bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Pulmonary Hydatid Cyst With Pleural Complications: A Case Series
Authors: Darbari Anshuman , Lahiri Raja , Mishra Mayank , Kumar Ajay , Gautam Sandeep , Kumar Navin
Published: February 2021

Introduction: The aim of this observational, retrospective study was to review and describe clinical presentations and management of patients with pulmonary hydatid cysts (PHC) and pleural complications.
Methods: Complete case records from the previous 2 years were reviewed, including operative steps and follow-up of patients with PHC and pleural complications. Only four cases that presented with pleural complications were found out of 14 cases of surgically managed PHC.
Results: The most common symptoms in all patients were chest pain and fever. In all cases, the lower lobes of the lung were involved. Lung resection surgery was not required in any case. There was no postoperative respiratory failure or immediate or late mortality in any of these patients. The mean follow-up was 10 months for all these cases, with no pulmonary recurrence or complications.
Conclusion: Pulmonary parenchymal sparing surgical interventions are deemed to be the safest curative treatment for complicated PHC. Spontaneous pyopneumothorax can also be caused by complicated PHC.
Fuzzy Logic Recommended Student Learning Levels
Authors: Abdul Rahman  , Destiarini  , Joko Kuswanto
Published: February 2021

Dalam proses penerimaan siswa kursus bahasa inggris menggunakan tes penempatan level belajar. Pada tahap penerapan tes menemui masalah seperti lambatnya penentuan tingkat belajar siswa berdasarkan hasil tes yang berbasis kertas. Tujuan dari penelitian ini adalah memberikan rekomendasi untuk tingkat pembelajaran siswa menggunakan metode Fuzzy.  Dimana level belajar bahasa inggris ini terbagi dalam kategori Foundation, Basic, Elementary, Intermediate dan Advance. Untuk inputan nilainya adalah Listening, Vocabulary, Structure dan Reading. Hasil penelitian diuji akurasi dataset dengan metode confusion matrix dengan hasil akurasi sebesar 88%
Cytokine Secretion, Viability, and Real-Time Proliferation of Apical-Papilla Stem Cells Upon Exposure to Oral Bacteria
Authors: Rakhimova Olena , Schmidt Alexej , Landström Maréne , Johansson Anders , Kelk Peyman , Romani Vestman Nelly
Published: February 2021

The use of stem cells from the apical papilla (SCAPs) has been proposed as a means of promoting root maturation in permanent immature teeth, and plays a significant role in regenerative dental procedures. However, the role of SCAPs may be compromised by microenvironmental factors, such as hypoxic conditions and the presence of bacteria from infected dental root canals. We aim to investigate oral bacterial modulation of SCAP in terms of binding capacity using flow cytometry and imaging, real-time cell proliferation monitoring, and cytokine secretion (IL-6, IL-8, and TGF-β isoforms) under anaerobic conditions. SCAPs were exposed to key species in dental root canal infection, namely Actinomyces gerensceriae, Slackia exigua, Fusobacterium nucleatum, and Enterococcus faecalis, as well as two probiotic strains, Lactobacillus gasseri strain B6 and Lactobacillus reuteri (DSM 17938). We found that A. gerensceriae, S. exigua, F. nucleatum, and E. faecalis, but not the Lactobacillus probiotic strains bind to SCAPs on anaerobic conditions. Enterococcus faecalis and F. nucleatum exhibited the strongest binding capacity, resulting in significantly reduced SCAP proliferation. Notably, F. nucleatum, but not E. faecalis, induce production of the proinflammatory chemokine IL-8 and IL-10 from SCAPs. Production of TGF-β1 and TGF-β2 by SCAPs was dependent on species, cell line, and time, but secretion of TGF-β3 did not vary significantly over time. In conclusion, SCAP response is compromised when exposed to bacterial stimuli from infected dental root canals in anaerobic conditions. Thus, stem cell-mediated endodontic regenerative studies need to include microenvironmental conditions, such as the presence of microorganisms to promote further advantage in the field.
Revisiting Drug Development Against the Neglected Tropical Disease, Amebiasis
Authors: Shrivastav Manish T. , Malik Zainab , Somlata
Published: February 2021

Amebiasis is a neglected tropical disease which is caused by the protozoan parasite Entamoeba histolytica. This disease is one of the leading causes of diarrhea globally, affecting largely impoverished residents in developing countries. Amebiasis also remains one of the top causes of gastrointestinal diseases in returning international travellers. Despite having many side effects, metronidazole remains the drug of choice as an amebicidal tissue-active agent. However, emergence of metronidazole resistance in pathogens having similar anaerobic metabolism and also in laboratory strains of E. histolytica has necessitated the identification and development of new drug targets and therapeutic strategies against the parasite. Recent research in the field of amebiasis has led to a better understanding of the parasite’s metabolic and cellular pathways and hence has been useful in identifying new drug targets. On the other hand, new molecules effective against amebiasis have been mined by modifying available compounds, thereby increasing their potency and efficacy and also by repurposing existing approved drugs. This review aims at compiling and examining up to date information on promising drug targets and drug molecules for the treatment of amebiasis.
TOX3 Promotes Ovarian Estrogen Synthesis: An RNA-Sequencing and Network Study
Authors: Man Yuanyuan , Zhao Rusong , Gao Xueying , Liu Yue , Zhao Shigang , Lu Gang , Chan Wai-Yee , Leung Peter C. K. , Bian Yuehong
Published: February 2021

Background

Women who undergo chronic exposure to excessive estrogen are at a high risk of developing breast cancer. TOX3 has been reported to be highly expressed in breast tumors and is closely related to estrogen receptors. However, the effect of TOX3 on estrogen synthesis remains poorly understood.

Methods

Using lentiviruses as a vector, we stably overexpressed TOX3 in the ovarian granulosa cell line KGN, the cells where estradiol is primarily produced, to investigate its role in estrogen production as well as cell viability and apoptosis. RNA-Sequencing was applied to uncover the global gene expression upon TOX3 overexpression.

Results

We observed an increased level of cell viability and a reduced cell apoptosis rate after TOX3 overexpression, and the level of estradiol in the cell culture supernatant also increased significantly. Gene set enrichment analysis of the transcriptome showed that the ovarian steroidogenesis pathway was significantly enriched. Similarly, pathway mapping using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses also showed that TOX3 overexpression affects the ovarian steroidogenesis pathway. Further experiments showed that upregulated FSHR, CYP19A1, and BMP6 accounted for the enhanced estrogen synthesis.

Conclusion

Our study demonstrated that TOX3 quantitatively and qualitatively stimulates estrogen synthesis by enhancing estrogen signaling pathway–related gene expression in ovarian granulosa cells. These findings suggest that TOX3 may play a vital role in the pathogenesis of breast cancer.
Stem Cell Paracrine Signaling for Treatment of Premature Ovarian Insufficiency
Authors: Polonio Alba M. , García-Velasco Juan A. , Herraiz Sonia
Published: February 2021

Premature ovarian insufficiency is a common disorder affecting young women and represents the worst-case ovarian scenario due to the substantial impact on the reproductive lifespan of these patients. Due to the complexity of this condition, which is not fully understood, non-effective treatments have yet been established for these patients. Different experimental approaches are being explored and strategies based on stem cells deserve special attention. The regenerative and immunomodulatory properties of stem cells have been successfully tested in different tissues, including ovary. Numerous works point out to the efficacy of stem cells in POI treatment, and a wide range of clinical trials have been developed in order to prove safety and effectiveness of stem cells therapy—in diminished ovarian reserve and POI women. The main purpose of this review is to describe the state of the art of the treatment of POI involving stem cells, especially those that use mobilization of stem cells or paracrine signaling.
Proteomic and Structural Manifestations of Cardiomyopathy in Rat Models of Obesity and Weight Loss
Authors: Liśkiewicz Arkadiusz D. , Marczak Łukasz , Bogus Katarzyna , Liśkiewicz Daniela , Przybyła Marta , Lewin-Kowalik Joanna
Published: February 2021

Obesity cardiomyopathy increases the risk of heart failure and death. Obesity is curable, leading to the restoration of the heart phenotype, but it is not clear if there are any after-effects of obesity present after weight loss. We characterize the proteomic landscape of obesity cardiomyopathy with an evaluation of whether the cardiac phenotype is still shaped after weight loss. Cardiomyopathy was validated by cardiac hypertrophy, fibrosis, oversized myocytes, and mTOR upregulation in a rat model of cafeteria diet-induced developmental obesity. By global proteomic techniques (LC-MS/MS) a plethora of molecular changes was observed in the heart and circulation of obese animals, suggesting abnormal utilization of metabolic substrates. This was confirmed by increased levels of cardiac ACSL-1, a key enzyme for fatty acid degradation and decreased GLUT-1, a glucose transporter in obese rats. Calorie restriction and weight loss led to the normalization of the heart’s size, but fibrosis was still excessive. The proteomic compositions of cardiac tissue and plasma were different after weight loss as compared to control. In addition to morphological consequences, obesity cardiomyopathy involves many proteomic changes. Weight loss provides for a partial repair of the heart’s architecture, but the trace of fibrotic deposition and proteomic alterations may occur.
Poor Status of Vitamin D: A Survey of Area With Lowest Sunlight Radiation in Sichuan, China
Authors: Fan Pianpian , Wang Qin , Li Jing , Lu Chunyan , Xu Yong , Cao Hongyi , Xie Xiaohua , Wu Xueyan , Guo Yanhong , Liu Ting , Chen Yan , Xu Shen , Huang Yuanyuan , Zhang Qi , Chen Decai
Published: February 2021

Objective

Vitamin D plays an important role in bone and mineral metabolism. Ultraviolet B (UVB) is the primary determinant for vitamin D synthesis. However, population-based data of vitamin D status was sparse in areas with sunlight deprivation in China. This study aimed to assess serum 25-hydroxyvitamin D [25(OH)D] levels among adult women in Sichuan basin with the lowest sunlight radiation in China, and the associations with sunlight exposure and age.

Methods

In the context of the same ethnicity, similar latitude and lifestyle in sunlight-limited basin and sunlight-abundant plateau, 1,057 women in basin and 337 in plateau aged 29–95 years were included in this study, from November 2012 to February 2013. Daily sunlight exposure duration of previous month was obtained using questionnaires. Serum 25(OH)D was measured by enzyme-linked immunosorbent assay.

Results

The prevalence of vitamin D severe deficiency [25(OH)D <30 nmol/L] and deficiency [30 ≤ 25(OH)D <50 nmol/L] was significantly higher in basin than plateau (21.85% vs. 10.09%, and 59.32% vs. 40.36%; P<0.0001). Women from basin exhibited lower serum 25(OH)D levels than those from plateau (40.66 ± 15.62 vs. 52.54 ± 19.94 nmol/L, P<0.0001). In basin, women more than 50 years old had higher 25(OH)D than younger counterparts, and 25(OH)D level of these groups was not associated with sunlight exposure duration. While in plateau, women younger than 60 years old had higher 25(OH)D than the older women. Furthermore, for those younger groups, women with long sunlight exposure (≥3 h daily) had higher 25(OH)D concentration than those with short sunlight exposure (<3 h daily). Serum PTH was negatively associated with 25(OH)D in basin, but not in plateau.

Conclusions

Alarmingly high prevalence of vitamin D deficiency was observed in women in sunlight-deprived basin in Sichuan. Only the vitamin D status of younger women from plateau with adequate solar radiation could benefit from sunlight exposure. Vitamin D supplementation and vitamin D-fortified food should be encouraged to improve vitamin D status for women living in sunlight-limited areas, or with old age.
Usefulness and Potential Pitfalls of Long-Acting Growth Hormone Analogs
Authors: Yuen Kevin C. J. , Miller Bradley S. , Boguszewski Cesar L. , Hoffman Andrew R.
Published: February 2021

Daily recombinant human GH (rhGH) is currently approved for use in children and adults with GH deficiency (GHD) in many countries with relatively few side-effects. Nevertheless, daily injections can be painful and distressing for some patients, often resulting in non-adherence and reduction of treatment outcomes. This has prompted the development of numerous long-acting GH (LAGH) analogs that allow for decreased injection frequency, ranging from weekly, bi-weekly to monthly. These LAGH analogs are attractive as they may theoretically offer increased patient acceptance, tolerability, and therapeutic flexibility. Conversely, there may also be pitfalls to these LAGH analogs, including an unphysiological GH profile and differing molecular structures that pose potential clinical issues in terms of dose initiation, therapeutic monitoring, incidence and duration of side-effects, and long-term safety. Furthermore, fluctuations of peak and trough serum GH and IGF-I levels and variations in therapeutic efficacy may depend on the technology used to prolong GH action. Previous studies of some LAGH analogs have demonstrated non-inferiority compared to daily rhGH in terms of increased growth velocity and improved body composition in children and adults with GHD, respectively, with no significant unanticipated adverse events. Currently, two LAGH analogs are marketed in Asia, one recently approved in the United States, another previously approved but not marketed in Europe, and several others proceeding through various stages of clinical development. Nevertheless, several practical questions still remain, including possible differences in dose initiation between naïve and switch-over patients, methodology of dose adjustment/s, timing of measuring serum IGF-I levels, safety, durability of efficacy and cost-effectiveness. Long-term surveillance of safety and efficacy of LAGH analogs are needed to answer these important questions.
Association of Sleep Duration With Atrial Fibrillation and Heart Failure: A Mendelian Randomization Analysis
Authors: Zhao Jianqiang , Yang Fangkun , Zhuo Chengui , Wang Qiyue , Qu Zihao , Wang Qiqi , Zheng Liangrong
Published: February 2021

Both short (<7 h per night) and long (≥9 h per night) sleep durations are related to atrial fibrillation (AF) and heart failure (HF), but their causality has not been confirmed. We applied Mendelian randomization (MR) approaches to estimate the causal association between genetically determined sleep duration and the risk of AF and HF. We performed two-sample MR analysis to obtain the effect of sleep duration on AF and HF. Instrumental variables were constructed using genetic variants known to be associated with continuous sleep duration, short sleep duration, and long sleep duration. MR estimates of the effect of sleep duration on AF and HF were derived based on two large meta-analyses of genome-wide association studies. The pooled MR estimate demonstrated a significant protective effect of continuous sleep duration on HF [odds ratio (OR) = 0.765, 95% confidence interval (CI) = 0.675–0.867; P = 2.64 × 10–5] and a suggestive inverse association of continuous sleep duration with AF (OR = 0.893, 95% CI = 0.804–0.991; P = 0.034). In addition, the results showed a suggestive detrimental effect of short sleep duration on the risk of AF (OR = 1.108, 95% CI = 1.017–1.207; P = 0.019) and HF (OR = 1.136, 95% CI = 1.025–1.258; P = 0.015). Conversely, there is no significant evidence for the causal protective effect of long sleep duration on AF (OR = 0.956, P = 0.410) and HF (OR = 0.921, P = 0.202). This MR study indicated that genetically determined continuous sleep duration has a significant protective effect on HF and a suggestive inverse association with AF. Short sleep duration is positively associated with the risk of AF and HF. Nevertheless, there is no significant evidence for the causal protective effect of long sleep duration on AF and HF. Larger intervention studies are required to confirm the effectiveness of improving sleep on reducing the incidence of AF and HF.
Global Transcriptomic Analyses Reveal Genes Involved in Conceptus Development During the Implantation Stages in Pigs
Authors: Zang Xupeng , Gu Ting , Hu Qun , Xu Zhiqian , Xie Yanshe , Zhou Chen , Zheng Enqin , Huang Sixiu , Xu Zheng , Meng Fanming , Cai Gengyuan , Wu Zhenfang , Hong Linjun
Published: February 2021

Prenatal mortality remains a significant concern to the pig farming industry around the world. Spontaneous fetal loss ranging from 20 to 45% by term occur after fertilization, with most of the loss happening during the implantation period. Since the factors regulating the high mortality rates of early conceptus during implantation phases are poorly understood, we sought to analyze the overall gene expression changes during this period, and identify the molecular mechanisms involved in conceptus development. This work employed Illumina’s next-generation sequencing (RNA-Seq) and quantitative real-time PCR to analyze differentially expressed genes (DEGs). Soft clustering was subsequently used for the cluster analysis of gene expression. We identified 8236 DEGs in porcine conceptus at day 9, 12, and 15 of pregnancy. Annotation analysis of these genes revealed rRNA processing (GO:0006364), cell adhesion (GO:1904874), and heart development (GO:0007507), as the most significantly enriched biological processes at day 9, 12, and 15 of pregnancy, respectively. In addition, we found various genes, such as T-complex 1, RuvB-like AAA ATPase 2, connective tissue growth factor, integrins, interferon gamma, SLA-1, chemokine ligand 9, PAG-2, transforming growth factor beta receptor 1, and Annexin A2, that play essential roles in conceptus morphological development and implantation in pigs. Furthermore, we investigated the function of PAG-2in vitroand found that PAG-2 can inhibit trophoblast cell proliferation and migration. Our analysis provides a valuable resource for understanding the mechanisms of conceptus development and implantation in pigs.
Comparison of Methods for Feature Selection in Clustering of High-Dimensional RNA-Sequencing Data to Identify Cancer Subtypes
Authors: Källberg David , Vidman Linda , Rydén Patrik
Published: February 2021

Cancer subtype identification is important to facilitate cancer diagnosis and select effective treatments. Clustering of cancer patients based on high-dimensional RNA-sequencing data can be used to detect novel subtypes, but only a subset of the features (e.g., genes) contains information related to the cancer subtype. Therefore, it is reasonable to assume that the clustering should be based on a set of carefully selected features rather than all features. Several feature selection methods have been proposed, but how and when to use these methods are still poorly understood. Thirteen feature selection methods were evaluated on four human cancer data sets, all with known subtypes (gold standards), which were only used for evaluation. The methods were characterized by considering mean expression and standard deviation (SD) of the selected genes, the overlap with other methods and their clustering performance, obtained comparing the clustering result with the gold standard using the adjusted Rand index (ARI). The results were compared to a supervised approach as a positive control and two negative controls in which either a random selection of genes or all genes were included. For all data sets, the best feature selection approach outperformed the negative control and for two data sets the gain was substantial with ARI increasing from (−0.01, 0.39) to (0.66, 0.72), respectively. No feature selection method completely outperformed the others but using the dip-rest statistic to select 1000 genes was overall a good choice. The commonly used approach, where genes with the highest SDs are selected, did not perform well in our study.
Triple-Negative Breast Cancer: Intact Mismatch Repair and Partial Co-Expression of PD-L1 and LAG-3
Authors: Wu Shafei , Shi Xiaohua , Wang Jing , Wang Xuefei , Liu Yuanyuan , Luo Yufeng , Mao Feng , Zeng Xuan
Published: February 2021

Background and Aim

Poor response to immune checkpoint inhibitors (ICIs) has been observed in most triple-negative breast cancer (TNBC) cases (around 80%). Our aim was to investigate the status of mismatch repair (MMR), microsatellite instability (MSI), programmed death-ligand 1 (PD-L1), and lymphocyte-activation gene 3 (LAG-3) in TNBC.

Methods

A total of 74 TNBC samples were retrospectively analyzed. MMR and MSI were evaluated by immunohistochemistry (IHC) and polymerase chain reaction (PCR) using Promega 1.2 and NCI panels, respectively. PD-L1, LAG-3, and CD8 expression was assessed by IHC.

Results

None of the cases demonstrated deficient MMR (dMMR) or MSI. In total, 43/74 cases (58.1%) were PD-L1+, including 1 tumor PD-L1+, 25 tumor-infiltrating lymphocytes (TILs) PD-L1+, and 17 cases involving concurrence of tumor and TIL PD-L1+. The rate of TIL PD-L1+ was remarkably higher than that of tumor PD-L1+ (P<0.001). We identified 20 LAG-3+ cases (27.0%, 20/74), all of which were PD-L1+. Co-expression of PD-L1 and LAG-3 was noted in 46.5% (20/43) of the PD-L1+ population. In the LAG-3+ subtype (co-expression of PD-L1 and LAG-3), high correlation between TILs PD-L1+ and LAG-3+ was observed (P<0.01). A high frequency of CD8+ (98.6%, 73/74) was observed.

Conclusion

dMMR/MSI characteristics may not be a practical predictive marker for ICIs in TNBC. PD-L1+ is more common in TILs than in tumors. In the PD-L1+ population, approximately half of the cases showed LAG-3 co-expression. For patients with a poor response to PD-1(L1) mono ICI, dual blockade of PD-1(L1) and LAG-3 may be a viable option for the management of TNBC.
The Role of Extracellular Vesicles in the Pathogenesis and Treatment of Autoimmune Disorders
Authors: Lu Mengrou , DiBernardo Emma , Parks Emily , Fox Hannah , Zheng Si-Yang , Wayne Elizabeth
Published: February 2021

Extracellular vesicles (EVs) are important players in autoimmune diseases, both in disease pathogenesis and as potential treatments. EVs can transport autoimmune triggers throughout the body, facilitating the process of antigen presentation. Understanding the link between cellular stress and EV biogenesis and intercellular trafficking will advance our understanding of autoimmune diseases. In addition, EVs can also be effective treatments for autoimmune diseases. The diversity of cell types that produce EVs leads to a wide range of molecules to be present in EVs, and thus EVs have a wide range of physiological effects. EVs derived from dendritic cells or mesenchymal stem cells have been shown to reduce inflammation. Since many autoimmune treatments are focused only on symptom management, EVs present a promising avenue for potential treatments. This review looks at the different roles EVs can play in autoimmune diseases, from disease pathology to diagnosis and treatment. We also overview various methodologies in isolating or generating EVs and look to the future for possible applications of EVs in autoimmune diseases.
Metabolism of Dendritic Cells in Tumor Microenvironment: For Immunotherapy
Authors: Peng Xin , He Youe , Huang Jun , Tao Yongguang , Liu Shuang
Published: February 2021

Dendritic cells (DCs) are a type of an antigen-presenting cell which undertake a job on capturing antigens coming from pathogens or tumors and presenting to T cells for immune response. The metabolism of DCs controls its development, polarization, and maturation processes and provides energy support for its functions. However, the immune activity of DCs in tumor microenvironment (TME) is inhibited generally. Abnormal metabolism of tumor cells causes metabolic changes in TME, such as hyperglycolysis, lactate and lipid accumulation, acidification, tryptophan deprivation, which limit the function of DCs and lead to the occurrence of tumor immune escape. Combined metabolic regulation with immunotherapy can strengthen the ability of antigen-presentation and T cell activation of DCs, improve the existing anti-tumor therapy, and overcome the defects of DC-related therapies in the current stage, which has great potential in oncology therapy. Therefore, we reviewed the glucose, lipid, and amino acid metabolism of DCs, as well as the metabolic changes after being affected by TME. Together with the potential metabolic targets of DCs, possible anti-tumor therapeutic pathways were summarized.
Functional Contributions of Antigen Presenting Cells in Chronic Graft-Versus-Host Disease
Authors: Hong Chao , Jin Rong , Dai Xiaoqiu , Gao Xiaoming
Published: February 2021

Chronic graft-versus-host disease (cGVHD) is one of the most common reasons of late non-relapse morbidity and mortality of patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). While acute GVHD is considered driven by a pathogenic T cell dominant mechanism, the pathogenesis of cGVHD is much complicated and involves participation of a variety of immune cells other than pathogenic T cells. Existing studies have revealed that antigen presenting cells (APCs) play crucial roles in the pathophysiology of cGVHD. APCs could not only present auto- and alloantigens to prime and activate pathogenic T cells, but also directly mediate the pathogenesis of cGVHDviamultiple mechanisms including infiltration into tissues/organs, production of inflammatory cytokines as well as auto- and alloantibodies. The studies of this field have led to several therapies targeting different APCs with promising results. This review will focus on the important roles of APCs and their contributions in the pathophysiology of cGVHD after allo-HSCT.
Multiple Origins of Extracellular DNA Traps
Authors: Ramos-Martínez Edgar , Hernández-González Leticia , Ramos-Martínez Iván , Pérez-Campos Mayoral Laura , López-Cortés Georgina I. , Pérez-Campos Eduardo , Mayoral Andrade Gabriel , Hernández-Huerta María Teresa , José Marco V.
Published: February 2021

Extracellular DNA traps (ETs) are evolutionarily conserved antimicrobial mechanisms present in protozoa, plants, and animals. In this review, we compare their similarities in species of different taxa, and put forward the hypothesis that ETs have multiple origins. Our results are consistent with a process of evolutionary convergence in multicellular organisms through the application of a congruency test. Furthermore, we discuss why multicellularity is related to the presence of a mechanism initiating the formation of ETs.
Artemisinin Attenuates Transplant Rejection by Inhibiting Multiple Lymphocytes and Prolongs Cardiac Allograft Survival
Authors: Yang Zhe , Han Fei , Liao Tao , Zheng Haofeng , Luo Zihuan , Ma Maolin , He Jiannan , Li Lei , Ye Yongrong , Zhang Rui , Huang Zhengyu , Zhang Yannan , Sun Qiquan
Published: February 2021

Immunological rejection is an important factor resulting in allograft dysfunction, and more valid therapeutic methods need to be explored to improve allograft outcomes. Many researches have indicated that artemisinin and its derivative exhibits immunosuppressive functions, apart from serving as a traditional anti-malarial drug. In this assay, we further explored the therapeutic effects of artemisinin for transplant rejection in a rat cardiac transplantation model. We found that it markedly attenuated allograft rejection and histological injury and significantly prolonged the survival of allograft. Upon further exploring the mechanism, we demonstrated that artemisinin not only attenuated T cell-mediated rejection (TCMR) by reducing effector T cell infiltration and inflammatory cytokine secretion and increasing regulatory T cell infiltration and immunoregulatory cytokine levels, but also attenuated antibody-mediated rejection (ABMR) through inhibition of B cells activation and antibody production. Furthermore, artemisinin also reduced macrophage infiltration in allografts, which was determined to be important for TCMR and ABMR. Moreover, we demonstrated that artemisinin significantly inhibited the function of pure T cells, B cells, and macrophages in vitro. All in all, this study provide evidence that artemisinin significantly attenuates TCMR and ABMR by targeting multiple effectors. Therefore, this agent might have potential for use in clinical settings to protect against transplant rejection.
Enhanced Growth Performance Physiological and Biochemical Indexes of Trachinotus ovatus Fed With Marine Microalgae Aurantiochytrium sp. Rich in n-3 Polyunsaturated Fatty Acids
Authors: Li Shuangfei , Wang Boyu , Liu Liangxu , Song Yingjie , Lv Chuhan , Zhu Xingyu , Luo Yanqing , Cheng Christopher H. K. , Chen Huapu , Yang Xuewei , Li Tao
Published: February 2021

Aurantiochytrium sp. is a major source of n-3 polyunsaturated fatty acids (n-3 PUFAs), which are essential nutrients for marine fish. n-3 PUFAs have drawn increasing attention because of their great potential for improving the biological functions of fish. The growth performance and immune response of Trachinotus ovatus were studied by applying diets with various microalgae content from 1.00 to 11.00% for 8 weeks. The results showed that, with the addition of Aurantiochytrium sp., the survival rate, weight gain rate, and specific growth rate of fish increased by a maximum of 1.02, 1.16, and 1.08 times, respectively, indicating that the intake of marine microalgae Aurantiochytrium sp. was beneficial for fish growth. As the microalgae content increased, the feed utilization efficiency index feed conversion ratio decreased (maximum 15.00%) and feed efficiency increased (maximum 1.17 times), showing that the addition of Aurantiochytrium sp. contributed to the assimilation of fish feed. Furthermore, our results showed that as the addition of Aurantiochytrium sp. increased (from 1.00 to 11.00%), the glucose content increased in the blood (from 9.04 to 27.80%). The content of fatty acids ARA, ALA, DHA, and EPA in fish was significantly increased after adding Aurantiochytrium sp. in diets. In liver, ARA content increased from 1.17 to 1.63%, ALA increased from 0.56 to 0.85%, DHA increased from 14.44 to 20.61%, and EPA increased from 1.86 to 4.40%. In muscle, ARA content increased from 0.97 to 1.24%, ALA increased from 0.59 to 0.81%, DHA increased from 14.63 to 14.82%, and EPA increased from 4.58 to 5.19%. Positive changes were observed in the blood cell count of immune related cells (white blood cells, lymphocytes, monocytes, neutrophils, and red blood cells). These results indicated that microalgae rich in n-3 PUFAs could increase the number of immune cells, thus helping to improve fish immunity and disease resistance.
Marine Litter Windrows: A Strategic Target to Understand and Manage the Ocean Plastic Pollution
Authors: Cózar Andrés , Aliani Stefano , Basurko Oihane C. , Arias Manuel , Isobe Atsuhiko , Topouzelis Konstantinos , Rubio Anna , Morales-Caselles Carmen
Published: February 2021

Windrow is a long-established term for the aggregations of seafoam, seaweeds, plankton and natural debris that appear on the ocean surface. Here, we define a “litter windrow” as any aggregation of floating litter at the submesoscale domain (<10 km horizontally), regardless of the force inducing the surface convergence, be it wind or other forces such as tides or density-driven currents. The marine litter windrows observed to date usually form stripes from tens up to thousands of meters long, with litter densities often exceeding 10 small items (<2 cm) per m2 or 1 large item (>2 cm) per 10 m2. Litter windrows are generally overlooked in research due to their dispersion, small size and ephemeral nature. However, applied research on windrows offers unique possibilities to advance on the knowledge and management of marine litter pollution. Litter windrows are hot spots of interaction with marine life. In addition, since the formation of dense litter windrows requires especially high loads of floating litter in the environment, their detection from space-borne sensors, aerial surveys or other platforms might be used to flag areas and periods of severe pollution. Monitoring and assessing of management plans, identification of pollution sources, or impact prevention are identified as some of the most promising fields of application for the marine litter windrows. In the present Perspective, we develop a conceptual framework and point out the main obstacles, opportunities and methodological approaches to address the study of litter windrows.
Interactive Effects of Elevated CO2 Concentration and Light on the Picophytoplankton Synechococcus
Authors: Bao Nanou , Gao Kunshan
Published: February 2021

Synechococcus is a major contributor to the primary production in tropic and subtropical oceans worldwide. Responses of this picophytoplankton to changing light and CO2 levels is of general concern to understand its ecophysiology in the context of ocean global changes. We grew Synechococcus sp. (WH7803), originally isolated from subtropic North Atlantic Ocean, under different PAR levels for about 15 generations and examined its growth, photochemical performance and the response of these parameters to elevated CO2 (1,000 μatm). The specific growth rate increased from 6 μmol m–2 s–1 to reach a maximum (0.547 ± 0.026) at 25 μmol m–2 s–1, and then became inhibited at PAR levels over 50 μmol m–2 s–1, with light use efficiency (α) and photoinhibition coefficient (β) being 0.093 and 0.002, respectively. When the cells were grown at ambient and elevated CO2 concentration (400 vs. 1,000 μatm), the high-CO2 grown cells showed significantly enhanced rates of electron transport and quantum yield as well as significant increase in specific growth rate at the limiting and inhibiting PAR levels. While the electron transport rate significantly increased at the elevated CO2 concentration under all tested light levels, the specific growth did not exhibit significant changes under the optimal growth light condition. Our results indicate that Synechococcus WH7803 grew faster under the ocean acidification (OA) treatment induced by CO2 enrichment only under limiting and inhibiting light levels, indicating the interactive effects and implying that the picophytoplankton respond differentially at different depths while exposing changing light conditions.
Research of Microstructure, Friction and Wear on Siliconized Aluminum-Bronze With Different Silicon Powder Ratio
Authors: Tian Feng , Wu Chunyan , Zhu Bin , Wang Liang , Liu Yong , Zhang Yisheng
Published: February 2021

In order to enhance the wear resistance without changing the mechanical properties of the substrate, the aluminum-bronze alloy was siliconized by pack cementation in this paper. Its surface hardness was improved by a certain thickness of siliconized layer. The different processes and their influences on the siliconized layer and the substrate were investigated by changing the ratio of siliconizing powder. The microstructure and phase composition of the siliconized layer was detected and analyzed. Compared with the non-siliconized sample, the hardness of the siliconized layer of 30% Si content is increased by 93.54%, and the average friction coefficient is reduced to 40.38%. The maximum thickness of siliconized layer in the experiment is 200 μm when the silicon powder content is 30%. It can be concluded that surface siliconizing is effective to reduce the friction coefficient of aluminum-bronze and improve wear resistance.
Efficacy of Individual Bacteriophages Does Not Predict Efficacy of Bacteriophage Cocktails for Control of Escherichia coli O157
Authors: Niu Yan D. , Liu Hui , Du Hechao , Meng Ruiqiang , Sayed Mahmoud El , Wang Guihua , McAllister Tim A. , Stanford Kim
Published: February 2021

Effectiveness of bacteriophages AKFV33 (Tequintavirus, T5) and AHP24 (Rogunavirus, T1), wV7 (Tequatrovirus, T4), and AHP24S (Vequintavirus, rV5), as well as 11 cocktails of combinations of the four phages, were evaluatedin vitrofor biocontrol of six common phage types ofEscherichia coliO157 (human and bovine origins) at different multiplicities of infection (MOIs; 0.01–1,000), temperatures (37 or 22°C), and exposure times (10–22 h). Phage efficacy against O157 was highest at MOI 1,000 (P< 0.001) and after 14-18 h of exposure at 22°C (P< 0.001). The activity of individual phages against O157 did not predict the activity of a cocktail of these phages even at the same temperature and MOI. Combinations of phages were neutral (no better or worse than the most effective constituent phages acting alone), displayed facilitation (greater efficacy than the most effective constituent phages acting alone), or antagonistic (lower efficacy than the most effective constituent phages acting alone). Across MOIs, temperatures, exposure time, and O157 strains, a cocktail of T1, T4, and rV5 was most effective (P< 0.05) against O157, although T1 and rV5 were less effective (P< 0.001) than other individual phages. T5 was the most effective individual phages (P< 0.05), but was antagonistic to other phages, particularly rV5 and T4 + rV5. Interactions among phages were influenced by phage genera and phage combination, O157 strains, MOIs, incubation temperatures, and times. Based on this study, future development of phage cocktails should, as a minimum, include confirmation of a lack of antagonism among constituent phages and preferably confirmation of facilitation or synergistic effects.
Cloning and Characterization of a New Chitosanase From a Deep-Sea Bacterium Serratia sp. QD07
Authors: Zheng Qiuling , Meng Xiangjun , Cheng Mingyang , Li Yanfeng , Liu Yuanpeng , Chen Xuehong
Published: February 2021

Chitosanase is a significant chitosan-degrading enzyme involved in industrial applications, which forms chitooligosaccharides (COS) as reaction products that are known to have various biological activities. In this study, the gene csnS was cloned from a deep-sea bacterium Serratia sp. QD07, as well as over-expressed in Escherichia coli, which is a new chitosanase encoding gene. The recombinant strain was cultured in a 5 L fermenter, which yielded 324 U/mL chitosanases. After purification, CsnS is a cold-adapted enzyme with the highest activity at 60°C, showing 37.5% of the maximal activity at 0°C and 42.6% of the maximal activity at 10°C. It exhibited optimum activity at pH 5.8 and was stable at a pH range of 3.4–8.8. Additionally, CsnS exhibited an endo-type cleavage pattern and hydrolyzed chitosan polymers to yield disaccharides and trisaccharides as the primary reaction products. These results make CsnS a potential candidate for the industrial manufacture of COS.
Binnacle: Using Scaffolds to Improve the Contiguity and Quality of Metagenomic Bins
Authors: Muralidharan Harihara Subrahmaniam , Shah Nidhi , Meisel Jacquelyn S. , Pop Mihai
Published: February 2021

High-throughput sequencing has revolutionized the field of microbiology, however, reconstructing complete genomes of organisms from whole metagenomic shotgun sequencing data remains a challenge. Recovered genomes are often highly fragmented, due to uneven abundances of organisms, repeats within and across genomes, sequencing errors, and strain-level variation. To address the fragmented nature of metagenomic assemblies, scientists rely on a process called binning, which clusters together contigs inferred to originate from the same organism. Existing binning algorithms use oligonucleotide frequencies and contig abundance (coverage) within and across samples to group together contigs from the same organism. However, these algorithms often miss short contigs and contigs from regions with unusual coverage or DNA composition characteristics, such as mobile elements. Here, we propose that information from assembly graphs can assist current strategies for metagenomic binning. We use MetaCarvel, a metagenomic scaffolding tool, to construct assembly graphs where contigs are nodes and edges are inferred based on paired-end reads. We developed a tool, Binnacle, that extracts information from the assembly graphs and clusters scaffolds into comprehensive bins. Binnacle also provides wrapper scripts to integrate with existing binning methods. The Binnacle pipeline can be found on GitHub (https://github.com/marbl/binnacle). We show that binning graph-based scaffolds, rather than contigs, improves the contiguity and quality of the resulting bins, and captures a broader set of the genes of the organisms being reconstructed.
Aging Alters Daily and Regional Calretinin Neuronal Expression in the Rat Non-image Forming Visual Thalamus
Authors: Fiuza Felipe P. , Queiroz José Pablo G. , Aquino Antônio Carlos Q. , Câmara Diego A. , Brandão Luiz Eduardo M. , Lima Ramon H. , Cavalcanti José Rodolfo L. P. , Engelberth Rovena Clara G. J. , Cavalcante Jeferson S.
Published: February 2021

Aging affects the overall physiology, including the image-forming and non-image forming visual systems. Among the components of the latter, the thalamic retinorecipient inter-geniculate leaflet (IGL) and ventral lateral geniculate (vLGN) nucleus conveys light information to subcortical regions, adjusting visuomotor, and circadian functions. It is noteworthy that several visual related cells, such as neuronal subpopulations in the IGL and vLGN are neurochemically characterized by the presence of calcium binding proteins. Calretinin (CR), a representative of such proteins, denotes region-specificity in a temporal manner by variable day–night expression. In parallel, age-related brain dysfunction and neurodegeneration are associated with abnormal intracellular concentrations of calcium. Here, we investigated whether daily changes in the number of CR neurons are a feature of the aged IGL and vLGN in rats. To this end, we perfused rats, ranging from 3 to 24 months of age, within distinct phases of the day, namely zeitgeber times (ZTs). Then, we evaluated CR immunolabeling through design-based stereological cell estimation. We observed distinct daily rhythms of CR expression in the IGL and in both the retinorecipient (vLGNe) and non-retinorecipient (vLGNi) portions of the vLGN. In the ZT 6, the middle of the light phase, the CR cells are reduced with aging in the IGL and vLGNe. In the ZT 12, the transition between light to dark, an age-related CR loss was found in all nuclei. While CR expression predominates in specific spatial domains of vLGN, age-related changes appear not to be restricted at particular portions. No alterations were found in the dark/light transition or in the middle of the dark phase, ZTs 0, and 18, respectively. These results are relevant in the understanding of how aging shifts the phenotype of visual related cells at topographically organized channels of visuomotor and circadian processing.
Blood Hemoglobin, in-vivo Alzheimer Pathologies, and Cognitive Impairment: A Cross-Sectional Study
Authors: Kim Jee Wook , Byun Min Soo , Yi Dahyun , Lee Jun Ho , Jeon So Yeon , Ko Kang , Joung Haejung , Jung Gijung , Lee Jun-Young , Sohn Chul-Ho , Lee Yun-Sang , Kim Yu Kyeong , Lee Dong Young
Published: February 2021

Background: Despite known associations between low blood hemoglobin level and Alzheimer's disease (AD) or cognitive impairment, the underlying neuropathological links are poorly understood. We aimed to examine the relationships of blood hemoglobin levels with in vivo AD pathologies (i.e., cerebral beta-amyloid [Aβ] deposition, tau deposition, and AD-signature degeneration) and white matter hyperintensities (WMHs), which are a measure of cerebrovascular injury. We also investigated the association between hemoglobin level and cognitive performance, and then assessed whether such an association is mediated by brain pathologies.

Methods: A total of 428 non-demented older adults underwent comprehensive clinical assessments, hemoglobin level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Episodic memory score and global cognition scores were also measured.

Results: A lower hemoglobin level was significantly associated with reduced AD-signature cerebral glucose metabolism (AD-CM), but not Aβ deposition, tau deposition, or WMH volume. A lower hemoglobin level was also significantly associated with poorer episodic memory and global cognition scores, but such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a moderating effect.

Conclusion: The present findings suggest that low blood hemoglobin in older adults is associated with cognitive decline via reduced brain metabolism, which seems to be independent of those aspects of AD-specific protein pathologies and cerebrovascular injury that are reflected in PET and MRI measures.
Local Homeostatic Regulation of the Spectral Radius of Echo-State Networks
Authors: Schubert Fabian , Gros Claudius
Published: February 2021

Recurrent cortical networks provide reservoirs of states that are thought to play a crucial role for sequential information processing in the brain. However, classical reservoir computing requires manual adjustments of global network parameters, particularly of the spectral radius of the recurrent synaptic weight matrix. It is hence not clear if the spectral radius is accessible to biological neural networks. Using random matrix theory, we show that the spectral radius is related to local properties of the neuronal dynamics whenever the overall dynamical state is only weakly correlated. This result allows us to introduce two local homeostatic synaptic scaling mechanisms, termed flow control and variance control, that implicitly drive the spectral radius toward the desired value. For both mechanisms the spectral radius is autonomously adapted while the network receives and processes inputs under working conditions. We demonstrate the effectiveness of the two adaptation mechanisms under different external input protocols. Moreover, we evaluated the network performance after adaptation by training the network to perform a time-delayed XOR operation on binary sequences. As our main result, we found that flow control reliably regulates the spectral radius for different types of input statistics. Precise tuning is however negatively affected when interneural correlations are substantial. Furthermore, we found a consistent task performance over a wide range of input strengths/variances. Variance control did however not yield the desired spectral radii with the same precision, being less consistent across different input strengths. Given the effectiveness and remarkably simple mathematical form of flow control, we conclude that self-consistent local control of the spectral radius via an implicit adaptation scheme is an interesting and biological plausible alternative to conventional methods using set point homeostatic feedback controls of neural firing.