bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of Oocyte Maturation and Related Epigenetic Regulation
Authors: He Meina , Zhang Tuo , Yang Yi , Wang Chao
Published: March 2021

Meiosis is the basis of sexual reproduction. In female mammals, meiosis of oocytes starts before birth and sustains at the dictyate stage of meiotic prophase I before gonadotropins-induced ovulation happens. Once meiosis gets started, the oocytes undergo the leptotene, zygotene, and pachytene stages, and then arrest at the dictyate stage. During each estrus cycle in mammals, or menstrual cycle in humans, a small portion of oocytes within preovulatory follicles may resume meiosis. It is crucial for females to supply high quality mature oocytes for sustaining fertility, which is generally achieved by fine-tuning oocyte meiotic arrest and resumption progression. Anything that disturbs the process may result in failure of oogenesis and seriously affect both the fertility and the health of females. Therefore, uncovering the regulatory network of oocyte meiosis progression illuminates not only how the foundations of mammalian reproduction are laid, but how mis-regulation of these steps result in infertility. In order to provide an overview of the recently uncovered cellular and molecular mechanism during oocyte maturation, especially epigenetic modification, the progress of the regulatory network of oocyte meiosis progression including meiosis arrest and meiosis resumption induced by gonadotropins is summarized. Then, advances in the epigenetic aspects, such as histone acetylation, phosphorylation, methylation, glycosylation, ubiquitination, and SUMOylation related to the quality of oocyte maturation are reviewed.
Comparative Study on Electrochemical Treatment of Cyanide Wastewater
Authors: Lei Siming , Song Yonghui
Published: March 2021

The electrochemical treatment of wastewater is widely used for cleaning due to its efficiency. In this paper, two-dimensional (2D) and three-dimensional (3D) electrochemical systems were used to treat cyanide wastewater. The effect of the applied voltage and the material of the main electrode on the removal of various ions and the characteristics of chemical reactions were mainly studied. The results show that the applied voltage was the key effect of the electrochemical treatment process. The removal of ions from the wastewater at 2 V is mainly due to the effect of electro adsorption and enrichment precipitation, while at 4 V, it is mainly due to anodization and cathodic deposition. The treatment effect of the 3D electrode system was significantly better than the 2D system. The 3D electrode system by used granular activated carbon as the particle electrode, with the carbon filled stainless mesh (CM) and coal based electrode (CB) as the main electrode, the treatment effect were better than main electrode of stainless steel mesh (M). The 3D system with CB as the main electrode had an applied voltage of 4 V, a treatment time of 5 h, plate spacing of 10 mm, and the dosage of activated carbon particles was 2 g. The removal rates of CNT, Cu, Zn, CN−, and SCN− were 94.14, 94.53, 98.14, 98.55, and 93.13%, respectively. The main reaction in anode was the electroly oxidation of CN− and SCN−, while the electrolytic deposition of Cu, Zn, and other metal ions in the cathode surface. There were not only adsorption and electric adsorption of various ions, but also an electrolytic deposition reaction of Cu, Zn, and other metal ions on the surface of the activated carbon particle electrode. During the electrochemical reaction, the concentration of hydrogen ions near the anode increases locally, which produces the precipitation of CuSCN, Cu2Fe(CN)6, and Zn2Fe(CN)6, etc. in the solution, which are helpful for the removal of cyanide and heavy metal ions in cyanide wastewater.
Dysbiosis of the Human Oral Microbiome During the Menstrual Cycle and Vulnerability to the External Exposures of Smoking and Dietary Sugar
Authors: Bostanci Nagihan , Krog Maria Christine , Hugerth Luisa W. , Bashir Zahra , Fransson Emma , Boulund Fredrik , Belibasakis Georgios N. , Wannerberger Kristin , Engstrand Lars , Nielsen Henriette Svarre , Schuppe-Koistinen Ina
Published: March 2021

Physiological hormonal fluctuations exert endogenous pressures on the structure and function of the human microbiome. As such, the menstrual cycle may selectively disrupt the homeostasis of the resident oral microbiome, thus compromising oral health. Hence, the aim of the present study was to structurally and functionally profile the salivary microbiome of 103 women in reproductive age with regular menstrual cycle, while evaluating the modifying influences of hormonal contraceptives, sex hormones, diet, and smoking. Whole saliva was sampled during the menstrual, follicular, and luteal phases (n = 309) of the cycle, and the participants reported questionnaire-based data concerning their life habits and oral or systemic health. No significant differences in alpha-diversity or phase-specific clustering of the overall microbiome were observed. Nevertheless, the salivary abundances of genera Campylobacter, Haemophilus, Prevotella, and Oribacterium varied throughout the cycle, and a higher species-richness was observed during the luteal phase. While the overall community structure maintained relatively intact, its functional properties were drastically affected. In particular, 11 functional modules were differentially abundant throughout the menstrual cycle, including pentose phosphate metabolism, and biosynthesis of cobalamin and neurotransmitter gamma-aminobutyric acid. The menstrual cycle phase, but not oral contraceptive usage, was accountable for greater variations in the metabolic pathways of the salivary microbiome. Further co-risk factor analysis demonstrated that Prevotella and Veillonella were increased in current smokers, whereas high dietary sugar consumption modified the richness and diversity of the microbiome during the cycle. This is the first large study to systematically address dysbiotic variations of the oral microbiome during the course of menstrual cycle, and document the additive effect of smoking and sugar consumption as environmental risk factors. It reveals the structural resilience and functional adaptability of the oral microbiome to the endogenous hormonal pressures of the menstrual cycle, while revealing its vulnerability to the exogenous exposures of diet and smoking.
Simulated Pediatric Blood Cultures to Assess the Inactivation of Clinically Relevant Antimicrobial Drug Concentrations in Resin-Containing Bottles
Authors: Giordano Liliana , Liotti Flora Marzia , Menchinelli Giulia , De Angelis Giulia , D’Inzeo Tiziana , Morandotti Grazia Angela , Sanguinetti Maurizio , Spanu Teresa , Posteraro Brunella
Published: March 2021

The bacteremia level as well as the administration of antibiotics before blood collection may significantly affect the recovery of bacterial pathogens from pediatric blood cultures in BacT/Alert Virtuo or Bactec FX BC systems, which remain the common techniques to diagnose bacteremia in pediatric patients. We simulated pediatric blood cultures with low or intermediate bacteremia level to evaluate BacT/Alert PF Plus and Bactec Peds Plus blood culture bottles for resin-based inactivation of 16 antibiotic–bacterium combinations. Overall, 105/192 (54.7%) of BacT/Alert PF Plus bottles and 69/192 (36.0%) of Bactec Peds Plus bottles allowed organisms to grow when exposed to antibiotics. In particular, both BacT/Alert PF Plus and Bactec Peds Plus bottles proved to be effective with piperacillin/tazobactam and Pseudomonas aeruginosa or with oxacillin and methicillin-susceptible Staphylococcus aureus (100% growth), whereas no effectiveness was apparent with ceftriaxone and Escherichia coli, Streptococcus agalactiae, or Streptococcus pneumoniae or with cefepime and E. coli (0% growth). In some relevant instances (e.g., with vancomycin and methicillin-resistant S. aureus or Streptococcus pneumoniae), BacT/Alert PF Plus bottles were superior to Bactec Peds Plus bottles. Together, these findings underscore the potentiality of resin-containing bottles to enhance diagnosis of bacteremia in pediatric patients on antimicrobial therapy. This is particularly true with one of the evaluated BC systems and with simulated intermediate bacteremia level only.
What Comprises a Successful Educational Science YouTube Video? A Five-Thousand User Survey on Viewing Behaviors and Self-Perceived Importance of Various Variables Controlled by Content Creators
Authors: Beautemps Jacob , Bresges André
Published: March 2021

Educational videos on digital platforms are an attractive way of learning, especially for the younger generation, as they provide easy, personalizable access to a wide variety of content. Allowing for simplified explanations and visual demonstrations, educational videos are highly suitable for scientific content. With 500 h of video content uploaded per minute, YouTube is the most used user-generated video content platform worldwide. This study provides an initial insight into the elements which influence the perceived quality of educational science videos by viewers, with a special focus on natural science videos. In response to a call for study participants via various German natural science and technology YouTube and Instagram channels, over 5,000 participants between the ages of 9 to 72 (M = 18, SD = 8.78) completed a web questionnaire. The questionnaire focused on the participants’ viewing behaviors and their self-perception of the importance of the content-creator controlled variables.It was found that there are six key elements for a successful educational YouTube video: 1) structure, 2) reliability, 3) quality, 4) community integration, 5) presenter, 6) topic. Based on these elements, a checklist with 17 recommendations for the creation of successful educational videos was developed, serving as a practical guideline for content creators.
miR-132/212 Impairs Cardiomyocytes Contractility in the Failing Heart by Suppressing SERCA2a
Authors: Lei Zhiyong , Wahlquist Christine , el Azzouzi Hamid , Deddens Janine C. , Kuster Diederik , van Mil Alain , Rojas-Munoz Agustin , Huibers Manon M. , Mercola Mark , de Weger Roel , Van der Velden Jolanda , Xiao Junjie , Doevendans Pieter A. , Sluijter Joost P. G.
Published: March 2021

Compromised cardiac function is a hallmark for heart failure, mostly appearing as decreased contractile capacity due to dysregulated calcium handling. Unfortunately, the underlying mechanism causing impaired calcium handling is still not fully understood. Previously the miR-132/212 family was identified as a regulator of cardiac function in the failing mouse heart, and pharmaceutically inhibition of miR-132 is beneficial for heart failure. In this study, we further investigated the molecular mechanisms of miR-132/212 in modulating cardiomyocyte contractility in the context of the pathological progression of heart failure. We found that upregulated miR-132/212 expressions in all examined hypertrophic heart failure mice models. The overexpression of miR-132/212 prolongs calcium decay in isolated neonatal rat cardiomyocytes, whereas cardiomyocytes isolated from miR-132/212 KO mice display enhanced contractility in comparison to wild type controls. In response to chronic pressure-overload, miR-132/212 KO mice exhibited a blunted deterioration of cardiac function. Using a combination of biochemical approaches and in vitro assays, we confirmed that miR-132/212 regulates SERCA2a by targeting the 3′-end untranslated region of SERCA2a. Additionally, we also confirmed PTEN as a direct target of miR-132/212 and potentially participates in the cardiac response to miR132/212. In end-stage heart failure patients, miR-132/212 is upregulated and correlates with reduced SERCA2a expression. The up-regulation of miR-132/212 in heart failure impairs cardiac contractile function by targeting SERCA2a, suggesting that pharmaceutical inhibition of miR-132/212 might be a promising therapeutic approach to promote cardiac function in heart failure patients.
Sweroside Protects Against Myocardial Ischemia–Reperfusion Injury by Inhibiting Oxidative Stress and Pyroptosis Partially via Modulation of the Keap1/Nrf2 Axis
Authors: Li Jun , Zhao Cuiting , Zhu Qing , Wang Yonghuai , Li Guangyuan , Li Xinxin , Li Yuhong , Wu Nan , Ma Chunyan
Published: March 2021

Aims: Sweroside, a secoiridoid glucoside extracted from Swertia pseudochinensis Hara, is reported to possess antioxidant and anti-inflammatory activities. However, whether sweroside has a protective effect on myocardial ischemia–reperfusion (IR) injury is yet to be elucidated. The present study aimed to confirm the cardioprotective effect of sweroside and to identify its underlying mechanism.

Methods and Results: H9c2 cells were pretreated with sweroside and then underwent hypoxia–reoxygenation. Cell Counting Kit-8, creatine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) assays were conducted to detect cell viability and myocardial injury, respectively. The Langendorff method was used to induce myocardial IR injury ex vivo. Triphenyltetrazolium chloride staining was performed to detect myocardial infarct size, while protein expression was analyzed using western blotting. Overall, the results indicated that sweroside pretreatment dose-dependently led to a significant enhancement in cell viability, a decrease in release of CK-MB and LDH, a reduction in infarct size, and an improvement in cardiac function. Additionally, sweroside pretreatment caused a marked suppression of oxidative stress, as evidenced by the fact that sweroside decreased the accumulation of reactive oxygen species and malondialdehyde, while enhancing the activities of superoxide dismutase and glutathione peroxidase. Moreover, sweroside was found to notably repress pyroptosis, as sweroside blocked pore formation in the cell membrane, inhibited caspase-1 and interleukin (IL)-1β activity, and decreased the expression levels of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, cleaved caspase-1, and IL-1β. Mechanistically, it was found that sweroside inhibited Kelch-like ECH-associated protein 1 (Keap1) and induced nuclear factor E2-associated factor 2 (Nrf2) nuclear translocation. Furthermore, the inhibition of oxidative stress and pyroptosis by sweroside could be abrogated via the inhibition of Nrf2 expression, which suggested that the protective effect induced by sweroside was Nrf2-dependent.

Conclusions: The present study demonstrated that sweroside pretreatment could protect against myocardial IR injury by inhibiting of oxidative stress and NLRP3 inflammasome-mediated pyroptosis partially via modulation of the Keap1/Nrf2 axis.
A Multidisciplinary Investigation Into the Eruptive Style, Processes, and Duration of a Cascades Back-Arc Tholeiitic Basalt: A Case Study of the Brushy Butte Flow Field, Northern California, United States
Authors: Downs Drew T. , Champion Duane E. , Clynne Michael A. , Muffler L. J. Patrick
Published: March 2021

The Cascades back-arc in northern California is dominated by monogenetic tholeiitic basalts that erupted throughout the Pleistocene. Elucidating their eruptive history and processes is important for understanding potential future eruptions here. We focus on the well-exposed monogenetic volcano that emplaced the Brushy Butte flow field, which constructed a ∼150 m tall edifice, has flow lobes up to >10 km long, and in total covers ∼150 km2 with an eruptive volume of 3.5 km3. We use a multidisciplinary approach of field mapping, petrography, geochemistry, paleomagnetism, geochronology, and lidar imagery to unravel the eruptive history and processes that emplaced this flow field. Tholeiitic basalts in northern California have diverse surface morphology and vegetation cover but similar petrographic appearances, which makes them hard to distinguish in the field. Geochemistry and paleomagnetism offer an independent means of distinguishing tholeiitic basalts. Brushy Butte flow field lavas are similar in major-oxide and trace-element abundances but differ from adjacent tholeiitic basalts. This is also apparent in remanent magnetic directions. Additionally, paleomagnetism indicates that the flow field was emplaced during a geologically brief time interval (10–20 years), which 36Cl cosmogenic dating puts at 35.7 ± 1.7 ka. Lidar imagery shows that these flows erupted from at least 28 vents encompassing multiple scoria cones, spatter cones, and craters. Flows can be grouped into four pulses using stratigraphic position and volume. Pulse 1 is the most voluminous, comprising eight eruptions and ∼2.3 km3. Each subsequent pulse started rapidly but decayed quickly, and each successive pulse erupted less lava (i.e., 2.3 km3 for pulse 1, 0.6 km3 for pulse 2, 0.3 km3 for pulse 3, and 0.2 km3 for pulse 4). Many of these flows host well-established lava channels and levees (with channel breakouts) that lead to lava fans, with some flows hosting lava ponds. Similar flow features from tholeiitic eruptions elsewhere demonstrate that these morphologies generally occur over weeks, months, or longer (e.g., Puʻu ʻŌʻō eruption at K–llauea, Hawaiʻi). This multidisciplinary study shows the range of eruptive styles and durations of a Cascades back-arc eruption and illustrates how potential future tholeiitic eruptive activity in the western United States might progress.
HMGB1 Mediated Inflammation and Autophagy Contribute to Endometriosis
Authors: Huang Jingying , Chen Xuan , Lv Yuchun
Published: March 2021

Aim

High mobility group box (HMGB)-1 has been implicated in endometriosis due to the important regulatory roles of inflammation in endometriosis. The aim of the present study was to explore the roles of HMGB-1 in endometriosis and to elucidate the underlying mechanism.

Methods

Endometrial specimens were collected from women with endometriosis and healthy volunteers. Immunohistochemistry staining was used to determine the expression patterns and localization of HMGB-1 in the normal, eutopic and ectopic endometrial tissues. Western blotting and qRT-PCR were used to determine the mRNA and protein levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β], autophagy-related markers [beclin-1, autophagy-related (atg)13, microtubule-associated protein light chain (LC)3-I, LC-II and p62] and HMGB-1, respectively. Spearman’s rank correlation analysis was employed to investigate the correlation between HMGB-1 with inflammatory cytokines and beclin-1. Besides, human endometrial stromal cells (HESCs) were isolated from ectopic endometrium and subsequently transfected with shRNA against HMGB-1. After the transfected cells were subjected to hypoxia, ELISA was used to determine the levels of HMGB-1 and inflammatory cytokines in the cell supernatant. Western blotting was used to determine the expression levels of autophagy-related markers in the cells.

Results

Positive correlations were observed between HMGB-1 and the inflammatory cytokines. In addition, a positive correlation was also identified between HMGB-1 and beclin-1 in the ectopic endometrium. Further results demonstrated that autophagy-related markers beclin-1, atg13 and p62 were significantly upregulated in the ectopic endometrium. In addition, HMGB-1 knockdown suppressed the levels of inflammatory cytokines IL-6, TNF-α and IL-1β and autophagy-related markers beclin-1 and atg13, while upregulated p62 in HESCs under hypoxic condition.

Conclusion

Knockdown of HMGB-1 under hypoxic condition regulated inflammatory cytokines and autophagy-related markers. HMGB-1 might contribute to the development of endometriosis in part through regulating inflammatory response and autophagy.
Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism
Authors: Zhang Cao-Xu , Zhang Jun-Xiu , Yang Liu , Zhang Chang-Run , Cheng Feng , Zhang Rui-Jia , Fang Ya , Wang Zheng , Wu Feng-Yao , Li Pei-Zhang , Liang Jun , Li Rui , Song Huai-Dong
Published: March 2021

Background and Objectives

Defects in the human sodium/iodide symporter (SLC5A5) gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC5A5 mutations in Chinese patients with CH and to evaluate the function of the mutation.

Methods

Two hundred and seventy-three patients with primary CH were screened for mutations in SLC5A5 using next-generation sequencing. We investigated the expression and cellular localization of the novel compound heterozygous mutation in SLC5A5. The functional activity of the mutants was further examined in vitro.

Results

In 273 patients with CH, two previously undescribed pathogenic mutations p.Gly51AlafsTer45 (G51fs) and p.Gly421Arg (G421R) in a compound heterozygous state in SLC5A5 were identified in a pediatric patient. G51fs was located in the first intercellular loop connecting transmembrane segment I and II, whereas G421R was in the transmembrane segment (TMS) XI. G51fs and G421R resulted in a truncated NIS and reduced protein expression, respectively. In vitro experiments further showed that the normal function of iodine transport of sodium-iodide symporter (NIS) mutants was markedly impaired.

Conclusion

The undescribed compound heterozygous mutation of SLC5A5 was discovered in a Chinese CH patient. The mutation led to significantly reduced NIS expression and impaired iodide transport function accompanied by the impaired location of the NIS on the plasma membrane. Our study thus provides further insights into the roles of SLC5A5 in CH pathogenesis.
New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect
Authors: Dias James A. , Ulloa-Aguirre Alfredo
Published: March 2021

It is well accepted that pituitary follitropin is secreted into the circulation as a mixture of variants, which differ not in primary structure but rather at the level of glycosylation. These glycosidic forms vary in the number of glycosylation sites filled, complexity of glycosidic chains, and sialylation and sulfation. It is generally agreed that high sialylation, 2,3 sialic acid capping of terminal N-acetyl galactosamine or galactose leads to longer circulating half-life, by blocking binding of asialoglycoprotein receptor (ASGPR) in the liver. In contrast, 2,6 sialic acid found in humans does not prevent recognition of galactose and N-acetyl galactosamine by ASGPR. Few studies on clinical outcomes comparing differences in sialylation of follitropin found in commercially available preparations are available. Thus, there is a clear need for a consortium of open data to address this unmet need. Recently, FSH glycosylation, primarily on the β-subunit, which varies as women age, has emerged as a key modifier of follitropin action, with profound biological effects in vivo in animal models. To date, limited information of recombinant follitropin hormone preparations is available. Thus, most of the studies with FSH that is well characterized biochemically have been done in vitro, with engineered non gonadal host cells bearing recombinant receptors or in animal models. Since limited studies in human granulosa cells are available, a question is whether structural differences in glycosylation in commercially available follitropin affects biological function and clinical effect in humans. The presence of fucose, for example, has not been studied greatly even though, in the case of antibody therapy it has been shown to have a large effect on antibody targeting. This review on glycosidic variability of follitropin from the biochemical/structural point of view reflects on this question and presents an assessment in the context of available published data. If clinical differences are to be expected or not, the readers will have a better understanding of the evidence for and limitations of such expectations.
Identifying the Drivers of Spatial Taxonomic and Functional Beta-Diversity of British Breeding Birds
Authors: Wayman Joseph P. , Sadler Jonathan P. , Pugh Thomas A. M. , Martin Thomas E. , Tobias Joseph A. , Matthews Thomas J.
Published: March 2021

Spatial variation in community composition may be driven by a variety of processes, including environmental filtering and dispersal limitation. While work has been conducted on the relative importance of these processes on various taxa and at varying resolutions, tests using high-resolution empirical data across large spatial extents are sparse. Here, we use a dataset on the presence/absence of breeding bird species collected at the 10 km × 10 km scale across the whole of Britain. Pairwise spatial taxonomic and functional beta diversity, and the constituent components of each (turnover and nestedness/richness loss or gain), were calculated alongside two other measures of functional change (mean nearest taxon distance and mean pairwise distance). Predictor variables included climate and land use measures, as well as a measure of elevation, human influence, and habitat diversity. Generalized dissimilarity modeling was used to analyze the contribution of each predictor variable to variation in the different beta diversity metrics. Overall, we found that there was a moderate and unique proportion of the variance explained by geographical distance per se, which could highlight the role of dispersal limitation in community dissimilarity. Climate, land use, and human influence all also contributed to the observed patterns, but a large proportion of the explained variance in beta diversity was shared between these variables and geographical distance. However, both taxonomic nestedness and functional nestedness were uniquely predicted by a combination of land use, human influence, elevation, and climate variables, indicating a key role for environmental filtering. These findings may have important conservation implications in the face of a warming climate and future land use change.
Exploring Common Therapeutic Targets for Neurodegenerative Disorders Using Transcriptome Study
Authors: Dharshini S. Akila Parvathy , Jemimah Sherlyn , Taguchi Y. H. , Gromiha M. Michael
Published: March 2021

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are well-known neuronal degenerative disorders that share common pathological events. Approved medications alleviate symptoms but do not address the root cause of the disease. Energy dysfunction in the neuronal population leads to various pathological events and ultimately results in neuronal death. Identifying common therapeutic targets for these disorders may help in the drug discovery process. The Brodmann area 9 (BA9) region is affected in both the disease conditions and plays an essential role in cognitive, motor, and memory-related functions. Analyzing transcriptome data of BA9 provides deep insights related to common pathological pathways involved in AD and PD. In this work, we map the preprocessed BA9 fastq files generated by RNA-seq for disease and control samples with reference hg38 genomic assembly and identify common variants and differentially expressed genes (DEG). These variants are predominantly located in the 3′ UTR (non-promoter) region, affecting the conserved transcription factor (TF) binding motifs involved in the methylation and acetylation process. We have constructed BA9-specific functional interaction networks, which show the relationship between TFs and DEGs. Based on expression signature analysis, we propose that MAPK1, VEGFR1/FLT1, and FGFR1 are promising drug targets to restore blood-brain barrier functionality by reducing neuroinflammation and may save neurons.
Advances in the Identification of Circular RNAs and Research Into circRNAs in Human Diseases
Authors: Jiao Shihu , Wu Song , Huang Shan , Liu Mingyang , Gao Bo
Published: March 2021

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a closed-loop structure that are mainly produced by variable processing of precursor mRNAs (pre-mRNAs). They are widely present in all eukaryotes and are very stable. Currently, circRNA studies have become a hotspot in RNA research. It has been reported that circRNAs constitute a significant proportion of transcript expression, and some are significantly more abundantly expressed than other transcripts. CircRNAs have regulatory roles in gene expression and critical biological functions in the development of organisms, such as acting as microRNA sponges or as endogenous RNAs and biomarkers. As such, they may have useful functions in the diagnosis and treatment of diseases. CircRNAs have been found to play an important role in the development of several diseases, including atherosclerosis, neurological disorders, diabetes, and cancer. In this paper, we review the status of circRNA research, describe circRNA-related databases and the identification of circRNAs, discuss the role of circRNAs in human diseases such as colon cancer, atherosclerosis, and gastric cancer, and identify remaining research questions related to circRNAs.
Pharmacological and Genetic Inhibition of PD-1 Demonstrate an Important Role of PD-1 in Ischemia-Induced Skeletal Muscle Inflammation, Oxidative Stress, and Angiogenesis
Authors: Liu Xiaoguang , Weng Xinyu , Xiao Weihua , Xu Xin , Chen Yingjie , Chen Peijie
Published: March 2021

Angiogenesis is an important process under both physiological and pathophysiological conditions. Here we investigated the role and the underlying mechanism of PD-1 in hindlimb ischemia-induced inflammation and angiogenesis in mice. We found that inhibition of PD-1 by genetic PD-1 knockout or pharmacological PD-1 blocking antibodies dramatically attenuated hindlimb blood perfusion, angiogenesis, and exercise capacity in mice after femoral artery ligation. Mechanistically, we found that PD-1 knockout significantly exacerbated ischemia-induced muscle oxidative stress, leukocyte infiltration and IFN-γ production before abnormal angiogenesis in these mice. In addition, we found that the percentages of IFN-γ positive macrophages and CD8 T cells were significantly increased in P-1 knockout mice after hindlimb ischemia. Macrophages were the major leukocyte subset infiltrated in skeletal muscle, which were responsible for the enhanced muscle leukocyte-derived IFN-γ production in PD-1 knockout mice after hindlimb ischemia. Moreover, we demonstrated that IFN-γ significantly attenuated vascular endothelial cell proliferation, tube formation and migration in vitro. IFN-γ also significantly enhanced vascular endothelial cell apoptosis. In addition, the total number of TNF-α positive leukocytes/muscle weight were significantly increased in PD-1-/- mice after hindlimb ischemia. These data indicate that PD-1 exerts an important role in ischemia-induced muscle inflammation and angiogenesis.
Adipocyte Fatty Acid-Binding Protein, Cardiovascular Diseases and Mortality
Authors: Lee Chi-Ho , Lui David T. W. , Lam Karen S. L.
Published: March 2021

It has been increasingly recognized that inflammation plays an important role in the pathogenesis of cardiovascular disease (CVD). In obesity, adipose tissue inflammation, especially in the visceral fat depots, contributes to systemic inflammation and promotes the development of atherosclerosis. Adipocyte fatty acid-binding protein (AFABP), a lipid chaperone abundantly secreted from the adipocytes and macrophages, is one of the key players mediating this adipose-vascular cross-talk, in part via its interaction with c-Jun NH2-terminal kinase (JNK) and activator protein-1 (AP-1) to form a positive feedback loop, and perpetuate inflammatory responses. In mice, selective JNK inactivation in the adipose tissue significantly reduced the expression of AFABP in their adipose tissue, as well as circulating AFABP levels. Importantly, fat transplant experiments showed that adipose-specific JNK inactivation in the visceral fat was sufficient to protect mice with apoE deficiency from atherosclerosis, with the beneficial effects attenuated by the continuous infusion of recombinant AFABP, supporting the role of AFABP as the link between visceral fat inflammation and atherosclerosis. In humans, raised circulating AFABP levels are associated with incident metabolic syndrome, type 2 diabetes and CVD, as well as non-alcoholic steatohepatitis, diabetic nephropathy and adverse renal outcomes, all being conditions closely related to inflammation and enhanced CV mortality. Collectively, these clinical data have provided support to AFABP as an important adipokine linking obesity, inflammation and CVD. This review will discuss recent findings on the role of AFABP in CVD and mortality, the possible underlying mechanisms, and pharmacological inhibition of AFABP as a potential strategy to combat CVD.
Immune Responses Following BCG Immunization of Infants in Uganda and United Kingdom Are Similar for Purified Protein Derivative but Differ for Secretory Proteins of Mycobacterium tuberculosis
Authors: Mawa Patrice A. , Hasso-Agopsowicz Mateusz , Lubyayi Lawrence , Nabakooza Grace , Nakibuule Marjorie , Blitz Rose , Dun Li , Govind Abha , Kaleebu Pontiano , Webb Emily L. , Elliott Alison M. , Dockrell Hazel M. , Cose Stephen , Smith Steven G.
Published: March 2021

Introduction:The immunogenicity of BCG vaccination in infants differs between populations. We hypothesized that prenatal exposure to mycobacterial antigens might explain the differences in immune responses to BCG seen in other studies of infants in Africa and the United Kingdom (UK) and we explored this in birth cohorts in Uganda and the UK.

Materials and Methods:Blood samples were obtained from BCG-immunized infants of mothers with (n= 110) and without (n= 121) latentMycobacterium tuberculosisinfection (LTBI) in Uganda and BCG-immunized infants of mothers without LTBI (n= 25) in the UK at 10 and 52 weeks after birth. Cytokine and chemokine responses to PPD were measured to assess responses to BCG immunization, and to ESAT6/CFP10 to assess exposure to or infection withM. tuberculosisor non-tuberculous mycobacteria (NTM) in 6-day whole blood culture supernatants by a 17-plex Luminex assay. Median responses were compared between Ugandan infants (together, and separated by maternal LTBI status) and UK infants.

Results:The IFN-γ response to BCG vaccination was similar between Ugandan and UK infants at 10 and 52 weeks. At week 52, TNF production was marginally higher in Ugandan infants, but after adjusting for multiple comparisons this difference was not significant. At weeks 10 and 52, stimulation of blood with ESAT6/CFP10 produced significantly higher IFN-γ, TNF, IL-12p40, IL-1α, IL-1β, IL-1Ra, IP-10, MIP-1α, MIP-1β, and GM-CSF in Ugandan compared to UK infants. Stimulation of blood with ESAT6/CFP10 produced significantly higher amounts of IL-8 (p= 0.0001), IL-10 (p= 0.0022), and IL-13 (p= 0.0020) in the UK than in Ugandan infants of mothers without LTBI at week 10, but not at week 52.

Conclusions:Immune responses to mycobacterial antigens following BCG immunization are similar for PPD, but differ for ESAT6/CFP10, between infants in Uganda and the UK. Neither maternal LTBI nor infant exposure to or infection with mycobacteria impacts the response to BCG. The observed global differences in immune response to BCG immunization are likely to be due to other causes.
The Protective Effects of IL-31RA Deficiency During Bleomycin-Induced Pulmonary Fibrosis
Authors: Yombo Dan J. K. , Odayar Varshini , Gupta Nishant , Jegga Anil G. , Madala Satish K.
Published: March 2021

Idiopathic Pulmonary Fibrosis (IPF) is a severe fibrotic lung disease characterized by excessive collagen deposition and progressive decline in lung function. Th2 T cell-derived cytokines including IL-4 and IL-13 have been shown to contribute to inflammation and fibrotic remodeling in multiple tissues. Interleukin-31 (IL-31) is a newly identified cytokine that is predominantly produced by CD4 Th2 T cells, but its signaling receptor IL-31RA is primarily expressed by non-hematopoietic cells. However, the potential role of the IL-31-IL31RA axis in pulmonary inflammation and fibrosis has remained largely unknown. To determine the role of IL-31RA deficiency in pulmonary fibrosis, wildtype, and IL-31RA knockout mice were treated with bleomycin and measured changes in collagen deposition and lung function. Notably, the loss of IL-31 signaling attenuated collagen deposition and lung function decline during bleomycin-induced pulmonary fibrosis. The total lung transcriptome analysis showed a significant reduction in fibrosis-associated gene transcripts including extracellular matrix and epithelial cell-associated gene networks. Furthermore, the lungs of human IPF showed an elevated expression of IL-31 when compared to healthy subjects. In support, the percentage of IL-31 producing CD4+ T cells was greater in the lungs and PBMCs from IPF patients compared to healthy controls. Our findings suggest a pathogenic role for IL-31/IL-31RA signaling during bleomycin-induced pulmonary fibrosis. Thus, therapeutic targeting the IL-31-IL-31RA axis may prevent collagen deposition, improve lung function, and have therapeutic potential in pulmonary fibrosis.
Transcriptome and IgH Repertoire Analyses Show That CD11chi B Cells Are a Distinct Population With Similarity to B Cells Arising in Autoimmunity and Infection
Authors: Maul Robert W. , Catalina Michelle D. , Kumar Varsha , Bachali Prathyusha , Grammer Amrie C. , Wang Shu , Yang William , Hasni Sarfaraz , Ettinger Rachel , Lipsky Peter E. , Gearhart Patricia J.
Published: March 2021

A distinct B cell population marked by elevated CD11c expression is found in patients with systemic lupus erythematosus (SLE). Cells with a similar phenotype have been described during chronic infection, but variable gating strategies and nomenclature have led to uncertainty of their relationship to each other. We isolated CD11chi cells from peripheral blood and characterized them using transcriptome and IgH repertoire analyses. Gene expression data revealed the CD11chi IgD+ and IgD− subsets were highly similar to each other, but distinct from naive, memory, and plasma cell subsets. Although CD11chi B cells were enriched in some germinal center (GC) transcripts and expressed numerous negative regulators of B cell receptor (BCR) activation, they were distinct from GC B cells. Gene expression patterns from SLE CD11chi B cells were shared with other human diseases, but not with mouse age-associated B cells. IgH V-gene sequencing analysis showed IgD+ and IgD− CD11chi B cells had somatic hypermutation and were clonally related to each other and to conventional memory and plasma cells. However, the IgH repertoires expressed by the different subsets suggested that defects in negative selection during GC transit could contribute to autoimmunity. The results portray a pervasive B cell population that accumulates during autoimmunity and chronic infection and is refractory to BCR signaling.
InN Quantum Dots by Metalorganic Chemical Vapor Deposition for Optoelectronic Applications
Authors: Reilly Caroline E. , Keller Stacia , Nakamura Shuji , DenBaars Steven P.
Published: March 2021

This review will cover recent work on InN quantum dots (QDs), specifically focusing on advances in metalorganic chemical vapor deposition (MOCVD) of metal-polar InN QDs for applications in optoelectronic devices. The ability to use InN in optoelectronic devices would expand the nitrides system from current visible and ultraviolet devices into the near infrared. Although there was a significant surge in InN research after the discovery that its bandgap provided potential infrared communication band emission, those studies failed to produce an electroluminescent InN device in part due to difficulties in achieving p-type InN films. Devices utilizing InN QDs, on the other hand, were hampered by the inability to cap the InN without causing intermixing with the capping material. The recent work on InN QDs has proven that it is possible to use capping methods to bury the QDs without significantly affecting their composition or photoluminescence. Herein, we will discuss the current state of metal-polar InN QD growth by MOCVD, focusing on density and size control, composition, relaxation, capping, and photoluminescence. The outstanding challenges which remain to be solved in order to achieve InN infrared devices will be discussed.
Patient Provider Continuity and Prostate Specific Antigen Testing: Impact of Continuity on Receipt of a Non-recommended Test
Authors: Mainous Arch G. , Rooks Benjamin J. , Mercado Elvira S. , Carek Peter J.
Published: March 2021

Background: Continuity of care with a regular physician has been associated with treatment adherence but it is unclear if continuity of care may lead to inappropriate treatments. We assessed the relationship between the receipt of prostate-specific antigen (PSA) screening, a non-recommended test, and having continuity with a single personal doctor.

Methods: We analyzed the 2016 and 2018 Behavioral Risk Factor Surveillance System (BRFSS). Responses from men aged 40 and older with no symptoms or family history of prostate cancer were analyzed (unweighted n = 232,548, representing 36,919,766 individuals). Continuity with one doctor was analyzed in relation to discussions of advantages and disadvantages of PSA tests, provider recommendation to receive a test and receipt of a PSA test.

Results: 39.5% of men received PSA screening during the time that the test was not recommended. Having a single personal doctor was associated with discussion of both advantages (53.3 vs. 29.7%, p < 0.001) and disadvantages (24.2 vs. 13.5%, p < 0.001) of PSA tests but also a recommendation to receive a PSA test (45.3 vs. 29.3%, p < 0.001). The adjusted odds of receiving a PSA test was higher among those with a single personal doctor compared to those without (OR 2.31; 95% CI, 2.17–2.46).

Conclusion: In a nationally representative sample during the time when PSA screening was not recommended by the US Preventive Services Taskforce, having a single personal doctor was associated with both recommendations for the test and receipt of the test. These findings emphasize the importance of the patient physician relationship and the need for evidence-based care.
Analysis of Ovarian Injury Associated With COVID-19 Disease in Reproductive-Aged Women in Wuhan, China: An Observational Study
Authors: Ding Ting , Wang Tian , Zhang Jinjin , Cui Pengfei , Chen Zhe , Zhou Su , Yuan Suzhen , Ma Wenqing , Zhang Minli , Rong Yueguang , Chang Jiang , Miao Xiaoping , Ma Xiangyi , Wang Shixuan
Published: March 2021

Objective: This study was intended to investigate the relationship between COVID-19 disease and ovarian function in reproductive-aged women.

Methods: Female COVID-19 patients of reproductive age were recruited between January 28 and March 8, 2020 from Tongji Hospital in Wuhan. Their baseline and clinical characteristics, as well as menstrual conditions, were recorded. Differentials in ovarian reserve markers and sex hormones (including anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], the ratio of FSH to luteinizing hormone [LH], estradiol [E2], progesterone [P], testosterone [T], and prolactin [PRL] were compared to those of healthy women who were randomly selected and individually matched for age, region, and menstrual status. Uni- and multi-variable hierarchical linear regression analyses were performed to identify risk factors associated with ovarian function in COVID-19 women.

Results: Seventy eight patients agreed to be tested for serum hormone, of whom 17 (21.79%) were diagnosed as the severe group and 39 (50%) were in the basal level group. Menstrual status (P = 0.55), menstrual volumes (P = 0.066), phase of menstrual cycle (P = 0.58), and dysmenorrhea history (P = 0.12) were similar without significant differences between non-severe and severe COVID-19 women. Significant lower serum AMH level/proportion (0.19/0.28 vs. 1.12 ng/ml, P = 0.003/0.027; AMH ≤
1.1 ng/ml: 75/70.4 vs. 49.7%, P = 0.009/0.004), higher serum T (0.38/0.39 vs. 0.22 ng/ml, P < 0.001/0.001) and PRL (25.43/24.10 vs. 12.12 ng/ml, P < 0.001/0.001) levels were observed in basal level and the all-COVID-19 group compared with healthy age-matched control. When adjusted for age, menstrual status and parity variations in multivariate hierarchical linear regression analysis, COVID-19 disease was significantly associated with serum AMH (β = −0.191; 95% CI: −1.177–0.327; P = 0.001), T (β = 0.411; 95% CI: 11.154–22.709; P < 0.001), and PRL (β = 0.497; 95% CI: 10.787–20.266; P < 0.001), suggesting an independent risk factor for ovarian function, which accounted for 3.2% of the decline in AMH, 14.3% of the increase in T, and 20.7% of the increase in PRL.

Conclusion: Ovarian injury, including declined ovarian reserve and reproductive endocrine disorder, can be observed in women with COVID-19. More attention should be paid to their ovarian function under this pandemic, especially regarding reproductive-aged women.

Clinical Trial Number: ChiCTR2000030015.
Antifungal Activity of Essential Oil From Zanthoxylum armatum DC. on Aspergillus flavus and Aflatoxins in Stored Platycladi Semen
Authors: Li Ting , Chen Mingyang , Ren Guangxi , Hua Guodong , Mi Jiu , Jiang Dan , Liu Chunsheng
Published: March 2021

The major objective of this study was to evaluate the inhibitory effect of essential oil (EO) from Zanthoxylum armatum DC. on Aspergillus flavus. The chemical composition of the EO was identified by gas chromatography–mass spectrometer. The minimum inhibitory concentration (MIC) of EO was investigated by liquid fermentation. The morphology, colony number, and aflatoxin content of A. flavus in platycladi semen were investigated by stereomicroscopy, scanning electron microscopy, plate counting, and high-performance liquid chromatography. The results indicated that the MIC of EO was 0.8 μL⋅mL–1, and the main components were β-phellandrene (7.53%), D-limonene (13.24%), linalool (41.73%), terpinen-4-ol (5.33%), and trans-nerolidol (6.30%). After the EO fumigated the platycladi semen, the growth of A. flavus slowed, and the mycelium shrank considerably. The number of colonies after EO treatment at room temperature and cold storage was significantly reduced, the inhibition effect was better under cold storage, and the aflatoxin B1 content did not exceed the standard within 100 days. Therefore, this study demonstrated the good potential of A. flavus growth inhibition during the storage of platycladi semen.
The Richness and Diversity of Catalases in Bacteria
Authors: Yuan Fang , Yin Shouliang , Xu Yang , Xiang Lijun , Wang Haiyan , Li Zilong , Fan Keqiang , Pan Guohui
Published: March 2021

Catalases play a key role in the defense against oxidative stress in bacteria by catalyzing the decomposition of H2O2. In addition, catalases are also involved in multiple cellular processes, such as cell development and differentiation, as well as metabolite production. However, little is known about the abundance, diversity, and distribution of catalases in bacteria. In this study, we systematically surveyed and classified the homologs of three catalase families from 2,634 bacterial genomes. It was found that both of the typical catalase and Mn-catalase families could be divided into distinct groups, while the catalase-peroxidase homologs formed a tight family. The typical catalases are rich in all the analyzed bacterial phyla except Chlorobi, in which the catalase-peroxidases are dominant. Catalase-peroxidases are rich in many phyla, but lacking in Deinococcus-Thermus, Spirochetes, and Firmicutes. Mn-catalases are found mainly in Firmicutes and Deinococcus-Thermus, but are rare in many other phyla. Given the fact that catalases were reported to be involved in secondary metabolite biosynthesis in several Streptomyces strains, the distribution of catalases in the genus Streptomyces was given more attention herein. On average, there are 2.99 typical catalases and 0.99 catalase-peroxidases in each Streptomyces genome, while no Mn-catalases were identified. To understand detailed properties of catalases in Streptomyces, we characterized all the five typical catalases from S. rimosus ATCC 10970, the oxytetracycline-producing strain. The five catalases showed typical catalase activity, but possessed different catalytic properties. Our findings contribute to the more detailed classification of catalases and facilitate further studies about their physiological roles in secondary metabolite biosynthesis and other cellular processes, which might facilitate the yield improvement of valuable secondary metabolites in engineered bacteria.