bluuebunny/crossref_metadata_2025 huggingface dataset:
Textbooks and Learning Materials in Physical Education in the International Context: Literature Review
Authors: Rodríguez Rodríguez Jesús , Álvarez-Seoane Denébola , Arufe-Giráldez Víctor , Navarro-Patón Rubén , Sanmiguel-Rodríguez Alberto
Published: June 2022

This paper presents a review of the research carried out internationally in recent years regarding textbooks, teaching materials, and the field of physical education. The objectives to which this article aims are as follows: To offer a compilation of current research papers published in the Scopus, Web of Science, and Dialnet databases and to provide a classification of the research lines undertaken on the subject. The information used is based on a review of studies listed in Scopus, Web of Science, and Dialnet. For this, a systematic review was carried out with the terms: “curricular resources”, “didactic materials”, “digital resources”, “educational resource”, “physical education”, and “textbooks”, allowing the selection of original articles, which included information on this line of research. For the literature review, only articles that presented scientific evidence were used, discarding merely descriptive articles or didactic experiences that were not investigated with the scientific protocol. A total of 589 articles were found, although after applying the review’s inclusion criteria, they were reduced to 54 articles. The investigations do not follow a common protocol and the researchers address multiple objectives in them, highlighting the studies on the implicit ideological discourse in the images of physical education textbooks. The results reveal a diversity of research, in particular, studies involving ideological discourse. Insofar as methodology, content analysis of textbooks and materials was the most common approach.
The Assessment of Indoor Formaldehyde and Bioaerosol Removal by Using Negative Discharge Electrostatic Air Cleaners
Authors: Liu Chao-Yun , Tseng Chao-Heng , Wang Kai-Feng
Published: June 2022

This study investigated the single-pass performance of a negative corona electrostatic precipitators (ESP) in removing suspended particulates (PM2.5 and PM10), formaldehyde (HCHO), and bioaerosols (bacteria and fungi) and measured the ozone (O3) concentration generated by ESP. The experimental results revealed that if the operational conditions for the ESP were set to high voltage (−10.5 kV) and low air flow rate (2.4 m3/min), ESP had optimal air pollutant removal efficiency. In the laboratory system, its PM2.5 and PM10 removal rates both reached 99% at optimal conditions, and its HCHO removal rate was 55%. In field tests, its PM2.5, PM10, HCHO, bacteria, and fungi removal rates reached 89%, 90%, 46%, 69%, and 85% respectively. The ESP in the laboratory system (−10.5 kV and 2.4 m3/min) generated 7.374 ppm of O3 under optimal conditions. Under the same operational conditions, O3 generated by ESP in the food waste storage room and the meeting room were 1.347 ppm and 1.749 ppm, respectively. The removal of HCHO and bioaerosols was primarily attributed to their destruction in the corona, as well as ozone oxidation, and collection on the dust collection plate.
Urban Inundation under Different Rainstorm Scenarios in Lin’an City, China
Authors: Chen Yan , Hou Hao , Li Yao , Wang Luoyang , Fan Jinjin , Wang Ben , Hu Tangao
Published: June 2022

Under the circumstances of global warming and rapid urbanization, damage caused by urban inundation are becoming increasingly severe, attracting the attention of both researchers and governors. The accurate simulation of urban inundation is essential for the prevention of inundation hazards. In this study, a 1D pipe network and a 2D urban inundation coupling model constructed by InfoWorks ICM was used to simulate the inundation conditions in the typical urbanized area in the north of Lin’an. Two historical rainfall events in 2020 were utilized to verify the modeling results. The spatial–temporal variation and the causes of urban inundation under different designed rainfalls were studied. The results were as follows: (1) The constructed model had a good simulation accuracy, the Nash–Sutcliffe efficiency coefficient was higher than 0.82, R2 was higher than 0.87, and the relative error was ±20%. (2) The simulation results of different designed rainfall scenarios indicated that the maximum inundation depth and inundation extent increased with the increase in the return period, rainfall peak position coefficient, and rainfall duration. According to the analysis results, the urban inundation in Lin’an is mainly affected by topography, drainage network (spatial distribution and pipe diameter), and rainfall patterns. The results are supposed to provide technical support and a decision-making reference for the urban management department of Lin’an to design inundation prevention measures.
Investigating Factors Related to Criminal Trips of Residential Burglars Using Spatial Interaction Modeling
Authors: Hirama Kazuki , Yokota Kaeko , Otsuka Yusuke , Watanabe Kazumi , Yabe Naoto , Hawai Yoshinori
Published: June 2022

This study used spatial interaction modeling to examine whether origin-specific and destination-specific factors, distance decay effects, and spatial structures explain the criminal trips of residential burglars. In total, 4041 criminal trips committed by 892 individual offenders who lived and committed residential burglary in Tokyo were analyzed. Each criminal trip was allocated to an origin–destination pair created from the combination of potential departure and arrival zones. The following explanatory variables were created from an external dataset and used: residential population, density of residential burglaries, and mobility patterns of the general population. The origin-specific factors served as indices of not only the production of criminal trips, but also the opportunity to commit crimes in the origin zones. Moreover, the criminal trips were related to the mobility patterns of the general population representing daily leisure (noncriminal) trips, and relatively large origin- and destination-based spatial spillover effects were estimated. It was shown that considering not only destination-specific but also origin-specific factors, spatial structures are important for investigating the criminal trips of residential burglars. The current findings could be applicable to future research on geographical profiling by incorporating neighborhood-level factors into existing models.
A Homozygous Loss-of-Function Mutation in MSH5 Abolishes MutSγ Axial Loading and Causes Meiotic Arrest in NOA-Affected Individuals
Authors: Gong Chenjia , Abbas Tanveer , Muhammad Zubair , Zhou Jianteng , Khan Ranjha , Ma Hui , Zhang Huan , Shi Qinghua , Shi Baolu
Published: June 2022

Non-obstructive azoospermia (NOA), characterized by spermatogenesis failure and the absence of sperm in ejaculation, is the most severe form of male infertility. However, the etiology and pathology between meiosis-associated monogenic alterations and human NOA remain largely unknown. A homozygous MSH5 mutation (c.1126del) was identified from two idiopathic NOA patients in the consanguineous family. This mutation led to the degradation of MSH5 mRNA and abolished chromosome axial localization of MutSγ in spermatocytes from the affected males. Chromosomal spreading analysis of the patient’s meiotic prophase I revealed that the meiosis progression was arrested at a zygotene-like stage with extensive failure of homologous synapsis and DSB repair. Therefore, our study demonstrates that the MSH5 c.1126del could cause meiotic recombination failure and lead to human infertility, improving the genetic diagnosis of NOA clinically. Furthermore, the study of human spermatocytes elucidates the meiosis defects caused by MSH5 variant, and reveals a conserved and indispensable role of MutSγ in human synapsis and meiotic recombination, which have not previously been well-described.
GWAS Reveals a Novel Candidate Gene CmoAP2/ERF in Pumpkin (Cucurbita moschata) Involved in Resistance to Powdery Mildew
Authors: Alavilli Hemasundar , Lee Jeong-Jin , You Chae-Rin , Poli Yugandhar , Kim Hyeon-Jai , Jain Ajay , Song Kihwan
Published: June 2022

Pumpkin (Cucurbita moschata Duchesne ex Poir.) is a multipurpose cash crop rich in antioxidants, minerals, and vitamins; the seeds are also a good source of quality oils. However, pumpkin is susceptible to the fungus Podosphaera xanthii, an obligate biotrophic pathogen, which usually causes powdery mildew (PM) on both sides of the leaves and reduces photosynthesis. The fruits of infected plants are often smaller than usual and unpalatable. This study identified a novel gene that involves PM resistance in pumpkins through a genome-wide association study (GWAS). The allelic variation identified in the CmoCh3G009850 gene encoding for AP2-like ethylene-responsive transcription factor (CmoAP2/ERF) was proven to be involved in PM resistance. Validation of the GWAS data revealed six single nucleotide polymorphism (SNP) variations in the CmoAP2/ERF coding sequence between the resistant (IT 274039 [PMR]) and the susceptible (IT 278592 [PMS]). A polymorphic marker (dCAPS) was developed based on the allelic diversity to differentiate these two haplotypes. Genetic analysis in the segregating population derived from PMS and PMR parents provided evidence for an incomplete dominant gene-mediated PM resistance. Further, the qRT-PCR assay validated the elevated expression of CmoAP2/ERF during PM infection in the PMR compared with PMS. These results highlighted the pivotal role of CmoAP2/ERF in conferring resistance to PM and identifies it as a valuable molecular entity for breeding resistant pumpkin cultivars.
Effect of Anti-Osteoporotic Treatments on Circulating and Bone MicroRNA Patterns in Osteopenic ZDF Rats
Authors: Carro Vázquez David , Emini Lejla , Rauner Martina , Hofbauer Christine , Grillari Johannes , Diendorfer Andreas B. , Eastell Richard , Hofbauer Lorenz C. , Hackl Matthias
Published: June 2022

Bone fragility is an adverse outcome of type 2 diabetes mellitus (T2DM). The underlying molecular mechanisms have, however, remained largely unknown. MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression in health and disease states. The aim of this study was to investigate the genome-wide regulation of miRNAs in T2DM bone disease by analyzing serum and bone tissue samples from a well-established rat model of T2DM, the Zucker Diabetic Fatty (ZDF) model. We performed small RNA-sequencing analysis to detect dysregulated miRNAs in the serum and ulna bone of the ZDF model under placebo and also under anti-sclerostin, PTH, and insulin treatments. The dysregulated circulating miRNAs were investigated for their cell-type enrichment to identify putative donor cells and were used to construct gene target networks. Our results show that unique sets of miRNAs are dysregulated in the serum (n = 12, FDR < 0.2) and bone tissue (n = 34, FDR < 0.2) of ZDF rats. Insulin treatment was found to induce a strong dysregulation of circulating miRNAs which are mainly involved in metabolism, thereby restoring seven circulating miRNAs in the ZDF model to normal levels. The effects of anti-sclerostin treatment on serum miRNA levels were weaker, but affected miRNAs were shown to be enriched in bone tissue. PTH treatment did not produce any effect on circulating or bone miRNAs in the ZDF rats. Altogether, this study provides the first comprehensive insights into the dysregulation of bone and serum miRNAs in the context of T2DM and the effect of insulin, PTH, and anti-sclerostin treatments on circulating miRNAs.
Flow Cytometric Analysis of Oxidative Stress in Escherichia coli B Strains Deficient in Genes of the Antioxidant Defence
Authors: Jávega Beatriz , Herrera Guadalupe , O’Connor José-Enrique
Published: June 2022

The detection of reactive oxygen species (ROS) and the analysis of oxidative stress are frequent applications of functional flow cytometry. Identifying and quantifying the ROS species generated during oxidative stress are crucial steps for the investigation of molecular mechanisms underlying stress responses. Currently, there is a wide availability of fluorogenic substrates for such purposes, but limitations in their specificity and sensitivity may affect the accuracy of the analysis. The aim of our work was to validate a new experimental model based in different strains of Escherichia coli B deficient in key genes for antioxidant defense, namely oxyR, sodA and sodB. We applied this model to systematically assess issues of specificity in fluorescent probes and the involvement of different ROS in a bacterial model of oxidative stress, as the probes can react with a variety of oxidants and free radical species. Our results confirm the higher sensitivity and specificity of the fluorescent probe mitochondrial peroxy yellow 1 (MitoPY1) for the detection of H2O2, and its very low capacity for organic hydroperoxides, thus extending MitoPY1′s specificity for H2O2 in mammalian cells to a bacterial model. On the contrary, the fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate (H2DCF-DA) is more sensitive to organic peroxides than to H2O2, confirming the lack of selectivity of H2DCF-DA to H2O2. Treatment with organic peroxides and H2O2 suggests a superoxide-independent oxidation of the fluorescent probe Hydroethidine (HE). We found a positive correlation between the lipophilicity of the peroxides and their toxicity to E. coli, suggesting greater quantitative importance of the peroxidative effects on the bacterial membrane and/or greater efficiency of the protection systems against the intracellular effects of H2O2 than against the membrane oxidative stress induced by organic peroxides. Altogether, our results may aid in preventing or minimizing experimental errors and providing recommendations for the proper design of cytometric studies of oxidative stress, in accordance with current recommendations and guidelines.
SCA® Slows the Decline of Functional Parameters Associated with Senescence in Skin Cells
Authors: Castro Begoña , de Paz Naiara , González Salvador , Rodríguez-Luna Azahara
Published: June 2022

The identification of compounds and natural ingredients that can counteract tissue stress and dysfunction induced by aging in skin cells is warranted. Here, we investigated the activity of the secretion from the snail Cryptomphalus aspersa (SCA®), an active compound with well-established beneficial effects on skin integrity and aging. To determinate its senescence-regulation mechanisms, we used a model where damage was induced by hydrogen peroxide (H2O2). The results showed that SCA® positively modulated factors involved in cell senescence such as β-galactosidase and cell morphology, secretory efficiency markers (SIRT1/6 and carboxymethyl-lysine), and metabolic and redox homeostasis (mTOR and ROS). This study demonstrated a novel compound that is activity-modulating, reduces cell senescence, and increases longevity to maintain skin homeostasis and functionality.
TLR/WNT: A Novel Relationship in Immunomodulation of Lung Cancer
Authors: Martín-Medina Aina , Cerón-Pisa Noemi , Martinez-Font Esther , Shafiek Hanaa , Obrador-Hevia Antònia , Sauleda Jaume , Iglesias Amanda
Published: June 2022

The most frequent cause of death by cancer worldwide is lung cancer, and the 5-year survival rate is still very poor for patients with advanced stage. Understanding the crosstalk between the signaling pathways that are involved in disease, especially in metastasis, is crucial to developing new targeted therapies. Toll-like receptors (TLRs) are master regulators of the immune responses, and their dysregulation in lung cancer is linked to immune escape and promotes tumor malignancy by facilitating angiogenesis and proliferation. On the other hand, over-activation of the WNT signaling pathway has been reported in lung cancer and is also associated with tumor metastasis via induction of Epithelial-to-mesenchymal-transition (EMT)-like processes. An interaction between both TLRs and the WNT pathway was discovered recently as it was found that the TLR pathway can be activated by WNT ligands in the tumor microenvironment; however, the implications of such interactions in the context of lung cancer have not been discussed yet. Here, we offer an overview of the interaction of TLR-WNT in the lung and its potential implications and role in the oncogenic process.
Silencing of the Prophenoloxidase Gene BtPPO1 Increased the Ability of Acquisition and Retention of Tomato chlorosis virus by Bemisia tabaci
Authors: Yang Nan , Ding Tianbo , Chu Dong
Published: June 2022

Tomato chlorosis virus (ToCV) has seriously impacted tomato production around the world. ToCV is semi-persistently transmitted by the whitefly, Bemisia tabaci, which is a serious agricultural pest in the world. However, the interaction mechanism between ToCV and its whitefly vector is still poorly understood. Our previous transcriptome analysis demonstrated that the expression level of an immune-related gene, prophenoloxidase (PPO), in B. tabaci increased after ToCV acquisition, which indicates that the PPO may be involved in the interaction mechanism between the ToCV and its vector. To determine the role of the PPO in the acquisition and retention of ToCV by B. tabaci, we cloned the complete Open Reading Frames (ORF) of the BtPPOs (BtPPO1 and BtPPO2), and then structure and phylogenetic analyses were performed. BtPPOs were closely related to the PPO genes of Hemiptera insects. Spatial-temporal expression detection was qualified by using reverse transcription quantitative PCR (RT-qPCR), and this revealed that BtPPOs were expressed in all tissues and developmental stages. We found that only BtPPO1 was significantly upregulated after B. tabaci acquired ToCV for 12 and 24 h. According to the paraffin-fluorescence probe-fluorescence in situ hybridization (FISH) experiment, we verified that ToCV and BtPPO1 were co-located in the thorax of B. tabaci, which further revealed the location of their interaction. Finally, the effects of the BtPPOs on ToCV acquisition and retention by B. tabaci were determined using RNA interference (RNAi). The results showed that the RNAi of the responsive gene (BtPPO1) significantly increased the titer of ToCV in B. tabaci. These results demonstrate that BtPPO1 participates in ToCV acquisition and retention by B. tabaci.
The Effectiveness of Antidiabetic Drugs in Treating Dementia: A Peek into Pharmacological and Pharmacokinetic Properties
Authors: Ogura Jiro , Yamaguchi Hiroaki
Published: June 2022

Dementia dramatically affects the activities of daily living and quality of life; thus, many therapeutic approaches for overcoming dementia have been developed. However, an effective treatment regimen is yet to be developed. As diabetes is a well-known risk factor for dementia, drug repositioning and repurposing of antidiabetic drugs are expected to be effective dementia treatments. Several observational studies have been useful for understanding the effectiveness of antidiabetic drugs in treating dementia, but it is difficult to conclusively analyze the association between antidiabetic drug treatment and the risk of developing dementia after correcting for potential confounding factors. Mechanism-based approaches may provide a better understanding of the effectiveness of antidiabetic drugs for treating dementia. Since the peripheral circulation and the central nerve system are separated by the blood–brain barrier, it is important to understand the regulation of the central glucose metabolism. In this review, we discuss the pharmacological and pharmacokinetic properties of antidiabetic drugs in relation to treating dementia.
Enrichment Methods for Murine Liver Non-Parenchymal Cells Differentially Affect Their Immunophenotype and Responsiveness towards Stimulation
Authors: Medina-Montano Carolina , Cacicedo Maximiliano Luis , Svensson Malin , Limeres Maria Jose , Zeyn Yanira , Chaves-Giraldo Jean Emiro , Röhrig Nadine , Grabbe Stephan , Gehring Stephan , Bros Matthias
Published: June 2022

Hepatocytes comprise the majority of the liver and largely exert metabolic functions, whereas non-parenchymal cells (NPCs)—comprising Kupffer cells, dendritic cells and liver sinusoidal endothelial cells—control the immunological state within this organ. Here, we compared the suitability of two isolation methods for murine liver NPCs. Liver perfusion (LP) with collagenase/DNase I applied via the portal vein leads to efficient liver digestion, whereas the modified liver dissociation (LD) method combines mechanical dissociation of the retrieved organ with enzymatic degradation of the extracellular matrix. In cases of both LP and LD, NPCs were enriched by subsequent gradient density centrifugation. Our results indicate that LP and LD are largely comparable with regards to the yield, purity, and composition of liver NPCs. However, LD-enriched liver NPCs displayed a higher degree of activation after overnight cultivation, and accordingly were less responsive towards stimulation with toll-like receptor ligands that are frequently used as adjuvants, e.g., in nano-vaccines. We conclude that LP is more suitable for obtaining liver NPCs for subsequent in vitro studies, whereas LD as the less laborious method, is more convenient for parallel isolation of larger numbers of samples for ex vivo analysis.
G-Protein Phosphorylation: Aspects of Binding Specificity and Function in the Plant Kingdom
Authors: Oliveira Celio Cabral , Jones Alan M. , Fontes Elizabeth Pacheco Batista , Reis Pedro A. Braga dos
Published: June 2022

Plant survival depends on adaptive mechanisms that constantly rely on signal recognition and transduction. The predominant class of signal discriminators is receptor kinases, with a vast member composition in plants. The transduction of signals occurs in part by a simple repertoire of heterotrimeric G proteins, with a core composed of α-, β-, and γ-subunits, together with a 7-transmembrane Regulator G Signaling (RGS) protein. With a small repertoire of G proteins in plants, phosphorylation by receptor kinases is critical in regulating the active state of the G-protein complex. This review describes the in vivo detected phosphosites in plant G proteins and conservation scores, and their in vitro corresponding kinases. Furthermore, recently described outcomes, including novel arrestin-like internalization of RGS and a non-canonical phosphorylation switching mechanism that drives G-protein plasticity, are discussed.
Ectopic Expression of Executor Gene Xa23 Enhances Resistance to Both Bacterial and Fungal Diseases in Rice
Authors: Ji Zhiyuan , Sun Hongda , Wei Yena , Li Man , Wang Hongjie , Xu Jiangmin , Lei Cailin , Wang Chunlian , Zhao Kaijun
Published: June 2022

Bacterial blight (BB) and bacterial leaf streak (BLS), caused by phytopathogenic bacteria Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively, are the most serious bacterial diseases of rice, while blast, caused by Magnaporthe oryzae (M. oryzae), is the most devastating fungal disease in rice. Generating broad-spectrum resistance to these diseases is one of the key approaches for the sustainable production of rice. Executor (E) genes are a unique type of plant resistance (R) genes, which can specifically trap transcription activator-like effectors (TALEs) of pathogens and trigger an intense defense reaction characterized by a hypersensitive response in the host. This strong resistance is a result of programed cell death induced by the E gene expression that is only activated upon the binding of a TALE to the effector-binding element (EBE) located in the E gene promoter during the pathogen infection. Our previous studies revealed that the E gene Xa23 has the broadest and highest resistance to BB. To investigate whether the Xa23-mediated resistance is efficient against Xanthomonas oryzae pv. oryzicola (Xoc), the causal agent of BLS, we generated a new version of Xa23, designated as Xa23p1.0, to specifically trap the conserved TALEs from multiple Xoc strains. The results showed that the Xa23p1.0 confers broad resistance against both BB and BLS in rice. Moreover, our further experiment on the Xa23p1.0 transgenic plants firstly demonstrated that the E-gene-mediated defensive reaction is also effective against M. oryzae, the causal agent of the most devastating fungal disease in rice. Our current work provides a new strategy to exploit the full potential of the E-gene-mediated disease resistance in rice.
Targeting Cell Cycle Progression in HER2+ Breast Cancer: An Emerging Treatment Opportunity
Authors: Koirala Nischal , Dey Nandini , Aske Jennifer , De Pradip
Published: June 2022

The development of HER2-targeted therapies has dramatically improved patient survival and patient management and increased the quality of life in the HER2+ breast cancer patient population. Due to the activation of compensatory pathways, patients eventually suffer from resistance to HER2-directed therapies and develop a more aggressive disease phenotype. One of these mechanisms is the crosstalk between ER and HER2 signaling, especially the CDK4/6-Cyclin D-Rb signaling axis that is commonly active and has received attention for its potential role in regulating tumor progression. CDK 4/6 inhibitors interfere with the binding of cell-cycle-dependent kinases (CDKs) with their cognate partner cyclins, and forestall the progression of the cell cycle by preventing Rb phosphorylation and E2F release that consequentially leads to cancer cell senescence. CDK 4/6 inhibitors, namely, palbociclib, ribociclib, and abemaciclib, in combination with anti-estrogen therapies, have shown impressive outcomes in hormonal receptor-positive (HR+) disease and have received approval for this disease context. As an extension of this concept, preclinical/clinical studies incorporating CDK 4/6 inhibitors with HER2-targeted drugs have been evaluated and have shown potency in limiting tumor progression, restoring therapeutic sensitivity, and may improving the management of the disease. Currently, several clinical trials are examining the synergistic effects of CDK 4/6 inhibitors with optimized HER2-directed therapies for the (ER+/-) HER2+ population in the metastatic setting. In this review, we aim to interrogate the burden of HER2+ disease in light of recent treatment progress in the field and examine the clinical benefit of CDK 4/6 inhibitors as a replacement for traditional chemotherapy to improve outcomes in HER2+ breast cancer.
Evaluation of Hydroxyl Radical Reactivity by Thioether Group Proximity in Model Peptide Backbone: Methionine versus S-Methyl-Cysteine
Authors: Chatgilialoglu Chryssostomos , Grzelak Magdalena , Skotnicki Konrad , Filipiak Piotr , Kazmierczak Franciszek , Hug Gordon L. , Bobrowski Krzysztof , Marciniak Bronislaw
Published: June 2022

Hydroxyl radicals (HO•) have long been regarded as a major source of cellular damage. The reaction of HO• with methionine residues (Met) in peptides and proteins is a complex multistep process. Although the reaction mechanism has been intensively studied, some essential parts remain unsolved. In the present study we examined the reaction of HO• generated by ionizing radiation in aqueous solutions under anoxic conditions with two compounds representing the simplest model peptide backbone CH3C(O)NHCHXC(O)NHCH3, where X = CH2CH2SCH3 or CH2SCH3, i.e., the Met derivative in comparison with the cysteine-methylated derivative. We performed the identification and quantification of transient species by pulse radiolysis and final products by LC–MS and high-resolution MS/MS after γ-radiolysis. The results allowed us to draw for each compound a mechanistic scheme. The fate of the initial one-electron oxidation at the sulfur atom depends on its distance from the peptide backbone and involves transient species of five-membered and/or six-membered ring formations with different heteroatoms present in the backbone as well as quite different rates of deprotonation in forming α-(alkylthio)alkyl radicals.
Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease
Authors: Folke Jonas , Bergholt Emil , Pakkenberg Bente , Aznar Susana , Brudek Tomasz
Published: June 2022

Multiple-system trophy (MSA) and Parkinson’s Disease (PD) are both progressive, neurodegenerative diseases characterized by neuropathological deposition of aggregated alpha-synuclein (αSyn). The causes behind this aggregation are still unknown. We have reported aberrancies in MSA and PD patients in naturally occurring autoantibodies (nAbs) against αSyn (anti-αSyn-nAbs), which are important partakers in anti-aggregatory processes, immune-mediated clearance, and anti-inflammatory functions. To elaborate further on the timeline of autoimmune aberrancies towards αSyn, we investigated here the Immunoglobulin (Ig) affinity profile and subclass composition (IgG-total, IgG1-4 and IgM) of anti-αSyn-nAbs in serum samples from prodromal (p) phases of MSA and PD. Using an electrochemiluminescence competition immunoassay, we confirmed that the repertoire of high-affinity anti-αSyn-nAbs is significantly reduced in pMSA and pPD. Further, we demonstrated that pPD had increased anti-αSyn IgG-total levels compared to pMSA and controls, concordant with increased anti-αSyn IgG1 levels in pPD. Anti-αSyn IgG2 and IgG4 levels were reduced in pMSA and pPD compared with controls, whereas anti-αSyn IgG3 levels were reduced in pMSA compared to pPD and controls. The results indicate that the impaired reactivity towards αSyn occurs prior to disease onset. The apparent lack of high-affinity anti-αSyn nAbs may result in reduced clearance of αSyn, leading to aggregation of the protein. Thus, this study provides novel insights into possible causes behind the pathogenesis in synucleinopathies such as MSA and PD.
Twelve-Nitrogen-Atom Cyclic Structure Stabilized by 3d-Element Atoms: Quantum Chemical Modeling
Authors: Mikhailov Oleg V. , Chachkov Denis V.
Published: June 2022

Using various versions of density functional theory (DFT), DFT M06/TZVP, DFT B3PW91/TZVP, DFT OPBE/TZVP, and, partially, the MP2 method, the possibility of the existence of 3d-element (M) compounds with nitrogen having unusual M: nitrogen ratio 1:12, unknown for these elements at the present, was shown. Structural parameter data were presented. It was shown that all MN4 groupings have tetragonal-pyramidal structure. It was noted that the bond lengths formed by nitrogen atoms and an M atom were equal to each other only in the case of M = Ti, V, Cr and Co, whereas for other Ms, they were slightly different; moreover, the bond angles formed by nitrogen atoms and an M atom were equal to 90.0°, or practically did not differ from this value. Thermodynamic parameters, NBO analysis data and HOMO/LUMO images for this compound were also presented. Good agreement between the calculated data obtained using the above three quantum chemical methods was also noted.
Bulge-Forming miRNases Cleave Oncogenic miRNAs at the Central Loop Region in a Sequence-Specific Manner
Authors: Patutina Olga , Chiglintseva Daria , Amirloo Bahareh , Clarke David , Gaponova Svetlana , Vlassov Valentin , Bichenkova Elena , Zenkova Marina
Published: June 2022

The selective degradation of disease-associated microRNA is promising for the development of new therapeutic approaches. In this study, we engineered a series of bulge-loop-forming oligonucleotides conjugated with catalytic peptide [(LeuArg)2Gly]2 (BC–miRNases) capable of recognizing and destroying oncogenic miR-17 and miR-21. The principle behind the design of BC–miRNase is the cleavage of miRNA at a three-nucleotide bulge loop that forms in the central loop region, which is essential for the biological competence of miRNA. A thorough study of mono- and bis-BC–miRNases (containing one or two catalytic peptides, respectively) revealed that: (i) the sequence of miRNA bulge loops and neighbouring motifs are of fundamental importance for efficient miRNA cleavage (i.e., motifs containing repeating pyrimidine–A bonds are more susceptible to cleavage); (ii) the incorporation of the second catalytic peptide in the same molecular scaffold increases the potency of BC–miRNase, providing a complete degradation of miR-17 within 72 h; (iii) the synergetic co-operation of BC–miRNases with RNase H accelerates the rate of miRNA catalytic cleavage by both the conjugate and the enzyme. Such synergy allows the rapid destruction of constantly emerging miRNA to maintain sufficient knockdown and achieve a desired therapeutic effect.
A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications
Authors: Teixeira Maria C. , Lameirinhas Nicole S. , Carvalho João P. F. , Silvestre Armando J. D. , Vilela Carla , Freire Carmen S. R.
Published: June 2022

Three-dimensional (3D) bioprinting is an innovative technology in the biomedical field, allowing the fabrication of living constructs through an approach of layer-by-layer deposition of cell-laden inks, the so-called bioinks. An ideal bioink should possess proper mechanical, rheological, chemical, and biological characteristics to ensure high cell viability and the production of tissue constructs with dimensional stability and shape fidelity. Among the several types of bioinks, hydrogels are extremely appealing as they have many similarities with the extracellular matrix, providing a highly hydrated environment for cell proliferation and tunability in terms of mechanical and rheological properties. Hydrogels derived from natural polymers, and polysaccharides, in particular, are an excellent platform to mimic the extracellular matrix, given their low cytotoxicity, high hydrophilicity, and diversity of structures. In fact, polysaccharide-based hydrogels are trendy materials for 3D bioprinting since they are abundant and combine adequate physicochemical and biomimetic features for the development of novel bioinks. Thus, this review portrays the most relevant advances in polysaccharide-based hydrogel bioinks for 3D bioprinting, focusing on the last five years, with emphasis on their properties, advantages, and limitations, considering polysaccharide families classified according to their source, namely from seaweed, higher plants, microbial, and animal (particularly crustaceans) origin.
Hydrogen Peroxide Stimulates Dihydrotestosterone Release in C2C12 Myotubes: A New Perspective for Exercise-Related Muscle Steroidogenesis?
Authors: Antinozzi Cristina , Duranti Guglielmo , Ceci Roberta , Lista Marco , Sabatini Stefania , Caporossi Daniela , Di Luigi Luigi , Sgrò Paolo , Dimauro Ivan
Published: June 2022

Skeletal muscle is a tissue that has recently been recognized for its ability to produce androgens under physiological conditions. The steroidogenesis process is known to be negatively influenced by reactive oxygen species (ROS) in reproductive Leydig and ovary cells, while their effect on muscle steroidogenesis is still an unexplored field. Muscle cells are continuously exposed to ROS, resulting from both their metabolic activity and the surrounding environment. Interestingly, the regulation of signaling pathways, induced by mild ROS levels, plays an important role in muscle fiber adaptation to exercise, in a process that also elicits a significant modulation in the hormonal response. The aim of the present study was to investigate whether ROS could influence steroidogenesis in skeletal muscle cells by evaluating the release of testosterone (T) and dihydrotestosterone (DHT), as well as the evaluation of the relative expression of the key steroidogenic enzymes 5α-reductase, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, and aromatase. C2C12 mouse myotubes were exposed to a non-cytotoxic concentration of hydrogen peroxide (H2O2), a condition intended to reproduce, in vitro, one of the main stimuli linked to the process of homeostasis and adaptation induced by exercise in skeletal muscle. Moreover, the influence of tadalafil (TAD), a phosphodiesterase 5 inhibitor (PDE5i) originally used to treat erectile dysfunction but often misused among athletes as a “performance-enhancing” drug, was evaluated in a single treatment or in combination with H2O2. Our data showed that a mild hydrogen peroxide exposure induced the release of DHT, but not T, and modulated the expression of the enzymes involved in steroidogenesis, while TAD treatment significantly reduced the H2O2-induced DHT release. This study adds a new piece of information about the adaptive skeletal muscle cell response to an oxidative environment, revealing that hydrogen peroxide plays an important role in activating muscle steroidogenesis.
Effect of Passage Number of Conditioned Medium Collected from Equine Amniotic Fluid Mesenchymal Stem Cells: Porcine Oocyte Maturation and Embryo Development
Authors: Park Ahyoung , Oh Hyun Ju , Ji Kukbin , Choi Eunha Miri , Kim Dongern , Kim Eunyoung , Kim Min Kyu
Published: June 2022

Oocyte in vitro maturation (IVM) is the most important first step in in vitro embryo production. One prerequisite for the success of IVM in oocytes is to provide a rich culture microenvironment that meets the nutritional needs of developing oocytes. We applied different equine amniotic fluid mesenchymal stem cell conditioned medium (eAFMSC-CM) from passages 7, 18, and 27 to porcine oocytes during IVM to determine its effects on oocyte development and subsequent embryo development, specifically. The eAFMSC-CM from passage 7 (eAFMSC-CMp7) has a considerable impact on 9 genes: BAX, BCL2, SOD2, NRF2, TNFAIP6, PTGS2, HAS2, Cx37, and Cx43, which are associated with cumulus cell mediated oocyte maturation. GSH levels and distribution of mitochondrial and cortical granules were significantly increased in oocytes incubated with eAFMSC-CMp7. In addition, catalase and superoxide dismutase activities were high after IVM 44 h with eAFMSC-CMp7. After in vitro fertilization, blastocyst quality was significantly increased in the eAFMSC-CMp7 group compared to control. Lastly, the antioxidant effect of eAFMSC-CMp7 substantially regulated the expression of apoptosis, pluripotency related genes and decreased autophagy activity in blastocysts. Taken together, this study demonstrated that the eAFMSC-CMp7 enhanced the cytoplasmic maturation of oocytes and subsequent embryonic development by generating high antioxidant activity.
Brexpiprazole Reduces 5-HT7 Receptor Function on Astroglial Transmission Systems
Authors: Fukuyama Kouji , Motomura Eishi , Okada Motohiro
Published: June 2022

Several atypical antipsychotics exert mood-stabilising effects via the modulation of various monoamine receptors and intracellular signallings. Recent pharmacodynamic studies suggested that tripartite synaptic transmission can contribute to the pathophysiology of schizophrenia and mood disorders, their associated cognitive impairment, and several adverse reactions to atypical antipsychotics. Therefore, to explore the mechanisms underlying the antidepressive mood-stabilising and antipsychotic effects of brexpiprazole (Brex), we determined the effects of subchronic administration of therapeutically relevant concentrations/doses of Brex on the protein expression of 5-HT receptors, connexin43, cAMP levels, and intracellular signalling in cultured astrocytes and rat hypothalamus using ultra-high-pressure liquid chromatography with mass spectrometry and capillary immunoblotting systems. Subchronic administration of a therapeutically relevant concentration of Brex (300 nM) downregulated both 5-HT1A (5-HT1AR) and 5-HT7 (5-HT7R) receptors, in addition to phosphorylated Erk (pErk), without affecting phosphorylated Akt in the astroglial plasma membrane. Subchronic administration of 300 nM Brex decreased and increased phosphorylated AMPK and connexin43, respectively, in the astroglial cytosol fraction. A therapeutically relevant concentration of Brex acutely decreased the astroglial cAMP level, whereas, under the inhibition of 5-HT1AR, Brex did not affect astroglial cAMP levels. However, the 5-HT7R-agonist-induced increased astroglial cAMP level was inhibited by Brex. In contrast to the in vitro study, systemic subchronic administration of effective doses of Brex (3 and 10 mg/kg/day for 14 days) increased the cAMP level but did not affect phosphorylated AMPK in the rat hypothalamus. These results suggest several complicated pharmacological features of Brex. Partial 5-HT1AR agonistic action predominates in the low range of therapeutically relevant concentrations of Brex, whereas in the high range, 5-HT7R inverse agonist-like action is overlapped on the 5-HT1A agonistic action. These unique suppressive effects of Brex on 5-HT7R play important roles in the clinical features of Brex regarding its antidepressive mood-stabilising actions.
Inhibition of N-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication
Authors: Ma Ningning , Liu Haijing , Wu Yaqian , Yao Mengfei , Zhang Bo
Published: June 2022

Cancer suppression through the inhibition of N-acetyltransferase 10 (NAT10) by its specific inhibitor Remodelin has been demonstrated in a variety of human cancers. Here, we report the inhibitory effects of Remodelin on prostate cancer (PCa) cells and the possible associated mechanisms. The prostate cancer cell lines VCaP, LNCaP, PC3, and DU145 were used. The in vitro proliferation, migration, and invasion of cells were measured by a cell proliferation assay, colony formation, wound healing, and Transwell assays, respectively. In vivo tumor growth was analyzed by transplantation into nude mice. The inhibition of NAT10 by Remodelin not only suppressed growth, migration, and invasion in vitro, but also the in vivo cancer growth of prostate cancer cells. The involvement of NAT10 in DNA replication was assessed by EdU labeling, DNA spreading, iPOND, and ChIP-PCR assays. The inhibition of NAT10 by Remodelin slowed DNA replication. NAT10 was detected in the prereplication complex, and it could also bind to DNA replication origins. Furthermore, the interaction between NAT10 and CDC6 was analyzed by Co-IP. The altered expression of NAT10 was measured by immunofluorescence staining and Western blotting. Remodelin markedly reduced the levels of CDC6 and AR. The expression of NAT10 could be altered under either castration or noncastration conditions, and Remodelin still suppressed the growth of in vitro-induced castration-resistant prostate cancers. The analysis of a TCGA database revealed that the overexpression of NAT10, CDC6, and MCM7 in prostate cancers were correlated with the Gleason score and node metastasis. Our data demonstrated that Remodelin, an inhibitor of NAT10, effectively inhibits the growth of prostate cancer cells under either no castration or castration conditions, likely by impairing DNA replication.
Application Progress of Modified Chitosan and Its Composite Biomaterials for Bone Tissue Engineering
Authors: Zhu Yuemeng , Zhang Yidi , Zhou Yanmin
Published: June 2022

In recent years, bone tissue engineering (BTE), as a multidisciplinary field, has shown considerable promise in replacing traditional treatment modalities (i.e., autografts, allografts, and xenografts). Since bone is such a complex and dynamic structure, the construction of bone tissue composite materials has become an attractive strategy to guide bone growth and regeneration. Chitosan and its derivatives have been promising vehicles for BTE owing to their unique physical and chemical properties. With intrinsic physicochemical characteristics and closeness to the extracellular matrix of bones, chitosan-based composite scaffolds have been proved to be a promising candidate for providing successful bone regeneration and defect repair capacity. Advances in chitosan-based scaffolds for BTE have produced efficient and efficacious bio-properties via material structural design and different modifications. Efforts have been put into the modification of chitosan to overcome its limitations, including insolubility in water, faster depolymerization in the body, and blood incompatibility. Herein, we discuss the various modification methods of chitosan that expand its fields of application, which would pave the way for future applied research in biomedical innovation and regenerative medicine.
Sleepers Spacing Analysis in Railway Track Infrastructure
Authors: Sañudo Roberto , Miranda Marina , Alonso Borja , Markine Valeri
Published: June 2022

Sleeper spacing has been a taboo subject throughout the railway’s history. Safety concerns related to the structural integrity have been the main causes of not addressing this matter. There are no specific and clear recommendations or guidelines in relation to this matter and the distances do not go more than 0.8 m. In order to go beyond this current situation, the following research paper analyses the influence of the spacing between sleepers on the behaviour of ballasted tracks by performing a dynamic simulation with finite elements in two dimensions for different track configurations, different elements, geometries, and separations within the frame of the ODSTRACK project. The variables studied are the vertical displacements, the forces and stresses on the most important elements of the superstructure, as well as the vertical accelerations in the sleepers and the train. The values obtained from the numerical simulations were compared with the maximum permitted values according to the guidelines. To limit this distance to the most restrictive variable among those analysed, it is necessary to make important assumptions, such as the permissible values and effective support contact areas between the sleepers and the ballast. The preliminary analyses carried out shed light on a possible increment of the spacing between sleepers’ axes up to more than 0.8 m. This suggests that important savings in railways construction costs can be achieved, and they will help to develop the next stage of the ODSTRACK project.
What Are the Best Pollinator Candidates for Camellia oleifera: Do Not Forget Hoverflies and Flies
Authors: Yuan Bin , Hu Guan-Xing , Zhang Xiao-Xiao , Yuan Jing-Kun , Fan Xiao-Ming , Yuan De-Yi
Published: June 2022

Camellia oleifera Abel. is an important woody oil plant, and its pollination success is essential for oil production. We conducted this study to select the best pollinator candidates for C. oleifera using principal component analysis and multi-attribute decision-making. Field observations of the flower-visiting characteristics of candidate pollinators were conducted at three sites. The insect species that visited flowers did not considerably differ between regions or time periods. However, the proportion of each species recorded did vary. We recorded eleven main candidates from two orders and six families at the three sites. The pollen amount carried by Apis mellifera was significantly higher than that of other insects. However, the visit frequency and body length of Apis mellifera were smaller than those of Vespa velutina. Statistical analysis showed that A. mellifera is the best candidate pollinator; Eristaliscerealis is a good candidate pollinator; Phytomia zonata, A. cerana, and V. velutina were ordinary candidate pollinators; and four fly species, Episyrphus balteatus, and Eristalinus arvorum were classified as inefficient candidate pollinators. Our study shows that flies and hoverflies play an important role in the pollination system. Given the global decline in bee populations, the role of flies should also be considered in C. oleifera seed production.