bluuebunny/crossref_metadata_2025 huggingface dataset:
Trabalho e Saúde Emocional em tempos de COVID-19
Authors: Souto Severo Valdete , Pimentel de Barros Isabela
Published: October 2020

Os fatores psicossociais trazem inúmeras consequências para a saúde e segurança do trabalhador, bem como para o mundo do trabalho. Além de difícil reconhecimento como doença ocupacional ou como acidente de trabalho, as doenças psíquicas não se relacionam somente com doenças como estresse e depressão, mas também com inúmeras outras como, a título de exemplo, as doenças cardiovasculares ou musculares, vez que os riscos psicossociais estão estreitamente relacionados ao estresse laboral. Apesar de ser um assunto extremamente relevante para a saúde pública e para a sociedade como um todo, o Direito do Trabalho pouco se ocupa com o seu estudo. Nesse sentido, em um primeiro momento, buscamos esclarecer ao leitor as principais medidas realizadas pelas reformas trabalhistas espanhola (2012) e brasileira (2017) para, após, analisar as consequências concretas das mesmas em termos de desemprego, desalento e afastamento do trabalho por doenças nesses dois países. Em seguida, indicaremos as medidas adotadas por esses países diante da realidade da pandemia da COVID-19 e discutiremos as suas eficiências como medida de estabilização social e cuidado com a saúde e a vida de quem depende do trabalho para sobreviver. Restou demonstrado o expressivo aumento do número de pessoas acometidas de doenças psíquicas em razão do trabalho, o que tende a agravar-se com a crise econômica instaurada, com o desemprego massivo, com as opções legislativas que priorizam o capital em detrimento de quem vende a sua força de trabalho e com a política adotada pelo Brasil em meio a mais de 140 mil mortos.
FUNCTIONS AND ROLES OF THE REGIONAL REPRESENTATIVE COUNCILS (DPD) OF THE REPUBLIC OF INDONESIA IN STRENGTHENING REGIONAL AUTONOMY IN THE BICAMERAL GOVERNMENT SYSTEM
Authors: Putra Muchtar Herman
Published: October 2020

Since the amendment of the 1945 Constitution, the Indonesian parliamentary system has changed from a unicameral system to a bicameral system. The manifestation of this institution has awakened the hopes of local people that regional problems can be fought for at the national level. However, if we pay attention to the functions, powers, and tasks that have been regulated in Article 22 D of the 1945 Constitution and Law Number 22 of 2003 concerning the composition and position of the in the People's Consultative Assembly (MPR), the House of Representatives (DPR), the Regional Representative Council (DPD) and Regional People's Representative Assembly (DPRD), there are many assumptions that whether the functions of the Regional Representative Council can be representing regional interests. The Regional Representative Council (DPD) does not only function as counseling for the regional autonomy council, it does not serve the legislative body as a country that adopts a bicameral system. Amendments to the 1945 constitution are the main way to strengthen the position of this institution as a companion to the DPR.
MAIN REGULARITIES GEOBOTANICAL INDICATION OF FLOODING AND SALINIZATION OF THE VOLGA REGION LANDS
Authors: Trofimov Ilya , Trofimova Lyudmila , Yakovleva Elena , Emelyanov Alexey , Skripnikova Elena Vladimirovna
Published: October 2020

In order to study the spatial distribution of biological and ecological patterns on the territory of the Volga region, geobotanical indication of flooding and salinization of the lands these regions was carried out. Geobotanical indication is used in the study, assessment, mapping and monitoring of territorial complexes and their components and is based on the analysis of the relationships of the geographical envelope as a whole. The article is the result of many years of interdisciplinary research. It is based both on the data obtained by the authors as a result of agro-landscape and ecological zoning and in the course of field expedition research, and on the analysis of long-term series of statistical information and literature sources. Intensive economic activity that requires the use of large amounts water resources, against the background of modern climate changes, leads to waterlogging in large areas. The weakening or termination of economic activity, the decrease in the volume of water resources used under certain conditions leads to the spread of land salinization. Flooding and salinization of arid lands near reservoirs, channels, reclamation facilities, functioning and abandoned irrigation fields, etc. occupy significant areas and are of great importance as environmental problems in the Volga region. The most dynamic and fast-responding biotic component of ecosystems to the occurrence of flooding and salinization is vegetation.
USE OF A DIETARY SUPPLEMENT BASED ON PROPOLIS IN FEED
Authors: Gaponov Nikolay
Published: October 2020

For the first time, the effect of propolis drug, when introduced into the diets of rearing pigs and fattening pigs, on metabolism, energy, hematological parameters was studied. To this end, two scientific and economic experiments were carried out with piglets rearing a large white breed and with pigs of the same breed during the fattening period, as well as two physiological experiments to determine the digestibility of the main nutrients of feed by animals and to determine the balance of energy, nitrogen, calcium, phosphorus, one of which was carried out at the end of the rearing period (at 4 months of age) and the other during the fattening period (at 6 months of age). During the experiments, it was found that the use of propolis water-alcohol emulsion in the diet helps to increase the average daily gain in rearing pigs by 30.13% and in young fattening pigs by 4.46%. The digestibility of crude protein in rearing pigs increases by 8.50%, nitrogen-free extractives by 1.8%, organic matter by 3.27%, fiber by 8.19%. In this case, the efficiency of using exchange energy increases by 5.45% and the use of nitrogen, calcium and phosphorus by 30.70%, 17.10% and 11.86%, respectively. And during the fattening period of young pigs, it contributes to a better use of nitrogen in comparison with the control group by 11.5%, calcium by 4.75% and phosphorus by 3.9%; increases the efficiency of metabolic energy use by 5.49%, improves the digestibility of crude protein by 1.61%, organic matter by 1.42%, crude fat by 5.16%, fiber by 6.3% and nitrogen-free extractives by 0.82%.
Protective Immunity to Dengue Virus Induced by DNA Vaccines Encoding Nonstructural Proteins in a Lethal Challenge Immunocompetent Mouse Model
Authors: Alves Rúbens Prince dos Santos , Andreata-Santos Robert , de Freitas Carla Longo , Pereira Lennon Ramos , Fabris-Maeda Denicar Lina Nascimento , Rodrigues-Jesus Mônica Josiane , Pereira Samuel Santos , Carvalho Alexia Adrianne Venceslau Brito , Sales Natiely Silva , Peron Jean Pierre Schatzmann , Amorim Jaime Henrique , Ferreira Luís Carlos de Souza
Published: October 2020

Dengue virus represents the main arbovirus affecting humans, but there are no effective drugs or available worldwide licensed vaccine formulations capable of conferring full protection against the infection. Experimental studies and results generated after the release of the licensed anti-DENV vaccine demonstrated that induction of high-titer neutralizing antibodies does not represent the sole protection correlate and that, indeed, T cell-based immune responses plays a relevant role in the establishment of an immune protective state. In this context, this study aimed to further demonstrate protective features of immune responses elicited in immunocompetent C57BL/6 mice immunized with three plasmids encoding DENV2 nonstructural proteins (NS1, NS3, and NS5), which were subsequently challenged with a DENV2 strain naturally capable of inducing lethal encephalitis in immunocompetent mouse strains. The animals were immunized intramuscularly with the DNA vaccine mix and complete protection was observed among vaccinated mice. Vaccine induced protection correlated with the cytokine profiles expressed by spleen cells and brain-infiltrating mononuclear cells. The results confirm the pivotal role of cellular immune responses targeting nonstructural DENV proteins and validate the experimental model based on a DENV2 strain capable of infecting and killing immunocompetent mice as a tool for the evaluation of protective immunity induced by anti-DENV vaccines.
Impacts of Multidrug-Resistant Pathogens and Inappropriate Initial Antibiotic Therapy on the Outcomes of Neonates with Ventilator-Associated Pneumonia
Authors: Wang Hsiao-Chin , Liao Chen-Chu , Chu Shih-Ming , Lai Mei-Yin , Huang Hsuan-Rong , Chiang Ming-Chou , Fu Ren-Huei , Hsu Jen-Fu , Tsai Ming-Horng
Published: October 2020

It is unknown whether neonatal ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) pathogens and inappropriate initial antibiotic treatment is associated with poor outcomes after adjusting for confounders. Methods: We prospectively observed all neonates with a definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and March 2020. All clinical features, therapeutic interventions, and outcomes were compared between the MDR–VAP and non-MDR–VAP groups. Multivariate regression analyses were used to investigate independent risk factors for treatment failure. Results: Of 720 neonates who were intubated for more than 2 days, 184 had a total of 245 VAP episodes. The incidence rate of neonatal VAP was 10.1 episodes/per 1000 ventilator days. Ninety-six cases (39.2%) were caused by MDR pathogens. Neonates with MDR–VAP were more likely to receive inadequate initial antibiotic therapy (51.0% versus 4.7%; p < 0.001) and had delayed resolution of clinical symptoms (38.5% versus 25.5%; p = 0.034), although final treatment outcomes were comparable with the non-MDR–VAP group. Inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. The VAP-attributable mortality rate and overall mortality rate of this cohort were 3.7% and 12.0%, respectively. Independent risk factors for treatment failure included presence of concurrent bacteremia (OR 4.83; 95% CI 2.03–11.51; p < 0.001), septic shock (OR 3.06; 95% CI 1.07–8.72; p = 0.037), neonates on high-frequency oscillatory ventilator (OR 4.10; 95% CI 1.70–9.88; p = 0.002), and underlying neurological sequelae (OR 3.35; 95% CI 1.47–7.67; p = 0.004). Conclusions: MDR–VAP accounted for 39.2% of all neonatal VAP in the neonatal intensive care unit (NICU), but neither inappropriate initial antibiotics nor MDR pathogens were associated with treatment failure. Neonatal VAP with concurrent bacteremia, septic shock, and underlying neurological sequelae were independently associated with final worse outcomes.
Estrogen Actions in Triple-Negative Breast Cancer
Authors: Treeck Oliver , Schüler-Toprak Susanne , Ortmann Olaf
Published: October 2020

Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER) α, but the expression of estrogen receptors ERβ and G protein-coupled estrogen receptor 1 (GPER-1) is able to trigger estrogen-responsivity in TNBC. Estrogen signaling in TNBC can also be activated and modulated by the constitutively active estrogen-related receptors (ERRs). In this review article, we discuss the role of ERβ and GPER-1 as mediators of E2 action in TNBC as well as the function of ERRs as activators and modulators of estrogen signaling in this cancer entity. For this purpose, original research articles on estrogen actions in TNBC were considered, which are listed in the PubMed database. Additionally, we performed meta-analyses of publicly accessible integrated gene expression and survival data to elucidate the association of ERβ, GPER-1, and ERR expression levels in TNBC with survival. Finally, options for endocrine therapy strategies for TNBC were discussed.
The Angiopoietin/Tie2 Pathway in Hepatocellular Carcinoma
Authors: Vanderborght Bart , Lefere Sander , Vlierberghe Hans Van , Devisscher Lindsey
Published: October 2020

Due to the usually late diagnosis and lack of effective therapies, hepatocellular carcinoma (HCC), which poses a growing global health problem, is characterized by a poor prognosis. Angiogenesis plays an important role in HCC progression, and vascular endothelial growth factor (VEGF) and angiopoietins (Angs) are key drivers of HCC angiogenesis. VEGF-targeting strategies already represent an important component of today’s systemic treatment landscape of HCC, whereas targeting the Ang/Tie2 signaling pathway may harbor future potential in this context due to reported beneficial anticancer effects when targeting this pathway. In addition, a better understanding of the relation between Angs and HCC angiogenesis and progression may reveal their potential as predictive factors for post-treatment disease progression and prognosis. In this review, we give a comprehensive overview of the complex role of Ang/Tie2 signaling in HCC, pinpointing its potential value as biomarker and target for HCC treatments, aiding HCC diagnosis and therapy.
Wetting and Evaporation of Solvents on Thin Soluble Substrates
Authors: Wolf Christian , Gambaryan-Roisman Tatiana
Published: October 2020

In this work, the wetting and evaporation behaviour of non-polar solvent droplets on thin soluble coatings is investigated experimentally. The wetting process on spin-coated polymer layers by toluene is captured using shadowgraphy. Initial spontaneous dynamic wetting as well as later stages of wetting are recorded and evaluated. Furthermore, structures obtained by wetting and subsequent evaporation of solvents on polymer coatings are studied by confocal microscopy. The solubility of the substrate has been varied by using polymers with different molecular masses. We observe that initial spreading dynamics does not depend on the molar mass in the studied range. However, we find a strong influence of the molar mass on the late stage wetting dynamics and on the surface structure after solvent evaporation.
PDE5 Inhibitors in Type 2 Diabetes Cardiovascular Complications
Authors: Barbagallo Federica , Campolo Federica , Franceschini Edoardo , Crecca Elena , Pofi Riccardo , Isidori Andrea M. , Venneri Mary Anna
Published: October 2020

Pharmacological inhibition of Phosphodiesterase type 5 (PDE5) proved its efficacy treating several pathological conditions, such as erectile dysfunction and pulmonary hypertension. Nowadays, its benefits on cardiovascular diseases are well documented, particularly in the treatment of type 2 diabetes (T2DM)-related cardiovascular complications. In this context, treatment of T2DM with PDE5 inhibitors, such as sildenafil, tadalafil or vardenafil ameliorates endothelial dysfunction both in patients and animal models through an augmented flow mediated dilation rate and an up-regulation of endothelial markers; it also reduces the inflammatory state by down-regulating inflammatory cytokines expression and improves diabetic cardiomyopathy and ischemia-reperfusion injury mainly through the activation of NO-cGMP-PKG pathway. The present review summarizes the state of art on PDE5 inhibition in the treatment of cardiovascular complications in T2DM.
Experimental Investigation of the Effect of Heat Flux on the Fire Behavior of Engineered Wood Samples
Authors: Kasymov Denis , Agafontsev Mikhail , Perminov Vladislav , Martynov Pavel , Reyno Vladimir , Loboda Egor
Published: October 2020

This paper presents the experimental study results on the effect of heat flux emitted by a standard source on the charring and ignition characteristics of wood construction materials (plywood, chipboard, and oriented strand board) using infrared thermography (IRT) in the narrow spectral ranges of infrared wavelength. The time to ignition (TTI), charring rate and depth were obtained for the samples. In addition, the effect of several fire retardants on the charring rate and depth of the samples and TTI was analyzed. All fire retardants contribute to an increase in TTI, which confirms their main function—fire protection. However, the effect of fire retardants differs noticeably depending on the material. A new experimental technique is suggested, with the infrared imaging of the temperature distribution along the end of a sample under the heat flux effect on its frontal surface. The uniqueness of this approach consists in the registration of the entire process of ignition and combustion of the presented materials, which occurs in real time without contact with high spatial and temporal resolution. Using the infrared camera of the research class, it becomes possible to record the entire process from the occurrence of the temperature exposure region to the deep carbonized crater in the body of the material. The results can serve as additional recommendations in the development of fire hazard testing methods for construction materials and fire retardants.
DNA Associated with Circulating Exosomes as a Biomarker for Glioma
Authors: Vaidya Manjusha , Sugaya Kiminobu
Published: October 2020

Cancerous and non-cancerous cells secrete exosomes, a type of nanovesicle known to carry the molecular signature of the parent for intercellular communications. Exosomes secreted by tumor cells carry abnormal DNA, RNA, and protein molecules that reflect the cancerous status. DNA is the master molecule that ultimately affects the function of RNA and proteins. Aberrations in DNA can potentially lead a cell to malignancy. Deviant quantities and the differential sequences of exosomal DNA are useful characteristics as cancer biomarkers. Since these alterations are either associated with specific stages of cancer or caused due to a clinical treatment, exosomal DNA is valuable as a diagnostic, prognostic, predictive, and therapeutic-intervention response biomarker. Notably, the exosomes can cross an intact blood–brain barrier and anatomical compartments by transcytosis. As such, the cancer-specific trademark molecules can be detected in systemic blood circulation and other body fluids, including cerebrospinal fluid, with non-invasive or minimally invasive procedures. This comprehensive review highlights the cancer-specific modulations of DNA associated with circulating exosomes that are beneficial as glioma biomarkers.
Cytokines and Pathogenesis of Central Retinal Vein Occlusion
Authors: Noma Hidetaka , Yasuda Kanako , Shimura Masahiko
Published: October 2020

Central retinal vein occlusion (CRVO) causes macular edema and subsequent vision loss and is common in people with diseases such as arteriosclerosis and hypertension. Various treatments for CRVO-associated macular edema have been trialed, including laser photocoagulation, with unsatisfactory results. However, when the important pathogenic role of vascular endothelial growth factor (VEGF) in macular edema was identified, the treatment of CRVO was revolutionized by anti-VEGF therapy. However, despite the success of intraocular injection of anti-VEGF agents in many patients with CRVO, some patients continue to suffer from refractory or recurring edema. In addition, the expression of inflammatory cytokines increases over time, causing more severe inflammation and a condition that is increasingly resistant to anti-VEGF therapy. This indicates that the pathogenesis of macular edema in CRVO is more complex than originally thought and may involve factors or cytokines associated with inflammation and ischemia other than VEGF. CRVO is also associated with leukocyte abnormalities and a gradual reduction in retinal blood flow velocity, which increase the likelihood of it developing from the nonischemic type into the more severe ischemic type; in turn, this results in excessive VEGF expression and subsequent neovascular glaucoma. Here, we review the role of different factors and cytokines involved in CRVO pathogenesis and propose a mechanism that holds promise for the development of novel therapies.
Development and Improvement of an Effective Method for Air and Surfaces Disinfection with Ozone Gas as a Decontaminating Agent
Authors: Moccia Giuseppina , De Caro Francesco , Pironti Concetta , Boccia Giovanni , Capunzo Mario , Borrelli Anna , Motta Oriana
Published: October 2020

Background and objectives: Ozone has been one of the most investigated and discussed sanitization methods. This paper reports a procedure to sanitize air hospital environments, in particular chirurgical surgery rooms that require high levels of disinfection. The purpose of this work was the development and implementation of a cleansing and sanitizing procedure for critical clinical settings with ozone, to prevent hospital infections by the elimination of all toxic and harmful microorganisms in the air, and ensure safe use for operators and patients. Materials and Methods: The protocol for the study involved a structured selection of a representative environment of healthcare structures such as high, medium, and low-risk settings in air and examples of hospital furniture. Results: The concentration of ozone was measured during sanitization treatment and the estimation of the total microbial count in the air and on different surfaces before and after the sanitization operations was performed. The results demonstrated a significant reduction in the microbial count that always fell below the threshold value. Conclusions: Currently, there are no air treatment strategies available for inactivating airborne organisms during hospital outbreaks, which is most probably due to the lack of approved protocols.
The Importance of Reporting Clinical and Epidemiological Data in Urology: Local Experiences and Insights from the International Literature
Authors: Gajdács Márió
Published: October 2020

Pathologies of the genito-urinary tract are responsible for a considerable disease burden worldwide, leading to significant losses of income, lost working days, increased expenditures for national healthcare systems, and decreased quality of life (QoL) in the affected patients [...]
Copper Ionophores as Novel Antiobesity Therapeutics
Authors: Meggyesy Peter M. , Masaldan Shashank , Clatworthy Sharnel A. S. , Volitakis Irene , Eyckens Daniel J. , Aston-Mourney Kathryn , Cater Michael A.
Published: October 2020

The therapeutic utility of the copper ionophore disulfiram was investigated in a diet-induced obesity mouse model (C57BL/6J background), both through administration in feed (0.05 to 1% (w/w)) and via oral gavage (150 mg/kg) for up to eight weeks. Mice were monitored for body weight, fat deposition (perigonadal fat pads), metabolic changes (e.g., glucose dyshomeostasis) and pathologies (e.g., hepatic steatosis, hyperglycaemia and hypertriglyceridemia) associated with a high-fat diet. Metal-related pharmacological effects across major organs and serums were investigated using inductively coupled plasma mass spectrometry (ICP-MS). Disulfiram treatments (all modes) augmented hepatic copper in mice, markedly moderated body weight and abolished the deleterious systemic changes associated with a high-fat diet. Likewise, another chemically distinct copper ionophore H2(gtsm), administered daily (oral gavage), also augmented hepatic copper and moderated mouse body weight. Postmortem histological examinations of the liver and other major organs, together with serum aminotransferases, supported the reported therapeutic safety of disulfiram. Disulfiram specifically altered systemic copper in mice and altered hepatic copper metabolism, perturbing the incorporation of copper into ceruloplasmin (holo-ceruloplasmin biosynthesis) and subsequently reducing serum copper concentrations. Serum ceruloplasmin represents a biomarker for disulfiram activity. Our results establish copper ionophores as a potential class of antiobesity agents.
Wine or Beer? Comparison, Changes and Improvement of Polyphenolic Compounds during Technological Phases
Authors: Radonjić Sanja , Maraš Vesna , Raičević Jovana , Košmerl Tatjana
Published: October 2020

Wine and beer are nowadays the most popular alcoholic beverages, and the benefits of their moderate consumption have been extensively supported by the scientific community. The main source of wine and beer’s antioxidant behavior are the phenolic substances. Phenolic compounds in wine and beer also influence final product quality, in terms of color, flavor, fragrance, stability, and clarity. Change in the quantity and quality of phenolic compounds in wine and beer depends on many parameters, beginning with the used raw material, its place of origin, environmental growing conditions, and on all the applied technological processes and the storage of the final product. This review represents current knowledge of phenolic compounds, comparing qualitative and quantitative profiles in wine and beer, changes of these compounds through all phases of wine and beer production are discussed, as well as the possibilities for increasing their content. Analytical methods and their importance for phenolic compound determination have also been pointed out. The observed data showed wine as the beverage with a more potent biological activity, due to a higher content of phenolic compounds. However, both of them contain, partly similar and different, phenolic compounds, and recommendations have to consider the drinking pattern, consumed quantity, and individual preferences. Furthermore, novel technologies have been developing rapidly in order to improve the polyphenolic content and antioxidant activity of these two beverages, particularly in the brewing industry.
Unraveling the Antioxidant, Binding and Health-Protecting Properties of Phenolic Compounds of Beers with Main Human Serum Proteins: In Vitro and In Silico Approaches
Authors: Shafreen Raja Mohamed Beema , Lakshmi Selvaraj Alagu , Pandian Shunmugiah Karutha , Park Yong Seo , Kim Young Mo , Paśko Paweł , Deutsch Joseph , Katrich Elena , Gorinstein Shela
Published: October 2020

Our recently published in vivo studies and growing evidence suggest that moderate consumption of beer possesses several health benefits, including antioxidant and cardiovascular effects. Although beer contains phenolic acids and flavonoids as the major composition, and upon consumption, the levels of major components increase in the blood, there is no report on how these beer components interact with main human serum proteins. Thus, to address the interaction potential between beer components and human serum proteins, the present study primarily aims to investigate the components of beer from different industrial sources as well as their mode of interaction through in silico analysis. The contents of the bioactive compounds, antioxidant capacities and their influence on binding properties of the main serum proteins in human metabolism (human serum albumin (HSA), plasma circulation fibrinogen (PCF), C-reactive protein (CRP) and glutathione peroxidase 3 (GPX3)) were studied. In vitro and in silico studies indicated that phenolic substances presented in beer interact with the key regions of the proteins to enhance their antioxidant and health properties. We hypothesize that moderate consumption of beer could be beneficial for patients suffering from coronary artery disease (CAD) and other health advantages by regulating the serum proteins.
Identification of Anti-Inflammatory Compounds from Hawaiian Noni (Morinda citrifolia L.) Fruit Juice
Authors: Lee Dahae , Yu Jae Sik , Huang Peng , Qader Mallique , Manavalan Arulmani , Wu Xiaohua , Kim Jin-Chul , Pang Changhyun , Cao Shugeng , Kang Ki Sung , Kim Ki Hyun
Published: October 2020

Noni (Morinda citrifolia L.) fruit juice has been used in Polynesia as a traditional folk medicine and is very popular worldwide as a functional food supplement. In this study, compounds present in Hawaiian Noni fruit juice, with anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were identified. Five compounds were isolated using a bioassay-driven technique and phytochemical analysis of noni fruit juice: asperulosidic acid (1), rutin (2), nonioside A (3), (2E,4E,7Z)-deca-2,4,7-trienoate-2-O-β-d-glucopyranosyl-β-d-glucopyranoside (4), and tricetin (5). The structures of these five compounds were determined via NMR spectroscopy and LC/MS. In an anti-inflammatory assay, compounds 1–5 inhibited the production of nitric oxide (NO), which is a proinflammatory mediator, in LPS-stimulated macrophages. Moreover, the mechanisms underlying the anti-inflammatory effects of compounds 1–5 were investigated. Parallel to the inhibition of NO production, treatment with compounds 1–5 downregulated the expression of IKKα/β, I-κBα, and NF-κB p65 in LPS-stimulated macrophages. Furthermore, treatment with compounds 1–5 downregulated the expression of nitric oxide synthase and cyclooxygenase-2. Thus, these data demonstrated that compounds 1–5 present in noni fruit juice, exhibited potential anti-inflammatory activity; these active compounds may contribute preventively and therapeutically against inflammatory diseases.
Recent Developments in Transition-Metal Catalyzed Direct C–H Alkenylation, Alkylation, and Alkynylation of Azoles
Authors: Chen Su , Ranjan Prabhat , Voskressensky Leonid G. , Van der Eycken Erik V. , Sharma Upendra K.
Published: October 2020

The transition metal-catalyzed C–H bond functionalization of azoles has emerged as one of the most important strategies to decorate these biologically important scaffolds. Despite significant progress in the C–H functionalization of various heteroarenes, the regioselective alkylation and alkenylation of azoles are still arduous transformations in many cases. This review covers recent advances in the direct C–H alkenylation, alkylation and alkynylation of azoles utilizing transition metal-catalysis. Moreover, the limitations of different strategies, chemoselectivity and regioselectivity issues will be discussed in this review.
Clusters of Hydroxyl-Functionalized Cations Stabilized by Cooperative Hydrogen Bonds: The Role of Polarizability and Alkyl Chain Length
Authors: Philipp Jule , Ludwig Ralf
Published: October 2020

We explore quantum chemical calculations for studying clusters of hydroxyl-functionalized cations kinetically stabilized by hydrogen bonding despite strongly repulsive electrostatic forces. In a comprehensive study, we calculate clusters of ammonium, piperidinium, pyrrolidinium, imidazolium, pyridinium, and imidazolium cations, which are prominent constituents of ionic liquids. All cations are decorated with hydroxy-alkyl chains allowing H-bond formation between ions of like charge. The cluster topologies comprise linear and cyclic clusters up to the size of hexamers. The ring structures exhibit cooperative hydrogen bonds opposing the repulsive Coulomb forces and leading to kinetic stability of the clusters. We discuss the importance of hydrogen bonding and dispersion forces for the stability of the differently sized clusters. We find the largest clusters when hydrogen bonding is maximized in cyclic topologies and dispersion interaction is properly taken into account. The kinetic stability of the clusters with short-chained cations is studied for the different types of cations ranging from hard to polarizable or exhibiting additional functional groups such as the acidic C(2)-H position in the imidazolium-based cation. Increasing the alkyl chain length, the cation effect diminishes and the kinetic stability is exclusively governed by the alkyl chain tether increasing the distance between the positively charged rings of the cations. With adding the counterion tetrafluoroborate (BF4−) to the cationic clusters, the binding energies immediately switch from strongly positive to strongly negative. In the neutral clusters, the OH functional groups of the cations can interact either with other cations or with the anions. The hexamer cluster with the cyclic H-bond motive and “released” anions is almost as stable as the hexamer built by H-bonded ion pairs exclusively, which is in accord with recent IR spectra of similar ionic liquids detecting both types of hydrogen bonding. For the cationic and neutral clusters, we discuss geometric and spectroscopic properties as sensitive probes of opposite- and like-charge interaction. Finally, we show that NMR proton chemical shifts and deuteron quadrupole coupling constants can be related to each other, allowing to predict properties which are not easily accessible by experiment.
Physicochemical Characteristics, Fatty Acid Profile, Alpha-Tocopherol Content, and Lipid Oxidation of Meat from Ewes Fed Different Levels of Distilled Myrtle Residues
Authors: Tibaoui Souha , Smeti Samir , Essid Ines , Bertolín Juan Ramón , Joy Margalida , Atti Naziha
Published: October 2020

The aim of this work was to study the sheep meat physicochemical traits as affected by distilled myrtle residues (MR) supplementation. For this, 27 culled ewes were divided into three groups receiving a ration composed by concentrate and hay for the Control group, concentrate and MR as a total substitute to hay for the Myrt-H group, or hay, less concentrate, and MR as a partial substitute to concentrate for the Myrt-C group. The meat chemical composition, pH, and color parameters were not affected by the MR intake. However, this animal’s dietary treatment resulted in higher meat polyphenol and α-tocopherol content for both MR groups (9.38 and 8.05 vs. 3.04 μg g−1 DM for Myrt-H, Myrt-C, and Control, respectively). In addition, since day 3 of meat storage, the lipid oxidation was improved by MR intake being lower for both MR groups than the Control (0.51 vs. 1.11 mg MDA/kg of meat). The total polyunsaturated fatty acid (PUFA) and saturated fatty acid (SFA) were similar among groups. However, the meat of Myrt-H had the highest C18:2n-6 and total PUFAn-6. In conclusion, the MR intake could be useful given it increases the meat content of vitamin E and improves its oxidative status without negative effects on the FA profile.
Naturally Occurring Calanolides: Occurrence, Biosynthesis, and Pharmacological Properties Including Therapeutic Potential
Authors: Nahar Lutfun , Talukdar Anupam Das , Nath Deepa , Nath Sushmita , Mehan Aman , Ismail Fyaz M. D. , Sarker Satyajit D.
Published: October 2020

Calanolides are tetracyclic 4-substituted dipyranocoumarins. Calanolide A, isolated from the leaves and twigs of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens, is the first member of this group of compounds with anti-HIV-1 activity mediated by reverse transcriptase inhibition. Calanolides are classified pharmacologically as non-nucleoside reverse transcriptase inhibitors (NNRTI). There are at least 15 naturally occurring calanolides distributed mainly within the genus Calophyllum, but some of them are also present in the genus Clausena. Besides significant anti-HIV properties, which have been exploited towards potential development of new NNRTIs for anti-HIV therapy, calanolides have also been found to possess anticancer, antimicrobial and antiparasitic potential. This review article provides a comprehensive update on all aspects of naturally occurring calanolides, including their chemistry, natural occurrence, biosynthesis, pharmacological and toxicological aspects including mechanism of action and structure activity relationships, pharmacokinetics, therapeutic potentials and available patents.
New Lead Discovery of Herbicide Safener for Metolachlor Based on a Scaffold-Hopping Strategy
Authors: Deng Xile , Zheng Wenna , Zhan Qingcai , Deng Yanan , Zhou Yong , Bai Lianyang
Published: October 2020

The use of herbicide safeners can significantly alleviate herbicide injury to protect crop plants and expand the application scope of the existing herbicides in the field. Sanshools, which are well known as spices, are N-alkyl substituted compounds extracted from the Zanthoxylum species and have several essential physiological and pharmacological functions. Sanshools display excellent safener activity for the herbicide metolachlor in rice seedlings. However, the high cost of sanshools extraction and difficulties in the synthesis of their complicated chemical structures limit their utilization in agricultural fields. Thus, the present study designed and synthesized various N-alkyl amide derivatives via the scaffold-hopping strategy to solve the challenge of complicated structures and find novel potential safeners for the herbicide metolachlor. In total, 33 N-alkyl amide derivatives (2a–k, 3a–k, and 4a–k) were synthesized using amines and saturated and unsaturated fatty acids as starting materials through acylation and condensation. The identity of all the target compounds was well confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectrometry (HRMS). The primary evaluation of safener activities for the compounds by the agar method indicated that most of the target compounds could protect rice seedlings from injury caused by metolachlor. Notably, compounds 2k and 4k displayed excellent herbicide safener activities on plant height and demonstrated relatively similar activities to the commercialized compound dichlormid. Moreover, we showed that compounds 2k and 4k had higher glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and polyphenol oxidase (PPO) activities in rice seedlings, compared to the metolachlor treatment. In particular, 2k and 4k are safer for aquatic organisms than dichlormid. Results from the current work exhibit that compounds 2k and 4k have excellent crop safener activities toward rice and can, thus, be promising candidates for further structural optimization in rice protection.
Authentication and Provenance of Walnut Combining Fourier Transform Mid-Infrared Spectroscopy with Machine Learning Algorithms
Authors: Zhu Hongyan , Xu Jun-Li
Published: October 2020

Different varieties and geographical origins of walnut usually lead to different nutritional values, contributing to a big difference in the final price. The conventional analytical techniques have some unavoidable limitations, e.g., chemical analysis is usually time-expensive and labor-intensive. Therefore, this work aims to apply Fourier transform mid-infrared spectroscopy coupled with machine learning algorithms for the rapid and accurate classification of walnut species that originated from ten varieties produced from four provinces. Three types of models were developed by using five machine learning classifiers to (1) differentiate four geographical origins; (2) identify varieties produced from the same origin; and (3) classify all 10 varieties from four origins. Prior to modeling, the wavelet transform algorithm was used to smooth and denoise the spectrum. The results showed that the identification of varieties under the same origin performed the best (i.e., accuracy = 100% for some origins), followed by the classification of four different origins (i.e., accuracy = 96.97%), while the discrimination of all 10 varieties is the least desirable (i.e., accuracy = 87.88%). Our results implicated that using the full spectral range of 700–4350 cm−1 is inferior to using the subsets of the optimal spectral variables for some classifiers. Additionally, it is demonstrated that back propagation neural network (BPNN) delivered the best model performance, while random forests (RF) produced the worst outcome. Hence, this work showed that the authentication and provenance of walnut can be realized effectively based on Fourier transform mid-infrared spectroscopy combined with machine learning algorithms.
Characterization of Modified Natural Minerals and Rocks for Possible Adsorption and Catalytic Use
Authors: Strejcová Kateřina , Tišler Zdeněk , Svobodová Eliška , Velvarská Romana
Published: October 2020

This study focused on natural materials such as clinoptilolite (CLI), metakaolin (MK), marlstone (MRL) and phonolite (PH). Clinoptilolite is one of the most known and common natural minerals (zeolites) with a unique porous structure, metakaolin is calcined kaolin clay, marlstone is a sedimentary rock and phonolite is an igneous rock composed of alkali feldspar and other minerals. These natural materials are mainly used in the building industry (additions for concrete mixtures, production of paving, gravels) or for water purification, but the modification of their chemical, textural and mechanical properties makes these materials potentially usable in other industries, especially in the chemical industry. The modification of these natural materials and rocks was carried out by leaching using 0.1 M HCl (D1 samples) and then using 3 M HCl (D2 samples). This treatment could be an effective tool to modify the structure and composition of these materials. Properties of modified materials were determined by N2 physisorption, Hg porosimetry, temperature programmed desorption of ammonia (NH3-TPD), X-ray fluorescence (XRF), X-ray powder diffraction (XRD), diffuse reflectance infrared Fourier transform (DRIFT) and CO2 adsorption using thermogravimetric analysis (TGA). The results of N2 physisorption measurements showed that that the largest increase of specific surface area was for clinoptilolite leached using 3M HCl. There was also a significant increase of the micropore volume in the D2 samples. The only exception was marlstone, where the volume of micropores was zero even in the leached sample. Clinoptilolite had the highest acidity and sorption capacity of CO2. TGA showed that the amount of CO2 adsorbed was not significantly related to the increase in specific surface area and the opening of micropores. Hg porosimetry showed that acid leaching using 0.1 M HCl and 3 M HCl resulted in a significant increase in the macropore volume in phonolite, and during leaching using 3M HCl there was an increase of the mesopore volume. From the better properties, cost-efficient and environmental points of view, the use of these materials could be an interesting solution for catalytic and sorption applications.
The Influence of Hemp Extract in Combination with Ginger on the Metabolic Activity of Metastatic Cells and Microorganisms
Authors: Žitek Taja , Leitgeb Maja , Golle Andrej , Dariš Barbara , Knez Željko , Knez Hrnčič Maša
Published: October 2020

This study presents an investigation of the anticancer and antimicrobial ability of a combination of ginger and cannabis extracts in different ratios (1:1, 7:3 and 3:7). Extracts were obtained using various methods (Soxhlet extractions, cold macerations, ultrasonic extractions and supercritical fluid extractions). The antioxidant activity and the presence of total phenols were measured in the extracts, and the effect of the application extracts in various concentrations (c = 50, 20, 10, 5, 1, 0.1, 0.01 mg/mL) on cells was investigated. Higher values of antioxidants were measured at the ratio where ginger was predominant, which is reflected in a higher concentration of total phenols. Depending on the polyphenol content, the extracts were most effective when prepared supercritically and ultrasonically. However, with respect to cell response, the ratio was shown to have no effect on inhibiting cancer cell division. The minimum concentration required to inhibit cancer cell growth was found to be 1 mg/mL. High-performance liquid chromatography (HPLC) analysis also confirmed the effectiveness of ultrasonic and supercritical fluid extraction, as their extracts reached higher cannabinoid contents. In both extractions, the cannabidiol (CBD) content was above 30% and the cannabidiolic acid (CBDA) content was above 45%. In the case of ultrasonic extraction, a higher quantity of cannabigerol (CBG) (5.75 ± 0.18) was detected, and in the case of supercritical fluid extraction, higher cannabichromene (CBC) (5.48 ± 0.13) content was detected, when compared to other extraction methods. The antimicrobial potential of extracts prepared with ultrasonic and supercritical extractions on three microorganisms (Staphylococcus aureus, Escherichia coli and Candida albicans) was checked. Ginger and cannabis extract show better growth inhibition of microorganisms in cannabis-dominated ratios for gram-positive bacterium S. aureus, MIC = 9.38 mg/mL, for gram-negative bacterium E. coli, MIC > 37.5 mg/mL and for the C. albicans fungus MIC = 4.69 mg/mL. This suggests guidelines for further work: a 1: 1 ratio of ginger and hemp will be chosen in a combination with supercritical and ultrasonic extraction.
Novel Function of α-Cubebenoate Derived from Schisandra chinensis as Lipogenesis Inhibitor, Lipolysis Stimulator and Inflammasome Suppressor
Authors: Bae Su Ji , Kim Ji Eun , Choi Yun Ju , Lee Su Jin , Gong Jeong Eun , Choi Young-Whan , Hwang Dae Youn
Published: October 2020

The efficacy of α-cubebenoate isolated from Schisandra chinensis has been previously studied in three disease areas, namely inflammation, sepsis, and allergy, and its role in other diseases is still being explored. To identify the novel function of α-cubebenoate on lipid metabolism and related inflammatory response, alterations in fat accumulation, lipogenesis, lipolysis, and inflammasome activation were measured in 3T3-L1 preadipocytes and primary adipocytes treated with α-cubebenoate. Lipid accumulation significantly decreased in MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-stimulated 3T3-L1 adipocytes treated with α-cubebenoate without any significant cytotoxicity. The mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT-enhancer binding protein (C/EBP) α for adipogenesis, as well as adipocyte fatty acid binding protein 2 (aP2) and fatty acid synthetase (FAS) for lipogenesis, were reduced after α-cubebenoate treatment, while cell cycle arrest at G2/M stage was restored in the same group. α-cubebenoate treatment induced glycerol release in primary adipocytes and enhanced expression of lipolytic proteins (HSL, perilipin, and ATGL) expression in MDI-stimulated 3T3-L1 adipocytes. Inflammasome activation and downstream cytokines expression were suppressed with α-cubebenoate treatment, but the expression of insulin receptor signaling factors was remarkably increased by α-cubebenoate treatment in MDI-stimulated 3T3-L1 adipocytes. These results indicate that α-cubebenoate may play a novel role as lipogenesis inhibitor, lipolysis stimulator, and inflammasome suppressor in MDI-stimulated 3T3-L1 adipocytes. Our results provide the possibility that α-cubebenoate can be considered as one of the candidates for obesity management.
Synthesis, Molecular Docking Screening and Anti-Proliferative Potency Evaluation of Some New Imidazo[2,1-b]Thiazole Linked Thiadiazole Conjugates
Authors: Rashdan Huda R. M. , Abdelmonsef Aboubakr H. , Shehadi Ihsan A. , Gomha Sobhi M. , Soliman Abdel Mohsen M. , Mahmoud Huda K.
Published: October 2020

Background: Imidazo[2,1-b]thiazole scaffolds were reported to possess various pharmaceutical activities. Results: The novel compound named methyl-2-(1-(3-methyl-6-(p-tolyl)imidazo[2,1-b]thiazol-2-yl)ethylidene)hydrazine-1-carbodithioate 3 acted as a predecessor molecule for the synthesis of new thiadiazole derivatives incorporating imidazo[2,1-b]thiazole moiety. The reaction of 3 with the appropriate hydrazonoyl halide derivatives 4a–j and 7–9 had produced the respective 1,3,4-thiadiazole derivatives 6a–j and 10–12. The chemical composition of all the newly synthesized derivatives were confirmed by their microanalytical and spectral data (FT-IR, mass spectrometry, 1H-NMR and 13C-NMR). All the produced novel compounds were screened for their anti-proliferative efficacy on hepatic cancer cell lines (HepG2). In addition, a computational molecular docking study was carried out to determine the ability of the synthesized thiadiazole molecules to interact with active site of the target Glypican-3 protein (GPC-3). Moreover, the physiochemical properties of the synthesized compounds were derived to determine the viability of the compounds as drug candidates for hepatic cancer. Conclusion: All the tested compounds had exhibited good anti-proliferative efficacy against hepatic cancer cell lines. In addition, the molecular docking results showed strong binding interactions of the synthesized compounds with the target GPC-3 protein with lower energy scores. Thus, such novel compounds may act as promising candidates as drugs against hepatocellular carcinoma.