bluuebunny/crossref_metadata_2025 huggingface dataset:
The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model
Authors: Duan Qianni , Liu Tong , Huang Cong , Shao Qingqing , Ma Yonggui , Wang Wenjia , Liu Tianli , Sun Jun , Fang Jianguo , Huang Guangying , Chen Zhuo
Published: September 2021

Chinese herbal prescription JieZe-1 is effective for genital herpes with no visible adverse effects clinically. It showed an excellent anti-HSV-2 effect in vitro. However, its mechanism of anti-HSV-2 effect in vivo remains unclear. This study was designed to evaluate the anti-HSV-2 effect of JieZe-1 and berberine in a genital herpes mouse model and explore the underlying mechanism. The fingerprint of JieZe-1 was determined by high-performance liquid chromatography. First, we optimized a mouse model of genital herpes. Next, the weight, symptom score, morphological changes, viral load, membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells of vaginal tissue in mice at different time points were measured. Finally, we treated the genital herpes mouse model with JieZe-1 gel (2.5, 1.5, and 0.5 g/ml) and tested the above experimental indexes at 12 h and on the 9th day after modeling. JieZe-1 improved the symptoms, weight, and histopathological damage of genital herpes mice, promoted the keratin repair of tissues, and protected organelles to maintain the typical morphology of cells. It downregulated the expression of membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells. The vaginal, vulvar, and spinal cord viral load and vaginal virus shedding were also significantly reduced. In summary, JieZe-1 shows significant anti-HSV-2 efficacy in vivo. The mechanism is related to the inhibition of membrane fusion, the Toll-like receptor signaling pathway, inflammatory cytokines, and cellular immunity. However, berberine, the main component of JieZe-1 monarch medicine, showed no efficacy at a concentration of 891.8 μM (0.3 mg/ml).
Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution
Authors: Kolnes Kristoffer Jensen , Petersen Maria Houborg , Lien-Iversen Teodor , Højlund Kurt , Jensen Jørgen
Published: September 2021

In obesity, excessive abdominal fat, especially the accumulation of visceral adipose tissue (VAT), increases the risk of metabolic disorders, such as type 2 diabetes mellitus (T2DM), cardiovascular disease, and non-alcoholic fatty liver disease. Excessive abdominal fat is associated with adipose tissue dysfunction, leading to systemic low-grade inflammation, fat overflow, ectopic lipid deposition, and reduced insulin sensitivity. Physical activity is recommended for primary prevention and treatment of obesity, T2DM, and related disorders. Achieving a stable reduction in body weight with exercise training alone has not shown promising effects on a population level. Because fat has a high energy content, a large amount of exercise training is required to achieve weight loss. However, even when there is no weight loss, exercise training is an effective method of improving body composition (increased muscle mass and reduced fat) as well as increasing insulin sensitivity and cardiorespiratory fitness. Compared with traditional low-to-moderate-intensity continuous endurance training, high-intensity interval training (HIIT) and sprint interval training (SIT) are more time-efficient as exercise regimens and produce comparable results in reducing total fat mass, as well as improving cardiorespiratory fitness and insulin sensitivity. During high-intensity exercise, carbohydrates are the main source of energy, whereas, with low-intensity exercise, fat becomes the predominant energy source. These observations imply that HIIT and SIT can reduce fat mass during bouts of exercise despite being associated with lower levels of fat oxidation. In this review, we explore the effects of different types of exercise training on energy expenditure and substrate oxidation during physical activity, and discuss the potential effects of exercise training on adipose tissue function and body fat distribution.
Exercise May Promote Skeletal Muscle Hypertrophy via Enhancing Leucine-Sensing: Preliminary Evidence
Authors: Zhao Yan , Cholewa Jason , Shang Huayu , Yang Yueqin , Ding Xiaomin , Liu Shaosheng , Xia Zhi , Zanchi Nelo Eidy , Wang Qianjin
Published: September 2021

Several studies have indicated a positive effect of exercise (especially resistance exercise) on the mTOR signaling that control muscle protein synthesis and muscle remodeling. However, the relationship between exercise, mTOR activation and leucine-sensing requires further clarification. Two month old Sprague-Dawley rats were subjected to aerobic exercise (treadmill running at 20 m/min, 6° incline for 60 min) and resistance exercise (incremental ladder climbing) for 4 weeks. The gastrocnemius muscles were removed for determination of muscle fibers diameter, cross-sectional area (CSA), protein concentration and proteins involved in muscle leucine-sensing and protein synthesis. The results show that 4 weeks of resistance exercise increased the diameter and CSA of gastrocnemius muscle fibers, protein concentration, the phosphorylation of mTOR (Ser2448), 4E-BP1(Thr37/46), p70S6K (Thr389), and the expression of LeuRS, while aerobic exercise just led to a significant increase in protein concentration and the phosphorylation of 4E-BP1(Thr37/46). Moreover, no difference was found for Sestrin2 expression between groups. The current study shows resistance exercise, but not aerobic exercise, may increase muscle protein synthesis and protein deposition, and induces muscle hypertrophy through LeuRS/mTOR signaling pathway. However, further studies are still warranted to clarify the exact effects of vary intensities and durations of aerobic exercise training.
Help-Seeking Intention in Obsessive-Compulsive Disorder: Predictors and Barriers in South Africa
Authors: Hathorn Sarah Kate , Lochner Christine , Stein Dan J. , Bantjes Jason
Published: September 2021

Introduction: Many individuals with obsessive-compulsive disorder (OCD) delay seeking help, leading to greater illness severity, additional comorbidity, and increased functional impairment. Patterns of help-seeking for OCD have however not yet been described in South Africa, a low-and middle-income country with many health service challenges. Using the health belief model as a conceptual framework, study aims were to identify predictors of and barriers to help-seeking among South Africans with OCD.

Methods: Fifty adults with OCD completed an online survey to assess (1) socio-demographic characteristics, (2) OCD symptom severity, (3) treatment barriers, (4) perceived treatment benefits, (5) self-efficacy, and (6) help-seeking intention. Multiple linear regression analysis was used to establish predictors of help-seeking intention. Descriptive statistics were used to determine the most endorsed help-seeking barriers.

Results: 42.6% of the variance in help-seeking intention was explained by the investigated constructs (R2 = 0.426, F = 4.45 and p < 0.01). Perceived treatment benefits were the only significant predictor of help-seeking intention (B = 1.37, t = 5.16, and p < 0.01). More than a third (36%) of the sample endorsed wanting to handle the problem independently as a significant barrier, followed by treatment concerns (26%), affordability (22%), and shame (20%).

Conclusion: An innovative analysis of help-seeking patterns suggested that perceived treatment benefits were the only significant predictor of help-seeking intention among South African adults with OCD. Psychoeducation and mental health literacy programmes may be useful in increasing public appreciation of the benefits of OCD treatment, and in mitigating key help-seeking barriers.
Predicting the Risk of Hypertension Based on Several Easy-to-Collect Risk Factors: A Machine Learning Method
Authors: Zhao Huanhuan , Zhang Xiaoyu , Xu Yang , Gao Lisheng , Ma Zuchang , Sun Yining , Wang Weimin
Published: September 2021

Hypertension is a widespread chronic disease. Risk prediction of hypertension is an intervention that contributes to the early prevention and management of hypertension. The implementation of such intervention requires an effective and easy-to-implement hypertension risk prediction model. This study evaluated and compared the performance of four machine learning algorithms on predicting the risk of hypertension based on easy-to-collect risk factors. A dataset of 29,700 samples collected through a physical examination was used for model training and testing. Firstly, we identified easy-to-collect risk factors of hypertension, through univariate logistic regression analysis. Then, based on the selected features, 10-fold cross-validation was utilized to optimize four models, random forest (RF), CatBoost, MLP neural network and logistic regression (LR), to find the best hyper-parameters on the training set. Finally, the performance of models was evaluated by AUC, accuracy, sensitivity and specificity on the test set. The experimental results showed that the RF model outperformed the other three models, and achieved an AUC of 0.92, an accuracy of 0.82, a sensitivity of 0.83 and a specificity of 0.81. In addition, Body Mass Index (BMI), age, family history and waist circumference (WC) are the four primary risk factors of hypertension. These findings reveal that it is feasible to use machine learning algorithms, especially RF, to predict hypertension risk without clinical or genetic data. The technique can provide a non-invasive and economical way for the prevention and management of hypertension in a large population.
Pharmacological Inhibition of PP2A Overcomes Nab-Paclitaxel Resistance by Downregulating MCL1 in Esophageal Squamous Cell Carcinoma (ESCC)
Authors: Song Qi , Wang Herui , Jiang Dongxian , Xu Chen , Cui Jing , Zhang Qi , Wang Haixing , Huang Jie , Su Jieakesu , Wu Gen Sheng , Zhuang Zhengping , Hou Yingyong
Published: September 2021

Paclitaxel-based chemotherapy is a treatment option for advanced esophageal squamous cell carcinoma (ESCC). However, the development of chemoresistance leads to treatment failure, and the underlying mechanism remains elusive. We investigated the mechanisms of nanoparticle albumin-bound paclitaxel (nab-PTX) resistance by establishing three nab-PTX resistant ESCC cell lines. Proteomics analysis revealed higher oxidative phosphorylation (OXPHOS) in resistant cell line DR150 than in its parental cell line KYSE150, which is likely caused by stabilized anti-apoptotic protein MCL1. Additionally, we discovered the elevated activity of protein phosphatase 2A (PP2A), the phosphatase that dephosphorylates and stabilizes MCL1, in nab-PTX resistant cell lines. Pharmacological inhibition of PP2A with small molecule compound LB-100 decreased MCL1 protein level, caused more apoptosis in nab-PTX resistant ESCC cell lines than in the parental cells in vitro, and significantly inhibited the tumor growth of nab-PTX resistant xenografts in vivo. Moreover, LB-100 pretreatment partially restored nab-PTX sensitivity in the resistant cell lines and synergistically inhibited the tumor growth of nab-PTX resistant xenografts with nab-PTX. In summary, our study identifies a novel mechanism whereby elevated PP2A activity stabilizes MCL1 protein, increases OXPHOS, and confers nab-PTX resistance, suggesting that targeting PP2A is a potential strategy for reversing nab-PTX resistance in patients with advanced ESCC.
A Study into the γ-Al2O3 Binder Influence on Nano-H-ZSM-5 via Scaled-Up Laboratory Methanol-to-Hydrocarbon Reaction
Authors: Liu Bonan , Zhu Xiaochun , Zhao Jun , Wang Duanda , Ma Wangjing
Published: September 2021

Development of a laboratory selected zeolite into an industrial zeolite-based catalyst faces many challenges due to the scaling-up of reaction which requires many upgrades of the as-prepared catalyst such as an enhanced physical strength. To meet this requirement zeolite powders are normally mixed with various binders and then shaped into bulky bodies. Despite the fact there are a lot of reports on the positive features brought by the shaping treatment, there is still a great need to further explore the zeolite properties after the binder introduction. In this case, a lot of studies have been continuously conducted, however, many results were limited due to the usage of much smaller laboratory samples rather than a real factory plant, and more importantly, the maximal/minimal proportion of zeolites in the shaped catalyst. In this research, our shaped catalysts are based on nano-H-ZSM-5 zeolites and alumina (γ–Al2O3) binder while keeping the zeolite content to a maximum. H-ZSM-5 samples and Al-H-ZSM-5 samples are compared in the designed methanol-to-hydrocarbons reaction. With a reduced weight-hourly-space-velocity (WHSV = 1.5 h−1) and a higher reaction pressure (6 bar) favorable for aromatization, together with the tailored instruments for catalyst volume scale-up (20 g samples are tested each time), our tests focus on the early period catalytic performance (during the first 5 h). Unlike a normal laboratory test, the results from the scaled-up experiments provide important guidance for a potential industrial application. The role of the γ–Al2O3 introduced, not only as binder, but also performing as co-catalyst, on tailoring the early time product distribution, and the corresponding coke deposition is systematically investigated and discussed in details. Notably, the Si/Al ratio of H-ZSM-5 still has a decisive influence on the reaction performance of the Al-H-ZSM-5 samples.
Lipid and Fatty Acids Accumulation Features of Entomoneis cf. paludosa during Exponential and Stationary Growth Phases in Laboratory Culture
Authors: Bedoshvili Yekaterina , Podunay Yulia , Nikonova Alyona , Marchenkov Artyom , Bairamova Elvira , Davidovich Nikolai , Likhoshway Yelena
Published: September 2021

Diatoms are capable of accumulating substantial amounts of triacylglycerides in their cells, which differ in the composition of fatty acids depending on the conditions of cultivation, making them attractive subjects in biotechnology. In the present study, we characterized the structural features of lipid bodies in the diatom Entomoneis cf. paludosa (W. Smith) Reimer strain 8.0727-B and revealed the peculiarities of fatty acid composition in cultures during the stationary and exponential growth phases. Laser scanning confocal microscopy revealed an increased number of lipid bodies in the cytoplasm during the stationary phase of culture growth. Electron microscopy of ultrathin sections showed that an extreme increase in the number and size of plastoglobules in the cells occurs in the stationary phase of culture growth. The gas chromatography with mass spectrometric detection method revealed differences in the fatty acid composition depending on the growth phase. The studied strain can be recommended as a source of hexadecanoic and octadecanoic fatty acids from the culture during the stationary growth phase, as well as eicosapentaenoic fatty acid from the culture during the exponential growth phase.
Corporate Social Responsibility and Financial Performance among Energy Sector Companies
Authors: Kludacz-Alessandri Magdalena , Cygańska Małgorzata
Published: September 2021

Corporate social responsibility (CSR) is one of the main drivers of corporate reputation. Many studies show that CSR can positively affect financial performance (FP) and vice versa. However, the relationship between FP and CSR depends on the type of industry in which the company operates, and there is little research regarding the energy sector in this area. The basis of empirical research in this study is slack resource theory which argues that financial performance is the cause of corporate social performance. This paper aims to analyze if financial performance affects corporate social responsibility adoption in energy sector companies. In order to achieve this goal, the study specifically examines the relationship between selected financial performance indicators and CSR adoption. Analyzing an international sample of 219 companies from thirty-two countries for 2020, we observed the statistically significant relations between financial performance and the implementing of the CSR strategy of the energy industry companies. The Return on Assets measure (ROA) and the Earnings Before Interest and Taxes measure (EBIT) were significantly higher among companies implementing the CSR strategy. The Enterprise Value to earnings before interest, taxes, depreciation, and amortization ratio (EV EBITDA) was lower among companies that adopted CSR. We did not confirm that the Return on Equity measure (ROE), Beta coefficient, and EBITDA per Share correlated with CSR adoption. Our research had implications for firms’ investment policies in social initiatives and highlighted the relation between the financial performance and CSR initiatives of the energy sector companies.
Proposal, Robustness Analysis and Equivalent Implementation of Optimization Method for Row-by-Row Fin Distribution in Multi-Row Frosting Evaporator
Authors: Sun Yu , Zhao Rijing , Wu Siyuan , Huang Dong
Published: September 2021

The evaporator in a frost-free refrigerator typically has more tube rows, but frost deposition reduces along the airflow direction. Correspondingly, the evaporator fin distribution is thinner in the upstream rows but denser downstream, and a good match between frost and fin distribution is achieved to recover evaporator capacity loss. However, quantitative design principles of non-uniform fin distribution are lacking. A quasi-static frosting evaporator model is established and experimentally verified considering a three-dimensional (3D) evaporator, 1D frost growth and 1D non-uniform fin distribution. An optimization method for row-by-row fin distribution of a multi-row frosting evaporator is proposed based on the air pressure drop’s increase rate. When the increase rate in the air pressure drop of each row is almost equal, the smallest overall evaporator pressure drop is obtained, leading to the highest air flowrate and the greatest evaporator capacity. By applying the method, the air flowrate and the evaporator capacity increase by 5.5% and 4.6%, respectively, compared to the original fin distribution scheme. Moreover, the robustness of the optimization method is validated under wide temperature and humidity operating conditions. An equivalent implementation under an initial no-frost condition is also proposed to facilitate the optimization method without calculating the whole frosting process.
Study on the Motion Characteristics of 10 MW Superconducting Floating Offshore Wind Turbine Considering 2nd Order Wave Effect
Authors: Yu Youngjae , Pham Thanh Dam , Shin Hyunkyoung , Ha Kwangtae
Published: September 2021

Recently, several countries have made commitments to move to a net-zero emission by the year 2050 in a response to climate change. Among various renewable energy systems to realize the target, wind energy system has been gaining much attention as a favorable alternative source to fossil fuel energy. In particular, many floating offshore wind turbines (FOWT) are expected to be installed because of vast installation resources without water depth limit conditions, stable and strong wind resources, relatively low constraints on noise emission, and space restriction compared to onshore wind turbines. In this study, a 10 MW superconducting floating offshore wind turbine was modeled with a 1/90 scale ratio and was experimentally tested at the Ocean Engineering Widetank of the University of Ulsan. The model calibration of the scaled model was performed with free decay test and showed a good correlation with simulation results calculated from FAST V8 of NREL. The motion characteristics of the 10 MW superconducting FOWT semi-submersible type platform was investigated under regular waves and irregular waves through the comparison of model test data and simulation results. The study on the motion characteristics of the model showed that the simulation considering the 2nd order wave effects to hydrodynamic forces and moments provided better accuracy close to the model test data.
Suicide Related Phenotypes in a Bipolar Sample: Genetic Underpinnings
Authors: Lybech Line K. M. , Calabró Marco , Briuglia Silvana , Drago Antonio , Crisafulli Concetta
Published: September 2021

Suicide in Bipolar Disorder (BD) is a relevant clinical concern. Genetics may shape the individual risk for suicide behavior in BD, together with known clinical factors. The lack of consistent replication in BD may be associated with its multigenetic component. In the present contribution we analyzed a sample of BD individuals (from STEP-BD database) to identify the genetic variants potentially associated with three different suicide-related phenotypes: (1) a feeling that the life was not worth living; (2) fantasies about committing a violent suicide; (3) previous attempted suicide. The sample under analysis included 1115 BD individuals. None of the SNPs reached genome-wide significance. However, a trend of association was evidenced for rs2767403, an intron variant of AOPEP gene, in association with phenotype #1 (p = 5.977 × 10−6). The molecular pathway analysis showed a significant enrichment in all the investigated phenotypes on pathways related to post synaptic signaling, neurotransmission and neurodevelopment. Further, NOTCH signaling or the γ-aminobutyric acid (GABA)-ergic signaling were found to be associated with specific suicide-related phenotypes. The present investigation contributes to the hypothesis that the genetic architecture of suicide behaviors in BD is related to alteration of entire pathways rather than single genes. In particular, our molecular pathway analysis points on some specific molecular events that could be the focus of further research in this field.
Development and Validation of a Brief Version of the Research Engagement Survey Tool
Authors: Goodman Melody S. , Ackermann Nicole , Pierce Kristyn A. , Bowen Deborah J. , Thompson Vetta Sanders
Published: September 2021

The Research Engagement Survey Tool (REST) examines the level of partner engagement in research studies. This study used mixed methods, including web-based surveys (N = 336), a modified Delphi process (N = 18), and cognitive response interviews (N = 16), with convenience sampling to develop and validate a short version of the REST. We conducted factor analysis and calculated internal consistency for the condensed REST. We validated the condensed REST against the comprehensive REST. All analyses were carried out on two scales (quality and quantity) based on Likert-type response options. We examined convergent validity with other measures theoretically associated with the REST (e.g., the Community Engagement Research Index and the Partnership Self-Assessment Tool). This study produced a 9-item condensed version of the REST. The condensed REST loads on 1 factor, has high internal consistency (Cronbach’s alpha = 0.92 for the quantity scale; 0.94 for the quality scale), is significantly correlated (ρ = 0.97; p < 0.001 for both scales) with the comprehensive (32-item) REST, and has negligible, low, and moderate correlation with other measures (e.g., the Partnership Assessment In community-based Research, trust in medical researchers, and the Coalition Self-Assessment Survey). Use of the condensed REST will reduce participant burden and time to complete. This standardized and validated quantitative measure is useful to compare engagement across projects or within a project over time.
Pyrimidine Biosynthetic Enzyme CAD: Its Function, Regulation, and Diagnostic Potential
Authors: Li Guanya , Li Dunhui , Wang Tao , He Shanping
Published: September 2021

CAD (Carbamoyl-phosphate synthetase 2, Aspartate transcarbamoylase, and Dihydroorotase) is a multifunctional protein that participates in the initial three speed-limiting steps of pyrimidine nucleotide synthesis. Over the past two decades, extensive investigations have been conducted to unmask CAD as a central player for the synthesis of nucleic acids, active intermediates, and cell membranes. Meanwhile, the important role of CAD in various physiopathological processes has also been emphasized. Deregulation of CAD-related pathways or CAD mutations cause cancer, neurological disorders, and inherited metabolic diseases. Here, we review the structure, function, and regulation of CAD in mammalian physiology as well as human diseases, and provide insights into the potential to target CAD in future clinical applications.
Human iPSC-Derived Glia as a Tool for Neuropsychiatric Research and Drug Development
Authors: Heider Johanna , Vogel Sabrina , Volkmer Hansjürgen , Breitmeyer Ricarda
Published: September 2021

Neuropsychiatric disorders such as schizophrenia or autism spectrum disorder represent a leading and growing burden on worldwide mental health. Fundamental lack in understanding the underlying pathobiology compromises efficient drug development despite the immense medical need. So far, antipsychotic drugs reduce symptom severity and enhance quality of life, but there is no cure available. On the molecular level, schizophrenia and autism spectrum disorders correlate with compromised neuronal phenotypes. There is increasing evidence that aberrant neuroinflammatory responses of glial cells account for synaptic pathologies through deregulated communication and reciprocal modulation. Consequently, microglia and astrocytes emerge as central targets for anti-inflammatory treatment to preserve organization and homeostasis of the central nervous system. Studying the impact of neuroinflammation in the context of neuropsychiatric disorders is, however, limited by the lack of relevant human cellular test systems that are able to represent the dynamic cellular processes and molecular changes observed in human tissue. Today, patient-derived induced pluripotent stem cells offer the opportunity to study neuroinflammatory mechanisms in vitro that comprise the genetic background of affected patients. In this review, we summarize the major findings of iPSC-based microglia and astrocyte research in the context of neuropsychiatric diseases and highlight the benefit of 2D and 3D co-culture models for the generation of efficient in vitro models for target screening and drug development.
Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?
Authors: Stefani Constantin , Miricescu Daniela , Stanescu-Spinu Iulia-Ioana , Nica Remus Iulian , Greabu Maria , Totan Alexandra Ripszky , Jinga Mariana
Published: September 2021

Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC.
MicroRNA-126b-5p Exacerbates Development of Adipose Tissue and Diet-Induced Obesity
Authors: Shen Linyuan , He Jin , Zhao Ye , Niu Lili , Chen Lei , Tang Guoqing , Jiang Yanzhi , Hao Xiaoxia , Bai Lin , Li Xuewei , Zhang Shunhua , Zhu Li
Published: September 2021

Obesity has become a worldwide epidemic, caused by many factors such as genetic regulatory elements, unhealthy diet, and lack of exercise. MicroRNAs (miRNAs) are non-coding single-stranded RNA classes, which are about 22 nucleotides in length and highly conserved among species. In the last decade, a series of miRNAs were identified as therapeutic targets for obesity. In the present study, we found that miR-126b-5p was associated with adipogenesis. miR-126b-5p overexpression promoted the proliferation of 3T3-L1 preadipocytes by upregulating the expression of proliferation-related genes and downregulating the expression of apoptosis-related genes; the inhibition of miR-126b-5p gave rise to opposite results. Similarly, miR-126b-5p overexpression could promote the differentiation of 3T3-L1 preadipocytes by increasing the expression of lipid deposition genes and triglyceride (TG) and total cholesterol (TC) levels. Moreover, luciferase reporter assay demonstrated that adiponectin receptor 2 (Adipor2) and acyl-CoA dehydrogenase, long chain (ACADL) were the direct target genes of miR-126b-5p. Moreover, overexpression of miR-126b-5p could exacerbate the clinical symptoms of obesity when mice were induced by a high-fat diet, including increased adipose tissue weight, adipocyte volume, and insulin resistance. Interestingly, overexpression of miR-126b-5p in preadipocytes and mice could significantly increase total fatty acid content and change the fatty acid composition of adipose tissue. Taken together, the present study showed that miR-126b-5p promotes lipid deposition in vivo and in vitro, indicating that miR-126b-5p is a potential target for treating obesity.
Tagging and Capturing of Lentiviral Vectors Using Short RNAs
Authors: Panigaj Martin , Marino Michael P. , Reiser Jakob
Published: September 2021

Lentiviral (LV) vectors have emerged as powerful tools for transgene delivery ex vivo but in vivo gene therapy applications involving LV vectors have faced a number of challenges, including the low efficiency of transgene delivery, a lack of tissue specificity, immunogenicity to both the product encoded by the transgene and the vector, and the inactivation of the vector by the human complement cascade. To mitigate these issues, several engineering approaches, involving the covalent modification of vector particles or the incorporation of specific protein domains into the vector’s envelope, have been tested. Short synthetic oligonucleotides, including aptamers bound to the surface of LV vectors, may provide a novel means with which to retarget LV vectors to specific cells and to shield these vectors from neutralization by sera. The purpose of this study was to develop strategies to tether nucleic acid sequences, including short RNA sequences, to LV vector particles in a specific and tight fashion. To bind short RNA sequences to LV vector particles, a bacteriophage lambda N protein-derived RNA binding domain (λN), fused to the measles virus hemagglutinin protein, was used. The λN protein bound RNA sequences bearing a boxB RNA hairpin. To test this approach, we used an RNA aptamer specific to the human epidermal growth factor receptor (EGFR), which was bound to LV vector particles via an RNA scaffold containing a boxB RNA motif. The results obtained confirmed that the EGFR-specific RNA aptamer bound to cells expressing EGFR and that the boxB containing the RNA scaffold was bound specifically to the λN RNA binding domain attached to the vector. These results show that LV vectors can be equipped with nucleic acid sequences to develop improved LV vectors for in vivo applications.
Meteorin-Like Protein (Metrnl) in Obesity, during Weight Loss and in Adipocyte Differentiation
Authors: Schmid Andreas , Karrasch Thomas , Schäffler Andreas
Published: September 2021

Meteorin-like protein (Metrnl) is an adipo-myokine with pleiotropic effects in adipose tissue (AT). Its systemic regulation in obesity and under weight loss is unclear. Circulating Metrnl concentrations were analyzed by ELISA in severely obese patients undergoing bariatric surgery (BS) or low calorie diet (LCD). Metrnl mRNA expression was analyzed in human and murine tissues and cell lines by quantitative real-time PCR. About 312 morbidly obese individuals underwent BS (n = 181; BMI 53.4 + 6.8 kg/m2) or LCD (n = 131; BMI 43.5 + 6.7 kg/m2). Serum samples were obtained at baseline and 3, 6, and 12 months after intervention. AT specimen from subcutaneous and visceral adipose tissue were resected during BS. Serum Metrnl levels were lower in type 2 diabetic patients and negatively correlated with HbA1c. In BS and LCD patients, Metrnl concentrations significantly increased after 3 months and returned to baseline levels after 12 months. There was no gender-specific effect. Metrnl mRNA expression did not differ between visceral and subcutaneous AT in n = 130 patients. In contrast, Metrnl gene expression in mice was highest in intra-abdominal AT followed by subcutaneous, peri-renal, and brown AT. In the murine 3T3-L1 cell line, Metrnl expression was high in pre-adipocytes and mature adipocytes with a transient downregulation during adipocyte differentiation. Metrnl expression remained unaffected upon treatment with glucose, insulin, fatty acids, bile acids, and incretins. Polyunsaturated omega-3 and omega-6 fatty acids downregulated Metrnl expression. Systemic Metrnl is transiently upregulated during massive weight loss and gene expression in adipocytes is differentially regulated.
Biodistribution of Quantum Dots-Labelled Halloysite Nanotubes: A Caenorhabditis elegans In Vivo Study
Authors: Stavitskaya Anna , Fakhrullina Gölnur , Nigamatzyanova Läysän , Sitmukhanova Eliza , Khusnetdenova Elnara , Fakhrullin Rawil , Vinokurov Vladimir
Published: September 2021

Halloysite is a promising building block in nanoarchitectonics of functional materials, especially in the development of novel biomaterials and smart coatings. Understanding the behavior of materials produced using halloysite nanotubes within living organisms is essential for their safe applications. In this study, quantum dots of different compositions were synthesized on the surface of modified clay nanotubes, and the biodistribution of this hybrid material was monitored within Caenorhabditis elegans nematodes. The influence of the modification agent as well as the particles’ composition on physicochemical properties of hybrid nanomaterials was investigated. Several microscopy techniques, such as fluorescence and dark-field microscopy, were compared in monitoring the distribution of nanomaterials in nematodes’ organisms. The effects of QDs-halloysite composites on the nematodes’ life cycle were investigated in vivo. Our fluorescent hybrid probes induced no acute toxic effects in model organisms. The stable fluorescence and low toxicity towards the organisms suggest that the proposed synthesis procedure yields safe nanoarchitectonic materials that will be helpful in monitoring the behavior of nanomaterials inside living cells and organisms.
Impact of Zinc Oxide Nanoparticles on the Composition of Gut Microbiota in Healthy and Autism Spectrum Disorder Children
Authors: Yu Rongrong , Ahmed Temoor , Jiang Hubiao , Zhou Guoling , Zhang Muchen , Lv Luqiong , Li Bin
Published: September 2021

Autism spectrum disorder (ASD) seriously affects children’s health, while the gut microbiome has been widely hypothesized to be involved in the regulation of ASD behavior. This study investigated and compared the number, diversity, and population structure of gut microbiota between healthy and ASD children and their susceptibility to zinc oxide nanoparticles (ZnONPs) based on the measurement of live cell number, living/dead bacterial staining test, flow cytometry observation and bacterial community analysis using 16S rRNA gene amplicon sequencing. The result of this present study revealed that ASD children not only significantly reduced the live cell number and the community diversity of gut bacteria, but also changed the gut bacterial community composition compared to the healthy children. In addition, this result revealed that ZnONPs significantly reduced the number of live bacterial cells in the gut of healthy children, but not in that of ASD children. In contrast, ZnONPs generally increased the gut bacterial community diversity in both ASD and healthy children, while a greater increase was found in ASD children than that of healthy children. Furthermore, this study successfully isolated and identified some representative nanoparticle-resistant bacteria based on the color, shape, and edge of colony as well as the 16S rDNA sequence analysis. The community of nanoparticle-resistant bacteria differed in between healthy and ASD children. Indeed, the representative strains 6-1, 6-2, 6-3 and 6-4 from healthy children were identified as Bacillus anthracis, Escherichia coli, Bacillus cereus and Escherichia coli with sequence similarity of 97.86%, 99.86%, 99.03% and 99.65%, respectively, while the representative strains 8-1, 8-2 and 8-3 from ASD children were identified as Bacillus cereus, with sequence similarities of 99.58%, 99.72% and 99.72%, respectively. Overall, this study demonstrated that ZnONPs caused a change in number, diversity, and species composition of gut bacteria, but differed in healthy and ASD children.
Borocarbonitride Layers on Titanium Dioxide Nanoribbons for Efficient Photoelectrocatalytic Water Splitting
Authors: Jiménez-Arévalo Nuria , Flores Eduardo , Giampietri Alessio , Sbroscia Marco , Betti Maria Grazia , Mariani Carlo , Ares José R. , J. Ferrer Isabel , Leardini Fabrice
Published: September 2021

Heterostructures formed by ultrathin borocarbonitride (BCN) layers grown on TiO2 nanoribbons were investigated as photoanodes for photoelectrochemical water splitting. TiO2 nanoribbons were obtained by thermal oxidation of TiS3 samples. Then, BCN layers were successfully grown by plasma enhanced chemical vapour deposition. The structure and the chemical composition of the starting TiS3, the TiO2 nanoribbons and the TiO2-BCN heterostructures were investigated by Raman spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Diffuse reflectance measurements showed a change in the gap from 0.94 eV (TiS3) to 3.3 eV (TiO2) after the thermal annealing of the starting material. Morphological characterizations, such as scanning electron microscopy and optical microscopy, show that the morphology of the samples was not affected by the change in the structure and composition. The obtained TiO2-BCN heterostructures were measured in a photoelectrochemical cell, showing an enhanced density of current under dark conditions and higher photocurrents when compared with TiO2. Finally, using electrochemical impedance spectroscopy, the flat band potential was determined to be equal in both TiO2 and TiO2-BCN samples, whereas the product of the dielectric constant and the density of donors was higher for TiO2-BCN.
Hollow Channel Formation inside Sodium Aluminoborate Glass by Femtosecond Laser Writing and Distilled Water Etching
Authors: Fedotov Sergey , Lipatiev Alexey , Lipateva Tatiana , Lotarev Sergey , Sigaev Vladimir
Published: September 2021

Recently, the effect of nanograting formation was demonstrated for binary sodium borate glass with the possibility of data storage with an enhanced level of security. The obvious disadvantage of such glass is poor chemical stability, which limits real applications. In this paper, we show that the introduction of Al2O3 allows preserving the possibility of nanograting formation with a significant increase of chemical resistance and thus to preserve optical memory applications. On the other hand, the possibility of selective etching of laser-written tracks by means of distilled water is revealed, which was not demonstrated for other types of glasses. The dependence of retardance of nanogratings form birefringence on laser writing parameters is established and discussed. Structural features of laser-modified microdomains are studied via Raman spectroscopy which revealed an increase of three-coordinated boron content. A possible mechanism of selective etching is discussed.
Recovery of Uranium by Se-Derivatives of Amidoximes and Composites Based on Them
Authors: Tokar Eduard , Maslov Konstantin , Tananaev Ivan , Egorin Andrei
Published: September 2021

An Se-derivative of amidoxime was synthesized for the first time as a result of the reaction of oxidative polycondensation of N’-hydroxy-1,2,5-oxadiazole-3-carboximidamide with SeO2: its elementary units are linked to each other due to the formation of strong diselenide bridges. The element composition of the material was established, and the structure of the elementary unit was suggested. The sorption-selective properties were evaluated, and it was found that the adsorbent can be used for the selective recovery of U (VI) from liquid media with a pH of 6–9. The effect of some anions and cations on the efficiency of recovery of U (VI) was estimated. Composite materials were fabricated, in which silica gel with a content of 35, 50, and 65 wt.% was used as a matrix to be applied in sorption columns. The maximum values of adsorption of U (VI) calculated using the Langmuir equation were 620–760 mg g−1 and 370 mg g−1 for the composite and non-composite adsorbents, respectively. The increase in the kinetic parameters of adsorption in comparison with those of the non-porous material was revealed, along with the increase in the specific surface area of the composite adsorbents. In particular, the maximum sorption capacity and the rate of absorption of uranium from the solution increased two-fold.
Design and Experimental Investigations of Shape and Attitude Carding System for the Wires of Micro Coreless Motor Winding
Authors: Wang Yuezong , Wang Liuqian , Chen Jiqiang
Published: September 2021

The shape and attitude (S&A) of the electrode wire are important characteristics of micro coreless motor winding. The purpose of this paper is to present the design of a robotic micro-manipulation system for micro wire carding with arbitrary S&A, which can be used as the pretreatment system for wire micro-gripper systems. The system is based on the principle of flexible carding, and uses nylon, bristle, nanometer-silk and wool as materials for the brushing micro-manipulator. The trajectory of the brushing micro-manipulator is designed, and the S&A of the electrode wires are straightened through the combined motion mode of horizontal and vertical brushing micro-manipulators. The experimental results show that the material of the brushing micro-manipulator has a great impact on the carding quality. Nanometer-silk material is more suitable for horizontal brushing micro-manipulators, and wool material is more suitable for vertical brushing micro-manipulators. The geometric dimension of the brushing micro-manipulator also affects the carding quality. When the diameter is in the range of 1 mm, the carding effect of the horizontal brushing micro-manipulator with a length of 4.9–8 mm is better. The system can realize the automatic carding of flexible electrode wires with arbitrary S&A, and it will not damage the structure of wires in the process.
Modeling of Statistical Variation Effects on DRAM Sense Amplifier Offset Voltage
Authors: Koo Kyung Min , Chung Woo Young , Lee Sang Yi , Yoon Gyu Han , Choi Woo Young
Published: September 2021

With the downscaling in device sizes, process-induced parameter variation has emerged as one of the most serious problems. In particular, the parameter fluctuation of the dynamic random access memory (DRAM) sense amplifiers causes an offset voltage, leading to sensing failure. Previous studies indicate that the threshold voltage mismatch between the paired transistors of a sense amplifier is the most critical factor. In this study, virtual wafers were generated, including statistical VT variation. Then, we numerically investigate the prediction accuracy and reliability of the offset voltage of DRAM wafers using test point measurement for the first time. We expect that this study will be helpful in strengthening the in-line controllability of wafers to secure the DRAM sensing margin.
Simulation of Onset of the Capillary Surface Wave in the Ultrasonic Atomizer
Authors: Song Yu-Lin , Cheng Chih-Hsiao , Reddy Manoj Kumar , Islam Md Saikhul
Published: September 2021

The novel drug delivery system refers to the formulations and technologies for transporting a pharmaceutical compound in the body as it is needed to safely achieve its desired therapeutic effects. In this study, the onset vibrational amplitude of capillary surface waves for ultrasonic atomization spray is explained based on Faraday instability. Using ultrasonic frequency, the vibrational amplitude approached a critical point, and the liquid surface broke up into tiny drops. The micro-droplets were are steadily and continuously formed after the liquid feeding rate was optimized. The simulation study reported a minimum vibrational amplitude or onset value of 0.38 μm at 500 kHz frequency. The required minimum energy to atomize the drops was simulated by COMSOL Multiphysics simulation software. The simulation result agreed well with the numerical results of a subharmonic vibrational model that ocurred at 250 kHz frequency on the liquid surface. This newly designed single frequency ultrasonic atomizer showed its true physical characteristic of resonance on the fluid surface plane. Hence, this research will contribute to the future development of a single-frequency ultrasonic nebulizer and mechatronics for the generation of uniform atomized droplets.
Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders
Authors: Arrhenius Bianca , Upadhyaya Subina , Hinkka-Yli-Salomäki Susanna , Brown Alan S. , Cheslack-Postava Keely , Öhman Hanna , Sourander Andre
Published: September 2021

Recent evidence has suggested potential harmful effects of vitamin D deficiency during pregnancy on offspring brain development, for example, elevated risks for neuropsychiatric disorders. Findings on general cognition and academic achievement are mixed, and no studies have examined the effect of prenatal 25-hydroxyvitamin D (25(OH)D) levels on diagnosed specific learning disorders, which was the aim of this study. We examined a nested case–control sample from the source cohort of all singleton-born children in Finland between 1996 and 1997 (n = 115,730). A total of 1607 cases with specific learning disorders (mean age at diagnosis: 9.9 years) and 1607 matched controls were identified from Finnish nationwide registers. Maternal 25(OH)D levels were analyzed from serum samples collected during the first trimester of pregnancy and stored in a national biobank. Conditional logistic regression was used to test the association between maternal 25(OH)D and offspring specific learning disorders. There were no significant associations between maternal 25(OH)D levels and specific learning disorders when vitamin D was examined as a log-transformed continuous variable (adjusted OR 0.98, 95% CI 0.82–1.18, p = 0.84) or as a categorical variable (25(OH)D < 30 nmol/L: adjusted OR 1.03, 95% CI 0.83–1.28, p = 0.77 compared to levels of >50 nmol/L), nor when it was divided into quintiles (adjusted OR for the lowest quintile 1.00, 95% CI 0.78–1.28, p = 0.99 compared to the highest quintile). This study found no association between low maternal 25(OH)D in early pregnancy and offspring specific learning disorders.