bluuebunny/crossref_metadata_2025 huggingface dataset:
The Regulatory Roles of PPARs in Skeletal Muscle Fuel Metabolism and Inflammation: Impact of PPAR Agonism on Muscle in Chronic Disease, Contraction and Sepsis
Authors: Crossland Hannah , Constantin-Teodosiu Dumitru , Greenhaff Paul L.
Published: September 2021

The peroxisome proliferator-activated receptor (PPAR) family of transcription factors has been demonstrated to play critical roles in regulating fuel selection, energy expenditure and inflammation in skeletal muscle and other tissues. Activation of PPARs, through endogenous fatty acids and fatty acid metabolites or synthetic compounds, has been demonstrated to have lipid-lowering and anti-diabetic actions. This review will aim to provide a comprehensive overview of the functions of PPARs in energy homeostasis, with a focus on the impacts of PPAR agonism on muscle metabolism and function. The dysregulation of energy homeostasis in skeletal muscle is a frequent underlying characteristic of inflammation-related conditions such as sepsis. However, the potential benefits of PPAR agonism on skeletal muscle protein and fuel metabolism under these conditions remains under-investigated and is an area of research opportunity. Thus, the effects of PPARγ agonism on muscle inflammation and protein and carbohydrate metabolism will be highlighted, particularly with its potential relevance in sepsis-related metabolic dysfunction. The impact of PPARδ agonism on muscle mitochondrial function, substrate metabolism and contractile function will also be described.
Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?
Authors: Grishin Sergei Y. , Domnin Pavel A. , Kravchenko Sergey V. , Azev Viacheslav N. , Mustaeva Leila G. , Gorbunova Elena Y. , Kobyakova Margarita I. , Surin Alexey K. , Makarova Maria A. , Kurpe Stanislav R. , Fadeev Roman S. , Vasilchenko Alexey S. , Firstova Victoria V. , Ermolaeva Svetlana A. , Galzitskaya Oxana V.
Published: September 2021

The development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as Pseudomonas aeruginosa, Gram-negative bacteria. Most AMPs achieve these goals through mechanisms that disrupt the normal permeability of the cell membrane, which ultimately leads to the death of the pathogenic cell. Here, we developed a unique combination of a membrane penetrating peptide and peptides prone to amyloidogenesis to create hybrid peptide: “cell penetrating peptide + linker + amyloidogenic peptide”. We evaluated the antimicrobial effects of two peptides that were developed from sequences with different propensities for amyloid formation. Among the two hybrid peptides, one was found with antibacterial activity comparable to antibiotic gentamicin sulfate. Our peptides showed no toxicity to eukaryotic cells. In addition, we evaluated the effect on the antimicrobial properties of amino acid substitutions in the non-amyloidogenic region of peptides. We compared the results with data on the predicted secondary structure, hydrophobicity, and antimicrobial properties of the original and modified peptides. In conclusion, our study demonstrates the promise of hybrid peptides based on amyloidogenic regions of the ribosomal S1 protein for the development of new antimicrobial drugs against P. aeruginosa.
Nanobodies Enhancing Cancer Visualization, Diagnosis and Therapeutics
Authors: Naidoo Dhaneshree Bestinee , Chuturgoon Anil Amichund
Published: September 2021

Worldwide, cancer is a serious health concern due to the increasing rates of incidence and mortality. Conventional cancer imaging, diagnosis and treatment practices continue to substantially contribute to the fight against cancer. However, these practices do have some risks, adverse effects and limitations, which can affect patient outcomes. Although antibodies have been developed, successfully used and proven beneficial in various oncology practices, the use of antibodies also comes with certain challenges and limitations (large in size, poor tumor penetration, high immunogenicity and a long half-life). Therefore, it is vital to develop new ways to visualize, diagnose and treat cancer. Nanobodies are novel antigen-binding fragments that possess many advantageous properties (small in size, low immunogenicity and a short half-life). Thus, the use of nanobodies in cancer practices may overcome the challenges experienced with using traditional antibodies. In this review, we discuss (1) the challenges with antibody usage and the superior qualities of nanobodies; (2) the use of antibodies and nanobodies in cancer imaging, diagnosis, drug delivery and therapy (surgery, radiotherapy, chemotherapy and immunotherapy); and (3) the potential improvements in oncology practices due to the use of nanobodies as compared to antibodies.
Genetic Aberrations of DNA Repair Pathways in Prostate Cancer: Translation to the Clinic
Authors: Ghose Aruni , Moschetta Michele , Pappas-Gogos George , Sheriff Matin , Boussios Stergios
Published: September 2021

Prostate cancer (PC) is the second most common cancer in men worldwide. Due to the large-scale sequencing efforts, there is currently a better understanding of the genomic landscape of PC. The identification of defects in DNA repair genes has led to clinical studies that provide a strong rationale for developing poly (ADP-ribose) polymerase (PARP) inhibitors and DNA-damaging agents in this molecularly defined subset of patients. The identification of molecularly defined subgroups of patients has also other clinical implications; for example, we now know that carriers of breast cancer 2 (BRCA2) pathogenic sequence variants (PSVs) have increased levels of serum prostate specific antigen (PSA) at diagnosis, increased proportion of high Gleason tumors, elevated rates of nodal and distant metastases, and high recurrence rate; BRCA2 PSVs confer lower overall survival (OS). Distinct tumor PSV, methylation, and expression patterns have been identified in BRCA2 compared with non-BRCA2 mutant prostate tumors. Several DNA damage response and repair (DDR)-targeting agents are currently being evaluated either as single agents or in combination in patients with PC. In this review article, we highlight the biology and clinical implications of deleterious inherited or acquired DNA repair pathway aberrations in PC and offer an overview of new agents being developed for the treatment of PC.
Four-Dimensional Chromosome Structure Prediction
Authors: Highsmith Max , Cheng Jianlin
Published: September 2021

Chromatin conformation plays an important role in a variety of genomic processes, including genome replication, gene expression, and gene methylation. Hi-C data is frequently used to analyze structural features of chromatin, such as AB compartments, topologically associated domains, and 3D structural models. Recently, the genomics community has displayed growing interest in chromatin dynamics. Here, we present 4DMax, a novel method, which uses time-series Hi-C data to predict dynamic chromosome conformation. Using both synthetic data and real time-series Hi-C data from processes, such as induced pluripotent stem cell reprogramming and cardiomyocyte differentiation, we construct smooth four-dimensional models of individual chromosomes. These predicted 4D models effectively interpolate chromatin position across time, permitting prediction of unknown Hi-C contact maps at intermittent time points. Furthermore, 4DMax correctly recovers higher order features of chromatin, such as AB compartments and topologically associated domains, even at time points where Hi-C data is not made available to the algorithm. Contact map predictions made using 4DMax outperform naïve numerical interpolation in 87.7% of predictions on the induced pluripotent stem cell dataset. A/B compartment profiles derived from 4DMax interpolation showed higher similarity to ground truth than at least one profile generated from a neighboring time point in 100% of induced pluripotent stem cell experiments. Use of 4DMax may alleviate the cost of expensive Hi-C experiments by interpolating intermediary time points while also providing valuable visualization of dynamic chromatin changes.
Hybrids as NO Donors
Authors: Tsopka Ioanna-Chrysoula , Hadjipavlou-Litina Dimitra
Published: September 2021

Cinnamic acid and its derivatives have been studied for a variety of biological properties, including anti-inflammatory, antioxidant, anticancer, antihypertensive, and antibacterial. Many hybrids of cinnamic derivatives with other bioactive molecules have been synthesized and evaluated as nitric oxide (NO) donors. Since NO plays a significant role in various biological processes, including vasodilation, inflammation, and neurotransmission, NO donor groups are incorporated into the structures of already-known bioactive molecules to enhance their biological properties. In this review, we present cinnamic hybrids with NO-donating ability useful in the treatment of several diseases.
Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride
Authors: Bruni Pia S. , Schürch Stefan
Published: September 2021

Bent metallocene dichlorides (Cp2MCl2, M = Ti, Mo, Nb, …) have found interest as anti-cancer drugs in order to overcome the drawbacks associated with platinum-based therapeutics. However, they suffer from poor hydrolytic stability at physiological pH. A promising approach to improve their hydrolytic stability is the formation of host-guest complexes with macrocyclic structures, such as cyclodextrins. In this work, we utilized nanoelectrospray ionization tandem mass spectrometry to probe the interaction of titanocene dichloride with β-cyclodextrin. Unlike the non-covalent binding of phenylalanine and oxaliplatin to β-cyclodextrin, the mixture of titanocene and β-cyclodextrin led to signals assigned as [βCD + Cp2Ti–H]+, indicating a covalent character of the interaction. This finding is supported by titanated cyclodextrin fragment ions occurring from collisional activation. Employing di- and trimethylated β-cyclodextrins as hosts enabled the elucidation of the influence of the cyclodextrin hydroxy groups on the interaction with guest structures. Masking of the hydroxy groups was found to impair the covalent interaction and enabling the encapsulation of the guest structure within the hydrophobic cavity of the cyclodextrin. Findings are further supported by breakdown curves obtained by gas-phase dissociation of the various complexes.
Sigma-1 Receptor Agonists Acting on Aquaporin-Mediated H2O2 Permeability: New Tools for Counteracting Oxidative Stress
Authors: Pellavio Giorgia , Rossino Giacomo , Gastaldi Giulia , Rossi Daniela , Linciano Pasquale , Collina Simona , Laforenza Umberto
Published: September 2021

Sigma1 Receptor (S1R) is involved in oxidative stress, since its activation is triggered by oxidative or endoplasmic reticulum stress. Since specific aquaporins (AQP), called peroxiporins, play a relevant role in controlling H2O2 permeability and ensure reactive oxygen species wasted during oxidative stress, we studied the effect of S1R modulators on AQP-dependent water and hydrogen peroxide permeability in the presence and in the absence of oxidative stress. Applying stopped-flow light scattering and fluorescent probe methods, water and hydrogen peroxide permeability in HeLa cells have been studied. Results evidenced that S1R agonists can restore water permeability in heat-stressed cells and the co-administration with a S1R antagonist totally counteracted the ability to restore the water permeability. Moreover, compounds were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together these results support the hypothesis that the antioxidant mechanism is mediated by both S1R and AQP-mediated H2O2 permeability. The finding that small molecules can act on both S1R and AQP-mediated H2O2 permeability opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, such as cancer and degenerative diseases.
The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence
Authors: Freitas João Augusto , Gullo Irene , Garcia Diogo , Miranda Sara , Spaans Louisa , Pinho Lídia , Reis Joana , Sousa Fabiana , Baptista Manuela , Resende Carlos , Leitão Dina , Durães Cecília , Costa José Luis , Carneiro Fátima , Machado José Carlos
Published: September 2021

Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma–carcinoma sequence (ACS). Methods. We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). Results. The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. Conclusions. The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.
The Se–S Bond Formation in the Covalent Inhibition Mechanism of SARS-CoV-2 Main Protease by Ebselen-like Inhibitors: A Computational Study
Authors: Parise Angela , Romeo Isabella , Russo Nino , Marino Tiziana
Published: September 2021

The inhibition mechanism of the main protease (Mpro) of SARS-CoV-2 by ebselen (EBS) and its analog with a hydroxyl group at position 2 of the benzisoselenazol-3(2H)-one ring (EBS-OH) was studied by using a density functional level of theory. Preliminary molecular dynamics simulations on the apo form of Mpro were performed taking into account both the hydrogen donor and acceptor natures of the Nδ and Nε of His41, a member of the catalytic dyad. The potential energy surfaces for the formation of the Se–S covalent bond mediated by EBS and EBS-OH on Mpro are discussed in detail. The EBS-OH shows a distinctive behavior with respect to EBS in the formation of the noncovalent complex. Due to the presence of canonical H-bonds and noncanonical ones involving less electronegative atoms, such as sulfur and selenium, the influence on the energy barriers and reaction energy of the Minnesota hybrid meta-GGA functionals M06, M06-2X and M08HX, and the more recent range-separated hybrid functional wB97X were also considered. The knowledge of the inhibition mechanism of Mpro by the small protease inhibitors EBS or EBS-OH can enlarge the possibilities for designing more potent and selective inhibitor-based drugs to be used in combination with other antiviral therapies.
Structural Dynamics of C2F4I2 in Cyclohexane Studied via Time-Resolved X-ray Liquidography
Authors: Gu Jain , Lee Seonggon , Eom Seunghwan , Ki Hosung , Choi Eun Hyuk , Lee Yunbeom , Nozawa Shunsuke , Adachi Shin-ichi , Kim Jeongho , Ihee Hyotcherl
Published: September 2021

The halogen elimination of 1,2-diiodoethane (C2H4I2) and 1,2-diiodotetrafluoroethane (C2F4I2) serves as a model reaction for investigating the influence of fluorination on reaction dynamics and solute–solvent interactions in solution-phase reactions. While the kinetics and reaction pathways of the halogen elimination reaction of C2H4I2 were reported to vary substantially depending on the solvent, the solvent effects on the photodissociation of C2F4I2 remain to be explored, as its reaction dynamics have only been studied in methanol. Here, to investigate the solvent dependence, we conducted a time-resolved X-ray liquidography (TRXL) experiment on C2F4I2 in cyclohexane. The data revealed that (ⅰ) the solvent dependence of the photoreaction of C2F4I2 is not as strong as that observed for C2H4I2, and (ⅱ) the nongeminate recombination leading to the formation of I2 is slower in cyclohexane than in methanol. We also show that the molecular structures of the relevant species determined from the structural analysis of TRXL data provide an excellent benchmark for DFT calculations, especially for investigating the relevance of exchange-correlation functionals used for the structural optimization of haloalkanes. This study demonstrates that TRXL is a powerful technique to study solvent dependence in the solution phase.
Immunomodulatory Properties of Umbilical Cord Blood-Derived Small Extracellular Vesicles and Their Therapeutic Potential for Inflammatory Skin Disorders
Authors: Rodrigues Sílvia C. , Cardoso Renato M. S. , Freire Patricia C. , Gomes Cláudia F. , Duarte Filipe V. , Neves Ricardo Pires das , Simões-Correia Joana
Published: September 2021

Umbilical cord blood (UCB) has long been seen as a rich source of naïve cells with strong regenerative potential, likely mediated by paracrine signals. More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell-derived sEV (UCB-MNC-sEV) and explore their therapeutic potential for inflammatory skin diseases. UCB-MNC-sEV were shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with UCB-MNC-sEV resulted in a reduction of total CD4+ and CD8+ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, UCB-MNC-sEV reduced the expression of inflammatory and psoriatic markers IL6, IL8, CXCL10, COX2, S100A7, and DEFB4. In vivo, UCB-MNC-sEV significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of UCB-MNC-sEV, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis.
Calmodulin Interactions with Voltage-Gated Sodium Channels
Authors: Wu Xin , Hong Liang
Published: September 2021

Calmodulin (CaM) is a small protein that acts as a ubiquitous signal transducer and regulates neuronal plasticity, muscle contraction, and immune response. It interacts with ion channels and plays regulatory roles in cellular electrophysiology. CaM modulates the voltage-gated sodium channel gating process, alters sodium current density, and regulates sodium channel protein trafficking and expression. Many mutations in the CaM-binding IQ domain give rise to diseases including epilepsy, autism, and arrhythmias by interfering with CaM interaction with the channel. In the present review, we discuss CaM interactions with the voltage-gated sodium channel and modulators involved in CaM regulation, as well as summarize CaM-binding IQ domain mutations associated with human diseases in the voltage-gated sodium channel family.
Optimised Heterologous Expression and Functional Analysis of the Yersinia pestis F1-Capsular Antigen Regulator Caf1R
Authors: Gahlot Dharmender K. , Ifill Gyles , MacIntyre Sheila
Published: September 2021

The bacterial pathogen, Yersinia pestis, has caused three historic pandemics and continues to cause small outbreaks worldwide. During infection, Y. pestis assembles a capsule-like protective coat of thin fibres of Caf1 subunits. This F1 capsular antigen has attracted much attention due to its clinical value in plague diagnostics and anti-plague vaccine development. Expression of F1 is tightly regulated by a transcriptional activator, Caf1R, of the AraC/XylS family, proteins notoriously prone to aggregation. Here, we have optimised the recombinant expression of soluble Caf1R. Expression from the native and synthetic codon-optimised caf1R cloned in three different expression plasmids was examined in a library of E. coli host strains. The functionality of His-tagged Caf1R was demonstrated in vivo, but insolubility was a problem with overproduction. High levels of soluble MBP-Caf1R were produced from codon optimised caf1R. Transcriptional-lacZ reporter fusions defined the PM promoter and Caf1R binding site responsible for transcription of the cafMA1 operon. Use of the identified Caf1R binding caf DNA sequence in an electrophoretic mobility shift assay (EMSA) confirmed correct folding and functionality of the Caf1R DNA-binding domain in recombinant MBP-Caf1R. Availability of functional recombinant Caf1R will be a valuable tool to elucidate control of expression of F1 and Caf1R-regulated pathophysiology of Y. pestis.
Neuroplasticity and Multilevel System of Connections Determine the Integrative Role of Nucleus Accumbens in the Brain Reward System
Authors: Bayassi-Jakowicka Martyna , Lietzau Grazyna , Czuba Ewelina , Steliga Aleksandra , Waśkow Monika , Kowiański Przemysław
Published: September 2021

A growing body of evidence suggests that nucleus accumbens (NAc) plays a significant role not only in the physiological processes associated with reward and satisfaction but also in many diseases of the central nervous system. Summary of the current state of knowledge on the morphological and functional basis of such a diverse function of this structure may be a good starting point for further basic and clinical research. The NAc is a part of the brain reward system (BRS) characterized by multilevel organization, extensive connections, and several neurotransmitter systems. The unique role of NAc in the BRS is a result of: (1) hierarchical connections with the other brain areas, (2) a well-developed morphological and functional plasticity regulating short- and long-term synaptic potentiation and signalling pathways, (3) cooperation among several neurotransmitter systems, and (4) a supportive role of neuroglia involved in both physiological and pathological processes. Understanding the complex function of NAc is possible by combining the results of morphological studies with molecular, genetic, and behavioral data. In this review, we present the current views on the NAc function in physiological conditions, emphasizing the role of its connections, neuroplasticity processes, and neurotransmitter systems.
SREBP1-Induced Glutamine Synthetase Triggers a Feedforward Loop to Upregulate SREBP1 through Sp1 O-GlcNAcylation and Augments Lipid Droplet Formation in Cancer Cells
Authors: Jhu Jin-Wei , Yan Jia-Bao , Lin Zou-Han , Lin Shih-Chieh , Peng I-Chen
Published: September 2021

Glutamine and lipids are two important components of proliferating cancer cells. Studies have demonstrated that glutamine synthetase (GS) boosts glutamine-dependent anabolic processes for nucleotide and protein synthesis, but the role of GS in regulating lipogenesis remains unclear. This study identified that insulin and glutamine deprivation activated the lipogenic transcription factor sterol regulatory element-binding protein 1 (SREBP1) that bound to the GS promoter and increased its transcription. Notably, GS enhanced the O-linked N-acetylglucosaminylation (O-GlcNAcylation) of the specificity protein 1 (Sp1) that induced SREBP1/acetyl-CoA carboxylase 1 (ACC1) expression resulting in lipid droplet (LD) accumulation upon insulin treatment. Moreover, glutamine deprivation induced LD formation through GS-mediated O-GlcNAc-Sp1/SREBP1/ACC1 signaling and supported cell survival. These findings demonstrate that insulin and glutamine deprivation induces SREBP1 that transcriptionally activates GS, resulting in Sp1 O-GlcNAcylation. Subsequently, O-GlcNAc-Sp1 transcriptionally upregulates the expression of SREBP1, resulting in a feedforward loop that increases lipogenesis and LD formation in liver and breast cancer cells.
Pharmacogenetics in Neuroblastoma: What Can Already Be Clinically Implemented and What Is Coming Next?
Authors: Olivera Gladys G. , Urtasun Andrea , Sendra Luis , Aliño Salvador F. , Yáñez Yania , Segura Vanessa , Gargallo Pablo , Berlanga Pablo , Castel Victoria , Cañete Adela , Herrero María José
Published: September 2021

Pharmacogenetics is one of the cornerstones of Personalized Precision Medicine that needs to be implemented in the routine of our patients’ clinical management in order to tailor their therapies as much as possible, with the aim of maximizing efficacy and minimizing toxicity. This is of great importance, especially in pediatric cancer and even more in complex malignancies such as neuroblastoma, where the rates of therapeutic success are still below those of many other types of tumors. The studies are mainly focused on germline genetic variants and in the present review, state of the art is presented: which are the variants that have a level of evidence high enough to be implemented in the clinic, and how to distinguish them from the ones that still need validation to confirm their utility. Further aspects as relevant characteristics regarding ontogeny and future directions in the research will also be discussed.
PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling
Authors: Yang Zelei , Tang Xiaoyun , McMullen Todd P. W. , Brindley David N. , Hemmings Denise G.
Published: September 2021

Human cytomegalovirus (HCMV) infects 40–70% of adults in developed countries. HCMV proteins and DNA are detected in tumors and metastases, suggesting an association with increased invasion. We investigated HCMV infection in human breast cancer cell lines compared to fibroblasts, a component of tumors, and the role of platelet-derived growth factor receptor-α (PDGFRα). HCMV productively infected HEL299 fibroblasts and, to a lesser extent, Hs578T breast cancer cells. Infection of another triple-negative cell line, MDA-MB-231, and also MCF-7 cells, was extremely low. These disparate infection rates correlated with expression of PDGFRA, which facilitates HCMV uptake. Increasing PDGFRA expression in T-47D breast cancer and BCPAP thyroid cancer cells markedly increased HCMV infection. Conversely, HCMV infection decreased PDGFRA expression, potentially attenuating signaling through this receptor. HCMV infection of fibroblasts promoted the secretion of proinflammatory factors, whereas an overall decreased secretion of inflammatory factors was observed in infected Hs578T cells. We conclude that HCMV infection in tumors will preferentially target tumor-associated fibroblasts and breast cancer cells expressing PDGFRα. HCMV infection in the tumor microenvironment, rather than cancer cells, will increase the inflammatory milieu that could enhance metastasis involving lysophosphatidate.
Impact of COVID-19 Pandemic on Remote Monitoring of Cardiac Implantable Electronic Devices in Italy: Results of a Survey Promoted by AIAC (Italian Association of Arrhythmology and Cardiac Pacing)
Authors: Maines Massimiliano , Palmisano Pietro , Del Greco Maurizio , Melissano Donato , De Bonis Silvana , Baccillieri Stella , Zanotto Gabriele , D’Onofrio Antonio , Ricci Renato Pietro , De Ponti Roberto , Boriani Giuseppe
Published: September 2021

The COVID-19 pandemic has had a profound impact on the organisation of health care in Italy, with an acceleration in the development of telemedicine. To assess the impact of the COVID-19 pandemic on the spread of remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) in Italy, a survey addressed to cardiologists operating in all Italian CIED-implanting centres was launched. A total of 127 cardiologists from 116 Italian arrhythmia centres took part in the survey, 41.0% of all 283 CIED-implanting centres operating in Italy in 2019. All participating centres declared to use RM of CIEDs. COVID-19 pandemic resulted in an increase in the use of RM in 83 (71.6%) participating centres. In a temporal perspective, an increase in the median number of patients per centre followed up by RM was found from 2012 to 2017, followed by an exponential increase from 2017 to 2020. In 36 participating centres (31.0%) a telehealth visits service was activated as a replacement for in-person outpatient visits (in patients with or without CIED) during the COVID-19 pandemic. COVID-19 pandemic has caused an acceleration in the use of RM of CIEDs and in the use of telemedicine in the clinical practice of cardiology.
Outcomes in Critically Ill Patients Sedated with Intravenous Lormetazepam or Midazolam: A Retrospective Cohort Study
Authors: Weiss Björn , Hilfrich David , Vorderwülbecke Gerald , Heinrich Maria , Grunow Julius J. , Paul Nicolas , Kruppa Jochen , Neuner Bruno , Drexler Berthold , Balzer Felix , Spies Claudia D.
Published: September 2021

The benzodiazepine, midazolam, is one of the most frequently used sedatives in intensive care medicine, but it has an unfavorable pharmacokinetic profile when continuously applied. As a consequence, patients are frequently prolonged and more deeply sedated than intended. Due to its distinct pharmacological features, including a cytochrome P450-independent metabolization, intravenous lormetazepam might be clinically advantageous compared to midazolam. In this retrospective cohort study, we compared patients who received either intravenous lormetazepam or midazolam with respect to their survival and sedation characteristics. The cohort included 3314 mechanically ventilated, critically ill patients that received one of the two drugs in a tertiary medical center in Germany between 2006 and 2018. A Cox proportional hazards model with mortality as outcome and APACHE II, age, gender, and admission mode as covariates revealed a hazard ratio of 1.75 [95% CI 1.46–2.09; p < 0.001] for in-hospital mortality associated with the use of midazolam. After additionally adjusting for sedation intensity, the HR became 1.04 [95% CI 0.83–1.31; p = 0.97]. Thus, we concluded that excessive sedation occurs more frequently in critically ill patients treated with midazolam than in patients treated with lormetazepam. These findings require further investigation in prospective trials to assess if lormetazepam, due to its ability to maintain light sedation, might be favorable over other benzodiazepines for sedation in the ICU.
Comparison of SARC-F Score among Gastrointestinal Diseases
Authors: Ushiro Kosuke , Nishikawa Hiroki , Matsui Masahiro , Ogura Takeshi , Takeuchi Toshihisa , Goto Masahiro , Nakamura Shiro , Kakimoto Kazuki , Miyazaki Takako , Fukunishi Shinya , Asai Akira , Ohama Hideko , Yokohama Keisuke , Yasuoka Hidetaka , Higuchi Kazuhide
Published: September 2021

SARC-F is a screening tool for sarcopenia. We sought to compare the SARC-F scores of patients with different gastrointestinal diseases (n = 1282 (762 males): upper gastrointestinal disease (UGD, n = 326), lower gastrointestinal disease (LGD, n = 357), biliary and pancreatic disease (BPD, n = 416), and liver disease (LD, n = 183)). Factors associated with SARC-F ≥4 points (highly suspicious of sarcopenia) were also examined. The median age was 71 years. Patients with SARC-F ≥4 points were found in 197 (15.4%). Advanced cancer was found in 339 patients (26.4%). The proportion of SARC-F ≥4 points in groups of UGD, LGD, BPD, and LD were 17.5% (57/326) in UGD, 12.0% (43/357) in LGD, 17.3% (72/416) in BPD, and 13.7% (25/183) in LD, respectively (overall p = 0.1235). In patients with and without advanced cancer, similar tendencies were observed. In the multivariate analysis, age (p < 0.0001), gender (p = 0.0011), serum albumin (p < 0.0001), lymphocyte count (p = 0.0019), C reactive protein (p = 0.0197), and the presence of advanced cancer (p = 0.0424) were significant factors linked to SARC-F ≥4 points. In patients with advanced cancer, SARC-F scores correlated well with their Glasgow prognostic scores. In conclusion, sarcopenia in gastrointestinal diseases may be affected not by disease type (i.e., the primary origin of the disease) but by aging, nutritional condition, inflammatory condition, and cancer burden.
Differences in Kinematic and Kinetic Patterns According to the Bone Tumor Location after Endoprosthetic Knee Replacement Following Bone Tumor Resection: A Comparative Gait Analysis between Distal Femur and Proximal Tibia
Authors: Kim Sungmin , Ryu Changhyun , Jung Sung-Taek
Published: September 2021

Modular endoprostheses are frequently used to reconstruct skeletal and knee defects from bone tumor resection and preserve joint function in patients with bone tumors around the knee. Depending on the tumor location, the muscles and extent of the tumor can vary, which can affect gait function. This study aimed to analyze kinetic and kinematic characteristics according to tumor location in patients with endoprosthetic knee replacements after bone tumor resection. Gait analyses were performed in 16 patients who underwent knee endoprosthesis due to tumors around the knee. We divided the patients into distal femur (n = 7) and proximal tibia (n = 9) groups and conducted between-group comparisons and comparisons with healthy participants. Compared with the control group, the distal femur group showed a tendency for knee extension, and the proximal tibia group showed increased maximal dorsiflexion during stance. The proximal tibia group maintained a flexed hip during the entire gait cycle, compared with the distal femur group. In summary, our results suggest a difference in gait between the distal femur and proximal tibia groups. Patients who have undergone knee prosthesis after knee tumor resection may require different rehabilitation strategies according to the tumor location.
A Two-Year Comparative Evaluation of Clinical Performance of a Nanohybrid Composite Resin to a Flowable Composite Resin
Authors: Badr Carelle , Spagnuolo Gianrico , Amenta Francesco , Khairallah Carlos , Mahdi Syed Sarosh , Daher Elie , Battineni Gopi , Baba Nadim Z. , Zogheib Tatiana , Qasim Syed Saad B. , Daher Tony , Chintalapudi Nalini , Zogheib Carina Mehanna
Published: September 2021

Objective: This prospective in vivo study aimed to compare the clinical behavior of a flowable composite resin (Genial Universal Flo, GC) and a nanohybrid universal composite resin (Tetric Evo Ceram, Ivoclar Vivadent) used in Class I and II direct esthetic restorations in posterior teeth. Methods: A total of 108 Class I and II direct restorations were performed in patients aged between 20 and 60 years. The originality of this study lies in the fact that both materials were placed in pairs, in the same clinical environment (i.e., the same patient and the same type of tooth). The evaluations were performed now of restoration and after 2-weeks, 6-, 12-, and 24-months intervals using clinical examination, clinical photographs, and radiological examination, according to modified USPHS criteria. Statistical analysis was performed using the Fisher exact test and chi-square analysis. Results: At baseline, the universal composite resin showed better esthetic properties such as surface luster, surface staining marginal staining. Both materials regressed significantly over time with no significant difference between groups. Conclusions: Both flowable and nanohybrid composite resins exhibit acceptable clinical performance. The present 24 months of evaluation of different composites showed that the G-ænial Universal Flo could be an effective esthetic material for posterior restoration. No significant difference between both materials over time concerning surface luster, surface staining, and marginal staining.
Oxygen as a Master Regulator of Human Pluripotent Stem Cell Function and Metabolism
Authors: Nit Kinga , Tyszka-Czochara Malgorzata , Bobis-Wozowicz Sylwia
Published: September 2021

Human-induced pluripotent stem cells (hiPSCs) offer numerous possibilities in science and medicine, particularly when combined with precise genome editing methods. hiPSCs are artificially generated equivalents of human embryonic stem cells (hESCs), which possess an unlimited ability to self-renew and the potential to differentiate into any cell type of the human body. Importantly, generating patient-specific hiPSCs enables personalized drug testing or autologous cell therapy upon differentiation into a desired cell line. However, to ensure the highest standard of hiPSC-based biomedical products, their safety and reliability need to be proved. One of the key factors influencing human pluripotent stem cell (hPSC) characteristics and function is oxygen concentration in their microenvironment. In recent years, emerging data have pointed toward the beneficial effect of low oxygen pressure (hypoxia) on both hiPSCs and hESCs. In this review, we examine the state-of-the-art research on the oxygen impact on hiPSC functions and activity with an emphasis on their niche, metabolic state, reprogramming efficiency, and differentiation potential. We also discuss the similarities and differences between PSCs and cancer stem cells (CSCs) with respect to the role of oxygen in both cell types.
Sustainability Determinants of Cultural and Creative Industries in Peripheral Areas
Authors: Imperiale Francesca , Fasiello Roberta , Adamo Stefano
Published: September 2021

Cultural and Creative Industries (CCIs) are increasingly recognized as part of the global economy and of growing importance for sustainable local development. However, the exploitation of their full potential depends on several issues concerning their entrepreneurial dimension and the context where they operate. The paper deals with these issues having the scope to investigate the main determinants of CCIs’ sustainability in peripheral areas, to understand what kind of policy could better support the survival of CCIs and development in these areas, according to an end-user perspective. The research is part of an Interreg Greece-Italy project carried out from mid-2018 until the end of 2020 with specific reference to CCIs in Apulia (IT) and Western Greece (EL). A two-step mixed methodology has been used to figure out regional specializations and the specific aspects of the entrepreneurial structure and business sustainability in the cultural and creative sector (CCs). In the end, the paper shows and discusses the main determinants considered crucial for CCI sustainability, suggesting guidelines for local authorities supporting their economic development.
A Comprehensive Review of Water-Based Nanolubricants
Authors: Morshed Afshana , Wu Hui , Jiang Zhengyi
Published: September 2021

Applying nanomaterials and nanotechnology in lubrication has become increasingly popular and important to further reduce the friction and wear in engineering applications. To achieve green manufacturing and its sustainable development, water-based nanolubricants are emerging as promising alternatives to the traditional oil-containing lubricants that inevitably pose environmental issues when burnt and discharged. This review presents an overview of recent advances in water-based nanolubricants, starting from the preparation of the lubricants using different types of nanoadditives, followed by the techniques to evaluate and enhance their dispersion stability, and the commonly used tribo-testing methods. The lubrication mechanisms and models are discussed with special attention given to the roles of the nanoadditives. Finally, the applications of water-based nanolubricants in metal rolling are summarised, and the outlook for future research directions is proposed.
The Low-Angle Boundaries Misorientation and Lattice Parameter Changes in the Root of Single-Crystalline CMSX-4 Superalloy Blades
Authors: Paszkowski Robert , Bogdanowicz Włodzimierz , Szeliga Dariusz
Published: September 2021

The relationship between the angles of misorientation of macroscopic low-angle boundaries (LABs) and changes in the lattice parameter of the γ′-phase around the LABs in the root of single-crystalline (SX) turbine blades made of CMSX-4 superalloy were studied. The blades with an axial orientation of the [001] type were solidified using an industrial Bridgman furnace with a 3 mm/min withdrawal rate. X-ray diffraction topography, the EFG Ω-scan X-ray diffraction method, scanning electron microscopy, and Laue diffraction were used to study the thin lamellar samples with a thickness of 0.5 mm and orientation of the surface perpendicular to the [001] direction. It is found that in the areas with a width of a few millimetres around LABs, decreases in the lattice parameter of the γ′-phase occur. These lattice parameter changes are related to the internal stresses of the γ′-phase caused by local changes in the concentration of alloying elements and/or to the dendrite bending near the LABs. X-ray topography used on two surfaces of thin lamellar samples coupled with the lattice parameter measurements of the γ′-phase near the LAB allows separating the misorientation component of LAB diffraction contrast from the component and visualising the internal stresses of the γ′-phase.
Revealing the Effect of Phase Composition and Transformation on the Mechanical Properties of a Cu–6Ni–6Sn–0.6Si Alloy
Authors: Liang Zhuanqin , Fan Wenxin , Wang Pengfei , Wang Yushuai , Zhang Kai , Zhao Junsheng , Peng Lijun
Published: September 2021

In the present study, a Cu–6Ni–6Sn–0.6Si alloy is fabricated through frequency induction melting, then subjected to solution treatment, rolling, and annealing. The phase composition, microstructure evolution, and transition mechanism of the Cu–6Ni–6Sn–0.6Si alloy are researched systematically through simulation calculation and experimental characterization. The ultimate as-annealed sample simultaneously performs with high strength and good ductility according to the uniaxial tensile test results at room temperature. There are amounts of precipitates generated, which are identified as belonging to the DO22 and L12 phases through the transmission electron microscope (TEM) analysis. The DO22 and L12 phase precipitates have a significant strengthening effect. Meanwhile, the generation of the common discontinuous precipitation of the γ phase, which is harmful to the mechanical properties of the copper–nickel–tin alloy, is inhibited mightily during the annealing process, possibly due to the existence of the Ni5Si2 primary phase. Therefore, the as-annealed sample of the Cu–6Ni–6Sn–0.6Si alloy possesses high tensile strength and elongation, which are 967 MPa and 12%, respectively.
Evolution of Microstructure in Friction Stir Processed Dissimilar CuZn37/AA5056 Stir Zone
Authors: Zykova Anna , Chumaevskii Andrey , Gusarova Anastasia , Gurianov Denis , Kalashnikova Tatiana , Savchenko Nickolai , Kolubaev Evgeny , Tarasov Sergei
Published: September 2021

Dissimilar friction stir processing on CuZn37/AA5056 was performed to study structural and phase evolution of a friction stir zone. Formation of 5–10 μm intermetallic compounds (IMCs) such as Al2Cu was the main type of diffusion reaction between copper and aluminum. Other alloying elements such as Mg and Zn were forced out of the forming Al2Cu grains and dissolved in the melt formed due to exothermic effect of the Al2Cu formation. When solidified, these Zn-enriched zones were represented by α-Al+Al2Cu+Zn phases or α-Al+Al2Cu+Zn+MgZn regions. Eutectic Zn+MgZn was undoubtedly formed the melt after stirring had stopped. These zones were proven to be weak ones with respect to pull-off test since MgZn was detected on the fracture surface. Tensile strength of the stirred zone metal was achieved at the level of that of AA5056.
Heat Treatment Effect on the Phase Composition of the Silica Electrochemical Coating and the Carbon Fiber Strength
Authors: Galyshev Sergei , Postnova Evgeniya , Shakhlevich Olga , Agarkov Dmitrii , Agarkova Ekaterina , Nekrasov Alexey , Mozhchil Rais
Published: September 2021

This work is devoted to the study of the chemical and phase composition of a carbon fiber coating obtained by the electrochemical sol-gel method. The experimental data obtained using several independent complementary methods, including X-ray phase analysis, thermogravimetric and differential thermal analysis, scanning electron microscopy and elemental analysis, and X-ray photoelectron spectroscopy, are in good agreement with each other. It was found that the resulting coating consists of amorphous silicon oxide and crystalline potassium carbonate. Heating above 870 °C leads to the crystallization of cristobalite from amorphous silicon dioxide. At a temperature of about 870 °C, the coating acquires a smooth surface, and heating above 1170 °C leads to its destruction. Thus, the optimum temperature for the heat treatment of the coating is about 870 °C. The loss of strength of carbon fiber at each stage of coating was estimated. A full coating cycle, including thermal cleaning from the sizing, coating, and heat treatment, results in a loss of fiber strength by only 11% compared to the initial state.
Metamorphic Buffer Layer Platform for 1550 nm Single-Photon Sources Grown by MBE on (100) GaAs Substrate
Authors: Wroński Piotr Andrzej , Wyborski Paweł , Musiał Anna , Podemski Paweł , Sęk Grzegorz , Höfling Sven , Jabeen Fauzia
Published: September 2021

We demonstrate single-photon emission with a low probability of multiphoton events of 5% in the C-band of telecommunication spectral range of standard silica fibers from molecular beam epitaxy grown (100)-GaAs-based structure with InAs quantum dots (QDs) on a metamorphic buffer layer. For this purpose, we propose and implement graded In content digitally alloyed InGaAs metamorphic buffer layer with maximal In content of 42% and GaAs/AlAs distributed Bragg reflector underneath to enhance the extraction efficiency of QD emission. The fundamental limit of the emission rate for the investigated structures is 0.5 GHz based on an emission lifetime of 1.95 ns determined from time-resolved photoluminescence. We prove the relevance of a proposed technology platform for the realization of non-classical light sources in the context of fiber-based quantum communication applications.
Field-Induced SMM and Vis/NIR Luminescence on Mononuclear Lanthanide Complexes with 9-Anthracenecarboxylate and 2,2′:6,2″-Terpyridine
Authors: Casanovas Berta , Porcar Oriol , Speed Saskia , Vicente Ramon , Font-Bardía Mercè , El Fallah Mohamed Salah
Published: September 2021

Five new mononuclear lanthanide complexes are synthesized by adding the several lanthanide nitrate hexahydrate salts, which for lanthanide (Ln) are Eu, Tb, Dy, Er, and Yb, with 9-anthracenecarboxylic acid (9-Hanthc) and 2,2′:6,2″-terpyridine (TPY) in mixed solution of methanol and dimethylformamide (DMF). The general formula is [Eu(9-anthc)3(TPY)(DMF)]·H2O (1Eu) where Eu(III) is ennea-coordinated or [Ln(9-anthc)3(TPY)(H2O)]·H2O·DMF (Ln = Tb (2Tb), Dy (3Dy), Er (4Er), and Yb (5Yb)) where Ln(III) is octa-coordinated. For compounds 3Dy, 4Er, and 5Yb, the dynamic ac magnetic study indicated field-induced single molecule magnet (SMM) behavior. The photoluminescence studies in the solid state of these complexes show the sensitization of 4f-4f transitions for 4Er and 5Yb in the NIR region.