bluuebunny/crossref_metadata_2025 huggingface dataset:
Gradient Heatmetry and PIV Investigation of Heat Transfer and Flow near Circular Cylinders
Authors: Seroshtanov Vladimir , Gusakov Andrey
Published: September 2022

This paper presents an experimental investigation of convective heat transfer around circular cylinders installed one after another. The experimental approach based on the combined application of gradient heatmetry and particle image velocimetry. The method made it possible to measure velocity fields and heat flux simultaneously. Investigation of the flow characteristics and the heat transfer coefficient distribution over a system of cylinders was carried out for various Reynolds numbers in the range of Re = (4…40) × 103. In addition, the distance between the cylinders varied in the experiment. The results showed the the influence of the re-circulation bubble length and the features of vortex formation on the flow pattern and characteristics for the configuration under study in the entire range of regimes. The results were compared with experimental and numerical data from previous literature and found to be in good agreement. Our innovative method based on gradient heatmetry showed high information content and a fairly high accuracy of measurement.
Stroke Risks in Primary Aldosteronism with Different Treatments: A Systematic Review and Meta-Analysis
Authors: Qian Ningjing , Xu Jingmiao , Wang Yaping
Published: September 2022

Background: Primary aldosteronism (PA) is a common cause of secondary hypertension and confers a higher risk of stroke. The treatment strategies of PA mainly include medical and adrenalectomy treatment, while there is still no solid conclusion on how these two different treatment strategies mitigate the detrimental effect of PA on stroke. Methods: PubMed, Embase, and Cochrane Library were searched for studies comparing stroke events in patients with PA receiving medical treatment versus adrenalectomy treatment published up to 19 March 2022, including patients with essential hypertension as a control group. We used either fixed or random effect models according to the heterogeneities. Sensitivity analysis was conducted by deleting each study one at a time. Results: We reviewed 201 articles, and three studies met the final criteria, including 3244 PA patients with medical treatment, 1611 PA patients with adrenalectomy treatment, and 20,568 EH patients. Patients with PA post adrenalectomy were observed with a significantly decreased risk of stroke compared to patients receiving medical treatment (OR: 0.57, 95% CI: 0.35–0.93, p = 0.03), and with no difference when compared to patients with essential hypertension. Patients with PA receiving medical treatment were still observed with higher stroke risks (OR: 1.88, 95% CI: 1.68–2.11, p < 0.00001) than patients with essential hypertension. Conclusion: PA is a critical modifiable risk factor for stroke. Adrenalectomy has a superior performance in the mitigation of stroke risks among patients with PA.
The Landscape of Cell Death Processes with Associated Immunogenic and Fibrogenic Effects in Arrhythmogenic Cardiomyopathy
Authors: Lu Wenzhao , Rao Yanfang , Li Yao , Dai Yan , Chen Keping
Published: September 2022

Arrhythmogenic cardiomyopathy (ACM) is a heritable myocardial disease characterized by life-threatening ventricular arrhythmias and sudden cardiac death. Cardiomyocyte death is an essential pathogenic mechanism in ACM, but the cell death landscape has never been elucidated. Our study aimed to address this problem based on RNA-sequencing (RNA-seq) data. Myocardial RNA-seq data from arrhythmogenic right ventricular cardiomyopathy (ARVC) patients and normal controls were obtained from the Gene Expression Omnibus database (GSE107475, GSE107311, GSE107156, GSE107125). Signature gene sets of cell death processes, immune cells, and pathways were collected. Single-sample gene-set enrichment analysis calculated the enrichment scores for these signature gene sets. The RNA-seq data of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from an ACM patient were used for validation (GSE115621). Weighted gene coexpression network analysis (WGCNA) was applied to identify coexpression modules. Immunogenic cell death, apoptosis, necroptosis, and pyroptosis were significantly up-regulated in ARVC. Positive correlations of these four up-regulated cell death processes with immune cells and pathways were found within the ARVC myocardium. In the ARVC sample cluster with higher cell death levels, central memory CD4 T cell, memory B cell, type 1 T helper cell, mast cell, natural killer T cell, and plasmacytoid dendritic cell were more substantially infiltrated. Similarly, immune pathways were more up-regulated in this cluster. Positive linear correlations were found between cell death, immune responses, and myocardial fibrosis within the ARVC samples. Eventually, WGCNA identified a shared coexpression module related to these mechanisms. This study first demonstrated the landscape of cell death processes in the ACM (ARVC) myocardium and their positive correlations with immune responses and myocardial fibrosis. These mechanisms have potential interactions and jointly contribute to the pathogenesis of ACM.
Experimental and Finite Element Study of a Novel Two-Way Corrugated Steel Deck System for Composite Slabs
Authors: John Keerthana , Ashraf Mahmud , Weiss Matthias , Al-Ameri Riyadh
Published: September 2022

This paper investigates the structural performance of a new two-way profiled steel decking system for steel-concrete composite slabs. Several studies have investigated steel decking for steel-concrete composite slabs and focused on utilising the conventional deck as a one-way floor system. The newly developed deck consists of top-hat sections formed by bending corrugated sheets at 90°, which are attached to a corrugated base sheet. The deck is designed for improved composite and two-way action contributed by its unique geometry due to corrugations in the transverse and longitudinal directions. This paper experimentally tested a novel steel decking geometry under construction stage loading. It was in the absence of concrete to establish the deck’s suitability for construction and contribution towards loading capacity and performance for future use as a two-way composite slab. Ultimate load, two-way action, and failure modes were identified. A finite element model was also developed, and parameters assessed that could influence the performance when the deck is potentially used in the composite stage. It was concluded that, while increasing the thickness of the corrugated base sheet significantly affects the load-carrying capacity, the thickness of the top hats has no significant impact. Improved load transfer with two-way behaviour is observed when the bottom flanges of the top hats are continuously connected to the bottom flanges of the adjacent top hats to form a deck. This contrasts with the concept deck, where individual top hats are attached to a corrugated base sheet. In this case, decks with a corrugated base sheet perform 54% better in ultimate load capacity than decks without a corrugated base sheet.
Polymer-Based Materials Built with Additive Manufacturing Methods for Orthopedic Applications: A Review
Authors: Gide Kunal Manoj , Islam Sabrina , Bagheri Z. Shaghayegh
Published: September 2022

Over the last few decades, polymers and their composites have shown a lot of promises in providing more viable alternatives to surgical procedures that require scaffolds and implants. With the advancement in biomaterial technologies, it is possible to overcome the limitations of current methods, including auto-transplantation, xeno-transplantation, and the implantation of artificial mechanical organs used to treat musculoskeletal conditions. The risks associated with these methods include complications, secondary injuries, and limited sources of donors. Three-dimensional (3D) printing technology has the potential to resolve some of these limitations. It can be used for the fabrication of tailored tissue-engineering scaffolds, and implants, repairing tissue defects in situ with cells, or even printing tissues and organs directly. In addition to perfectly matching the patient’s damaged tissue, printed biomaterials can have engineered microstructures and cellular arrangements to promote cell growth and differentiation. As a result, such biomaterials allow the desired tissue repair to be achieved, and could eventually alleviate the shortage of organ donors. As such, this paper provides an overview of different 3D-printed polymers and their composites for orthopedic applications reported in the literature since 2010. For the benefit of the readers, general information regarding the material, the type of manufacturing method, and the biomechanical tests are also reported.
Postural Assessment Systems in the Prevention of Haemophilic Arthropathy: A Narrative Review
Authors: Scaturro Dalila , Vitagliani Fabio , Tomasello Sofia , Mangano Maria Silvia , Signa Gabriele , Letizia Mauro Giulia
Published: September 2022

This narrative review aims to give an overview of some postural evaluation systems currently used in patients with haemophilia. Among them, first, we analyse the HJHS scale, recognized as a specific evaluation tool for haemophilic arthropathy. Second, we focus on other systems usually used in non-haemophilic patients that have also shown good applicability in this patient category, such as gait analysis, stabilometry, and baropodometric examination. This review underlines the use these tools could have in clinical practice to identify the early postural alterations in patients with haemophilia and set up personalised rehabilitation programs.
Fuzzy Color Aura Matrices for Texture Image Segmentation
Authors: Haliche Zohra , Hammouche Kamal , Losson Olivier , Macaire Ludovic
Published: September 2022

Fuzzy gray-level aura matrices have been developed from fuzzy set theory and the aura concept to characterize texture images. They have proven to be powerful descriptors for color texture classification. However, using them for color texture segmentation is difficult because of their high memory and computation requirements. To overcome this problem, we propose to extend fuzzy gray-level aura matrices to fuzzy color aura matrices, which would allow us to apply them to color texture image segmentation. Unlike the marginal approach that requires one fuzzy gray-level aura matrix for each color channel, a single fuzzy color aura matrix is required to locally characterize the interactions between colors of neighboring pixels. Furthermore, all works about fuzzy gray-level aura matrices consider the same neighborhood function for each site. Another contribution of this paper is to define an adaptive neighborhood function based on information about neighboring sites provided by a pre-segmentation method. For this purpose, we propose a modified simple linear iterative clustering algorithm that incorporates a regional feature in order to partition the image into superpixels. All in all, the proposed color texture image segmentation boils down to a superpixel classification using a simple supervised classifier, each superpixel being characterized by a fuzzy color aura matrix. Experimental results on the Prague texture segmentation benchmark show that our method outperforms the classical state-of-the-art supervised segmentation methods and is similar to recent methods based on deep learning.
The Influence of Different Pretreatment Methods of Highland Barley by Solid-State Fermentation with Agaricus sinodeliciosus var. Chaidam ZJU-TP-08 on Its Nutrient Content, Functional Properties and Physicochemical Characteristics
Authors: Liu Biao , Lu Hongyun , Shu Qin , Chen Qihe , Wang Jinling
Published: September 2022

To enhance the nutritional value of highland barley (HB), this work investigated the effects of solid-state fermentation (SSF) by Agaricus sinodeliciosus var. Chaidam ZJU-TP-08 on nutrient content, phenolic components, antioxidant activities, and physicochemical characteristics of HB upon different pretreatments (germination, ultrasound and soaking). The results showed that germinated highland barley (GHB) exhibited higher levels of ergosterol (0.19 ± 0.01 mg/g) in all fermentation groups. The content of β-glucan was higher in the SSF-GHB, with an increase of 24.21% compared to the control. The content of total amino acids, dietary fiber, total phenols and flavonoids were higher in the fermentation HB pretreated by ultrasound, increasing respectively by 5.60%, 61.50%, 25.10% and 65.32% compared to the control group. In addition, the colonized HB exhibited excellent physicochemical characteristics, including increased water solubility index and decreased pasting characteristics. Herein, the nutritional value and the biological activities were enriched in the pretreated HB through SSF, indicating its potential application for nutrition-enriched functional foods.
Metabarcoding and Metabolome Analyses Reveal Mechanisms of Leymus chinensis Growth Promotion by Fairy Ring of Leucocalocybe mongolica
Authors: Duan Mingzheng , Lu Jia , Yang Wenjing , Lu Meiling , Wang Jibin , Li Suli , Chen Yiting , Hu Lihua , Wang Lingqiang
Published: September 2022

Fairy rings are a unique ecological phenomenon caused by the growth of the fungal mycelium in the soil. Fairy rings formed by Leucocalocybe mongolica (LM) are generally distributed in the Mongolian Plateau, where they promote plant growth without fertilization and alleviate fertilizer use. We previously investigated the soil factors regulating growth promotion in a fairy ring ecosystem; however, the aspects of the plant (Leymus chinensis, LC) that promote growth have not been explored. Therefore, the present study investigated the endophyte diversity and metabolome of LC in an LM fairy ring ecosystem. We analyzed the leaf and root samples of LC from the DARK (FR) and OUT (CK) zones. The fairy rings significantly improved the fungal diversity of roots and leaves and the bacterial diversity of leaves in the FR zone. Ralstonia was the dominant bacteria detected in the LC leaves. In addition, Marasmius, another fairy ring fungal genus, was also detected with a high abundance in the roots of the FR zone. Furthermore, widely targeted metabolome analysis combined with KEGG annotation identified 1011 novel metabolites from the leaves and roots of LC and seven pathways significantly regulated by the fairy ring in the FR zone. The fairy ring ecosystem significantly downregulated the flavonoid metabolism in the leaves and roots of LC. The correlation analysis found Ralstonia is a potential regulatory factor of flavonoid biosynthesis in LC. In addition, salicylic acid and jasmonic acid were found upregulated in the leaves, probably related to Marasmius enrichment. Thus, the study details plant factors associated with enhanced growth in an LM fairy ring ecosystem. These findings lay a theoretical foundation for developing the fairy ring ecosystem in an agricultural system.
Reply to Paterson, R.R.M. Comment on “Castillo et al. Ganoderma zonatum Is the Causal Agent of Basal Stem Rot in Oil Palm in Colombia. J. Fungi 2022, 8, 230”
Authors: Castillo Sandra Yulieth , Rodríguez María Camila , González Luis Felipe , Zúñiga León Franky , Mestizo Yuri Adriana , Medina Héctor Camilo , Montoya Carmenza , Morales Anuar , Romero Hernán Mauricio , Sarria Greicy Andrea
Published: September 2022

Reader Q: There was no morphological information provided for the isolated specimens, and so it is not known if they are even Ganoderma [...]
Simulated Micro-, Lunar, and Martian Gravities on Earth—Effects on Escherichia coli Growth, Phenotype, and Sensitivity to Antibiotics
Authors: Allen Lily A. , Kalani Amir H. , Estante Frederico , Rosengren Aaron J. , Stodieck Louis , Klaus David , Zea Luis
Published: September 2022

Bacterial behavior has been studied under microgravity conditions, but very little is known about it under lunar and Martian gravitational regimes. An Earth-based approach was designed and implemented using inclined clinostats and an in-house-developed code to determine the optimal clinorotation angular speed for bacterial liquid cultures of 5 RPM. With this setup, growth dynamics, phenotypic changes, and sensitivity to antibiotics (minimum inhibitory concentration (MIC) of two different classes of antibiotics) for three Escherichia coli strains (including uropathogenic) were examined under simulated micro-, lunar, and Martian gravities. The results included increased growth under simulated micro- and lunar gravities for some strains, and higher concentrations of antibiotics needed under simulated lunar gravity with respect to simulated micro- and Martian gravities. Clinostat-produced results can be considered suggestive but not determinative of what might be expected in altered gravity, as there is still a need to systematically verify these simulation devices’ ability to accurately replicate phenomena observed in space. Nevertheless, this approach serves as a baseline to start interrogating key cellular and molecular aspects relevant to microbial processes on the lunar and Martian surfaces.
Structures of Hydrated Metal Ions in Solid State and Aqueous Solution
Authors: Persson Ingmar
Published: September 2022

This review article summarizes the reported crystallographically determined structures of compounds containing a hydrated metal ion and the reported structures of hydrated metal ions in aqueous solution. A short overview of the methods available to study structures of metal complexes in solution is given.
Spinal Cord Injury and Postdural Puncture Headache following Cervical Interlaminar Epidural Steroid Injection: A Case Report
Authors: Park Hyung Joon , Kim Heezoo , Jeong Sung Jin , Lee Jae Hak , Choi Sang Sik , Lee Chung Hun
Published: September 2022

Background: Cervical interlaminar epidural steroid injection (CIESI) is increasingly used as an interventional treatment for pain originating from the cervical spine. However, serious neurological complications may occur during CIESI because of direct nerve damage following inappropriate needle placement. Case report: A 35-year-old woman presented with posterior neck pain radiating to the left upper arm. Cervical magnetic resonance imaging (MRI) revealed left C6 nerve impingement. CIESI under fluoroscopic guidance was performed at another hospital using the left C5/6 interlaminar approach. Immediately after the procedure, the patient experienced dizziness, decreased blood pressure, motor weakness in the left upper arm, and sensory loss. She visited our emergency department with postdural puncture headache (PDPH) that worsened after the procedure. Post-admission cervical MRI revealed intramedullary T2 high signal intensity and cord swelling from the C4/5 to C6/7 levels; thus, a diagnosis of spinal cord injury was made. The patient’s PDPH spontaneously improved after 48 h. However, despite conservative treatment with steroids, the decrease in abduction of the left fifth finger and loss of sensation in the dorsum of the left hand persisted for up to 6 months after the procedure. As noticed in the follow-up MRI performed 6 months post-procedure, the T2 high signal intensity in the left intramedullary region had decreased compared to that observed previously; however, cord swelling persisted. Furthermore, left C7/8 radiculopathy with acute denervation was confirmed by electromyography performed 6 months after the procedure. Conclusions: Fluoroscopy does not guarantee the prevention of spinal cord penetration during CIESI. Moreover, persistent neurological deficits may occur, particularly due to intrathecal perforation or drug administration during CIESI. Therefore, in accordance with the recommendations of the Multisociety Pain Workgroup, we recommend performing CIESI at the C6/7 or C7/T1 levels, where the epidural space is relatively large, rather than at the C5/6 level or higher.
Relative Leukocyte Telomere Length and Telomerase Complex Regulatory Markers Association with Leber’s Hereditary Optic Neuropathy
Authors: Liutkeviciene Rasa , Mikalauskaite Rasa , Gedvilaite Greta , Glebauskiene Brigita , Kriauciuniene Loresa , Žemaitienė Reda
Published: September 2022

Background and Objectives: To evaluate the association of relative leukocyte telomere length (RLTL) and telomerase complex regulatory markers with Leber’s hereditary optic neuropathy (LHON). Material and Methods: A case-control study was performed in patients with LHON (≥18 years) and healthy subjects. The diagnosis of LHON was based on a genetic blood test (next-generation sequencing with Illumina MiSeq, computer analysis: BWA2.1 Illumina BaseSpace, Alamut, and mtDNA Variant analyzer 1000 were performed) and diagnostic criteria approved by the LHON disease protocol. Statistical analysis was performed using the standard statistical software package, IBM SPSS Statistics 27. Statistically significant results were considered when p < 0.05. Results: Significantly longer RLTL was observed in LHON patients than in healthy controls (p < 0.001). RLTL was significantly longer in women and men with LOHN than in healthy women and men in the control group (p < 0.001 and p = 0.003, respectively). In the elderly group (>32 years), RLTL was statistically significantly longer in LHON patients compared with healthy subjects (p < 0.001). The GG genotype of the TERC rs12696304 polymorphism was found to be statistically significantly higher in the LHON group (p = 0.041), and the C allele in the TERC rs12696304 polymorphism was found to be statistically significantly less common in the LHON group (p < 0.001). The RLTL of LHON patients was found to be statistically significantly longer in the TERC rs12696304 polymorphism in all tested genotypes (CC, p = 0.005; CG, p = 0.008; GG, p = 0.025), TEP1 rs1760904 polymorphism in the GA genotype (p < 0.001), and TEP1 gene rs1713418 in the AA and AG genotypes (p = 0.011 and p < 0.001, respectively). Conclusions: The RLTL in LHON patients was found to be longer than in healthy subjects regardless of treatment with idebenone. The TERC rs12696304 polymorphism, of all studied polymorphisms, was the most significantly associated with changes in LHON and telomere length.
Undetectable Macular Neovascularization on OCT Angiography in Age Related Macular Degeneration: Comparison between Different Devices
Authors: Filali Ansary Meryem , Crincoli Emanuele , Semoun Oudy , Uzzan Joel , Amoroso Francesca , Jung Camille , Miere Alexandra , Souied Eric
Published: September 2022

Background and Objectives: The aim of this study was to report the characteristics of macular neovascularization (MNV) with undetectable flow on optical coherence tomography angiography (OCTA) in neovascular age related macular degeneration (nAMD), and compare them with the characteristics of detectable MNV. Materials and Methods: Patients with a diagnosis of nAMD who underwent dye imaging and OCTA in the same day were included and divided into two groups: undetectable and detectable flow on OCTA. Three OCTA devices were used, two with spectral-domain technology (AngioVue, RTVue 100xAvanti, Optovue, Freemont, CA, USA and Heidelberg OCT2 Beta Angiography Module, Heidelberg Engineering, Germany) and one swept-source OCTA (PlexElite 9000; Carl Zeiss Meditec, Inc., Dublin, CA, USA). We studied the demographics, neovascularization characteristics, and OCTA device and acquisition characteristics for both groups. Results: A global comparison between Group 1 and Group 2 was made, followed by an analysis of variables associated with (un)detectability for each OCTA device. A total of 108 eyes were included: 90 in the detectable group (Group 1) and 18 in the undetectable group (Group 2), corresponding to a global sensitivity of OCTA for the detection of MNV of 83.49%. There was a statistically significant difference between the two groups regarding MNV type (p = 0.02) and PED height (p = 0.017). For the three devices, detection sensitivity with automatic segmentation was significantly lower than with manual segmentation. For Heidelberg, PED Height and scan quality explained 68.3% of the undetectability. For AngioVue, PED Height and absence of hemorrhage explained 67.9% of undetectability. Conclusions: In this study, we found a global sensitivity of 83.49% for the three OCTA devices combined, with a range from 55.5% to 96.26% depending on the segmentation and OCTA device. This means that undetectable/undetected MNV can represent up to 45% of the examinations, eventually misdiagnosing choroidal neovascularization for 1 out every 2 patients.
Enteric Methane Emission from Sheep Fed with Rhodes Grass Hay (Chloris gayana) Alone or Supplemented with Dried Distillers’ Grains with Solubles
Authors: Gere José Ignacio , Feksa Frasson Mónica , Wawrzkiewicz Marisa , Fernández Pepi María Gabriela , Ramos María Laura , Bualó Ricardo , Cerón-Cucchi María Esperanza , Jaurena Gustavo
Published: September 2022

Livestock systems based on subtropical and tropical pastures are characterized by the low productivity of livestock due to the poor nutritional value of the forage (low nitrogen concentration and digestibility, and high fiber and lignin concentrations). These conditions lead to low productivity and, consequently, high absolute emissions of methane (CH4) per unit of product. Dry distilled grains with solubles (DDGS) are the main by-product resulting from ethanol production, and they are characterized by their high-energy fibrous and protein content, thus becoming an option for the supplementation of low-quality forage. This research investigated the effects of dietary DDGS inclusion on dry matter digestibility (DMD) and enteric CH4 emission. Eight adult sheep of 64 ± 8 kg live weight were used. The duration of the study was 54 days, divided into two periods (changeover design), which comprised a 17-day pre-experimental period and 10 days for experimental data collection. Animals were allocated to one of two treatments used: hay (H) as a control treatment, where animals were fed with Rhodes grass hay alone; and H + DDGS, where animals were fed with H supplemented with DDGS. CH4 emissions were estimated using the sulfur hexafluoride (SF6) tracer technique. Diets containing DDGS increased DMI by 22% (p < 0.05) and reduced daily CH4 emissions by 24% (g/d), the CH4 yield by 35% (g/kg DMI), and the average value of CH4 energy per gross energy intake (Ym) by 44%, compared to the control treatment (p < 0.05). The experiment demonstrated that supplementation with DDGS in low-quality roughage reduced daily CH4 emissions, yields, and Ym.
Assessment of Polyester Fabrics, Effluents and Filtrates after Standard and Innovative Washing Processes
Authors: Pušić Tanja , Vojnović Branka , Čurlin Mirjana , Bekavac Ivica , Kaurin Tea , Grgić Katia , Šimić Kristina , Kovačević Zorana
Published: September 2022

Textile materials from polyester fibres are sensitive to washing, especially at higher temperatures, due to their thermoplastic properties, hydrophobic nature and sensitivity to the alkaline medium. The issue of microplastic fibres’ (MFs’) release from polyester textiles is a topic that attracts the attention of researchers from different scientific fields, since microplastics are now among the serious environmental risks. In this study, two washing protocols, a standard and an innovative procedure, were presented, aiming to preserve the properties of polyester fabrics and reduce the pollution of washing effluents. The standard procedure followed HRN EN ISO 6330, while the innovative procedure was a modification of the standard that involved gradually cooling the bath before rinsing. The effects of these washing protocols were studied based on the physicochemical properties of the fabrics compared to the unwashed material, the composition of the effluents, and the filtrates after 10 cycles. The characterisation parameters of the fabrics, effluents and filtrates according to the standard and the innovative washing protocols showed differences in the observed parameters during the 10 washing cycles. The obtained results show the usefulness of the proposed concept of cooling the bath before rinsing in order to preserve the properties of polyester fabrics and reduce the load of washing effluents. Hierarchical cluster analysis (HCA) also confirmed differences in pH, conductivity and turbidity for effluents and filtrates from standard and innovative washing protocols.
Microsecond MD Simulations to Explore the Structural and Energetic Differences between the Human RXRα-PPARγ vs. RXRα-PPARγ-DNA
Authors: Azam Faizul , Bello Martiniano
Published: September 2022

The heterodimeric complex between retinoic X receptor alpha (RXRα) and peroxisome proliferator-activated receptor gamma (PPARγ) is one of the most important and predominant regulatory systems, controlling lipid metabolism by binding to specific DNA promoter regions. X-ray and molecular dynamics (MD) simulations have revealed the average conformation adopted by the RXRα-PPARγ heterodimer bound to DNA, providing information about how multiple domains communicate to regulate receptor properties. However, knowledge of the energetic basis of the protein-ligand and protein-protein interactions is still lacking. Here we explore the structural and energetic mechanism of RXRα-PPARγ heterodimer bound or unbound to DNA and forming complex with co-crystallized ligands (rosiglitazone and 9-cis-retinoic acid) through microsecond MD simulations, molecular mechanics generalized Born surface area binding free energy calculations, principal component analysis, the free energy landscape, and correlated motion analysis. Our results suggest that DNA binding alters correlated motions and conformational mobility within RXRα–PPARγ system that impact the dimerization and the binding affinity on both receptors. Intradomain correlated motions denotes a stronger correlation map for RXRα-PPARγ-DNA than RXRα-PPARγ, involving residues at the ligand binding site. In addition, our results also corroborated the greater role of PPARγ in regulation of the free and bound DNA state.
Isatin Bis-Indole and Bis-Imidazothiazole Hybrids: Synthesis and Antimicrobial Activity
Authors: Bonvicini Francesca , Locatelli Alessandra , Morigi Rita , Leoni Alberto , Gentilomi Giovanna Angela
Published: September 2022

Isatin and its derivatives are important heterocycles found in nature and present in numerous bioactive compounds which possess various biological activities. Moreover, it is an essential building block in organic synthesis. The discovery of novel compounds active against human pathogenic bacteria and fungi is an urgent need, and the isatin may represent the suitable scaffold in the design of biologically relevant antimicrobials. A small library of 18 isatin hybrids was synthetized and evaluated for their antimicrobial potential on three reference strains: S. aureus, E. coli, both important human pathogens infamous for causing community- and hospital-acquired severe systemic infections; and C. albicans, responsible for devastating invasive infections, mainly in immunocompromised individuals. The study highlighted two lead compounds, 6k and 6m, endowed with inhibitory activity against S. aureus at very low concentrations (39.12 and 24.83 µg/mL, respectively).
Therapeutic Effect of Icaritin on Cerebral Ischemia-Reperfusion-Induced Senescence and Apoptosis in an Acute Ischemic Stroke Mouse Model
Authors: Wu Cheng-Tien , Yang Ting-Hua , Chen Man-Chih , Guan Siao-Syun , Chen Chang-Mu , Liu Shing-Hwa
Published: September 2022

An ischemic stroke is brain damage caused by interruption of blood supply to the brain that can cause death and long-term disability. New medical strategies or therapies are urgently needed for ischemic stroke. Icaritin (ICT) is a metabolite of icariin (ICA), which are two active flavonoid components extracted from Herba epimedii and considered neuroprotective agents in animal models of Alzheimer’s disease and ischemic stroke. The therapeutic effect of ICT on ischemic still remains to be clarified. The aim of this study was to investigate the therapeutic effect of ICT on cerebral ischemia-reperfusion-associated senescence and apoptosis in a middle cerebral artery occlusion (MCAO) mouse model (ischemia for 50 min and reperfusion for 24 h). Administration of ICT after ischemia significantly reduced MCAO-induced neurological damage, infarct volume, and histopathological changes in the brain of acute ischemic stroke mice. ICT treatment could also reduce neuronal apoptosis and senescence and reversed the expression of apoptosis- and senescence-related signaling proteins. These findings suggest that ICT may have therapeutic potential to ameliorate acute ischemic stroke.
Integrating Anti-Influenza Virus Activity and Chemical Pattern Recognition to Explore the Quality Evaluation Method of Lonicerae Japonicae Flos
Authors: Xie Xueqing , Gu Lifei , Xu Wanyi , Yu Xiean , Yin Guo , Wang Jue , Jin Yibao , Wang Lijun , Wang Bing , Wang Tiejie
Published: September 2022

Lonicerae japonicae flos (LJF, Lonicera japonica Thunb.) is adopted as a core herb for preventing and treating influenza. However, the anti-influenza virus components of LJF and the impact of quality-affecting factors on the anti-influenza activity of LJF have not been systematically investigated. In this study, a strategy integrating anti-influenza virus activity, ultrahigh-performance liquid chromatography fingerprint and chemical pattern recognition was proposed for the efficacy and quality evaluation of LJF. As a result, six bioactive compounds were screened out and identified as neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 4,5-Di-O-caffeoylquinic acid, sweroside and secoxyloganin. Based on the bioactive compounds, chemical pattern recognition models of LJF were established by a linear discriminant analysis (LDA). The results of the LDA models and anti-influenza virus activity demonstrated that cultivation pattern significantly affected the anti-influenza effect of LJF and that the neuraminidase inhibition rate of wild LJF was significantly higher than that of cultivated LJF. Moreover, the quality of LJF samples with different processing methods and geographical origins showed no obvious difference. Overall, the proposed strategy in the current study revealed the anti-influenza virus components of LJF and provided a feasible method for thequality evaluation of LJF, which has great importance for assuring the clinical effect against influenza of LJF.
In-Silico Analysis of Phytocompounds of Olea europaea as Potential Anti-Cancer Agents to Target PKM2 Protein
Authors: Qais Faizan Abul , Alomar Suliman Yousef , Imran Mohammad Azhar , Hashmi Md Amiruddin
Published: September 2022

Globally, cancer is the second leading cause of mortality and morbidity. The growth and development of cancer are extremely complex. It is caused by a variety of pathways and involves various types of enzymes. Pyruvate kinase M2 (PKM2) is an isoform of pyruvate kinase, that catalyses the last steps of glycolysis to produce energy. PKM2 is relatively more expressed in tumour cells where it tends to exist in a dimer form. Various medicinal plants are available that contain a variety of micronutrients to combat against different cancers. The phytocompounds of the olive tree (Olea europaea) leaves play an important role in inhibiting the proliferation of several cancers. In this study, the phytocompounds of olive leaf extract (OLE) were studied using various in silico tools, such as pkCSM software to predict ADMET properties and PASS Online software to predict anticancer activity. However, the molecular docking study provided the binding energies and inhibition constant and confirmed the interaction between PKM2 and the ligands. The dynamic behaviour, conformational changes, and stability between PKM2 and the top three hit compounds (Verbascoside (Ver), Rutin (Rut), and Luteolin_7_O_glucoside (Lut)) are studied by MD simulations.
Ultrasound-Assisted Extraction of Flavonoids from Potentilla fruticosa L. Using Natural Deep Eutectic Solvents
Authors: Xue He , Li Jinping , Wang Guiyao , Zuo Wenming , Zeng Yang , Liu Likuan
Published: September 2022

A series of natural deep eutectic solvents (NADESs) were prepared with choline chloride, betaine, and a variety of natural organic acids in order to find new environmentally-friendly green solvents to replace the traditional solvents. The NADESs were employed to extract flavonoids from Potentilla fruticosa L. (PFL) with the help of ultrasound. The eutectic solvent diluted with an appropriate amount of water improved the extraction ability of flavonoids due to the decrease of solution viscosity. The microstructure of the raw sample and the samples subjected to ultrasonic bath in different solutions were observed using scanning electron microscope (SEM) to determine the role of the NADESs in the extraction process. The DPPH method and glucose consumption method were used to study the antioxidant and hypoglycemic ability of flavonoid compounds in PFL. Single factor method and response surface methodology (RSM) were designed to analyze the effects of three extraction parameters, including solvent/solid ratio, ultrasonic power, and extraction time, on the extraction yield, antioxidant capacity, and hypoglycemic capacity, and the corresponding second-order polynomial prediction models were established. The optimal extraction conditions for the maximum extraction yield, antioxidant capacity, and hypoglycemic capacity were predicted by RSM, and the reliability of RSM simulation results was verified by a one-off experiment.
Immobilized Stenotrophomonas maltophilia KB2 in Naproxen Degradation
Authors: Wojcieszyńska Danuta , Klamka Judyta , Marchlewicz Ariel , Potocka Izabela , Żur-Pińska Joanna , Guzik Urszula
Published: September 2022

Immobilization is a commonly used method in response to the need to increase the resistance of microorganisms to the toxic effects of xenobiotics. In this study, a plant sponge from Luffa cylindrica was used as a carrier for the immobilization of the Stenotrophomonas maltophilia KB2 strain since such a carrier meets the criteria for high-quality carriers, i.e., low price and biodegradability. The optimal immobilization conditions were established as a temperature of 30 °C, pH 7.2, incubation time of 72 h, and an optical density of the culture of 1.4. The strain immobilized in such conditions was used for the biodegradation of naproxen, and an average rate of degradation of 3.8 µg/hour was obtained under cometabolic conditions with glucose. The obtained results indicate that a microbiological preparation based on immobilized cells on a luffa sponge can be used in bioremediation processes where it is necessary to remove the introduced carrier.
Valorization of Amaranth (Amaranthus cruentus) Grain Extracts for the Development of Alginate-Based Active Films
Authors: Coelho Laylla Marques , Faria Carla , Madalena Daniel , Genisheva Zlatina , Martins Joana T. , Vicente António A. , Pinheiro Ana C.
Published: September 2022

This research work investigates the development of alginate-based films incorporating phenolic compounds extracted from Amaranthus cruentus grain using different solvents. Alginate, glycerol, and amaranth grain phenolic compounds at various concentrations were used to produce the films. An experimental Central Composite Rotatable Design (CCRD) was used to evaluate the effect of these variables on different film’s properties, i.e., water vapor permeability, hydrophobicity, moisture content, solubility, thermal, mechanical, and optical properties. This study demonstrated that high phenolic compound content and antioxidant capacity were obtained from amaranth grain using ethanol as the extraction solvent. Alginate films incorporating amaranth phenolic compounds were successfully manufactured, and this study can be used to tailor the formulation of alginate films containing amaranth phenolic compounds, depending on their final food application. For example, less flexible but more resistant and water-soluble films can be produced by increasing the alginate concentration, which was confirmed by a Principal Component Analysis (PCA) and Partial Least Squares (PLS) analysis. This study showed that active alginate films with amaranth phenolic compounds can be tailored to be used as food packaging material with potential antioxidant activity.
Facile Access to 2-Selenoxo-1,2,3,4-tetrahydro-4-quinazolinone Scaffolds and Corresponding Diselenides via Cyclization between Methyl Anthranilate and Isoselenocyanates: Synthesis and Structural Features
Authors: Osmanov Vladimir K. , Chipinsky Evgeniy V. , Khrustalev Victor N. , Novikov Alexander S. , Askerov Rizvan Kamiloglu , Chizhov Alexander O. , Borisova Galina N. , Borisov Alexander V. , Grishina Maria M. , Kurasova Margarita N. , Kirichuk Anatoly A. , Peregudov Alexander S. , Kritchenkov Andreii S. , Tskhovrebov Alexander G.
Published: September 2022

A practical method for the synthesis of 2-selenoxo-1,2,3,4-tetrahydro-4-quinazolinone was reported. The latter compounds were found to undergo facile oxidation with H2O2 into corresponding diselenides. Novel organoselenium derivatives were characterized by the 1H, 77Se, and 13C NMR spectroscopies, high-resolution electrospray ionization mass spectrometry, IR, elemental analyses (C, H, N), and X-ray diffraction analysis for several of them. Novel heterocycles exhibited multiple remarkable chalcogen bonding (ChB) interactions in the solid state, which were studied theoretically.
Nitric Oxide Is Essential for Melatonin to Enhance Nitrate Tolerance of Cucumber Seedlings
Authors: Zhang Yiting , Liu Ailong , Hao Yanwei , Su Wei , Sun Guangwen , Song Shiwei , Liu Houcheng , Chen Riyuan
Published: September 2022

Melatonin (MT) and nitric oxide (NO) in plants can function cooperatively to alleviate salt stress, sodic alkaline stress and immune response, as well as adventitious root formation. The interaction of MT and NO on the nitrate stress tolerance of cucumber seedlings are not well understood. We investigated the effects of exogenous MT, NO donor (SNP) and NO scavenger (cPTIO) on the growth; photosynthesis; characteristics of root morphological; accumulation of mineral elements, endogenous NO, MT, IAA and ABA; and related genes expression in cucumber (Cucumis sativus L. “Jin You No. 1”) seedlings grown under high nitrate condition (HN). The results showed that MT and NO independently alleviated the inhibition of growth and photosynthesis capacity of cucumber seedlings under nitrate stress. NO was required for MT to enhance the root activity, root length, lateral root number and the accumulation of calcium, magnesium and iron in the roots of cucumber seedlings grown under nitrate stress. Consistently, the expression of adventitious rootless 1 gene (CsARL1) was modulated. Furthermore, exogenous MT induced accumulation of endogenous MT, NO, indole-3-acetic acid (IAA) and abscisic acid (ABA), mainly within 24 h after treatment, in which MT and NO were further increased at 48 h and 96 h, IAA and ABA were further increased at 16 h in the presence of SNP. In contrast, the accumulation of endogenous IAA, MT and ABA slightly decreased within 24 h, NO significantly decreased at 192 h in the presence of cPTIO. Correspondingly, the expression levels of genes involved in nitrogen metabolism (CsNR1 and CsNR2), MT metabolism (CsT5H, CsSNAT2 and Cs2-ODD33), auxin carriers and response factors (CsAUX1, CsGH3.5, CsARF17), ABA synthesis and catabolism (CsNCED1, CsNCED3 and CsCYP707A1) were upregulated by MT, in which CsNR1, CsNR2, CsAUX1, CsNCED3 and CsT5H were further induced in the presence of SNP in roots of cucumber seedlings. These observations indicated that NO act as a crucial factor in MT, alleviating nitrate stress through regulating the mechanism of root growth in cucumber seedlings.
Behaviors of Organic Ligands and Phosphate during Biochar-Driven Nitrate Adsorption in the Presence of Low-Molecular-Weight Organic Acids
Authors: Xiong Wenming , Li Yongjun , Ying Jidong , Lin Chuxia , Qin Junhao
Published: September 2022

A batch experiment was conducted to examine the behavior of nitrate, organic ligands, and phosphate in the co-presence of biochar and three common low-molecular-weight organic acids (LMWOAs). The results show that citrate, oxalate, and malate ions competed with nitrate ion for the available adsorption sites on the biochar surfaces. The removal rate of LMWOA ligands by the biochar via adsorption grew with increasing solution pH. The adsorbed divalent organic ligands created negatively charged sites to allow binding of cationic metal nitrate complexes. A higher degree of biochar surface protonation does not necessarily enhance nitrate adsorption. More acidic conditions formed under a higher dose of LMWOAs tended to make organic ligands predominantly in monovalent forms and failed to create negatively charged sites to bind cationic metal nitrate complexes. This could adversely affect nitrate removal efficiency in the investigated systems. LMWOAs caused significant release of phosphate from the biochar. The phosphate in the malic acid treatment tended to decrease over time, while the opposite was observed in the citric- and oxalic-acid treatments. This was caused by re-immobilization of phosphate in the former due to the marked increase in solution pH over time.
Antimicrobial Activities of Saponaria cypria Boiss. Root Extracts, and the Identification of Nine Saponins and Six Phenolic Compounds
Authors: Charalambous Despina , Christoforou Michalis , Kitiri Elina N. , Andreou Marios , Partassides Dora , Papachrysostomou Christoforos , Frantzi Myriam , Karikas George A. , Pantelidou Maria
Published: September 2022

The purpose of this study was to identify the chemical components in root extracts of Saponaria cypria, an endemic species of Cyprus. Subsequently, the synergistic bioactivity of its root extracts through different extraction procedures was also investigated for the first time. A total of nine saponins, along with six phenolic compounds, were identified and quantified using the UHPLC/Q-TOF-MS method. Additionally, S. cypria root extracts demonstrated antibacterial potential against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Salmonella enteritidis. S. aureus presented the highest susceptibility among all bacteria tested. These findings provide the first phytochemical data regarding the saponin, phenolic content and antimicrobial activity of S. cypria extracts, indicating that the Cyprus saponaria species is a rich natural source for bioactive compounds with a potentially wider bioactivity spectrum.
Ligand-Free Signaling of G-Protein-Coupled Receptors: Relevance to μ Opioid Receptors in Analgesia and Addiction
Authors: Sadee Wolfgang , McKew John C.
Published: September 2022

Numerous G-protein-coupled receptors (GPCRs) display ligand-free basal signaling with potential physiological functions, a target in drug development. As an example, the μ opioid receptor (MOR) signals in ligand-free form (MOR-μ*), influencing opioid responses. In addition, agonists bind to MOR but can dissociate upon MOR activation, with ligand-free MOR-μ* carrying out signaling. Opioid pain therapy is effective but incurs adverse effects (ADRs) and risk of opioid use disorder (OUD). Sustained opioid agonist exposure increases persistent basal MOR-μ* activity, which could be a driving force for OUD and ADRs. Antagonists competitively prevent resting MOR (MOR-μ) activation to MOR-μ*, while common antagonists, such as naloxone and naltrexone, also bind to and block ligand-free MOR-μ*, acting as potent inverse agonists. A neutral antagonist, 6β-naltrexol (6BN), binds to but does not block MOR-μ*, preventing MOR-μ activation only competitively with reduced potency. We hypothesize that 6BN gradually accelerates MOR-μ* reversal to resting-state MOR-μ. Thus, 6BN potently prevents opioid dependence in rodents, at doses well below those blocking antinociception or causing withdrawal. Acting as a ‘retrograde addiction modulator’, 6BN could represent a novel class of therapeutics for OUD. Further studies need to address regulation of MOR-μ* and, more broadly, the physiological and pharmacological significance of ligand-free signaling in GPCRs.