bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Affecting Grazing and Rumination Behaviours of Dairy Cows in a Pasture-Based System in New Zealand
Authors: Iqbal Muhammad Wasim , Draganova Ina , Morel Patrick C. H. , Morris Stephen T.
Published: November 2022

This study investigated the variation in daily time spent grazing and rumination in spring-calved grazing dairy cows (n = 162) of three breeds, Holstein-Friesian (HFR), Jersey (JE), and KiwiCross (KC) with different breeding worth index, and in different years of lactation (1st, 2nd, 3rd, 4th). The cows were managed through a rotational grazing system and milked once a day at 05:00 a.m. The cows grazed mainly pasture and received supplementary feeds depending on the season. Automated AfiCollar device continuously monitored and recorded grazing time and rumination time of the individual cows throughout the lactation period for three study years (Year-1, Year-2, Year-3) with 54 cows per year. A general linear mixed model fitted with breed × lactation year with days in milk (DIM), breeding worth (BW) index value, individual cow, season, and feed, and their interactions was performed in SAS. Variance partitioning was used to quantify the effect size of study factors and their interactions. Individual cows, DIM, and BW (except Year-3) had effects on grazing and rumination times throughout the study years. Grazing time and rumination time were different for different seasons due to varying supplementary feeds. Grazing time varied among breeds in Year-2 and Year-3, and among lactation years only in Year-1. Although rumination time differed among breeds in Year-3, it remained the same within different lactation years. Grazing time and rumination time had a negative relationship with each other, and their regression lines varied for different seasons. The total variance explained by the model in grazing time was 36–39%, mainly contributed by the individual cow (12–20%), season (5–12%), supplementary feed (2–6%), breed (1–5%), and lactation year (1–6%). The total variance explained in rumination was 40–41%, mainly contributed by the individual cow (16–24%), season (2–17%), supplementary feed (1–2%), breed (2–8%), and lactation year (~1%). These findings could contribute to improving the measures for feed resource management during different seasons over the lactation period for a mixed herd comprising JE, HFR and KC breeds in different years of lactation.
FastICA Algorithm Applied on Black Sea Water-Level Ultrasound Measurements
Authors: Ghita Cristian , Tuta Leontin , Moldovan Iren-Adelina , Ionescu Constantin , Nicolaescu Mircea
Published: November 2022

The parameters influencing the sea level measured with ultrasonic devices that are analyzed in this paper are the air temperature, atmospheric pressure and wind speed. As these variations are independent to each other and to the sea level, they can be removed from the measured sea level by applying a filtering algorithm based on independent component analysis (FastICA), adapted and improved for this application. The sound speed increases with temperature, so an internal temperature sensor is required to compensate for the sound-speed variation. Though this may improve the measurement accuracy, it is not enough to achieve the best results because there is a discrepancy between the internal sensor and the actual environment temperature. For high accuracy measurements, an external temperature sensor is required. In our case, we imported temperature datasets from a weather station, along with other datasets regarding atmospheric pressure and wind speed. The use of these external datasets, along with an algorithm based on principal component analysis (PCA) for error removal and the filtering algorithm based on FastICA for environmental phenomena extraction, allows us to achieve more accurate values for the Black Sea level in Constanta (2017–2020), independent of external influences.
Composite Cathodes Based on Lithium-Iron Phosphate and N-Doped Carbon Materials
Authors: Stenina Irina , Safikanov Danis , Minakova Polina , Novikova Svetlana , Kulova Tatiana , Yaroslavtsev Andrey
Published: November 2022

The effect of different nitrogen-doped carbon additives (carbon coating from polyaniline, N-doped carbon nanotubes, and N-doped carbon nanoparticles) on electrochemical performance of nanocomposites based on the olivine-type LiFePO4 was investigated. Prepared materials were characterized by XRD, SEM, TGA-MS, CHNS-analysis, IR-, Raman, and impedance spectroscopies. Polyaniline deposition on the LiFePO4 precursor with following annealing lead to the formation of a LiFePO4/C nanocomposite with a carbon coating doped with nitrogen. Due to nitrogen atoms presence in carbon coating, the LiFePO4/N-doped carbon nanocomposites showed enhanced conductivity and C-rate capability. The discharge capacities of the synthesized materials in LIBs were close to the theoretical value at 0.1 C and retained high values with increasing current density. At high C-rates, the best results were obtained for a more dispersed LiFePO4/C composite with carbon coating prepared from polyaniline previously in situ deposited on LiFePO4 precursor particles. Its discharge capacity reached 96, 84, 73, and 47 mAh g−1 at 5, 10, 20, and 60 C-rates, respectively.
Image Segmentation for Mitral Regurgitation with Convolutional Neural Network Based on UNet, Resnet, Vnet, FractalNet and SegNet: A Preliminary Study
Authors: Atika Linda , Nurmaini Siti , Partan Radiyati Umi , Sukandi Erwin
Published: November 2022

The heart’s mitral valve is the valve that separates the chambers of the heart between the left atrium and left ventricle. Heart valve disease is a fairly common heart disease, and one type of heart valve disease is mitral regurgitation, which is an abnormality of the mitral valve on the left side of the heart that causes an inability of the mitral valve to close properly. Convolutional Neural Network (CNN) is a type of deep learning that is suitable for use in image analysis. Segmentation is widely used in analyzing medical images because it can divide images into simpler ones to facilitate the analysis process by separating objects that are not analyzed into backgrounds and objects to be analyzed into foregrounds. This study builds a dataset from the data of patients with mitral regurgitation and patients who have normal hearts, and heart valve image analysis is done by segmenting the images of their mitral heart valves. Several types of CNN architecture were applied in this research, including U-Net, SegNet, V-Net, FractalNet, and ResNet architectures. The experimental results show that the best architecture is U-Net3 in terms of Pixel Accuracy (97.59%), Intersection over Union (86.98%), Mean Accuracy (93.46%), Precision (85.60%), Recall (88.39%), and Dice Coefficient (86.58%).
Pulsed Electric Field Ablation of Epicardial Autonomic Ganglia: Computer Analysis of Monopolar Electric Field across the Tissues Involved
Authors: González-Suárez Ana , O’Brien Barry , O’Halloran Martin , Elahi Adnan
Published: November 2022

Background and objectives: Pulsed Electric Field (PEF) ablation has been proposed as a non-thermal energy to treat atrial fibrillation (AF) by epicardial ablation of ganglionated plexi (GP), which are embedded within epicardial fat. Our objective was to study the distribution of the electric field through the involved tissues (fat, GPs, myocardium and blood) during epicardial PEF ablation. Methods: A two-dimensional model was built considering different tissue layers below the ablation device which consists of an irrigated electrode. The 1000 V/cm threshold was used to estimate the ‘PEF-zone’. Results: The PEF-zone was almost 100% circumscribed in the epicardial fat layer, with very little incidence in the myocardium. The presence of the saline on the epicardial fat causes the PEF-zone to spread laterally around the electrode from ~5 mm to ~15 mm, relatively independently of how embedded the electrode is in the saline layer. For a saline layer well spread over the tissue surface and an electrode fully embedded in the saline layer, the PEF-zone width decreases as the fat layer thickens: from ~15 mm for fat thickness of 1 and 2 mm, down to ~10 mm for fat thickness of 5 mm. The presence of a GP in the center of the fat layer hardly affects the size of the PEF-zone, but significantly alters the distribution of the electric field around the GP, resulting in progressively lower values than in the surrounding adipose tissue as the fat layer thickness increased. Conclusions: Our results suggest how some procedural (irrigation) and anatomical parameters (fat thicknesses and presence of GPs) could be relevant in terms of the size of the tissue area affected by pulsed field ablation.
Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice
Authors: Li Yunxian , Lin Shixin , Xiong Sheng , Xie Qiuling
Published: November 2022

Chronic refractory wounds are one of the complications of diabetes mellitus that require effective therapy. The dermal-wound-healing property of IL-33 in diabetics is little understood. Therefore, this study aimed to express recombinant humanized mature IL-33 (rhmatIL-33) in Escherichia coli BL21 (DE3) and demonstrate its efficacy on dermal wounds in streptozotocin (STZ)-induced diabetic and nondiabetic mice by the dorsal incisional skin wound model. Results revealed that the rhmatIL-33 accelerated the scratch-healing of keratinocytes and fibroblasts at the cellular level. The wounds of diabetic mice (DM) showed more severe ulceration and inflammation than wild-type mice (WT), and the exogenous administration of rhmatIL-33 increased wound healing in both diabetic and wild-type mice. Compared with the up-regulation of endogenous IL-33 mRNA after injury in WT mice, the IL-33 mRNA decreased after injury in DM mice. Exogenous IL-33 administration increased the endogenous IL-33 mRNA in the DM group but decreased the IL-33 mRNA expression level of the WT group, indicating that IL-33 plays a balancing role in wound healing. IL-33 administration also elevated ILC2 cells in the wounds of diabetic and non-diabetic mice and improve the transcript levels of YM1, a marker of M2 macrophages. In conclusion, Hyperglycemia in diabetic mice inhibited the expression of IL-33 in the dermal wound. Exogenous addition of recombinant IL-33 promoted wound healing in diabetic mice by effectively increasing the level of IL-33 in wound tissue, increasing ILC2 cells, and accelerating the transformation of macrophage M1 to M2 phenotype.
Contact Electrification of Biological and Bio-Inspired Adhesive Materials on SiO2 Surfaces: Perspectives from DFT Calculations
Authors: Tao Jing , Wang Linfeng , Kong Kaixuan , Hu Minhao , Dai Zhendong
Published: November 2022

In this study, we investigate the contact electrification properties of glycine, cysteine, and dimethyl siloxane on silicon dioxide (SiO2) surfaces using density functional theory calculations. Molecule contacting through the sulfhydryl group has stronger adhesion to the SiO2-O and SiO2-OH surfaces. The SiOH/SiO2-Si system has the largest adhesion energy in all molecule/SiO2-Si contact systems and charge transfers from the molecule to the SiO2-O and SiO2-Si surfaces. The molecule/SiO2-OH systems have a reverse charge transfer direction. Molecules with their sulfhydryl and hydroxyl groups facing the SiO2-O and SiO2-OH surfaces have more transferred charges. The NH2/SiO2-Si system has a larger transferred charge than other molecule/SiO2-Si systems. The direction of charge transfer is determined by the Bader charge of the isolated surface atoms. The respective energy difference in the lowest unoccupied occupied molecular orbitals between contacting atoms influences the charge transfer. The respective energy difference in the highest occupied molecular orbitals reflects the electron attraction and affects charge transfer. Finally, the quantitative relationship between the transferred charge and energy gaps is established to evaluate the charge transfer. The findings propose a new perspective and in-depth understanding of contact electrification and shed light on the bio-inspired adhesive materials design and fabrication for engineering applications.
Growing Brains, Nurturing Minds—Neuroscience as an Educational Tool to Support Students’ Development as Life-Long Learners
Authors: Goldberg Hagar
Published: November 2022

Compared to other primates, humans are late bloomers, with exceptionally long childhood and adolescence. The extensive developmental period of humans is thought to facilitate the learning processes required for the growth and maturation of the complex human brain. During the first two and a half decades of life, the human brain is a construction site, and learning processes direct its shaping through experience-dependent neuroplasticity. Formal and informal learning, which generates long-term and accessible knowledge, is mediated by neuroplasticity to create adaptive structural and functional changes in brain networks. Since experience-dependent neuroplasticity is at full force during school years, it holds a tremendous educational opportunity. In order to fulfill this developmental and learning potential, educational practices should be human-brain-friendly and “ride” the neuroplasticity wave. Neuroscience can inform educators about the natural learning mechanisms of the brain to support student learning. This review takes a neuroscientific lens to explore central concepts in education (e.g., mindset, motivation, meaning-making, and attention) and suggests two methods of using neuroscience as an educational tool: teaching students about their brain (content level) and considering the neuro-mechanisms of learning in educational design (design level).
Validation of the Achievement Emotions Questionnaire for Experimental Science Education (AEQ-S)
Authors: Macías León Kevin , de las Heras Pérez M. Ángeles , Romero Fernández Raquel , González Castanedo Yolanda , Sáenz-López Pedro
Published: November 2022

The Achievement Emotions Questionnaire (AEQ), based on the control-value theory of achievement emotions, has been used in many fields of knowledge and has been translated into many languages. The main objective of this study was to adapt and validate it for the experimental sciences. A sample of 491 participants aged between 11 and 17 years (M = 13.73, SD = 1.19) from secondary schools in different localities in the provinces of Huelva and Lanzarote, Spain was used. The results obtained from the various statistical analyses showed that the questionnaire was valid and reliable. The main contribution of the work presented is to broaden the field of application of a test on emotions, AEQ-S, to experimental sciences. The AEQ-ES will allow us to learn the emotional profiles of students, thus providing information to teachers, and will be very useful for future research aimed at the study of emotions in experimental sciences.
Elaiophylin Inhibits Tumorigenesis of Human Lung Adenocarcinoma by Inhibiting Mitophagy via Suppression of SIRT1/Nrf2 Signaling
Authors: Ji Jiali , Wang Ke , Meng Xinmin , Zhong Hongqin , Li Xiyue , Zhao Hongqing , Xie Guijuan , Xie Yunying , Wang Xun , Zhu Xue
Published: November 2022

Lung adenocarcinoma (LADC), the most common type of lung cancer, is still one of the most aggressive and rapidly fatal tumor types, even though achievements in new therapeutic approaches have been developed. Elaiophylin as a C2 symmetrically glycosylated 16 macrolides has been reported to be a late-stage autophagy inhibitor with a potent anti-tumor effect on various cancers. This study investigated the anti-tumor effect of elaiophylin on human LADC for the first time in in vitro and in vivo models. The in vitro study in LADC A549 cells showed that elaiophylin significantly inhibited cell viability and induced cell apoptosis through the suppression of mitophagy and induction of cellular and mitochondrial oxidative stress. Proteomic analysis and molecular docking assay implicated that SIRT1 was likely the direct target of elaiophylin in A549 cells. Further mechanistic study verified that elaiophylin reduced Nrf2 deacetylation, expression, and transcriptional activity as well as cytoplasm translocation by downregulating SIRT1 expression and deacetylase activity. Additionally, SIRT1/Nrf2 activation could attenuate elaiophylin-induced mitophagy inhibition and oxidative stress. The in vivo study in the A549-xenograft mice model showed that the anti-tumor effect of elaiophylin was accompanied by the decreased expressions of SIRT1, Nrf2, Parkin, and PINK1. Thus, the present study reports that elaiophylin has potent anti-tumor properties in LADC, which effect is likely mediated through suppressing the SIRT1/Nrf2 signaling. In conclusion, elaiophylin may be a novel drug candidate for LADC and SIRT1 may be a new therapeutic target for such devastating malignancy.
The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
Authors: Zgajnar Nadia R. , Daneri-Becerra Cristina , Cauerhff Ana , Galigniana Mario D.
Published: November 2022

The immunophilin FKBP51 forms heterocomplexes with molecular chaperones, protein-kinases, protein-phosphatases, autophagy-related factors, and transcription factors. Like most scaffold proteins, FKBP51 can use a simple tethering mechanism to favor the efficiency of interactions with partner molecules, but it can also exert more complex allosteric controls over client factors, the immunophilin itself being a putative regulation target. One of the simplest strategies for regulating pathways and subcellular localization of proteins is phosphorylation. In this study, it is shown that scaffold immunophilin FKBP51 is resolved by resolutive electrophoresis in various phosphorylated isoforms. This was evidenced by their reactivity with specific anti-phosphoamino acid antibodies and their fade-out by treatment with alkaline phosphatase. Interestingly, stress situations such as exposure to oxidants or in vivo fasting favors FKBP51 translocation from mitochondria to the nucleus. While fasting involves phosphothreonine residues, oxidative stress involves tyrosine residues. Molecular modeling predicts the existence of potential targets located at the FK1 domain of the immunophilin. Thus, oxidative stress favors FKBP51 dephosphorylation and protein degradation by the proteasome, whereas FK506 binding protects the persistence of the post-translational modification in tyrosine, leading to FKBP51 stability under oxidative conditions. Therefore, FKBP51 is revealed as a phosphoprotein that undergoes differential phosphorylations according to the stimulus.
Canonical and Noncanonical ER Stress-Mediated Autophagy Is a Bite the Bullet in View of Cancer Therapy
Authors: Alam Rashedul , Kabir Mohammad Fazlul , Kim Hyung-Ryong , Chae Han-Jung
Published: November 2022

Cancer cells adapt multiple mechanisms to counter intense stress on their way to growth. Tumor microenvironment stress leads to canonical and noncanonical endoplasmic stress (ER) responses, which mediate autophagy and are engaged during proteotoxic challenges to clear unfolded or misfolded proteins and damaged organelles to mitigate stress. In these conditions, autophagy functions as a cytoprotective mechanism in which malignant tumor cells reuse degraded materials to generate energy under adverse growing conditions. However, cellular protection by autophagy is thought to be complicated, contentious, and context-dependent; the stress response to autophagy is suggested to support tumorigenesis and drug resistance, which must be adequately addressed. This review describes significant findings that suggest accelerated autophagy in cancer, a novel obstacle for anticancer therapy, and discusses the UPR components that have been suggested to be untreatable. Thus, addressing the UPR or noncanonical ER stress components is the most effective approach to suppressing cytoprotective autophagy for better and more effective cancer treatment.
Parental Genetics Communicate with Intrauterine Environment to Reprogram Newborn Telomeres and Immunity
Authors: Farrukh Sadia , Baig Saeeda , Hussain Rubina , Imad Rehan , Khalid Maria
Published: November 2022

Telomeres, markers for cellular senescence, have been found substantially influenced by parental inheritance. It is well known that genomic stability is preserved by the DNA repair mechanism through telomerase. This study aimed to determine the association between parents–newborn telomere length (TL) and telomerase gene (TERT), highlighting DNA repair combined with TL/TERT polymorphism and immunosenescence of the triad. The mother–father–newborn triad blood samples (n = 312) were collected from Ziauddin Hospitals, Pakistan, between September 2021 and June 2022. The telomere length (T/S ratio) was quantified by qPCR, polymorphism was identified by Sanger sequencing, and immunosenescence by flow cytometry. The linear regression was applied to TL and gene association. The newborns had longest TL (2.51 ± 2.87) and strong positive association (R = 0.25, p ≤ 0.0001) (transgenerational health effects) with mothers’ TL (1.6 ± 2.00). Maternal demographics—socioeconomic status, education, and occupation—showed significant effects on TL of newborns (p < 0.015, 0.034, 0.04, respectively). The TERT risk genotype CC (rs2736100) was predominant in the triad (0.6, 0.5, 0.65, respectively) with a strong positive association with newborn TL (β = 2.91, <0.0011). Further analysis highlighted the expression of KLRG 1+ in T-cells with shorter TL but less frequent among newborns. The study concludes that TERT, parental TL, antenatal maternal health, and immunity have a significantly positive effect on the repair of newborn TL.
New Insights into Mechanisms of Ferroptosis Associated with Immune Infiltration in Neonatal Hypoxic-Ischemic Brain Damage
Authors: Li Shangbin , Wan Li , Sun Jingfei , Yan Weichen , Wang Jie , Gao Xiong , Ren Changjun , Hao Ling
Published: November 2022

Background: The mechanisms underlying ferroptosis in neonatal hypoxic-ischemic brain damage (HIBD) remain unclear. Method: Four microarray datasets were collected from the GEO database (three mRNA datasets GSE23317, GSE144456, and GSE112137, and one miRNA microarray dataset GSE184939). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of HIBD-related genes. The ferroptosis-related genes were extracted from FerrDb, of which closely correlated to HIBD were obtained after the intersection with existing HIBD’s DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as protein–protein interaction (PPI) network analysis were subsequently conducted. Cytoscape was used to identify central genes. Immune cell infiltration analysis was performed by the CIBERSORT algorithm. Result: Fifty-six ferroptosis-related differentially expressed genes (FRDEGs) were screened, mainly related to ferroptosis, autophagy, hypoxia response, metabolic pathways, and immune inflammation. The seven optimal hub FRDEGs were obtained by intersecting with key modules of WGCNA. Then, the expression levels of the seven optimal hub FRDEGs were validated in the GSE144456 and GSE112137 datasets, and the ferroptosis-related mRNA-miRNA network was established. In addition, this study revealed immune cell infiltration in the HIBD cerebral cortex and the interaction between immune cells. Moreover, notably, specific FRDEGs were strongly positively correlated with immune function. Conclusions: The mechanism of ferroptosis is intricate and closely related to neonatal HIBD. Therefore, targeting ferroptosis-related gene therapy and immunotherapy may have therapeutic prospects for neonatal HIBD.
Current Perspectives of Neuroendocrine Regulation in Liver Fibrosis
Authors: Li Bowen , Wang Hui , Zhang Yudian , Liu Ying , Zhou Tiejun , Zhou Bingru , Zhang Ying , Chen Rong , Xing Juan , He Longfei , Salinas Jennifer Mata , Koyama Sachiko , Meng Fanyin , Wan Ying
Published: November 2022

Liver fibrosis is a complicated process that involves different cell types and pathological factors. The excessive accumulation of extracellular matrix (ECM) and the formation of fibrotic scar disrupt the tissue homeostasis of the liver, eventually leading to cirrhosis and even liver failure. Myofibroblasts derived from hepatic stellate cells (HSCs) contribute to the development of liver fibrosis by producing ECM in the area of injuries. It has been reported that the secretion of the neuroendocrine hormone in chronic liver injury is different from a healthy liver. Activated HSCs and cholangiocytes express specific receptors in response to these neuropeptides released from the neuroendocrine system and other neuroendocrine cells. Neuroendocrine hormones and their receptors form a complicated network that regulates hepatic inflammation, which controls the progression of liver fibrosis. This review summarizes neuroendocrine regulation in liver fibrosis from three aspects. The first part describes the mechanisms of liver fibrosis. The second part presents the neuroendocrine sources and neuroendocrine compartments in the liver. The third section discusses the effects of various neuroendocrine factors, such as substance P (SP), melatonin, as well as α-calcitonin gene-related peptide (α-CGRP), on liver fibrosis and the potential therapeutic interventions for liver fibrosis.
Efficacy of Clinically Used PARP Inhibitors in a Murine Model of Acute Lung Injury
Authors: Martins Vanessa , Santos Sidneia S. , Rodrigues Larissa de O. C. P. , Salomao Reinaldo , Liaudet Lucas , Szabo Csaba
Published: November 2022

Poly(ADP-ribose) polymerase 1 (PARP1), as a potential target for the experimental therapy of acute lung injury (ALI), was identified over 20 years ago. However, clinical translation of this concept was not possible due to the lack of clinically useful PARP inhibitors. With the clinical introduction of several novel, ultrapotent PARP inhibitors, the concept of PARP inhibitor repurposing has re-emerged. Here, we evaluated the effect of 5 clinical-stage PARP inhibitors in oxidatively stressed cultured human epithelial cells and monocytes in vitro and demonstrated that all inhibitors (1–30 µM) provide a comparable degree of cytoprotection. Subsequent in vivo studies using a murine model of ALI compared the efficacy of olaparib and rucaparib. Both inhibitors (1–10 mg/kg) provided beneficial effects against lung extravasation and pro-inflammatory mediator production—both in pre- and post-treatment paradigms. The underlying mechanisms include protection against cell dysfunction/necrosis, inhibition of NF-kB and caspase 3 activation, suppression of the NLRP3 inflammasome, and the modulation of pro-inflammatory mediators. Importantly, the efficacy of PARP inhibitors was demonstrated without any potentiation of DNA damage, at least as assessed by the TUNEL method. These results support the concept that clinically approved PARP inhibitors may be repurposable for the experimental therapy of ALI.
Cloning, Expression Analysis, and Functional Characterization of Candidate Oxalate Transporter Genes of HbOT1 and HbOT2 from Rubber Tree (Hevea brasiliensis)
Authors: Yang Zongming , Zhao Pingjuan , Peng Wentao , Liu Zifan , Xie Guishui , Ma Xiaowei , An Zewei , An Feng
Published: November 2022

Secretion of oxalic acid from roots is an important aluminum detoxification mechanism for many plants such as Hevea brasiliensis (rubber tree). However, the underlying molecular mechanism and oxalate transporter genes in plants have not yet been reported. In this study, the oxalate transporter candidate genes HbOT1 and HbOT2 from the rubber tree were cloned and preliminarily identified. It was found that HbOT1 had a full length of 1163 bp with CDS size of 792 bp, encoding 263 amino acids, and HbOT2 had a full length of 1647 bp with a CDS region length of 840 bp, encoding 279 amino acid residues. HbOT1 and HbOT2 were both stable hydrophobic proteins with transmembrane structure and SNARE_assoc domains, possibly belonging to the SNARE_assoc subfamily proteins of the SNARE superfamily. qRT-PCR assays revealed that HbOT1 and HbOT2 were constitutively expressed in different tissues, with HbOT1 highly expressed in roots, stems, barks, and latex, while HbOT2 was highly expressed in latex. In addition, the expressions of HbOT1 and HbOT2 were up-regulated in response to aluminum stress, and they were inducible by metals, such as copper and manganese. Heterologous expression of HbOT1 and HbOT2 in the yeast mutant AD12345678 enhanced the tolerance to oxalic acid and high concentration aluminum stress, which was closely correlated with the secretion of oxalic acid. This study is the first report on oxalate transporter genes in plants, which provides a theoretical reference for the study on the molecular mechanism of oxalic acid secretion to relieve aluminum toxicity and on aluminum-tolerance genetic engineering breeding.
The Role of 8-oxoG Repair Systems in Tumorigenesis and Cancer Therapy
Authors: Li Chunshuang , Xue Yaoyao , Ba Xueqing , Wang Ruoxi
Published: November 2022

Tumorigenesis is highly correlated with the accumulation of mutations. The abundant and extensive DNA oxidation product, 8-Oxoguanine (8-oxoG), can cause mutations if it is not repaired by 8-oxoG repair systems. Therefore, the accumulation of 8-oxoG plays an essential role in tumorigenesis. To avoid the accumulation of 8-oxoG in the genome, base excision repair (BER), initiated by 8-oxoguanine DNA glycosylase1 (OGG1), is responsible for the removal of genomic 8-oxoG. It has been proven that 8-oxoG levels are significantly elevated in cancer cells compared with cells of normal tissues, and the induction of DNA damage by some antitumor drugs involves direct or indirect interference with BER, especially through inducing the production and accumulation of reactive oxygen species (ROS), which can lead to tumor cell death. In addition, the absence of the core components of BER can result in embryonic or early post-natal lethality in mice. Therefore, targeting 8-oxoG repair systems with inhibitors is a promising avenue for tumor therapy. In this study, we summarize the impact of 8-oxoG accumulation on tumorigenesis and the current status of cancer therapy approaches exploiting 8-oxoG repair enzyme targeting, as well as possible synergistic lethality strategies involving exogenous ROS-inducing agents.
Replicative Senescence-Associated LINE1 Methylation and LINE1-Alu Expression Levels in Human Endothelial Cells
Authors: Ramini Deborah , Latini Silvia , Giuliani Angelica , Matacchione Giulia , Sabbatinelli Jacopo , Mensà Emanuela , Bacalini Maria Giulia , Garagnani Paolo , Rippo Maria Rita , Bronte Giuseppe , Bonafè Massimiliano , Cardelli Maurizio , Olivieri Fabiola
Published: November 2022

One of the main challenges of current research on aging is to identify the complex epigenetic mechanisms involved in the acquisition of the cellular senescent phenotype. Despite some evidence suggested that epigenetic changes of DNA repetitive elements, including transposable elements (TE) sequences, are associated with replicative senescence of fibroblasts, data on different types of cells are scarce. We previously analysed genome-wide DNA methylation of young and replicative senescent human endothelial cells (HUVECs), highlighting increased levels of demethylated sequences in senescent cells. Here, we aligned the most significantly demethylated single CpG sites to the reference genome and annotated their localization inside TE sequences and found a significant hypomethylation of sequences belonging to the Long-Interspersed Element-1 (LINE-1 or L1) subfamilies L1M, L1P, and L1HS. To verify the hypothesis that L1 demethylation could be associated with increased transcription/activation of L1s and/or Alu elements (non-autonomous retroelements that usually depend on L1 sequences for reverse transcription and retrotransposition), we quantified the RNA expression levels of both L1 (generic L1 elements or site-specific L1PA2 on chromosome 14) and Alu elements in young and senescent HUVECs and human dermal fibroblasts (NHDFs). The RNA expression of Alu and L1 sequences was significantly increased in both senescent HUVECs and NHDFs, whereas the RNA transcript of L1PA2 on chromosome 14 was not significantly modulated in senescent cells. Moreover, we found an increased amount of TE DNA copies in the cytoplasm of senescent HUVECs and NHDFs. Our results support the hypothesis that TE, which are significantly increased in senescent cells, could be retrotranscribed to DNA sequences.
Anatomical Development of the Cerebellothalamic Tract in Embryonic Mice
Authors: Dumas Daniël B. , Gornati Simona V. , Adolfs Youri , Shimogori Tomomi , Pasterkamp R. Jeroen , Hoebeek Freek E.
Published: November 2022

The main connection from cerebellum to cerebrum is formed by cerebellar nuclei axons that synapse in the thalamus. Apart from its role in coordinating sensorimotor integration in the adult brain, the cerebello-thalamic tract (CbT) has also been implicated in developmental disorders, such as autism spectrum disorders. Although the development of the cerebellum, thalamus and cerebral cortex have been studied, there is no detailed description of the ontogeny of the mammalian CbT. Here we investigated the development of the CbT at embryonic stages using transgenic Ntsr1-Cre/Ai14 mice and in utero electroporation of wild type mice. Wide-field, confocal and 3D light-sheet microscopy of immunohistochemical stainings showed that CbT fibers arrive in the prethalamus between E14.5 and E15.5, but only invade the thalamus after E16.5. We quantified the spread of CbT fibers throughout the various thalamic nuclei and found that at E17.5 and E18.5 the ventrolateral, ventromedial and parafascicular nuclei, but also the mediodorsal and posterior complex, become increasingly innervated. Several CbT fiber varicosities express vesicular glutamate transporter type 2 at E18.5, indicating cerebello-thalamic synapses. Our results provide the first quantitative data on the developing murine CbT, which provides guidance for future investigations of the impact that cerebellum has on thalamo-cortical networks during development.
The Revelation of Continuously Organized, Co-Overexpressed Protein-Coding Genes with Roles in Cellular Communications in Breast Cancer
Authors: Paul Aswathy Mary , Amjesh Revikumar , George Bijesh , Sankaran Deivendran , Sandiford Oleta A. , Rameshwar Pranela , Pillai Madhavan Radhakrishna , Kumar Rakesh
Published: November 2022

Many human cancers, including breast cancer, are polygenic and involve the co-dysregulation of multiple regulatory molecules and pathways. Though the overexpression of genes and amplified chromosomal regions have been closely linked in breast cancer, the notion of the co-upregulation of genes at a single locus remains poorly described. Here, we describe the co-overexpression of 34 continuously organized protein-coding genes with diverse functions at 8q.24.3(143437655-144326919) in breast and other cancer types, the CanCord34 genes. In total, 10 out of 34 genes have not been reported to be overexpressed in breast cancer. Interestingly, the overexpression of CanCord34 genes is not necessarily associated with genomic amplification and is independent of hormonal or HER2 status in breast cancer. CanCord34 genes exhibit diverse known and predicted functions, including enzymatic activities, cell viability, multipotency, cancer stem cells, and secretory activities, including extracellular vesicles. The co-overexpression of 33 of the CanCord34 genes in a multivariant analysis was correlated with poor survival among patients with breast cancer. The analysis of the genome-wide RNAi functional screening, cell dependency fitness, and breast cancer stem cell databases indicated that three diverse overexpressed CanCord34 genes, including a component of spliceosome PUF60, a component of exosome complex EXOSC4, and a ribosomal biogenesis factor BOP1, shared roles in cell viability, cell fitness, and stem cell phenotypes. In addition, 17 of the CanCord34 genes were found in the microvesicles (MVs) secreted from the mesenchymal stem cells that were primed with MDA-MB-231 breast cancer cells. Since these MVs were important in the chemoresistance and dedifferentiation of breast cancer cells into cancer stem cells, these findings highlight the significance of the CanCord34 genes in cellular communications. In brief, the persistent co-overexpression of CanCord34 genes with diverse functions can lead to the dysregulation of complementary functions in breast cancer. In brief, the present study provides new insights into the polygenic nature of breast cancer and opens new research avenues for basic, preclinical, and therapeutic studies in human cancer.
Monochromatic Light Pollution Exacerbates High-Fat Diet-Induced Adipocytic Hypertrophy in Mice
Authors: Guan Qingyun , Li Yixuan , Wang Zixu , Cao Jing , Dong Yulan , Ren Fazheng , Chen Yaoxing
Published: November 2022

Light pollution worldwide promotes the progression of obesity, which is widely considered a consequence of circadian rhythm disruptions. However, the role of environmental light wavelength in mammalian obesity is not fully understood. Herein, mice fed a normal chow diet (NCD) or a high-fat diet (HFD) were exposed to daytime white (WL), blue (BL), green (GL), and red light (RL) for 8 weeks. Compared with WL and RL, BL significantly increased weight gain and white adipose tissue (WAT) weight, and it disrupted glucose homeostasis in mice fed with HFD but not NCD. The analysis of WAT found that BL significantly aggravated HFD-induced WAT hypertrophy, with a decrease in IL-10 and an increase in NLRP3, p-P65, p-IκB, TLR4, Cd36, Chrebp, Srebp-1c, Fasn, and Cpt1β relative to WL or RL. More interestingly, BL upregulated the expression of circadian clocks in the WAT, including Clock, Bmal1, Per1, Cry1, Cry2, Rorα, Rev-erbα, and Rev-erbβ compared with WL or RL. However, most of the changes had no statistical difference between BL and GL. Mechanistically, BL significantly increased plasma corticosterone (CORT) levels and glucocorticoid receptors in the WAT, which may account for the changes in circadian clocks. Further, in vitro study confirmed that CORT treatment did promote the expression of circadian clocks in 3T3-L1 cells, accompanied by an increase in Chrebp, Cd36, Hsp90, P23, NLRP3, and p-P65. Thus, daily BL, rather than RL exposure-induced CORT elevation, may drive changes in the WAT circadian clocks, ultimately exacerbating lipid dysmetabolism and adipocytic hypertrophy in the HFD-fed mice.
Membrane Contact Sites in Autophagy
Authors: Zwilling Emma , Reggiori Fulvio
Published: November 2022

Eukaryotes utilize different communication strategies to coordinate processes between different cellular compartments either indirectly, through vesicular transport, or directly, via membrane contact sites (MCSs). MCSs have been implicated in lipid metabolism, calcium signaling and the regulation of organelle biogenesis in various cell types. Several studies have shown that MCSs play a crucial role in the regulation of macroautophagy, an intracellular catabolic transport route that is characterized by the delivery of cargoes (proteins, protein complexes or aggregates, organelles and pathogens) to yeast and plant vacuoles or mammalian lysosomes, for their degradation and recycling into basic metabolites. Macroautophagy is characterized by the de novo formation of double-membrane vesicles called autophagosomes, and their biogenesis requires an enormous amount of lipids. MCSs appear to have a central role in this supply, as well as in the organization of the autophagy-related (ATG) machinery. In this review, we will summarize the evidence for the participation of specific MCSs in autophagosome formation, with a focus on the budding yeast and mammalian systems.
Mortality and Comorbidities in Extremely Low Birth Weight Thai Infants: A Nationwide Data Analysis
Authors: Kiatchoosakun Pakaphan , Jirapradittha Junya , Paopongsawan Pongsatorn , Techasatian Leelawadee , Lumbiganon Pagakrong , Thepsuthammarat Kaewjai , Sutra Sumitr
Published: November 2022

This is the first nationwide study aimed to evaluate in-hospital mortality and comorbidities of extremely low birth weight (ELBW) infants in Thailand between 2015–2020. Data of ELBW infants were collected from the National Health Coverage Scheme. The incidence of ELBW Thai infants was 1.75 per 1000 live births. Sixty-five percent of ELBW infants were delivered in tertiary-care facilities, with 63% surviving until discharge. In-hospital mortality was 36.9%. Non-invasive respiratory supports were documented in just 17.6% of the study population, whereas total parenteral nutrition was used in 52.3% of neonates. There were several comorbidities, with the three most frequent including respiratory distress syndrome (70.7%), neonatal jaundice (66.7%), and sepsis (60.4%). The median hospitalization cost for one ELBW infant who survived was 296,438.40 baht ($8719). Conclusion: Thailand had an acceptable ELBW infant survival rate (63%), but comorbidities remained particularly severe and cost one hundred times the median hospital cost for one ELBW infant that survived in comparison to a normal newborn infant. Better health outcomes require strategies to raise awareness of the issues and the appropriate implementation of evidence-based solutions, particularly improving neonatal care facilities, as well as early referral of high-risk pregnant women and neonates, which will aid in the future reduction of neonatal morbidities and mortalities.
Congenital Cystic Adenomatoid Malformation (CCAM) Type II: A Rare Case of Sudden Infant Death
Authors: Salerno Monica , Sessa Francesco , Cocimano Giuseppe , Roccuzzo Salvatore , Esposito Massimiliano , Pomara Cristoforo
Published: November 2022

Congenital cystic adenomatoid malformation (CCAM) is a developmental lesion of the lungs and terminal respiratory structures, which is characterized by pseudocysts, lesions, and cystically dilated airways. CCAM is also known as congenital pulmonary airway malformation (CPAM). Various classification systems for CCAM have been described, and based on a recent classification, CCAMs are classified morphologically into five different types (Type 0, I, II, III, and IV) based on lesion sizes. The most common manifestation of CCAM in neonates and children is respiratory distress (RD). Spontaneous pneumothorax is a rare manifestation of CCAM. In this case report, we discuss a CCAM type-II case of a 38-day-old female infant with a radiological post-mortem diagnosis of a large left-side spontaneous pneumothorax. The gross examination of the lungs revealed multiple emphysematous air bubbles up to 0.5 cm in diameter, and the histological examination revealed focal pleural fibrosis, accompanied by thickened septa and atelectasis. In this scenario, the routine use of prenatal ultrasonography would be important to obtain a timely prenatal diagnosis. At the same time, improvements in surgical techniques, as well as greatly improved imaging techniques, have improved the outcome of these patients. Finally, it is important to remark on the importance of autopsy in the case of sudden infant death with a suspected CCAM.
Bibliometric Analysis of Psychomotricity Research Trends: The Current Role of Childhood
Authors: Denche-Zamorano Ángel , Mendoza-Muñoz María , Barrios-Fernandez Sabina , Parraca José A.
Published: November 2022

Psychomotricity is a wide broad term, which encompasses different bodily action approaches to support children and adolescents to achieve their highest potential. A search on the Web of Science (WoS) Core Collection database was performed on this topic, using traditional bibliometric laws. Finally, 118 publications (112 articles and 6 reviews) documents were found. Annual publications presented an exponentially growing trend (R2 = 84.7%). Spain was the most productive country/region worldwide. Paola Magioncalda, Matteo Martino y Víctor Arufe Giraldez were highlighted as the most prolific co-authors. “Retos Nuevas Tendencias en Educación Física, Deporte y Recreación” was the most productive journal and the “International Journal of Environmental Research and Public Health”, was the second most productive; the third in the list was the most productive in the JCR ranking. Thus, research on psychomotricity is experiencing exponential growth, causing this topic to generate great interest among researchers, publishers and journals. The most cited paper was “Neurocognitive Effects of Alcohol Hangover”. The author keywords that were first raised together with psychomotricity were related to rehabilitation and psychomotor development, while the current trend was focused on physical activity and early childhood education.
The Relationship between Anthropometric Measurements and Vitamin D Levels and Insulin Resistance in Obese Children and Adolescents
Authors: Çığrı Emrah , İnan Funda Çatan
Published: November 2022

Objective: Our investigation aimed to determine the effect of vitamin D levels on the development of insulin resistance in obese adolescents and children and the influences of anthropometric measurements on predicting the development of insulin resistance. Materials and Methods: In this study, demographic data, laboratory findings, and anthropometric measurements of 150 adolescents and children that had obesity diagnoses between May 2021 and September 2022 were evaluated retrospectively. Those with and without insulin resistance were studied with regard to vitamin D levels, biochemical parameters, and anthropometric measurements. Three groups of patients were created: those with low levels of vitamin D (<20 ng/mL), those with insufficient levels (20–30 ng/mL), and those having normal levels (≥30 ng/mL). Groups were compared in terms of homeostatic model score (HOMA-IR) and anthropometric measurements. Correlation analysis was carried out to ascertain the correlation of anthropometric measurements with HOMA-IR. To ascertain the cutoff, specificity, and sensitivity values of anthropometric parameters in predicting insulin resistance in patients, receiver operating characteristic (ROC) analysis was carried out. Results: Vitamin D levels of obese adolescents and children with insulin resistance were substantially lower than those without insulin resistance (p < 0.001). As the vitamin D level increased, all anthropometric measurements except for the body fat percentage decreased significantly with the HOMA-IR score (p < 0.05). HOMA-IR demonstrated a strong positive relation with waist circumference (rs = 0.726, p < 0.001). Waist circumference had high specificity and sensitivity in predicting insulin resistance (87.3% and 87.4%, respectively). Conclusions: A significant relationship was observed between insulin resistance development and low levels of vitamin D in obese children and adolescents. As vitamin D levels increase, anthropometric measurements are more stable and do not increase. Waist circumference is the most effective anthropometric measurement for predicting the development of insulin resistance in obese adolescents and children.