bluuebunny/crossref_metadata_2025 huggingface dataset:
A Framework of Global Credit-Scoring Modeling Using Outlier Detection and Machine Learning in a P2P Lending Platform
Authors: Shih Dong-Her , Wu Ting-Wei , Shih Po-Yuan , Lu Nai-An , Shih Ming-Hung
Published: June 2022

A great challenge for credit-scoring models in online peer-to-peer (P2P) lending platforms is that credit-scoring models simply discard rejected applicants. This selective discard can lead to an inability to increase the number of potentially qualified applicants, ultimately affecting the revenue of the lending platform. One way to deal with this is to employ reject inference, a technique that infers the state of a rejected sample and incorporates the results into a credit-scoring model. The most popular approach to reject inference is to use a credit-scoring model built only on accepted samples to directly predict the status of rejected samples. However, the distribution of accepted samples in online P2P lending is different from the distribution of rejected samples, and the credit-scoring model on the original accepted sample may no longer apply. In addition, the acceptance sample may also include applicants who cannot repay the loan. If these applicants can be filtered out, the losses to the lending platform can also be reduced. Therefore, we propose a global credit-scoring model framework that combines multiple feature selection methods and classifiers to better evaluate the model after adding rejected samples. In addition, this study uses outlier detection methods to explore the internal relationships of all samples, which can delete outlier applicants in accepted samples or increase outlier applicants in rejected samples. Finally, this study uses four data samples and reject inference to construct four different credit-scoring models. The experimental results show that the credit-scoring model combining Pearson and random forest proposed in this study has significantly better accuracy and AUC than other scholars. Compared with previous studies, using outlier detection to remove outliers in loan acceptance samples and identify potentially creditworthy loan applicants from loan rejection samples is a good strategy. Furthermore, this study not only improves the accuracy of the credit-scoring model but also increases the number of lenders, which in turn increases the profitability of the lending platform.
β-Carotene from the Alga Dunaliella bardawil Decreases Gene Expression of Adipose Tissue Macrophage Recruitment Markers and Plasma Lipid Concentrations in Mice Fed a High-Fat Diet
Authors: Melnikov Nir , Kamari Yehuda , Kandel-Kfir Michal , Barshack Iris , Ben-Amotz Ami , Harats Dror , Shaish Aviv , Harari Ayelet
Published: June 2022

Vitamin A and provitamin A carotenoids are involved in the regulation of adipose tissue metabolism and inflammation. We examined the effect of dietary supplementation using all-trans and 9-cis β-carotene-rich Dunaliella bardawil alga as the sole source of vitamin A on obesity-associated comorbidities and adipose tissue dysfunction in a diet-induced obesity mouse model. Three-week-old male mice (C57BL/6) were randomly allocated into two groups and fed a high-fat, vitamin A-deficient diet supplemented with either vitamin A (HFD) or β-carotene (BC) (HFD-BC). Vitamin A levels in the liver, WATs, and BAT of the HFD-BC group were 1.5–2.4-fold higher than of the HFD group. BC concentrations were 5–6-fold greater in BAT compared to WAT in the HFD-BC group. The eWAT mRNA levels of the Mcp-1 and Cd68 were 1.6- and 2.1-fold lower, respectively, and the plasma cholesterol and triglyceride concentrations were 30% and 28% lower in the HFD-BC group compared with the HFD group. Dietary BC can be the exclusive vitamin A source in mice fed a high-fat diet, as shown by the vitamin A concentration in the plasma and tissues. Feeding BC rather than vitamin A reduces adipose tissue macrophage recruitment markers and plasma lipid concentrations.
Nodular Cast Iron GGG40, 60, 70 Mechanical Characterization from Bars and Blocks Obtained from Brazilian Foundry
Authors: de Oliveira Fernandes Daniel , Anflor Carla Tatiana Mota , Goulart Jhon Nero Vaz , Baranoğlu Besim
Published: June 2022

Nodular cast iron has been commonly applied in industry and many engineering applications due to its low production cost and the similarity of its mechanical properties to carbon steel. The mechanical properties of nodular cast iron are very dependent on its microstructure and also on the characteristics of the graphite nodules. In this sense, the main objective of this paper was to evaluate and characterize the nodular cast iron grades GGG40, GGG60 and GGG70 in the absence of heat treatment. In addition, specimens were obtained from casted bars and blocks without the Y-block casting process. The microstructure was analyzed by optical microscopy with the support of computational image analysis for determination of the attributes of the graphite nodules and the quantification of each phase present in the microstructure of the nodular cast iron. The results showed that the microstructure has a strong effect on the material’s strength, especially the density of graphite nodules in the material. This difference reinforces the idea that cast iron can undergo mechanical changes due to changes in the casting process, confirming the importance of checking the characteristics of the cast batch before engineering applications of the material.
Why Color Matters—Proposing a Quantitative Stability Criterion for Laser Beam Processing of Metals Based on Their Fundamental Optical Properties
Authors: Kohl Stefanie , Kaufmann Florian , Schmidt Michael
Published: June 2022

With its excellent automation capability and localized energy input enabling precise, reproducible welds, laser beam welding represents a preferred industrial joining technology. Electro-mobility drastically increases the need for defect-free and automatable copper joining technologies. However, copper welds that are produced with state-of-the-art infrared lasers often suffer from spattering and porosity. Recent publications show distinct improvements using novel beam sources at visible wavelengths, attributing them to increased absorptivity. Nevertheless, this cannot fully explain the steadier process behavior. This wavelength-dependent process stability has not yet been investigated sufficiently. Therefore, we have developed a predictive material-dependent criterion indicating process stability based on the example of copper heat-conduction spot welding. For this purpose, we combined energy balances with thermo-physical material properties, taking into account the wavelength and temperature dependence of the optical properties. This paper presents the key mechanism that we identified as decisive for process stability. The criterion revealed that X-points (unique, material-specific wavelengths) represent critical stability indicators. Our calculations agree very well with experimental results on copper, steel and aluminum using two different wavelengths and demonstrate the decisive, material-dependent wavelength impact on process stability. This knowledge will help guide manufacturers and users to choose and develop beam sources that are tailored to the material being processed.
Strength Prediction of Spherical Electronic Cabins with Pitting Corrosion
Authors: Wang Hao , Zhu Yongmei , He Xialei , Guan Wei , Zhan Ming , Zhang Jian
Published: June 2022

In this paper, strength prediction of spherical electronic cabins with pitting corrosion under external pressure was investigated. The finite element model of a spherical electronic cabin with random pitting was established using self-written code. The effects of the pitting distribution shape, pitting morphology and size on the ultimate buckling load were numerically studied. In addition, the analytical formula for predicting the ultimate load of spherical cabin with random pitting corrosion was proposed and verified by experiments. This study can be used by engineering designers for relevant design and evaluation basis and provides a reference for the development of a new design code for the buckling stability of spherical cabins with pitting corrosion.
Cutinase ACut2 from Blastobotrysraffinosifermentans for the Selective Desymmetrization of the Symmetric Diester Diethyl Adipate to the Monoester Monoethyl Adipate
Authors: Rauter Marion , Nietz Daniela , Kunze Gotthard
Published: June 2022

Monoethyl adipate (MEA) is a highly valuable monoester for activating resistance mechanisms and improving protective effects in pathogen-attacked plants. The cutinase ACut2 from the non-conventional yeast Blastobotrys (Arxula) raffinosifermentans (adeninivorans) was used for its synthesis by the desymmetrization of dicarboxylic acid diester diethyl adipate (DEA). Up to 78% MEA with 19% diacid adipic acid (AA) as by-product could be synthesized by the unpurified ACut2 culture supernatant from the B. raffinosifermentans overexpression strain. By adjusting pH and enzyme concentration, the selectivity of the free ACut2 culture supernatant was increased, yielding 95% MEA with 5% AA. Selectivity of the carrier immobilized ACut2 culture supernatant was also improved by pH adjustment during immobilization, as well as carrier enzyme loading, ultimately yielding 93% MEA with an even lower AA concentration of 3–4%. Thus, optimizations enabled the selective hydrolysis of DEA into MEA with only a minor AA impurity. In the up-scaling, a maximum of 98% chemical and 87.8% isolated MEA yield were obtained by the adsorbed enzyme preparation with a space time yield of 2.6 g L−1 h−1. The high monoester yields establish the ACut2-catalyzed biosynthesis as an alternative to existing methods.
Sodium N-Lauroylsarcosinate (SNLS) as a Selective Collector for Calcareous Phosphate Beneficiation
Authors: Abdel-Halim Mohamed , Abdel Khalek Mohamed , Zheng Renji , Gao Zhiyong
Published: June 2022

Sodium N-lauroylsarcosinate (SNLS) was employed as a selective flotation collector for dolomite–apatite separation. The influence of pH, condition time, and collector dose on the flotation performance of both apatite and dolomite minerals was investigated using single mineral and binary mixed mineral flotation experiments. The performance of SNLS was compared to sodium oleate (NaOL), as a standard collector. In this study, the adsorption mechanism of SNLS on both minerals was studied using zeta-potential and FT-IR measurements. The results showed that SNLS prefers to adsorb on the dolomite mineral. The maximum difference in floatability was 83% for single dolomite and apatite minerals at pH 10 in the presence of 0.05 mmol/L SNLS. Binary mixtures of dolomite and apatite minerals of different ratios were applied, to evaluate their separation efficiency. The SNLS could separate dolomite from its mixtures with apatite minerals. Using 0.2 mmol/L of SNLS at pH 10, a concentrate of 30.9% P2O5 and 0.79% MgO was obtained from a natural phosphate ore having 25.8% P2O5 and 5.16% MgO.
Pyrite Characteristics and Its Environmental Significance in Marine Shale: A Case Study from the Upper Ordovician Wufeng–Lower Silurian Longmaxi Formation in the Southeast Sichuan Basin, SW China
Authors: Chen Lei , Chen Xin , Tan Xiucheng , Hu Xuetao , Wang Gaoxiang
Published: June 2022

Pyrite, as a characteristic mineral in organic-rich marine shale, is a significant index for the interpretation of paleoredox conditions. In this study, based on drilling cores and focused ion beam-scanning electron microscopy (FIB-SEM), the occurrence, diameter and particle size distribution of pyrites from 32 samples obtained from the Wufeng–Longmaxi Formation in the southeast Sichuan Basin were analyzed. The results show that pyrite displays various occurrences at the macro-scale and micro-scale. At the macro-scale (mm–cm), pyrite laminations, nodular pyrites and lenticular pyrites can be found from drilling cores. At the micro-scale (nm–µm), the common occurrences of pyrite are pyrite framboids, euhedral pyrites and infilled pyrite framboids. According to the formation mechanism of pyrites, pyrites can be divided into syngenetic pyrites and diagenetic pyrites. The infilled pyrite framboids are categorized as diagenetic pyrites. The mean pyrite framboid diameters (Mean, D) range from 2.94 µm to 5.33 µm (average of 4.26 µm), with most samples showing pyrite framboid diameters from 3.5 μm to 4.8 μm. Most of the diameters of the framboid microcrystals (Mean, d) are less than 0.4 µm. Therefore, according to the (Mean, D) and the (Mean, d), the pyrite framboids can be divided into three sizes: syngenetic framboids (SF, D < 4.8 µm, d ≤ 0.4 µm), early diagenetic framboids (EDF, D > 4.8 µm, d > 0.4 µm) and late diagenetic framboids (LDF, D < 4.8 µm, d > 0.4 µm). Additionally, box-and-whisker charts of the diameter, standard deviation/skewness value of the mean diameter of pyrite framboids (Mean, D) and the ratio of trace elements indicate that the sedimentary water body was a euxinic–dysoxic environment. Euxinic conditions dominated the Wufeng Formation to the lower part of the Long11-3 section, which is beneficial for the preservation of organic matter. However, the middle-upper part of the Long13-Long12 sub-member is a dysoxic sedimentary environment.
Interpretation of Strengthening Mechanism of Densified Wood from Supramolecular Structures
Authors: Li Kunpeng , Zhao Lihong , Ren Junli , He Beihai
Published: June 2022

In this study, densified wood was prepared by hot pressing after partial lignin and hemicellulose were removed through alkaline solution cooking. The tensile strength and elastic modulus of densified wood were improved up to 398.5 MPa and 22.5 GPa as compared with the original wood, and the characterization of its supramolecular structures showed that the crystal plane spacing of the densified wood decreased, the crystallite size increased, and the maximum crystallinity (CI) of cellulose increased by 15.05%; outstandingly, the content of O(6)H⋯O(3′) intermolecular H-bonds increased by approximately one-fold at most. It was found that the intermolecular H-bond content was significantly positively correlated with the tensile strength and elastic modulus, and accordingly, their Pearson correlation coefficients were 0.952 (p < 0.01) and 0.822 (p < 0.05), respectively. This work provides a supramolecular explanation for the enhancement of tensile strength of densified wood.
Inclusion Complex between Local Anesthetic/2-hydroxypropyl-β-cyclodextrin in Stealth Liposome
Authors: Souza Gredson Keiff , Gallo André , Novicki Luiza Hauser , Neto Heitor Rodrigues , de Paula Eneida , Marsaioli Anita Jocelyne , Cabeça Luis Fernando
Published: June 2022

The drugs delivery system in the treatment of diseases has advantages such as reduced toxicity, increased availability of the drug, etc. Therefore, studies of the supramolecular interactions between local anesthetics (LAs) butamben (BTB) or ropivacaine (RVC) complexed with 2-hydroxypropyl-β-cyclodextrin (HP-βCD) and carried in Stealth liposomal (SL) are performed. 1H-NMR nuclear magnetic resonance (DOSY and STD) were used as the main tools. The displacements observed in the 1H-NMR presented the complexion between LAs and HP-βCD. The diffusion coefficients of free BTB and RVC were 7.70 × 10−10 m2 s−1 and 4.07 × 10−10 m2 s−1, and in the complex with HP-βCD were 1.90 × 10−10 m2 s−1 and 3.64 × 10−10 m2 s−1, respectively, which indicate a strong interaction between the BTB molecule and HP-βCD (98.3% molar fraction and Ka = 72.279 L/mol). With STD-NMR, the encapsulation of the BTB/HP-βCD and RVC/HP-βCD in SL vesicles was proven. Beyond the saturation transfer to the LAs, there is the magnetization transfer to the hydrogens of HP-βCD. BTB and RVC have already been studied in normal liposome systems; however, little is known of their behavior in SL.
Effects of Frankincense Compounds on Infection, Inflammation, and Oral Health
Authors: Almeida-da-Silva Cássio Luiz Coutinho , Sivakumar Nallusamy , Asadi Homer , Chang-Chien Anna , Qoronfleh M. Walid , Ojcius David M. , Essa Musthafa Mohamed
Published: June 2022

Boswellia trees, found throughout the Middle East and parts of Africa and Asia, are the source of frankincense oil. Since antiquity, frankincense has been traded as a precious commodity, but it has also been used for the treatment of chronic disease, inflammation, oral health, and microbial infection. More recently, the bioactive components of Boswellia trees have been identified and characterized for their effects on cancer, microbial infection (especially infection by oral pathogens), and inflammation. Most studies have focused on cell lines, but more recent research has also investigated effects in animal models of disease. As natural products are considered to be safer than synthetic drugs, there is growing interest in further developing the use of substances such as frankincense oil for therapeutic treatment.
A Water-Soluble Epoxy-Based Green Crosslinking System for Stabilizing PVA Nanofibers
Authors: Zhang Yujian , Fang Kuanjun , Wang Wei , Niu Haitao
Published: June 2022

With the ever-growing concern about environmental conservation, green production and water-based nanofibers have attracted more and more interest from both academic and industrial fields; nevertheless, the stabilization process of water-based nanofibers is primarily relying on the application of organic solvent-based crosslinking agents. In this work, we develop a green approach to fabricate water-resistant polyvinyl alcohol (PVA) nanofibers by using a water-based epoxy compound, N1, N6-bis(oxiran-2-ylmethyl) hexane-1,6-diamine (EH), as the crosslinker. This EH/sodium carbonate/sodium bicarbonate (CBS) solution system can break down large aggregates of PVA molecules into small ones and promote the uniform distribution of EH in the solution, resulting in the improved stability of crosslinked PVA nanofibers. We firstly report that the uniform dispersion of crosslinking agents in the electrospinning solution plays a vital role in improving the stability of spinning solutions and the water resistance of crosslinked PVA nanofibers by comparing crosslinking performances between water-based epoxy and conventional water-based blocked isocyanate (BI). This work could open up a novel strategy and green approach for the stabilization of water-based nanofibers.
Polyphenols for the Treatment of Ischemic Stroke: New Applications and Insights
Authors: Liu Shuhan , Lin Feng , Wang Jian , Pan Xiaoqiang , Sun Liguang , Wu Wei
Published: June 2022

Ischemic stroke (IS) is a leading cause of death and disability worldwide. Currently, the main therapeutic strategy involves the use of intravenous thrombolysis to restore cerebral blood flow to prevent the transition of the penumbra to the infarct core. However, due to various limitations and complications, including the narrow time window in which this approach is effective, less than 10% of patients benefit from such therapy. Thus, there is an urgent need for alternative therapeutic strategies, with neuroprotection against the ischemic cascade response after IS being one of the most promising options. In the past few decades, polyphenolic compounds have shown great potential in animal models of IS because of their high biocompatibility and ability to target multiple ischemic cascade signaling pathways, although low bioavailability is an issue that limits the applications of several polyphenols. Here, we review the pathophysiological changes following cerebral ischemia and summarize the research progress regarding the applications of polyphenolic compounds in the treatment of IS over the past 5 years. Furthermore, we discuss several potential strategies for improving the bioavailability of polyphenolic compounds as well as some essential issues that remain to be addressed for the translation of the related therapies to the clinic.
Synergistic Effect of Bioactive Monoterpenes against the Mosquito, Culex pipiens (Diptera: Culicidae)
Authors: Ramzi Amal , El Ouali Lalami Abdelhakim , Annemer Saoussan , Ez zoubi Yassine , Assouguem Amine , Almutairi Mikhlid H. , Kamel Mohamed , Peluso Ilaria , Ercisli Sezai , Farah Abdellah
Published: June 2022

Mosquitoes represent one of the most important vectors and are responsible for the transmission of many arboviruses that affect human and animal health. The chemical method using synthetic insecticides disturbs the environmental system and promotes the appearance of resistant insect species. Therefore, this study investigated the insecticidal effect of some binary monoterpene combinations (1,8 cineole + α-pinene and carvone + R (+)-pulegone) using a mixture design approach. The fumigant toxicity was evaluated against Culex pipiens female adults using glass jars. The results show that the toxicity varies according to the proportions of each compound. Indeed, Mixture 1 (1,8-cineole + α-pinene) displayed a strong toxic effect (51.00 ± 0.86% after 24 h and 100.00 ± 0.70% after 48 h) when the pure compounds were tested at 0.25/0.75 proportions of 1,8-cineole and α-pinene, respectively. Nevertheless, the equal proportion (0.5/0.5) of carvone and R (+)-pulegone in Mixture 2 exhibited a toxic effect of 54.35 ± 0.75% after 24 h and 89.96 ± 0.14% after 48 h, respectively. For Mixture 1, the maximum area of mortality that the proposed model indicated was obtained between 0/1 and 0.25/0.75, while the maximum area of mortality in the case of Mixture 2 was obtained between 0.25/0.75 and 0.75/0.25. Moreover, the maximum possible values of mortality that could be achieved by the validated model were found to be 51.44% (after 24 h) and 100.24% (after 48 h) for Mixture 1 and 54.67% (after 24 h) and 89.99% (after 48 h) for Mixture 2. It can be said that all purev molecules tested through the binary mixtures acted together, which enhanced the insecticide’s effectiveness. These findings are very promising, as the chemical insecticide (deltamethrin) killed only 19.29 ± 0.01% and 34.05 ± 1.01% of the female adults after 24 h and 48 h, respectively. Thus, the findings of our research could help with the development of botanical insecticides that might contribute to management programs for controlling vectors of important diseases.
Emerging Lipids from Arecaceae Palm Fruits in Brazil
Authors: Teixeira Gerson Lopes , Ibañez Elena , Block Jane Mara
Published: June 2022

Arecaceae palm tree fruits (APTFs) with pulp or kernel rich in oil are widely distributed in six Brazilian biomes. APTFs represent a great potential for the sustainable exploitation of products with high added value, but few literature studies have reported their properties and industrial applications. The lack of information leads to underutilization, low consumption, commercialization, and processing of these fruit species. This review presents and discusses the occurrence of 13 APTFs and the composition, physicochemical properties, bioactive compounds, and potential applications of their 25 oils and fats. The reported studies showed that the species present different lipid profiles. Multivariate analysis based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) indicated a correlation between the composition of pulp and kernel oils. Myristic, caprylic, capric, and lauric acids are the main saturated fatty acids, while oleic acid is the main unsaturated. Carotenoids and phenolic compounds are the main bioactive compounds in APTFs, contributing to their high oxidative stability. The APTFs oils have a potential for use as foods and ingredients in the cosmetic, pharmaceutical, and biofuel industries. However, more studies are still necessary to better understand and exploit these species.
Phytochemical Investigation, Antioxidant Properties and In Vivo Evaluation of the Toxic Effects of Parthenium hysterophorus
Authors: Iqbal Javed , Khan Ayaz Ali , Aziz Tariq , Ali Waqar , Ahmad Saeed , Rahman Shafiq Ur , Iqbal Zafar , Dablool Anas S. , Alruways Mashael W. , Almalki Abdulraheem Ali , Alamri Abdulhakeem S. , Alhomrani Majid
Published: June 2022

Parthenium hysterophorus L. is a poisonous Asteraceae weed. The phytochemical profile, antioxidant activity, total phenolic contents (TPC), total flavonoid contents (TFC), and cytotoxicity of Parthenium hysterophorus L. flower extract were evaluated in this study, and the toxic effects were assessed in rabbits. The HPLC-DAD system was used for phytochemical analysis. The hemolytic and DPPH assays were performed. The effects of orally administering the flower crude extract to rabbits (n = 5) at four different doses (10, 20, 40, and 80 mg/kg) for ten days on hematological and biochemical parameters were investigated. The crude extract of the flower contained phenolic compounds such as Gallic acid, Chlorogenic acid, Ellagic acid, and P Coumaric acid, which were detected at different retention times, according to the HPLC results. With a sample peak of 4667.475 %, chlorogenic acid was abundant. At concentrations of 80 µg, the methanolic extract of flowers had total phenolic contents (89.364 ± 4.715 g GAE/g) and total flavonoid contents (65.022 ± 2.694 g QE/g). In the DPPH free radical scavenging assay, 80 µg of extract had the highest cell inhibition of 76.90% with an IC50 value of 54.278 µg/µL, while in the hemolytic assay 200 µg of extract had the highest cell inhibition of 76.90% with an IC50 > 500. The biochemical and hematological parameters were altered in the flower extract-fed groups as compared to the control (p < 0.05). The toxic effects on the blood, liver, and kidneys were confirmed. The findings also confirmed the presence of phenolic and flavonoid content in the flower extract, both of which contribute to the plant’s antioxidant potential.
Potential Stereoselective Binding of Trans-(±)-Kusunokinin and Cis-(±)-Kusunokinin Isomers to CSF1R
Authors: Chompunud Na Ayudhya Chompunud , Graidist Potchanapond , Tipmanee Varomyalin
Published: June 2022

Breast cancer cell proliferation and migration are inhibited by naturally extracted trans-(−)-kusunokinin. However, three additional enantiomers of kusunokinin have yet to be investigated: trans-(+)-kusunokinin, cis-(−)-isomer and cis-(+)-isomer. According to the results of molecular docking studies of kusunokinin isomers on 60 breast cancer-related proteins, trans-(−)-kusunokinin was the most preferable and active component of the trans-racemic mixture. Trans-(−)-kusunokinin targeted proteins involved in cell growth and proliferation, whereas the cis-(+)-isomer targeted proteins involved in metastasis. Trans-(−)-kusunokinin targeted CSF1R specifically, whereas trans-(+)-kusunokinin and both cis-isomers may have bound AKR1B1. Interestingly, the compound’s stereoisomeric effect may influence protein selectivity. CSF1R preferred trans-(−)-kusunokinin over trans-(+)-kusunokinin because the binding pocket required a ligand planar arrangement to form a π-π interaction with a selective Trp550. Because of its large binding pocket, EGFR exhibited no stereoselectivity. MD simulation revealed that trans-(−)-kusunokinin, trans-(+)-kusunokinin and pexidartinib bound CSF1R differently. Pexidartinib had the highest binding affinity, followed by trans-(−)-kusunokinin and trans-(+)-kusunokinin, respectively. The trans-(−)-kusunokinin-CSF1R complex was found to be stable, whereas trans-(+)-kusunokinin was not. Trans-(±)-kusunokinin, a potential racemic compound, could be developed as a selective CSF1R inhibitor when combined.
Novel D-A-π-A1 Type Organic Sensitizers from 4,7-Dibromobenzo[d][1,2,3]thiadiazole and Indoline Donors for Dye-Sensitized Solar Cells
Authors: Gudim Nikita S. , Knyazeva Ekaterina A. , Mikhalchenko Ludmila V. , Mikhailov Maksim S. , Zhang Lu , Robertson Neil , Rakitin Oleg A.
Published: June 2022

Two novel D-A-π-A1 metal-free organic dyes of the KEA series containing benzo[d][1,2,3]thiadiazole (isoBT) internal acceptor, indoline donors fused with cyclopentane or cyclohexane rings (D), a thiophene as a π-spacer, and a cyanoacrylate as an anchor part were synthesized. Monoarylation of 4,7-dibromobenzo[d][1,2,3]thiadiazole by Suzuki-Miyamura cross-coupling reaction showed that in the case of indoline and carbazole donors, the reaction was non-selective, i.e., two monosubstituted derivatives were isolated in each case, whereas only one mono-isomer was formed with phenyl- and 2-thienylboronic acids. This was explained by the fact that heterocyclic indoline and carbazole fragments are much stronger donor groups compared to thiophene and benzene, as confirmed by cyclic voltammetry measurements and calculation of HOMO energies of indoline, carbazole, thiophene and benzene molecules. The structure of monoaryl(hetaryl) derivatives was strictly proven by NMR spectroscopy and X-ray diffraction. The optical and photovoltaic properties observed for the KEA dyes showed that these compounds are promising for the creation of solar cells. A comparison with symmetrical benzo[c][1,2,3]thiadiazole dyes WS-2 and MAX114 showed that the asymmetric nature of benzo[d][1,2,3]thiadiazole KEA dyes leads to a hypsochromic shift of the ICT band in comparison with the corresponding benzo[c][1,2,5]thiadiazole isomers. KEA dyes have a narrow HOMO-LUMO gap of 1.5–1.6 eV. Amongst these dyes, KEA321 recorded the best power efficiency (PCE), i.e., 5.17%, which is superior to the corresponding symmetrical benzo[c][1,2,3]thiadiazole dyes WS-2 and MAX114 (5.07 and 4.90%).
Rutin Inhibits Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation by Inducing Autophagy and Modulating PI3K/ATK Signaling
Authors: Li Ben , Ji Yumeng , Yi Chenlong , Wang Xufeng , Liu Chaoyang , Wang Chufan , Lu Xiaohu , Xu Xiaohan , Wang Xiaowei
Published: June 2022

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.
Antitumor Effect of Glandora rosmarinifolia (Boraginaceae) Essential Oil through Inhibition of the Activity of the Topo II Enzyme in Acute Myeloid Leukemia
Authors: Labbozzetta Manuela , Poma Paola , Occhipinti Chiara , Sajeva Maurizio , Notarbartolo Monica
Published: June 2022

It was previously shown that the antitumor and cytotoxic activity of the essential oil (EO) extracted from the aerial parts of Glandora rosmarinifolia appears to involve a pro-oxidant mechanism in hepatocellular carcinoma (HCC) and in triple-negative breast cancer (TNBC) cell lines. Its most abundant compound is a hydroxy-methyl-naphthoquinone isomer. Important pharmacological activities, such as antitumor, antibacterial, antifungal, antiviral and antiparasitic activities, are attributed to naphthoquinones, probably due to their pro-oxidant or electrophilic potential; for some naphthoquinones, a mechanism of action of topoisomerase inhibition has been reported, in which they appear to act both as catalytic inhibitors and as topoisomerase II poisons. Our aim was to evaluate the cytotoxic activity of the essential oil on an acute myeloid leukemia cell line HL-60 and on its multidrug-resistant (MDR) variant HL-60R and verify its ability to interfere with topoisomerase II activity. MTS assay showed that G. rosmarinifolia EO induced a decrease in tumor cell viability equivalent in the two cell lines; this antitumor effect could depend on the pro-oxidant activity of EO in both cell lines. Furthermore, G. rosmarinifolia EO reduced the activity of Topo II in the nuclear extracts of HL-60 and HL-60R cells, as inferred from the inability to convert the kinetoplast DNA into the decatenated form and then not inducing linear kDNA. Confirming this result, flow cytometric analysis proved that EO induced a G0-G1 phase arrest, with cell reduction in the S-phase. In addition, the combination of EO with etoposide showed a good potentiation effect in terms of cytotoxicity in both cell lines. Our results highlight the antitumor activity of EO in the HL-60 cell line and its MDR variant with a peculiar mechanism as a Topo II modulator. Unlike etoposide, EO does not cause stabilization of a covalent Topo II-DNA intermediate but acts as a catalytic inhibitor. These data make G. rosmarinifolia EO a potential anticancer drug candidate due to its cytotoxic action, which is not affected by multidrug resistance.
The Natural Janus Kinase Inhibitor Agerarin Downregulates Interleukin-4-Induced PER2 Expression in HaCaT Keratinocytes
Authors: Lee Jeong Yeon , Jung Euitaek , Yeo Hyunjin , Ahn Sung Shin , Lim Yoongho , Lee Young Han
Published: June 2022

The circadian clock system is closely associated with inflammatory responses. Dysregulation of the circadian clock genes in the skin impairs the skin barrier function and affects the pathophysiology of atopic dermatitis. Interleukin 4 (IL-4) is a proinflammatory cytokine derived from T-helper type 2 cells; it plays a critical role in the pathogenesis of atopic dermatitis. Agerarin (6,7-dimethoxy-2,2-dimethyl-2H-chromene) is a natural JAK1/2/3 inhibitor isolated from Ageratum houstonianum that has a protective effect on the epidermal skin barrier. However, it remains unclear whether agerarin affects the circadian clock system. The aim of this study is to investigate the effect of agerarin on IL-4-induced PER2 gene expression in human keratinocytes through reverse transcription (RT)-PCR, quantitative real-time PCR (qPCR), immunoblotting, immunofluorescence microscopic analysis, and real-time bioluminescence analysis. We found that agerarin reduced IL-4-induced PER2 mRNA expression by suppressing the JAK-STAT3 pathway. In addition, real-time bioluminescence analysis in PER2:luc2p promoter-reporter cells revealed that agerarin restored the oscillatory rhythmicity of PER2 promoter activity altered by IL-4. These findings suggest that agerarin may be useful as a cosmeceutical agent against inflammatory skin conditions associated with disrupted circadian rhythms, such as atopic dermatitis.
Improving the Insulating Capacity of Polyurethane Foams through Polyurethane Aerogel Inclusion: From Insulation to Superinsulation
Authors: Merillas Beatriz , Villafañe Fernando , Rodríguez-Pérez Miguel Ángel
Published: June 2022

A novel synthesis of polyurethane foam/polyurethane aerogel (PUF–PUA) composites is presented. Three different polyurethane reticulated foams which present the same density but different pore sizes (named S for small, M for medium, and L for large) have been used. After the characterization of the reference materials (either, foams, and pure aerogel), the obtained composites have been characterized in order to study the effect of the foam pore size on the final properties, so that density, shrinkage, porous structure, mechanical properties, and thermal conductivity are determined. A clear influence of the pore size on the density and shrinkage was found, and the lowest densities are those obtained from L composites (123 kg/m3). Moreover, the aerogel density and shrinkage have been significantly reduced through the employment of the polyurethane (PU) foam skeleton. Due to the enhanced mechanical properties of polyurethane aerogels, the inclusion of polyurethane aerogel into the foam skeleton helps to increase the elastic modulus of the foams from 0.03 and 0.08 MPa to 0.85 MPa, while keeping great flexibility and recovery ratios. Moreover, the synthesized PUF–PUA composites show an excellent insulating performance, reducing the initial thermal conductivity values from 34.1, 40.3, and 50.6 mW/(m K) at 10 °C for the foams S, M, and L, to 15.8, 16.6, and 16.1 mW/(m K), respectively. Additionally, the effect of the different heat transfer mechanisms to the total thermal conductivity is herein analyzed by using a theoretical model as well as the influence of the measurement temperature.
Direct Observation of the Epitaxial Growth of Bismuth Telluride Topological Insulators from One-Dimensional Heterostructured Nanowires
Authors: Li Rei-Ping , Lu Shiang-Yi , Lin Yen-Jen , Chen Chih-Yen
Published: June 2022

As extraordinary topological insulators, 2D bismuth telluride (Bi2Te3) nanosheets have been synthesized and controlled with a few-layer structure by a facile and fast solvothermal process. The detail-oriented growth evolution of 2D Bi2Te3 in an ethylene glycol reducing solution is discovered and recorded for direct observation of the liquid–solid interactions through the use of environmental SEM. At the initial synthesis stage, Te nanowires are rapidly synthesized and observed in solution. In the next stage, Bi nanoclusters slowly adhere to the Te nanowires and react to form hierarchical Te-Bi2Te3 nanostructured materials. Additionally, the Te nanowires shorten in-plane in an orderly manner, while the Bi2Te3 nanosheets exhibit directional out-of-plane epitaxial growth. In the last procedure, Bi2Te3 nanosheets with a clear hexagonal appearance can be largely obtained. Experiments performed under these rigorous conditions require careful consideration of the temperature, time, and alkaline environment for each reaction process. In addition, the yield of a wider and thinner Bi2Te3 nanosheet is synthesized by manipulating the crystal growth with an optimal alkaline concentration, which is found through statistical analysis of the AFM results. In the UV–Vis–NIR spectroscopy results, the main peak in the spectrum tends to redshift, while the other peak in the ultraviolet range decreases during Bi2Te3 nanosheet synthesis, facilitating a rapid understanding of the trends in the morphological evolution of the Bi2Te3 materials in solution. By rationalizing the above observations, we are the first to report the success of environmental SEM, HAADF-STEM, and UV–Vis–NIR spectroscopy for confirming the Bi2Te3 nanosheet formation mechanism and the physical properties in the solvent media. This research promotes the future optimization of promising Bi2Te3 nanomaterials that can be used in the fabrication of thermoelectric and topological components.
Composite Materials Based on Polymeric Fibers Doped with Magnetic Nanoparticles: Synthesis, Properties and Applications
Authors: Bica Ioan
Published: June 2022

The increasingly sophisticated requirements of contemporary society, in relation to the assessment of environmental and health factors, are receiving much attention from the scientific community [...]
Enterohepatic Takeda G-Protein Coupled Receptor 5 Agonism in Metabolic Dysfunction-Associated Fatty Liver Disease and Related Glucose Dysmetabolism
Authors: Gillard Justine , Picalausa Corinne , Ullmer Christoph , Adorini Luciano , Staels Bart , Tailleux Anne , Leclercq Isabelle A.
Published: June 2022

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a major health concern with no approved pharmacological therapies. Molecules developed to activate the bile acid-receptor TGR5 regulate pathways involved in MALFD pathogenesis, but the therapeutic value of TGR5 activation on the active form of MAFLD, non-alcoholic steatohepatitis (NASH), still needs to be evaluated. As TGR5 agonism is low in MAFLD, we used strategies to promote the production of endogenous TGR5 ligands or administered pharmacological TGR5 agonists, INT-777 and RO5527239, to study the effect of TGR5 activation on liver and metabolic diseases in high-fat diet-fed foz/foz mice. Although described in the literature, treatment with fexaramine, an intestine-restricted FXR agonist, did not raise the concentrations of TGR5 ligands nor modulate TGR5 signaling and, accordingly, did not improve dysmetabolic status. INT-777 and RO5527239 directly activated TGR5. INT-777 only increased the TGR5 activation capacity of the portal blood; RO5527239 also amplified the TGR5 activation capacity of systemic blood. Both molecules improved glucose tolerance. In spite of the TGR5 activation capacity, INT-777, but not RO5527239, reduced liver disease severity. In conclusion, TGR5 activation in enterohepatic, rather than in peripheral, tissues has beneficial effects on glucose tolerance and MAFLD.
Women Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review
Authors: Ledowsky Carolyn , Mahimbo Abela , Scarf Vanessa , Steel Amie
Published: June 2022

Background: In preconception and pregnancy, women are encouraged to take folic acid-based supplements over and above food intake. The upper tolerable limit of folic acid is 1000 mcg per day; however, this level was determined to avoid masking a vitamin B12 deficiency and not based on folic acid bioavailability and metabolism. This review’s aim is to assess the total all-source intake of folate in women of childbearing age and in pregnancy in high-income countries with folate food fortification programs. Methods: A systematic search was conducted in five databases to find studies published since 1998 that reported folate and folic acid intake in countries with a mandatory fortification policy. Results: Women of childbearing age do not receive sufficient folate intake from food sources alone even when consuming fortified food products; however, almost all women taking a folic acid-based supplement exceed the upper tolerable limit of folic acid intake. Conclusions: Folic acid supplement recommendations and the upper tolerable limit of 1000 mcg set by policy makers warrant careful review in light of potential adverse effects of exceeding the upper tolerable limit on folic acid absorption and metabolism, and subsequent impacts on women’s health during their childbearing years.
Overview of the Analytes Applied in Genotypic HIV Drug Resistance Testing
Authors: Ji Hezhao , Sandstrom Paul
Published: June 2022

The close monitoring of HIV drug resistance using genotypic HIV drug resistance testing (HIVDRT) has become essential for effective HIV/AIDS management at both individual and population levels. Over the years, a broad spectrum of analytes or specimens have been applied or attempted in HIVDRT; however, the suitability and performance of these analytes in HIVDRT and the clinical relevance of the results from them may vary significantly. This article provides a focused overview of the performance, strengths, and weaknesses of various analytes while used in HIVDRT, which may inform the optimal analytes selection in different application contexts.
In Vitro Activity of the Arylaminoartemisinin GC012 against Helicobacter pylori and Its Effects on Biofilm
Authors: Sisto Francesca , Carradori Simone , D’Alessandro Sarah , Santo Nadia , Lattuada Norma , Haynes Richard K. , Taramelli Donatella , Grande Rossella
Published: June 2022

This study evaluated the in vitro activity of the arylaminoartemisinin GC012, readily obtained from dihydroartemisinin (DHA), against clinical strains of Helicobacter pylori (H. pylori) with different antibiotic susceptibilities in the planktonic and sessile state. The activity was assessed in terms of bacteriostatic and bactericidal potential. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by the broth microdilution method. After treatment with GC012, all bacterial strains showed significantly lower MIC and MBC values compared to those of DHA. The effect of combination of GC012 with antibiotics was examined using the checkerboard method. GC012 displayed synergistic interactions with metronidazole, clarithromycin, and amoxicillin in all the strains. The antibiofilm activity was evaluated via crystal violet staining, AlamarBlue® assay, colony-forming unit count, and fluorescence microscopy. At ½ MIC and ¼ MIC concentration, both GC012 and DHA inhibited biofilm formation, but only GC012 showed a minimal biofilm eradication concentration (MBEC) on mature biofilm. Furthermore, both compounds induced structural changes in the bacterial membrane, as observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). It is thereby demonstrated that GC012 has the potential to be efficacious against H. pylori infection.
Serological Evidence of Zika Virus Circulation in Burkina Faso
Authors: Tinto Bachirou , Kaboré Didier Patindé Alexandre , Kania Dramane , Kagoné Thérèse Samdapawindé , Kiba-Koumaré Alice , Pinceloup Laura , Thaurignac Guillaume , Perre Philippe Van de , Dabire Roch Kounbobr , Baldet Thierry , Guitierrez Serafin , Gil Patricia , Ayouba Ahidjo , Salinas Sara , Simonin Yannick
Published: June 2022

Zika virus (ZIKV) and dengue virus (DENV) are two closely related members of the Flaviviridae family, both transmitted by mosquitoes of the genus Aedes, and are among the arboviruses most at risk to human health. Burkina Faso has been facing an upsurge in DENV outbreaks since 2013. Unlike DENV, there is no serological evidence of ZIKV circulation in humans in Burkina Faso. The main objective of our study was to determine the seroprevalence of ZIKV and DENV in blood donors in Burkina Faso. A total of 501 donor samples collected in the two major cities of the country in 2020 were first tested by a competitive enzyme-linked immunosorbent assay to detect flavivirus antibodies. Positive sera were then tested using Luminex to detect ZIKV and DENV antibodies and virus-specific microneutralization tests against ZIKV were performed. The ZIKV seroprevalence was 22.75% in the donor samples and we found seropositivity for all DENV-serotypes ranging from 19.56% for DENV-1 to 48.86% for DENV-2. Molecular analyses performed on samples from febrile patients and Aedes aegypti mosquitoes between 2019 and 2021 were negative. Our study showed the important circulation of ZIKV and DENV detected by serology although molecular evidence of the circulation of ZIKV could not be demonstrated. It is essential to strengthen existing arbovirus surveillance in Burkina Faso and more broadly in West Africa by focusing on fevers of unknown origin and integrating vector surveillance to assess the extent of ZIKV circulation and identify the circulating strain. Further studies are needed to better understand the epidemiology of this virus in order to define appropriate prevention and response methods.
A First Assessment of SARS-CoV-2 Circulation in Bats of Central–Southern Italy
Authors: Dakroub Hiba , Russo Danilo , Cistrone Luca , Serra Francesco , Fusco Giovanna , De Carlo Esterina , Amoroso Maria Grazia
Published: June 2022

One serious concern associated with the SARS-CoV-2 pandemic is that the virus might spill back from humans to wildlife, which would render some animal species reservoirs of the human virus. We assessed the potential circulation of SARS-CoV-2 caused by reverse infection from humans to bats, by performing bat surveillance from different sites in Central–Southern Italy. We restricted our survey to sampling techniques that are minimally invasive and can therefore be broadly applied by non-medical operators such as bat workers. We collected 240 droppings or saliva from 129 bats and tested them using specific and general primers for SARS-CoV-2 and coronaviruses, respectively. All samples (127 nasal swabs and 113 faecal droppings) were negative for SARS-CoV-2, and these results were confirmed by testing the samples with the Droplet Digital PCR. Additionally, pancoronavirus end-point RT-PCR was performed, and no sample showed specific bands. This outcome is a first step towards a better understanding of the reverse transmission of this virus to bats. Although the occurrence of a reverse zoonotic pattern can only be fully established by serological testing, the latter might represent an in-depth follow-up to a broad-scale preliminary assessment performed with our approach. We encourage the systematic surveillance of bats to help prevent reverse zoonotic episodes that would jeopardize human health, as well as biodiversity conservation and management.