bluuebunny/crossref_metadata_2025 huggingface dataset:
Removal of an Azo Dye from Wastewater through the Use of Two Technologies: Magnetic Cyclodextrin Polymers and Pulsed Light
Authors: Rodríguez-López María Isabel , Pellicer José Antonio , Gómez-Morte Teresa , Auñón David , Gómez-López Vicente M. , Yáñez-Gascón María José , Gil-Izquierdo Ángel , Cerón-Carrasco José Pedro , Crini Grégorio , Núñez-Delicado Estrella , Gabaldón José Antonio
Published: August 2022

Water pollution by dyes is a huge environmental problem; there is a necessity to produce new decolorization methods that are effective, cost-attractive, and acceptable in industrial use. Magnetic cyclodextrin polymers offer the advantage of easy separation from the dye solution. In this work, the β-CD-EPI-magnetic (β-cyclodextrin-epichlorohydrin) polymer was synthesized, characterized, and tested for removal of the azo dye Direct Red 83:1 from water, and the fraction of non-adsorbed dye was degraded by an advanced oxidation process. The polymer was characterized in terms of the particle size distribution and surface morphology (FE-SEM), elemental analysis (EA), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), infrared spectrophotometry (IR), and X-ray powder diffraction (XRD). The reported results hint that 0.5 g and pH 5.0 were the best conditions to carry out both kinetic and isotherm models. A 30 min contact time was needed to reach equilibrium with a qmax of 32.0 mg/g. The results indicated that the pseudo-second-order and intraparticle diffusion models were involved in the assembly of Direct Red 83:1 onto the magnetic adsorbent. Regarding the isotherms discussed, the Freundlich model correctly reproduced the experimental data so that adsorption was confirmed to take place onto heterogeneous surfaces. The calculation of the thermodynamic parameters further demonstrates the spontaneous character of the adsorption phenomena (ΔG° = −27,556.9 J/mol) and endothermic phenomena (ΔH° = 8757.1 J/mol) at 25 °C. Furthermore, a good reusability of the polymer was evidenced after six cycles of regeneration, with a negligible decline in the adsorption extent (10%) regarding its initial capacity. Finally, the residual dye in solution after treatment with magnetic adsorbents was degraded by using an advanced oxidation process (AOP) with pulsed light and hydrogen peroxide (343 mg/L); >90% of the dye was degraded after receiving a fluence of 118 J/cm2; the discoloration followed a pseudo first-order kinetics where the degradation rate was 0.0196 cm2/J. The newly synthesized β-CD-EPI-magnetic polymer exhibited good adsorption properties and separability from water which, when complemented with a pulsed light-AOP, may offer a good alternative to remove dyes such as Direct Red 83:1 from water. It allows for the reuse of both the polymer and the dye in the dyeing process.
Facile Construction of Iron/Nickel Phosphide Nanocrystals Anchored on N-B-Doped Carbon-Based Composites with Advanced Catalytic Capacity for 4-Nitrophenol and Methylene Blue
Authors: Pan Cheng , Yang Guangying , Yang Haitao , Wu Feifan , Wang Lei , Jiang Jungang , Zhang Yifan , Yuan Junxia
Published: August 2022

The search for a simple and effective method to remove organic dyes and color intermediates that threaten human safety from the water environment is urgent. Herein, we report a simple method for constructing iron/nickel phosphide nanocrystals anchored on N-B-doped carbon-based composites, using steam-exploded poplar (SEP) and graphene oxide (GO) as a carrier. The stability and catalytic activity of N-B-NixFeyP/SEP and GO were achieved by thermal conversion in a N2 atmosphere and modifying the Fe/Ni ratio in gel precursors. N-B-Ni7Fe3P/SEP was employed for the catalytic hydrogenation of 4-nitrophenol (4-NP) and methylene blue (MB), using sodium borohydride in aqueous media at room temperature. This showed much better catalytic performances in terms of reaction rate constant (0.016 S−1 and 0.041 S−1, respectively) and the activity factor, K (1.6 S−1·g−1 and 8.2 S−1·g−1, respectively) compared to the GO carrier (0.0053 S−1 and 0.035 S−1 for 4-NP and MB, respectively). The strong interaction between the carrier’s morphology and structure, and the vertically grown bimetallic phosphide nanoclusters on its surface, enhances charge transfer, electron transfer kinetics at the interface and Ni-Fe phosphide dispersion on the nanoclusters, and prevents dissolution of the nanoparticles during catalysis, thereby improving stability and achieving catalysis durability. These findings provide a green and simple route to efficient catalyst preparation and provide guidance for the rational selection of catalyst carriers.
Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure
Authors: Dawuti Awaguli , Sun Shuchan , Wang Ranran , Gong Difei , Yuan Tianyi , Zhang Li , Yang Shiying , Xing Jianguo , Zheng Ruifang , Lu Yang , Wang Shoubao , Fang Lianhua , Du Guanhua
Published: August 2022

Heart failure (HF) is a clinical syndrome of cardiac insufficiency caused by abnormalities in cardiac structure and function that arise for various reasons, and it is the final stage of most cardiovascular diseases’ progression. Total flavonoid extract from Dracocephalum moldavica L. (TFDM) has many pharmacological and biological roles, such as cardioprotective, neuroprotective, anti-atherogenic, antihypertensive, anti-diabetic, anti-inflammatory, antioxidant, etc. However, its effect on HF and its molecular mechanism are still unclear. In this study, we used systems pharmacology and an animal model of HF to investigate the cardioprotective effect of TFDM and its molecular mechanism. Eleven compounds in TFDM were obtained from the literature, and 114 overlapping genes related to TFDM and HF were collected from several databases. A PPI network and C-T network were established, and GO enrichment analysis and KEGG pathway analysis were performed. The top targets from the PPI network and C-T network were validated using molecular docking. The pharmacological activity was investigated in an HFpEF (heart failure with preserved ejection fraction) mouse model. This study shows that TFDM has a protective effect on HFpEF, and its protective mechanism may be related to the regulation of proinflammatory cytokines, apoptosis-related genes, fibrosis-related genes, etc. Collectively, this study offers new insights for researchers to understand the protective effect and mechanism of TFDM against HFpEF using a network pharmacology method and a murine model of HFpEF, which suggest that TFDM is a promising therapy for HFpEF in the clinic.
Correction of Fanconi Anemia Mutations Using Digital Genome Engineering
Authors: Sipe Christopher J. , Kluesner Mitchell G. , Bingea Samuel P. , Lahr Walker S. , Andrew Aneesha A. , Wang Minjing , DeFeo Anthony P. , Hinkel Timothy L. , Laoharawee Kanut , Wagner John E. , MacMillan Margaret L. , Vercellotti Gregory M. , Tolar Jakub , Osborn Mark J. , McIvor R. Scott , Webber Beau R. , Moriarity Branden S.
Published: August 2022

Fanconi anemia (FA) is a rare genetic disease in which genes essential for DNA repair are mutated. Both the interstrand crosslink (ICL) and double-strand break (DSB) repair pathways are disrupted in FA, leading to patient bone marrow failure (BMF) and cancer predisposition. The only curative therapy for the hematological manifestations of FA is an allogeneic hematopoietic cell transplant (HCT); however, many (>70%) patients lack a suitable human leukocyte antigen (HLA)-matched donor, often resulting in increased rates of graft-versus-host disease (GvHD) and, potentially, the exacerbation of cancer risk. Successful engraftment of gene-corrected autologous hematopoietic stem cells (HSC) circumvents the need for an allogeneic HCT and has been achieved in other genetic diseases using targeted nucleases to induce site specific DSBs and the correction of mutated genes through homology-directed repair (HDR). However, this process is extremely inefficient in FA cells, as they are inherently deficient in DNA repair. Here, we demonstrate the correction of FANCA mutations in primary patient cells using ‘digital’ genome editing with the cytosine and adenine base editors (BEs). These Cas9-based tools allow for C:G > T:A or A:T > C:G base transitions without the induction of a toxic DSB or the need for a DNA donor molecule. These genetic corrections or conservative codon substitution strategies lead to phenotypic rescue as illustrated by a resistance to the alkylating crosslinking agent Mitomycin C (MMC). Further, FANCA protein expression was restored, and an intact FA pathway was demonstrated by downstream FANCD2 monoubiquitination induction. This BE digital correction strategy will enable the use of gene-corrected FA patient hematopoietic stem and progenitor cells (HSPCs) for autologous HCT, obviating the risks associated with allogeneic HCT and DSB induction during autologous HSC gene therapy.
Targeting Fibronectin to Overcome Remyelination Failure in Multiple Sclerosis: The Need for Brain- and Lesion-Targeted Drug Delivery
Authors: van Schaik Pauline E. M. , Zuhorn Inge S. , Baron Wia
Published: August 2022

Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease with unknown etiology that can be characterized by the presence of demyelinated lesions. Prevailing treatment protocols in MS rely on the modulation of the inflammatory process but do not impact disease progression. Remyelination is an essential factor for both axonal survival and functional neurological recovery but is often insufficient. The extracellular matrix protein fibronectin contributes to the inhibitory environment created in MS lesions and likely plays a causative role in remyelination failure. The presence of the blood–brain barrier (BBB) hinders the delivery of remyelination therapeutics to lesions. Therefore, therapeutic interventions to normalize the pathogenic MS lesion environment need to be able to cross the BBB. In this review, we outline the multifaceted roles of fibronectin in MS pathogenesis and discuss promising therapeutic targets and agents to overcome fibronectin-mediated inhibition of remyelination. In addition, to pave the way for clinical use, we reflect on opportunities to deliver MS therapeutics to lesions through the utilization of nanomedicine and discuss strategies to deliver fibronectin-directed therapeutics across the BBB. The use of well-designed nanocarriers with appropriate surface functionalization to cross the BBB and target the lesion sites is recommended.
Diacylglycerol Kinases in Signal Transduction
Authors: Centonze Sara , Baldanzi Gianluca
Published: August 2022

In recent years, the significant research efforts put into the clarification of the PI3K/AKT/mTOR pathway resulted in the approval of the first targeted therapies based on lipid kinase inhibitors [...]
Sulforaphane Increase Mitochondrial Biogenesis-Related Gene Expression in the Hippocampus and Suppresses Age-Related Cognitive Decline in Mice
Authors: Shimizu Sunao , Kasai Shuya , Yamazaki Hiromi , Tatara Yota , Mimura Junsei , Engler Máté János , Tanji Kunikazu , Nikaido Yoshikazu , Inoue Takuro , Suganuma Hiroyuki , Wakabayashi Koichi , Itoh Ken
Published: August 2022

Sulforaphane (SFN) is a potent activator of the transcriptional factor, Nuclear Factor Erythroid 2 (NF-E2)-Related factor 2 (NRF2). SFN and its precursor, glucoraphanin (sulforaphane glucosinolate, SGS), have been shown to ameliorate cognitive function in clinical trials and in vivo studies. However, the effects of SGS on age-related cognitive decline in Senescence-Accelerated Mouse Prone 8 (SAMP8) is unknown. In this study, we determined the preventive potential of SGS on age-related cognitive decline. One-month old SAMP8 mice or control SAM resistance 1 (SAMR1) mice were fed an ad libitum diet with or without SGS-containing broccoli sprout powder (0.3% w/w SGS in diet) until 13 months of age. SGS significantly improved long-term memory in SAMP8 at 12 months of age. Interestingly, SGS increased hippocampal mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) and mitochondrial transcription factor A (TFAM), which are master regulators of mitochondrial biogenesis, both in SAMR1 and SAMP8 at 13 months of age. Furthermore, mRNAs for nuclear respiratory factor-1 (NRF-1) and mitochondrial DNA-encoded respiratory complex enzymes, but not mitochondrial DNA itself, were increased by SGS in SAMP8 mice. These results suggest that SGS prevents age-related cognitive decline by maintaining mitochondrial function in senescence-accelerated mice.
Telocytes and Macrophages in the Gut: From Morphology to Function, Do the Two Cell Types Interact with Each Other? Which Helps Which?
Authors: Vannucchi Maria Giuliana
Published: August 2022

Telocytes and macrophages are ubiquitous cells located in loose connective tissues and share the same mesenchymal origin. Despite these common elements, depending on where they reside, these two cell types are profoundly different in terms of their morphology and functions. The purpose of this review is to provide an update on the knowledge regarding telocytes and macrophages in the gut, where their presence and significance have long been underestimated or misunderstood. The focus will be on the possibility that these two cell types interact with each other and on the potential meaning of these interactions. Based on the complexity of the topic, the variety of possible methodological approaches and the expertise of the author, the point of view in the discussion of the literature data will be mainly morphological. Furthermore, considering the relatively recent period in which these cell types have acquired a primary role in gastrointestinal functions, the attention will be greatly confined to those articles published in the last decade. The microbiota, another main protagonist in this context, will be mentioned only in passing. It is hoped that this review, although not exhaustive, will highlight the importance of macrophages and telocytes in the complex mechanisms that ensure intestinal functions.
Targeting Fatty Acid-Binding Protein 4 Improves Pathologic Features of Aortic Stenosis
Authors: Garaikoetxea Mattie , Martín-Núñez Ernesto , Navarro Adela , Matilla Lara , Fernández-Celis Amaya , Arrieta Vanessa , García-Peña Amaia , Gainza Alicia , Álvarez Virginia , Sádaba Rafael , Jover Eva , López-Andrés Natalia
Published: August 2022

Aortic stenosis (AS) is a fibrocalcific disease of the aortic valves (AVs). Sex-differences in AS pathophysiology have recently been described. High levels of fatty acid-binding protein 4 (FAPB4) in atherosclerotic plaques have been associated with increased local inflammation, endothelial dysfunction, and plaque vulnerability. FABP4 pharmacological blockade has been shown to be effective for the treatment of atherosclerosis by modulating metabolic and inflammatory pathways. We aimed to analyze the sex-specific expression of FABP4 in AS and its potential role as a therapeutic target. A total of 226 patients (61.5% men) with severe AS undergoing surgical AV replacement were recruited. The FABP4 levels were increased in the AVs of AS patients compared to the control subjects, showing greater expression in the fibrocalcific regions. Male AVs exhibited higher levels of FABP4 compared to females, correlating with markers of inflammation (IL-6, Rantes), apoptosis (Bax, caspase-3, Bcl-2), and calcification (IL-8, BMP-2 and BMP-4). VICs derived from AS patients showed the basal expression of FABP4 in vitro. Osteogenic media induced upregulation of intracellular and secreted FABP4 levels in male VICs after 7 days, along with increased levels of inflammatory, pro-apoptotic, and osteogenic markers. Treatment with BMS309403, a specific inhibitor of FABP4, prevented from all of these changes. Thus, we propose FABP4 as a new sex-specific pharmacological therapeutic target in AS.
Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants
Authors: Belorusova Anna Y. , Rovito Daniela , Chebaro Yassmine , Doms Stefanie , Verlinden Lieve , Verstuyf Annemieke , Metzger Daniel , Rochel Natacha , Laverny Gilles
Published: August 2022

The Vitamin D receptor (VDR) plays a key role in calcium homeostasis, as well as in cell proliferation and differentiation. Among the large number of VDR ligands that have been developed, we have previously shown that BXL-62 and Gemini-72, two C-20-modified vitamin D analogs are highly potent VDR agonists. In this study, we show that both VDR ligands restore the transcriptional activities of VDR variants unresponsive to the natural ligand and identified in patients with rickets. The elucidated mechanisms of action underlying the activities of these C-20-modified analogs emphasize the mutual adaptation of the ligand and the VDR ligand-binding pocket.
Thermal-Induced Percolation Phenomena and Elasticity of Highly Oriented Electrospun Conductive Nanofibrous Biocomposites for Tissue Engineering
Authors: Munawar Muhammad A. , Schubert Dirk W.
Published: August 2022

Highly oriented electrospun conductive nanofibrous biocomposites (CNBs) of polylactic acid (PLA) and polyaniline (PANi) are fabricated using electrospinning. At the percolation threshold (φc), the growth of continuous paths between PANi particles leads to a steep increase in the electrical conductivity of fibers, and the McLachlan equation is fitted to identify φc. Annealing generates additional conductive channels, which lead to higher conductivity for dynamic percolation. For the first time, dynamic percolation is investigated for revealing time-temperature superposition in oriented conductive nanofibrous biocomposites. The crystallinity (χc) displays a linear dependence on annealing temperature within the confined fiber of CNBs. The increase in crystallinity due to annealing also increases the Young’s modulus E of CNBs. The present study outlines a reliable approach to determining the conductivity and elasticity of nanofibers that are highly desirable for a wide range of biological tissue applications.
Key Residues Affecting Binding Affinity of Sirex noctilio Fabricius Odorant-Binding Protein (SnocOBP9) to Aggregation Pheromone
Authors: Hao Enhua , Li Yini , Guo Bing , Yang Xi , Lu Pengfei , Qiao Haili
Published: August 2022

Sirex noctilio Fabricius (Hymenoptera Siricidae) is a major quarantine pest responsible for substantial economic losses in the pine industry. To achieve better pest control, (Z)-3-decen-ol was identified as the male pheromone and used as a field chemical trapping agent. However, the interactions between odorant-binding proteins (OBPs) and pheromones are poorly described. In this study, SnocOBP9 had a higher binding affinity with Z3D (Ki = 1.53 ± 0.09 μM) than other chemical ligands. Molecular dynamics simulation and binding mode analysis revealed that several nonpolar residues were the main drivers for hydrophobic interactions between SnocOBP9 and Z3D. Additionally, computational alanine scanning results indicated that five amino acids (MET54, PHE57, PHE71, PHE74, LEU116) in SnocOBP9 could potentially alter the binding affinity to Z3D. Finally, we used single-site-directed mutagenesis to substitute these five residues with alanine. These results imply that the five residues play crucial roles in the SnocOBP9-Z3D complex. Our research confirmed the function of SnocOBP9, uncovered the key residues involved in SnocOBP9-Z3D interactions, and provides an inspiration to improve the effects of pheromone agent traps.
Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden
Authors: Szpor Joanna , Streb Joanna , Glajcar Anna , Sadowski Piotr , Streb-Smoleń Anna , Jach Robert , Hodorowicz-Zaniewska Diana
Published: August 2022

BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.
Evaluation of Phage Display Biopanning Strategies for the Selection of Anti-Cell Surface Receptor Antibodies
Authors: Panagides Nadya , Zacchi Lucia F. , De Souza Mitchell J. , Morales Rodrigo A. V. , Karnowski Alexander , Liddament Mark T. , Owczarek Catherine M. , Mahler Stephen M. , Panousis Con , Jones Martina L. , Fercher Christian
Published: August 2022

Monoclonal antibodies (mAbs) are one of the most successful and versatile protein-based pharmaceutical products used to treat multiple pathological conditions. The remarkable specificity of mAbs and their affinity for biological targets has led to the implementation of mAbs in the therapeutic regime of oncogenic, chronic inflammatory, cardiovascular, and infectious diseases. Thus, the discovery of novel mAbs with defined functional activities is of crucial importance to expand our ability to address current and future clinical challenges. In vitro, antigen-driven affinity selection employing phage display biopanning is a commonly used technique to isolate mAbs. The success of biopanning is dependent on the quality and the presentation format of the antigen, which is critical when isolating mAbs against membrane protein targets. Here, we provide a comprehensive investigation of two established panning strategies, surface-tethering of a recombinant extracellular domain and cell-based biopanning, to examine the impact of antigen presentation on selection outcomes with regards to the isolation of positive mAbs with functional potential against a proof-of-concept type I cell surface receptor. Based on the higher sequence diversity of the resulting antibody repertoire, presentation of a type I membrane protein in soluble form was more advantageous over presentation in cell-based format. Our results will contribute to inform and guide future antibody discovery campaigns against cell surface proteins.
Toll-like Receptor 7 (TLR7) Is Expressed in Adipocytes and the Pharmacological TLR7 Agonist Imiquimod and Adipocyte-Derived Cell-Free Nucleic Acids (cfDNA) Regulate Adipocyte Function
Authors: Thomalla Miriam , Schmid Andreas , Hehner Julia , Koehler Sebastian , Neumann Elena , Müller-Ladner Ulf , Schäffler Andreas , Karrasch Thomas
Published: August 2022

Endosome-localized Toll-like receptors (TLRs) 3 and 9 are expressed and functionally active in adipocytes. The functionality and role of TLR7 in adipocyte biology and innate immunity of adipose tissue (AT) is poorly characterized. We analyzed TLR7 mRNA and protein expression in murine 3T3-L1 and primary adipocytes, in co-cultures of 3T3-L1 adipocytes with murine J774A.1 monocytes and in human AT. The effects of TLR7 agonists imiquimod (IMQ) and cell-free nucleic acids (cfDNA) on adipokine concentration in cell-culture supernatants and gene expression profile were investigated. We found that TLR7 expression is strongly induced during adipocyte differentiation. TLR7 gene expression in adipocytes and AT stroma-vascular cells (SVC) seems to be independent of TLR9. IMQ downregulates resistin concentration in adipocyte cell-culture supernatants and modulates gene expression of glucose transporter Glut4. Adipocyte-derived cfDNA reduces adiponectin and resistin in cell-culture supernatants and potentially inhibits Glut4 gene expression. The responsiveness of 3T3-L1 adipocytes to imiquimod is preserved in co-culture with J774A.1 monocytes. Obesity-related, adipocyte-derived cfDNA engages adipocytic pattern recognition receptors (PRRs), modulating AT immune and metabolic homeostasis during adipose inflammation.
Maximising the Use of Scarce qPCR Master Mixes
Authors: Bustin Stephen , Bustin Claire , Kirvell Sara , Nolan Tania , Mueller Reinhold , Shipley Gregory
Published: August 2022

The COVID-19 pandemic resulted in a universal, immediate, and vast demand for comprehensive molecular diagnostic testing, especially real-time quantitative (qPCR)-based methods. This rapidly triggered a global shortage of testing capacity, equipment, and reagents. Even today, supply times for chemicals from date of order to delivery are often much longer than pre-pandemic. Furthermore, many companies have ratcheted up the price for minimum volumes of reaction master mixes essential for qPCR assays, causing additional problems for academic laboratories often operating on a shoestring. We have validated two strategies that stretch reagent supplies and, whilst particularly applicable in case of scarcity, can readily be incorporated into standard qPCR protocols, with appropriate validation. The first strategy demonstrates equivalent performance of a selection of “past expiry date” and newly purchased master mixes. This approach is valid for both standard and fast qPCR protocols. The second validates the use of these master mixes at less than 1x final concentration without loss of qPCR efficiency or sensitivity.
Bile Acid–Drug Interaction via Organic Anion-Transporting Polypeptide 4C1 Is a Potential Mechanism of Altered Pharmacokinetics of Renally Excreted Drugs
Authors: Yamauchi Minami , Sato Toshihiro , Otake Ayana , Kumondai Masaki , Sato Yu , Kikuchi Masafumi , Maekawa Masamitsu , Yamaguchi Hiroaki , Abe Takaaki , Mano Nariyasu
Published: August 2022

Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC50, Ki values, and bile acid–drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics.
New Insights into Treating Early and Advanced Stage Diabetic Retinopathy
Authors: Simó Rafael , Hernández Cristina
Published: August 2022

Diabetic retinopathy (DR) is the leading cause of preventable blindness in the working-age population. The disease progresses slowly, and we can roughly differentiate two stages: early-stage (ESDR), in which there are mild retinal lesions and visual acuity is generally preserved, and advanced-stage (ASDR), in which the structural lesions are significant and visual acuity is compromised. At present, there are no specific treatments for ESDR and the current recommended action is to optimize metabolic control and maintain close control of blood pressure. However, in the coming years, it is foreseeable that therapeutic strategies based in neuroprotection will be introduced in the clinical arena. This means that screening aimed at identifying patients in whom neuroprotective treatment might be beneficial will be crucial. Regarding the treatment of ASDR, the current primary course is based on laser photocoagulation and intravitreal injections of anti-angiogenic factors or corticosteroids. Repeated intravitreal injections of anti-VEGF agents as the first-line treatment would be replaced by more cost-effective and personalized treatments based on the results of “liquid biopsies” of aqueous humor. Finally, topical administration (i.e., eye drops) of neuroprotective, anti-inflammatory and anti-angiogenic agents will represent a revolution in the treatment of DR in the coming decade. In this article, all these approaches and others will be critically discussed from a holistic perspective.
High-Light-Induced Degradation of Photosystem II Subunits’ Involvement in the Albino Phenotype in Tea Plants
Authors: Cai Wen-He , Zheng Xin-Qiang , Liang Yue-Rong
Published: August 2022

The light-sensitive (LS) albino tea plant grows albinic shoots lacking chlorophylls (Chls) under high-light (HL) conditions, and the albinic shoots re-green under low light (LL) conditions. The albinic shoots contain a high level of amino acids and are preferential materials for processing quality green tea. The young plants of the albino tea cultivars are difficult to be cultivated owing to lacking Chls. The mechanisms of the tea leaf bleaching and re-greening are unknown. We detected the activity and composition of photosystem II (PSII) subunits in LS albino tea cultivar “Huangjinya” (HJY), with a normal green-leaf cultivar “Jinxuan” (JX) as control so as to find the relationship of PSII impairment to the albino phenotype in tea. The PSII of HJY is more vulnerable to HL-stress than JX. HL-induced degradation of PSII subunits CP43, CP47, PsbP, PsbR. and light-harvest chlorophyll–protein complexes led to the exposure and degradation of D1 and D2, in which partial fragments of the degraded subunits were crosslinked to form larger aggregates. Two copies of subunits PsbO, psbN, and Lhcb1 were expressed in response to HL stress. The cDNA sequencing of CP43 shows that there is no difference in sequences of PsbC cDNA and putative amino acids of CP43 between HJY and JX. The de novo synthesis and/or repair of PSII subunits is considered to be involved in the impairment of PSII complexes, and the latter played a predominant role in the albino phenotype in the LS albino tea plant.
Solid Polymer Electrolytes for Lithium Batteries: A Tribute to Michel Armand
Authors: Mauger Alain , Julien Christian M.
Published: August 2022

In a previous publication, a tribute to Michel Armand was provided, which highlighted his outstanding contribution to all aspects of research and development of lithium-metal and lithium-ion batteries. This area is in constant progress and rather than an overview of the work of Armand et al. since the seventies, we mainly restrict this review to his contribution to advances in solid polymer electrolytes (SPEs) and their performance in all-solid-state lithium-metal batteries in recent years.
Adenoid Cystic Carcinoma of the Breast May Be Exempt from Adjuvant Chemotherapy
Authors: Li Lixi , Zhang Di , Ma Fei
Published: August 2022

Consistent standards regarding whether postoperative adjuvant chemotherapy is required in the treatment of adenoid cystic carcinoma of the breast (ACCB) are currently lacking. Using clinical data from the Surveillance, Epidemiology, and End Results (SEER) database (1988–2015), and the National Cancer Center of China (2004–2020), we retrospectively analyzed patients with ACCB who received radical treatment. A total of 661 patients were eligible. The median age at diagnosis was 61 years; 99.5% of patients were initially diagnosed with stage I and II breast cancer, and 76.7% had triple-negative breast cancer. Only 12.4% of patients received adjuvant chemotherapy. Multivariate analysis showed that patients with lymph node metastasis and non-radiotherapy had worse overall survival (OS) (p < 0.05). Patients with lymph node metastasis, stage IIB and III, histological grade ≥ 2, and non-radiotherapy had worse breast cancer-specific survival (BCSS) (p < 0.05). Adjuvant chemotherapy did not improve the OS or BCSS. Patients treated with adjuvant chemotherapy also had no better survival outcomes after propensity score matching. External data verification confirmed that chemotherapy did not improve disease-free survival or OS. Adjuvant chemotherapy cannot improve the clinical outcomes of ACCB, even in subgroups with a high risk of recurrence and metastasis.
Diversity and Distribution of Calonectria Species from Plantation and Forest Soils in Fujian Province, China
Authors: Liu Qianli , Wingfield Michael J. , Duong Tuan A. , Wingfield Brenda D. , Chen Shuaifei
Published: August 2022

To meet the growing demand for wood and pulp products, Eucalyptus plantations have expanded rapidly during the past two decades, becoming an integral part of the southern China landscape. Leaf blight caused by various Calonectria spp., is a serious threat to these plantations. In order to explore the diversity and distribution of Calonectria spp. in Fujian Province soils, samples were collected in Eucalyptus plantations and adjacent plantings of Cunninghamia lanceolata, Phyllostachys heterocycle and Pinus massoniana as well as in natural forests. Three hundred and fifty-three Calonectria isolates were recovered from soil samples and they were identified based on a comparison of multilocus DNA sequence data for the act (actin), cmdA (calmodulin), his3 (histone H3), rpb2 (the second largest subunit of RNA polymerase), tef1 (translation elongation factor 1-alpha) and tub2 (β-tubulin) gene regions, as well as morphological characteristics. Six known taxa including Calonectria aconidialis, Ca. hongkongensis, Ca. ilicicola, Ca. kyotensis, Ca. pacifica, Ca. pseudoreteaudii and one novel species described here as Ca. minensis sp. nov. were identified. Of these, Ca. aconidialis and Ca. kyotensis were the most prevalent species, and found in eight and seven sites, and four and five forest types, respectively. Calonectria spp. were most abundant in soils from Eucalyptus stands, followed by P. heterocycle and natural forests. Relatively few species were found in the soils associated with Cunninghamia lanceolata and Pinus massoniana. The abundance of known Calonectria spp. suggests that these fungi have been relatively well sampled in Fujian. The results are also consistent with the fact that most Calonectria diseases are found on Angiosperm as opposed to Gymnosperm plants.
Introduction of a Corporate Security Risk Management System: The Experience of Poland
Authors: Kalina Iryna , Khurdei Viktoriia , Shevchuk Vira , Vlasiuk Tetiana , Leonidov Ihor
Published: August 2022

To ensure the economic security of companies, it is necessary to introduce a risk management system based on the use of various tools, especially financial ones. The purpose of the article is to scientifically substantiate the paradigm of integration of the risk management mechanism into the system of economic security in companies on the basis of risk-oriented management. The main study method was an online survey of 50 Polish companies in January–April 2021 using a developed questionnaire consisting of 40 questions. According to the results of the expert survey, it is determined that regardless of the type of economic activity of the enterprise, the main goal of introducing risk-oriented management is to preserve assets and increase the efficiency of financial and economic processes. The introduction of risk-oriented management is perceived as a tool to increase the value of the company and ensure the achievement of strategic goals. Fraud is a significant risk to the state of economic security for modern enterprises. To prevent the fact of fraud, taking into account the specifics of the operation of companies, it is suggested to conduct an annual examination. As a result, the suggested procedure should include an audit (audit of financial statements, forensics, transition to international financial reporting standards, audit of systems and processes), assessment (assessment for audit and reporting in accordance with international financial reporting standards, risk management assessment in accordance with international standards, assessment of the effectiveness of economic security), tax analytics (identification of tax risks, analysis of compliance with tax legislation, tax audit), and a due diligence procedure for investment objects.
Tempforming Strengthening of a Low-Alloy Steel
Authors: Dolzhenko Anastasiia , Kaibyshev Rustam , Belyakov Andrey
Published: August 2022

Low-alloy structural steels subjected to quenching and tempering to achieve high strength possess a common drawback associated with low-impact toughness at low temperatures. An additional warm rolling, i.e., tempforming, is a promising approach to strengthen the rolled semi-products along with increasing their impact toughness. The effect of tempforming at 823–923 K on the microstructures and the mechanical properties of a low-alloy steel was studied in comparison with ordinary tempering at the same temperatures. The tempformed microstructures consisted of highly flattened grains with a transverse grain size of 245 nm to 360 nm depending on tempering temperature. A decrease in the transverse grain size with a decreasing temperature was accompanied by an increase in the total dislocation density (including sub-boundary dislocations) from 3.3 × 1015 m−2 to 5.9 × 1015 m−2. The steel samples subjected to tempforming exhibited enhanced mechanical properties. The yield strength increased by more than 300 MPa, approaching about 1200–1500 MPa depending on tempforming temperature. Moreover, strengthening by tempforming was accompanied by an increase in the impact toughness, especially inthe low temperature range down to 77 K, where the impact toughness was above 80 J cm−2.
Modelling Compression Strength of Waste PET and SCM Blended Cementitious Grout Using Hybrid of LSSVM Models
Authors: Khan Kaffayatullah , Gudainiyan Jitendra , Iqbal Mudassir , Jamal Arshad , Amin Muhammad Nasir , Mohammed Ibrahim , Al-Faiad Majdi Adel , Abu-Arab Abdullah M.
Published: August 2022

Nowadays, concretes blended with pozzolanic additives such as fly ash (FA), silica fume (SF), slag, etc., are often used in construction practices. The utilization of pozzolanic additives and industrial by-products in concrete and grouting materials has an important role in reducing the Portland cement usage, the CO2 emissions, and disposal issues. Thus, the goal of the present work is to estimate the compressive strength (CS) of polyethylene terephthalate (PET) and two supplementary cementitious materials (SCMs), namely FA and SF, blended cementitious grouts to produce green mix. For this purpose, five hybrid least-square support vector machine (LSSVM) models were constructed using swarm intelligence algorithms, including particle swarm optimization, grey wolf optimizer, salp swarm algorithm, Harris hawks optimization, and slime mold algorithm. To construct and validate the developed hybrid models, a sum of 156 samples were generated in the lab with varying percentages of PET and SCM. To estimate the CS, five influencing parameters, namely PET, SCM, FLOW, 1-day CS (CS1D), and 7-day CS (CS7D), were considered. The performance of the developed models was assessed in terms of multiple performance indices. Based on the results, the proposed LSSVM-PSO (a hybrid model of LSSVM and particle swarm optimization) was determined to be the best performing model with R2 = 0.9708, RMSE = 0.0424, and total score = 40 in the validation phase. The results of sensitivity analysis demonstrate that all the input parameters substantially impact the 28-day CS (CS28D) of cementitious grouts. Among them, the CS7D has the most significant effect. From the experimental results, it can be deduced that PET/SCM has no detrimental impact on CS28D of cementitious grouts, making PET a viable alternative for generating sustainable and green concrete. In addition, the proposed LSSVM-PSO model can be utilized as a novel alternative for estimating the CS of cementitious grouts, which will aid engineers during the design phase of civil engineering projects.
Influence of the Electron Beam and the Choice of Heating Membrane on the Evolution of Si Nanowires’ Morphology in In Situ TEM
Authors: Shen Ya , Zhao Xuechun , Gong Ruiling , Ngo Eric , Maurice Jean-Luc , Roca i Cabarrocas Pere , Chen Wanghua
Published: August 2022

We used in situ transmission electron microscopy (TEM) to observe the dynamic changes of Si nanowires under electron beam irradiation. We found evidence of structural evolutions under TEM observation due to a combination of electron beam and thermal effects. Two types of heating holders were used: a carbon membrane, and a silicon nitride membrane. Different evolution of Si nanowires on these membranes was observed. Regarding the heating of Si nanowires on a C membrane at 800 °C and above, a serious degradation dependent on the diameter of the Si nanowire was observed under the electron beam, with the formation of Si carbide. When the membrane was changed to Si nitride, a reversible sectioning and welding of the Si nanowire was observed.
Experimental Research on Flexural Mechanical Properties of Ultrahigh Strength Concrete Filled Steel Tubes
Authors: Zhou Xiaojun , Zhan Yulin , Mou Tingmin , Li Zhilun
Published: August 2022

Based on the project of the Guansheng Qujiang Bridge, the flexural mechanical properties of an ultrahigh strength concrete filled steel tube (UHSCFST) were discussed. A total of six UHSCFST beam specimens were tested, and the cube strength (fcu) of the core concrete reached 80.3–115.2 MPa. The effects of concrete strength on flexural bearing capacity, deformation characteristics, and failure modes of UHSCFST specimens were discussed. Test results showed that the bending failure modes of UHSCFST specimens were the same as those of ordinary ones. The failure of UHSCFST specimens was attributed to excessive deflection, and local buckling occurred in the compression zone. Moreover, the bending capacity of the specimens did not decrease, even if they had yielded. Although ultrahigh strength concrete was poured, all of the specimens displayed outstanding bending ductility. The main function of core concrete was to provide radial restraint for the steel tube to avoid premature buckling. When the steel content of the specimen section was constant, the strength increases of core concrete had a slight impact on the bending failure mode, bearing capacity and ductility of UHSCFST specimen. The research results can deepen the understanding of the mechanical behaviors of the UHSCFST composite truss structure.
Synthesis and Characterization of Li2MgGeO4:Ho3+
Authors: Bednarska-Adam Nikola , Kuwik Marta , Pietrasik Ewa , Pisarski Wojciech A. , Goryczka Tomasz , Macalik Bogusław , Pisarska Joanna
Published: August 2022

In this work, the synthesis and characterization of Li2MgGeO4:Ho3+ ceramics were reported. The X-ray diffraction measurements revealed that the studied ceramics belong to the monoclinic Li2MgGeO4. Luminescence properties were analyzed in the visible spectral range. Green and red emission bands correspondent to the 5F4,5S2→5I8 and 5F5→5I8 transitions of Ho3+ were observed, and their intensities were significantly dependent on activator concentration. Luminescence spectra were also measured under direct excitation of holmium ions or ceramic matrix. Holmium ions were inserted in crystal lattice Li2MgGeO4, giving broad blue emission and characteristic 4f-4f luminescent transitions of rare earths under the selective excitation of the ceramic matrix. The presence of the energy transfer process between the host lattice and Ho3+ ions was suggested.
A Three-Dimensional Equivalent Stiffness Model of Composite Laminates with Wrinkle Defects
Authors: Hu Haozhong , Mei Zhiyuan , Li Huadong
Published: August 2022

The stiffness of composite laminates is easily affected by wrinkle defects. In this paper, a new effective analytical model was proposed to predict the three-dimensional equivalent elastic properties of multidirectional composite laminates with wrinkle defects. Firstly, a geometric model was established according to the microscopic characteristics of wrinkle defects. Then, based on the classical laminate theory and homogenization method, the constitutive equation and flexibility matrix of the wrinkle region were established. Finally, the equivalent stiffness parameters of unidirectional and multidirectional laminates were derived, and the effects of different wrinkle parameters and ply-stacking sequences on the stiffness of unidirectional and multidirectional laminates were studied by using the analytical model. The results show that the mechanical properties of the lamina and laminates are affected by the out-of-plane angle and in-plane angle of the wrinkle defects. The accuracy of the analytical model has been verified by the numerical model and other theoretical models, and it has the characteristics of few parameters and a high efficiency. The analytical model can be used to predict the stiffness of composite structures with wrinkle defects simply, effectively, and quantitatively. It can also be used as a tool to provide the mechanical response information of laminates with wrinkle defects.
Advanced Zinc–Magnesium Alloys Prepared by Mechanical Alloying and Spark Plasma Sintering
Authors: Nečas David , Marek Ivo , Pinc Jan , Vojtěch Dalibor , Kubásek Jiří
Published: August 2022

Zinc and its alloys are considered as promising materials for the preparation of biodegradable medical devices (stents and bone fixation screws) due to their enhanced biocompatibility. These materials must achieve an ideal combination of mechanical and corrosion properties that can be influenced by alloying or thermomechanical processes. This paper presents the effects of different mechanical alloying (MA) parameters on the composition of Zn-1Mg powder. At the same time, this study describes the influence of preparation by MA on Zn-6Mg and Zn-16Mg alloys. The selected powders were compacted by the spark plasma sintering (SPS) method. Subsequently, their microstructures were studied and their mechanical properties were tested. The overall process led to a significant grain refinement (629 ± 274 nm for Zn-1Mg) and the formation of new intermetallic phases (Mg2Zn11, MgZn2). The compressive properties of the sintered samples were mainly related to the concentration of the alloying elements, where an increase in concentration led to an improvement in strength but a deterioration in ductility. According to the obtained results, the best properties were obtained for the Zn-1Mg alloy.