bluuebunny/crossref_metadata_2025 huggingface dataset:
Refractive Index Change of Cellulose Nanocrystal-Based Electroactive Polyurethane by an Electric Field
Authors: Kim Jaehwan , Ko Hyun-U , Kim Hyun Chan
Published: January 2021

A tunable optical lens can tune or reconfigure the lens material itself such that it can eliminate the moving part of the lens, which brings broad technological impacts. Many tunable optical lenses have been implemented using electroactive polymers that can change the shape of the lens. However, the refractive index (RI) change of electroactive polymers has not been well investigated. This paper investigated the RI change of CNC-based transparent and electroactive polyurethane (CPPU) in the presence of an actuating electric field. The prepared CPPU was electrically poled to enhance its electro-optical performance, and the poling conditions in terms of frequency and electric field were optimized. The poled CPPU was characterized using a Fourier transform infrared spectroscopy and a refractometer. To investigate the RI change in the presence of an actuating electric field, the poled CPPU was constrained between two electrodes with a fixed distance. The RI linearly increased as the actuating electric field increased. The RI change mechanism and the optimized poling conditions are illustrated. The tunable RI is a promising property for implementing a tunable optical lens.
Controllable Synthesis of Biocompatible Fluorescent Carbon Dots From Cellulose Hydrogel for the Specific Detection of Hg2+
Authors: Huang Hailong , Ge Hao , Ren Zhipeng , Huang Zhijian , Xu Min , Wang Xianghui
Published: January 2021

Heavy metal ions overload can seriously harm human health. Simple and effective strategies for the specific detection of heavy metal ions are of great important. In this work, using different pretreatment methods, a series of carbon dots (CDs) with different particle sizes and doped with varying amounts of elements (O, N, S) were prepared based on the natural polymer, cellulose hydrogel. The CDs exhibit excellent fluorescence and biocompatibility. When the particle size decreased from 8.72 to 2.11 nm, the fluorescence quantum yield increased from 0.029 to 0.183. In addition, doping with elements (N) also effectively enhanced the fluorescent performance of the CDs. The fluorescence of the CDs, especially for the smallest, CD-4a, was significantly quenched in the presence of the heavy metal ion, Hg2+. Thus, CD-4a may be used as a fluorescence sensor for the detection of Hg2+. The fluorescence intensity of CD-4a exhibited a two-stage, concentration-dependent fluorescence response in the range 0.2–10 and 10–100 μmol/L Hg2+, with each stage having different slopes; the detection limit was 0.2 μM. More importantly, even in the presence of interfering metal ions, the detection of Hg2+ using the CDs-4a remained stable. Therefore, these biocompatible CDs may serve as a promising candidate for the specific detection of Hg2+.
Automated Pipeline to Generate Anatomically Accurate Patient-Specific Biomechanical Models of Healthy and Pathological FSUs
Authors: Caprara Sebastiano , Carrillo Fabio , Snedeker Jess G. , Farshad Mazda , Senteler Marco
Published: January 2021

State-of-the-art preoperative biomechanical analysis for the planning of spinal surgery not only requires the generation of three-dimensional patient-specific models but also the accurate biomechanical representation of vertebral joints. The benefits offered by computational models suitable for such purposes are still outweighed by the time and effort required for their generation, thus compromising their applicability in a clinical environment. In this work, we aim to ease the integration of computerized methods into patient-specific planning of spinal surgery. We present the first pipeline combining deep learning and finite element methods that allows a completely automated model generation of functional spine units (FSUs) of the lumbar spine for patient-specific FE simulations (FEBio). The pipeline consists of three steps: (a) multiclass segmentation of cropped 3D CT images containing lumbar vertebrae using the DenseVNet network, (b) automatic landmark-based mesh fitting of statistical shape models onto 3D semantic segmented meshes of the vertebral models, and (c) automatic generation of patient-specific FE models of lumbar segments for the simulation of flexion-extension, lateral bending, and axial rotation movements. The automatic segmentation of FSUs was evaluated against the gold standard (manual segmentation) using 10-fold cross-validation. The obtained Dice coefficient was 93.7% on average, with a mean surface distance of 0.88 mm and a mean Hausdorff distance of 11.16 mm (N = 150). Automatic generation of finite element models to simulate the range of motion (ROM) was successfully performed for five healthy and five pathological FSUs. The results of the simulations were evaluated against the literature and showed comparable ROMs in both healthy and pathological cases, including the alteration of ROM typically observed in severely degenerated FSUs. The major intent of this work is to automate the creation of anatomically accurate patient-specific models by a single pipeline allowing functional modeling of spinal motion in healthy and pathological FSUs. Our approach reduces manual efforts to a minimum and the execution of the entire pipeline including simulations takes approximately 2 h. The automation, time-efficiency and robustness level of the pipeline represents a first step toward its clinical integration.
Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3
Authors: Chen Xijuan , Liu Yingqiang , Zhang Qinglan , Liu Baoxing , Cheng Yan , Zhang Yonglei , Sun Yanan , Liu Junqi , Gen Hong
Published: January 2021

It has been reported that long non-coding RNA HOXA distal transcript antisense RNA (lncRNA HOTTIP) functions as a tumor promoter in colorectal cancer (CRC). Hence, we paid attention to exploring whether exosomes could carry lncRNA HOTTIP to affect the mitomycin resistance in CRC and to identify the underlying mechanisms. High expression of HOTTIP was detected in mitomycin-resistant CRC cells. Inhibition of HOTTIP reduced the mitomycin resistance. In the co-culture system of mitomycin-resistant cells or their derived exosomes with CRC cells, the HOTTIP was found to be transferred into the parental cells via extracellular vesicles (EVs) secreted from mitomycin-resistant cells and to contribute to the mitomycin resistance. Based on the bioinformatics databases, possible interaction network of HOTTIP, microRNA-214 (miR-214) and Karyopherin subunit alpha 3 (KPNA3) in CRC was predicted, which was further analyzed by dual-luciferase reporter, RNA binding protein immunoprecipitation and RNA pull-down assays. As HOTTIP down-regulated miR-214 to elevate the KPNA3 expression, HOTTIP enhanced the mitomycin resistance through impairing miR-214-dependent inhibition of KPNA3. Finally, HOTTIP was suggested as an independent factor predicting mitomycin response in patients with CRC. Those data together confirmed the promotive effects of EV-carried HOTTIP on the mitomycin resistance, while targeting HOTTIP might be a promising strategy overcoming drug resistance in CRC.
Regulatory Mechanisms of Vitellogenesis in Insects
Authors: Wu Zhongxia , Yang Libin , He Qiongjie , Zhou Shutang
Published: January 2021

Vitellogenesis is pre-requisite to insect egg production and embryonic development after oviposition. During insect vitellogenesis, the yolk protein precursor vitellogenin (Vg) is mainly synthesized in the fat body, transported by the hemolymph through the intercellular spaces (known as patency) in the follicular epithelium to reach the membrane of maturing oocytes, and sequestered into the maturing oocytes via receptor-mediated endocytosis. Insect vitellogenesis is governed by two critical hormones, the sesquiterpenoid juvenile hormone (JH) and the ecdysteriod 20-hydroxyecdysone (20E). JH acts as the principal gonadotropic hormone to stimulate vitellogenesis in basal hemimetabolous and most holometabolous insects. 20E is critical for vitellogenesis in some hymenopterans, lepidopterans and dipterans. Furthermore, microRNA (miRNA) and nutritional (amino acid/Target of Rapamycin and insulin) pathways interplay with JH and 20E signaling cascades to control insect vitellogenesis. Revealing the regulatory mechanisms underlying insect vitellogenesis is critical for understanding insect reproduction and helpful for developing new strategies of insect pest control. Here, we outline the recent research progress in the molecular action of gonadotropic JH and 20E along with the role of miRNA and nutritional sensor in regulating insect vitellogenesis. We highlight the advancements in the regulatory mechanisms of insect vitellogenesis by the coordination of hormone, miRNA and nutritional signaling pathways.
MiR-146a-5p Mimic Inhibits NLRP3 Inflammasome Downstream Inflammatory Factors and CLIC4 in Neonatal Necrotizing Enterocolitis
Authors: Chen Jianglong , Chen Tong , Zhou Jin , Zhao Xiuhao , Sheng Qingfeng , Lv Zhibao
Published: January 2021

Objective: Necrotizing enterocolitis (NEC) is a gastrointestinal emergency with a severe inflammation storm, intestinal necrosis, and perforation. MicroRNA-146a-5p (miR-146a-5p) has been reported to be a valuable anti-inflammatory factor in various intestinal inflammatory disorders. However, the role of miR-146a-5p in NEC, its effects on nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome, and its downstream inflammatory factors remain unknown. This study aimed to investigate the role of miR-146a-5p and NLRP3 inflammasome and its downstream inflammatory factors in NEC development.

Methods: The expression levels of miR-146a and NLRP3 inflammasome were investigated in intestinal tissues. Next, the mechanism by which miR-146a-5p regulates NLRP3 inflammasome activation was explored in vitro in THP-1 cells. Finally, to identify the effects of miR-146a-5p on NEC in vivo, NEC mice were transinfected with miR-146a-5p overexpression adenovirus before the occurrence of NEC.

Results: NLRP3 inflammasome enzymatic protein caspase-1 and its downstream inflammatory factors increased in NEC intestinal samples in both humans and mice, and miR-146a-5p expression level was increased and mainly expressed in the macrophages of the affected intestine. In vitro, only miR-146a-5p mimic inhibited NLRP3 inflammasome downstream inflammatory factors and its upstream protein chloride intracellular channel protein 4 (CLIC4) expression in cellular membrane in the THP-1 cell line, and this only occurred under mild/moderate LPS concentration. MiR-146a-5p overexpression adenovirus transfection reduced CLIC4 cellular membrane expression and inhibited NLRP3 downstream factors increasing in vivo. After the transfection of miR-146a-5p adenovirus, the survival rate of NEC mice was increased, and intestinal injury was ameliorated.

Conclusion: MiR-146a-5p inhibited NLRP3 inflammasome downstream inflammatory factors and CLIC4 membrane expression in NEC. Additionally, miR-146a-5p could attenuate inflammation and intestinal injury in the NEC-affected intestine.
Plasma Exosomes Derived From Patients With End-Stage Renal Disease and Renal Transplant Recipients Have Different Effects on Vascular Calcification
Authors: Lin Xiao , Zhu Ting , Xu Feng , Zhong Jia-Yu , Li Fuxingzi , Shan Su-Kang , Wu Feng , Guo Bei , Zheng Ming-Hui , Wang Yi , Xu Qiu-Shuang , Liao Xiao-Bo , Lu Hong-Yu , Xie Xu-Biao , Yuan Ling-Qing
Published: January 2021

End-stage renal disease (ESRD) patients usually develop extensive and progressive vascular calcification, and lots of calcification inhibitors as well as procalcifying factors are involved in the process. However, the mechanisms of vascular calcification in ESRD patients are still ill-defined. In the present study, we found that the plasma exosomes derived from ESRD patients (ESRD-Ex) promoted calcification of vascular smooth muscle cells (VSMCs) significantly, while plasma exosomes from renal transplant recipients (RTR-Ex) could partially attenuate VSMCs calcification. Moreover, the protein concentration of ESRD-Ex was significantly higher than plasma exosomes from the normal health control group (Nor-Ex) and RTR-Ex, and the content of both matrix gla protein (MGP) and Fetuin-A, the calcification inhibitors, were prominently lower in ESRD-Ex than those in Nor-Ex. The content of Annexin-A2, one of the calcification promoters, was significantly higher in ESRD-Ex and RTR-Ex than that in Nor-Ex. However, bone morphogenetic protein (BMP-2) and receptor activator for nuclear factor-κB ligand (Rankl) had no significant difference among the three groups. In addition, the content of Fetuin-A in RTR-Ex was higher than that in ESRD-Ex, although it was still lower than that in Nor-Ex. Furthermore, the levels of both Fetuin-A and MGP in plasma exosomes were negatively while the levels of Annexin-A2 in plasma exosomes was positively correlated to coronary artery calcification scores (CACS). These results indicated that ESRD-Ex significantly promoted VSMCs calcification, while renal transplantation could partially attenuate the procalcification effect of exosomes. Fetuin-A and MGP were decreased, but Annexin-A2 was increased in ESRD-Ex, and renal transplantation could increase the level of Fetuin-A rather than MGP.
Redox Regulation of the Actin Cytoskeleton in Cell Migration and Adhesion: On the Way to a Spatiotemporal View
Authors: Balta Emre , Kramer Johanna , Samstag Yvonne
Published: January 2021

The actin cytoskeleton of eukaryotic cells is a dynamic, fibrous network that is regulated by the concerted action of actin-binding proteins (ABPs). In particular, rapid polarization of cells in response to internal and external stimuli is fundamental to cell migration and invasion. Various isoforms of ABPs in different tissues equip cells with variable degrees of migratory and adhesive capacities. In addition, regulation of ABPs by posttranslational modifications (PTM) is pivotal to the rapid responsiveness of cells. In this context, phosphorylation of ABPs and its functional consequences have been studied extensively. However, the study of reduction/oxidation (redox) modifications of oxidation-sensitive cysteine and methionine residues of actin, ABPs, adhesion molecules, and signaling proteins regulating actin cytoskeletal dynamics has only recently emerged as a field. The relevance of such protein oxidations to cellular physiology and pathophysiology has remained largely elusive. Importantly, studying protein oxidation spatiotemporally can provide novel insights into localized redox regulation of cellular functions. In this review, we focus on the redox regulation of the actin cytoskeleton, its challenges, and recently developed tools to study its physiological and pathophysiological consequences.
Secreted Phosphoprotein 1 Expression in Retinal Mononuclear Phagocytes Links Murine to Human Choroidal Neovascularization
Authors: Schlecht Anja , Zhang Peipei , Wolf Julian , Thien Adrian , Rosmus Dennis-Dominik , Boneva Stefaniya , Schlunck Günther , Lange Clemens , Wieghofer Peter
Published: January 2021

Age-related macular degeneration (AMD) represents the most common cause of blindness in the elderly in the Western world. An impairment of the outer blood-retina barrier and a localized inflammatory microenvironment cause sprouting of choroidal neovascular membranes (CNV) in neovascular AMD that are in intimate contact with surrounding myeloid cells, such as retinal microglia, and ultimately lead to visual impairment. The discovery of novel target molecules to interfere with angiogenesis and inflammation is vital for future treatment approaches in AMD patients. To explore the transcriptional profile and the function of retinal microglia at sites of CNV, we performed a comprehensive RNA-seq analysis of retinal microglia in the mouse model of laser-induced choroidal neovascularization (mCNV). Here, we identified the angiogenic factor Osteopontin (Opn), also known as “secreted phosphoprotein 1” (Spp1), as one of the most highly expressed genes in retinal microglia in the course of CNV formation. We confirmed the presence of SPP1 at the lesion site in recruited retinal microglia in Cx3cr1CreER:Rosa26-tdTomato reporter mice by confocal microscopy and in whole retinal tissue lysates by ELISA highlighting a massive local production of SPP1. Inhibition of SPP1 by intravitreal injection of an anti-SPP1 antibody significantly increased the lesion size compared to IgG-treated control eyes. In line with our results in rodents, we found an increased SPP1 mRNA expression in surgically extracted human choroidal neovascular (hCNV) membranes by the quantitative RNA-seq approach of massive analysis of cDNA ends (MACE). Numerous IBA1+SPP1+ myeloid cells were detected in human CNV membranes. Taken together, these results highlight the importance of SPP1 in the formation of CNV and potentially offer new opportunities for therapeutic intervention by modulating the SPP1 pathway.
Mitochondrial and Sarcoplasmic Reticulum Interconnection in Cardiac Arrhythmia
Authors: Salazar-Ramírez Felipe , Ramos-Mondragón Roberto , García-Rivas Gerardo
Published: January 2021

Ca2+ plays a pivotal role in mitochondrial energy production, contraction, and apoptosis. Mitochondrial Ca2+-targeted fluorescent probes have demonstrated that mitochondria Ca2+ transients are synchronized with Ca2+ fluxes occurring in the sarcoplasmic reticulum (SR). The presence of specialized proteins tethering SR to mitochondria ensures the local Ca2+ flux between these organelles. Furthermore, communication between SR and mitochondria impacts their functionality in a bidirectional manner. Mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniplex is essential for ATP production and controlled reactive oxygen species levels for proper cellular signaling. Conversely, mitochondrial ATP ensures the proper functioning of SR Ca2+-handling proteins, which ensures that mitochondria receive an adequate supply of Ca2+. Recent evidence suggests that altered SR Ca2+ proteins, such as ryanodine receptors and the sarco/endoplasmic reticulum Ca2+ ATPase pump, play an important role in maintaining proper cardiac membrane excitability, which may be initiated and potentiated when mitochondria are dysfunctional. This recognized mitochondrial role offers the opportunity to develop new therapeutic approaches aimed at preventing cardiac arrhythmias in cardiac disease.
In vitro Characterization of Insulin−Producing β-Cell Spheroids
Authors: Ntamo Yonela , Samodien Ebrahim , Burger Joleen , Muller Nolan , Muller Christo J. F. , Chellan Nireshni
Published: January 2021

Over the years, immortalized rodent β-cell lines such as RIN, HIT, MIN, βTC, and INS-1 have been used to investigate pancreatic β-cell physiology using conventional two-dimensional (2D) culture techniques. However, physical and physiological limitations inherent to 2D cell culture necessitates confirmatory follow up studies using sentient animals. Three-dimensional (3D) culture models are gaining popularity for their recapitulation of key features of in vivo organ physiology, and thus could pose as potential surrogates for animal experiments. In this study, we aimed to develop and characterize a rat insulinoma INS-1 3D spheroid model to compare with 2D monolayers of the same cell line. Ultrastructural verification was done by transmission electron microscopy and toluidine blue staining, which showed that both 2D monolayers and 3D spheroids contained highly granulated cells with ultrastructural features synonymous with mature pancreatic β-cells, with increased prominence of these features observed in 3D spheroids. Viability, as assessed by cellular ATP quantification, size profiling and glucose utilization, showed that our spheroids remained viable for the experimental period of 30 days, compared to the limiting 5-day passage period of INS-1 monolayers. In fact, increasing ATP content together with spheroid size was observed over time, without adverse changes in glucose utilization. Additionally, β-cell function, assessed by determining insulin and amylin secretion, showed that the 3D spheroids retained glucose sensing and insulin secretory capability, that was more acute when compared to 2D monolayer cultures. Thus, we were able to successfully demonstrate that our in vitro INS-1 β-cell 3D spheroid model exhibits in vivo tissue-like structural features with extended viability and lifespan. This offers enhanced predictive capacity of the model in the study of metabolic disease, β-cell pathophysiology and the potential treatment thereof.
Exploring the Effect of Differentially Expressed Long Non-coding RNAs Driven by Copy Number Variation on Competing Endogenous RNA Network by Mining Lung Adenocarcinoma Data
Authors: Hu Huihui , Xu Hangdi , Lu Fen , Zhang Jisong , Xu Li , Xu Shan , Jiang Hanliang , Zeng Qingxin , Chen Enguo , He Zhengfu
Published: January 2021

Lung cancer is the first cause of cancer death, and gene copy number variation (CNV) is a vital cause of lung cancer progression. Prognosis prediction of patients followed by medication guidance by detecting CNV of lung cancer is emerging as a promising precise treatment in the future. In this paper, the differences in CNV and gene expression between cancer tissue and normal tissue of lung adenocarcinoma (LUAD) from The Cancer Genome Atlas Lung Adenocarcinoma data set were firstly analyzed, and greater differences were observed. Furthermore, CNV-driven differentially expressed long non-coding RNAs (lncRNAs) were screened out, and then, a competing endogenous RNA (ceRNA) regulatory network related to the gene CNV was established, which involved 9 lncRNAs, seven microRNAs, and 178 downstream messenger RNAs (mRNAs). Pathway enrichment analyses sequentially performed revealed that the downstream mRNAs were mainly enriched in biological pathways related to cell division, DNA repair, and so on, indicating that these mRNAs mainly affected the replication and growth of tumor cells. Besides, the relationship between lncRNAs and drug effects was explored based on previous studies, and it was found that LINC00511 and LINC00942 in the CNV-associated ceRNA network could be used to determine tumor response to drug treatment. As examined, the drugs affected by these two lncRNAs mainly targeted metabolism, target of rapamycin signaling pathway, phosphatidylinositol-3-kinase signaling pathway, epidermal growth factor receptor signaling pathway, and cell cycle. In summary, the present research was devoted to analyzing CNV, lncRNA, mRNA, and microRNA of lung cancer, and nine lncRNAs that could affect the CNV-associated ceRNA network we constructed were identified, two of which are promising in determining tumor response to drug treatment.
Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients
Authors: Li Jiaxing , Qi Jia , Yao Guangxin , Zhu Qinling , Li Xinyu , Xu Rui , Zhu Zhenyi , Zhao Hanting , Wang Yuan , Ding Ying , Sun Yun
Published: January 2021

Decidualization is driven by differentiation of human endometrial stromal cells (ESCs), and is a prerequisite for successful implantation and establishment of pregnancy. The critical role of impaired decidualization in women suffered recurrent implantation failure (RIF) has been established, while the underlying mechanism is poorly understood. In the present study, we verified the essential role of Sirtuin1 (SIRT1) in regulating differentiation and maintaining reactive oxygen species (ROS) homeostasis of human ESCs during decidualization. The abundance of SIRT1 was decreased in RIF patients both in the endometria during window of implantation phase and in the decidualized ESCs. Downregulation of SIRT1 disrupted the intracellular ROS homeostasis during decidualization of ESC, manifested as the accumulation of intracellular ROS level and the reduction of antioxidant stress molecules. Elimination of ROS with N-acetyl-L-cysteine (NAC) could rescued the decidualization inhibition caused by SIRT1 knockdown. Further, we explored the insufficient expression of SIRT1 in ESC affected the deacetylation of forkhead box O1 (FOXO1), and thus inhibited the transcriptional activity of FOXO1. This could account for the dysregulation of intracellular ROS homeostasis during decidualization and decreased expression of decidual markers. Collectively, our findings provided insight into the role of down-regulated SIRT1 in the poor decidual response of ESCs in RIF patients.
Hypoxia in Cell Reprogramming and the Epigenetic Regulations
Authors: Nakamura Nariaki , Shi Xiaobing , Darabi Radbod , Li Yong
Published: January 2021

Cellular reprogramming is a fundamental topic in the research of stem cells and molecular biology. It is widely investigated and its understanding is crucial for learning about different aspects of development such as cell proliferation, determination of cell fate and stem cell renewal. Other factors involved during development include hypoxia and epigenetics, which play major roles in the development of tissues and organs. This review will discuss the involvement of hypoxia and epigenetics in the regulation of cellular reprogramming and how interplay between each factor can contribute to different cellular functions as well as tissue regeneration.
Mitochondria-Associated Endoplasmic Reticulum Membranes in Breast Cancer
Authors: Yu Hongjiao , Sun Chaonan , Gong Qing , Feng Du
Published: January 2021

Mitochondria-associated ER membranes (MAMs) represent a crucial intracellular signaling hub, that regulates various cellular events including Ca2+ homeostasis, lipid metabolism, mitochondrial function, and cellular survival and death. All of these MAM-mediated cellular events contribute to carcinogenesis. Indeed, altered functions of MAMs in several types of cancers have been documented, in particular for breast cancer. Over the past years, altered expression of many MAM-resident proteins have been reported in breast cancer. These MAM-resident proteins play an important role in regulation of breast cancer initiation and progression. In the current review, we discuss our current knowledge about the functions of MAMs, and address the underlying mechanisms through which MAM-resident proteins regulate breast cancer. A fuller understanding of the pathways through which MAMs regulate breast cancer, and identification of breast cancer-specific MAM-resident proteins may help to develop novel therapeutic strategies for breast cancer.
The p38MAPK-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission
Authors: Beamer Edward , Corrêa Sonia A. L.
Published: January 2021

p38 is a mitogen-activated protein kinase (MAPK), that responds primarily to stress stimuli. p38 has a number of targets for phosphorylation, including MAPK-activated protein kinase 2 (MK2). MK2 primarily functions as a master regulator of RNA-binding proteins, indirectly controlling gene expression at the level of translation. The role of MK2 in regulating the synthesis of pro-inflammatory cytokines downstream of inflammation and cellular stress is well-described. A significant amount of evidence, however, now points to a role for the p38MAPK-MK2 signaling axis in mediating synaptic plasticity through control of AMPA receptor trafficking and the morphology of dendritic spines. These processes are mediated through control of cytoskeletal dynamics via the activation of cofilin-1 and possibly control of the expression of Arc/Arg3.1. There is evidence that MK2 is necessary for group I metabotropic glutamate receptors long-term depression (mGluR-LTD). Disruption of this signaling may play an important role in mediating cognitive dysfunction in neurological disorders such as fragile X syndrome and Alzheimer’s disease. To date, the role of neuronal MK2 mediating synaptic plasticity in response to inflammatory stimuli has not yet been investigated. In immune cells, it is clear that MK2 is phosphorylated following activation of a broad range of cell surface receptors for cytokines and other inflammatory mediators. We propose that neuronal MK2 may be an important player in the link between inflammatory states and dysregulation of synaptic plasticity underlying cognitive functions. Finally, we discuss the potential of the p38MAPK-MK2 signaling axis as target for therapeutic intervention in a number of neurological disorders.
Representative Pores: An Efficient Method to Characterize Activated Carbons
Authors: de Oliveira Jose Carlos Alexandre , Galdino Ana Luisa , Gonçalves Daniel V , Silvino Pedro F. G. , Cavalcante Celio L. , Bastos-Neto Moises , Azevedo Diana C.S. , Lucena Sebastiao M. P.
Published: January 2021

We propose a pore size analysis methodology for carbonaceous materials that reduces complexity while maintaining the significant elements of the structure-property relationship. This method chooses a limited number of representative pores, which will constitute a simplified kernel to describe the pore size distribution (PSD) of an activated carbon. In this study we use the representative pore sizes of 7.0, 8.9, 18.5, and 27.9 Å and N2 isotherms at 77.4 K to determine the PSD which is later applied to predict the adsorption equilibrium of other gases. In this study we demonstrate the ability to predict adsorption of different gas molecules on activated carbon from the PSD generated with representative pores (PSDrep). The methodology allows quick solutions for large-scale calculations for carbonaceous materials screening, in addition to make accessible an easily understood and prompt evaluation of the structure-property relationship of activated carbons. In addition to the details of the methodology already tested in different fields of application of carbonaceous materials, we present a new application related to the removal of organic contaminants in dilute aqueous solutions.
Copper Recovery From Ammonia Solutions Through Electro-Electrodialysis (EED)
Authors: Garrido Belen , Cifuentes Gerardo , Fredes Pedro , Pino Eduardo , Calderón Cristian , Cifuentes-Cabezas Magdalena
Published: January 2021

Alkaline leaching with highly selective ammoniacal complexing agents is an interesting alternative for the treatment of copper concentrates. This treatment is beneficial for copper recovery because it allows the formation of soluble amines complexes, with cupric tetramine ( Cu(NH3)42+) being the most stable. In order to suppress the unit operation of solvent extraction (SX) and move directly to the electrochemical process, an electro-electrodialysis (EED) process using ion exchange membranes to obtain copper is proposed. The study contemplates the operation with synthetic ammonia solutions containing copper at different concentrations and current density under standard conditions of pressure and temperature. The presented data demonstrate that the concentration of copper in the solution and the excess of ammonia are inversely related to the efficiency of the current and the voltage of the cell, whereas an increase in current density causes an increase in current efficiency, contrary to what happens in sulfuric systems.
Synthesis and Characterization of Macrocyclic Chiral Tröger’s Base Phenhomazine Candidates as Anticancer Agent
Authors: Ibrahim Alhussein A. , Ali Korany A. , Hafez Naglaa A. Abdel , Elsayed Mohamed A. , Mohamed Khalid M. H. , Hosni Hanaa M. , Amr Abd El-Galil E. , Elsayed Elsayed A.
Published: January 2021

1,4,7,10-Tetraoxa[10](2,8)trögerophane 5 was synthesized from its corresponding precursors. Heating of 2 with p-nitrophenoxide afforded bis(p-nitrophenyl)ether 3, which was treated with hydrazine hydrate to give bis(p-aminophenyl)ether 4. Treatment of 4 with paraformaldehyde and triflouroacetic anhydride gave trögerophane 5. Reaction of 5 with trifluroacetic anhydride afforded phenhomazine derivative 6, which was treated with potassium carbonate to afford tetrahydrophenhomazine 7. Finally, reaction of 7 with phenacylchloride, bromoacetic acid, or ethyl bromoacetate in the presence of triethyl amine under reflux, afforded the corresponding macrocyclic compounds 8, 9 and 10, respectively. The synthesized trögerophane,precursors and its newly synthesized phenhomazines derivatives were screened for anticancer activity. Results revealed that 1,4,7,10-tetraoxa[10](2,8)trögerophane had a promising selectivity towards colon cancer cell line with an IC50 of 92.7 µg/ml.
Tsunami Hazard Evaluation for the Head of the Gulf of Elat–Aqaba, Northeastern Red Sea
Authors: Salamon Amos , Frucht Eran , Ward Steven N. , Gal Erez , Grigorovitch Marina , Shem-Tov Rachamim , Calvo Ran , Ginat Hanan
Published: January 2021

Unique geological and seismotectonic settings may trigger a multicascading hazard and should be identified beforehand. Such is the head of the Gulf of Elat–Aqaba (HGEA) at the northeastern end of the Red Sea where its geology, tectonics, bathymetry, and earthquake and tsunami history exhibit clear potential for earthquake and submarine-landslide tsunami generation. We thus investigated the possible tsunamigenic sources in the gulf and evaluated the resulting hazard at the HGEA. First, we assembled a bathymetric grid and adopted GeoClaw software to simulate most of the earthquake-tsunami scenarios. Next, we resolved the scheme of the largest possible tsunamigenic earthquakes along the deep basins of the Gulf of Elat (GEA) and the associated Dead Sea rift valley, as well as the potential tsunamigenic submarine landslides in the HGEA. The use of GeoClaw was verified against the 1995 tsunami generated by the Nuweiba Mw 7.2 earthquake, and then operated to simulate a suite of earthquake scenarios. Results showed that the marginal faults of Elat Basin pose the highest tsunami hazard to the Israeli part of the HGEA. To better assess that hazard, we screened the geology and seismotectonics of the HGEA and found that the Elat normal fault presents the worst-case scenario for Elat city. It is capable of generating a multicascading threat of earthquake and submarine-landslide tsunami, local subsidence that can increase inundation, and above all, destructive ground motion. Scenarios of a tsunami caused by the worst-case earthquake on the Elat fault simulated by GeoClaw and Ward’s (Tsunami, The encyclopedia of solid earth geophysics. 2011, 1473–1493) approach, and submarine landslide in the HGEA simulated by Wang et al.’s (Geophys. J. Int., 2015, 201, 1534–1544) ‘Tsunami Squares’ approach, demonstrated waves as high as 4 m along these coasts. Accordingly, we constructed a map of the evacuation zone. We also show that strong ground-shaking and retreat of the sea at the HGEA should be considered a tsunami warning, although false alarms are inevitable. Furthermore, tsunami hazard exists all along the gulf and further assessments are needed to quantify this hazard and increase awareness among the area's population.
Responding to COVID-19 With the Aid of Mutually Beneficial Partnerships in Education
Authors: Biag Manuelito , Gomez Louis M. , Imig David G. , Vasudeva Ash
Published: January 2021

The COVID-19 pandemic has altered the structures and routines of K-12 education. Districts and school systems worldwide continue to adapt their ways of working to address a variety of challenges–many of whose dimensions are complex, dynamic, and not entirely known. Without cooperation and collaboration among stakeholders, institutions, and communities, we will be less able to address students’ social, emotional, and learning needs. In this paper, we present evidence that suggests mutually beneficial partnerships between local education agencies (LEAs) and institutions of higher education (IHEs), grounded in improvement science, can serve as an essential resource to address dilemmas brought about by the pandemic. We examine the work of four partnerships in the Improvement Leadership Education and Development (iLEAD) Network. Our analysis suggests that what matters in this period of uncertainty is that partnerships take a systems perspective, pay direct attention to the needs of critical users, avoid pre-determined programs and solutions, and engage in disciplined inquiry across institutional boundaries to affect positive and lasting change. A deeper understanding of how these partnerships operate–their principles, routines, methods, and tools–can help educational systems support students during the current global health crisis.
Detecting Resource Limitation in a Large Herbivore Population Is Enhanced With Measures of Nutritional Condition
Authors: Oates Brendan A. , Monteith Kevin L. , Goheen Jacob R. , Merkle Jerod A. , Fralick Gary L. , Kauffman Matthew J.
Published: January 2021

Resource limitation at the population level is a function of forage quality and its abundance relative to its per capita availability, which in turn, determines nutritional condition of individuals. Effects of resource limitation on population dynamics in ungulates often occur through predictable and sequential changes in vital rates, which can enable assessments of how resource limitation influences population growth. We tested theoretical predictions of bottom-up (i.e., resource limitation) forcing on moose (Alces alces) through the lens of vital rates by quantifying the relative influence of intrinsic measures of nutritional condition and extrinsic measures of remotely sensed environmental data on demographic rates. We measured rates of pregnancy, parturition, juvenile, and adult survival for 82 adult females in a population where predators largely were absent. Life stage simulation analyses (LSAs) indicated that interannual fluctuations in adult survival contributed to most of the variability in λ. We then extended the LSA to estimate vital rates as a function of bottom-up covariates to evaluate their influence on λ. We detected weak signatures of effects from environmental covariates that were remotely sensed and spatially explicit to each seasonal range. Instead, nutritional condition strongly influenced rates of pregnancy, parturition, and overwinter survival of adults, clearly implicating resource limitation on λ. Our findings depart from the classic life-history paradigm of population dynamics in ungulates in that adult survival was highly variable and generated most of the variability in population growth rates. At the surface, lack of variation explained by environmental covariates may suggest weak evidence of resource limitation in the population, when nutritional condition actually underpinned most demographics. We suggest that variability in vital rates and effects of resource limitation may depend on context more than previously appreciated, and density dependence can obfuscate the relationships between remotely sensed data and demographic rates.
Assessing the Role of Selected Osmolytes in Mediterranean High-Mountain Specialists
Authors: Magaña Ugarte Rosina , Escudero Adrián , Gavilán Rosario G.
Published: January 2021

Despite the constraining weight of summer drought over plant life which distinguishes Mediterranean high-mountains, and its anticipated exacerbation under the current climate crisis, there is still little knowledge of the underlying drought-endurance mechanisms in Mediterranean high-mountain species, such as osmolyte accumulation. To fill this gap, we studied the role of two of the most frequent osmoregulators in plants, proline and osmotically active carbohydrates (OAC), as pointers of the drought-stress response in seven high-mountain plant species representative of the high-mountain plant communities in Central Spain, along an elevation gradient. Overall, our results are consistent with the escalation of summer drought and suggest the involvement of osmolytes to sustain plant activity in these specialists during the growing season. Proline content showed a steadily increasing pattern in line with the seasonal aggravation of summer drought. The significant rise in mean proline in most species, coinciding with the periods with the greatest decline in soil water content, suggests the recurrent role of proline in the drought-stress response in the studied specialists. The lack of significant differences between elevations and the minimal seasonal variations in the OAC content suggest a fixed OAC content independent of functional type to sustain metabolic functions under summer drought. Moreover, these findings allow inferring the action of both OAC and proline as osmoregulators, allowing to support plant functions in these specialists under atypically dry conditions. Overall, our findings are consistent with proline as a major osmoprotectant strategy over OAC buildup in these specialists, which may be related to an adaptation strategy associated with the briefness of the growing season and the incidence of less favorable conditions in Mediterranean high-mountains.
The Development of Arthropod Segmentation Across the Embryonic/Post-embryonic Divide – An Evolutionary Perspective
Authors: Fusco Giuseppe , Minelli Alessandro
Published: January 2021

In many arthropods, the appearance of new segments and their differentiation are not completed by the end of embryogenesis but continue, in different form and degree, well after hatching, in some cases up to the last post-embryonic molt. Focusing on the segmentation process currently described as post-embryonic segment addition (or, anamorphosis), we revise here the current knowledge and discuss it in an evolutionary framework which involves data from fossils, comparative morphology of extant taxa and gene expression. We advise that for a better understanding of the developmental changes underlying the evolution of arthropod segmentation, some key concepts should be applied in a critical way. These include the notion of the segment as a body block and the idea that hatching represents a well-defined divide, shared by all arthropods, between two contrasting developmental phases, embryonic vs. post-embryonic. This eventually reveals the complexity of the developmental processes occurring across hatching, which can evolve in different directions and with a different pace, creating the observed vagueness of the embryonic/post-embryonic divide.
Computational Method for Classification of Avian Influenza A Virus Using DNA Sequence Information and Physicochemical Properties
Authors: Humayun Fahad , Khan Fatima , Fawad Nasim , Shamas Shazia , Fazal Sahar , Khan Abbas , Ali Arif , Farhan Ali , Wei Dong-Qing
Published: January 2021

Accurate and fast characterization of the subtype sequences of Avian influenza A virus (AIAV) hemagglutinin (HA) and neuraminidase (NA) depends on expanding diagnostic services and is embedded in molecular epidemiological studies. A new approach for classifying the AIAV sequences of the HA and NA genes into subtypes using DNA sequence data and physicochemical properties is proposed. This method simply requires unaligned, full-length, or partial sequences of HA or NA DNA as input. It allows for quick and highly accurate assignments of HA sequences to subtypes H1–H16 and NA sequences to subtypes N1–N9. For feature extraction, k-gram, discrete wavelet transformation, and multivariate mutual information were used, and different classifiers were trained for prediction. Four different classifiers, Naïve Bayes, Support Vector Machine (SVM), K nearest neighbor (KNN), and Decision Tree, were compared using our feature selection method. This comparison is based on the 30% dataset separated from the original dataset for testing purposes. Among the four classifiers, Decision Tree was the best, and Precision, Recall, F1 score, and Accuracy were 0.9514, 0.9535, 0.9524, and 0.9571, respectively. Decision Tree had considerable improvements over the other three classifiers using our method. Results show that the proposed feature selection method, when trained with a Decision Tree classifier, gives the best results for accurate prediction of the AIAV subtype.
Clinical Perspectives on Liquid Biopsy in Metastatic Colorectal Cancer
Authors: Gao Wei , Chen Yigui , Yang Jianwei , Zhuo Changhua , Huang Sha , Zhang Hui , Shi Yi
Published: January 2021

Liquid biopsy, which generally refers to the analysis of biological components such as circulating nuclear acids and circulating tumor cells in body fluids, particularly in peripheral blood, has shown good capacity to overcome several limitations faced by conventional tissue biopsies. Emerging evidence in recent decades has confirmed the promising role of liquid biopsy in the clinical management of various cancers, including colorectal cancer, which is one of the most prevalent cancers and the second leading cause of cancer-related deaths worldwide. Despite the challenges and poor clinical outcomes, patients with metastatic colorectal cancer can expect potential clinical benefits with liquid biopsy. Therefore, in this review, we focus on the clinical prospects of liquid biopsy in metastatic colorectal cancer, specifically with regard to the recently discovered various biomarkers identified on liquid biopsy. These biomarkers have been shown to be potentially useful in multiple aspects of metastatic colorectal cancer, such as auxiliary diagnosis of metastasis, prognosis prediction, and monitoring of therapy response.
A Review of Genetic and Physiological Disease Mechanisms Associated With Cav1 Channels: Implications for Incomplete Congenital Stationary Night Blindness Treatment
Authors: Sadeh Tal T. , Black Graeme C. , Manson Forbes
Published: January 2021

Calcium channels are crucial to a number of cellular functions. The high voltage-gated calcium channel family comprise four heteromeric channels (Cav1.1-1.4) that function in a similar manner, but that have distinct expression profiles. Three of the pore-forming α1 subunits are located on autosomes and the forth on the X chromosome, which has consequences for the type of pathogenic mutation and the disease mechanism associated with each gene. Mutations in this family of channels are associated with malignant hyperthermia (Cav1.1), various QT syndromes (Cav1.2), deafness (Cav1.3), and incomplete congenital stationary night blindness (iCSNB; Cav1.4). In this study we performed a bioinformatic analysis on reported mutations in all four Cav α1 subunits and correlated these with variant frequency in the general population, phenotype and the effect on channel conductance to produce a comprehensive composite Cav1 mutation analysis. We describe regions of mutation clustering, identify conserved residues that are mutated in multiple family members and regions likely to cause a loss- or gain-of-function in Cav1.4. Our research highlights that therapeutic treatments for each of the Cav1 channels will have to consider channel-specific mechanisms, especially for the treatment of X-linked iCSNB.
Case Report: Therapeutic Response to Chemo-Immunotherapy in an Advanced Large Cell Lung Carcinoma Patient With Low Values of Multiple Predictive Biomarkers
Authors: Wang Guihua , Chai Qin , Xiao Yajie , Peng Wenying , Teng Miao , Wang Jingyi , Lin Hanqing , Su Xiaofan , Wu Lin
Published: January 2021

Immune checkpoint inhibitors have revolutionized the treatments of lung cancers, and multiple predictive biomarkers alone or in combination help clinicians with the appropriate therapeutic selections. Recently, chemo-immunotherapy has been recommended for treating advanced non-small cell lung cancers in patients without driver mutations. However, the clinical relevance of predictive biomarkers and the treatment efficacy of chemo-immunotherapy in large cell lung carcinoma (LCLC) remain unclear. Here, we reported a rare case of LCLC with none driver gene mutations and low values of multiple predictive biomarkers. These biomarkers included a low PD-L1 expression of 5–10%, a low tumor mutational burden (TMB) of 2.5 muts/mb, a low CD8(+) tumor-infiltrating lymphocyte density of 147.91 psc/mm². After one-cycle chemotherapy, the patient progressed rapidly and then was switched to pembrolizumab combining paclitaxel plus cisplatin. Interestingly, he achieved a partial response after two cycles of chemo-immunotherapy, showing multiple lymph nodes obviously shrunk on CT scan, and other clinical symptoms were relieved when compared with the baseline findings. After five cycles of chemo-immunotherapy, this advanced patient still benefited and was changed to maintenance immunotherapy monotherapy. This case suggests that chemo-immunotherapy may provide an effective therapeutic option for those LCLC patients with low values of multiple predictive biomarkers, particularly for those who progressed from first-line classical treatments.