bluuebunny/crossref_metadata_2025 huggingface dataset:
New Potential Biomarkers for Chronic Kidney Disease Management—A Review of the Literature
Authors: Lousa Irina , Reis Flávio , Beirão Idalina , Alves Rui , Belo Luís , Santos-Silva Alice
Published: December 2020

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and the mortality rate continues to be unacceptably high. The biomarkers currently used in clinical practice are considered relevant when there is already significant renal impairment compromising the early use of potentially successful therapeutic interventions. More sensitive and specific biomarkers to detect CKD earlier on and improve patients’ prognoses are an important unmet medical need. The aim of this review is to summarize the recent literature on new promising early CKD biomarkers of renal function, tubular lesions, endothelial dysfunction and inflammation, and on the auspicious findings from metabolomic studies in this field. Most of the studied biomarkers require further validation in large studies and in a broad range of populations in order to be implemented into routine CKD management. A panel of biomarkers, including earlier biomarkers of renal damage, seems to be a reasonable approach to be applied in clinical practice to allow earlier diagnosis and better disease characterization based on the underlying etiologic process.
Initiators of Classical and Lectin Complement Pathways Are Differently Engaged after Traumatic Brain Injury—Time-Dependent Changes in the Cortex, Striatum, Thalamus and Hippocampus in a Mouse Model
Authors: Ciechanowska Agata , Ciapała Katarzyna , Pawlik Katarzyna , Oggioni Marco , Mercurio Domenico , De Simoni Maria-Grazia , Mika Joanna
Published: December 2020

The complement system is involved in promoting secondary injury after traumatic brain injury (TBI), but the roles of the classical and lectin pathways leading to complement activation need to be clarified. To this end, we aimed to determine the ability of the brain to activate the synthesis of classical and lectin pathway initiators in response to TBI and to examine their expression in primary microglial cell cultures. We have modeled TBI in mice by controlled cortical impact (CCI), a clinically relevant experimental model. Using Real-time quantitative polymerase chain reaction (RT-qPCR) we analyzed the expression of initiators of classical the complement component 1q, 1r and 1s (C1q, C1r, and C1s) and lectin (mannose binding lectin A, mannose binding lectin C, collectin 11, ficolin A, and ficolin B) complement pathways and other cellular markers in four brain areas (cortex, striatum, thalamus and hippocampus) of mice exposed to CCI from 24 h and up to 5 weeks. In all murine ipsilateral brain structures assessed, we detected long-lasting, time- and area-dependent significant increases in the mRNA levels of all classical (C1q, C1s, C1r) and some lectin (collectin 11, ficolin A, ficolin B) initiator molecules after TBI. In parallel, we observed significantly enhanced expression of cellular markers for neutrophils (Cd177), T cells (Cd8), astrocytes (glial fibrillary acidic protein—GFAP), microglia/macrophages (allograft inflammatory factor 1—IBA-1), and microglia (transmembrane protein 119—TMEM119); moreover, we detected astrocytes (GFAP) and microglia/macrophages (IBA-1) protein level strong upregulation in all analyzed brain areas. Further, the results obtained in primary microglial cell cultures suggested that these cells may be largely responsible for the biosynthesis of classical pathway initiators. However, microglia are unlikely to be responsible for the production of the lectin pathway initiators. Immunofluorescence analysis confirmed that at the site of brain injury, the C1q is localized in microglia/macrophages and neurons but not in astroglial cells. In sum, the brain strongly reacts to TBI by activating the local synthesis of classical and lectin complement pathway activators. Thus, the brain responds to TBI with a strong, widespread and persistent upregulation of complement components, the targeting of which may provide protection in TBI.
Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (H2S) in Hemolytic and Hemorrhagic Vascular Disorders—Interaction between the Heme Oxygenase and H2S-Producing Systems
Authors: Gáll Tamás , Pethő Dávid , Nagy Annamária , Balla György , Balla József
Published: December 2020

Over the past decades, substantial work has established that hemoglobin oxidation and heme release play a pivotal role in hemolytic/hemorrhagic disorders. Recent reports have shown that oxidized hemoglobins, globin-derived peptides, and heme trigger diverse biological responses, such as toll-like receptor 4 activation with inflammatory response, reprogramming of cellular metabolism, differentiation, stress, and even death. Here, we discuss these cellular responses with particular focus on their mechanisms that are linked to the pathological consequences of hemorrhage and hemolysis. In recent years, endogenous gasotransmitters, such as carbon monoxide (CO) and hydrogen sulfide (H2S), have gained a lot of interest in connection with various human pathologies. Thus, many CO and H2S-releasing molecules have been developed and applied in various human disorders, including hemolytic and hemorrhagic diseases. Here, we discuss our current understanding of oxidized hemoglobin and heme-induced cell and tissue damage with particular focus on inflammation, cellular metabolism and differentiation, and endoplasmic reticulum stress in hemolytic/hemorrhagic human diseases, and the potential beneficial role of CO and H2S in these pathologies. More detailed mechanistic insights into the complex pathology of hemolytic/hemorrhagic diseases through heme oxygenase-1/CO as well as H2S pathways would reveal new therapeutic approaches that can be exploited for clinical benefit.
Flow Cytometry Analysis of Circulating Extracellular Vesicle Subtypes from Fresh Peripheral Blood Samples
Authors: Marchisio Marco , Simeone Pasquale , Bologna Giuseppina , Ercolino Eva , Pierdomenico Laura , Pieragostino Damiana , Ventrella Alessia , Antonini Francesca , Del Zotto Genny , Vergara Daniele , Celia Christian , Di Marzio Luisa , Del Boccio Piero , Fontana Antonella , Bosco Domenico , Miscia Sebastiano , Lanuti Paola
Published: December 2020

Extracellular vesicles (EVs) are released by shedding during different physiological processes and are increasingly thought to be new potential biomarkers. However, the impact of pre-analytical processing phases on the final measurement is not predictable and for this reason, the translation of basic research into clinical practice has been precluded. Here we have optimized a simple procedure in combination with polychromatic flow cytometry (PFC), to identify, classify, enumerate, and separate circulating EVs from different cell origins. This protocol takes advantage of a lipophilic cationic dye (LCD) able to probe EVs. Moreover, the application of the newly optimized PFC protocol here described allowed the obtainment of repeatable EVs counts. The translation of this PFC protocol to fluorescence-activated cell sorting allowed us to separate EVs from fresh peripheral blood samples. Sorted EVs preparations resulted particularly suitable for proteomic analyses, which we applied to study their protein cargo. Here we show that LCD staining allowed PFC detection and sorting of EVs from fresh body fluids, avoiding pre-analytical steps of enrichment that could impact final results. Therefore, LCD staining is an essential step towards the assessment of EVs clinical significance.
The Aryl Hydrocarbon Receptor in Energy Balance: The Road from Dioxin-Induced Wasting Syndrome to Combating Obesity with Ahr Ligands
Authors: Girer Nathaniel G. , Tomlinson Craig R. , Elferink Cornelis J.
Published: December 2020

The aryl hydrocarbon receptor (AHR) has been studied for over 40 years, yet our understanding of this ligand-activated transcription factor remains incomplete. Each year, novel findings continually force us to rethink the role of the AHR in mammalian biology. The AHR has historically been studied within the context of potent activation via AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with a focus on how the AHR mediates TCDD toxicity. Research has subsequently revealed that the AHR is actively involved in distinct physiological processes ranging from the development of the liver and reproductive organs, to immune system function and wound healing. More recently, the AHR was implicated in the regulation of energy metabolism and is currently being investigated as a potential therapeutic target for obesity. In this review, we re-trace the steps through which the early toxicological studies of TCDD led to the conceptual framework for the AHR as a potential therapeutic target in metabolic disease. We additionally discuss the key discoveries that have been made concerning the role of the AHR in energy metabolism, as well as the current and future directions of the field.
Fake It ‘Till You Make It—The Pursuit of Suitable Membrane Mimetics for Membrane Protein Biophysics
Authors: Thoma Johannes , Burmann Björn M.
Published: December 2020

Membrane proteins evolved to reside in the hydrophobic lipid bilayers of cellular membranes. Therefore, membrane proteins bridge the different aqueous compartments separated by the membrane, and furthermore, dynamically interact with their surrounding lipid environment. The latter not only stabilizes membrane proteins, but directly impacts their folding, structure and function. In order to be characterized with biophysical and structural biological methods, membrane proteins are typically extracted and subsequently purified from their native lipid environment. This approach requires that lipid membranes are replaced by suitable surrogates, which ideally closely mimic the native bilayer, in order to maintain the membrane proteins structural and functional integrity. In this review, we survey the currently available membrane mimetic environments ranging from detergent micelles to bicelles, nanodiscs, lipidic-cubic phase (LCP), liposomes, and polymersomes. We discuss their respective advantages and disadvantages as well as their suitability for downstream biophysical and structural characterization. Finally, we take a look at ongoing methodological developments, which aim for direct in-situ characterization of membrane proteins within native membranes instead of relying on membrane mimetics.
Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model
Authors: Zhu Sheng , Häussling Victor , Aspera-Werz Romina H. , Chen Tao , Braun Bianca , Weng Weidong , Histing Tina , Nussler Andreas K.
Published: December 2020

Co-culture models have become mandatory for obtaining better insights into bone homeostasis, which relies on the balance between osteoblasts and osteoclasts. Cigarette smoking (CS) has been proven to increase the risk of osteoporosis; however, there is currently no proven treatment for osteoporosis in smokers excluding cessation. Bisphosphonates (BPs) are classical anti-osteoclastic drugs that are commonly used in examining the suitability of bone co-culture systems in vitro as well as to verify the response to osteoporotic stimuli. In the present study, we tested the effects of BPs on cigarette smoke extract (CSE)-affected cells in the co-culture of osteoblasts and osteoclasts. Our results showed that BPs were able to reduce CSE-induced osteoporotic alterations in the co-culture of osteoblasts and osteoclasts such as decreased matrix remodeling, enhanced osteoclast activation, and an up-regulated receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/osteoprotegerin (OPG) ratio. In summary, BPs may be an effective alternative therapy for reversing osteoporotic alterations in smokers, and the potential mechanism is through modulation of the RANKL/OPG ratio.
Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs
Authors: Nelson Corey R. , Mrozowich Tyler , Park Sean M. , D’souza Simmone , Henrickson Amy , Vigar Justin R. J. , Wieden Hans-Joachim , Owens Raymond J. , Demeler Borries , Patel Trushar R.
Published: December 2020

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17135–555 interacting with and unwinding RVFV non-coding regions.
T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes
Authors: Gong Jialei , Zeng Qunxiong , Yu Di , Duan Yong-Gang
Published: December 2020

The immune privilege of the testes is necessary to prevent immune attacks to gamete-specific antigens and paternal major histocompatibility complex (MHC) antigens, allowing for normal spermatogenesis. However, infection and inflammation of the male genital tract can break the immune tolerance and represent a significant cause of male infertility. Different T cell subsets have been identified in mammalian testes, which may be involved in the maintenance of immune tolerance and pathogenic immune responses in testicular infection and inflammation. We reviewed the evidence in the published literature on different T subtypes (regulatory T cells, helper T cells, cytotoxic T cells, γδ T cells, and natural killer T cells) in human and animal testes that support their regulatory roles in infertility and the orchitis pathology. While many in vitro studies have indicated the regulation potential of functional T cell subsets and their possible interaction with Sertoli cells, Leydig cells, and spermatogenesis, both under physiological and pathological processes, there have been no in situ studies to date. Nevertheless, the normal distribution and function of T cell subsets are essential for the immune privilege of the testes and intact spermatogenesis, and T cell-mediated immune response drives testicular inflammation. The distinct function of different T cell subsets in testicular homeostasis and the orchitis pathology suggests a considerable potential of targeting specific T cell subsets for therapies targeting chronic orchitis and immune infertility.
Extended Interactions between HIV-1 Viral RNA and tRNALys3 Are Important to Maintain Viral RNA Integrity
Authors: Gremminger Thomas , Song Zhenwei , Ji Juan , Foster Avery , Weng Kexin , Heng Xiao
Published: December 2020

The reverse transcription of the human immunodeficiency virus 1 (HIV-1) initiates upon annealing of the 3′-18-nt of tRNALys3 onto the primer binding site (PBS) in viral RNA (vRNA). Additional intermolecular interactions between tRNALys3 and vRNA have been reported, but their functions remain unclear. Here, we show that abolishing one potential interaction, the A-rich loop: tRNALys3 anticodon interaction in the HIV-1 MAL strain, led to a decrease in viral infectivity and reduced the synthesis of reverse transcription products in newly infected cells. In vitro biophysical and functional experiments revealed that disruption of the extended interaction resulted in an increased affinity for reverse transcriptase (RT) and enhanced primer extension efficiency. In the absence of deoxyribose nucleoside triphosphates (dNTPs), vRNA was degraded by the RNaseH activity of RT, and the degradation rate was slower in the complex with the extended interaction. Consistently, the loss of vRNA integrity was detected in virions containing A-rich loop mutations. Similar results were observed in the HIV-1 NL4.3 strain, and we show that the nucleocapsid (NC) protein is necessary to promote the extended vRNA: tRNALys3 interactions in vitro. In summary, our data revealed that the additional intermolecular interaction between tRNALys3 and vRNA is likely a conserved mechanism among various HIV-1 strains and protects the vRNA from RNaseH degradation in mature virions.
Butyrate and Propionate Restore the Cytokine and House Dust Mite Compromised Barrier Function of Human Bronchial Airway Epithelial Cells
Authors: Richards Levi B. , Li Meng , Folkerts Gert , Henricks Paul A.J. , Garssen Johan , van Esch Betty C.A.M.
Published: December 2020

Barrier dysfunction of airway epithelium contributes to the development of allergies, airway hyper-responsiveness and immunological respiratory diseases. Short-chain fatty acids (SCFA) enhance and restore the barrier function of the intestinal epithelium. This study investigated whether acetate, propionate and butyrate enhance the integrity of bronchial epithelial cells. Differentiating human bronchial epithelial cells (16HBE) grown on transwells were exposed to butyrate, propionate and acetate while trans-epithelial electrical resistance was monitored over time. Restorative effects of SCFA were investigated by subsequent incubation of cells with IL-4, IL-13 or house dust mite extract and SCFA. SCFA effects on IL-4-induced cytokine production and the expression of zonula occludens-1 (ZO-1) and Mitogen-activated protein kinases (MAPK) signalling pathways were investigated by ELISA and Western blot assays. Propionate and butyrate enhanced the barrier function of differentiating 16HBE cells and induced complete recovery of the barrier function after exposure to the above-mentioned stimuli. Butyrate decreased IL-4-induced IL-6 production. IL-4 decreased ZO-1 protein expression and induced phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in 16HBE cells, both of which could be restored by SCFA. SCFA showed prophylactic and restorative effects on airway epithelial barrier function, which might be induced by increased ZO-1 expression.
Fluctuating NMDA Receptor Subunit Levels in Perirhinal Cortex Relate to Their Dynamic Roles in Object Memory Destabilization and Reconsolidation
Authors: Wideman Cassidy E. , Nguyen James , Jeffries Sean D. , Winters Boyer D.
Published: December 2020

Reminder cues can destabilize consolidated memories, rendering them modifiable before they return to a stable state through the process of reconsolidation. Older and stronger memories resist this process and require the presentation of reminders along with salient novel information in order to destabilize. Previously, we demonstrated in rats that novelty-induced object memory destabilization requires acetylcholine (ACh) activity at M1 muscarinic receptors. Other research predominantly has focused on glutamate, which modulates fear memory destabilization and reconsolidation through GluN2B- and GluN2A-containing NMDARs, respectively. In the current study, we demonstrate the same dissociable roles of GluN2B- and N2A-containing NMDARs in perirhinal cortex (PRh) for object memory destabilization and reconsolidation when boundary conditions are absent. However, neither GluN2 receptor subtype was required for novelty-induced destabilization of remote, resistant memories. Furthermore, GluN2B and GluN2A subunit proteins were upregulated selectively in PRh 24 h after learning, but returned to baseline by 48 h, suggesting that NMDARs, unlike muscarinic receptors, have only a temporary role in object memory destabilization. Indeed, activation of M1 receptors in PRh at the time of reactivation effectively destabilized remote memories despite inhibition of GluN2B-containing NMDARs. These findings suggest that cholinergic activity at M1 receptors overrides boundary conditions to destabilize resistant memories when other established mechanisms are insufficient.
Use of a Mixture of Polyols Based on Metasilicic Acid and Recycled PLA for Synthesis of Rigid Polyurethane Foams Susceptible to Biodegradation
Authors: Paciorek-Sadowska Joanna , Borowicz Marcin , Chmiel Ewelina , Lubczak Jacek
Published: December 2020

Two polyol raw materials were obtained in the conducted research, one based on metasilicic acid (MSA), the other based on poly(lactic acid) (PLA) waste. The obtained polyols were characterized in terms of their applicability for the production of rigid polyurethane foams (RPUFs). Their basic analytical properties (hydroxyl number, acid number, elemental analysis) and physicochemical properties (density, viscosity) were determined. The assumed chemical structure of the obtained new compounds was confirmed by performing FTIR and 1H NMR spectroscopic tests. Formulations for the synthesis of RPUFs were developed on the basis of the obtained research results. A mixture of polyols based on MSA and PLA in a weight ratio of 1:1 was used as the polyol component in the polyurethane formulation. The reference foam in these tests was a foam that was synthesized only on the basis of MSA-polyol. The obtained RPUFs were tested for basic functional properties (apparent density, compressive strength, water absorption, thermal conductivity coefficient etc.). Susceptibility to biodegradation in soil environment was also tested. It was found that the use of mixture of polyols based on MSA and PLA positively affected the properties of the obtained foam. The polyurethane foam based on this polyol mixture showed good thermal resistance and significantly reduced flammability in comparison with the foam based MSA-polyol. Moreover, it showed higher compressive strength, lower thermal conductivity and biodegradability in soil. The results of the conducted tests confirmed that the new foam was characterized by very good performance properties. In addition, this research provides information on new waste management opportunities and fits into the doctrine of sustainable resource management offered by the circular economy.
Pathogenic Impacts of Dysregulated Polycomb Repressive Complex Function in Hematological Malignancies
Authors: Kaito Satoshi , Iwama Atsushi
Published: December 2020

Polycomb repressive complexes (PRCs) are epigenetic regulators that mediate repressive histone modifications. PRCs play a pivotal role in the maintenance of hematopoietic stem cells through repression of target genes involved in cell proliferation and differentiation. Next-generation sequencing technologies have revealed that various hematologic malignancies harbor mutations in PRC2 genes, such as EZH2, EED, and SUZ12, and PRC1.1 genes, such as BCOR and BCORL1. Except for the activating EZH2 mutations detected in lymphoma, most of these mutations compromise PRC function and are frequently associated with resistance to chemotherapeutic agents and poor prognosis. Recent studies have shown that mutations in PRC genes are druggable targets. Several PRC2 inhibitors, including EZH2-specific inhibitors and EZH1 and EZH2 dual inhibitors have shown therapeutic efficacy for tumors with and without activating EZH2 mutations. Moreover, EZH2 loss-of-function mutations appear to be attractive therapeutic targets for implementing the concept of synthetic lethality. Further understanding of the epigenetic dysregulation associated with PRCs in hematological malignancies should improve treatment outcomes.
Remodeler Catalyzed Nucleosome Repositioning: Influence of Structure and Stability
Authors: Morgan Aaron , LeGresley Sarah , Fischer Christopher
Published: December 2020

The packaging of the eukaryotic genome into chromatin regulates the storage of genetic information, including the access of the cell’s DNA metabolism machinery. Indeed, since the processes of DNA replication, translation, and repair require access to the underlying DNA, several mechanisms, both active and passive, have evolved by which chromatin structure can be regulated and modified. One mechanism relies upon the function of chromatin remodeling enzymes which couple the free energy obtained from the binding and hydrolysis of ATP to the mechanical work of repositioning and rearranging nucleosomes. Here, we review recent work on the nucleosome mobilization activity of this essential family of molecular machines.
Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements
Authors: Tagliamonte Massimiliano S. , Abid Nabil , Borocci Stefano , Sangiovanni Elisa , Ostrov David A. , Kosakovsky Pond Sergei L. , Salemi Marco , Chillemi Giovanni , Mavian Carla
Published: December 2020

Our evolutionary and structural analyses revealed that the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) spike gene is a complex mosaic resulting from several recombination events. Additionally, the fixation of variants has mainly been driven by purifying selection, suggesting the presence of conserved structural features. Our dynamic simulations identified two main long-range covariant dynamic movements of the novel glycoprotein, and showed that, as a result of the evolutionary duality, they are preserved. The first movement involves the receptor binding domain with the N-terminal domain and the C-terminal domain 2 and is maintained across human, bat and pangolin coronaviruses. The second is a complex network of long-range dynamics specific to SARS-CoV-2 involving the novel PRRA and the conserved KR*SF cleavage sites, as well as conserved segments in C-terminal domain 3. These movements, essential for host cell binding, are maintained by hinges conserved across human, bat, and pangolin coronaviruses glycoproteins. The hinges, located around Threonine 333 and Proline 527 within the N-terminal domain and C-terminal domain 2, represent candidate targets for the future development of novel pan-coronavirus inhibitors. In summary, we show that while recombination created a new configuration that increased the covariant dynamic movements of the SARS-CoV-2 glycoprotein, negative selection preserved its inter-domain structure throughout evolution in different hosts and inter-species transmissions.
MicroRNAs as Biomarkers for Nephrotic Syndrome
Authors: Tsuji Kenji , Kitamura Shinji , Wada Jun
Published: December 2020

Nephrotic syndrome represents the clinical situation characterized by presence of massive proteinuria and low serum protein caused by a variety of diseases, including minimal change nephrotic syndrome (MCNS), focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephropathy. Differentiating between diagnoses requires invasive renal biopsies in general. Even with the biopsy, we encounter difficulties to differentiate MCNS and FSGS in some cases. There is no other better option currently available for the diagnosis other than renal biopsy. MicroRNAs (miRNAs) are no-coding RNAs of approximately 20 nucleotides in length, which regulate target genes in the post-transcriptional processes and have essential roles in many diseases. MiRNAs in serum and urine have been shown as non-invasive biomarkers in multiple diseases, including renal diseases. In this article, we summarize the current knowledge of miRNAs as the promising biomarkers for nephrotic syndrome.
The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia
Authors: Romanello Vanina
Published: December 2020

Sarcopenia is a chronic disease characterized by the progressive loss of skeletal muscle mass, force, and function during aging. It is an emerging public problem associated with poor quality of life, disability, frailty, and high mortality. A decline in mitochondria quality control pathways constitutes a major mechanism driving aging sarcopenia, causing abnormal organelle accumulation over a lifetime. The resulting mitochondrial dysfunction in sarcopenic muscles feedbacks systemically by releasing the myomitokines fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), influencing the whole-body homeostasis and dictating healthy or unhealthy aging. This review describes the principal pathways controlling mitochondrial quality, many of which are potential therapeutic targets against muscle aging, and the connection between mitochondrial dysfunction and the myomitokines FGF21 and GDF15 in the pathogenesis of aging sarcopenia.
Dimensionality Reduction for Human Activity Recognition Using Google Colab
Authors: Ray Sujan , Alshouiliy Khaldoon , Agrawal Dharma P.
Published: December 2020

Human activity recognition (HAR) is a classification task that involves predicting the movement of a person based on sensor data. As we can see, there has been a huge growth and development of smartphones over the last 10–15 years—they could be used as a medium of mobile sensing to recognize human activity. Nowadays, deep learning methods are in a great demand and we could use those methods to recognize human activity. A great way is to build a convolutional neural network (CNN). HAR using Smartphone dataset has been widely used by researchers to develop machine learning models to recognize human activity. The dataset has two parts: training and testing. In this paper, we propose a hybrid approach to analyze and recognize human activity on the same dataset using deep learning method on cloud-based platform. We have applied principal component analysis on the dataset to get the most important features. Next, we have executed the experiment for all the features as well as the top 48, 92, 138, and 164 features. We have run all the experiments on Google Colab. In the experiment, for the evaluation of our proposed methodology, datasets are split into two different ratios such as 70–10–20% and 80–10–10% for training, validation, and testing, respectively. We have set the performance of CNN (70% training–10% validation–20% testing) with 48 features as a benchmark for our work. In this work, we have achieved maximum accuracy of 98.70% with CNN. On the other hand, we have obtained 96.36% accuracy with the top 92 features of the dataset. We can see from the experimental results that if we could select the features properly then not only could the accuracy be improved but also the training and testing time of the model.
Kinematics of the Ship’s Wake in the Presence of a Shear Flow
Authors: Shugan Igor , Chen Yang-Yih
Published: December 2020

We present the kinematic model of the ship wake in the presence of horizontal subsurface current linearly varying with the depth of water. An extension of the Whitham–Lighthill theory for calm water is developed. It has been established that the structure of ship waves under the action of a shear flow can radically differ from the classical Kelvin ship wake model. Co propagating ship and shear current lead to increasing the total wedge angle up to full one 180° and decreases for the counter shear current. At relatively large unidirectional values of the shear current, cusp waves in the vicinity of the wedge boundary are represented by transverse waves and, conversely, by diverging waves directed almost perpendicular to the ship track for the opposite shear current. The presence of a shear flow crossing the direction of the ship’s movement gives a strong asymmetry of the wake. An increase in the perpendicular shear flow leads to an increase in the difference between the angles of the wake arms. The limiting value of the shear current corresponds to one or both arms angles equal to 90°. Transverse and divergent edge waves for this limiting case coincide.
Clinical Management of Bile Duct Diseases: Role of Endoscopic Ultrasound in a Personalized Approach
Authors: Beyna Torsten , Gerges Christian
Published: December 2020

Biliary diseases are common, but clinical symptoms are often unspecific and direct access and visualization of the biliopancreatic system for diagnostic purpose is difficult. In the last decades endoscopic ultrasound (EUS) has become a primary method in the gastrointestinal tract. It significantly changed the role of endoscopy in diagnostic imaging in the gastrointestinal tract and adjacent organs. EUS has become an effective diagnostic tool in biliary stone disease as well as in the diagnosis of indeterminate biliary strictures. Furthermore, an EUS-directed transmural approach emerged as a safe and effective alternative to ERCP in patients requiring biliary drainage, in particular as a backup method if standard ERCP-approach fails. Development of new techniques, specific accessories and stents during the last decade led to an enormous step forward in terms of efficacy and safety of an EUS-directed approach. In the current article technical and clinical aspects of EUS-guided diagnostic and therapeutic approaches in different clinical indications will be discussed together with a review of the available data.
Structure and Properties of Biodegradable PLLA/ZnO Composite Membrane Produced via Electrospinning
Authors: Goncharova Daria A. , Bolbasov Evgeny N. , Nemoykina Anna L. , Aljulaih Ali A. , Tverdokhlebova Tamara S. , Kulinich Sergei A. , Svetlichnyi Valery A.
Published: December 2020

These days, composite materials based on polymers and inorganic nanoparticles (NPs) are widely used in optoelectronics and biomedicine. In this work, composite membranes of polylactic acid and ZnO NPs containing 5–40 wt.% of the latter NPs were produced by means of electrospinning. For the first time, polymer material loaded with up to 40 wt.% of ZnO NPs (produced via laser ablation in air and having non-modified surface) was used to prepare fiber-based composite membranes. The morphology, phase composition, mechanical, spectral and antibacterial properties of the membranes were tested by a set of analytical techniques including SEM, XRD, FTIR, UV-vis, and photoluminescence spectroscopy. Antibacterial activity of the materials was evaluated following standard procedures (ISO 20743:2013) and using S. aureus and E. coli bacteria. It is shown that incorporation of 5–10 wt.% of NPs led to improved mechanical properties of the composite membranes, while further increase of ZnO content up to 20 wt.% and above resulted in their noticeable deterioration. At the same time, the antibacterial properties of ZnO-rich membranes were more pronounced, which is explained by a larger number of surface-exposed ZnO NPs, in addition to those embedded into the bulk of fiber material.
Radiolabeled Gold Nanoparticles for Imaging and Therapy of Cancer
Authors: Silva Francisco , Cabral Campello Maria Paula , Paulo António
Published: December 2020

In the Last decades, nanotechnology has provided novel and alternative methodologies and tools in the field of medical oncology, in order to tackle the issues regarding the control and treatment of cancer in modern society. In particular, the use of gold nanoparticles (AuNPs) in radiopharmaceutical development has provided various nanometric platforms for the delivery of medically relevant radioisotopes for SPECT/PET diagnosis and/or radionuclide therapy. In this review, we intend to provide insight on the methodologies used to obtain and characterize radiolabeled AuNPs while reporting relevant examples of AuNPs developed during the last decade for applications in nuclear imaging and/or radionuclide therapy, and highlighting the most significant preclinical studies and results.
Determination of Selected Texture Features on a Single-Layer Grinding Wheel Active Surface for Tracking Their Changes as a Result of Wear
Authors: Bazan Anna , Kawalec Andrzej , Rydzak Tomasz , Kubik Paweł , Olko Adam
Published: December 2020

Measurements of the active surface microgeometry of the grinding wheel by contact and optical methods are commonly used to obtain a cloud of points representing the surface of the examined tool. Parameters that can be determined on the basis of the above-mentioned measurements can be universal parameters, which are commonly used to assess the geometric structure of a surface or parameters taking into account specific properties of the grinding wheel active surface (GWAS) structure. This article proposes a methodology for determining the average level of binder, which allows the definition the cut-off level required to separate from the measurement data: (i) the areas representing grains, (ii) the areas of gumming up of the grinding wheel, and (iii) deep cavities in approximately the same places on the investigated grinding wheel, regardless of the degree of its wear. This, in turn, allows one to track changes in characteristic parameters computed from measurements of texture in the above-mentioned areas due to different GWAS wear processes. The research was based on the analysis of data obtained from measurements of single-layer grinding wheels using the replica technique. The adopted measurement methodology enables measurement of approximately the same (94% coverage) areas of the GWAS at four stages of grinding wheel operation. Errors that were computed related to the determination of the volume of abrasive on the GWAS at various stages of wear using the developed methodology were lower, on average, by 48% compared to the automatic recognition of islands made with a commercial software.
Solid-State Polymerization as a Vitrimerization Tool Starting from Available Thermoplastics: The Effect of Reaction Temperature
Authors: Panagiotopoulos Christos , Porfyris Athanasios , Korres Dimitrios , Vouyiouka Stamatina
Published: December 2020

In the current work, solid-state polymerization (SSP) was studied for the synthesis of poly(butylene terephthalate), PBT-based vitrimers. A two-step process was followed; the first step involved alcoholysis reactions and the incorporation of glycerol in the polymer chains. The second step comprised transesterification reactions in the solid state (SSP) in the presence of zinc(II) catalyst resulting in the formation of a dynamic crosslinked network with glycerol moieties serving as the crosslinkers. The optimum SSP conditions were found to be 3 h at 180 °C under N2 flow (0.5 L/min) to reach high vitrimer insolubility (up to 75%) and melt strength (2.1 times reduction in the melt flow rate) while increasing the crosslinker concentration (from 3.5 to 7 wt.%) improved further the properties. Glass transition temperature (Tg) was almost tripled in vitrimers compared to initial thermoplastic, reaching a maximum of 97 °C, whereas the melting point (Tm) was slightly decreased, due to loss of symmetry perfection under the influence of the crosslinks. Moreover, the effect of the dynamic crosslinked structure on PBT crystallization behavior was investigated in detail by studying the kinetics of non-isothermal crystallization. The calculated effective activation energy using the Kissinger model and the nucleating activity revealed that the higher crosslinker content impeded and slowed down vitrimers melt crystallization, also inducing an alteration in the crystallization mechanism towards sporadic heterogeneous growth.
Mercury Removal from Aqueous Solution Using ETS-4 in the Presence of Cations of Distinct Sizes
Authors: Cardoso Simão P. , Faria Tiago L. , Pereira Eduarda , Portugal Inês , Lopes Cláudia B. , Silva Carlos M.
Published: December 2020

The removal of the hazardous Hg2+ from aqueous solutions was studied by ion exchange using titanosilicate in sodium form (Na-ETS-4). Isothermal batch experiments at fixed pH were performed to measure equilibrium and kinetic data, considering two very distinct situations to assess the influence of competition effects: (i) the counter ions initially in solution are Na+ and Hg2+ (both are exchangeable); (ii) the initial counter ions in solution are tetrapropylammonium (TPA+) and Hg2+ (only Hg2+ is exchangeable, since TPA+ is larger than the ETS-4 micropores). The results confirmed that ETS-4 is highly selective for Hg2+, with more than 90% of the mercury being exchanged from the fluid phase. The final equilibrium attained under the presence of TPA+ or Na+ in solution was very similar, however, the Hg2+/Na+/ETS-4 system in the presence of Na+ required more 100 h to reach equilibrium than in the presence of TPA+. The Hg2+/Na+/ETS-4 system was modelled and analyzed in terms of equilibrium (mass action law) and mass transfer (Maxwell–Stefan (MS) formalism). Concerning equilibrium, no major deviations from ideality were found in the range of studied concentrations. On the other hand, the MS based model described successfully (average deviation of 5.81%) all kinetic curves of mercury removal.
Hydrogen Gas Phase and Electrochemical Hydriding of LaNi5−xMx (M = Sn, Co, Al) Alloys
Authors: Todorova Stanislava , Abrashev Borislav , Rangelova Vesselina , Mihaylov Lyuben , Vassileva Evelina , Petrov Konstantin , Spassov Tony
Published: December 2020

Hydriding/dehydriding properties of a series of LaNi5 based alloys were compared by applying both hydrogen gas phase and electrochemical hydrogen charge/discharge methods. The highest hydrogen absorption capacity of 1.4 wt.% H2 was found for LaNi4.3Co0.4Al0.3, although LaNi4.8Sn0.2 also reveals comparable hydrogen capacity (>1.3%). A significant difference in the hydriding kinetics was observed for all studied alloys before and after activation. The activated alloys (5 cycles at 65 °C, 40 atm. H2) reach their maximum capacities after less than a minute, whereas the pure LaNi5 alloy needs several minutes for complete hydriding. The electrochemical hydriding/dehydriding behavior of the alloys reveals superior performance of LaNi4.3Co0.4Al0.3 and LaNi4.8Sn0.2 compared to the other compositions studied, as the capacity of LaNi4.8Sn0.2 decreases by only 10% for 60 charge/discharge cycles at a current density of 100 mA/g. Good agreement between the hydrogen sorption kinetics of the alloys obtained electrochemically and from hydrogen gas phase has also been observed.
Skew Rolling of Bimetallic Rods
Authors: Tomczak Janusz , Bulzak Tomasz , Pater Zbigniew , Wójcik Łukasz , Kusiak Tomasz
Published: December 2020

The present article reports selected results of a preliminary study of the process of skew rolling of bimetallic rods. The experiments were conducted using a numerically controlled three-roller skew rolling mill. During the tests, bimetallic rods were rolled from billets whose cores and outer sleeves (bushings) were made of different types of steel. The results demonstrate that the proposed method can be successfully used in the production of bimetallic rods. However, proper fastening of the two materials depends on the geometrical parameters of the billets, and the quality of bimetallic rods depends on the heating method used. When the rods are heated without protective atmospheres, the surface layer of the core gets decarburized and the surfaces of the materials being joined together are oxidized, which hinders the welding process and adversely affects the physical and chemical properties of such products. The results of numerical modeling indicate that the material near the surface tends to flow, which may have a negative impact on the welding process. In addition, the distribution of stress in the tool–workpiece contact zone may make welding of the materials difficult. The results reported in this paper are preliminary and constitute a prelude to a more detailed analysis of bimetallic rod rolling.
Variably Sized and Multi-Colored Silica-Nanoparticles Characterized by Fluorescence Correlation Methods for Cellular Dynamics
Authors: Pack Chan-Gi , Paulson Bjorn , Shin Yeonhee , Jung Min Kyo , Kim Jun Sung , Kim Jun Ki
Published: December 2020

Controlling the uptake of nanoparticles into cells so as to balance therapeutic effects with toxicity is an essential unsolved problem in the development of nanomedicine technologies. From this point of view, it is useful to use standard nanoparticles to quantitatively evaluate the physical properties of the nanoparticles in solution and in cells, and to analyze the intracellular dynamic motion and distribution of these nanoparticles at a single-particle level. In this study, standard nanoparticles are developed based on a variant silica-based nanoparticle incorporating fluorescein isothiocyanate (FITC) or/and rhodamine B isothiocyanate (RITC) with a variety of accessible diameters and a matching fluorescent cobalt ferrite core-shell structure (Fe2O4/SiO2). The physical and optical properties of the nanoparticles in vitro are fully evaluated with the complementary methods of dynamic light scattering, electron microscopy, and two fluorescence correlation methods. In addition, cell uptake of dual-colored and core/shell nanoparticles via endocytosis in live HeLa cells is detected by fluorescence correlation spectroscopy and electron microscopy, indicating the suitability of the nanoparticles as standards for further studies of intracellular dynamics with multi-modal methods.
Chemical, Physical, and Mechanical Properties of 95-Year-Old Concrete Built-In Arch Bridge
Authors: Ambroziak Andrzej , Haustein Elżbieta , Niedostatkiewicz Maciej
Published: December 2020

This research aimed to determine the durability and strength of an old concrete built-in arch bridge based on selected mechanical, physical, and chemical properties of the concrete. The bridge was erected in 1925 and is located in Jagodnik (northern Poland). Cylindrical specimens were taken from the side ribs connected to the top plate using a concrete core borehole diamond drill machine. The properties of the old concrete were compared with the present and previous standard requirements and guidelines. The laboratory testing program consisted of the following set of tests: measurements of the depth of carbonated zone and dry density, water absorption tests, determination of concrete compressive strength and frost resistance, determination of modulus of elasticity, measurement of the pH value, determination of water-soluble chloride salt and sulfate ion content, and X-ray diffraction analyses. Large variations in the cylindrical compressive strength (14.9 to 22.0 MPa), modulus of elasticity (17,900 to 26,483 MPa), density (2064 to 2231 kg/m3), and water absorption (3.88 to 6.58%) were observed. In addition to the experiments, a brief literature survey relating to old concrete properties was also conducted. This paper can provide scientists, engineers, and designers an experimental basis in the field of old concrete built-in bridge construction.
Morphology, Mechanical Properties and Shape Memory Effects of Polyamide12/Polyolefin Elastomer Blends Compatibilized by Glycidylisobutyl POSS
Authors: Lee Dong-Hun , Chang Young-Wook , Jang Keon-Soo
Published: December 2020

Small amounts of glycidylisobutyl polyhedral oligomericsilsesquioxane (G-POSS) (up to 10 phr) were added into a immiscible polyamide12 (PA12)/polyolefin elastomer (POE) blend (70 wt%/30 wt%) by simple melt mixing. The effects of the G-POSS on phase morphology and mechanical properties were investigated by FE-SEM, tensile testing, Izod impact test and dynamic mechanical analysis. FE-SEM analysis revealed that domain size of the dispersed POE phase in matrix PA12 is decreased significantly by adding the G-POSS, indicating a compatibilization effect of the G-POSS for the immiscible PA12/POE blend. The PA12/POE blend compatibilized with POSS showed simultaneous enhancement in mechanical properties including tensile modulus, strength and toughness. Further, thermally triggered shape memory effect was observed in this compatibilized blend.