bluuebunny/crossref_metadata_2025 huggingface dataset:
Partial Biotinidase Deficiency Revealed Imbalances in Acylcarnitines Profile at Tandem Mass Spectrometry Newborn Screening
Authors: Cicalini Ilaria , Pieragostino Damiana , Rizzo Cristiano , Verrocchio Sara , Semeraro Daniela , Zucchelli Mirco , Di Michele Silvia , Dionisi-Vici Carlo , Stuppia Liborio , De Laurenzi Vincenzo , Bucci Ines , Rossi Claudia
Published: February 2021

Biotinidase (BTD) deficiency is an autosomal recessive inherited neurocutaneous disorder. BTD recycles the vitamin biotin, a coenzyme essential for the function of four biotin-dependent carboxylases, including propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, pyruvate carboxylase, and acetyl-CoA carboxylase. Due to deficient activities of the carboxylases, BTD deficiency is also recognized as late-onset multiple carboxylase deficiency and is associated with secondary alterations in the metabolism of amino acids, carbohydrates, and fatty acids. BTD deficiency can be classified as “profound”, with less than 10% of mean normal activity, and as “partial” with 10–30% of mean normal activity. Newborn screening (NBS) of BTD deficiency is performed in most countries and is able to detect both variants. Moreover, mild metabolic alterations related to carboxylase deficiency in profound BTD deficiency could result and possibly be revealed in the metabolic profile by tandem mass spectrometry (MS/MS) NBS. Here, we report the case of a newborn female infant with an initial suspected BTD deficiency at the NBS test, finally confirmed as a partial variant by molecular testing. Although BTD deficiency was partial, interestingly her metabolic profile at birth and during the follow-up tests revealed, for the first time, alterations in specific acylcarnitines as a possible result of the deficient activity of biotin-dependent carboxylases.
Health Synergies across International Sustainability and Development Agendas: Pathways to Strengthen National Action
Authors: Bowen Kathryn J. , Murphy Nabreesa , Dickin Sarah , Dzebo Adis , Ebikeme Charles
Published: February 2021

Since 2015 there has been a surge of international agendas to address a range of global challenges: climate change (Paris Agreement), sustainable development (Agenda 2030), disaster risk reduction (Sendai Framework) and sustainable urban transformation (New Urban Agenda). Health is relevant to all of these agendas. Policymakers must now translate these global agendas into national level policies to implement the agreed goals in a coherent manner. However, approaches to synergise health activities within and across these agendas are needed, in order to achieve better coherence and maximise national level implementation. This research evaluated the framing of human health within these agendas. A content analysis of the agendas was conducted. Findings indicate (i) the importance of increased awareness of health systems strengthening as a helpful framework to guide the integration of health issues across the agendas, (ii) only two health themes had synergies across the agendas, (iii) the lack of a governance mechanism to support the integration of these four agendas to enable national (and sub-national) governments to more feasibly implement their ambitions, and (iv) the vital component of health leadership. Finally, planetary health is a relevant and timely concept that can support the urgent shift to a healthy planet and people.
Evaluation of the Use of Sterilized and Non-Sterilized Peruibe Black Mud in Patients with Knee Osteoarthritis
Authors: Gouvêa Paulo Fávio Macedo , Britschka Zélia Maria Nogueira , Gomes Cristina de Oliveira Massoco Salles , Queiroz Nicolle Gilda Teixeira de , Salvador Pablo Antonio Vásquez , Silva Paulo Sergio Cardoso
Published: February 2021

This study aimed to evaluate the effects of treatment with Peruíbe Black Mud (PBM) on the clinical parameters and quality of life of patients with knee osteoarthritis and to compare the effects of PBM samples simply matured in seawater and PBM sterilized by gamma radiation. A controlled, double-blind trial was conducted with 41 patients divided into two treatment groups composed of 20 and 21 patients: one group was treated with matured PBM and the other with sterilized PBM. Evaluations were done using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Medical Outcomes Study Short Form 36 (SF-36) questionnaires, the Kellgren and Lawrence (KL) radiographic scale, and the quantification of the serum levels of inflammatory biomarkers. An improvement in pain, physical functions, and quality of life was observed in all of the patients who underwent treatment with both simply matured and sterilized PBM. Nine patients showed remission in the KL radiographic scale, but no statistically significant differences were observed in the serum levels of inflammatory mediators before or after treatment. Peruíbe Black Mud proves to be a useful tool as an adjuvant treatment for knee osteoarthritis (OA), as shown by the results of the WOMAC and SF-36 questionnaires and by the remission of the radiographic grade of some patients on the Kellgren and Lawrence scale.
The Impact of Menstrual Cycle Phase on Athletes’ Performance: A Narrative Review
Authors: Carmichael Mikaeli Anne , Thomson Rebecca Louise , Moran Lisa Jane , Wycherley Thomas Philip
Published: February 2021

The effect of the menstrual cycle on physical performance is being increasingly recognised as a key consideration for women’s sport and a critical field for further research. This narrative review explores the findings of studies investigating the effects of menstrual cycle phase on perceived and objectively measured performance in an athletic population. Studies examining perceived performance consistently report that female athletes identify their performance to be relatively worse during the early follicular and late luteal phases. Studies examining objective performance (using anaerobic, aerobic or strength-related tests) do not report clear, consistent effects of the impact of menstrual cycle phase on physical performance. Overall sport performance can be influenced by both perceived and physical factors. Hence, to optimise performance and management of eumenorrheic female athletes, there is a need for further research to quantify the impact of menstrual cycle phase on perceived and physical performance outcomes and to identify factors affecting variability in objective performance outcomes between studies.
Sense of Coherence and Quality of Life in Patients Treated with Antivitamin K Oral Anticoagulants: A Cross-Sectional Study
Authors: Anguas-Gracia Ana , Subirón-Valera Ana Belén , Rodríguez-Roca Beatriz , Gasch-Gallén Ángel , Antón-Solanas Isabel , Urcola-Pardo Fernando
Published: February 2021

The aim of this study was to analyze the correlation between the participants’ self-reported quality of life and their sense of coherence in a sample (n = 85) of patients on treatment with oral antivitamin K anticoagulants. A cross-sectional design was used. The measurement instruments included a questionnaire on sociodemographic variables, the Spanish version of the Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-BREF), an oral-anticoagulant-treatment-specific quality-of-life questionnaire, and the sense-of-coherence (SOC) scale. We analyzed the correlations between the participants’ characteristics and the results from the quality-of-life and SOC scales. Age, level of education, employment status, living arrangement, and treatment length were the determinants of the quality of life in people treated with oral anticoagulants. We found a significant association between the four domains of the WHOQOL-BREF questionnaire and general treatment satisfaction (p < 0.01); no significant correlations were found between the SOC subscales and the oral-anticoagulant-treatment-specific quality of life in our sample. Women had a worse level of self-management than men. Nursing interventions should be tailored to the needs of the populations on treatment with oral anticoagulants in order to facilitate a higher level of self-management.
The Effects of Multi-Sociodemographic Characteristics of Construction Sites Personnel on Perceptions of Safety Climate-Influencing Factors: The Construction Industry in Saudi Arabia
Authors: Mosly Ibrahim , Makki Anas A.
Published: February 2021

The construction industry in Saudi Arabia relies prominently on migrant workers of multi-sociodemographic characteristics with different perceptions of a safety climate. The exploration of the perceptions regarding the safety climate among various groups of migrant workers may help identify effective means of improving safety levels at construction sites in Saudi Arabia. This study aimed to examine the effects of multi-sociodemographic characteristics of construction site personnel on their perceptions of the factors that influence the safety climate at construction sites in Saudi Arabia. Data were collected from 401 construction site workers, employed at ongoing construction project sites in Saudi Arabia, using a designed questionnaire. A generalized, linear model approach was applied, using the single ordinal logistic regression method, to analyze the collected data. The results revealed the significant sets of sociodemographic characteristics and their associated subgroups that had significant effects on the perception of importance assigned to each safety climate-influencing factor. These findings provide a better understanding of the views of construction site personnel on the safety climate and can assist construction industry decision-makers, safety policy designers, government agencies, and stakeholders when designing better-targeted enhancement plans and strategies to improve the safety climate of construction sites, based on the sociodemographic makeup of the personnel at each construction site.
Proteomics Complementation of the Rat Uterotrophic Assay for Estrogenic Endocrine Disruptors: A Roadmap of Advancing High Resolution Mass Spectrometry-Based Shotgun Survey to Targeted Biomarker Quantifications
Authors: Prokai Laszlo , Rahlouni Fatima , Zaman Khadiza , Nguyen Vien , Prokai-Tatrai Katalin
Published: February 2021

The widely used rat uterotrophic assay to assess known and potential estrogenic compounds only considers uterine weight gain as endpoint measurement. To complement this method with an advanced technology that reveals molecular targets, we analyzed changes in protein expression using label-free quantitative proteomics by nanoflow liquid chromatography coupled with high-resolution mass spectrometry and tandem mass spectrometry from uterine protein extracts of ovariectomized rats after daily 17β-estradiol exposure for five days in comparison with those of vehicle-treated control animals. Our discovery-driven study revealed 165 uterine proteins significantly regulated by estrogen treatment and mapped by pathway analyses. Estrogen-regulated proteins represented cell death, survival and development, cellular growth and proliferation, and protein synthesis as top molecular and cellular functions, and a network found with the presence of nuclear estrogen receptor(s) as a prominent molecular node confirmed the relevance of our findings to hormone-associated events. An exploratory application of targeted proteomics to bisphenol A as a well-known example of an estrogenic endocrine disruptor is also presented. Overall, the results of this study have demonstrated the power of combining untargeted and targeted quantitative proteomic strategies to identify and verify candidate molecular markers for the evaluation of endocrine-disrupting chemicals to complement a conventional bioassay.
Protein Expression of Angiotensin-Converting Enzyme 2 (ACE2) is Upregulated in Brains with Alzheimer’s Disease
Authors: Ding Qiyue , Shults Nataliia V. , Gychka Sergiy G. , Harris Brent T. , Suzuki Yuichiro J.
Published: February 2021

Alzheimer’s disease is a chronic neurodegenerative disorder and represents the main cause of dementia globally. Currently, the world is suffering from the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. In COVID-19, neurological manifestations have been reported to occur. The present study demonstrates that the protein expression level of ACE2 is upregulated in the brain of patients with Alzheimer’s disease. The increased ACE2 expression is not age-dependent, suggesting the direct relationship between Alzheimer’s disease and ACE2 expression. Oxidative stress has been implicated in the pathogenesis of Alzheimer’s disease, and brains with the disease examined in this study also exhibited higher carbonylated proteins, as well as an increased thiol oxidation state of peroxiredoxin 6 (Prx6). A moderate positive correlation was found between the increased ACE2 protein expression and oxidative stress in brains with Alzheimer’s disease. In summary, the present study reveals the relationships between Alzheimer’s disease and ACE2, the receptor for SARS-CoV-2. These results suggest the importance of carefully monitoring patients with both Alzheimer’s disease and COVID-19 in order to identify higher viral loads in the brain and long-term adverse neurological consequences.
Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?
Authors: Paganelli Franck , Mottola Giovanna , Fromonot Julien , Marlinge Marion , Deharo Pierre , Guieu Régis , Ruf Jean
Published: February 2021

The influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H2S) is a cardioprotector. Previous research proposed a positive role of H2S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H2S, which decreases the expression of adenosine A2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively.
The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target
Authors: Domingues Alison , Jolibois Julia , Marquet de Rougé Perrine , Nivet-Antoine Valérie
Published: February 2021

Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel identified target for preventive and curative medicine. The goal of this review is to focus on the novelties concerning TXNIP. After an overview in TXNIP involvement in oxidative stress, inflammation and metabolism, the remainder of this review presents the clues used to define TXNIP as a new marker at the genetic, blood, or ischemic site level in the context of cardiovascular and ischemic diseases.
In Silico Investigation of the New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a Focus at the ACE2–Spike RBD Interface
Authors: Villoutreix Bruno O. , Calvez Vincent , Marcelin Anne-Geneviève , Khatib Abdel-Majid
Published: February 2021

SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually in part due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor, several in silico methods and numerous experimental data reported recently to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both the UK and South African strains) should be favorable for the interaction with ACE2, while the K417N and E484K substitutions (South African strain) would seem neutral or even unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the K417N and E484K Spike replacements with regard to ACE2 binding. Our finding suggests that the UK strain should have higher affinity toward ACE2 and therefore likely increased transmissibility and possibly pathogenicity. If indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions located outside the direct Spike–ACE2 interface but not so much to the K417N and E484K replacements. Yet, it should be noted that amino acid changes at Spike position 484 can lead to viral escape from neutralizing antibodies. Further, these amino acid substitutions do not seem to induce major structural changes in this region of the Spike protein. This structure–function study allows us to rationalize some observations made for the UK strain but raises questions for the South African strain.
Particle Size and Biological Fate of ZnO Do Not Cause Acute Toxicity, but Affect Toxicokinetics and Gene Expression Profiles in the Rat Livers after Oral Administration
Authors: Yu Jin , Choi Soo-Jin
Published: February 2021

Zinc oxide (ZnO) particles have been used as dietary supplements because zinc is an essential trace element for humans. Along with the rapid development of nanotechnology, the use of ZnO nanoparticles (NPs) is increasing in the food industry, but their oral toxicity potential still remains to be answered. In this study, the effects of particle size and biological fate of ZnO on acute toxicity, toxicokinetics, and gene expression profiles in the livers were investigated after oral administration of ZnO NPs (N-ZnO), bulk-sized ZnO (B-ZnO) or Zn ions in rats. The plasma concentration-time profiles after a single-dose oral administration of ZnOs differed depending on particle/ionic forms and particle size, showing high absorption of Zn ions, followed by N-ZnO and B-ZnO, although in vivo solubility did not differ from particle size. No significant acute toxicity was found after oral administration of ZnOs for 14 days in rats. However, transcriptomic responses in the livers were differently affected, showing that metabolic process and metal biding were up-regulated by Zn ions and N-ZnO, respectively, which were not pronounced in the liver treated with B-ZnO. These findings will be useful to predict the potential oral toxicity of ZnO NPs and further mechanistic and long-term exposure studies are required to assume their safety.
A Novel Artificially Humanized Anti-Cripto-1 Antibody Suppressing Cancer Cell Growth
Authors: Ishii Hiroko , Zahra Maram H. , Takayanagi Atushi , Seno Masaharu
Published: February 2021

Cripto-1 is a member of the EGF-CFC/FRL1/Cryptic family and is involved in embryonic development and carcinogenesis. We designed a novel anti-Cripto-1 artificial antibody and assessed the recognition to the antigen and the potential to suppress the growth of cancer stem cells. First, single chain antibody clones were isolated by bio-panning with the affinity to recombinant Cripto-1 protein from our original phage-display library. Then, the variable regions of heavy chain VH and light chain VL in each clone were fused to constant regions of heavy chain CH and light chain CL regions respectively. These fused genes were expressed in ExpiCHO-S cells to produce artificial humanized antibodies against Cripto-1. After evaluation of the expression levels, one clone was selected and the anti-Cripto-1 antibody was produced and purified. The purified antibody showed affinity to recombinant Cripto-1 at 1.1 pmol and immunoreactivity to cancer tissues and cell lines. The antibody was available to detect the immunoreactivity in tissue microarrays of malignant tumors as well as in Cripto-1 overexpressing cells. Simultaneously, the antibody exhibited the potential to suppress the growth of human colon cancer derived GEO cells overexpressing Cripto-1 with IC50 at approximately 110 nM. The artificially humanized antibody is proposed to be a good candidate to target cancer cells overexpressing Cripto-1.
Impact of Liposomal Drug Formulations on the RBCs Shape, Transmembrane Potential, and Mechanical Properties
Authors: Cyboran-Mikołajczyk Sylwia , Sareło Przemysław , Pasławski Robert , Pasławska Urszula , Przybyło Magdalena , Nowak Kacper , Płóciennik Michał , Podbielska Halina , Kopaczyńska Marta , Wawrzyńska Magdalena
Published: February 2021

Liposomal technologies are used in order to improve the effectiveness of current therapies or to reduce their negative side effects. However, the liposome–erythrocyte interaction during the intravenous administration of liposomal drug formulations may result in changes within the red blood cells (RBCs). In this study, it was shown that phosphatidylcholine-composed liposomal formulations of Photolon, used as a drug model, significantly influences the transmembrane potential, stiffness, as well as the shape of RBCs. These changes caused decreasing the number of stomatocytes and irregular shapes proportion within the cells exposed to liposomes. Thus, the reduction of anisocytosis was observed. Therefore, some nanodrugs in phosphatidylcholine liposomal formulation may have a beneficial effect on the survival time of erythrocytes.
Role of Exosomal miRNA in Bladder Cancer: A Promising Liquid Biopsy Biomarker
Authors: Piao Xuan-Mei , Cha Eun-Jong , Yun Seok Joong , Kim Wun-Jae
Published: February 2021

Bladder cancer (BCa) is the most prevalent neoplasia of the urinary tract. Unfortunately, limited improvements in effective BCa management have meant that it remains a challenging disease. Cystoscopy has been the gold standard for BCa diagnosis and surveillance for over two centuries but is an invasive and expensive approach. Recently, liquid biopsy has been identified as a promising field of cancer research, due to its noninvasiveness and ease of sampling. Liquid biopsy samples could provide comprehensive information regarding the genetic landscape of cancer and could track genomic evolution of the disease over time. Exosomes, which contain RNAs, DNAs, and proteins, are a potential source of tumor biomarkers in liquid biopsy samples. In particular, exosomal miRNAs (exomiRs) hold great promise as biomarkers for tumor development and progression. In this review, we provide an overview of liquid biopsy biomarkers, with a particular focus on the use of exomiRs as biomarkers of cancer, and summarize their clinical implications for BCa. Finally, we discuss the future perspectives of these biomarkers in cancer research.
Cytotoxic Potential of a-Azepano- and 3-Amino-3,4-SeCo-Triterpenoids
Authors: Kazakova Oxana , Smirnova Irina , Tret’yakova Elena , Csuk René , Hoenke Sophie , Fischer Lucie
Published: February 2021

Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative 11 was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound 11 to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds 3, 4, 7, 8, 9, 11, 15, 16, 19, and 20 showed growth inhibitory (GI50) against the most sensitive cell lines at submicromolar concentrations (0.20–0.94 μM), and their cytotoxic activity (LC50) was also high (1–6 μM). Derivatives 3, 8, 11, 15, and 16 demonstrated a certain selectivity profile at GI50 level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol 3 at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI50 level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group.
Packaging Covered with Antiviral and Antibacterial Coatings Based on ZnO Nanoparticles Supplemented with Geraniol and Carvacrol
Authors: Mizielińska Małgorzata , Nawrotek Paweł , Stachurska Xymena , Ordon Magdalena , Bartkowiak Artur
Published: February 2021

The purpose of the study was to obtain an external coating based on nanoparticles of ZnO, carvacrol, and geraniol that could be active against viruses such as SARS-Co-V2. Additionally, the synergistic effect of the chosen substances in coatings was analyzed. The goal of the study was to measure the possible antibacterial activity of the coatings obtained. Testing antiviral activity with human pathogen viruses, such as SARS-Co-V2, requires immense safety measures. Bacteriophages such as phi 6 phage represent good surrogates for the study of airborne viruses. The results of the study indicated that the ZC1 and ZG1 coatings containing an increased amount of geraniol or carvacrol and a very small amount of nanoZnO were found to be active against Gram-positive and Gram-negative bacteria. It is also important that a synergistic effect between these active substances was noted. This explains why polyethylene (PE) films covered with the ZC1 or ZG1 coatings (as internal coatings) were found to be the best packaging materials to extend the quality and freshness of food products. The same coatings may be used as the external coatings with antiviral properties. The ZC1 and ZG1 coatings showed moderate activity against the phi 6 phage that has been selected as a surrogate for viruses such as coronaviruses. It can be assumed that coatings ZG1 and ZC1 will also be active against SARS-CoV-2 that is transmitted via respiratory droplets.
PEG-Coated Large Mesoporous Silicas as Smart Platform for Protein Delivery and Their Use in a Collagen-Based Formulation for 3D Printing
Authors: Banche-Niclot Federica , Montalbano Giorgia , Fiorilli Sonia , Vitale-Brovarone Chiara
Published: February 2021

Silica-based mesoporous systems have gained great interest in drug delivery applications due to their excellent biocompatibility and high loading capability. However, these materials face challenges in terms of pore-size limitations since they are characterized by nanopores ranging between 6–8 nm and thus unsuitable to host large molecular weight molecules such as proteins, enzymes and growth factors (GFs). In this work, for an application in the field of bone regeneration, large-pore mesoporous silicas (LPMSs) were developed to vehicle large biomolecules and release them under a pH stimulus. Considering bone remodeling, the proposed pH-triggered mechanism aims to mimic the release of GFs encased in the bone matrix due to bone resorption by osteoclasts (OCs) and the associated pH drop. To this aim, LPMSs were prepared by using 1,3,5-trimethyl benzene (TMB) as a swelling agent and the synthesis solution was hydrothermally treated and the influence of different process temperatures and durations on the resulting mesostructure was investigated. The synthesized particles exhibited a cage-like mesoporous structure with accessible pores of diameter up to 23 nm. LPMSs produced at 140 °C for 24 h showed the best compromise in terms of specific surface area, pores size and shape and hence, were selected for further experiments. Horseradish peroxidase (HRP) was used as model protein to evaluate the ability of the LPMSs to adsorb and release large biomolecules. After HRP-loading, LPMSs were coated with a pH-responsive polymer, poly(ethylene glycol) (PEG), allowing the release of the incorporated biomolecules in response to a pH decrease, in an attempt to mimic GFs release in bone under the acidic pH generated by the resorption activity of OCs. The reported results proved that PEG-coated carriers released HRP more quickly in an acidic environment, due to the protonation of PEG at low pH that catalyzes polymer hydrolysis reaction. Our findings indicate that LPMSs could be used as carriers to deliver large biomolecules and prove the effectiveness of PEG as pH-responsive coating. Finally, as proof of concept, a collagen-based suspension was obtained by incorporating PEG-coated LPMS carriers into a type I collagen matrix with the aim of designing a hybrid formulation for 3D-printing of bone scaffolds.
Allosteric Interactions between Adenosine A2A and Dopamine D2 Receptors in Heteromeric Complexes: Biochemical and Pharmacological Characteristics, and Opportunities for PET Imaging
Authors: Prasad Kavya , de Vries Erik F. J. , Elsinga Philip H. , Dierckx Rudi A. J. O. , van Waarde Aren
Published: February 2021

Adenosine and dopamine interact antagonistically in living mammals. These interactions are mediated via adenosine A2A and dopamine D2 receptors (R). Stimulation of A2AR inhibits and blockade of A2AR enhances D2R-mediated locomotor activation and goal-directed behavior in rodents. In striatal membrane preparations, adenosine decreases both the affinity and the signal transduction of D2R via its interaction with A2AR. Reciprocal A2AR/D2R interactions occur mainly in striatopallidal GABAergic medium spiny neurons (MSNs) of the indirect pathway that are involved in motor control, and in striatal astrocytes. In the nucleus accumbens, they also take place in MSNs involved in reward-related behavior. A2AR and D2R co-aggregate, co-internalize, and co-desensitize. They are at very close distance in biomembranes and form heteromers. Antagonistic interactions between adenosine and dopamine are (at least partially) caused by allosteric receptor–receptor interactions within A2AR/D2R heteromeric complexes. Such interactions may be exploited in novel strategies for the treatment of Parkinson’s disease, schizophrenia, substance abuse, and perhaps also attention deficit-hyperactivity disorder. Little is known about shifting A2AR/D2R heteromer/homodimer equilibria in the brain. Positron emission tomography with suitable ligands may provide in vivo information about receptor crosstalk in the living organism. Some experimental approaches, and strategies for the design of novel imaging agents (e.g., heterobivalent ligands) are proposed in this review.
Robust Ruthenium Catalysts Supported on Mesoporous Cyclodextrin-Templated TiO2-SiO2 Mixed Oxides for the Hydrogenation of Levulinic Acid to γ-Valerolactone
Authors: Decarpigny Cédric , Noël Sébastien , Addad Ahmed , Ponchel Anne , Monflier Eric , Bleta Rudina
Published: February 2021

In this paper, we present a versatile template-directed colloidal self-assembly method for the fabrication in aqueous phase of composition-tuned mesoporous RuO2@TiO2-SiO2 catalysts. Randomly methylated β-cyclodextrin/Pluronic F127 supramolecular assemblies were used as soft templates, TiO2 colloids as building blocks, and tetraethyl orthosilicate as a silica source. Catalysts were characterized at different stages of their synthesis using dynamic light scattering, N2-adsorption analysis, powder X-ray diffraction, temperature programmed reduction, high-resolution transmission electron microscopy, high-angle annular bright-field and dark-field scanning transmission electron microscopy, together with EDS elemental mapping. Results revealed that both the supramolecular template and the silica loading had a strong impact on the pore characteristics and crystalline structure of the mixed oxides, as well as on the morphology of the RuO2 nanocrystals. Their catalytic performance was then evaluated in the aqueous phase hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) under mild conditions (50 °C, 50 bar H2). Results showed that the cyclodextrin-derived catalyst displayed almost quantitative LA conversion and 99% GVL yield in less than one hour. Moreover, this catalyst could be reused at least five times without loss of activity. This work offers an effective approach to the utilization of cyclodextrins for engineering the surface morphology of Ru nanocrystals and pore characteristics of TiO2-based materials for catalytic applications in hydrogenation reactions.
Genomic Architecture of Phenotypic Plasticity in Response to Water Stress in Tetraploid Wheat
Authors: Fatiukha Andrii , Deblieck Mathieu , Klymiuk Valentyna , Merchuk-Ovnat Lianne , Peleg Zvi , Ordon Frank , Fahima Tzion , Korol Abraham , Saranga Yehoshua , Krugman Tamar
Published: February 2021

Phenotypic plasticity is one of the main mechanisms of adaptation to abiotic stresses via changes in critical developmental stages. Altering flowering phenology is a key evolutionary strategy of plant adaptation to abiotic stresses, to achieve the maximum possible reproduction. The current study is the first to apply the linear regression residuals as drought plasticity scores while considering the variation in flowering phenology and traits under non-stress conditions. We characterized the genomic architecture of 17 complex traits and their drought plasticity scores for quantitative trait loci (QTL) mapping, using a mapping population derived from a cross between durum wheat (Triticum turgidum ssp. durum) and wild emmer wheat (T. turgidum ssp. dicoccoides). We identified 79 QTLs affected observed traits and their plasticity scores, of which 33 reflected plasticity in response to water stress and exhibited epistatic interactions and/or pleiotropy between the observed and plasticity traits. Vrn-B3 (TaTF1) residing within an interval of a major drought-escape QTL was proposed as a candidate gene. The favorable alleles for most of the plasticity QTLs were contributed by wild emmer wheat, demonstrating its high potential for wheat improvement. Our study presents a new approach for the quantification of plant adaptation to various stresses and provides new insights into the genetic basis of wheat complex traits under water-deficit stress.
Characterization of the FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 Homolog SlFKF1 in Tomato as a Model for Plants with Fleshy Fruit
Authors: Shibuya Tomoki , Nishiyama Manabu , Kato Kazuhisa , Kanayama Yoshinori
Published: February 2021

FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) is a blue-light receptor whose function is related to flowering promotion under long-day conditions in Arabidopsis thaliana. However, information about the physiological role of FKF1 in day-neutral plants and even the physiological role other than photoperiodic flowering is lacking. Thus, the FKF1 homolog SlFKF1 was investigated in tomato, a day-neutral plant and a useful model for plants with fleshy fruit. It was confirmed that SlFKF1 belongs to the FKF1 group by phylogenetic tree analysis. The high sequence identity with A. thaliana FKF1, the conserved amino acids essential for function, and the similarity in the diurnal change in expression suggested that SlFKF1 may have similar functions to A. thaliana FKF1. CONSTANS (CO) is a transcription factor regulated by FKF1 and is responsible for the transcription of genes downstream of CO. cis-Regulatory elements targeted by CO were found in the promoter region of SINGLE FLOWER TRUSS (SFT) and RIN, which are involved in the regulation of flowering and fruit ripening, respectively. The blue-light effects on SlFKF1 expression, flowering, and fruit lycopene concentration have been observed in this study and previous studies. It was confirmed in RNA interference lines that the low expression of SlFKF1 is associated with late flowering with increased leaflets and low lycopene concentrations. This study sheds light on the various physiological roles of FKF1 in plants.
CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration
Authors: Hsieh Chia-Chu , Hsu Szu-Chun , Yao Ming , Huang Dong-Ming
Published: February 2021

Tetraspanin CD9 is widely expressed on various cell types, such as cancer cells and mesenchymal stem cells (MSCs), and/or cell-released exosomes. It has been reported that exosomal CD9 plays an important role in intercellular communications involved in cancer cell migration and metastasis. However, reports on the effect of the CD9 of MSCs or MSC-derived exosomes on cancer cell migration are still lacking. In this study, using a transwell migration assay, we found that both dextran-coated iron oxide nanoparticles (dex-IO NPs) and ionomycin stimulated exosomal CD9 expression in human MSCs (hMSCs); however, hMSCs could not deliver them to melanoma cells to affect cell migration. Interestingly, a reduced migration of melanoma cell line was observed when the ionomycin-incubated hMSC-conditioned media but not dex-IO NP-labeled hMSC-conditioned media were in the bottom chamber. In addition, we found that dex-IO NPs decreased cellular CD9 expression in hMSCs but ionomycin increased this. Simultaneously, we found that ionomycin suppressed the expression and secretion of the chemokine CCL21 in hMSCs. The silencing of CD9 demonstrated an inhibitory role of cellular CD9 in CCL21 expression in hMSCs, suggesting that ionomycin could upregulate cellular CD9 to decrease CCL21 expression and secretion of hMSCs, which would reduce the migration of B16F10, A549 and U87MG cancer cell lines due to chemoattraction reduction of CCL21. The present study not only highlights the important role of bone marrow-derived hMSCs’ CD9-mediated CCL21 regulation in cancer bone metastasis but also suggests a new distinct pharmaceutical strategy for prevention or/and therapy of cancer metastasis.
Efficient Chitosan/Nitrogen-Doped Reduced Graphene Oxide Composite Membranes for Direct Alkaline Ethanol Fuel Cells
Authors: Gorgieva Selestina , Osmić Azra , Hribernik Silvo , Božič Mojca , Svete Jurij , Hacker Viktor , Wolf Sigrid , Genorio Boštjan
Published: February 2021

Herein, we prepared a series of nanocomposite membranes based on chitosan (CS) and three compositionally and structurally different N-doped graphene derivatives. Two-dimensional (2D) and quasi 1D N-doped reduced graphene oxides (N-rGO) and nanoribbons (N-rGONRs), as well as 3D porous N-doped graphitic polyenaminone particles (N-pEAO), were synthesized and characterized fully to confirm their graphitic structure, morphology, and nitrogen (pyridinic, pyrrolic, and quaternary or graphitic) group contents. The largest (0.07%) loading of N-doped graphene derivatives impacted the morphology of the CS membrane significantly, reducing the crystallinity, tensile properties, and the KOH uptake, and increasing (by almost 10-fold) the ethanol permeability. Within direct alkaline ethanol test cells, it was found that CS/N rGONRs (0.07 %) membrane (Pmax. = 3.7 mWcm−2) outperformed the pristine CS membrane significantly (Pmax. = 2.2 mWcm−2), suggesting the potential of the newly proposed membranes for application in direct ethanol fuel cells.
Time-Course Changes of Extracellular Matrix Encoding Genes Expression Level in the Spinal Cord Following Contusion Injury—A Data-Driven Approach
Authors: Bighinati Andrea , Khalajzeyqami Zahra , Baldassarro Vito Antonio , Lorenzini Luca , Cescatti Maura , Moretti Marzia , Giardino Luciana , Calzà Laura
Published: February 2021

The involvement of the extracellular matrix (ECM) in lesion evolution and functional outcome is well recognized in spinal cord injury. Most attention has been dedicated to the “core” area of the lesion and scar formation, while only scattered reports consider ECM modification based on the temporal evolution and the segments adjacent to the lesion. In this study, we investigated the expression profile of 100 genes encoding for ECM proteins at 1, 8 and 45 days post-injury, in the spinal cord segments rostral and caudal to the lesion and in the scar segment, in a rat model. During both the active lesion phases and the lesion stabilization, we observed an asymmetric gene expression induced by the injury, with a higher regulation in the rostral segment of genes involved in ECM remodeling, adhesion and cell migration. Using bioinformatic approaches, the metalloproteases inhibitor Timp1 and the hyaluronan receptor Cd44 emerged as the hub genes at all post-lesion times. Results from the bioinformatic gene expression analysis were then confirmed at protein level by tissue analysis and by cell culture using primary astrocytes. These results indicated that ECM regulation also takes place outside of the lesion area in spinal cord injury.
Stereometric and Tribometric Studies of Polymeric Pin and Ceramic Plate Friction Pair Components
Authors: Niemczewska-Wójcik Magdalena , Wójcik Artur
Published: February 2021

Two complementary approaches should be used for the full characterisation of friction pair components. The first approach consists of stereometric studies of machined as well as worn surface topography of the friction components with multiple measurement methods used. The second approach, tribometric studies, enables the tribological characteristics of the friction pair. This work presents the complete characterisation of polymeric pin and ceramic plate friction pair components based on studies with the use of three research instruments: an interference microscope, a scanning electron microscope and a tribological tester. The results of the studies showed that the same treatment conditions used for different but similar ceramic materials did not provide exactly the same characteristics of both the machined and worn surface topography. Moreover, the results showed that the material properties and machined surface topography of the ceramic component significantly affected the friction coefficient and linear wear as well as the wear intensity of the polymeric component. Connecting the two approaches, stereometric studies and tribometric studies, allowed for a better identification of the wear mechanism of the polymeric pin (i.e., abrasion, fatigue and adhesion wear) and the kind of wear products (polymeric material).
PFAS Degradation in Ultrapure and Groundwater Using Non-Thermal Plasma
Authors: Palma Davide , Papagiannaki Dimitra , Lai Manuel , Binetti Rita , Sleiman Mohamad , Minella Marco , Richard Claire
Published: February 2021

Perfluoroalkyl substances (PFAS) represent one of the most recalcitrant class of compounds of emerging concern and their removal from water is a challenging goal. In this study, we investigated the removal efficiency of three selected PFAS from water, namely, perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA) and pefluorooctanesulfonic acid (PFOS) using a custom-built non-thermal plasma generator. A modified full factorial design (with 2 levels, 3 variables and the central point in which both quadratic terms and interactions between couple of variables were considered) was used to investigate the effect of plasma discharge frequency, distance between the electrodes and water conductivity on treatment efficiency. Then, the plasma treatment running on optimized conditions was used to degrade PFAS at ppb level both individually and in mixture, in ultrapure and groundwater matrices. PFOS 1 ppb exhibited the best degradation reaching complete removal after 30 min of treatment in both water matrices (first order rate constant 0.107 min−1 in ultrapure water and 0.0633 min−1 in groundwater), while the degradation rate of PFOA and PFHxA was slower of around 65% and 83%, respectively. During plasma treatment, the production of reactive species in the liquid phase (hydroxyl radical, hydrogen peroxide) and in the gas phase (ozone, NOx) was investigated. Particular attention was dedicated to the nitrogen balance in solution where, following to NOx hydrolysis, total nitrogen (TN) was accumulated at the rate of up to 40 mgN L−1 h−1.
The Decoration of ZnO Nanoparticles by Gamma Aminobutyric Acid, Curcumin Derivative and Silver Nanoparticles: Synthesis, Characterization and Antibacterial Evaluation
Authors: Talodthaisong Chanon , Plaeyao Kittiya , Mongseetong Chatariga , Boonta Wissuta , Srichaiyapol Oranee , Patramanon Rina , Kayunkid Navaphun , Kulchat Sirinan
Published: February 2021

Zinc oxide nanoparticles (ZnO NPs) are applied in various applications in catalysis, biosensing, imaging, and as antibacterial agents. Here we prepared ZnO nanomaterials decorated by γ-aminobutyric acid (GABA), curcumin derivatives (CurBF2) and silver nanoparticles (CurBF2-AgNPs). The structures of all ZnO nanostructures were characterized using Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), UV–VIS spectrophotometry, fluorescence spectrophotometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HR-TEM). Further, their antibacterial activities against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria were investigated through analysis of minimum inhibitory concentration (MIC) method. Among the prepared nanostructures, the ZnO NPs-GABA/CurBF2-AgNPs showed excellent antibacterial activity against both Gram-positive and Gram-negative bacteria. ZnO NPs fabricated here may have potential use in future anti-bacterial compositions and coatings technologies.
Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases
Authors: López-Cano José Javier , Sigen A.  , Andrés-Guerrero Vanessa , Tai Hongyun , Bravo-Osuna Irene , Molina-Martínez Irene Teresa , Wang Wenxin , Herrero-Vanrell Rocío
Published: February 2021

The present study aims to develop a thermo-responsive-injectable hydrogel (HyG) based on PLGA-PEG-PLGA (PLGA = poly-(DL-lactic acid co-glycolic acid); PEG = polyethylene glycol) to deliver neuroprotective agents to the retina over time. Two PLGA-PEG PLGA copolymers with different PEG:LA:GA ratios (1:1.54:23.1 and 1:2.25:22.5) for HyG-1 and HyG-2 development respectively were synthetized and characterized by different techniques (gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), critical micelle concentration (CMC), gelation and rheological behaviour). According to the physicochemical characterization, HyG-1 was selected for further studies and loaded with anti-inflammatory drugs: dexamethasone (0.2%), and ketorolac (0.5%), alone or in combination with the antioxidants idebenone (1 µM) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) (0.002%). In vitro drug release and cytotoxicity studies were performed for the active substances and hydrogels (loaded and drug-free). A cellular model based on oxidative stress was optimized for anti-inflammatory and antioxidant screening of the formulations by using retinal-pigmented epithelial cell line hTERT (RPE-1). The copolymer 1, used to prepare thermo-responsive HyG-1, showed low polydispersity (PDI = 1.22) and a strong gel behaviour at 25% (w/v) in an isotonic buffer solution close to the vitreous temperature (31–34 °C). Sustained release of dexamethasone and ketorolac was achieved between 47 and 62 days, depending on the composition. HyG-1 was well tolerated (84.5 ± 3.2%) in retinal cells, with values near 100% when the anti-inflammatory and antioxidant agents were included. The combination of idebenone and dexamethasone promoted high oxidative protection in the cells exposed to H2O2, with viability values of 86.2 ± 14.7%. Ketorolac and dexamethasone-based formulations ameliorated the production of TNF-α, showing significant results (p ≤ 0.0001). The hydrogels developed in the present study entail a novel biodegradable tool to treat neurodegenerative processes of the retina overtime.