bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher Urine Exosomal miR-193a Is Associated With a Higher Probability of Primary Focal Segmental Glomerulosclerosis and an Increased Risk of Poor Prognosis Among Children With Nephrotic Syndrome
Authors: Wang Lixia , Wang Jie , Wang Zhimin , Zhou Jianhua , Zhang Yu
Published: October 2021

Background: In children, focal segmental glomerulosclerosis (FSGS) is one of the most common primary glomerular diseases leading to end-stage renal disease. Exosomes facilitate communication between cells by transporting proteins and microRNAs. We aimed to investigate the utility of urine exosomal miR-193a for diagnosis and prognosis estimation among patients with primary FSGS, and preliminarily explore the regulation mechanism of exosome secretion from podocytes.

Methods: Specimens of urine were obtained from patients with primary FSGS, minimal change nephropathy (MCN) and IgA nephropathy (IgAN), followed by exosome isolation. We quantified urine exosomal miR-193a based on quantitative reverse transcription-polymerase chain reaction, and evaluated its applicability using area-under-receiver-operating-characteristics curves (AUROCs). The semiquantitative glomerulosclerosis index (GSI) was used to evaluate the degree of glomerulosclerosis according to the method of Raij et al. We further used FAM-labeled miR-193a-5p to examine exosome shuttling using confocal microscopy for visualization, and explored the regulation mechanism of exosomes release from podocytes using Fluo-3AM dye.

Results: Urine exosomal miR-193a levels were significantly higher in patients with primary FSGS than those with MCN and IgAN. The AUROCs for discriminating between primary FSGS and MCN or IgAN were 0.85 and 0.821, respectively. Urine exosomal miR-193a levels positively correlated with GSI in patients with primary FSGS. We further found that kidney tissues from these patients had increased CD63 expression involving podocytes in non-sclerotic tufts. Exosomes from cultured podocytes could transport miR-193a-5p to recipient cells, potentially through a calcium-dependent release mechanism.

Conclusion: Urine exosomal miR-193a might be harnessed as a non-invasive marker for diagnosis and outcome assessment among patients with primary FSGS. Exosomes were potential vehicles for miRNAs shuttling between podocytes, and released from podocytes in a calcium-dependent manner.
Characterization of the Drosophila Adult Hematopoietic System Reveals a Rare Cell Population With Differentiation and Proliferation Potential
Authors: Boulet Manon , Renaud Yoan , Lapraz François , Benmimoun Billel , Vandel Laurence , Waltzer Lucas
Published: October 2021

While many studies have described Drosophila embryonic and larval blood cells, the hematopoietic system of the imago remains poorly characterized and conflicting data have been published concerning adult hematopoiesis. Using a combination of blood cell markers, we show that the adult hematopoietic system is essentially composed of a few distinct mature blood cell types. In addition, our transcriptomics results indicate that adult and larval blood cells have both common and specific features and it appears that adult hemocytes reactivate many genes expressed in embryonic blood cells. Interestingly, we identify a small set of blood cells that does not express differentiation markers but rather maintains the expression of the progenitor marker domeMeso. Yet, we show that these cells are derived from the posterior signaling center, a specialized population of cells present in the larval lymph gland, rather than from larval blood cell progenitors, and that their maintenance depends on the EBF transcription factor Collier. Furthermore, while these cells are normally quiescent, we find that some of them can differentiate and proliferate in response to bacterial infection. In sum, our results indicate that adult flies harbor a small population of specialized cells with limited hematopoietic potential and further support the idea that no substantial hematopoiesis takes place during adulthood.
Identification of an Immune-Related Prognostic Gene CLEC5A Based on Immune Microenvironment and Risk Modeling of Ovarian Cancer
Authors: Shen Jiacheng , Liu Tingwei , Lv Jia , Xu Shaohua
Published: October 2021

Objective: To understand the immune characteristics of the ovarian cancer (OC) microenvironment and explore the differences of immune-related molecules and cells to establish an effective risk model and identify the molecules that significantly affected the immune response of OC, to help guide the diagnosis.

Methods: First, we calculate the TMEscore which reflects the immune microenvironment, and then analyze the molecular differences between patients with different immune characteristics, and determine the prognostic genes. Then, the risk model was established by least absolute shrinkage and selection operator (LASSO) analysis and combined with clinical data into a nomogram for diagnosis and prediction. Subsequently, the potential gene CLEC5A influencing the immune response of OC was identified from the prognostic genes by integrative immune-stromal analysis. The genomic alteration was explored based on copy number variant (CNV) and somatic mutation data.

Results: TMEscore was a prognostic indicator of OC. The prognosis of patients with high TMEscore was better. The risk model based on immune characteristics was a reliable index to predict the prognosis of patients, and the nomogram could comprehensively evaluate the prognosis of patients. Besides, CLEC5A was closely related to the abundance of immune cells, immune response, and the expression of immune checkpoints in the OC microenvironment. OC cells with high expression of CLEC5A increased the polarization of M2 macrophages. CLEC5A expression was significantly associated with TTN and CDK12 mutations and affected the copy number of tumor progression and immune-related genes.

Conclusion: The study of immune characteristics in the OC microenvironment and the risk model can reveal the factors affecting the prognosis and guide the clinical hierarchical treatment. CLEC5A can be used as a potential key gene affecting the immune microenvironment remodeling of OC, which provides a new perspective for improving the effect of OC immunotherapy.
Age-Dependent Changes in Bone Architecture, Patterning, and Biomechanics During Skeletal Regeneration
Authors: Hoffseth Kevin , Busse Emily , Jaramillo Josue , Simkin Jennifer , Lacey Michelle , Sammarco Mimi C.
Published: October 2021

Mouse digit amputation provides a useful model of bone growth after injury, in that the injury promotes intramembranous bone formation in an adult animal. The digit tip is composed of skin, nerves, blood vessels, bones, and tendons, all of which regenerate after digit tip amputation, making it a powerful model for multi-tissue regeneration. Bone integrity relies upon a balanced remodeling between bone resorption and formation, which, when disrupted, results in changes to bone architecture and biomechanics, particularly during aging. In this study, we used recently developed techniques to evaluate bone patterning differences between young and aged regenerated bone. This analysis suggests that aged mice have altered trabecular spacing and patterning and increased mineral density of the regenerated bone. To further characterize the biomechanics of regenerated bone, we measured elasticity using a micro-computed tomography image-processing method combined with nanoindentation. This analysis suggests that the regenerated bone demonstrates decreased elasticity compared with the uninjured bone, but there is no significant difference in elasticity between aged and young regenerated bone. These data highlight distinct architectural and biomechanical differences in regenerated bone in both young and aged mice and provide a new analysis tool for the digit amputation model to aid in evaluating the outcomes for potential therapeutic treatments to promote regeneration.
Interactions Among lncRNA/circRNA, miRNA, and mRNA in Musculoskeletal Degenerative Diseases
Authors: Zheng Yi-Li , Song Ge , Guo Jia-Bao , Su Xuan , Chen Yu-Meng , Yang Zheng , Chen Pei-Jie , Wang Xue-Qiang
Published: October 2021

Musculoskeletal degenerative diseases (MSDDs) are pathological conditions that affect muscle, bone, cartilage, joint and connective tissue, leading to physical and functional impairments in patients, mainly consist of osteoarthritis (OA), intervertebral disc degeneration (IDD), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression that play an important role in biological regulation, involving in chondrocyte proliferation and apoptosis, extracellular matrix degradation and peripheral blood mononuclear cell inflammation. Research on MSDD pathogenesis, especially on RA and AS, is still in its infancy and major knowledge gaps remain to be filled. The effects of lncRNA/circRNA-miRNA-mRNA axis on MSDD progression help us to fully understand their contribution to the dynamic cellular processes, provide the potential OA, IDD, RA and AS therapeutic strategies. Further studies are needed to explore the mutual regulatory mechanisms between lncRNA/circRNA regulation and effective therapeutic interventions in the pathology of MSDD.
Diversity of Nuclear Lamin A/C Action as a Key to Tissue-Specific Regulation of Cellular Identity in Health and Disease
Authors: Malashicheva Anna , Perepelina Kseniya
Published: October 2021

A-type lamins are the main structural components of the nucleus, which are mainly localized at the nucleus periphery. First of all, A-type lamins, together with B-type lamins and proteins of the inner nuclear membrane, form a stiff structure—the nuclear lamina. Besides maintaining the nucleus cell shape, A-type lamins play a critical role in many cellular events, such as gene transcription and epigenetic regulation. Nowadays it is clear that lamins play a very important role in determining cell fate decisions. Various mutations in genes encoding A-type lamins lead to damages of different types of tissues in humans, collectively known as laminopathies, and it is clear that A-type lamins are involved in the regulation of cell differentiation and stemness. However, the mechanisms of this regulation remain unclear. In this review, we discuss how A-type lamins can execute their regulatory role in determining the differentiation status of a cell. We have summarized recent data focused on lamin A/C action mechanisms in regulation of cell differentiation and identity development of stem cells of different origin. We also discuss how this knowledge can promote further research toward a deeper understanding of the role of lamin A/C mutations in laminopathies.
A Numerical Investigation of Electrically-Heated Methane Steam Reforming Over Structured Catalysts
Authors: Ambrosetti Matteo , Beretta Alessandra , Groppi Gianpiero , Tronconi Enrico
Published: October 2021

The use of electric energy as an alternative system to provide heat of reaction enables the cut-off of CO2 emissions of several chemical processes. Among these, electrification of steam methane reforming results in a cleaner production method of hydrogen. In this work, we perform for the first time a numerical investigation of a compact steam reforming unit that exploits the electrical heating of the catalyst support. First, for such unit we consider the optimal thermodynamic conditions to perform the power to hydrogen conversion; the process should be run at atmospheric pressure and in a close temperature range. Then, among possible materials currently used for manufacturing structured supports we identify silicon carbide as the best material to run electrified steam reforming at moderate voltages and currents. The temperature and concentration profiles in idealized units are studied to understand the impact of the catalyst geometry on the process performances and open-cell foams, despite lower surface to volume show the best potential. Finally, the impact of heat losses is analyzed by considering different operative conditions and reactor geometries, showing that it is possible to obtain relatively high thermal efficiencies with the proposed methodology.
Co-Addition of Mg2Si and Graphene for Synergistically Improving the Hydrogen Storage Properties of Mg−Li Alloy
Authors: Huang Xiantun , Liu Haizhen , Duan Xingqing , Lan Zhiqiang , Guo Jin
Published: October 2021

Mg−Li alloy possesses a high hydrogen capacity. However, the hydrogenation and dehydrogenation performances are still far from practical application. In this work, Mg2Si (MS) and graphene (G) were employed together to synergistically improve the hydrogen storage properties of Mg−Li alloy. The structures of the samples were studied by XRD and SEM methods. The hydrogen storage performances of the samples were studied by nonisothermal and isothermal hydrogenation and dehydrogenation, thermal analysis, respectively. It is shown that the onset dehydrogenation temperature of Mg−Li alloy was synergistically reduced from 360°C to 310°C after co-addition of Mg2Si and graphene. At a constant temperature of 325°C, the Mg−Li−MS−G composite can release 2.7 wt.% of hydrogen within 2 h, while only 0.2 wt.% of hydrogen is released for the undoped Mg−Li alloy. The hydrogenation activation energy of the Mg−Li−MS−G composite was calculated to be 86.5 kJ mol−1. Microstructure and hydrogen storage properties studies show that graphene can act as a grinding aid during the ball milling process, which leads to a smaller particle size for the composites. This work demonstrates that coaddition of Mg2Si and graphene can synergistically improve the hydrogen storage properties of Mg−Si alloy and offers an insight into the role of graphene in the Mg−Li−MS−G composite.
New Insights Into Blue Light Phototherapy in Experimental Trypanosoma cruzi Infection
Authors: Ivanova Natália , Leite Ana Luísa Junqueira , Vieira Marcel Barbosa , Silva Otto Henrique Cezar e , Mota Ludmilla Walter Reis , Costa Guilherme de Paula , Azevedo Cristiano Schetini de , Auharek Sarah Alves , Novaes Romulo Dias , Pinto Kelerson Mauro de Castro , Bianchi Rodrigo Fernando , Talvani André
Published: October 2021

The search for an effective etiologic treatment to eliminate Trypanosoma cruzi, the causative agent of Chagas disease, has continued for decades and yielded controversial results. In the 1970s, nifurtimox and benznidazole were introduced for clinical assessment, but factors such as parasite resistance, high cellular toxicity, and efficacy in acute and chronic phases of the infection have been debated even today. This study proposes an innovative strategy to support the controlling of the T. cruzi using blue light phototherapy or blue light-emitting diode (LED) intervention. In in vitro assays, axenic cultures of Y and CL strains of T. cruzi were exposed to 460 nm and 40 µW/cm2 of blue light for 5 days (6 h/day), and parasite replication was evaluated daily. For in vivo experiments, C57BL6 mice were infected with the Y strain of T. cruzi and exposed to 460 nm and 7 µW/cm2 of blue light for 9 days (12 h/day). Parasite count in the blood and cardiac tissue was determined, and plasma interleukin (IL-6), tumoral necrosis factor (TNF), chemokine ligand 2 (CCL2), and IL-10 levels and the morphometry of the cardiac tissue were evaluated. Blue light induced a 50% reduction in T. cruzi (epimastigote forms) replication in vitro after 5 days of exposure. This blue light-mediated parasite control was also observed by the T. cruzi reduction in the blood (trypomastigote forms) and in the cardiac tissue (parasite DNA and amastigote nests) of infected mice. Phototherapy reduced plasma IL-6, TNF and IL-10, but not CCL2, levels in infected animals. This non-chemical therapy reduced the volume density of the heart stroma in the cardiac connective tissue but did not ameliorate the mouse myocarditis, maintaining a predominance of pericellular and perivascular mononuclear inflammatory infiltration with an increase in polymorphonuclear cells. Together, these data highlight, for the first time, the use of blue light therapy to control circulating and tissue forms of T. cruzi. Further investigation would demonstrate the application of this promising and potential complementary strategy for the treatment of Chagas disease.
CD8+ T Cell Response Quality Is Related to Parasite Control in an Animal Model of Single and Mixed Chronic Trypanosoma cruzi Infections
Authors: Mateus Jose , Nocua Paola , Lasso Paola , López Manuel Carlos , Thomas M. Carmen , Egui Adriana , Cuervo Claudia , González John Mario , Puerta Concepción J. , Cuéllar Adriana
Published: October 2021

Chagas disease (ChD) is a chronic infection caused by Trypanosoma cruzi. This highly diverse intracellular parasite is classified into seven genotypes or discrete typing units (DTUs) and they overlap in geographic ranges, vectors, and clinical characteristics. Although studies have suggested that ChD progression is due to a decline in the immune response quality, a direct relationship between T cell responses and disease outcome is still unclear. To investigate the relationship between parasite control and immune T cell responses, we used two distinct infection approaches in an animal model to explore the histological and parasitological outcomes and dissect the T cell responses in T. cruzi-infected mice. First, we performed single infection experiments with DA (TcI) or Y (TcII) T. cruzi strains to compare the infection outcomes and evaluate its relationship with the T cell response. Second, because infections with diverse T. cruzi genotypes can occur in naturally infected individuals, mice were infected with the Y or DA strain and subsequently reinfected with the Y strain. We found different infection outcomes in the two infection approaches used. The single chronic infection showed differences in the inflammatory infiltrate level, while mixed chronic infection by different T. cruzi DTUs showed dissimilarities in the parasite loads. Chronically infected mice with a low inflammatory infiltrate (DA-infected mice) or low parasitemia and parasitism (Y/Y-infected mice) showed increases in early-differentiated CD8+ T cells, a multifunctional T cell response and lower expression of inhibitory receptors on CD8+ T cells. In contrast, infected mice with a high inflammatory infiltrate (Y-infected mice) or high parasitemia and parasitism (DA/Y-infected mice) showed a CD8+ T cell response distinguished by an increase in late-differentiated cells, a monofunctional response, and enhanced expression of inhibitory receptors. Overall, our results demonstrated that the infection outcomes caused by single or mixed T. cruzi infection with different genotypes induce a differential immune CD8+ T cell response quality. These findings suggest that the CD8+ T cell response might dictate differences in the infection outcomes at the chronic T. cruzi stage. This study shows that the T cell response quality is related to parasite control during chronic T. cruzi infection.
Rapid Increase of Oral Bacteria in Nasopharyngeal Microbiota After Antibiotic Treatment in Children With Invasive Pneumococcal Disease
Authors: Henares Desiree , Rocafort Muntsa , Brotons Pedro , de Sevilla Mariona F. , Mira Alex , Launes Cristian , Cabrera-Rubio Raul , Muñoz-Almagro Carmen
Published: October 2021

Introduction

Antibiotics are commonly prescribed to young children for treating bacterial infections such as invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Despite the obvious benefits of antibiotics, little is known about their possible side effects on children’s nasopharyngeal microbiota. In other ecological niches, antibiotics have been described to perturb the balanced microbiota with short- and long-term effects on children’s health. The present study aims to evaluate and compare the nasopharyngeal microbiota of children with IPD and different degree of antibiotic exposure.

Methods

We investigated differences in nasopharyngeal microbiota of two groups of children <18 years with IPD: children not exposed to antibiotics before sample collection (n=27) compared to children previously exposed (n=54). Epidemiological/clinical data were collected from subjects, and microbiota was characterized by Illumina sequencing of V3-V4 amplicons of the 16S rRNA gene.

Results

Main epidemiological/clinical factors were similar across groups. Antibiotic-exposed patients were treated during a median of 4 days (IQR: 3–6) with at least one beta-lactam (100.0%). Higher bacterial richness and diversity were found in the group exposed to antibiotics. Different streptococcal amplicon sequence variants (ASVs) were differentially abundant across groups: antibiotic use was associated to lower relative abundances of Streptococcus ASV2 and Streptococcus ASV11 (phylogenetically close to S. pneumoniae), and higher relative abundances of Streptococcus ASV3 and Streptococcus ASV12 (phylogenetically close to viridans group streptococci). ASVs assigned to typical bacteria from the oral cavity, including Veillonella, Alloprevotella, Porphyromonas, Granulicatella, or Capnocytophaga, were associated to the antibiotic-exposed group. Common nosocomial genera such as Staphylococcus, Acinetobacter, and Pseudomonas were also enriched in the group exposed to antibiotics.

Conclusion

Our results point toward a reduction of S. pneumoniae abundance on the nasopharynx of children with IPD after antibiotic treatment and a short-term repopulation of this altered niche by oral and nosocomial bacteria. Future research studies will have to evaluate the clinical implications of these findings and if these populations would benefit from the probiotic/prebiotic administration or even from the improvement on oral hygiene practices frequently neglected among hospitalized children.
Comparison of Molecular and Parasitological Methods for Diagnosis of Human Trichostrongylosis
Authors: Pandi Mehdi , Sharifdini Meysam , Ashrafi Keyhan , Atrkar Roushan Zahra , Rahmati Behnaz , Hajipour Nayereh
Published: October 2021

Human trichostrongyliasis is a zoonotic disease that is prevalent among rural populations in some countries. This study was performed to evaluate various parasitological methods and polymerase chain reaction (PCR) for the diagnosis of human trichostrongyliasis. A total of 206 fresh stool samples were collected from residents of endemic villages of Northern Iran. All samples were examined using conventional parasitological methods, including wet mount, formalin ethyl acetate concentration (FEAC), agar plate culture (APC), Harada–Mori culture (HMC), and Willis, along with the PCR technique. Among the total of 206 individuals examined, 72 people (35%) were found infected with Trichostrongylus species using combined parasitological methods. By considering the combined results of parasitological methods as the diagnostic gold standard, the Willis technique had a sensitivity of 91.7% compared with 52.8% for the APC, 40.3% for the HMC, 37.5% for FEAC, and 5.6% for the wet mount technique. The diagnostic specificity of all the parasitological methods was 100%. Furthermore, the PCR method detected Trichostrongylus spp. DNA in 79 fecal samples (38.3%) with a sensitivity of 97.2% and a specificity of 93.3%. According to the current findings, the Willis method was more sensitive than are the other parasitological methods in the diagnosis of human trichostrongyliasis. However, the PCR assay was more sensitive and more reliable in the detection of human trichostrongyliasis in comparison with the parasitological methods.
Immunomodulatory Proteins in Tick Saliva From a Structural Perspective
Authors: Denisov Stepan S. , Dijkgraaf Ingrid
Published: October 2021

To feed successfully, ticks must bypass or suppress the host’s defense mechanisms, particularly the immune system. To accomplish this, ticks secrete specialized immunomodulatory proteins into their saliva, just like many other blood-sucking parasites. However, the strategy of ticks is rather unique compared to their counterparts. Ticks’ tendency for gene duplication has led to a diverse arsenal of dozens of closely related proteins from several classes to modulate the immune system’s response. Among these are chemokine-binding proteins, complement pathways inhibitors, ion channels modulators, and numerous poorly characterized proteins whose functions are yet to be uncovered. Studying tick immunomodulatory proteins would not only help to elucidate tick-host relationships but would also provide a rich pool of potential candidates for the development of immunomodulatory intervention drugs and potentially new vaccines. In the present review, we will attempt to summarize novel findings on the salivary immunomodulatory proteins of ticks, focusing on biomolecular targets, structure-activity relationships, and the perspective of their development into therapeutics.
Arylmalonate Decarboxylase—A Versatile Biocatalyst for the Synthesis of Optically Pure Carboxylic Acids
Authors: Schweiger Anna K. , Miyamoto Kenji , Kourist Robert
Published: October 2021

Bacterial arylmalonate decarboxylase (AMDase) is an intriguing cofactor-independent enzyme with a broad substrate spectrum. Particularly, the highly stereoselective transformation of diverse arylmalonic acids into the corresponding chiral α-arylpropionates has contributed to the broad recognition of this biocatalyst. While, more than 30 years after its discovery, the native substrate and function of AMDase still remain undiscovered, contributions from multiple fields have ever since brought forth a powerful collection of AMDase variants to access a wide variety of optically pure α-substituted propionates. This review aims at providing a comprehensive overview of the development of AMDase from an enzyme with unknown function up to a powerful tailored biocatalyst for the synthesis of industrially relevant optically pure α-arylpropionates. Historical perspectives as well as recent achievements in the field will be covered within this work.
Abrogation of CC Chemokine Receptor 9 Ameliorates Ventricular Electrical Remodeling in Mice After Myocardial Infarction
Authors: Huang Yan , Ding Hua-Sheng , Song Tao , Chen Yu-Ting , Wang Teng , Tang Yan-Hong , Barajas-Martinez Hector , Huang Cong-Xin , Hu Dan
Published: October 2021

Introduction: Myocardial infarction (MI) triggers structural and electrical remodeling. CC chemokine receptor 9 (CCR9) mediates chemotaxis of inflammatory cells in MI. In our previous study, CCR9 knockout has been found to improve structural remodeling after MI. Here, we further investigate the potential influence of CCR9 on electrical remodeling following MI in order to explore potential new measures to improve the prognosis of MI.

Methods and Results: Mice was used and divided into four groups: CCR9+/+/Sham, CCR9−/−/Sham, CCR9+/+/MI, CCR9−/−/MI. Animals were used at 1 week after MI surgery. Cardiomyocytes in the infracted border zone were acutely dissociated and the whole-cell patch clamp was used to record action potential duration (APD), L-type calcium current (ICa,L) and transient outward potassium current (Ito). Calcium transient and sarcoplasmic reticulum (SR) calcium content under stimulation of Caffeine were measured in isolated cardiomyocytes by confocal microscopy. Multielectrode array (MEA) was used to measure the conduction of the left ventricle. The western-blot was performed for the expression level of connexin 43. We observed prolonged APD90, increased ICa,L and decreased Ito following MI, while CCR9 knockout attenuated these changes (APD90: 50.57 ± 6.51 ms in CCR9−/−/MI vs. 76.53 ± 5.98 ms in CCR9+/+/MI, p < 0.05; ICa,L: −13.15 ± 0.86 pA/pF in CCR9−/−/MI group vs. −17.05 ± 1.11 pA/pF in CCR9+/+/MI, p < 0.05; Ito: 4.01 ± 0.17 pA/pF in CCR9−/−/MI group vs. 2.71 ± 0.16 pA/pF in CCR9+/+/MI, p < 0.05). The confocal microscopy results revealed CCR9 knockout reversed the calcium transient and calcium content reduction in sarcoplasmic reticulum following MI. MEA measurements showed improved conduction velocity in CCR9−/−/MI mice (290.1 ± 34.47 cm/s in CCR9−/−/MI group vs. 113.2 ± 14.4 cm/s in CCR9+/+/MI group, p < 0.05). Western-blot results suggested connexin 43 expression was lowered after MI while CCR9 knockout improved its expression.

Conclusion: This study shows CCR9 knockout prevents the electrical remodeling by normalizing ion currents, the calcium homeostasis, and the gap junction to maintain APD and the conduction function. It suggests CCR9 is a promising therapeutic target for MI-induced arrhythmia, which warrants further investigation.
Association Between Apelin and Atrial Fibrillation in Patients With High Risk of Ischemic Stroke
Authors: Bohm Allan , Snopek Peter , Tothova Lubomira , Bezak Branislav , Jajcay Nikola , Vachalcova Marianna , Uher Tomas , Kurecko Marian , Kissova Viera , Danova Katarina , Olejnik Peter , Michalek Peter , Hlavata Tereza , Petrikova Katarina , Mojto Viliam , Kyselovic Jan , Farsky Stefan
Published: October 2021

Background: Atrial fibrillation (AF) is associated with high risk of stroke preventable by timely initiation of anticoagulation. Currently available screening tools based on ECG are not optimal due to inconvenience and high costs. Aim of this study was to study the diagnostic value of apelin for AF in patients with high risk of stroke.

Methods: We designed a multicenter, matched-cohort study. The population consisted of three study groups: a healthy control group (34 patients) and two matched groups of 60 patients with high risk of stroke (AF and non-AF group). Apelin levels were examined from peripheral blood.

Results: Apelin was significantly lower in AF group compared to non-AF group (0.694 ± 0.148 vs. 0.975 ± 0.458 ng/ml, p = 0.001) and control group (0.982 ± 0.060 ng/ml, p < 0.001), respectively. Receiver operating characteristic (ROC) analysis of apelin as a predictor of AF scored area under the curve (AUC) of 0.658. Apelin's concentration of 0.969 [ng/ml] had sensitivity = 0.966 and specificity = 0.467. Logistic regression based on manual feature selection showed that only apelin and NT-proBNP were independent predictors of AF. Logistic regression based on selection from bivariate analysis showed that only apelin was an independent predictor of AF. A logistic regression model using repeated stratified K-Fold cross-validation strategy scored an AUC of 0.725 ± 0.131.

Conclusions: Our results suggest that apelin might be used to rule out AF in patients with high risk of stroke.
Extracorporeal Cardiac Shock Waves Therapy Improves the Function of Endothelial Progenitor Cells After Hypoxia Injury via Activating PI3K/Akt/eNOS Signal Pathway
Authors: Wang Mingqiang , Yang Dan , Hu Zhao , Shi Yunke , Ma Yiming , Cao Xingyu , Guo Tao , Cai Hongbo , Cai Hongyan
Published: October 2021

Background: Extracorporeal cardiac shock waves (ECSW) have great potential in the treatment of coronary heart disease. Endothelial progenitor cells (EPCs) are a class of pluripotent progenitor cells derived from bone marrow or peripheral blood, which have the capacity to migrate to ischemic myocardium and differentiate into mature endothelial cells and play an important role in neovascularization and endothelial repair. In this study, we investigated whether ECSW therapy can improve EPCs dysfunction and apoptosis induced by hypoxia and explored the underlying mechanisms.

Methods: EPCs were separated from ApoE gene knockout rat bone marrow and identified using flow cytometry and fluorescence staining. EPCs were used to produce in vitro hypoxia-injury models which were then divided into six groups: Control, Hypoxia, Hypoxia + ECSW, Hypoxia + LY294002 + ECSW, Hypoxia + MK-2206 + ECSW, and Hypoxia + L-NAME + ECSW. EPCs from the Control, Hypoxia, and Hypoxia + ECSW groups were used in mRNA sequencing reactions. mRNA and protein expression levels were analyzed using qRT-PCR and western blot analysis, respectively. Proliferation, apoptosis, adhesion, migration, and angiogenesis were measured using CCK-8, flow cytometry, gelatin, transwell, and tube formation, respectively. Nitric oxide (NO) levels were measured using an NO assay kit.

Results: Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that differentially expressed genes were enriched in cancer signaling, PI3K-Akt signaling, and Rap1 signaling pathways. We selected differentially expressed genes in the PI3K-Akt signaling pathway and verified them using a series of experiments. The results showed that ECSW therapy (500 shots at 0.09 mJ/mm2) significantly improved proliferation, adhesion, migration, and tube formation abilities of EPCs following hypoxic injury, accompanied by upregulation of p-PI3K, p-Akt, p-eNOS, Bcl-2 protein and NO, PI3K, and Akt mRNA expression, and downregulation of Bax and Caspase3 protein expression. All these effects of ECSW were eliminated using inhibitors specific to PI3K (LY294002), Akt (MK-2206), and eNOS (L-NAME).

Conclusion: ECSW exerted a strong repaired effect on EPCs suffering inhibited hypoxia injury by inhibiting cell apoptosis and promoting angiogenesis, mainly through activating the PI3K/Akt/eNOS signaling pathway, which provide new evidence for ECSW therapy in CHD.
Trends in Mortality From Aortic Stenosis in Europe: 2000–2017
Authors: Hartley Adam , Hammond-Haley Matthew , Marshall Dominic C. , Salciccioli Justin D. , Malik Iqbal S. , Khamis Ramzi Y. , Shalhoub Joseph
Published: October 2021

Background: Trends in mortality from aortic stenosis across European countries are not well-understood, especially given the significant growth in transcatheter aortic valve implantation (TAVI) in the last 10 years.

Methods: Age-standardised death rates were extracted from the World Health Organisation Mortality Database, using the International Classification of Diseases 10th edition code for non-rheumatic aortic stenosis for those aged > 45 years between 2000 and 2017. The UK and countries from the European Union with at least 1,000,000 inhabitants and at least 50% available datapoints over the study period were included: a total of 23 countries. Trends were described using Joinpoint regression analysis.

Results: No reductions in mortality were demonstrated across all countries 2000–2017. Large increases in mortality were found for Croatia, Poland and Slovakia for both sexes (>300% change). Mortality plateaued in Germany from 2008 in females and 2012 in males, whilst mortality in the Netherlands declined for both sexes from 2007. Mortality differences between the sexes were observed, with greater mortality for males than females across most countries.

Conclusions: Mortality from aortic stenosis has increased across Europe from 2000 to 2017. There are, however, sizable differences in mortality trends between Eastern and Western European countries. The need for health resource planning strategies to specifically target AS, particularly given the expected increase with ageing populations, is highlighted.
Luteolin Prevents Cardiac Dysfunction and Improves the Chemotherapeutic Efficacy of Doxorubicin in Breast Cancer
Authors: Shi Youyang , Li Feifei , Shen Man , Sun Chenpin , Hao Wei , Wu Chunyu , Xie Ying , Zhang Shuai , Gao Hongzhi , Yang Jianfeng , Zhou Zhongyan , Gao Dongwen , Qin Yuenong , Han Xianghui , Liu Sheng
Published: October 2021

Background: Doxorubicin (Dox) is one of the most effective chemotherapy agents used in the treatment of solid tumors and hematological malignancies. However, it causes dose-related cardiotoxicity that may lead to heart failure in patients. Luteolin (Lut) is a common flavonoid that exists in many types of plants. It has been studied for treating various diseases such as hypertension, inflammatory disorders, and cancer. In this study, we evaluated the cardioprotective and anticancer effects of Lut on Dox-induced cardiomyopathy in vitro and in vivo to explore related mechanisms in alleviating dynamin-related protein (Drp1)-mediated mitochondrial apoptosis.

Methods: MTT and LDH assay were used to determine the viability and toxicity of cardiomyocytes treated with Dox and Lut. Flow cytometry was used to examine ROS levels, and electron and confocal microscopy was employed to assess the mitochondrial morphology. The level of apoptosis was examined by Hoechst 33258 staining. The protein levels of myocardial fission protein and apoptosis-related protein were examined using Western blot. Transcriptome analysis of the protective effect of Lut against Dox-induced cardiac toxicity in myocardial cells was performed using RNA sequencing technology. The protective effects of Lut against cardiotoxicity mediated by Dox in zebrafish were quantified. The effect of Lut increase the antitumor activity of Dox in breast cancer both in vitro and in vivo were further employed.

Results: Lut ameliorated Dox-induced toxicity in H9c2 and AC16 cells. The level of oxidative stress was downregulated by Lut after Dox treatment of myocardial cells. Lut effectively reduced the increased mitochondrial fission post Dox stimulation in cardiomyocytes. Apoptosis, fission protein Drp1, and Ser616 phosphorylation were also increased post Dox and reduced by Lut. In the zebrafish model, Lut significantly preserved the ventricular function of zebrafish after Dox treatment. Moreover, in the mouse model, Lut prevented Dox-induced cardiotoxicity and enhanced the cytotoxicity in triple-negative breast cancer by inhibiting proliferation and metastasis and inducing apoptosis.
Body Mass Index and Long-Term Follow-Up Outcomes in Patients With Acute Myocardial Infarction by the Median of Non-HDL Cholesterol: Results From an Observational Cohort Study in China
Authors: Gao Hui , Shen Aidong , Chen Hui , Li Hongwei
Published: October 2021

Background: The association between obesity, non-HDL cholesterol, and clinical outcomes in subjects with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) is incompletely understood. The aim of this investigation was to explore the association between body mass index (BMI), non-high density lipoprotein (non-HDL) cholesterol, and long-term follow-up prognosis.

Methods: This present study used data obtained by the Cardiovascular Center of Beijing Friendship Hospital Database Bank. We identified 3,780 consecutive AMI populations aged 25–93 years from 2013 to 2020. Participants were categorized as normal weight (18.5 ≤ BMI <22.9 kg/m2), overweight (23.0 ≤ BMI <24.9 kg/m2), obese class I (25.0 ≤ BMI <29.9 kg/m2), and obese class II (BMI ≥ 30.0 kg/m2). The endpoint of interest was cardiovascular (CV) death, all-cause death, myocardial infarction (MI), stroke, unplanned revascularization, and cardiac hospitalization.

Results:Participants with higher BMI were younger and more likely to be males compared with lower BMI groups. Elevated non-HDL cholesterol was present in 8.7, 11.0, 24.3, and 5.9% of the normal, overweight, obese class I, and obese class II groups, respectively. After multivariate adjustment, compared to normal-weight participants with decreased non-HDL cholesterol (reference group), obese participants with and without elevated non-HDL cholesterol had a lower risk of mortality (with obese class I and elevated non-HDL cholesterol: hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.28–0.67; with obese class I and decreased non-HDL cholesterol: HR, 0.68, 95% CI, 0.47–0.98; with obese class II and elevated non-HDL cholesterol: HR, 0.42, 95% CI, 0.20–0.87; with obese class II and decreased non-HDL cholesterol: HR, 0.35, 95% CI, 0.16–0.72).

Conclusion: In AMI participants performing with PCI, obesity had a better long-term prognosis which probably unaffected by the level of non-HDL cholesterol.
Compound Hydrometeorological Extremes: Drivers, Mechanisms and Methods
Authors: Zhang Wei , Luo Ming , Gao Si , Chen Weilin , Hari Vittal , Khouakhi Abdou
Published: October 2021

Compound extremes pose immense challenges and hazards to communities, and this is particularly true for compound hydrometeorological extremes associated with deadly floods, surges, droughts, and heat waves. To mitigate and better adapt to compound hydrometeorological extremes, we need to better understand the state of knowledge of such extremes. Here we review the current advances in understanding compound hydrometeorological extremes: compound heat wave and drought (hot-dry), compound heat stress and extreme precipitation (hot-wet), cold-wet, cold-dry and compound flooding. We focus on the drivers of these extremes and methods used to investigate and quantify their associated risk. Overall, hot-dry compound extremes are tied to subtropical highs, blocking highs, atmospheric stagnation events, and planetary wave patterns, which are modulated by atmosphere-land feedbacks. Compared with hot-dry compound extremes, hot-wet events are less examined in the literature with most works focusing on case studies. The cold-wet compound events are commonly associated with snowfall and cold frontal systems. Although cold-dry events have been found to decrease, their underlying mechanisms require further investigation. Compound flooding encompasses storm surge and high rainfall, storm surge and sea level rise, storm surge and riverine flooding, and coastal and riverine flooding. Overall, there is a growing risk of compound flooding in the future due to changes in sea level rise, storm intensity, storm precipitation, and land-use-land-cover change. To understand processes and interactions underlying compound extremes, numerical models have been used to complement statistical modeling of the dependence between the components of compound extremes. While global climate models can simulate certain types of compound extremes, high-resolution regional models coupled with land and hydrological models are required to simulate the variability of compound extremes and to project changes in the risk of such extremes. In terms of statistical modeling of compound extremes, previous studies have used empirical approach, event coincidence analysis, multivariate distribution, the indicator approach, quantile regression and the Markov Chain method to understand the dependence, greatly advancing the state of science of compound extremes. Overall, the selection of methods depends on the type of compound extremes of interests and relevant variables.
Investigation on Coal Skeleton Deformation in CO2 Injection Enhanced CH4 Drainage From Underground Coal Seam
Authors: Fan Chaojun , Yang Lei , Wang Gang , Huang Qiming , Fu Xiang , Wen Haiou
Published: October 2021

To reveal the evolution law of coal skeleton deformation during the process of CO2 flooding and displacing CH4 in coal seam, a fluid-solid coupling mathematical model of CO2 injection enhanced CH4 drainage was established based on Fick’s law, Darcy’s law, ideal gas state equation, and Langmuir equation. Meanwhile, numerical simulations were carried out by implementing the mathematical model in the COMSOL Multiphysics. Results show that the CH4 content of both regular gas drainage and CO2 enhanced gas drainage gradually decreases with time, and the decreasing rate is high between 10 and 60 days. Compared with regular gas drainage, the efficiency of CO2 enhanced gas drainage is more obvious with greater amount of CH4 extracted out. When coal seam gas is extracted for 10, 60, 120, and 180 days, CH4 content in coal seam is reduced by 5.2, 17.2, 23.6, and 26.7%, respectively. For regular gas drainage, the deformation of coal skeleton is dominated by the shrink of coal matrix induced by gas desorption, and the strain curve shows a continuous downward trend. For CO2 enhanced gas drainage, the strain curve of coal skeleton showed a decrease—rapid increase—slow increase trend. The evolution of permeability is opposite to the evolution of coal skeleton strain. Higher gas injection pressure will lead to a greater coal skeleton strain. The pumping pressure affects the deformation of coal skeleton slightly compared with that of initial water saturation and initial temperature. Greater initial water saturation leads to larger deformation of coal skeleton in the early stage. The strain value of coal skeleton gradually tends to be consistent as gas injection prolongs. Higher initial temperature leads to greater reduction in coal skeleton strain when the gas injection continues. Research achievements provide a basis for the field application of CO2 injection enhanced CH4 drainage in underground coal mines.
Experimental Investigation of the Outburst Discharge of Landslide Dam Overtopping Failure
Authors: Zhou Mingjun , Shi Zhenming , Zhou Gordon G. D. , Cui Kahlil Fredrick E. , Peng Ming
Published: October 2021

Research on the factors and mechanisms that influence outburst floods are essential for estimating outflow hydrographs and the resulting inundation. In this study, large flume tests are conducted to investigate the effects of the upstream inflow and the presence of loose erodible deposits on the breaching flow and the subsequent outburst floods. Experimental results reveal that hydrographs of the breaching flow and outburst flood can be divided into three stages where each stage is separated by inflection points and peak discharges. It is found that the larger the inflow discharge, the larger the peak discharge of the outburst flood and the shorter the time needed to reach the peak and inflection discharges of the outburst flood. The breaching flow decreases along the longitudinal direction at rates that increase with the inflow discharge. The ratio between the length of the upstream dam shoulder and the dam width is inversely related to the ratio of the outburst discharge to inflow discharge. We also show that the presence of loose deposits at the dam toe can amplify the peak discharge of outburst flood by increasing the solids content of the water flow.
Brief Research Report: Agreement Between Teacher and Student Reports on Students’ Acceptance and Rejection
Authors: Schoop-Kasteler Noemi , Müller Christoph M.
Published: October 2021

Student-reported peer nominations are typically used to obtain information on the social status (i.e., acceptance and rejection) of students in their classrooms. However, under certain circumstances this assessment method cannot be used, for example for logistical reasons or with students with intellectual disabilities (ID) who are not always able to fill out peer nominations. In such instances, teacher reports on students’ expected nominations may serve as a proxy. As part of a larger study on students with ID, we evaluated the agreement between teachers’ and students’ peer reports regarding individual students’ acceptance and rejection using unlimited nomination procedures in Grades 4–6 mainstream classrooms. As many students with ID cannot fill out peer nominations, this evaluation study used a sample of typically developing students without ID. Teachers (n = 27, Mage = 34.24 years, SD = 10.85; 85.2% female) nominated all peers from the classroom who they believed individual students would report as “liked” and “not liked”. For direct comparison, students (n = 441, Mage = 11.36 years, SD = 0.89; 46.8% female) themselves were also asked to report their “liked” and “not liked” nominations. Students received both more “liked” and more “not liked” nominations from their peers than from their teachers. Students’ social status as calculated from teacher reports showed only partial agreement with social status as calculated from student reports, suggesting that in mainstream classrooms student reports cannot be easily replaced by teacher reports. Perspectives on the application of teacher-reported peer nominations in special needs settings are discussed.