bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Melatonin on the Transcriptome of Human Granulosa Cells, Fertilization and Blastocyst Formation
Authors: Tamura Isao , Tamura Hiroshi , Kawamoto-Jozaki Mai , Shirafuta Yuichiro , Fujimura Taishi , Doi-Tanaka Yumiko , Mihara Yumiko , Taketani Toshiaki , Sugino Norihiro
Published: June 2022

Melatonin is a promising reagent that can improve assisted reproductive technology (ART) outcomes in infertility patients. However, melatonin is not effective for all infertile patients, and it remains unclear for which patients melatonin would be effective. This study examined the effects of melatonin on ART outcomes and examined its mechanisms. Melatonin increased the fertilization rate in patients whose fertilization rates in the previous cycle were less than 50%, but not in patients whose fertilization rates were more than 50% in the previous cycle. Melatonin increased the blastocyst formation rate in patients whose embryo development rates in the previous cycle were less than 50%, but not in patients whose embryo development rates were more than 50% in the previous cycle. To clarify its mechanisms, transcriptome changes by melatonin treatment in granulosa cells (GCs) of the patients were examined by RNA-sequence. Melatonin treatment altered the transcriptomes of GCs of patients with poor ART outcomes so that they were similar to the transcriptomes of patients with good ART outcomes. The altered genes were associated with the inhibition of cell death and T-cell activity, and the activation of steroidogenesis and angiogenesis. Melatonin treatment was effective for patients with poor fertilization rates and poor embryo development rates in the previous ART cycle. Melatonin alters the GCs transcriptome and, thus, their functions, and this could improve the oocyte quality, leading to good ART outcomes.
To Die or Not to Die: Cell Death in Biology and Disease
Authors: Krüger Marcus , Richter Peter
Published: June 2022

Cell death is a fundamental and highly organized biological phenomenon that was long considered nothing more than the inevitable endpoint of life; this is reflected in the meaning of the Greek word, ἀπόπτωσις (“falling leaves from a tree”) [...]
A Proteomic Approach to Elucidate the Changes in Saliva and Serum Proteins of Pigs with Septic and Non-Septic Inflammation
Authors: López-Martínez María José , Cerón José Joaquín , Ortín-Bustillo Alba , Escribano Damián , Kuleš Josipa , Beletić Anđelo , Rubić Ivana , González-Sánchez Juan Carlos , Mrljak Vladimir , Martínez-Subiela Silvia , Muñoz-Prieto Alberto
Published: June 2022

Sepsis is a systemic inflammatory response triggered by an infectious agent and is recognized by the World Health Organization as a global concern, since it is one of the major causes of severe illness in humans and animals. The study of the changes that can occur in saliva and serum in sepsis can contribute to a better understanding of the pathophysiological mechanisms involved in the process and also to discover potential biomarkers that can help in its diagnosis and monitoring. The objective of this study was to characterize the changes that occur in the salivary and serum proteome of pigs with experimentally-induced sepsis. The study included five pigs with sepsis induced by LPS administration and five pigs with non-septic inflammation induced by turpentine for comparative purposes. In saliva, there were eighteen salivary proteins differentially expressed in the sepsis condition and nine in non-septic inflammation. Among these, significant increments in aldolase A and serpin B12 only occurred in the sepsis model. Changes in aldolase A were validated in a larger population of pigs with sepsis due to Streptococcus suis infection. In serum, there were 30 proteins differentially expressed in sepsis group and 26 proteins in the non-septic group, and most of the proteins that changed in both groups were related to non-specific inflammation. In the saliva of the septic animals there were some specific pathways activated, such as the organonitrogen compound metabolic process and lipid transport, whereas, in the serum, one of the main activated pathways was the regulation of protein secretion. Overall, saliva and serum showed different proteome variations in response to septic inflammation and could provide complementary information about the pathophysiological mechanisms occurring in this condition. Additionally, salivary aldolase A could be a potential biomarker of sepsis in pigs that should be confirmed in a larger population.
Modified Fluoroquinolones as Antimicrobial Compounds Targeting Chlamydia trachomatis
Authors: Vu Thi Huyen , Adhel Erika , Vielfort Katarina , Ha Duong Ngûyet-Thanh , Anquetin Guillaume , Jeannot Katy , Verbeke Philippe , Hjalmar Sofia , Gylfe Åsa , Serradji Nawal
Published: June 2022

Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC50) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced.
Extracellular Vesicles in Facial Aesthetics: A Review
Authors: Kee Li Ting , Ng Chiew Yong , Al-Masawa Maimonah Eissa , Foo Jhi Biau , How Chee Wun , Ng Min Hwei , Law Jia Xian
Published: June 2022

Facial aesthetics involve the application of non-invasive or minimally invasive techniques to improve facial appearance. Currently, extracellular vesicles (EVs) are attracting much interest as nanocarriers in facial aesthetics due to their lipid bilayer membrane, nanosized dimensions, biological origin, intercellular communication ability, and capability to modulate the molecular activities of recipient cells that play important roles in skin rejuvenation. Therefore, EVs have been suggested to have therapeutic potential in improving skin conditions, and these highlighted the potential to develop EV-based cosmetic products. This review summarizes EVs’ latest research, reporting applications in facial aesthetics, including scar removal, facial rejuvenation, anti-aging, and anti-pigmentation. This review also discussed the advanced delivery strategy of EVs, the therapeutic potential of plant EVs, and clinical studies using EVs to improve skin conditions. In summary, EV therapy reduces scarring, rejuvenates aging skin, and reduces pigmentation. These observations warrant the development of EV-based cosmetic products. However, more efforts are needed to establish a large-scale EV production platform that can consistently produce functional EVs and understand EVs’ underlying mechanism of action to improve their efficacy.
Strain Typing of Classical Scrapie and Bovine Spongiform Encephalopathy (BSE) by Using Ovine PrP (ARQ/ARQ) Overexpressing Transgenic Mice
Authors: Fatola Olanrewaju I. , Keller Markus , Balkema-Buschmann Anne , Olopade James , Groschup Martin H. , Fast Christine
Published: June 2022

Transmissible spongiform encephalopathies (TSE), caused by abnormal prion protein (PrPSc), affect many species. The most classical scrapie isolates harbor mixtures of strains in different proportions. While the characterization of isolates has evolved from using wild-type mice to transgenic mice, no standardization is established yet. Here, we investigated the incubation period, lesion profile and PrPSc profile induced by well-defined sheep scrapie isolates, bovine spongiform encephalopathy (BSE) and ovine BSE after intracerebral inoculation into two lines of ovine PrP (both ARQ/ARQ) overexpressing transgenic mice (Tgshp IX and Tgshp XI). All isolates were transmitted to both mouse models with an attack rate of almost 100%, but genotype-dependent differences became obvious between the ARQ and VRQ isolates. Surprisingly, BSE induced a much longer incubation period in Tgshp XI compared to Tgshp IX. In contrast to the histopathological lesion profiles, the immunohistochemical PrPSc profiles revealed discriminating patterns in certain brain regions in both models with clear differentiation of both BSE isolates from scrapie. These data provide the basis for the use of Tgshp IX and XI mice in the characterization of TSE isolates. Furthermore, the results enable a deeper appreciation of TSE strain diversity using ovine PrP overexpressing transgenic mice as a biological prion strain typing approach.
Thyroid Homeostasis: An Intricate Network of Production, Transport, Metabolism and Receptors Interaction
Authors: Laurino Annunziatina , Raimondi Laura
Published: June 2022

Correct thyroid function is regarded essential for maintaining the growth, differentiation and survival of most mammalian cells at homeostatic conditions [...]
Regeneration-Associated Transitional State Cells in Pulmonary Fibrosis
Authors: Shen Mengxia , Luo Ziqiang , Zhou Yan
Published: June 2022

Pulmonary fibrosis is a chronic, progressive fibrosing interstitial disease. It is characterized by fibroblast proliferation, myofibroblast activation, and massive extracellular matrix deposition. These processes result in loss of lung parenchyma function. The transdifferentiation of alveolar epithelial type II (AEC2) to alveolar epithelial type I cells (AEC1) plays an important role in the epithelial repair after lung injury. Pulmonary fibrosis begins when this transdifferentiation process is blocked. Several recent studies have found that novel transitional state cells (intermediate states in the transdifferentiation of AEC2 to AEC1) can potentially regenerate the alveolar epithelium surface and promote a repair process. During the AEC2 to AEC1 trans-differentiation process after injury, AEC2 lose their specific markers and become transitional state cells. Furthermore, transdifferentiation of transitional state cells into AEC1 is the critical step for lung repair. However, transitional cells stagnate in the intermediate states in which failure of transdifferentiation to AEC1 may induce an inadequate repair process and pulmonary fibrosis. In this review, we focus on the traits, origins, functions, and activation of signaling pathways of the transitional state cell and its communication with other cells. We also provide a new opinion on pulmonary fibrosis pathogenesis mechanisms and novel therapeutic targets.
Action Mechanisms of Effectors in Plant-Pathogen Interaction
Authors: Zhang Shiyi , Li Cong , Si Jinping , Han Zhigang , Chen Donghong
Published: June 2022

Plant pathogens are one of the main factors hindering the breeding of cash crops. Pathogens, including oomycetes, fungus, and bacteria, secrete effectors as invasion weapons to successfully invade and propagate in host plants. Here, we review recent advances made in the field of plant-pathogen interaction models and the action mechanisms of phytopathogenic effectors. The review illustrates how effectors from different species use similar and distinct strategies to infect host plants. We classify the main action mechanisms of effectors in plant-pathogen interactions according to the infestation process: targeting physical barriers for disruption, creating conditions conducive to infestation, protecting or masking themselves, interfering with host cell physiological activity, and manipulating plant downstream immune responses. The investigation of the functioning of plant pathogen effectors contributes to improved understanding of the molecular mechanisms of plant-pathogen interactions. This understanding has important theoretical value and is of practical significance in plant pathology and disease resistance genetics and breeding.
SAMM50 Regulates Thermogenesis of Beige Adipocytes Differentiated from Human Adipose-Derived Stem Cells by Balancing Mitochondrial Dynamics
Authors: Park Se-Jun , Shon Dong-Hyun , Kim Jae-Hyun , Ryu Yang-Hwan , Ko Yong
Published: June 2022

Brown/beige adipocyte thermogenesis is a process that is important for energy balance. The thermogenesis of brown/beige adipocytes occurs in the mitochondria, which is modulated by the dynamic balance between mitochondrial fusion and fission. Mitophagy is also involved in mitochondrial dynamics. The sorting and assembly machinery (SAM) complex protein, SAMM50, plays a key role in mitochondrial dynamics and quality control through regulating mitophagy. However, the roles of SAMM50 in the thermogenesis of beige adipocytes remain unknown. Thus, the objective of this study was to conduct functional analyses of SAMM50. The expression of mitochondrial fusion genes was repressed by SAMM50 knockdown but was not altered by SAMM50 overexpression. These results agreed with the distribution of the fluorescence-stained mitochondria and an mtDNA copy number. In contrast, the expression of mitochondrial fission genes showed an opposite outcome. As a result, suppression by the SAMM50 shRNA inhibited the expression of thermogenic genes (UCP1, PPARGC1A, DIO2, ELOVL3, CIDEA, and CIDEC) and mitochondrial-related genes (CYCS, COX7A1, TFAM, CPT1B, and CPT2). Conversely, SAMM50 overexpression promoted the expression of the thermogenic genes and mitochondrial genes. Thus, SAMM50 links the balance between the mitochondrial dynamics and thermogenesis of beige adipocytes.
In Vitro Effect of Δ9-Tetrahydrocannabinol and Cannabidiol on Cancer-Associated Fibroblasts Isolated from Lung Cancer
Authors: Milián Lara , Monleón-Guinot Irene , Sancho-Tello María , Galbis José Marcelo , Cremades Antonio , Almenar-Ordaz María , Peñaroja-Martinez Josep , Farras Rosa , Martín de Llano José Javier , Carda Carmen , Mata Manuel
Published: June 2022

There is evidence that demonstrates the effect of cannabinoid agonists inhibiting relevant aspects in lung cancer, such as proliferation or epithelial-to-mesenchymal transition (EMT). Most of these studies are based on evidence observed in in vitro models developed on cancer cell lines. These studies do not consider the complexity of the tumor microenvironment (TME). One of the main components of the TME is cancer-associated fibroblasts (CAFs), cells that are relevant in the control of proliferation and metastasis in lung cancer. In this work, we evaluated the direct effects of two cannabinoid agonists, tetrahydrocannabinol (THC) and cannabidiol (CBD), used alone or in combination, on CAFs and non-tumor normal fibroblasts (NFs) isolated from adenocarcinoma or from healthy lung tissue from the same patients. We observed that these compounds decrease cell density in vitro and inhibit the increase in the relative expression of type 1 collagen (COL1A1) and fibroblast-specific protein 1 (FSP1) induced by transforming growth factor beta (TGFβ). On the other hand, we studied whether THC and CBD could modulate the interactions between CAFs or NFs and cancer cells. We conditioned the culture medium with stromal cells treated or not with THC and/or CBD and cultured A549 cells with them. We found that culture media conditioned with CAFs or NFs increased cell density, induced morphological changes consistent with EMT, inhibited cadherin-1 (CDH1) gene expression, and induced an increase in the relative expression of cadherin-2 (CDH2) and vimentin (VIM) genes in A549 cells. These changes were inhibited or decreased by THC and CBD administered alone or in combination. In another series of experiments, we conditioned culture media with A549 cells treated or not with THC and/or CBD, in the presence or absence of TGFβ. We observed that culture media conditioned with A549 in the presence of TGFβ induced an increase in the expression of COL1A1 and VIM, both in CAFs and in non-tumor NFs. Both THC and CBD ameliorated these effects. In summary, the results presented here reinforce the usefulness of cannabinoid agonists for the treatment of some relevant aspects of lung cancer pathology, and demonstrate in a novel way their possible effects on CAFs as a result of their relationship with cancer cells. Likewise, the results reinforce the usefulness of the combined use of THC and CBD, which has important advantages in relation to the possibility of using lower doses, thus minimizing the psychoactive effects of THC.
Electrochemical Determination of Interaction between SARS-CoV-2 Spike Protein and Specific Antibodies
Authors: Drobysh Maryia , Liustrovaite Viktorija , Baradoke Ausra , Rucinskiene Alma , Ramanaviciene Almira , Ratautaite Vilma , Viter Roman , Chen Chien-Fu , Plikusiene Ieva , Samukaite-Bubniene Urte , Slibinskas Rimantas , Ciplys Evaldas , Simanavicius Martynas , Zvirbliene Aurelija , Kucinskaite-Kodze Indre , Ramanavicius Arunas
Published: June 2022

The serologic diagnosis of coronavirus disease 2019 (COVID-19) and the evaluation of vaccination effectiveness are identified by the presence of antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, we present the electrochemical-based biosensing technique for the detection of antibodies specific to the SARS-CoV-2 proteins. Recombinant SARS-CoV-2 spike proteins (rSpike) were immobilised on the surface of a gold electrode modified by a self-assembled monolayer (SAM). This modified electrode was used as a sensitive element for the detection of polyclonal mouse antibodies against the rSpike (anti-rSpike). Electrochemical impedance spectroscopy (EIS) was used to observe the formation of immunocomplexes while cyclic voltammetry (CV) was used for additional analysis of the surface modifications. It was revealed that the impedimetric method and the elaborate experimental conditions are appropriate for the further development of electrochemical biosensors for the serological diagnosis of COVID-19 and/or the confirmation of successful vaccination against SARS-CoV-2.
Identification of 8-Hydroxyquinoline Derivatives That Decrease Cystathionine Beta Synthase (CBS) Activity
Authors: Conan Pierre , Léon Alice , Gourdel Mathilde , Rollet Claire , Chaïr Loubna , Caroff Noéline , Le Goux Nelig , Le Jossic-Corcos Catherine , Sinane Maha , Gentile Lucile , Maillebouis Louise , Loaëc Nadège , Martin Jennifer , Vilaire Marie , Corcos Laurent , Mignen Olivier , Croyal Mikael , Voisset Cécile , Bihel Frédéric , Friocourt Gaëlle
Published: June 2022

CBS encodes a pyridoxal 5′-phosphate-dependent enzyme that catalyses the condensation of homocysteine and serine to form cystathionine. Due to its implication in some cancers and in the cognitive pathophysiology of Down syndrome, the identification of pharmacological inhibitors of this enzyme is urgently required. However, thus far, attempts to identify such molecules have only led to the identification of compounds with low potency and limited selectivity. We consequently developed an original, yeast-based screening method that identified three FDA-approved drugs of the 8-hydroxyquinoline family: clioquinol, chloroxine and nitroxoline. These molecules reduce CBS enzymatic activity in different cellular models, proving that the molecular mechanisms involved in yeast phenotypic rescue are conserved in mammalian cells. A combination of genetic and chemical biology approaches also revealed the importance of copper and zinc intracellular levels in the regulation of CBS enzymatic activity—copper promoting CBS activity and zinc inhibiting its activity. Taken together, these results indicate that our effective screening approach identified three new potent CBS inhibitors and provides new findings for the regulation of CBS activity, which is crucial to develop new therapies for CBS-related human disorders.
Bioconjugated Thymol-Zinc Oxide Nanocomposite as a Selective and Biocompatible Antibacterial Agent against Staphylococcus Species
Authors: Shin Joonho , Naskar Atanu , Ko Dongjoon , Kim Semi , Kim Kwang-sun
Published: June 2022

Owing to the rapid spread of antibiotic resistance among Staphylococcus species, effective and low-risk alternatives to antibiotics are being actively searched. Thymol (THO), the most abundant component of the oil extracted from thyme, can be considered as a natural antibacterial alternative. However, the low antibacterial activity and non-selectivity of THO limit its usage as a universal anti-Staphylococcus agent. Herein, we report the bioconjugation of THO with ZnO nanoparticle (ZO), which resulted in the TZ nanocomposite (NC), as a potent and selective antibacterial agent against Staphylococcus species, particularly S. epidermidis. The cell-free supernatant (CFS) of ATCC 25923 cultures was employed for the production of TZ NC. Successful production of TZ NC was confirmed via X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, and ultraviolet–visible (UV–Vis) studies. TZ NC had selective efficacy against Staphylococcus species, with MIC values 2–32-fold lower than THO. The antibacterial mechanisms of TZ NC are proposed to involve membrane rupture, suppression of biofilm formation, and modulation of new cell wall and protein-synthesis-associated cellular pathways. Its biocompatibility against HCT116 cells was also checked. Our findings suggest that the TZ nanocomposite could improve the selectivity and bactericidal activity of THO against target species.
Effects of miRNA-149-5p and Platelet-Activating Factor-Receptor Signaling on the Growth and Targeted Therapy Response on Lung Cancer Cells
Authors: Chauhan Shreepa J. , Thyagarajan Anita , Sahu Ravi P.
Published: June 2022

Accumulating evidence indicates that microRNAs (miRs) play critical roles in essentially all biological processes and their altered expression has been documented in various disease conditions, including human malignancies. Although several cellular mechanisms have been identified in mediating the effects of miRs, the involvement of G-protein-coupled, platelet-activating factor-receptor (PAFR) signaling in miR-149-5p-induced effects on lung cancer growth and therapeutic potential has not been studied. To that end, we first evaluated the functional significance of PAFR and miR-149-5p in A549 and H1299 human non-small cell lung cancer (NSCLC) cell lines. We observed that these tumor lines express endogenous PAFR and miR-149-5p and that PAFR activation by PAF agonist (CPAF) significantly increased, whereas miR-149-5p mimic transfection inhibited cell proliferation in a dose-dependent manner. Interestingly, miR-149-5p mimic significantly attenuated CPAF-mediated increased proliferation of NSCLC cells, as confirmed by miR-149-5p, cyclin D1, and forkhead box protein M1 (FOXM1) expression analysis via qPCR. Our next studies examined PAFR- and miR-149-5p-mediated effects on targeted therapy (i.e., erlotinib and gefitinib) responses. We observed that erlotinib and gefitinib inhibited A549 and H1299 cell survival in a dose- and time-dependent manner, and CPAF significantly blocked this effect. These findings indicate that miR-149-5p blocks PAFR-mediated increased cell proliferation, and PAFR activation attenuates the cytotoxic effects of targeted therapy.
Reconstruction of Full-Length circRNA Sequences Using Chimeric Alignment Information
Authors: Hossain Md. Tofazzal , Zhang Jingjing , Reza Md. Selim , Peng Yin , Feng Shengzhong , Wei Yanjie
Published: June 2022

Circular RNAs (circRNAs) are RNA molecules formed by joining a downstream 3 splice donor site and an upstream 5 splice acceptor site. Several recent studies have identified circRNAs as potential biomarker for different diseases. A number of methods are available for the identification of circRNAs. The circRNA identification methods cannot provide full-length sequences. Reconstruction of the full-length sequences is crucial for the downstream analyses of circRNA research including differential expression analysis, circRNA-miRNA interaction analysis and other functional studies of the circRNAs. However, a limited number of methods are available in the literature for the reconstruction of full-length circRNA sequences. We developed a new method, circRNA-full, for full-length circRNA sequence reconstruction utilizing chimeric alignment information from the STAR aligner. To evaluate our method, we used full-length circRNA sequences produced by isocirc and ciri-long using long-reads RNA-seq data. Our method achieved better reconstruction rate, precision, sensitivity and F1 score than the existing full-length circRNA sequence reconstruction tool ciri-full for both human and mouse data.
The Use of Envi-Met for the Assessment of Nature-Based Solutions’ Potential Benefits in Industrial Parks—A Case Study of Argales Industrial Park (Valladolid, Spain)
Authors: Alves Felipe Macedo , Gonçalves Artur , del Caz-Enjuto M. Rosario
Published: June 2022

Urbanization causes major changes in environmental systems, including those related with radiation balances and other meteorological conditions because of changes in surfaces and the physical environment. In addition, cities generate specific microclimates as a consequence of the diverse conditions within the urban fabric. Industrial parks represent vast urban areas, often neglected, contributing to the degradation of the urban environment, including poor thermal comfort as a result of soil sealing and low albedo surfaces. Nature-Based Solutions (NBS) can promote the mitigation of the anthropic effects of urbanization using nature as an inspiration. The present study, aimed at estimating the microclimate conditions in a fraction of the Argales industrial park in the city of Valladolid (Spain), with the use of the ENVI-Met software, assesses the current situation and a planned NBS scenario. Base scenario simulation results demonstrate different conditions across the simulations, with higher temperatures on sun-exposed surfaces with low albedo, and lower temperature spots, mostly associated with shadowed areas near existent buildings. After the simulation of the NBS scenario, the results show that, when compared with the base scenario, the projected air temperature changes reach reductions of up to 4.30 °C for the locations where changes are projected from impervious low albedo surfaces to shaded areas in the vicinity of trees and a water body.
Molecular Structures and Redox Properties of Homoleptic Aluminum(III) Complexes with Azobisphenolate (azp) Ligands
Authors: Takahashi Kazuyuki , Noguchi Takumi , Ueda Keiji , Miyawaki Atsuhiro , Murata Suguru
Published: June 2022

To elucidate the oxidation behavior of the 2,2′-azobisphenolate (azp) ligand, a series of homoleptic 1:2 AlIII complexes of four azp derivatives (L1) with 5,5′-dichloro-, 5,5′-dimethyl-, 5,5′-di-t-butyl-, 3,3′,5,5′-tetramethyl-substituents and of one imino derivative (L2) were synthesized and obtained as TPP[Al(L)2]·solvent (TPP = tetraphenylphosphonium ion). The X-ray crystal structure analyses showed that the two ONO-tridentate ligands were meridionally coordinated to a central AlIII ion in an almost perpendicular manner to give a homoleptic octahedral coordination structure in all the AlIII complexes. The proton nuclear magnetic resonance spectra suggested that all the AlIII complexes retained the homoleptic coordination structure in solution. From the cyclic voltammetry measurements in dichloromethane solutions, all the AlIII complexes with the azp ligands showed two partially reversible oxidation waves, and an additional reversible or partially reversible reduction wave. The substitution effects on the first oxidation and reduction peak potentials were revealed in the AlIII complexes with the azp ligands. On the other hand, the imino complex showed a partially reversible oxidation wave accompanying a film deposition. The density functional theory (DFT) calculations indicated that the molecular orbital (MO) coefficients of the frontier MOs in the AlIII complexes were present on the ligands and were absent on the AlIII ion. These results confirmed that the azp ligands are susceptible to oxidation and can give a relatively stable oxidation species depending upon substituent effects.
Effect of Doping Different Cu Valence States in HfO2 on Resistive Switching Properties of RRAM
Authors: Yang Jin , Chen Jun , Hong Yingzheng
Published: June 2022

Metal dopants are important for HfO2-based resistive switching mechanisms in resistive random-access memory (RRAM) because they can improve the performance of RRAM devices. Although Cu ions have been widely explored as metal dopants, Cu dopants with different valence states have received little attention. Using the first principles method and the Vienna ab initio simulation package (VASP), the effect of electron gain or loss in different doped Cu states in hafnium oxide (HfO2) was investigated. The electron affinity, defect formation energy, and charge density difference suggest that Cu doping results in a loss of electrons, thereby stabilizing the system. The population, the isosurface of partial charge density, and the migration barrier of the Cu-doped systems with different ionic valence states (+2 and 0) were calculated. Furthermore, the impact of doping ions on the formation of conductive filaments and the stability of the system were investigated in this study. The results indicate that the average population of the Cu-doped (+2) system is smaller than that of the Cu (0) system, and the Cu-O bond length increases in the Cu-doped (+2) system. At the same isosurface level, the electronic local clusters in the Cu (+2) system are stable; however, by increasing the isosurface level, the conductive filament of the Cu (0) system breaks first. At the same starting and ending positions, the migration barrier of the Cu (+2) system was much lower. In the transition state of the Cu (+2) system, the number of atoms whose atomic structure changes by more than 0.1 Å is lower than that in the Cu (0) system, which has a relatively small displacement deviation. This study, which indicates that the Cu (+2) system helps to form conductive channels upon applying current or voltage, can provide theoretical guidance for preparing RRAM and improving its performance.
Methods for Competitiveness Improvement of High-Temperature Steam Turbine Power Plants
Authors: Rogalev Andrey , Rogalev Nikolay , Komarov Ivan , Kindra Vladimir , Osipov Sergey
Published: June 2022

The paper is concerned with the problem of the development of high-temperature steam turbine power plants with ultra-supercritical (USC) initial parameters. One of the main disadvantages of the USC power unit’s creation is high price due to the application of expensive heat-resistant materials for boiler, live and reheat steam pipelines in turbines. To solve this problem, the following technical improvements to reduce the application of the heat-resistant materials and equipment metal consumption are proposed: horizontal boiler layout, high temperature steam turbine with a cooling system, oxy-hydrogen combustion chambers, and two-tier low-pressure turbine. The influence of the above-mentioned solutions on the high-temperature steam turbine power plant efficiency was estimated using thermodynamic analysis. The promising equipment design was developed based on the results of numerical and experimental research. The analysis of the proposed solutions’ influence upon the economic parameters of a high-temperature power facility was investigated based on the developed cost analysis model, which included the equipment metal and manufacturing expenses. The introduction of all the mentioned cost reduction methods led to a decrease in the facility’s price by RUB 10.5 billion or 15%. The discounted payback period was reduced from 27.5 to 10 years and the net present value increased by RUB 9.6 billion or 16 times.
Perspectives on Wider Integration of the Health-Assistive Smart Home
Authors: Dermody Gordana , Mikus Jenna , Porock Davina , Sugarman Dov , Janjua Naeem K. , How Christopher , Fritz Roschelle
Published: June 2022

Most older adults desire to be as independent as possible and remain living in their ancestral home as they age. Aging-in-place maximizes the independence of older adults, enhancing their wellbeing and quality of life while decreasing the financial burden of residential care costs. However, due to chronic disease, multimorbidity, and age-related changes, appropriate conditions are required to make aging-in-place possible. Remote monitoring with smart home technologies could provide the infrastructure that enables older adults to remain living independently in their own homes safely. The health-assistive smart home shows great promise, but there are challenges to integrating smart homes on a larger scale. The purpose of this discussion paper is to propose a Design Thinking (DT) process to improve the possibility of integrating a smart home for health monitoring more widely and making it more accessible to all older adults wishing to continue living independently in their ancestral homes. From a nursing perspective, we discuss the necessary stakeholder groups and describe how these stakeholders should engage to accelerate the integration of health smart homes into real-world settings.
Nutritional Status and Potentially Inappropriate Medications in Elderly
Authors: Loddo Simona , Salis Francesco , Rundeddu Samuele , Serchisu Luca , Peralta Maria Monica , Mandas Antonella
Published: June 2022

(1) Background: The association between polypharmacy and malnutrition has been investigated in several studies; however, few of these specifically deepened the relationship between potentially inappropriate medication and malnutrition. With a descriptive approach, the primary aim of our study was to evaluate the impact of the nutritional status, assessed with the Mini Nutritional Assessment (MNA), on potentially inappropriate medications (PIM), estimated 10-year survival, and the risk of adverse drug reactions in elderly patients; the secondary aim was to evaluate how the Screening Tool of Older People’s Prescriptions (STOPP), Screening Tool to Alert to Right Treatment (START), and BEERS 2019 criteria identify PIM compared to nutritional status. (2) Methods: In this study, 3091 subjects were enrolled, of whom 2748 (71.7%) were women; the median age was 80 years, with an interquartile range between 75 and 85 years of age. The subjects were assessed at the outpatient service for frail older people of the University Hospital of Cagliari. The study population was evaluated for their: MNA, Charlson Comorbidity Index, 10-year survival estimation, BEERS 2019, STOPP and START criteria, and ADR Risk scores. (3) Results: We divided the study population into three groups: MNA1 (MNA score ≥ 24), MNA2 (23.5–17), and MNA3 (<17): the severity of comorbidities, STOPP and START alerts, and BEERS 2019 criteria were significantly worse in both MNA2 and MNA3 compared to MNA1—with the exception of BEERS “non-anti-infective medications that should be avoided or have their dosage reduced with varying levels of kidney function in older adults”. Moreover, the estimated 10-year survival was significantly higher in MNA1 than in MNA2 and MNA3, and also in MNA2 compared to MNA3. Finally, the ADR risk scores were significantly lower in MNA1 than in MNA2 and MNA3. (4) Conclusions: Our study demonstrated the association between nutritional status and PIM checked with the BEERS 2019 criteria, and, for the first time, with the STOPP and START criteria.
Long-Term Outcome of Critically Ill Advanced Cancer Patients Managed in an Intermediate Care Unit
Authors: Fernández Ros Nerea , Alegre Félix , Rodríguez Rodriguez Javier , Landecho Manuel F. , Sunsundegui Patricia , Gúrpide Alfonso , Lecumberri Ramón , Sanz Eva , García Nicolás , Quiroga Jorge , Lucena Juan Felipe
Published: June 2022

Background: To analyze the long-term outcomes for advanced cancer patients admitted to an intermediate care unit (ImCU), an analysis of a do not resuscitate orders (DNR) subgroup was made. Methods: A retrospective observational study was conducted from 2006 to January 2019 in a single academic medical center of cancer patients with stage IV disease who suffered acute severe complications. The Simplified Acute Physiology Score 3 (SAPS 3) was used as a prognostic and severity score. In-hospital mortality, 30-day mortality and survival after hospital discharge were calculated. Results: Two hundred and forty patients with stage IV cancer who attended at an ImCU were included. In total, 47.5% of the cohort had DNR orders. The two most frequent reasons for admission were sepsis (32.1%) and acute respiratory failure (excluding sepsis) (38.7%). Mortality in the ImCU was 10.8%. The mean predicted in-hospital mortality according to SAPS 3 was 51.9%. The observed in-hospital mortality was 37.5% (standard mortality ratio of 0.72). Patients discharged from hospital had a median survival of 81 (30.75–391.25) days (patients with DNR orders 46 days (19.5–92.25), patients without DNR orders 162 days (39.5–632)). The observed mortality was higher in patients with DNR orders: 52.6% vs. 23.8%, p 0 < 0.001. By multivariate logistic regression, a worse ECOG performance status (3–4 vs. 0–2), a higher SAPS 3 Score and DNR orders were associated with a higher in-hospital mortality. By multivariate analysis, non-invasive mechanical ventilation, higher bilirubin levels and DNR orders were significantly associated with 30-day mortality. Conclusion: For patients with advanced cancer disease, even those with DNR orders, who suffer from acute complications or require continuous monitoring, an ImCU-centered multidisciplinary management shows encouraging results in terms of observed-to-expected mortality ratios.
Pharmacokinetics and Clinical Implications of Two Non-Tablet Oral Formulations of L-Thyroxine in Patients with Hypothyroidism
Authors: Trimboli Pierpaolo , Mouly Stéphane
Published: June 2022

Background: Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T4) has improved individualization of dosing regimens. However, up to 40–45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T4 replacement therapy includes all situations of unintended drug–drug and drug–food interactions as well as fasting conditions that are not necessarily respected by patients. Results: In this specific context, the overall information concerning those factors with the potential to affect L-T4 absorption refers only to tablet formulation. Indeed, this is the reason why new non-tablet formulations of L-T4 were introduced some years ago. In this regard, the current literature review was designed to summarize pharmacokinetic, drug and food interactions and clinical data focusing on two new oral L-T4 formulations, i.e., liquid and soft-gel capsule in healthy volunteers and patients with primary hypothyroidism. The non-tablet L-T4 soft-gel capsules and solution have proven bioequivalence with the usual L-T4 tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence. The impact of gastrointestinal conditions and variation of gastric pH was lower with either soft gel/solution than with tablets. In addition, the extent of drug–drug and drug–food interactions remains low and of uncertain clinical relevance. Conclusions: Pending further studies allowing one to extend the use of soft-gel/solution preparations in unselected patients, non-tablet L-T4 formulations should be considered as a first-line choice, especially in those patients with moderate-to-high potential of suboptimal tablet performance.
Vacuum-Assisted Delivery Complication Rates Based on Ultrasound-Estimated Fetal Weight
Authors: Schreiber Hanoch , Cohen Gal , Farladansky-Gershnabel Sivan , Sharon-Weiner Maya , Shechter Maor Gil , Biron-Shental Tal , Markovitch Ofer
Published: June 2022

This retrospective cohort study investigated the association between ultrasonographic estimated fetal weight (EFW) and adverse maternal and neonatal outcomes after vacuum-assisted delivery (VAD). It included women with singleton pregnancies at 34–41 weeks gestation, who underwent ultrasonographic pre-labor EFW and VAD in an academic institution, over 6 years. Adverse neonatal and maternal outcomes included shoulder dystocia, clavicular fracture, or third- and fourth-degree perineal tears. A receiver–operator characteristic curve was used to identify the optimal weight cut-off value to predict adverse outcomes. Fetuses above and below this point were compared. Multivariate analysis was used to control for factors that could lead to adverse outcomes. Eight-hundred and fifty women met the inclusion criteria and had sonographic EFW within two-weeks before delivery. Receiver–operator characteristic curve analysis found that ultrasonographic EFW 3666 g is the optimal threshold for adverse outcomes. Based on these results, outcomes were compared using EFW 3700 g. The average EFW in the ≥3700 g group (n = 220, 25.9%) was 3898 ± 154 g (average birthweight 3710 ± 324 g). In the group <3700 g (n = 630, 74.1%), average EFW was 3064 ± 411 g (birthweight 3120 ± 464 g). Shoulder dystocia and clavicular fractures were more frequent in the higher EFW group (6.4% and 2.3% vs. 1.6% and 0.5%, respectively; p < 0.05). Women in the ≥3700 g group experienced more third- and fourth-degree perineal tears (3.2% vs. 1%, p = 0.02). Multivariate logistic regression analysis found maternal age, diabetes and sonographic EFW ≥ 3700 g as independent risk-factors for adverse outcomes. Sonographic EFW ≥ 3700 g is an independent risk-factor for adverse outcomes in VAD. This should be considered when choosing the optimal mode of delivery.
Contact Lenses Loaded with Melatonin Analogs: A Promising Therapeutic Tool against Dry Eye Disease
Authors: Navarro-Gil Francisco Javier , Huete-Toral Fernando , Domínguez-Godínez Carmen Olalla , Carracedo Gonzalo , Crooke Almudena
Published: June 2022

Melatonin analogs topically administered evoke a potent tear secretagogue effect in rabbits. This route of drug administration requires high drug concentration and frequent dosing due to its reduced ocular surface retention. Therefore, contact lenses (CLs) have emerged as an alternative drug-delivery system that prolongs drug retention in the cornea, improving its therapeutic performance. This study explores the in vitro ability of five commercially available hydrogel CLs to act as a delivery system for melatonin analogs and the in vivo secretagogue effect of melatonin analog-loaded CLs. We soaked CLs with melatonin or melatonin analog solutions (1 mM) for 12 h. Spectroscopic assays showed that IIK7-loaded CLs led to the inadequate delivery of this compound. Conventional hydrogel lenses loaded with agomelatine released more agomelatine than silicone ones (16–33% more). In contrast, the CLs of silicone materials are more effective as a delivery system of 5-MCA-NAT than CLs of conventional materials (24–29%). The adaptation of CLs loaded with agomelatine or 5-MCA-NAT in rabbits triggered a higher tear secretion than the corresponding eye drops (78% and 59% more, respectively). These data suggest that CLs preloaded with melatonin analogs could be an adequate strategy to combat aqueous tear deficient dry eye disease.
Application Progress of High-Throughput Sequencing in Ocular Diseases
Authors: He Xuejun , Zhang Ningzhi , Cao Wenye , Xing Yiqiao , Yang Ning
Published: June 2022

Ocular diseases affect multiple eye parts and can be caused by pathogenic infections, complications of systemic diseases, genetics, environment, and old age. Understanding the etiology and pathogenesis of eye diseases and improving their diagnosis and treatment are critical for preventing any adverse consequences of these diseases. Recently, the advancement of high-throughput sequencing (HTS) technology has paved wide prospects for identifying the pathogenesis, signaling pathways, and biomarkers involved in eye diseases. Due to the advantages of HTS in nucleic acid sequence recognition, HTS has not only identified several normal ocular surface microorganisms but has also discovered many pathogenic bacteria, fungi, parasites, and viruses associated with eye diseases, including rare pathogens that were previously difficult to identify. At present, HTS can directly sequence RNA, which will promote research on the occurrence, development, and underlying mechanism of eye diseases. Although HTS has certain limitations, including low effectiveness, contamination, and high cost, it is still superior to traditional diagnostic methods for its efficient and comprehensive diagnosis of ocular diseases. This review summarizes the progress of the application of HTS in ocular diseases, intending to explore the pathogenesis of eye diseases and improve their diagnosis.
Postpartum Depression in COVID-19 Days: Longitudinal Study of Risk and Protective Factors
Authors: Gluska Hadar , Shiffman Noga , Mayer Yael , Margalit Shiri , Daher Rawan , Elyasyan Lior , Sharon Weiner Maya , Miremberg Hadas , Kovo Michal , Biron-Shental Tal , Helpman Liat , Gabbay-Benziv Rinat
Published: June 2022

COVID-19 impacted the childbirth experience and increased the rates of postpartum depression (PPD). We assessed the longitudinal effects of the pandemic on the rates of PPD and evaluated the PPD causes and symptoms among women who delivered during the first COVID-19 quarantine in Israel. The participants completed online questionnaires 3 (T1) and 6 months (T2) following delivery. We used the ‘COVID-19 exposure’ questionnaire, while PPD symptoms, situational anxiety, and social support were evaluated with the EPDS, STAI, and MSPSS questionnaires. The mean EPDS scores increased between T1 and T2 (6.31 ± 5.6 vs. 6.92 ± 5.9, mean difference −0.64 ± 4.59 (95% CI (−1.21)–(−0.06)); t (244) = −2.17, p = 0.031), and the STAI scores decreased (45.35 ± 16.4 vs. 41.47 ± 14.0, t(234) = 4.39, p = 0.000). Despite the exposure to an increased number of COVID-19 events (3.63 ± 1.8 vs. (6.34 ± 2.3)), the impact of exposure decreased between T1 and T2 (8.91 ± 4.6 vs. 7.47 ± 4.1), p < 0.001). In the MSPSS, significant differences were noted on the family scale between the T1 (6.10 ± 1.3) and T2 (5.91 ± 1.4) scores; t (216) = 2.68, p = 0.0008. A regression analysis showed three statistically significant variables that correlated with increased EPDS scores: the MSPSS family subscale (F (1212.00) = 4.308, p = 0.039), the STAI scores (F (1212.00) = 31.988, p = 0.000), and the impact of exposure to COVID-19 (F (1212.00) = 5.038, p = 0.026). The rates of PPD increased for women who delivered during the first COVID-19 lockdown. Further research is warranted to help reduce PPD among these women.