value of an observable, i.e., an inherently statistical quantity, by measuring a single particle, without the need for any statistics. This peculiar property, in sharp contrast to the framework of traditional (projective) quantum measurement, might constitute a groundbreaking advance for several quantum technology related fields.
Dynamics of Changes in Climate Zones and Building Energy Demand. A Case Study in Spain
Authors: Díaz-López Carmen , Jódar Joaquín , Verichev Konstantin , Rodríguez Miguel Luis , Carpio Manuel , Zamorano Montserrat
Published: May 2021

In the current context of the climate crisis, it is essential to design buildings that can cope with climate dynamics throughout their life cycle. It will ensure the development of sustainable and resilient building stock. Thus, this study’s primary objective has been to demonstrate that the current climatic zones for buildings in peninsular Spain do not represent the current climatic reality and are not adapted to climate change and the impact on the energy demand of buildings. For this reason, the climatic zones of 7967 peninsular cities have been updated and adapted to the RCP 4.5 and RCP 8.5 scenarios by using the data measured in 77 meteorological reference stations. The results obtained have shown that in more than 80% of the cities, buildings are designed and constructed according to an obsolete climatic classification that does not take into account the current or future climatic reality, which will significantly affect the thermal performance of a building and highlights the need to review the climatic zoning in the country. The results obtained can be extrapolated to other regions. The methodology defined in this work can be used as a reference, thus making an essential scientific contribution in reflecting on current capacities and the possibilities of improving the building stock.
RNA-Seq Analysis of Gene Expression Changes Related to Delay of Flowering Time under Drought Stress in Tropical Maize
Authors: Kim Kyung-Hee , Song Kitae , Park Jeong-Min , Kim Jae-Yoon , Lee Byung-Moo
Published: May 2021

Few studies have reported on the flowering time mechanism of tropical maize under short-day conditions. Drought, another important factor that affects flowering time, has been reported to delay the silking date in tropical maize. However, due to the lack of genetic information related to flowering in maize, the mechanism by which drought delays flowering is unclear. To further understand this process, we analyzed drought-responsive genes using RNA sequencing and identified genes related to flowering time, including contigs from de novo assembly. The results revealed changes in the expression of flowering-time genes, including INDETERMINATE1 (ID1), Heading date 3a (Hd3a), CONSTANS-like genes, and ZEA MAYS CENTRORADIALES8 (ZCN8), which are known to be crucial factors in flowering. In particular, Hd3a, CONZ1, and ZCN8, which have been reported to accelerate flowering under short-day conditions, were downregulated by drought stress. Changes in gene expression appear to play an important role in changes in flowering time under drought. These expression profiles will help to further understand the flowering-time genes of tropical maize and the delayed flowering time resulting from drought.
Design and Operation of Empirical Manganese-Removing Bioreactors and Integration into a Composite Modular System for Remediating and Recovering Metals from Acidic Mine Waters
Authors: Santos Ana Laura , Johnson D. Barrie
Published: May 2021

Packed bed bioreactors were used to remove soluble manganese from a synthetic mine water as the final stage of an integrated bioremediation process. The synthetic mine water had undergone initial processing using a sulfidogenic bioreactor (pH 4.0–5.5) which removed all transition metals present in elevated concentrations (Cu, Ni, Zn and Co) apart from manganese. The aerobic bioreactors were packed with pebbles collected from a freshwater stream that were coated with black-colored, Mn(IV)-containing biofilms, and their capacity to remove soluble Mn (II) from the synthetic mine water was tested at varying hydraulic retention times (11–45 h) and influent liquor pH values (5.0 or 6.5). Over 99% of manganese was removed from the partly processed mine water when operated at pH 6.5 and a HRT of 45 h. Molecular techniques (clone libraries and T-RFLP analysis) were used to characterize the biofilms and identified two heterotrophic Mn-oxidizing microorganisms: the bacterium Leptothrix discophora and what appears to be a novel fungal species. The latter was isolated and characterized in vitro.
Impact of Grid Strength and Impedance Characteristics on the Maximum Power Transfer Capability of Grid-Connected Inverters
Authors: Huang Liang , Wu Chao , Zhou Dao , Blaabjerg Frede
Published: May 2021

Continuously expanding deployments of distributed power generation systems are transforming conventional centralized power grids into mixed distributed electrical networks. The higher penetration and longer distance from the renewable energy source to the main power grid result in lower grid strength, which stimulates the power limitation problem. Aimed at this problem, case studies of inductive and resistive grid impedance with different grid strengths have been carried out to evaluate the maximum power transfer capability of grid-connected inverters. It is revealed that power grids with a higher short circuit ratio (SCR) or lower resistance-inductance ratio (R/X) provide higher power transfer capability. Moreover, under the resistive grid conditions, a higher voltage at the point of common coupling (PCC) is beneficial to increase the power transfer capability. Based on mathematical analysis, the maximum power curves in the inductive and resistive grids can be found. Moreover, a performance index is proposed in this paper to quantify the performance of the system with different parameter values. Finally, the effectiveness of the analysis is verified by simulation.
Tuning ANN Hyperparameters for Forecasting Drinking Water Demand
Authors: Menapace Andrea , Zanfei Ariele , Righetti Maurizio
Published: May 2021

The evolution of smart water grids leads to new Big Data challenges boosting the development and application of Machine Learning techniques to support efficient and sustainable drinking water management. These powerful techniques rely on hyperparameters making the models’ tuning a tricky and crucial task. We hence propose an insightful analysis of the tuning of Artificial Neural Networks for drinking water demand forecasting. This study focuses on layers and nodes’ hyperparameters fitting of different Neural Network architectures through a grid search method by varying dataset, prediction horizon and set of inputs. In particular, the architectures involved are the Feed Forward Neural Network, the Long Short Term Memory, the Simple Recurrent Neural Network and the Gated Recurrent Unit, while the prediction interval ranges from 1 h to 1 week. To avoid the problem of the Neural Networks tuning stochasticity, we propose the selection of the median model among several repetitions for each hyperparameter’s configurations. The proposed iterative tuning procedure highlights the change of the required number of layers and nodes depending on Neural Network architectures, prediction horizon and dataset. Significant trends and considerations are pointed out to support Neural Network application in drinking water prediction.
Research on a Low Melting Point Al-Si-Cu (Ni) Filler Metal for 6063 Aluminum Alloy Brazing
Authors: Peng Chengyin , Zhu Dandan , Li Kaifeng , Du Xiang , Zhao Fei , Wan Mingpan , Tan Yuanbiao
Published: May 2021

A new type of low melting point Al-Si-Cu (Ni) filler metal for brazed 6063 aluminum alloy was designed, and the microstructure and properties of the filler metal were systematically studied. The results show that when the content of Cu in the Al-Si-Cu filler metal increased from 10 wt.% to 20 wt.%, the liquidus temperature of the filler metal decreased from 587.8 °C to 533.4 °C. Its microstructures were mainly composed of the α-Al phase, a primary Si phase, and a θ(Al2Cu) phase. After a proper amount of Ni was added to the Al-Si-20Cu filler metal, its melting range was narrowed, the spreading wettability was improved, and the microstructure was refined. Its microstructure mainly includes α-Al solid solution, Si particles, and θ(Al2Cu) and δ(Al3Ni2) intermetallic compounds. The results of the shear strength test indicate that the shear strength of the brazed joint with Al-6.5Si-20Cu-2.0Ni filler metal was 150.4 MPa, which was 28.32% higher than that of the brazed joint with Al-6.5Si-20Cu filler metal.
MR Imaging–Pathologic Correlation of Uveal Melanomas Undergoing Secondary Enucleation after Proton Beam Radiotherapy
Authors: Foti Pietro Valerio , Inì Corrado , Travali Mario , Farina Renato , Palmucci Stefano , Spatola Corrado , Liardo Rocco Luca Emanuele , Milazzotto Roberto , Raffaele Luigi , Salamone Vincenzo , Caltabiano Rosario , Broggi Giuseppe , Puzzo Lidia , Russo Andrea , Reibaldi Michele , Longo Antonio , Vigneri Paolo , Venturini Massimo , Basile Antonio
Published: May 2021

Background: Currently, radiotherapy represents the most widely employed therapeutic option in patients with uveal melanoma. Although the effects of proton beam radiotherapy on uveal melanoma end ocular tissues have been histologically documented, their appearance at MR imaging is still poorly understood. The purpose of our study was to elucidate the magnetic resonance (MR) semiotics of radiotherapy-induced changes to neoplastic tissues and ocular structures in patients with uveal melanoma undergoing secondary enucleation after proton beam radiotherapy. Methods: Nine patients with uveal melanoma who had undergone proton beam radiotherapy, MR imaging, and subsequent secondary enucleation were retrospectively selected. The histopathologic findings evaluated for irradiated tumors were necrosis, fibrosis, and viable tumor, while the histopathologic findings evaluated for extratumoral ocular/periocular tissues were radiation-related intraocular inflammation, vitreous hemorrhage, optic nerve degeneration, iris neovascularization, and periocular fibrotic adhesions. On MR images, the appearance of the abovementioned histologic features was assessed on conventional and diffusion-weighted sequences. Results: T2-weighted sequences performed better in detecting radiation-induced necrosis, fibrosis, optic nerve degeneration, and periocular fibrotic adhesions. T1-weighted sequences were preferable for identifying cataracts, vitreous hemorrhage, and inflammatory complications. Contrast-enhanced T1-weighted sequences were irreplaceable in assessing iris neovascularization, and in confirming inflammatory complications. Conclusions: In the light of their increasing role in the multidisciplinary management of patients with uveal melanoma, radiologists should be aware of the MR appearance of the effects of radiotherapy on neoplastic and ocular tissue, in order to improve the accuracy of follow-up MR examinations.
Heat Treatment and Wounding as Abiotic Stresses to Enhance the Bioactive Composition of Pineapple By-Products
Authors: Santos Diana I. , Faria Diana L. , Lourenço Sofia C. , Alves Vitor D. , Saraiva Jorge A. , Vicente António A. , Moldão-Martins Margarida
Published: May 2021

Abiotic stress, like heat treatment and wounding, applied to pineapple by-products induce the accumulation of new compounds and add value. In this work the effect of the individual or combined application of wounding and heat treatment stresses on total phenolic content, antioxidant activity through complementary methods (DPPH, FRAP, and ABTS) and enzymatic activity (bromelain, phenylalanine ammonia lyase (PAL) and polyphenol oxidase) were evaluated. Whole and wounded pineapple shell and core were dipped in a hot water bath at 30 ± 1 °C or 40 ± 1 °C for 10 min and stored under refrigeration conditions (4 ± 1 °C) for 24 h or 48 h. Results allowed that pineapple by-products reacted differently to the tested stresses. For the core, the application of wounding and heat treatment (40 °C) before storage (24 h) induced a synergistic effect on the accumulation of phenols (increased 17%) and antioxidant activity (4–22%). For the shell samples, the treatment that most increased the content of phenols (14%) and antioxidant activity (38–45%) was heat treatment at 30 °C and storage for 48 h. Treatments that positively influenced the content of phenols and antioxidant activity of the samples did not affect the activity of bromelain or PAL. This study showed that proper abiotic stresses could increase the functional value of by-products.
MiR-21 in the Cancers of the Digestive System and Its Potential Role as a Diagnostic, Predictive, and Therapeutic Biomarker
Authors: Nguyen Ha Thi , Kacimi Salah Eddine Oussama , Nguyen Truc Ly , Suman Kamrul Hassan , Lemus-Martin Roselyn , Saleem Humaira , Do Duy Ngoc
Published: May 2021

MicroRNAs (miRNAs) are small non-coding RNAs. They can regulate the expression of their target genes, and thus, their dysregulation significantly contributes to the development of cancer. Growing evidence suggests that miRNAs could be used as cancer biomarkers. As an oncogenic miRNA, the roles of miR-21 as a diagnostic and prognostic biomarker, and its therapeutic applications have been extensively studied. In this review, the roles of miR-21 are first demonstrated via its different molecular networks. Then, a comprehensive review on the potential targets and the current applications as a diagnostic and prognostic cancer biomarker and the therapeutic roles of miR-21 in six different cancers in the digestive system is provided. Lastly, a brief discussion on the challenges for the use of miR-21 as a therapeutic tool for these cancers is added.
Microarray and qPCR Analysis of Mitochondrial Metabolism Activation during Prenatal and Early Postnatal Development in Rats and Humans with Emphasis on CoQ10 Biosynthesis
Authors: Krizova Jana , Hulkova Martina , Capek Vaclav , Mlejnek Petr , Silhavy Jan , Tesarova Marketa , Zeman Jiri , Hansikova Hana
Published: May 2021

At the end of the mammalian intra-uterine foetal development, a rapid switch from glycolytic to oxidative metabolism must proceed. Using microarray techniques, qPCR, enzyme activities and coenzyme Q content measurements, we describe perinatal mitochondrial metabolism acceleration in rat liver and skeletal muscle during the perinatal period and correlate the results with those in humans. Out of 1546 mitochondrial genes, we found significant changes in expression in 1119 and 827 genes in rat liver and skeletal muscle, respectively. The most remarkable expression shift occurred in the rat liver at least two days before birth. Coenzyme Q-based evaluation in both the rat model and human tissues showed the same trend: the total CoQ content is low prenatally, significantly increasing after birth in both the liver and skeletal muscle. We propose that an important regulator of rat coenzyme Q biosynthesis might be COQ8A, an atypical kinase involved in the biosynthesis of coenzyme Q. Our microarray data, a total of 16,557 RefSeq (Entrez) genes, have been deposited in NCBI’s Gene Expression Omnibus and are freely available to the broad scientific community. Our microarray data could serve as a suitable background for finding key factors regulating mitochondrial metabolism and the preparation of the foetus for the transition to extra-uterine conditions.
Digital PCR for Genotype Quantification: A Case Study in a Pasta Production Chain
Authors: Morcia Caterina , Terzi Valeria , Ghizzoni Roberta , Vaiuso Chiara , Delogu Chiara , Andreani Lorella , Venturini Andrea , Carnevali Paola , Pompa Pier Paolo , Tumino Giorgio
Published: May 2021

Digital polymerase chain reaction (dPCR) is a breakthrough technology based on the partitioning of the analytical sample and detection of individual end-point amplifications into the separate compartments. Among the numerous applications of this technology, its suitability in mutation detection is relevant and characterized by unprecedented levels of precision. The actual applicability of this analytical technique to quantify the presence of a specific plant genotype, in both raw materials and transformed products, by exploiting a point polymorphism has been evaluated. As proof of concept, an Italian premium pasta production chain was considered and a dPCR assay based on a durum wheat target variety private point mutation was designed and evaluated in supply-chain samples. From the results obtained, the assay can be applied to confirm the presence of a target variety and to quantify it in raw materials and transformed products, such as commercial grain lots and pasta. The performance, costs, and applicability of the assay has been compared to analytical alternatives, namely simple sequence repeats (SSRs) and genotype-by-sequencing based on Diversity Arrays Technology sequencing (DArTseqTM).
Crop Improvement: Now and Beyond
Authors: Sourdille Pierre , Devaux Pierre
Published: May 2021

There is an urgent need to increase and improve the production of most agronomic species to meet the current food security challenge [...]
Survival, Growth, and Reproduction: Comparison of Marbled Crayfish with Four Prominent Crayfish Invaders
Authors: Kouba Antonín , Lipták Boris , Kubec Jan , Bláha Martin , Veselý Lukáš , Haubrock Phillip J. , Oficialdegui Francisco J. , Niksirat Hamid , Patoka Jiří , Buřič Miloš
Published: May 2021

Biological invasions are increasingly recognized ecological and economic threats to biodiversity and are projected to increase in the future. Introduced freshwater crayfish in particular are protruding invaders, exerting tremendous impacts on native biodiversity and ecosystem functioning, as exemplified by the North American spiny-cheek, signal and red swamp crayfish as well as the Australian common yabby. The marbled crayfish is among the most outstanding freshwater crayfish invaders due to its parthenogenetic reproduction combined with early maturation and high fecundity. As their introduced ranges expand, their sympatric populations become more frequent. The question of which species and under what circumstances will dominate in their introduced communities is of great interest to biodiversity conservation as it can offer valuable insights for understanding and prioritization of management efforts. In order to examine which of the aforementioned species may be more successful as an invader, we conducted a set of independent trials evaluating survival, growth, claw injury, and reproduction using single-species stocks (intraspecific interactions) and mixed stocks (interspecific interactions) of marbled crayfish vs. other crayfish invaders since the onset of exogenous feeding. In both single and mixed stocks, red swamp crayfish and yabby grew faster than marbled crayfish, while marbled crayfish were superior to both spiny-cheek and signal crayfish in terms of growth. With the exception of signal crayfish, the faster-growing species consistently reached a higher survival rate. The faster-growing species tended to negatively impair smaller counterparts by greater claw injury, delayed maturation, and reduced fecundity. Only marbled crayfish laid eggs as early as 14 weeks in this study, which is earlier than previously reported in the literature. Thus, the success of marbled crayfish among invasive crayfish is significantly driven by relatively fast growth as well as an early and frequent reproduction. These results shed light on how interactions between invasive populations can unfold when their expansion ranges overlap in the wild, thereby contributing to the knowledge base on the complex population dynamics between existing and emerging invasive species.
Immunology of Acute and Chronic Wound Healing
Authors: Raziyeva Kamila , Kim Yevgeniy , Zharkinbekov Zharylkasyn , Kassymbek Kuat , Jimi Shiro , Saparov Arman
Published: May 2021

Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.
Flexibility of Oxidized and Reduced States of the Chloroplast Regulatory Protein CP12 in Isolation and in Cell Extracts
Authors: Launay Helene , Shao Hui , Bornet Olivier , Cantrelle Francois-Xavier , Lebrun Regine , Receveur-Brechot Veronique , Gontero Brigitte
Published: May 2021

In the chloroplast, Calvin–Benson–Bassham enzymes are active in the reducing environment created in the light by electrons from the photosystems. In the dark, these enzymes are inhibited, mainly caused by oxidation of key regulatory cysteine residues. CP12 is a small protein that plays a role in this regulation with four cysteine residues that undergo a redox transition. Using amide-proton exchange with solvent, measured by nuclear magnetic resonance (NMR) and mass-spectrometry, we confirmed that reduced CP12 is intrinsically disordered. Using real-time NMR, we showed that the oxidation of the two disulfide bridges is simultaneous. In oxidized CP12, the C23–C31 pair is in a region that undergoes a conformational exchange in the NMR-intermediate timescale. The C66–C75 pair is in the C-terminus that folds into a stable helical turn. We confirmed that these structural states exist in a physiologically relevant environment: a cell extract from Chlamydomonas reinhardtii. Consistent with these structural equilibria, the reduction is slower for the C66–C75 pair than for the C23–C31 pair. The redox mid-potentials for the two cysteine pairs differ and are similar to those found for glyceraldehyde 3-phosphate dehydrogenase and phosphoribulokinase, consistent with the regulatory role of CP12.
Salicylic Acid Biosynthesis and Metabolism: A Divergent Pathway for Plants and Bacteria
Authors: Mishra Awdhesh , Baek Kwang-Hyun
Published: May 2021

Salicylic acid (SA) is an active secondary metabolite that occurs in bacteria, fungi, and plants. SA and its derivatives (collectively called salicylates) are synthesized from chorismate (derived from shikimate pathway). SA is considered an important phytohormone that regulates various aspects of plant growth, environmental stress, and defense responses against pathogens. Besides plants, a large number of bacterial species, such as Pseudomonas, Bacillus, Azospirillum, Salmonella, Achromobacter, Vibrio, Yersinia, and Mycobacteria, have been reported to synthesize salicylates through the NRPS/PKS biosynthetic gene clusters. This bacterial salicylate production is often linked to the biosynthesis of small ferric-ion-chelating molecules, salicyl-derived siderophores (known as catecholate) under iron-limited conditions. Although bacteria possess entirely different biosynthetic pathways from plants, they share one common biosynthetic enzyme, isochorismate synthase, which converts chorismate to isochorismate, a common precursor for synthesizing SA. Additionally, SA in plants and bacteria can undergo several modifications to carry out their specific functions. In this review, we will systematically focus on the plant and bacterial salicylate biosynthesis and its metabolism.
Susceptibility of Women to Cardiovascular Disease and the Prevention Potential of Mind–Body Intervention by Changes in Neural Circuits and Cardiovascular Physiology
Authors: Yang Hyun-Jeong , Koh Eugene , Kang Yunjeong
Published: May 2021

Women have been reported to be more vulnerable to the development, prognosis and mortality of cardiovascular diseases, yet the understanding of the underlying mechanisms and strategies to overcome them are still relatively undeveloped. Studies show that women’s brains are more sensitive to factors affecting mental health such as depression and stress than men’s brains. In women, poor mental health increases the risk of cardiovascular disease, and conversely, cardiovascular disease increases the incidence of mental illness such as depression. In connection with mental health and cardiovascular health, the presence of gender differences in brain activation, cortisol secretion, autonomic nervous system, vascular health and inflammatory response has been observed. This connection suggests that strategies to manage women’s mental health can contribute to preventing cardiovascular disease. Mind–body interventions, such as meditation, yoga and qigong are forms of exercise that strive to actively manage both mind and body. They can provide beneficial effects on stress reduction and mental health. They are also seen as structurally and functionally changing the brain, as well as affecting cortisol secretion, blood pressure, heart rate variability, immune reactions and reducing menopausal symptoms, thus positively affecting women’s cardiovascular health. In this review, we investigate the link between mental health, brain activation, HPA axis, autonomic nervous system, blood pressure and immune system associated with cardiovascular health in women and discuss the effects of mind–body intervention in modulating these factors.
Injectable Hydrogels for Chronic Skin Wound Management: A Concise Review
Authors: Zawani Mazlan , Fauzi Mh Busra
Published: May 2021

Diabetic foot ulcers (DFU) are a predominant impediment among diabetic patients, increasing morbidity and wound care costs. There are various strategies including using biomaterials have been explored for the management of DFU. This paper will review the injectable hydrogel application as the most studied polymer-based hydrogel based on published journals and articles. The main key factors that will be discussed in chronic wounds focusing on diabetic ulcers include the socioeconomic burden of chronic wounds, biomaterials implicated by the government for DFU management, commercial hydrogel product, mechanism of injectable hydrogel, the current study of novel injectable hydrogel and the future perspectives of injectable hydrogel for the management of DFU.
Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety
Authors: Vlatkovic Irena
Published: May 2021

Lipid nanoparticle (LNP) formulated messenger RNA-based (LNP-mRNA) vaccines came into the spotlight as the first vaccines against SARS-CoV-2 virus to be applied worldwide. Long-known benefits of mRNA-based technologies consisting of relatively simple and fast engineering of mRNA encoding for antigens and proteins of interest, no genomic integration, and fast and efficient manufacturing process compared with other biologics have been verified, thus establishing a basis for a broad range of applications. The intrinsic immunogenicity of LNP formulated in vitro transcribed (IVT) mRNA is beneficial to the LNP-mRNA vaccines. However, avoiding immune activation is critical for therapeutic applications of LNP-mRNA for protein replacement where targeted mRNA expression and repetitive administration of high doses for a lifetime are required. This review summarizes our current understanding of immune activation induced by mRNA, IVT byproducts, and LNP. It gives a comprehensive overview of the present status of preclinical and clinical studies in which LNP-mRNA is used for protein replacement and treatment of rare diseases with an emphasis on safety. Moreover, the review outlines innovations and strategies to advance pharmacology and safety of LNP-mRNA for non-immunotherapy applications.
Long-Term Outcomes and Evaluation of Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Eradication by Direct-Acting Antiviral Treatment: All Kagawa Liver Disease Group (AKLDG) Study
Authors: Tani Joji , Senoh Tomonori , Moriya Akio , Ogawa Chikara , Deguchi Akihiro , Sakamoto Teppei , Takuma Kei , Nakahara Mai , Oura Kyoko , Tadokoro Tomoko , Mimura Shima , Fujita Koji , Yoneyama Hirohito , Kobara Hideki , Morishita Asahiro , Himoto Takashi , Tsutsui Akemi , Nagano Takuya , Takaguchi Koichi , Masaki Tsutomu
Published: May 2021

There are limited studies that have evaluated the long-term outcomes in patients with hepatocellular carcinoma (HCC) recurrence after direct-acting antiviral (DAA) treatment. In this retrospective study, we aimed to investigate the recurrence rates, recurrence factors, and prognosis of 130 patients who were treated with IFN-free DAA treatment after treatment for HCC. The median observation time was 41 ± 13.9 months after DAA treatment. The recurrence rates of HCC were 23.2%, 32.5%, 46.3%, and 59.4% at 6, 12, 24, and 36 months, respectively. A multivariate analysis showed that palliative treatment prior to DAA treatment (HR = 3.974, 95% CI 1.924–8.207, p = 0.0006) and alpha-fetoprotein at sustained virological response 12 (HR = 1.048, 95% CI 1.016–1.077, p = 0.0046) were associated with independent factors for HCC recurrence (HCC-R). The 12-, 24-, and 36-month overall survival rates were 97.6%, 94.0%, and 89.8%, respectively. The 12-, 24-, and 36-month survival rates of the non-recurrence and recurrence groups were 97.7%, 97.7%, and 94.1% and 97.6%, 92.3%, and 87.9%, respectively (p = 0.3404). The size of the main tumor lesion and the serological data were significantly improved at the time of HCC-R after DAA treatment. This study showed an improved prognosis regardless of recurrence rate, which suggests that DAA treatment in HCV patients should be considered.
Molecular Crosstalk between the Hepatitis C Virus and the Extracellular Matrix in Liver Fibrogenesis and Early Carcinogenesis
Authors: Reungoat Emma , Grigorov Boyan , Zoulim Fabien , Pécheur Eve-Isabelle
Published: May 2021

Chronic infection by the hepatitis C virus (HCV) is a major cause of liver diseases, predisposing to fibrosis and hepatocellular carcinoma. Liver fibrosis is characterized by an overly abundant accumulation of components of the hepatic extracellular matrix, such as collagen and elastin, with consequences on the properties of this microenvironment and cancer initiation and growth. This review will provide an update on mechanistic concepts of HCV-related liver fibrosis/cirrhosis and early stages of carcinogenesis, with a dissection of the molecular details of the crosstalk during disease progression between hepatocytes, the extracellular matrix, and hepatic stellate cells.
Clinical Indications for Treatment with Multi-Kinase Inhibitors in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer
Authors: Fukuda Naoki , Takahashi Shunji
Published: May 2021

Differentiated thyroid cancer is usually a slow-growing disease, even if the patients develop distant metastasis. For recurrent or metastatic disease, radioactive iodine therapy is a standard treatment. However, the disease gradually progresses in some of the patients and can ultimately develop into life-threatening conditions. For patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), multi-kinase inhibitors (MKIs) including sorafenib and lenvatinib prolonged progression-free survival compared with placebo in pivotal randomized phase 3 trials, although the benefit in overall survival has not been clearly confirmed, possibly because the patients who received placebo were permitted to cross-over to lenvatinib upon disease progression. Moreover, the adverse events related to MKIs were not negligible. Therefore, the optimal timing of MKI initiation has long been controversial, and physicians should consider various patient and disease factors. Herein, we comprehensively review the clinical factors that can be helpful in determining the initiation of MKIs for patients with RR-DTC.