bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin-Medicated Neural JNK3 Up-Regulation Promotes Ameloblastic Mineralization
Authors: Ren Qianhui , Pan Jing , Chen Yunshuo , Shen Zhecheng , Yang Zhao , Kwon Kubin , Guo Ying , Wang Yueying , Ji Fang
Published: December 2021

Introduction: Melatonin, an endogenous neurohormone, modulates the biological circadian rhythms of vertebrates. It functions have been reported in previous stomatological studies as anti-inflammation, antioxidant, osseointegration of dental implants and stimulation to dental pulp stem cells differentiation, but its role in ameloblastic differentiation and mineralization has been rarely studied.

Objective: To reveal the effects of melatonin on the mineralization of ameloblast lineage cells (ALCs), and to identify the change in gene expression and the potential mechanism based on ribonucleic acid sequencing (RNA-seq) analysis.

Method: ALCs were induced in melatonin-conditioned medium. After 7-days culture, Western blot, real-time PCR, alkaline phosphatase (ALP) activity test, RNA-seq were accordingly used to detect the change in molecular level. After 1-month odontogenic induction in melatonin medium, Alizarin Red-S (ARS) staining showed the changes of mineral nodules. Differentially expressed genes (DEGs), enrichment of functions and signaling pathways analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) database were performed. The JNK3 antagonist (JNK3 inhibitor IX, SR3576) and β-arrestin1 (Arrb1) overexpression were applied to confirm the fluctuation of melatonin-medicated JNK3 and Arrb1 expression.

Results: In this study, we found out melatonin contributed to the ameloblastic mineralization, from which we can observed the elevated expression of enamel matrix protein, and increased ALP activity and mineralized nodules formation. RNA-seq analysis showed the up-regulation of neural JNK3 and down-regulation of Arrb1 in ALCs. Meanwhile, phosphorylated JNK3 deficiency (phosphorylated JNK3 inhibitor---SR3576 added to culture medium) led to mineralization delay, and Arrb1 overexpression proved Arrb1 takes bridge between melatonin receptors (MTNR) and JNK3 in MAPK signaling pathway.
HIF-1α Induces HECTD2 Up-Regulation and Aggravates the Malignant Progression of Renal Cell Cancer via Repressing miR-320a
Authors: Lv Dong , Shen Taimin , Yao Juncheng , Yang Qi , Xiang Ying , Ma Zhiwei
Published: December 2021

Renal cell carcinoma (RCC) is a frequent malignancy of the urinary system. It has been found that hypoxia mediates the malignant evolvement of RCC. Here, we probe the impact and potential mechanism of HECT domain E3 ubiquitin-protein ligase 2 (HECTD2) and HIF-1α on regulating RCC evolvement. RCC tissues and adjacent normal tissues were collected, and the association between the expression profiles of HECTD2 and HIF-1α and the clinicopathological features was analyzed. Additionally, we constructed HECTD2/HIF-1α overexpression and knockdown models in RCC cell lines to ascertain the impacts of HECTD2 and HIF-1α on RCC cell proliferation, apoptosis, migration, and growth in vivo. We applied bioinformatics to predict the upstream miRNA targets of HECTD2. Meanwhile, RNA immunoprecipitation (RIP), and the dual-luciferase reporter assays were employed to clarify the targeting association between HECTD2 and miR-320a. The effect of miR-320a on HECTD2-mediated RCC progression was investigated. The results suggested that both HIF-1α and HECTD2 were up-regulated in RCC (compared with adjacent non-tumor tissues), and they had positive relationship. Moreover, higher level of HECTD2 and HIF-1α is associated with poorer overall survival of RCC patients. HECTD2 overexpression heightened RCC cell proliferation and migration, and weakened cell apoptosis. On the other hand, the malignant phenotypes of RCC cells were signally impeded by HECTD2 or HIF-1α knockdown. Moreover, miR-320a targeted the 3′-untranslated region of HECTD2 and suppressed HECTD2 expression. The rescue experiments showed that miR-320a restrained HECTD2-mediated malignant progression in RCC, while up-regulation of HIF-1α hampered miR-320a expression. Collectively, HIF-1α mediated HECTD2 up-regulation and aggravated RCC progression by attenuating miR-320a.
Nuclear Receptor Interacting Protein-2 Mediates the Stabilization and Activation of β-Catenin During Podocyte Injury
Authors: Hou Qing , Le Weibo , Kan Shuyan , Shi Jinsong , Lang Yue , Liu Zhihong , Chen Zhaohong
Published: December 2021

Objective: Activation of β-catenin causes podocyte injury and proteinuria, but how β-catenin signalling is regulated during podocyte injury remains elusive. Nuclear receptor interacting protein 2 (NRIP2) modulates the Wnt pathway in colorectal cancer-initiating cells, but the role of NRIP2 in podocyte injury has not yet been investigated. We aimed to examine the interaction between NRIP2 and β-catenin signalling.

Materials and Methods: Knockdown or overexpression of NRIP2 and β-catenin and chemical treatments were performed in cultured human podocytes. Immunoprecipitation, immunoblotting and immunofluorescence assays were used to assess protein interactions and expression. Data from the GEO dataset and kidney tissues from patients with focal segmental glomerulosclerosis (FSGS) and surgical nephrectomy were examined. An adriamycin (ADR) nephropathy model was established in NRIP2 knockout mice.

Results: NRIP2 knockdown accelerated β-catenin degradation, which was reversed by MG132; specifically, NRIP2 bound β-catenin and stabilized it to prevent its degradation through the ubiquitin proteasomal pathway. Overexpression of NRIP2 led to β-catenin activation and Snail1 induction, and these effects were attenuated by β-catenin knockdown. NRIP2 knockdown blocked ADR-stimulated β-catenin activation. In ADR mice, genetic knockout of Nrip2 ameliorated podocyte injury and loss, glomerulosclerosis, and proteinuria by inhibiting β-catenin activation. Moreover, NRIP2 was significantly upregulated in podocytes of FSGS patients and colocalized with nuclear β-catenin.

Conclusion: These results established NRIP2 as a stabilizer of β-catenin activation through the ubiquitin proteasomal pathway in podocyte injury.
Nomograms Involving HER2 for Predicting Lymph Node Metastasis in Early Gastric Cancer
Authors: Mei Yu , Wang Shuo , Feng Tienan , Yan Min , Yuan Fei , Zhu Zhenggang , Li Tian , Zhu Zhenglun
Published: December 2021

Objective: We aimed to establish a nomogram for predicting lymph node metastasis in early gastric cancer (EGC) involving human epidermal growth factor receptor 2 (HER2).

Methods: We collected clinicopathological data of patients with EGC who underwent radical gastrectomy and D2 lymphadenectomy at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between January 2012 and August 2018. Univariate and multivariate logistic regression analysis were used to examine the relationship between lymph node metastasis and clinicopathological features. A nomogram was constructed based on a multivariate prediction model. Internal validation from the training set was performed using receiver operating characteristic (ROC) and calibration plots to evaluate discrimination and calibration, respectively. External validation from the validation set was utilized to examine the external validity of the prediction model using the ROC plot. A decision curve analysis was used to evaluate the benefit of the treatment.

Results: Among 1,212 patients with EGC, 210 (17.32%) presented with lymph node metastasis. Multivariable analysis showed that age, tumor size, submucosal invasion, histological subtype, and HER2 positivity were independent risk factors for lymph node metastasis in EGC. The area under the ROC curve of the model was 0.760 (95% CI: 0.719–0.800) in the training set (n = 794) and 0.771 (95% CI: 0.714–0.828) in the validation set (n = 418). A predictive nomogram was constructed based on a multivariable prediction model. The decision curve showed that using the prediction model to guide treatment had a higher net benefit than using endoscopic submucosal dissection (ESD) absolute criteria over a range of threshold probabilities.

Conclusion: A clinical prediction model and an effective nomogram with an integrated HER2 status were used to predict EGC lymph node metastasis with better accuracy and clinical performance.
Overlapping Genetic Architecture Between Schizophrenia and Neurodegenerative Disorders
Authors: Li Chunyu , Yang Tianmi , Ou Ruwei , Shang Huifang
Published: December 2021

Epidemiological and clinical studies have suggested comorbidity between schizophrenia and several neurodegenerative disorders. However, little is known whether there exists shared genetic architecture. To explore their relationship from a genetic and transcriptomic perspective, we applied polygenic and linkage disequilibrium-informed methods to examine the genetic correlation between schizophrenia and amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Alzheimer’s disease and frontotemporal dementia. We further combined genome-wide association summary statistics with large-scale transcriptomic datasets, to identify putative shared genes and explore related pathological tissues. We identified positive and significant correlation between schizophrenia and ALS at genetic (correlation 0.22; 95% CI: 0.16–0.28; p = 4.00E-04) and transcriptomic (correlation 0.08; 95% CI: 0.04–0.11; p = 0.034) levels. We further demonstrated that schizophrenia- and ALS-inferred gene expression overlap significantly in four tissues including skin, small intestine, brain cortex and lung, and highlighted three genes, namely GLB1L3, ZNHIT3 and TMEM194A as potential mediators of the correlation between schizophrenia and ALS. Our findings revealed overlapped gene expression profiles in specific tissues between schizophrenia and ALS, and identified novel potential shared genes. These results provided a better understanding for the pleiotropy of schizophrenia, and paved way for future studies to further elucidate the molecular drivers of schizophrenia.
Targeting and Insertion of Membrane Proteins in Mitochondria
Authors: Eaglesfield Ross , Tokatlidis Kostas
Published: December 2021

Mitochondrial membrane proteins play an essential role in all major mitochondrial functions. The respiratory complexes of the inner membrane are key for the generation of energy. The carrier proteins for the influx/efflux of essential metabolites to/from the matrix. Many other inner membrane proteins play critical roles in the import and processing of nuclear encoded proteins (∼99% of all mitochondrial proteins). The outer membrane provides another lipidic barrier to nuclear-encoded protein translocation and is home to many proteins involved in the import process, maintenance of ionic balance, as well as the assembly of outer membrane components. While many aspects of the import and assembly pathways of mitochondrial membrane proteins have been elucidated, many open questions remain, especially surrounding the assembly of the respiratory complexes where certain highly hydrophobic subunits are encoded by the mitochondrial DNA and synthesised and inserted into the membrane from the matrix side. This review will examine the various assembly pathways for inner and outer mitochondrial membrane proteins while discussing the most recent structural and biochemical data examining the biogenesis process.
Characterization of a Geopolymer Foam by X-ray Tomography
Authors: Petlitckaia Svetlana , Vincente Jérôme , Poulesquen Arnaud
Published: December 2021

Metakaolin based geopolymer foams were synthesized at room temperature by direct foaming using hydrogen peroxide (H2O2) as a blowing agent and two types of surfactants such as AER5 and CTAB allowing to tune the connection between two adjacent cells. In the field of decontamination process of liquid wastes, the knowledge of the topology of the generated macroporous network is a primary of interest. Due to the complex structure of porous material, 2D conventional techniques as optical or scanning electron microscopy are often not able to provide all the necessary informations. The 3D networks were therefore characterized by X-ray tomography to determine the morphological structure parameters that is useful to manufacture geopolymer material for filtration applications. The porosity, the pore size distribution and constriction between adjacent cells, as well as the connection rates between pores were analyzed by the iMorph program. The results show that the total porosity increases from 26 to 74% when the initial concentration of H2O2 increases, which is in complete agreement with the tomography results. Materials synthetized from CTAB surfactant are poorly connected whereas those generated from AER5 surfactant have a higher mean cell size (at equivalent initial H2O2 concentration) and are fully connected, which will facilitate the transport of fluid through the material. These features have a strong impact on the value of permeability coefficients of the geopolymer foams. Indeed, permeabilities calculated from a Pore Network Modeling (PNM) approach or Kozeny-Carman equation, are ranged in between 10−14 to 10−10 m2 depending on the cell connectivity, the throat size and the total porosity.
Red-Shift (2-Hydroxyphenyl)-Benzothiazole Emission by Mimicking the Excited-State Intramolecular Proton Transfer Effect
Authors: Ren Yong , Zhou Lei , Li Xin
Published: December 2021

Novel strategies to optimize the photophysical properties of organic fluorophores are of great significance to the design of imaging probes to interrogate biology. While the 2-(2-hydroxyphenyl)-benzothiazole (HBT) fluorophore has attracted considerable attention in the field of fluorescence imaging, its short emission in the blue region and low quantum yield restrict its wide application. Herein, by mimicking the excited-state intramolecular proton transfer (ESIPT) effect, we designed a series of 2-(2-hydroxyphenyl)-benzothiazole (HBT) derivatives by complexing the heteroatoms therein with a boron atom to enhance the chance of the tautomerized keto-like resonance form. This strategy significantly red-shifted the emission wavelengths of HBT, greatly enhanced its quantum yields, and caused little effect on molecular size. Typically, compounds 12B and 13B were observed to emit in the near-infrared region, making them among the smallest organic structures with emission above 650 nm.
In Vivo Kinetics and Biotransformation of Aflatoxin B1 in Dairy Cows Based on the Establishment of a Reliable UHPLC-MS/MS Method
Authors: Guo Wenbo , Fan Zhichen , Fan Kai , Meng Jiajia , Nie Dongxia , Tangni Emmanuel K. , Li Zenghe , Zhao Zhihui , Han Zheng
Published: December 2021

The in vivo kinetics of aflatoxin B1 (AFB1) and its carry-over as aflatoxin M1 (AFM1) in milk as well as the toxin loads in the tissue of dairy cows were assessed through a repetitive feeding trial of an AFB1-contaminated diet of 4 μg kg−1 body weight (b.w.) for 13 days. This was followed by a clearance period that ended with a single dose trial of an AFB1-contaminated diet of 40 μg kg−1 b.w. An ultra-high performance liquid chromatography tandem mass spectrometry method was developed and successfully validated by the determination of linearity (R2 ≥ 0.990), sensitivity (lower limit of quantification, 0.1–0.2 ng ml−1), recovery (79.5–111.2%), and precision relative standard deviation (RSD) ≤14.7%) in plasma, milk, and various tissues. The repetitive ingestion of AFB1 indicated that the biotransformation of AFB1 to AFM1 occurred within 48 h, and the clearance period of AFM1 in milk was not more than 2 days. The carry-over rate of AFM1 in milk during the continuous ingestion experiment was in the range of 1.15–2.30% at a steady state. The in vivo kinetic results indicated that AFB1 reached a maximum concentration of 3.8 ± 0.9 ng ml−1 within 35.0 ± 10.2 min and was slowly eliminated from the plasma, with a half-life time (T1/2) of 931.1 ± 30.8 min. Meanwhile, AFM1 reached a plateau in plasma (0.5 ± 0.1 ng ml−1) at 4 h after the ingestion. AFB1 was found in the heart, spleen, lungs, and kidneys at concentrations of 1.6 ± 0.3, 4.1 ± 1.2, 3.3 ± 0.9 and 5.6 ± 1.4 μg kg−1, respectively. AFM1 was observed in the spleen and kidneys at concentrations of only 0.7 ± 0.2 and 0.8 ± 0.1 μg kg−1, respectively. In conclusion, the in vivo kinetics and biotransformation of AFB1 in dairy cows were determined using the developed UHPLC-MS/MS method, and the present findings could be helpful in assessing the health risks to consumers.
Light-Assisted Enhancement of Gas Sensing Property for Micro-Nanostructure Electronic Device: A Mini Review
Authors: Ma Zongtao , Wang Ziying , Gao Lingxiao
Published: December 2021

In recent years, gas sensing electronic devices have always attracted wide attention in the field of environment, industry, aviation and others. In order to improve the gas sensing properties, many micro- and nano-fabrication technologies have been proposed and investigated to develop high-performance gas sensing devices. It is worth noting that light irradiation is an effective strategy to enhance gas sensitivity, shorten the response and recovery time, reduce operating temperature. In this review, firstly, the latest research advances of gas sensors based on different micro-nanostructure materials under UV light and visible light activation is introduced. Then, the gas sensing mechanism of light-assisted gas sensor is discussed in detail. Finally, this review describes the present application of gas sensors with improved properties under light activation assisted conditions and the perspective of their applications.
A Simple Colorimetric Assay for Sensitive Cu2+ Detection Based on the Glutathione-Mediated Etching of MnO2 Nanosheets
Authors: Tang Shurong , Liu Qiao , Hu Jie , Chen Wei , An Fengping , Xu Hui , Song Hongbo , Wang Yi-Wei
Published: December 2021

In this paper, we developed a quick, economical and sensitive colorimetric strategy for copper ions (Cu2+) quantification via the redox response of MnO2 nanosheets with glutathione (GSH). This reaction consumed MnO2 nanosheets, which acted as a catalyst for the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to a blue product (oxTMB). In the presence of Cu2+, the GSH was catalyzed to GSSG (oxidized glutathione), and the solution changed from colorless to deep blue. Under the optimum conditions, the absorption signal of the oxidized product (oxTMB) became proportional to Cu2+ concentration in the range from 10 to 300 nM with a detection limit of 6.9 nM. This detection system showed high specificity for Cu2+. Moreover, the system has been efficaciously implemented for Cu2+ detection in actual tap water samples. The layered-nanostructures of MnO2 nanosheets make it possess high chemical and thermal stability. TMB can be quickly oxidized within 10 min by the catalyzing of MnO2 nanosheets with high oxidase-like activity. There is no need of expensive reagents, additional H2O2 and complicated modification processes during the colorimetric assay. Therefore, the strategy primarily based on MnO2 nanosheets is promising for real-time, rapid and highly sensitive detection of Cu2+ under practical conditions.
Systemic Antibiotics Influence Periodontal Parameters and Oral Microbiota, But Not Serological Markers
Authors: Kopra Elisa , Lahdentausta Laura , Pietiäinen Milla , Buhlin Kåre , Mäntylä Päivi , Hörkkö Sohvi , Persson Rutger , Paju Susanna , Sinisalo Juha , Salminen Aino , Pussinen Pirkko J.
Published: December 2021

The use of systemic antibiotics may influence the oral microbiota composition. Our aim was to investigate in this retrospective study whether the use of prescribed antibiotics associate with periodontal status, oral microbiota, and antibodies against the periodontal pathogens. The Social Insurance Institution of Finland Data provided the data on the use of systemic antibiotics by record linkage to purchased medications and entitled reimbursements up to 1 year before the oral examination and sampling. Six different classes of antibiotics were considered. The Parogene cohort included 505 subjects undergoing coronary angiography with the mean (SD) age of 63.4 (9.2) years and 65% of males. Subgingival plaque samples were analysed using the checkerboard DNA-DNA hybridisation. Serum and saliva antibody levels to periodontal pathogens were analysed with immunoassays and lipopolysaccharide (LPS) activity with the LAL assay. Systemic antibiotics were prescribed for 261 (51.7%) patients during the preceding year. The mean number of prescriptions among them was 2.13 (range 1–12), and 29.4% of the prescriptions were cephalosporins, 25.7% penicillins, 14.3% quinolones, 12.7% macrolides or lincomycin, 12.0% tetracycline, and 5.8% trimethoprim or sulphonamides. In linear regression models adjusted for age, sex, current smoking, and diabetes, number of antibiotic courses associated significantly with low periodontal inflammation burden index (PIBI, p < 0.001), bleeding on probing (BOP, p = 0.006), and alveolar bone loss (ABL, p = 0.042). Cephalosporins associated with all the parameters. The phyla mainly affected by the antibiotics were Bacteroidetes and Spirochaetes. Their levels were inversely associated with the number of prescriptions (p = 0.010 and p < 0.001) and directly associated with the time since the last prescription (p = 0.019 and p < 0.001). Significant inverse associations were observed between the number of prescriptions and saliva concentrations of Prevotella intermedia, Tannerella forsythia, and Treponema denticola and subgingival bacterial amounts of Porphyromonas gingivalis, P. intermedia, T. forsythia, and T. denticola. Saliva or serum antibody levels did not present an association with the use of antibiotics. Both serum (p = 0.031) and saliva (p = 0.032) LPS activity was lower in patients having any antibiotic course less than 1 month before sampling. Systemic antibiotics have effects on periodontal inflammation and oral microbiota composition, whereas the effects on host immune responses against the periodontal biomarker species seem unchanged.
Circulating Chromogranin B Is Associated With Left Ventricular Functional Recovery After Successful Recanalization of Chronic Total Occlusion
Authors: Shen Ying , Aihemaiti Muladili , Shu Xin Yi , Yang Chen Die , Chen Jia Wei , Dai Yang , Ding Feng Hua , Yang Zhen Kun , Hu Jian , Zhang Rui Yan , Lu Lin , Wang Xiao Qun , Shen Wei Feng
Published: December 2021

Background: Chromogranin B (CgB) is increased in heart failure and proportionate to disease severity. We investigated whether circulating CgB level is associated with left ventricular (LV) functional recovery potential after successful recanalization of chronic total occlusion (CTO).

Methods: Serum levels of CgB were assayed in 53 patients with stable angina with LV functional recovery [an absolute increase in LV ejection fraction (EF) of ≥5%] and 53 age- and sex-matched non-recovery controls after successful recanalization of CTO during 12-month follow-up.

Results: We found that CgB level was significantly lower in the recovery group than in the non-recovery group (593 [IQR 454–934] vs. 1,108 [IQR 696–2020] pg/ml, P < 0.001), and that it was inversely correlated with changes in LVEF (Spearman's r = −0.31, P = 0.001). Receiver operating characteristic (ROC) analysis showed that the area under the curve of CgB for predicting LVEF improvement was 0.76 (95% CI 0.664–0.856), and that the optimal cutoff value was 972.5 pg/ml. In multivariate analyses, after adjusting for confounding factors, high CgB level remained an independent determinant of impaired LV functional recovery after CTO recanalization. LV functional improvement appeared to be more responsive to CgB in patients with poor than with good coronary collaterals.

Conclusions: Elevated circulating CgB level confers an increased risk of impaired LV functional recovery after successful recanalization of CTO in patients with stable coronary artery disease.
Center-To-Periphery Arterial Stiffness Gradient Is Attenuated and/or Reversed in Pregnancy-Associated Hypertension
Authors: Pereira María M. , Torrado Juan , Sosa Claudio , Diaz Alejandro , Bia Daniel , Zócalo Yanina
Published: December 2021

Background: Non-pregnant (NP) women have a progressive increase in arterial stiffness from central-to-peripheral arteries [“stiffness gradient” (SG)], which is of physiologic importance since excessive pulsatility is filtered by the creation of wave reflections. If the aorta gets stiff with minimal or no change in the periphery, the SG is dissipated transmitting pressure disturbances to the microcirculation. It remains unknown the status of the SG in both women with healthy pregnancies (HP) and complicated by pregnancy-associated hypertension (PAH).

Objective: To determine whether HP and PAH are associated with changes in SG. Secondarily, we aim at identifying potential differences between the subgroups of PAH (pre-eclampsia and gestational hypertension).

Methods: HP (n = 10), PAH (n = 16), and healthy NP women (n = 401, to be matched for age, and cardiovascular risk with the pregnant women) were included. Carotid-to-femoral (cfPWV) and carotid-to-radial pulse wave velocity (crPWV), common carotid artery (CCA) and brachial artery (BA) diameters and elastic modulus (EM), and regional (cfPWV/crPWV or “PWV ratio”) and local (CCA EM/BA EM or “EM ratio”) SG were quantified.

Results: HP showed no changes in PWV ratio compared with NP, in the presence of significantly lower cfPWV and crPWV. HP exhibited higher arterial diameters and lower CCA EM/BA EM compared to NP, without differences with PAH. PAH was associated with a significant increase in the PWV ratio that exceeded the levels of both NP and HP, explained by a lower (although significant) reduction of cfPWV with respect to that observed in HP with respect to NP, and a higher reduction in crPWV with respect to that observed between HP and NP. The blunted reduction in cfPWV observed in PAH coincided with an increase in the CCA EM.

Conclusions: Compared with NP, HP was associated with unchanged PWV ratio but with a reduction in CCA EM/BA EM, in the setting of a generalized drop in arterial stiffness. Compared with NP and HP, PAH was associated with an “exaggerated rise” in the PWV ratio without changes in CCA EM/BA EM, in the setting of a blunt reduction in cfPWV but exaggerated crPWV drop. The SG attenuation/reversal in PAH was mainly driven by pre-eclampsia.
Biocompatibility and Application of Carbon Fibers in Heart Valve Tissue Engineering
Authors: Tseng Yuan-Tsan , Grace Nabil F. , Aguib Heba , Sarathchandra Padmini , McCormack Ann , Ebeid Ahmed , Shehata Nairouz , Nagy Mohamed , El-Nashar Hussam , Yacoub Magdi H. , Chester Adrian , Latif Najma
Published: December 2021

The success of tissue-engineered heart valves rely on a balance between polymer degradation, appropriate cell repopulation, and extracellular matrix (ECM) deposition, in order for the valves to continue their vital function. However, the process of remodeling is highly dynamic and species dependent. The carbon fibers have been well used in the construction industry for their high tensile strength and flexibility and, therefore, might be relevant to support tissue-engineered hearts valve during this transition in the mechanically demanding environment of the circulation. The aim of this study was to assess the suitability of the carbon fibers to be incorporated into tissue-engineered heart valves, with respect to optimizing their cellular interaction and mechanical flexibility during valve opening and closure. The morphology and surface oxidation of the carbon fibers were characterized by scanning electron microscopy (SEM). Their ability to interact with human adipose-derived stem cells (hADSCs) was assessed with respect to cell attachment and phenotypic changes. hADSCs attached and maintained their expression of stem cell markers with negligible differentiation to other lineages. Incorporation of the carbon fibers into a stand-alone tissue-engineered aortic root, comprised of jet-sprayed polycaprolactone aligned carbon fibers, had no negative effects on the opening and closure characteristics of the valve when simulated in a pulsatile bioreactor. In conclusion, the carbon fibers were found to be conducive to hADSC attachment and maintaining their phenotype. The carbon fibers were sufficiently flexible for full motion of valvular opening and closure. This study provides a proof-of-concept for the incorporation of the carbon fibers into tissue-engineered heart valves to continue their vital function during scaffold degradation.
Targeted Genetic Reduction of Mutant Huntingtin Lessens Cardiac Pathology in the BACHD Mouse Model of Huntington's Disease
Authors: Park Saemi , Luk Shu Hon Christopher , Bains Raj S. , Whittaker Daniel S. , Chiem Emily , Jordan Maria C. , Roos Kenneth P. , Ghiani Cristina A. , Colwell Christopher S.
Published: December 2021

Individuals affected by Huntington's disease (HD) present with progressive degeneration that results in a wide range of symptoms, including cardiovascular (CV) dysfunction. The huntingtin gene (HTT) and its product are ubiquitously expressed, hence, the cardiomyopathy could also be driven by defects caused by its mutated form (mHTT) in the cardiomyocytes themselves. In the present study, we sought to determine the contribution of themHTTexpressed in the cardiomyocytes to CV symptoms. We utilized the BACHD mouse model, which exhibits many of the HD core symptoms, including CV dysfunction. This model allows the targeted genetic reduction ofmHTTexpression in the cardiomyocytes while maintaining the expression of themHTTin the rest of the body. The BACHD line was crossed with a line of mice in which the expression of Cre recombinase is driven by the cardiac-specific alpha myosin-heavy chain (Myh6) promoter. The offspring of this cross (BMYO mice) exhibited a dramatic reduction inmHTTin the heart but not in the striatum. The BMYO mice were evaluated at 6 months old, as at this age, the BACHD line displays a strong CV phenotype. Echocardiogram measurements found improvement in the ejection fraction in the BMYO line compared to the BACHD, while hypertrophy was observed in both mutant lines. Next, we examined the expression of genes known to be upregulated during pathological cardiac hypertrophy. As measured by qPCR, the BMYO hearts exhibited significantly less expression ofcollagen1aas well asGata4, andbrain natriuretic peptidecompared to the BACHD. Fibrosis in the hearts assessed by Masson's trichrome stain and the protein levels of fibronectin were reduced in the BMYO hearts compared to BACHD. Finally, we examined the performance of the mice on CV-sensitive motor tasks. Both the overall activity levels and grip strength were improved in the BMYO mice. Therefore, we conclude that the reduction ofmHttexpression in the heart benefits CV function in the BACHD model, and suggest that cardiomyopathy should be considered in the treatment strategies for HD.
Seasonal Evolution of Supraglacial Lakes on Baltoro Glacier From 2016 to 2020
Authors: Wendleder Anna , Schmitt Andreas , Erbertseder Thilo , D’Angelo Pablo , Mayer Christoph , Braun Matthias H.
Published: December 2021

The existence of supraglacial lakes influences debris-covered glaciers in two ways. The absorption of solar radiation in the water leads to a higher ice ablation, and water draining through the glacier to its bed leads to a higher velocity. Rising air temperatures and changes in precipitation patterns provoke an increase in the supraglacial lakes in number and total area. However, the seasonal evolution of supraglacial lakes and thus their potential for influencing mass balance and ice dynamics have not yet been sufficiently analyzed. We present a summertime series of supraglacial lake evolution on Baltoro Glacier in the Karakoram from 2016 to 2020. The dense time series is enabled by a multi-sensor and multi-temporal approach based on optical (Sentinel-2 and PlanetScope) and Synthetic Aperture Radar (SAR; Sentinel-1 and TerraSAR-X) remote sensing data. The mapping of the seasonal lake evolution uses a semi-automatic approach, which includes a random forest classifier applied separately to each sensor. A combination of linear regression and the Hausdorff distance is used to harmonize between SAR- and optical-derived lake areas, producing consistent and internally robust time series dynamics. Seasonal variations in the lake area are linked with the Standardized Precipitation Index (SPI) and Standardized Temperature Index (STI) based on air temperature and precipitation data derived from the climate reanalysis dataset ERA5-Land. The largest aggregated lake area was found in 2018 with 5.783 km2, followed by 2019 with 4.703 km2, and 2020 with 4.606 km2. The years 2016 and 2017 showed the smallest areas with 3.606 and 3.653 km2, respectively. Our data suggest that warmer spring seasons (April–May) with higher precipitation rates lead to increased formation of supraglacial lakes. The time series decomposition shows a linear increase in the lake area of 11.12 ± 9.57% per year. Although the five-year observation period is too short to derive a significant trend, the tendency for a possible increase in the supraglacial lake area is in line with the pronounced positive anomalies of the SPI and STI during the observation period.
Intermittent Growth of a Newly-Born Volcanic Island and Its Feeding System Revealed by Geological and Geochemical Monitoring 2013–2020, Nishinoshima, Ogasawara, Japan
Authors: Maeno Fukashi , Yasuda Atsushi , Hokanishi Natsumi , Kaneko Takayuki , Tamura Yoshihiko , Yoshimoto Mitsuhiro , Nakano Shun , Takagi Akimichi , Takeo Minoru , Nakada Setsuya
Published: December 2021

The island-forming Nishinoshima eruptions in the Ogasawara Islands, Japan, provide a rare opportunity to examine how the terrestrial part of Earth’s surface increases via volcanism. Here, the sequence of recent eruptive activity of Nishinoshima is described based on long-term geological and geochemical monitoring of eruptive products. Processes of island growth and temporal changes in the magma chemistry are discussed. The growth of Nishinoshima was sustained by the effusion of low-viscosity andesite lava flows since 2013. The lava flows spread radially with numerous branches, resulting in compound lava flows. Lava flows form the coherent base of the new volcanic edifice; however, pyroclastic eruptions further developed the subaerial volcanic edifice. The duration of three consecutive eruptive episodes decreased from 2 years to a week through the entire eruptive sequence, with a decreasing eruptive volume and discharge rate through time. However, the latest, fourth episode was the most intense and largest, with a magma discharge rate on the order of 106 m3/day. The temporal change in the chemical composition of the magma indicates that more mafic magma was involved in the later episodes. The initial andesite magma with ∼60 wt% SiO2 changed to basaltic andesite magma with ∼55 wt% SiO2, including olivine phenocryst, during the last episode. The eruptive behavior and geochemical characteristics suggest that the 2013–2020 Nishinoshima eruption was fueled by magma resulting from the mixing of silicic and mafic components in a shallow reservoir and by magma episodically supplied from deeper reservoirs. The lava effusion and the occasional explosive eruptions, sustained by the discharge of magma caused by the interactions of these multiple magma reservoirs at different depths, contributed to the formation and growth of the new Nishinoshima volcanic island since 2013. Comparisons with several examples of island-forming eruptions in shallow seas indicate that a long-lasting voluminous lava effusion with a discharge rate on the order of at least 104 m3/day (annual average) to 105 m3/day (monthly average) is required for the formation and growth of a new volcanic island with a diameter on km-scale that can survive sea-wave erosion over the years.
Bio-Compatible Sensor for Middle Ear Pressure Monitoring on a Bio-Degradable Substrate
Authors: Mosshammer Klara , Lüdke Theresa , Spitzner Sarah , Firzlaff Daniel , Harre Kathrin , Kleemann Hans , Neudert Marcus , Zahnert Thomas , Leo Karl
Published: December 2021

Hypotension in the middle ear can cause serious diseases and hearing disorders. Until now, pressure in the middle ear is measured indirectly by using the impedance of the tympanic membrane (tympanometry). Direct methods are just described in scientific studies and would be harmful in clinical routine. Here, we demonstrate a bio-compatible pressure sensor, which can resolve pressure changes in the range of −7.5 kPa up to +7.5 kPa, and due to its compact design (area of 2 × 4 mm2), can be directly implanted in the human middle ear. Furthermore, the read-out of the pressure sensor can be conveniently done using wireless data communication technologies employing a plate capacitor with an elastic dielectric for pressure monitoring and a planar coil. Thus, our sensor allows for direct pressure measurements in the middle ear, avoiding additional surgeries after device implantation.
Puberty Status Modifies the Effects of Genetic Variants, Lifestyle Factors and Their Interactions on Adiponectin: The BCAMS Study
Authors: Wu Yunpeng , Zhong Ling , Li Ge , Han Lanwen , Fu Junling , Li Yu , Li Lujiao , Zhang Qian , Guo Yiran , Xiao Xinhua , Qi Lu , Li Ming , Gao Shan , Willi Steven. M.
Published: December 2021

Background

Hypoadiponectinemia has been associated with various cardiometabolic disease states. Previous studies in adults have shown that adiponectin levels were regulated by specific genetic and behavioral or lifestyle factors. However, little is known about the influence of these factors on adiponectin levels in children, particularly as mitigated by pubertal development.

Methods

We performed a cross-sectional analysis of data from 3,402 children aged 6-18 years from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. Pubertal progress was classified as prepubertal, midpuberty, and postpuberty. Six relevant single nucleotide polymorphisms (SNPs) were selected from previous genome-wide association studies of adiponectin in East Asians. Individual SNPs and two weighted genetic predisposition scores, as well as their interactions with 14 lifestyle factors, were analyzed to investigate their influence on adiponectin levels across puberty. The effect of these factors on adiponectin was analyzed using general linear models adjusted for age, sex, and BMI.

Results

After adjustment for age, sex, and BMI, the associations between adiponectin levels and diet items, and diet score were significant at prepuberty or postpuberty, while the effect of exercise on adiponectin levels was more prominent at mid- and postpuberty. Walking to school was found to be associated with increased adiponectin levels throughout puberty. Meanwhile, the effect of WDR11-FGFR2-rs3943077 was stronger at midpuberty (P = 0.002), and ADIPOQ-rs6773957 was more effective at postpuberty (P = 0.005), while CDH13-rs4783244 showed the strongest association with adiponectin levels at all pubertal stages (all P < 3.24 × 10-15). We further found that effects of diet score (Pinteraction = 0.022) and exercise (Pinteraction = 0.049) were stronger in children with higher genetic risk of hypoadiponectinemia, while higher diet score and exercise frequency attenuated the differences in adiponectin levels among children with different genetic risks.

Conclusions

Our study confirmed puberty modulates the associations between adiponectin, and genetic variants, lifestyle factors, and gene-by-lifestyle interactions. These findings provide new insight into puberty-specific lifestyle suggestions, especially in genetically susceptible individuals.
1-Deoxysphingolipids, Early Predictors of Type 2 Diabetes, Compromise the Functionality of Skeletal Myoblasts
Authors: Tran Duyen , Myers Stephen , McGowan Courtney , Henstridge Darren , Eri Rajaraman , Sonda Sabrina , Caruso Vanni
Published: December 2021

Metabolic dysfunction, dysregulated differentiation, and atrophy of skeletal muscle occur as part of a cluster of abnormalities associated with the development of Type 2 diabetes mellitus (T2DM). Recent interest has turned to the attention of the role of 1-deoxysphingolipids (1-DSL), atypical class of sphingolipids which are found significantly elevated in patients diagnosed with T2DM but also in the asymptomatic population who later develop T2DM. In vitro studies demonstrated that 1-DSL have cytotoxic properties and compromise the secretion of insulin from pancreatic beta cells. However, the role of 1-DSL on the functionality of skeletal muscle cells in the pathophysiology of T2DM still remains unclear. This study aimed to investigate whether 1-DSL are cytotoxic and disrupt the cellular processes of skeletal muscle precursors (myoblasts) and differentiated cells (myotubes) by performing a battery of in vitro assays including cell viability adenosine triphosphate assay, migration assay, myoblast fusion assay, glucose uptake assay, and immunocytochemistry. Our results demonstrated that 1-DSL significantly reduced the viability of myoblasts in a concentration and time-dependent manner, and induced apoptosis as well as cellular necrosis. Importantly, myoblasts were more sensitive to the cytotoxic effects induced by 1-DSL rather than by saturated fatty acids, such as palmitate, which are critical mediators of skeletal muscle dysfunction in T2DM. Additionally, 1-DSL significantly reduced the migration ability of myoblasts and the differentiation process of myoblasts into myotubes. 1-DSL also triggered autophagy in myoblasts and significantly reduced insulin-stimulated glucose uptake in myotubes. These findings demonstrate that 1-DSL directly compromise the functionality of skeletal muscle cells and suggest that increased levels of 1-DSL observed during the development of T2DM are likely to contribute to the pathophysiology of muscle dysfunction detected in this disease.
Let-7e-5p Regulates IGF2BP2, and Induces Muscle Atrophy
Authors: Okamura Takuro , Okada Hiroshi , Hashimoto Yoshitaka , Majima Saori , Senmaru Takafumi , Nakanishi Naoko , Asano Mai , Yamazaki Masahiro , Hamaguchi Masahide , Fukui Michiaki
Published: December 2021

Background and Aims

To understand the role of microRNAs in muscle atrophy caused by androgen-depletion, we performed microarray analysis of microRNA expression in the skeletal muscles of Sham, orchiectomized (ORX), and androgen-treated ORX mice.

Methods

To clarify role and mechanisms of let-7e-5p in the muscle, the effect of let-7e-5p overexpression or knockdown on the expression of myosin heavy chain, glucose uptake, and mitochondrial function was investigated in C2C12 myotube cells. Moreover, we examined serum let-7e-5p levels among male subjects with type 2 diabetes.

Results

We found that the expression of the miRNA, lethal (let)-7e-5p was significantly lower in ORX mice than that in Sham mice (p = 0.027); however, let-7e-5p expression in androgen-treated ORX mice was higher (p = 0.047). Suppression of let-7e-5p significantly upregulated the expression of myosin heavy chain, glucose uptake, and mitochondrial function. Real-time PCR revealed a possible regulation involving let-7e-5p and Igf2bp2 mRNA and protein in C2C12 cells. The serum let-7e-5p levels were significantly lower, which might be in compensation, in subjects with decreased muscle mass compared to subjects without decreased muscle mass. Let-7e-5p downregulates the expression of Igf2bp2 in myotube cells and inhibits the growth of the myosin heavy chain.

Conclusions

Based on our study, serum level of let-7e-5p may be used as a potential diagnostic marker for muscle atrophy.
Effect of Metformin on Testosterone Levels in Male Patients With Type 2 Diabetes Mellitus Treated With Insulin
Authors: Cai Tingting , Hu Yun , Ding Bo , Yan Rengna , Liu Bingli , Cai Ling , Jing Ting , Jiang Lanlan , Xie Xiaojing , Wang Yuming , Wang Huiying , Zhou Yunting , He Ke , Xu Lan , Chen Liang , Cheng Cheng , Ma Jianhua
Published: December 2021

Aim

To explore the chronic effects of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).

Methods

This is a secondary analysis of a real-world study evaluating the efficacy and safety of premixed insulin treatment in patients with T2DM via 3-month intermittent flash glucose monitoring. Male patients aged 18-60 who were using metformin during the 3-month study period were included as the metformin group. The control group included males without metformin therapy by propensity score matching analysis with age as a covariate. Testosterone levels were measured at baseline and after 3-month treatment.

Results

After 3-month treatment, the control group had higher levels of total testosterone, free and bioavailable testosterone than those at baseline (P<0.05). Compared with the control group, the change of total (-0.82 ± 0.59 vs. 0.99 ± 0.59 nmol/L) and bioavailable (-0.13 ± 0.16 vs. 0.36 ± 0.16 nmol/L) testosterone levels in the metformin group significantly decreased (P=0.036 and 0.029, respectively). In Glycated Albumin (GA) improved subgroup, the TT, FT, and Bio-T levels in the control subgroup were higher than their baseline levels (P < 0.05). Compared with the metformin subgroup, TT level in the control subgroup also increased significantly (P=0.044). In GA unimproved subgroup, the change of TT level in the metformin subgroup was significantly lower than that in the control subgroup (P=0.040).

Conclusion

In men with T2DM, 3-month metformin therapy can reduce testosterone levels, and counteract the testosterone elevation that accompanied with the improvement of blood glucose.

Clinical Trial Registration

https://www.clinicaltrials.gov/ct2/show/NCT04847219?term=04847219&draw=2&rank=1.
Nanoremediation: Nanomaterials and Nanotechnologies for Environmental Cleanup
Authors: Del Prado-Audelo M. L. , García Kerdan I. , Escutia-Guadarrama L. , Reyna-González J. M. , Magaña J. J. , Leyva-Gómez G.
Published: December 2021

Different global events such as industrial development and the population increment have triggered the presence and persistence of several organic and inorganic contaminants, representing a risk for the environment and human health. Consequently, the search and application of novel technologies for alleviating the challenge of environmental pollution are urgent. Nanotechnology is an emerging science that could be employed in different fields. In particular, Nanoremediation is a promising strategy defined as the engineered materials employed to clean up the environment, is an effective, rapid, and efficient technology to deal with persistent compounds such as pesticides, chlorinated solvents, halogenated chemicals, or heavy metals. Furthermore, nanoremediation is a sustainable alternative to eliminate emerging pollutants such as pharmaceutics or personal care products. Due to the variety of nanomaterials and their versatility, they could be employed in water, soil, or air media. This review provides an overview of the application of nanomaterials for media remediation. It analyzes the state of the art of different nanomaterials such as metal, carbon, polymer, and silica employed for water, soil, and air remediation.
The Reproduction of “Petro-Nationalism” in Ethnic Media: A Case Study of WeChat Public Accounts’ Coverage of the Trans Mountain Pipeline Controversy
Authors: Chen Sibo
Published: December 2021

Over the past 2 decades, Alberta’s bitumen industry has emerged as a major point of contention in Canadian politics, with the Trans Mountain pipeline expansion (TMX) project being a recent controversy that has attracted both domestic and international media attention. This brief research report focuses on news coverage of TMX in a rarely studied form of ethnic media: WeChat newsfeeds (known as “public accounts”) targeting Chinese diasporas across Canadian metropolises. A thematic analysis of TMX-related WeChat articles published between January 2016 and May 2021 reveals an overall negative attitude toward the project’s opponents. This stance is mainly due to WeChat public accounts’ heavy reliance on the Canadian mainstream media’s framing of TMX. As a result, the Canadian mainstream media’s downplay of the climate emergency and decarbonization sets the news agendas of the surveyed WeChat public accounts. Accordingly, there is an urgent need to develop non-English alternative media to engage ethnic minority groups in broader public conversations on climate change mitigation.