bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory T-Cell Enhancement, Expression of Adhesion Molecules, and Production of Anti-Inflammatory Factors Are Differentially Modulated by Spheroid-Cultured Mesenchymal Stem Cells
Authors: Silva-Carvalho Amandda Évelin , da Silva Ingrid Gracielle Martins da , Corrêa José Raimundo , Saldanha-Araujo Felipe
Published: November 2022

The culture of mesenchymal stem cells (MSCs) as spheroids promotes a more physiological cellular behavior, as it more accurately reflects the biological microenvironment. Nevertheless, mixed results have been found regarding the immunosuppressive properties of spheroid-cultured MSCs (3D-MSCs), the mechanisms of immunoregulation of 3D-MSCs being scarcely described at this point. In the present study, we constructed spheroids from MSCs and compared their immunosuppressive potential with that of MSCs cultured in monolayer (2D-MSCs). First, we evaluated the ability of 2D-MSCs and 3D-MSCs to control the activation and proliferation of T-cells. Next, we evaluated the percentage of regulatory T-cells (Tregs) after the co-culturing of peripheral blood mononuclear cells (PBMCs) with 2D-MSCs and 3D-MSCs. Finally, we investigated the expression of adhesion molecules, as well as the expressions of several anti-inflammatory transcripts in 2D-MSCs and 3D-MSCs maintained in both inflammatory and non-inflammatory conditions. Interestingly, our data show that several anti-inflammatory genes are up-regulated in 3D-MSCs, and that these cells can control T-cell proliferation. Nevertheless, 2D-MSCs are more efficient in suppressing the immune cell proliferation. Importantly, contrary to what was observed in 3D-MSCs, the expressions of ICAM-1 and VCAM-1 are significantly upregulated in 2D-MSCs exposed to an inflammatory environment. Furthermore, only 2D-MSCs are able to promote the enhancement of Tregs. Taken together, our data clearly show that the immunosuppressive potential of MSCs is significantly impacted by their shape, and highlights the important role of cell–cell adhesion molecules for optimal MSC immunomodulatory function.
Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets
Authors: di Meo Nicola Antonio , Lasorsa Francesco , Rutigliano Monica , Loizzo Davide , Ferro Matteo , Stella Alessandro , Bizzoca Cinzia , Vincenti Leonardo , Pandolfo Savio Domenico , Autorino Riccardo , Crocetto Felice , Montanari Emanuele , Spilotros Marco , Battaglia Michele , Ditonno Pasquale , Lucarelli Giuseppe
Published: November 2022

Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.
Long-Term In Vitro Assessment of Biodegradable Radiopaque Composites for Fiducial Marker Fabrication
Authors: Górecka Żaneta , Choińska Emilia , Heljak Marcin , Święszkowski Wojciech
Published: November 2022

Biodegradable polymer-based composite materials may be successfully utilised to fabricate fiducial markers (FMs), which are intended to precisely label tumour margins during image-guided surgery or radiotherapy. However, due to matrix degradability, the stability of the functional properties of FMs depends on the chosen polymer. Thus, this study aimed to investigate novel radiopaque composites which varied in the polymeric matrix—polycaprolactone (PCL), poly(L-lactide-co-caprolactone) (P[LAcoCL]) with two molar ratios (70:30 and 85:15), and poly(L-lactide-co-glycolide) (with molar ratio 82:18). The radiopaque component of the materials was a mixture of barium sulphate and hydroxyapatite. The changes in water contact angle, stiffness, and radiopacity occurring during the 24-week-long degradation experiment were examined for the first time. This study comprehensively analyses the microstructural causes of composites behaviour within degradation experiments using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), gel permitted chromatography (GPC), and scanning electron microscopy (SEM). The obtained results suggest that the utilized biodegradable matrix plays an essential role in radiopaque composite properties and stability thereof. This long-term in vitro assessment enabled a comparison of the materials and aided in choosing the most favourable composite for FMs’ fabrication.
Mechanism of Phase Separation in Aqueous Two-Phase Systems
Authors: Titus Amber R. , Madeira Pedro P. , Ferreira Luisa A. , Chernyak Vladimir Y. , Uversky Vladimir N. , Zaslavsky Boris Y.
Published: November 2022

Liquid-liquid phase separation underlies the formation of membrane-less organelles inside living cells. The mechanism of this process can be examined using simple aqueous mixtures of two or more solutes, which are able to phase separate at specific concentration thresholds. This work presents the first experimental evidence that mesoscopic changes precede visually detected macroscopic phase separation in aqueous mixtures of two polymers and a single polymer and salt. Dynamic light scattering (DLS) analysis indicates the formation of mesoscopic polymer agglomerates in these systems. These agglomerates increase in size with increasing polymer concentrations prior to visual phase separation. Such mesoscopic changes are paralleled by changes in water structure as evidenced by Attenuated Total Reflection—Fourier Transform Infrared (ATR-FTIR) spectroscopic analysis of OH-stretch bands. Through OH-stretch band analysis, we obtain quantitative estimates of the relative fractions of four subpopulations of water structures coexisting in aqueous solutions. These estimates indicate that abrupt changes in hydrogen bond arrangement take place at concentrations below the threshold of macroscopic phase separation. We used these experimental observations to develop a model of phase separation in aqueous media.
4-Hydroxynonenal Modulates Blood–Brain Barrier Permeability In Vitro through Changes in Lipid Composition and Oxidative Status of Endothelial Cells and Astrocytes
Authors: Cindrić Marina , Čipak Gašparović Ana , Milković Lidija , Bujak Ivana Tartaro , Mihaljević Branka , Žarković Neven , Žarković Kamelija
Published: November 2022

Blood brain barrier (BBB) is a dynamic interface responsible for proper functioning of brain, but also a major obstacle for effective treatment of neurological diseases. Increased levels of free radicals, in high ferrous and high lipid content surrounding, induce lipid peroxidation, leading to production of 4-hydroxynonenal (HNE). HNE modifies all key proteins responsible for proper brain functioning thus playing a major role in the onset of neurological diseases. To investigate HNE effects on BBB permeability, we developed two in vitro BBB models–‘physiological’ and ‘pathological’. The latter mimicked HNE modified extracellular matrix under oxidative stress conditions in brain pathologies. We showed that exogenous HNE induce activation of antioxidative defense systems by increasing catalase activity and glutathione content as well as reducing lipid peroxide levels in endothelial cells and astrocytes of ‘physiological’ model. While in ‘pathological’ model, exogenous HNE further increased lipid peroxidation levels of endothelial cells and astrocytes, followed by increase in Nrf2 and glutathione levels in endothelial cells. At lipid composition level, HNE caused increase in ω3 polyunsaturated fatty acid (PUFA) level in endothelial cells, followed by decrease in ω3 PUFA level and increase in monounsaturated fatty acid level in astrocytes. Using these models, we showed for the first time that HNE in ‘pathological’ model can reduce BBB permeability.
Obesity-Associated Vitamin D Deficiency Correlates with Adipose Tissue DNA Hypomethylation, Inflammation, and Vascular Dysfunction
Authors: Mirza Imaduddin , Mohamed Ariej , Deen Hania , Balaji Swetha , Elsabbahi Duaa , Munasser Amier , Naquiallah Dina , Abdulbaseer Uzma , Hassan Chandra , Masrur Mario , Bianco Francesco M. , Ali Mohamed M. , Mahmoud Abeer M.
Published: November 2022

Vitamin D (VD) deficiency is a hallmark of obesity and vascular dysfunction. We sought to test the hypothesis that VD deficiency may contribute to obesity-related vascular dysfunction by inducing adipokine hypomethylation and augmented expression. To this end, we collected blood and adipose tissues (ATs) from a cohort of 77 obese participants who were classified as having mild, moderate, or severe VD deficiency. The body composition, vascular reactivity, cardiometabolic profiles, and DNA methylation of 94 inflammation-related adipokines were measured. Our results show that higher degrees of VD deficiency were associated with lower DNA methylation and induced the expression of inflammatory adipokines such as B-cell lymphoma 6 (BCL6), C-X-C Motif Chemokine Ligand 8 (CXCL8), histone deacetylase 5 (HDAC5), interleukin 12A (IL12A), and nuclear factor κB (NFκB) in the ATs. They were also associated with higher BMI and total and visceral fat mass, impaired insulin sensitivity and lipid profiles, AT hypoxia, and higher concentrations of circulating inflammatory markers. Moderate and severe VD deficiency correlated with impaired vasoreactivity of the brachial artery and AT-isolated arterioles, reduced nitric oxide generation, and increased arterial stiffness. In a multivariate regression analysis, the VD deficiency level strongly predicted the adipokine methylation score, systemic inflammation, and microvascular dysfunction. In conclusion, our findings suggest that VD deficiency is a possible contributor to obesity-related adipokine hypomethylation, inflammation, and vascular dysfunction.
The Dual PDE7-GSK3β Inhibitor, VP3.15, as Neuroprotective Disease-Modifying Treatment in a Model of Primary Progressive Multiple Sclerosis
Authors: Benítez-Fernández Rocio , Gil Carmen , Guaza Carmen , Mestre Leyre , Martínez Ana
Published: November 2022

Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune and degenerative disease with axonal damage and demyelination as its main features. Its dual neurological and autoimmune nature makes it a disease that is difficult to treat. Treatments that simultaneously stop the immune response while protecting and repairing the nervous system are urgent. That is of utmost importance for the primary progressive multiple sclerosis (PPMS), a rare and severe variant of MS, characterized by worsening neurological function from the onset of symptoms. In this sense, inhibitors of glycogen synthase kinase 3β (GSK3β) and phosphodiesterase 7 (PDE7) have recently shown great therapeutic potential for the treatment of demyelinating diseases. Here we investigated a dual inhibitor of these two targets, the small molecule VP3.15, in a preclinical model, which resembles primary-progressive MS (PPMS), the Theiler’s mouse encephalomyelitis virus-induced demyelinated disease (TMEV-IDD). In our study, VP3.15 ameliorates the disease course improving motor deficits of infected mice. Chronic treatment with VP3.15 also showed significant efficacy in the immunomodulation process, as well as in the proliferation and differentiation of oligodendroglial precursors, improving the preservation of myelin and axonal integrity. Therefore, our results support a treatment with the safe VP3.15 as an integrative therapeutic strategy for the treatment of PPMS.
Highly Selective Electrochemical CO2 Reduction to C2 Products on a g-C3N4-Supported Copper-Based Catalyst
Authors: Yan Zijun , Wu Tao
Published: November 2022

Herein, a novel approach used to enhance the conversion of electrochemical CO2 reduction (CO2R), as well as the capacity to produce C2 products, is reported. A copper oxide catalyst supported by graphite phase carbon nitride (CuO/g-C3N4) was prepared using a one-step hydrothermal method and exhibited a better performance than pure copper oxide nanosheets (CuO NSs) and spherical copper oxide particles (CuO SPs). The Faradaic efficiency reached 64.7% for all the C2 products, specifically 37.0% for C2H4, with a good durability at −1.0 V vs. RHE. The results suggest that the interaction between CuO and the two-dimensional g-C3N4 planes promoted CO2 adsorption, its activation and C-C coupling. This work offers a practical method that can be used to enhance the activity of electrochemical CO2R and the selectivity of C2 products through synergistic effects.
The Hidden Secrets of the Dental Calculus: Calibration of a Mass Spectrometry Protocol for Dental Calculus Protein Analysis
Authors: Bender Omer , Megreli Dana , Gavish Talia , Meyrom Noa , Zamir Neta , May Hila , Sarig Rachel , Bar Daniel Z.
Published: November 2022

Dental calculus is a solid deposit that forms and accumulates on the tooth surface, entrapping oral microorganisms, biomolecules, and other micro-debris found in the oral cavity. A mass spectrometry analysis of its protein content opens a vista into the subject’s diet, oral flora, and even some aspects of health, thus providing new insight and expanding our knowledge of archaic cultures. Multiple experimental protocols have been proposed for the optimal extraction of proteins from dental calculus. Herein, we compared various experimental conditions in order to calibrate and validate a protocol for protein extraction. Our results show that a high concentration of acetic acid followed by mechanical crushing and sonication provided the highest protein yield, while acetone precipitation enabled the identification of more distinct proteins. We validated this protocol using archeological samples, identifying human and microbial proteins in specimens from the eighth and seventeenth centuries (approximately 250–1300 years ago). These findings demonstrate that the developed protocol is useful for studying excavated archaeological samples and that it might be utilized to explore the biohistory, dietary habits, and microbiome of archaic populations.
High-frequency Contactless Sensor for the Detection of Heparin-Induced Thrombocytopenia Antibodies via Platelet Aggregation
Authors: Khan Nida Zaman , Martin Daniel , Pliquett Uwe , Zaikou Yahor , Thomas Nacke , Heinrich Doris , Köhler J. Michael , Nguyen Thi-Huong
Published: November 2022

Heparin-induced thrombocytopenia (HIT), a severe autoimmune disorder, occurs in patients undergoing heparin therapy. The presence of platelet-activating antibodies against platelet factor 4/Heparin in the blood confirms patients suffering from HIT. The most widely used methods for HIT diagnosis are immunoassays but the results only suit to rule out HIT as the assays provide only around 50% specificity. To confirm HIT, samples with positive results in immunoassays are retested in functional assays (>98% specificity) that track platelet-activating antibodies via platelet aggregation. However, the protocols in functional assays are either time-consuming (due to the requirement of the detection of serotonin release) or require highly trained staff for the visualization of platelets. Here, we applied a cheap and easy-to-use contactless sensor, which employs high-frequency microwaves to detect the changes in the resonant frequency caused by platelet aggregation/activation. Analysis of change in conductivity and permittivity allowed us to distinguish between HIT-like (KKO) and non-HIT-like (RTO) antibodies. KKO caused a stronger reduction of conductivity of platelet samples than RTO. Our results imply that the high-frequency contactless sensor can be a promising approach for the development of a better and easier method for the detection of HIT.
Computational Tactics for Precision Cancer Network Biology
Authors: Park Heewon , Miyano Satoru
Published: November 2022

Network biology has garnered tremendous attention in understanding complex systems of cancer, because the mechanisms underlying cancer involve the perturbations in the specific function of molecular networks, rather than a disorder of a single gene. In this article, we review the various computational tactics for gene regulatory network analysis, focused especially on personalized anti-cancer therapy. This paper covers three major topics: (1) cell line’s (or patient’s) cancer characteristics specific gene regulatory network estimation, which enables us to reveal molecular interplays under varying conditions of cancer characteristics of cell lines (or patient); (2) computational approaches to interpret the multitudinous and massive networks; (3) network-based application to uncover molecular mechanisms of cancer and related marker identification. We expect that this review will help readers understand personalized computational network biology that plays a significant role in precision cancer medicine.
The Role of Insulin Signaling in Hippocampal-Related Diseases: A Focus on Alzheimer’s Disease
Authors: Liu Qi , Wang Zixu , Cao Jing , Dong Yulan , Chen Yaoxing
Published: November 2022

Alzheimer’s disease (AD) is a global concern and has become a major public health event affecting human health. Insulin is a metabolic hormone secreted mainly by the peripheral tissue pancreas. In recent years, more and more evidence has proved that insulin regulates various functions of the brain. The hippocampus, one of the earliest brain regions affected by AD, is widely distributed with insulin receptors. Studies have shown that type 2 diabetes mellitus, characterized by insulin resistance, is closely related to AD, which has drawn extensive attention to the relationship between hippocampal insulin signaling and AD. Therefore, we provide an overview of intranasal insulin administration on memory and its underlying mechanism. We also highlight the molecular link between hippocampal insulin resistance and AD and provide a theoretical basis for finding new therapeutic targets for AD in clinical practice.
Effect of Bladder Injection of OnabotulinumtoxinA on the Central Expression of Genes Associated with the Control of the Lower Urinary Tract: A Study in Normal Rats
Authors: Markopoulou Soultana , Vardouli Lina , Dimitriadis Fotios , Psalla Dimitra , Lambropoulos Alexandros , Apostolidis Apostolos
Published: November 2022

To investigate a possible central mechanism of action of Botulinum toxin A (BoNT/A) following injection in the bladder, complementary to the acknowledged peripheral bladder effect, we studied changes in the expression of neuropeptides and receptors involved in lower urinary tract function in the spinal cord (SC) and dorsal root ganglia (DRG) of normal rats following BoNT/A bladder injection. Thirty-six Sprague-Dawley rats, divided into three groups of n = 12, received bladder injections of 2U or 5U OnabotulinumtoxinA (BOTOX®), or saline. Six animals from each group were sacrificed on days 7 and 14. Expression of Tachykinin 1 (Tac1), capsaicin receptor (TRPV1), neuropeptide Y (NPY), proenkephalin (PENK) and muscarinic receptors M1, M2, M3, was evaluated in the bladder, L6-S1 DRG, and SC segments using real-time PCR and Western blotting. Real-time PCR revealed increased expression of NPY in all tissues except for SC, and increased TRPV1 and PENK expression in DRG and SC, whereas expression of Tac1, M1 and M2 was decreased. Less significant changes were noted in protein levels. These findings suggest that bladder injections of OnabotulinumtoxinA may be followed by changes in the expression of sensory, sympathetic and cholinergic bladder function regulators at the DRG/SC level.
1,2,3,4,6-O-Pentagalloylglucose Protects against Acute Lung Injury by Activating the AMPK/PI3K/Akt/Nrf2 Pathway
Authors: Zhang Qi , Cheng Sai , Xin Zhiming , Deng Haohua , Wang Ying , Li Qiang , Wu Gangwei , Chen Wei
Published: November 2022

An acute lung injury (ALI) is a serious lung disease with a high mortality rate, warranting the development of novel therapies. Previously, we reported that 1,2,3,4,6-O-pentagalloylglucose (PGG) could afford protection against ALI, however, the PGG-mediated protective effects remain elusive. Herein, PGG (60 and 30 mg/kg) markedly inhibited the lung wet/drug weight ratio and attenuated histological changes in the lungs (p < 0.05). A pretreatment with PGG (60 and 30 mg/kg) reduced the number of total leukocytes and the production of pro-inflammatory cytokines IL-6 and IL-1β in bronchoalveolar lavage fluid (p < 0.05). In addition, PGG (60 and 30 mg/kg) also attenuated oxidative stress by reducing the formation of formation and the depletion of superoxide dismutase to treat an ALI (p < 0.05). To further explore the PGG-induced mechanism against an ALI, we screened the PGG pathway using immunohistochemical analysis, immunofluorescence assays, and Western blotting (WB). WB revealed that the expression levels of adenosine monophosphate-activated protein kinase phosphorylation (p-AMPK), phosphoinositide 3-kinase (PI3K), protein kinase B phosphorylation (P-Akt), and nuclear factor erythroid 2-related factor (Nrf2) were significantly higher in the PGG group (60 and 30 mg/kg) than in the lipopolysaccharide group (p < 0.05); these findings were confirmed by the immunohistochemical and immunofluorescence results. Accordingly, PGG could be effective against an ALI by inhibiting inflammation and oxidative stress via AMPK/PI3K/Akt/Nrf2 signaling, allowing for the potential development of this as a natural drug against an ALI.
Morusin Protected Ruminal Epithelial Cells against Lipopolysaccharide-Induced Inflammation through Inhibiting EGFR-AKT/NF-κB Signaling and Improving Barrier Functions
Authors: Yang Chunlei , Deng Xiangfei , Wu Linjun , Jiang Tianrui , Fu Zhengwei , Li Jinjun
Published: November 2022

Using phytogenic extracts for preventing or treating rumen epithelial inflammatory injury is a potential alternative to antibiotic use due to their residue-free characteristics. In this study, the efficacy of Morus root bark extract Morusin on ruminal epithelial cells (RECs) against pathogenic stimulus was investigated for the first time. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and quantitative real-time polymerase chain reaction (qPCR) results showed that the Morusin did not affect the cell viability of RECs and exerted anti-inflammatory effects in a concentration-dependent manner. Transcriptome analysis further revealed that the Morusin significantly downregulated the inflammatory-response-related cell signaling, while it upregulated the cell-proliferation-inhibition- and barrier-function-related processes in RECs upon lipopolysaccharide (LPS) stimulation. The epidermal growth factor receptor (EGFR) blocking and immunoblotting analysis further confirmed that the Morusin suppressed LPS-induced inflammation in RECs by downregulating the phosphorylation of protein kinase B (AKT) and nuclear factor-kappaB (NF-κB) p65 protein via inhibiting the EGFR signaling. These findings demonstrate the protective roles of Morusin in LPS-induced inflammation in RECs.
Self-Diffusion in Confined Water: A Comparison between the Dynamics of Supercooled Water in Hydrophobic Carbon Nanotubes and Hydrophilic Porous Silica
Authors: Fardis Michael , Karagianni Marina , Gkoura Lydia , Papavassiliou George
Published: November 2022

Confined liquids are model systems for the study of the metastable supercooled state, especially for bulk water, in which the onset of crystallization below 230 K hinders the application of experimental techniques. Nevertheless, in addition to suppressing crystallization, confinement at the nanoscale drastically alters the properties of water. Evidently, the behavior of confined water depends critically on the nature of the confining environment and the interactions of confined water molecules with the confining matrix. A comparative study of the dynamics of water under hydrophobic and hydrophilic confinement could therefore help to clarify the underlying interactions. As we demonstrate in this work using a few representative results from the relevant literature, the accurate assessment of the translational mobility of water molecules, especially in the supercooled state, can unmistakably distinguish between the hydrophilic and hydrophobic nature of the confining environments. Among the numerous experimental methods currently available, we selected nuclear magnetic resonance (NMR) in a field gradient, which directly measures the macroscopic translational self-diffusion coefficient, and quasi-elastic neutron scattering (QENS), which can determine the microscopic translational dynamics of the water molecules. Dielectric relaxation, which probes the re-orientational degrees of freedom, are also discussed.
TGF-β Signaling in Metastatic Colorectal Cancer (mCRC): From Underlying Mechanism to Potential Applications in Clinical Development
Authors: Li Xiaoshuang , Wu Yanmin , Tian Tian
Published: November 2022

Colorectal cancer (CRC) is a serious public health issue, and it has the leading incidence and mortality among malignant tumors worldwide. CRC patients with metastasis in the liver, lung or other distant sites always have poor prognosis. Thus, there is an urgent need to discover the underlying mechanisms of metastatic colorectal cancer (mCRC) and to develop optimal therapy for mCRC. Transforming growth factor-β (TGF-β) signaling plays a significant role in various physiologic and pathologic processes, and aberrant TGF-β signal transduction contributes to mCRC progression. In this review, we summarize the alterations of the TGF-β signaling pathway in mCRC patients, the functional mechanisms of TGF-β signaling, its promotion of epithelial–mesenchymal transition, its facilitation of angiogenesis, its suppression of anti-tumor activity of immune cells in the microenvironment and its contribution to stemness of CRC cells. We also discuss the possible applications of TGF-β signaling in mCRC diagnosis, prognosis and targeted therapies in clinical trials. Hopefully, these research advances in TGF-β signaling in mCRC will improve the development of new strategies that can be combined with molecular targeted therapy, immunotherapy and traditional therapies to achieve better efficacy and benefit mCRC patients in the near future.
Influence of the Photodegradation of Azathioprine on DNA and Cells
Authors: Bunea Mihaela-Cristina , Diculescu Victor-Constantin , Enculescu Monica , Oprea Daniela , Enache Teodor Adrian
Published: November 2022

Azathioprine (AZA) is a pharmacologic immunosuppressive agent administrated in various conditions such as autoimmune disease or to prevent the rejection of organ transplantation. The mechanism of action is based on its biologically active metabolite 6-mercaptopurine (6-MP), which is converted, among others, into thioguanine nucleotides capable of incorporating into replicating DNA, which may act as a strong UV chromophore and trigger DNA oxidation. The interaction between azathioprine and DNA, before and after exposure to solar simulator radiation, was investigated using UV–vis spectrometry and differential pulse voltammetry at a glassy carbon electrode. The results indicated that the interaction of AZA with UV radiation was pH-dependent and occurred with the formation of several metabolites, which induced oxidative damage in DNA, and the formation of DNA-metabolite adducts. Moreover, the viability assays obtained for the L929 cell culture showed that both azathioprine and degraded azathioprine induced a decrease in cell proliferation.
Toward a Green and Sustainable Silver Conservation: Development and Validation of Chitosan-Based Protective Coatings
Authors: Boccaccini Francesca , Giuliani Chiara , Pascucci Marianna , Riccucci Cristina , Messina Elena , Staccioli Maria Paola , Ingo Gabriel Maria , Di Carlo Gabriella
Published: November 2022

When exposed to air, silver artifacts undergo an unpleasant darkening and shiny loss, commonly known as tarnishing. At the present, the development of protective coatings by using eco-friendly and biocompatible materials, able to ensure high transparency and to hinder the degradation of silver objects, remains a huge challenge. In this study, chitosan was used for the first time to realize sustainable coatings for silver protection. Both pure and benzotriazole-containing chitosan coatings were prepared and applied on sterling silver disks. A commercial product based on acrylic resin was used as a reference. The aesthetic features and protective properties of these coatings were evaluated by performing two different types of aging treatments. In particular, the assessment of the protective efficacy was carried out by reproducing both highly aggressive polluted environments and real-like museums’ storage conditions. In the first case, chitosan-based coatings with benzotriazole performed better, whereas in storage conditions all the chitosan films showed comparable efficacy. Compositional, morphological and structural analyses were used to evaluate the protective properties of the coatings and to detect any physical or chemical modifications after the aging treatments. Our findings reveal that the two different testing methods provide complementary information. Moreover, chitosan coatings can achieve protective efficacy comparable with that of the commercial product but using non-toxic solvents and a renewable biopolymer. Chitosan coatings, designed for cultural heritage conservation, are thus promising for the protection of common sterling silver objects.
Object Detection Based on YOLOv5 and GhostNet for Orchard Pests
Authors: Zhang Yitao , Cai Weiming , Fan Shengli , Song Ruiyin , Jin Jing
Published: November 2022

Real-time detection and identification of orchard pests is related to the economy of the orchard industry. Using lab picture collections and pictures from web crawling, a dataset of common pests in orchards has been created. It contains 24,748 color images and covers seven types of orchard pests. Based on this dataset, this paper combines YOLOv5 and GhostNet and explains the benefits of this method using feature maps, heatmaps and loss curve. The results show that the mAP of the proposed method increases by 1.5% compared to the original YOLOv5, with 2× or 3× fewer parameters, less GFLOPs and the same or less detection time. Considering the fewer parameters of the Ghost convolution, our new method can reach a higher mAP with the same epochs. Smaller neural networks are more feasible to deploy on FPGAs and other embedding devices which have limited memory. This research provides a method to deploy the algorithm on embedding devices.
Convenient Access to Ferrocene Fused aza-Heterocycles via the Intramolecular Ritter Reaction: Synthesis of Novel Racemic Planar-Chiral 3,4-Dihydroferroceno[c]pyridines and 1H-Ferroceno[c]pyrroles
Authors: Rozhkova Yuliya S. , Plekhanova Irina V. , Gorbunov Alexey A. , Shklyaev Yurii V.
Published: November 2022

An efficient and easy approach to the synthesis of novel racemic planar-chiral 3,4-dihydroferroceno[c]pyridines and 1H-ferroceno[c]pyrroles via the intramolecular Ritter reaction of 2-ferrocenyl-3,3-dimethylbutan-2-ol with nitriles and thiocyanates in the presence of MeSO3H was developed. Aromatic and aliphatic nitriles, phenylacetonitriles, and β-oxonitriles produced exclusively 3,4-dihydroferroceno[c]pyridines. The condensation of 2-ferrocenyl-3,3-dimethylbutan-2-ol with various thiocyanates, including alkyl thiocyanates, benzyl thiocyanate, and ethyl 2-thiocyanatoacetate, yielded not only 3,4-dihydroferroceno[c]pyridines but also 1H-ferroceno[c]pyrroles. The selectivity of these reactions depended on the temperature and the order of addition. The size of substituents at the α-position to the sulfur atom of thiocyanates also had a significant effect on the distribution of products.
A Non-Invasive Method of Estimating Populations of Tomicus Piniperda on Scots Pine (Pinus Sylvestris L.)
Authors: Zubek Karol , Czerwik-Marcinkowska Joanna , Borkowski Andrzej
Published: November 2022

The fully non-invasive method presented here can be used to evaluate Tomicus piniperda L. population sizes in areas subject to strict protection. Data were collected in 2021–2022 in forests containing P. sylvestris, with different stand structures, in the Suchedniowsko-Oblęgorski Landscape Park, Poland. Entomological analyses were carried out on natural traps made from live uncolonised trees. Stepwise regression was used to describe the size of T. piniperda populations. From a set of features representing stem colonisation parameters, stem traits and habitat, the following had a significant effect (p < 0.05) on the total number of galleries of T. piniperda on stems: (1) the number of T. piniperda maternal tunnels in the sixth stem section covering 2.5% of the total length, (2) the length of the stem section with bark thickness greater than 7 mm, and (3) stand structure (homogeneous Scots pine stands). The model can explain 93% (Radj2=0.9333) of the variability in the total number of T. piniperda galleries on trap trees. The mean relative error of estimation is 20.1%. The proposed method is particularly valuable in a climate context. The data obtained enable the prediction of the direct effects of climate change on the population dynamics of T. piniperda in natural forests.
Correction: Żerebecki et al. (2022). I Want to Be You(r Friend): An Investigation of the Effects of Gendered Personality Traits on Engagement with Different Modern Family Characters. Journalism and Media 3: 362–81
Authors: Żerebecki Bartosz G. , van der Vliet Esther , Kneer Julia
Published: November 2022

In the original publication, there was a mistake in Table 1, Table 3 and Table 5 [...]
Characteristics and Trends of COVID-19 Infection in a Tertiary Hospital in Romania: A Retrospective Study
Authors: Loghin Isabela Ioana , Mihai Ioana Florina , Roşu Manuel Florin , Diaconu Iulia Elena , Vâţă Andrei , Popa Radu , Luca Mihaela Cătălina
Published: November 2022

(1) Background: The outbreak of the COVID-19 pandemic represented a real challenge for all of humanity. Characterized by a complex spectrum of signs and symptoms, by various severity degrees, the disease spread rapidly around the world. After more than two and half years since the beginning of COVID-19 pandemic, in the context of a paradoxical, enigmatic, and relentless COVID-19, the objective of the current study was to evaluate the characteristics and evolution of patients with SARS-CoV-2 infection, hospitalized in “St. Parascheva” Clinical Hospital of Infectious Diseases (Iasi, Romania). (2) Methods: This is a retrospective study that used the medical database recorded between July and November 2021 in order to highlight the characteristics of SARS-CoV-2 infection in patients from the northeastern region of Romania. (3) Results: We enrolled in the study a total of 1732 SARS-CoV-2 infected patients, mean age 67 ± 3.4 years, the female gender predominating (987 cases; 56.98%) as well as patients from the urban environment (982 patients; 56.69%). Moderate form of the disease predominated (814 cases; 47%), pulmonary imaging changes were found in 1042 (60.16%) cases, and 1242 (71.71%) patients had at least one underlying disease. After a median length of hospitalization of 9.5 days, 1359 (78.46%) patients were discharged cured, 48 (2.77%) were transferred to other services by decompensating the associated pathologies, 302 (17.43%) patients needed extensive support in the intensive care unit and there were 325 (18.76%) deaths. (4) Conclusions: The epidemiological characteristics of SARS-CoV-2 infection recorded in our study were mostly the same as characteristics of COVID-19 from all over the world.
Workforce Considerations When Building a Precision Medicine Program
Authors: Blout Zawatsky Carrie L. , Leonhard Jennifer R. , Bell Megan , Moore Michelle M. , Petry Natasha J. , Platt Dylan M. , Green Robert C. , Hajek Catherine , Christensen Kurt D.
Published: November 2022

This paper describes one healthcare system’s approach to strategically deploying genetic specialists and pharmacists to support the implementation of a precision medicine program. In 2013, Sanford Health initiated the development of a healthcare system-wide precision medicine program. Here, we report the necessary staffing including the genetic counselors, genetic counseling assistants, pharmacists, and geneticists. We examined the administrative and electronic medical records data to summarize genetic referrals over time as well as the uptake and results of an enterprise-wide genetic screening test. Between 2013 and 2020, the number of genetic specialists employed at Sanford Health increased by 190%, from 10.1 full-time equivalents (FTEs) to 29.3 FTEs. Over the same period, referrals from multiple provider types to genetic services increased by 423%, from 1438 referrals to 7517 referrals. Between 2018 and 2020, 11,771 patients received a genetic screening, with 4% identified with potential monogenic medically actionable predisposition (MAP) findings and 95% identified with at least one informative pharmacogenetic result. Of the MAP-positive patients, 85% had completed a session with a genetics provider. A strategic workforce staffing and deployment allowed Sanford Health to manage a new genetic screening program, which prompted a large increase in genetic referrals. This approach can be used as a template for other healthcare systems interested in the development of a precision medicine program.
Isolation of Scalimides A–L: β-Alanine-Bearing Scalarane Analogs from the Marine Sponge Spongia sp.
Authors: Shin A-Young , Lee Hyi-Seung , Lee Jihoon
Published: November 2022

A chemical investigation of a methanol extract of Spongia sp., a marine sponge collected from the Philippines, identified 12 unreported scalarane-type alkaloids—scalimides A–L (1–12)—together with two previously described scalarin derivatives. The elucidation of the structure of the scalaranes based on the interpretation of their NMR and HRMS data revealed that 1–12 featured a β-alanine-substituted E-ring but differed from each other through variations in their oxidation states and substitutions occurring at C16, C24, and C25. Evaluation of the antimicrobial activity of 1–12 against several Gram-positive and Gram-negative bacteria showed that 10 and 11 were active against Micrococcus luteus and Bacillus subtilis, respectively, with MIC values ranging from 4 to 16 μg/mL.
Orchestrated Response of Intracellular Zwitterionic Metabolites in Stress Adaptation of the Halophilic Heterotrophic Bacterium Pelagibaca bermudensis
Authors: Azizah Muhaiminatul , Pohnert Georg
Published: November 2022

Osmolytes are naturally occurring organic compounds that protect cells against various forms of stress. Highly polar, zwitterionic osmolytes are often used by marine algae and bacteria to counteract salinity or temperature stress. We investigated the effect of several stress conditions including different salinities, temperatures, and exposure to organic metabolites released by the alga Tetraselmis striata on the halophilic heterotrophic bacterium Pelagibaca bermudensis. Using ultra-high-performance liquid chromatography (UHPLC) on a ZIC-HILIC column and high-resolution electrospray ionization mass spectrometry, we simultaneously detected and quantified the eleven highly polar compounds dimethylsulfoxonium propionate (DMSOP), dimethylsulfoniopropionate (DMSP), gonyol, cysteinolic acid, ectoine, glycine betaine (GBT), carnitine, sarcosine, choline, proline, and 4-hydroxyproline. All compounds are newly described in P. bermudensis and potentially involved in physiological functions essential for bacterial survival under variable environmental conditions. We report that adaptation to various forms of stress is accomplished by adjusting the pattern and amount of the zwitterionic metabolites.
Insulin Pump Therapy Efficacy and Key Factors Influencing Adherence in Pediatric Population—A Narrative Review
Authors: Trandafir Laura Mihaela , Moisa Stefana Maria , Vlaiculescu Mihaela Victoria , Butnariu Lacramioara Ionela , Boca Laura Otilia , Constantin Maria Magdalena Leon , Lupu Paula Madalina , Brinza Crischentian , Temneanu Oana Raluca , Burlacu Alexandru
Published: November 2022

Objective: we aimed to highlight the state of the art in terms of pediatric population adherence to insulin pumps. This study intends to underline the significance of identifying and minimizing, to the greatest extent feasible, the factors that adversely affect the juvenile population’s adherence to insulin pump therapy. Materials and methods: articles from PubMed, Embase, and Science Direct databases were evaluated using the following search terms: adherence, pump insulin therapy, children, pediatric population, and type 1 diabetes, in combination with several synonyms such as compliance, treatment adherence, pump adherence, patient dropouts, and treatment refusal. Results: A better glycemic control is connected to a better adherence to diabetes management. We identify, enumerate, and discuss a number of variables which make it difficult to follow an insulin pump therapy regimen. Several key factors might improve adherence to insulin pump therapy: efficient communication between care provider and patients (including home-based video-visits), continuous diabetes education, family support and parental involvement, as well as informational, practical assistance, and emotional support from the society. Conclusions: every cause and obstacle that prevents young patients from adhering to insulin pumps optimally is an opportunity for intervention to improve glycemic control and, as a result, their quality of life.
Transosseous Suturing for the Correction of Juvenile Hallux Valgus: A Preliminary Case Series Study
Authors: Hung Wei-Chen , Yao Shu-Hsin , Wang Ting-Ming , Chen Chun-Ho
Published: November 2022

Background and Objectives: Many treatment modalities are available for juvenile hallux valgus. However, all of them have some disadvantages. Therefore, we developed a transosseous suturing procedure. Materials and Methods: Six patients (seven feet) with juvenile hallux valgus received transosseous suturing procedure. Clinical and radiological examinations were performed preoperatively and postoperatively. All patients underwent the soft tissue release procedure, followed by transosseous suturing with Fiberwire (in which sutures are anchored with mini plates). Results: The mean IMA and HVA decreased from 15.6° ± 2.6° to 7.3° ± 1.1° and 39.2° ± 3.3° to 12.5° ± 3.1°, respectively. Corrections achieved in the IMA and HVA of all patients were maintained through the last follow-up. The mean American Orthopedic Foot & Ankle Society score improved from 53.3 ± 3.5 to 86.9 ± 4.7 points. Conclusions: Based on these preliminary data, the transosseous suturing technique demonstrated satisfactory results and apparent improvements in the IMA and HVA without early complications.
Current Distribution in the Discharge Unit of a 10-Cell Vanadium Redox Flow Battery: Comparison of the Computational Model with Experiment
Authors: Glazkov Artem , Pichugov Roman , Loktionov Pavel , Konev Dmitry , Tolstel Dmitry , Petrov Mikhail , Antipov Anatoly , Vorotyntsev Mikhail
Published: November 2022

Shunting currents are among the main problems of all-vanadium redox flow battery stacks since, in addition to capacity losses, they cause negative effects associated with the local destruction of electrodes and bipolar plates. The values of both the shunting currents and their destructive effects on materials can be reduced at the battery development stage by adjusting the resistance of the electrolyte supply channels. The solution to this problem can be found using a calculation model for current distribution based on the current balance in the nodes as well as voltage drops and electromotive force in internal circuits according to Kirchhoff’s laws. This paper presents the verification of the model of current distribution in an all-vanadium redox flow battery stack of an original design that allows for the determination of membrane-electrode assembly resistances and electrolyte supply channels via direct measurements. Based on a comparison of the calculated and experimental values of the coulombic efficiency of charge–discharge cycles, the capacity fade associated with the crossover of vanadium compounds through the membrane has been determined.
Selective Separation Recovery of Copper and Arsenic from the Leaching Solution of Copper Soot
Authors: Yang Zhizhao , Zhang Yongbing , Zhou Hepeng , Luo Xianping , Tang Xuekun , Liu Zishuai
Published: November 2022

Through the main chemical reaction of metal ions and S2−, a new type of sulfide precipitant was first prepared and used to realize the selective separation recovery of copper and arsenic from the leaching solution of copper soot. It is proven by experimental results that the prepared sulfide precipitant could realize the efficient separation recovery of copper and arsenic. Indeed, the copper sulfide slag with Cu grade of about 47% and arsenic trisulfide slag with As operation recovery of about 98% could be obtained. The results of chemical reaction energy calculation analysis and SEM images analysis illustrate that the selective separation recovery of copper and arsenic mainly depended on the chemical reactions of sulfide precipitation. The ions of S2− and HS− produced by the prepared sulfide precipitant could react with Cu2+ and arsenic components to form CuS and As2S, respectively, in the copper and arsenic recovery procedure. In addition, the smaller solubility of CuS and the lower rate of S2− engendered by the sulfide precipitant were key to achieving the efficient separation and recovery of copper and arsenic.
Structure and Properties of Al-Co-Cr-Fe-Ni High-Entropy Alloy Subjected to Electron–Ion Plasma Treatment
Authors: Ivanov Yurii , Gromov Victor , Konovalov Sergey , Shugurov Vladimir , Efimov Mikhail , Teresov Anton , Petrikova Elizaveta , Panchenko Irina , Shliarova Yulia
Published: November 2022

High-entropy alloys (HEAs) are a new class of materials consisting of at least five elements in equiatomic or near-equiatomic ratio. HEAs are subjected to various types of surface treatment to improve their properties. One of the most promising methods of surface hardening is electron beam processing. This study aims to examine the structure, elemental, and phase composition of the AlCrFeCoNi HEA surface layer after the deposition of a (B + Cr) film and irradiation with a pulsed electron beam. HEA samples of non-equiatomic composition (33.4 Al; 8.3 Cr; 17.1 Fe; 5.4 Co; 35.7 Ni, at. %), fabricated by wire-arc additive manufacturing (WAAM), were used as study objects. Modification of the HEA surface layer was carried out by a complex method combining deposition of (B + Cr) film samples on the surface and irradiation with a pulsed electron beam in an argon medium. The mode of modification was identified. It makes it possible to increase microhardness (almost two times) and wear resistance (more than five times), reduce the friction coefficient of the HEA surface layer by 1.3 times due to the decrease in the average grain size, formation of particles of borides and oxyborides of complex elemental composition, the introduction of boron atoms into the crystal lattice of HEA.