bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship of the Mechanisms of the Pathogenesis of Multiple Sclerosis and the Expression of Endogenous Retroviruses
Authors: Lezhnyova Vera R. , Martynova Ekaterina V. , Khaiboullin Timur I. , Urbanowicz Richard A. , Khaiboullina Svetlana F. , Rizvanov Albert A.
Published: December 2020

Two human endogenous retroviruses of the HERV-W family can act as cofactors triggering multiple sclerosis (MS): MS-associated retrovirus (MSRV) and ERVWE1. Endogenous retroviral elements are believed to have integrated in our ancestors’ DNA millions of years ago. Their involvement in the pathogenesis of various diseases, including neurodegenerative pathologies, has been demonstrated. Numerous studies have shown a correlation between the deterioration of patients’ health and increased expression of endogenous retroviruses. The exact causes and mechanisms of endogenous retroviruses activation remains unknown, which hampers development of therapeutics. In this review, we will summarize the main characteristics of human endogenous W retroviruses and describe the putative mechanisms of activation, including epigenetic mechanisms, humoral factors as well as the role of the exogenous viral infections.
GAG-DB, the New Interface of the Three-Dimensional Landscape of Glycosaminoglycans
Authors: Pérez Serge , Bonnardel François , Lisacek Frédérique , Imberty Anne , Ricard Blum Sylvie , Makshakova Olga
Published: December 2020

Glycosaminoglycans (GAGs) are complex linear polysaccharides. GAG-DB is a curated database that classifies the three-dimensional features of the six mammalian GAGs (chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate) and their oligosaccharides complexed with proteins. The entries are structures of GAG and GAG-protein complexes determined by X-ray single-crystal diffraction methods, X-ray fiber diffractometry, solution NMR spectroscopy, and scattering data often associated with molecular modeling. We designed the database architecture and the navigation tools to query the database with the Protein Data Bank (PDB), UniProtKB, and GlyTouCan (universal glycan repository) identifiers. Special attention was devoted to the description of the bound glycan ligands using simple graphical representation and numerical format for cross-referencing to other databases in glycoscience and functional data. GAG-DB provides detailed information on GAGs, their bound protein ligands, and features their interactions using several open access applications. Binding covers interactions between monosaccharides and protein monosaccharide units and the evaluation of quaternary structure. GAG-DB is freely available.
Transforming Growth Factor-β Signaling in Fibrotic Diseases and Cancer-Associated Fibroblasts
Authors: Shi Xueke , Young Christian D. , Zhou Hongmei , Wang Xiao-Jing
Published: December 2020

Transforming growth factor-β (TGF-β) signaling is essential in embryo development and maintaining normal homeostasis. Extensive evidence shows that TGF-β activation acts on several cell types, including epithelial cells, fibroblasts, and immune cells, to form a pro-fibrotic environment, ultimately leading to fibrotic diseases. TGF-β is stored in the matrix in a latent form; once activated, it promotes a fibroblast to myofibroblast transition and regulates extracellular matrix (ECM) formation and remodeling in fibrosis. TGF-β signaling can also promote cancer progression through its effects on the tumor microenvironment. In cancer, TGF-β contributes to the generation of cancer-associated fibroblasts (CAFs) that have different molecular and cellular properties from activated or fibrotic fibroblasts. CAFs promote tumor progression and chronic tumor fibrosis via TGF-β signaling. Fibrosis and CAF-mediated cancer progression share several common traits and are closely related. In this review, we consider how TGF-β promotes fibrosis and CAF-mediated cancer progression. We also discuss recent evidence suggesting TGF-β inhibition as a defense against fibrotic disorders or CAF-mediated cancer progression to highlight the potential implications of TGF-β-targeted therapies for fibrosis and cancer.
Brewer’s Spent Grains—Valuable Beer Industry By-Product
Authors: Jackowski Mateusz , Niedźwiecki Łukasz , Jagiełło Kacper , Uchańska Oliwia , Trusek Anna
Published: December 2020

The brewing sector is a significant part of the global food industry. Breweries produce large quantities of wastes, including wastewater and brewer’s spent grains. Currently, upcycling of food industry by-products is one of the principles of the circular economy. The aim of this review is to present possible ways to utilize common solid by-product from the brewing sector. Brewer’s spent grains (BSG) is a good material for sorption and processing into activated carbon. Another way to utilize spent grains is to use them as a fuel in raw form, after hydrothermal carbonization or as a feedstock for anaerobic digestion. The mentioned by-products may also be utilized in animal and human nutrition. Moreover, BSG is a waste rich in various substances that may be extracted for further utilization. It is likely that, in upcoming years, brewer’s spent grains will not be considered as a by-product, but as a desirable raw material for various branches of industry.
Isolation and Antitrypanosomal Characterization of Furoquinoline and Oxylipin from Zanthoxylum zanthoxyloides
Authors: Dofuor Aboagye Kwarteng , Ayertey Frederick , Bolah Peter , Djameh Georgina Isabella , Kyeremeh Kwaku , Ohashi Mitsuko , Okine Laud Kenneth , Gwira Theresa Manful
Published: December 2020

In the absence of vaccines, there is a need for alternative sources of effective chemotherapy for African trypanosomiasis (AT). The increasing rate of resistance and toxicity of commercially available antitrypanosomal drugs also necessitates an investigation into the mode of action of new antitrypanosomals for AT. In this study, furoquinoline 4, 7, 8-trimethoxyfuro (2, 3-b) quinoline (compound 1) and oxylipin 9-oxo-10, 12-octadecadienoic acid (compound 2) were isolated from the plant species Zanthoxylum zanthoxyloides (Lam) Zepern and Timler (root), and their in vitro efficacy and mechanisms of action investigated in Trypanosoma brucei (T. brucei), the species responsible for AT. Both compounds resulted in a selectively significant growth inhibition of T. brucei (compound 1, half-maximal effective concentration EC50 = 1.7 μM, selectivity indices SI = 74.9; compound 2, EC50 = 1.2 μM, SI = 107.3). With regards to effect on the cell cycle phases of T. brucei, only compound 1 significantly arrested the second growth-mitotic (G2-M) phase progression even though G2-M and DNA replication (S) phase arrest resulted in the overall reduction of T. brucei cells in G0-G1 for both compounds. Moreover, both compounds resulted in the aggregation and distortion of the elongated slender morphology of T. brucei. Analysis of antioxidant potential revealed that at their minimum and maximum concentrations, the compounds exhibited significant oxidative activities in T. brucei (compound 1, 22.7 μM Trolox equivalent (TE), 221.2 μM TE; compound 2, 15.0 μM TE, 297.7 μM TE). Analysis of growth kinetics also showed that compound 1 exhibited a relatively consistent growth inhibition of T. brucei at different concentrations as compared to compound 2. The results suggest that compounds 1 and 2 are promising antitrypanosomals with the potential for further development into novel AT chemotherapy.
Isolation of a Lactobacillus paracasei Strain with Probiotic Attributes from Kefir Grains
Authors: Plessas Stavros , Kiousi Despoina Eugenia , Rathosi Marina , Alexopoulos Athanasios , Kourkoutas Yiannis , Mantzourani Ioanna , Galanis Alex , Bezirtzoglou Eugenia
Published: December 2020

Κefir is a rich source of potentially probiotic bacteria. In the present study, firstly, in vitro screening for probiotic characteristics of ten lactic acid bacteria (LAB) isolated from kefir grains was performed. Strain AGR 4 was selected for further studies. Molecular characterization of strain AGR 4, confirmed that AGR 4 belongs to the Lactobacillus paracasei (reclassified to Lacticaseibacillus paracasei subsp. paracasei) species. Further testing revealed that L. paracasei AGR 4 displayed adhesion capacity on human adenocarcinoma cells, HT-29, similar to that of the reference strain, L. casei ATCC 393. In addition, the novel strain exerted significant time- and dose-dependent antiproliferative activity against HT-29 cells and human melanoma cell line, A375, as demonstrated by the sulforhodamine B cytotoxicity assay. Flow cytometry analysis was employed to investigate the mechanism of cellular death; however, it was found that AGR 4 did not act by inducing cell cycle arrest and/or apoptotic cell death. Taken together, these findings promote the probiotic character of the newly isolated strain L. paracasei AGR 4, while further studies are needed for the detailed description of its biological properties.
The Role of Soluble Uric Acid in Modulating Autophagy Flux and Inflammasome Activation during Bacterial Infection in Macrophages
Authors: Al-Awad Duha , Al-Emadi Nada , Abu-Madi Marawan , Al-Thani Asmaa A. , Zughaier Susu M.
Published: December 2020

Autophagy is a homeostatic process that regulates and recycles intracellular structures and is a host defense mechanism that facilitates bacterial clearance. Uric acid in plasma is a major antioxidant but in certain conditions acts as an inflammatory danger signal. The aim of this study is to investigate the effect of soluble uric acid on autophagy and the inflammatory responses in macrophages during bacterial infection. Herein, we employed murine RAW264.7 macrophages that express uricase enzyme and human THP-1 cells that are uricase-deficient. Three different strains of Staphylococcus aureus and two different strains of Klebsiella pneumoniae were used to infect macrophages in presence and absence of soluble uric acid. We found that soluble uric acid enhanced autophagy flux in infected macrophages. We observed that IL-1β increased during bacterial infection but decreased when macrophages were co-stimulated with bacteria and uric acid. In contrast to IL-1β, soluble uric acid did not affect TNFα release and there were no dramatic differences when macrophages were infected with S. aureus or K. pneumoniae. In conclusion, uric acid enhances autophagy flux during bacterial infection, consequently reducing inflammasome activation in macrophages. Understanding the effect of uric acid on the interplay between autophagy and inflammation will facilitate therapeutic design.
Roles of Interleukin-1 Receptor Antagonist in Prostate Cancer Progression
Authors: Fan Yu-Ching , Lee Kuan-Der , Tsai Yuan-Chin
Published: December 2020

Background: Inflammation is known to promote tumor formation and progression; however, we found a natural anti-inflammatory factor, interleukin (IL)-1 receptor antagonist (IL1RN), in a mouse transgenic adenocarcinoma of the mouse prostate (TRAMP)-C1-derived tumor microenvironment (TME). We sought to characterize the functions of the IL1RN-secreting cells in the TME. Methods: We compared tumors collected from two syngeneic mouse models and isolated tumor-infiltrating leukocytes (TILs) with different cluster of differentiation 11b (CD11b) statuses. We examined the proliferation functions of the TILs and the IL1RN using several approaches, including a colony-formation assay and DNA synthesis levels. Results: We demonstrated that CD11b-deficient TILs (TILs/CD11b−) secreted the IL1RN and promoted proliferation by analyzing conditioned media. In addition to mouse TRAMP-C1, proliferation functions of the IL1RN were confirmed in several human castration-resistant prostate cancer (CRPC) cell lines and one normal epithelial cell line. The androgen-sensitive lymph node carcinoma of the prostate (LNCaP) cell line showed cytotoxic responses to IL1β treatment and androgen-dependent regulation of IL-1 receptor type 1 (IL1R1), while the C4-2 CRPC cell line did not. IL1RN rescued LNCaP cells from the cytotoxic effects of IL1β/IL1R1 signaling. Conclusions: Our results support TILs/CD11b− cells being able to protect androgen-dependent cells from inflammatory damage and promote the malignant progression of prostate cancers partly through the IL1RN in the TME.
The Incorporation of Amplified Metal-Enhanced Fluorescence in a CMOS-Based Biosensor Increased the Detection Sensitivity of a DNA Marker of the Pathogenic Fungus Colletotrichum gloeosporioides
Authors: Harpaz Dorin , Alkan Noam , Eltzov Evgeni
Published: December 2020

Half of the global agricultural fresh produce is lost, mainly because of rots that are caused by various pathogenic fungi. In this study, a complementary metal-oxide-semiconductor (CMOS)-based biosensor was developed, which integrates specific DNA strands that allow the detection of enoyl-CoA-hydratase/isomerase, which is a quiescent marker of Colletotrichum gloeosporioides fungi. The developed biosensor mechanism is based on the metal-enhanced fluorescence (MEF) phenomenon, which is amplified by depositing silver onto a glass surface. A surface DNA strand is then immobilized on the surface, and in the presence of the target mRNA within the sample, the reporter DNA strand that is linked to horseradish peroxidase (HRP) enzyme will also bind to it. The light signal that is later produced from the HRP enzyme and its substrate is enhanced and detected by the coupled CMOS sensor. Several parameters that affect the silver-deposition procedure were examined, including silver solution temperature and volume, heating mode, and the tank material. Moreover, the effect of blocking treatment (skim milk or bovine serum albumin (BSA)) on the silver-layer stability and nonspecific DNA absorption was tested. Most importantly, the effect of the deposition reaction duration on the silver-layer formation and the MEF amplification was also investigated. In the study findings a preferred silver-deposition reaction duration was identified as 5–8 min, which increased the deposition of silver on the glass surface up to 13-times, and also resulted in the amplification of the MEF phenomenon with a maximum light signal of 50 relative light units (RLU). It was found that MEF can be amplified by a customized silver-deposition procedure that results in increased detection sensitivity. The implementation of the improved conditions increased the biosensor sensitivity to 3.3 nM (4500 RLU) with a higher detected light signal as compared to the initial protocol (400 RLU). Moreover, the light signal was amplified 18.75-, 11.11-, 5.5-, 11.25-, and 3.75-times in the improved protocol for all the tested concentrations of the target DNA strand of 1000, 100, 10, 3.3, and 2 nM, respectively. The developed biosensor system may allow the detection of the pathogenic fungus in postharvest produce and determine its pathogenicity state.
Alternative Method to the Replication of Wind Effects into the Buildings Thermal Simulation
Authors: Albatayneh Aiman , Alterman Dariusz , Page Adrian , Moghtaderi Behdad
Published: December 2020

To design energy-efficient buildings, energy assessment programs need to be developed for determining the inside air temperature, so that thermal comfort of the occupant can be sustained. The internal temperatures could be calculated through computational fluid dynamics (CFD) analysis; however, miniscule time steps (seconds and milliseconds) are used by a long-term simulation (i.e., weeks, months) that require excessive time for computing wind effects results even for high-performance personal computers. This paper examines a new method, wherein the wind effect surrounding the buildings is integrated with the external air temperature to facilitate wind simulation in building analysis over long periods. This was done with the help of an equivalent temperature (known as Tnatural), where the convection heat loss is produced in an equal capacity by this air temperature and by the built-in wind effects. Subsequently, this new external air temperature Tnatural can be used to calculate the internal air temperature. Upon inclusion of wind effects, above 90% of the results were found to be within 0–3 °C of the perceived temperatures compared to the real data (99% for insulated cavity brick (InsCB), 91% for cavity brick (CB), 93% for insulated reverse brick veneer (InsRBV) and 94% for insulated brick veneer (InsBV) modules). However, a decline of 83–88% was observed in the results after ignoring the wind effects. Hence, the presence of wind effects holds greater importance in correct simulation of the thermal performance of the modules. Moreover, the simulation time will expectedly reduce to below 1% of the original simulation time.
Study of Prepared α-Chymotrypsin as Enzyme Nanoparticles and of Biocatalytic Membrane Reactor
Authors: Hegedüs Imre , Vitai Marta , Jakab Miklós , Nagy Endre
Published: December 2020

Biocatalytic kinetic effect of α-chymotrypsin enzyme has been investigated in its free and pretreated forms (it was covered by a very thin, porous polymer layer, called enzyme nanoparticle) as well as its immobilized form into pores of polysulfone/polyamide asymmetric, hydrophilic membrane. Trimethoxysilyl and acrylamide-bisacrylamide polymers have been used for synthesis of enzyme nanoparticles. Applying Michaelis-Menten kinetics, the KM and vmax values of enzyme-polyacrylamide nanoparticles are about the same, as that of free enzyme. On the other hand, enzyme nanoparticles retain their activity 20–80 fold longer time period than that of the free enzyme, but their initial activity values are reduced to 13–55% of those of free enzymes, at 37 °C. Enzyme immobilized into asymmetric porous membrane layer remained active about 2.3-fold longer time period than that of native enzyme (at pH = 7.4 and at 23 °C), while its reaction rate was about 8-fold higher than that of free enzyme, measured in mixed tank reactor. The conversion degree of substrate was gradually decreased in presence of increasing convective flux of the inlet fluid phase. Biocatalytic membrane reactor has transformed 2.5 times more amount of substrate than the same amount of enzyme nanoparticles and 19 times more amount of substrate than free enzyme, measured in mixed tank reactor.
Non-Thermal Plasma-Modified Ru-Sn-Ti Catalyst for Chlorinated Volatile Organic Compound Degradation
Authors: Fu Yujie , Zhang You , Xin Qi , Zheng Zhong , Zhang Yu , Yang Yang , Liu Shaojun , Zhang Xiao , Zheng Chenghang , Gao Xiang
Published: December 2020

Chlorinated volatile organic compounds (CVOCs) are vital environmental concerns due to their low biodegradability and long-term persistence. Catalytic combustion technology is one of the more commonly used technologies for the treatment of CVOCs. Catalysts with high low-temperature activity, superior selectivity of non-toxic products, and resistance to chlorine poisoning are desirable. Here we adopted a plasma treatment method to synthesize a tin-doped titania loaded with ruthenium dioxide (RuO2) catalyst, possessing enhanced activity (T90%, the temperature at which 90% of dichloromethane (DCM) is decomposed, is 262 °C) compared to the catalyst prepared by the conventional calcination method. As revealed by transmission electron microscopy, X-ray diffraction, N2 adsorption, X-ray photoelectron spectroscopy, and hydrogen temperature-programmed reduction, the high surface area of the tin-doped titania catalyst and the enhanced dispersion and surface oxidation of RuO2 induced by plasma treatment were found to be the main factors determining excellent catalytic activities.
Direct Electrochemical Enzyme Electron Transfer on Electrodes Modified by Self-Assembled Molecular Monolayers
Authors: Yan Xiaomei , Tang Jing , Tanner David , Ulstrup Jens , Xiao Xinxin
Published: December 2020

Self-assembled molecular monolayers (SAMs) have long been recognized as crucial “bridges” between redox enzymes and solid electrode surfaces, on which the enzymes undergo direct electron transfer (DET)—for example, in enzymatic biofuel cells (EBFCs) and biosensors. SAMs possess a wide range of terminal groups that enable productive enzyme adsorption and fine-tuning in favorable orientations on the electrode. The tunneling distance and SAM chain length, and the contacting terminal SAM groups, are the most significant controlling factors in DET-type bioelectrocatalysis. In particular, SAM-modified nanostructured electrode materials have recently been extensively explored to improve the catalytic activity and stability of redox proteins immobilized on electrochemical surfaces. In this report, we present an overview of recent investigations of electrochemical enzyme DET processes on SAMs with a focus on single-crystal and nanoporous gold electrodes. Specifically, we consider the preparation and characterization methods of SAMs, as well as SAM applications in promoting interfacial electrochemical electron transfer of redox proteins and enzymes. The strategic selection of SAMs to accord with the properties of the core redox protein/enzymes is also highlighted.
Novel Insights in Anti-CD38 Therapy Based on CD38-Receptor Expression and Function: The Multiple Myeloma Model
Authors: Zannetti Beatrice Anna , Faini Angelo Corso , Massari Evita , Geuna Massimo , Maffini Enrico , Poletti Giovanni , Cerchione Claudio , Martinelli Giovanni , Malavasi Fabio , Lanza Francesco
Published: December 2020

Multiple myeloma (MM) is a hematological disease characterized by the proliferation and accumulation of malignant plasmacells (PCs) in the bone marrow (BM). Despite widespread use of high-dose chemotherapy in combination with autologous stem cell transplantation (ASCT) and the introduction of novel agents (immunomodulatory drugs, IMiDs, and proteasome inhibitors, PIs), the prognosis of MM patients is still poor. CD38 is a multifunctional cell-surface glycoprotein with receptor and ectoenzymatic activities. The very high and homogeneous expression of CD38 on myeloma PCs makes it an attractive target for novel therapeutic strategies. Several anti-CD38 monoclonal antibodies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab. Here we provide an in-depth look atCD38 biology, the role of CD38 in MM progression and its complex interactions with the BM microenvironment, the importance of anti-CD38 monoclonal antibodies, and the main mechanisms of antibody resistance. We then review a number of multiparametric flow cytometry techniques exploiting CD38 antigen expression on PCs to diagnose and monitor the response to treatment in MM patients.
Effect of a Lens Protein in Low-Temperature Culture of Novel Immortalized Human Lens Epithelial Cells (iHLEC-NY2)
Authors: Yamamoto Naoki , Takeda Shun , Hatsusaka Natsuko , Hiramatsu Noriko , Nagai Noriaki , Deguchi Saori , Nakazawa Yosuke , Takata Takumi , Kodera Sachiko , Hirata Akimasa , Kubo Eri , Sasaki Hiroshi
Published: December 2020

The prevalence of nuclear cataracts was observed to be significantly higher among residents of tropical and subtropical regions compared to those of temperate and subarctic regions. We hypothesized that elevated environmental temperatures may pose a risk of nuclear cataract development. The results of our in silico simulation revealed that in temperate and tropical regions, the human lens temperature ranges from 35.0 °C to 37.5 °C depending on the environmental temperature. The medium temperature changes during the replacement regularly in the cell culture experiment were carefully monitored using a sensor connected to a thermometer and showed a decrease of 1.9 °C, 3.0 °C, 1.7 °C, and 0.1 °C, after 5 min when setting the temperature of the heat plate device at 35.0 °C, 37.5 °C, 40.0 °C, and 42.5 °C, respectively. In the newly created immortalized human lens epithelial cell line clone NY2 (iHLEC-NY2), the amounts of RNA synthesis of αA crystallin, protein expression, and amyloid β (Aβ)1-40 secreted into the medium were increased at the culture temperature of 37.5 °C compared to 35.0 °C. In short-term culture experiments, the secretion of Aβ1-40 observed in cataracts was increased at 37.5 °C compared to 35.0 °C, suggesting that the long-term exposure to a high-temperature environment may increase the risk of cataracts.
Current Advances in Burkholderia Vaccines Development
Authors: Wang Guanbo , Zarodkiewicz Paulina , Valvano Miguel A.
Published: December 2020

The genus Burkholderia includes a wide range of Gram-negative bacterial species some of which are pathogenic to humans and other vertebrates. The most pathogenic species are Burkholderia mallei, Burkholderia pseudomallei, and the members of the Burkholderia cepacia complex (Bcc). B. mallei and B. pseudomallei, the cause of glanders and melioidosis, respectively, are considered potential bioweapons. The Bcc comprises a subset of Burkholderia species associated with respiratory infections in people with chronic granulomatous disease and cystic fibrosis. Antimicrobial treatment of Burkholderia infections is difficult due to the intrinsic multidrug antibiotic resistance of these bacteria; prophylactic vaccines provide an attractive alternative to counteract these infections. Although commercial vaccines against Burkholderia infections are still unavailable, substantial progress has been made over recent years in the development of vaccines against B. pseudomallei and B. mallei. This review critically discusses the current advances in vaccine development against B. mallei, B. pseudomallei, and the Bcc.
Preemptive Analgesic Effect of Intrathecal Applications of Neuroactive Steroids in a Rodent Model of Post-Surgical Pain: Evidence for the Role of T-Type Calcium Channels
Authors: Tat Quy L. , Joksimovic Srdjan M. , Krishnan Kathiresan , Covey Douglas F. , Todorovic Slobodan M. , Jevtovic-Todorovic Vesna
Published: December 2020

Preemptive management of post-incisional pain remains challenging. Here, we examined the role of preemptive use of neuroactive steroids with activity on low-voltage activated T-type Ca2+ channels (T-channels) and γ-aminobutyric acid A (GABAA) receptors in the development and maintenance of post-incisional pain. We use neuroactive steroids with distinct effects on GABAA receptors and/or T-channels: Alphaxalone (combined GABAergic agent and T-channel inhibitor), ECN (T-channel inhibitor), CDNC24 (GABAergic agent), and compared them with an established analgesic, morphine (an opioid agonist without known effect on either T-channels or GABAA receptors). Adult female rats sustained the skin and muscle incision on the plantar surface of the right paw. We injected the agents of choice intrathecally either before or after the development of post-incisional pain. The pain development was monitored by studying mechanical hypersensitivity. Alphaxalone and ECN, but not morphine, are effective in alleviating mechanical hyperalgesia when administered preemptively whereas morphine provides dose-dependent pain relief only when administered once the pain had developed. CDNC24 on the other hand did not offer any analgesic benefit. Neuroactive steroids that inhibit T-currents—Alphaxalone and ECN—unlike morphine, are effective preemptive analgesics that may offer a promising therapeutic approach to the treatment of post-incisional pain, especially mechanical hypersensitivity.
Taming the Autophagy as a Strategy for Treating COVID-19
Authors: García-Pérez Blanca Estela , González-Rojas Juan Antonio , Salazar Ma Isabel , Torres-Torres Carlos , Castrejón-Jiménez Nayeli Shantal
Published: December 2020

Currently, an efficient treatment for COVID-19 is still unavailable, and people are continuing to die from complications associated with SARS-CoV-2 infection. Thus, the development of new therapeutic approaches is urgently needed, and one alternative is to target the mechanisms of autophagy. Due to its multifaceted role in physiological processes, many questions remain unanswered about the possible advantages of inhibiting or activating autophagy. Based on a search of the literature in this field, a novel analysis has been made to highlight the relation between the mechanisms of autophagy in antiviral and inflammatory activity in contrast with those of the pathogenesis of COVID-19. The present analysis reveals a remarkable coincidence between the uncontrolled inflammation triggered by SARS-CoV-2 and autophagy defects. Particularly, there is conclusive evidence about the substantial contribution of two concomitant factors to the development of severe COVID-19: a delayed or absent type I and III interferon (IFN-I and IFN-III) response together with robust cytokine and chemokine production. In addition, a negative interplay exists between autophagy and an IFN-I response. According to previous studies, the clinical decision to inhibit or activate autophagy should depend on the underlying context of the pathological timeline of COVID-19. Several treatment options are herein discussed as a guide for future research on this topic.
TRPML1—Emerging Roles in Cancer
Authors: Yang Yiming , Zhai Xingjian , El Hiani Yassine
Published: December 2020

The mucolipin-1 (TRPML1) channel maintains lysosomal ionic homeostasis and regulates autophagic flux. Defects of TRPML1 lead to lysosomal storage diseases and neurodegeneration. In this report, we discuss emerging evidence pertaining to differential regulation of TRPML1 signaling pathways in cancer progression with the goal of leveraging the oncogenic potential of TRPML1 to inspire therapeutic interventions.
The Consequences of Delaying Telling Children with Perinatal HIV About Their Diagnosis as Perceived by Healthcare Workers in the Eastern Cape; A Qualitative Study
Authors: Madiba Sphiwe , Diko Cynthia
Published: December 2020

Although the benefits of disclosure are considerable, informing children with perinatal HIV of their own HIV status is often delayed to late adolescence. This study examined the social and contextual challenges that influence delaying disclosure to children and assessed the outcomes of delayed disclosure on the psychosocial health of children as perceived by the healthcare workers (HCWs) providing care to these children. Data were collected from HCWs via focus group discussions. Nurses, lay counsellors, social workers, and dieticians were selected from facilities in a rural South African health district. Thematic analysis was performed. The caregivers’ social context was the main barrier against informing children timely about their HIV diagnosis. The extent of the internalised HIV stigma influenced the delay in disclosing to the children. Delaying disclosure contributes to children’s refusing to take their medication, leads to the accidental disclosure of HIV, give rise to anger and resentment towards the caregiver, increase the risk of secondary transmitting of HIV, and poor health outcomes. It is essential to train HCWs to support caregivers and children through the disclosure process to ensure that caregivers realise the benefits of disclosure. Strategies to encourage caregivers to disclose early should be sensitive to their concerns about the negative impacts of disclosure.
Critical Analysis and Evaluation of the Technology Pathways for Carbon Capture and Utilization
Authors: Philbin Simon P.
Published: December 2020

Carbon capture and utilization (CCU) is the process of capturing unwanted carbon dioxide (CO2) and utilizing for further use. CCU offers significant potential as part of a sustainable circular economy solution to help mitigate the impact of climate change resulting from the burning of hydrocarbons and alongside adoption of other renewable energy technologies. However, implementation of CCU technologies faces a number of challenges, including identifying optimal pathways, technology maturity, economic viability, environmental considerations as well as regulatory and public perception issues. Consequently, this research study provides a critical analysis and evaluation of the technology pathways for CCU in order to explore the potential from a circular economy perspective of this emerging area of clean technology. This includes a bibliographic study on CCU, evaluation of carbon utilization processes, trend estimation of CO2 usage as well as evaluation of methane and methanol production. A value chain analysis is provided to support the development of CCU technologies. The research study aims to inform policy-makers engaged in developing strategies to mitigate climate change through reduced carbon dioxide emission levels and improve our understanding of the circular economy considerations of CCU in regard to production of alternative products. The study will also be of use to researchers concerned with pursuing empirical investigations of this important area of sustainability.
Impurity Phases and Optoelectronic Properties of CuSbSe2 Thin Films Prepared by Cosputtering Process for Absorber Layer in Solar Cells
Authors: Kim Sara , Kim Nam-Hoon
Published: December 2020

When there is a choice of materials for an application, particular emphasis should be given to the development of those that are low-cost, nontoxic, and Earth-abundant. Chalcostibite CuSbSe2 has gained attention as a potential absorber material for thin-film solar cells, since it exhibits a high absorption coefficient. In this study, CuSbSe2 thin films were deposited by radio frequency magnetron cosputtering with CuSe2 and Sb targets. A series of CuSbxSe2 thin films were prepared with different Sb contents adjusted by sputtering power, followed by rapid thermal annealing. Impurity phases and surface morphology of Cu–Sb–Se systems were directly affected by the Sb sputtering power, with the formation of volatile components. The crystallinity of the CuSbSe2 thin films was also enhanced in the near-stoichiometric system at an Sb sputtering power of 15 W, and considerable degradation in crystallinity occurred with a slight increase over 19 W. Resistivity, carrier mobility, and carrier concentration of the near-stoichiometric thin film were 14.4 Ω-cm, 3.27 cm2/V∙s, and 1.33 × 1017 cm−3, respectively. The optical band gap and absorption coefficient under the same conditions were 1.7 eV and 1.75 × 105 cm−1, which are acceptable for highly efficient thin-film solar cells.
Peroxide Post-Treatment of Wood Impregnated with Micronized Basic Copper Carbonate
Authors: Stirling Rod , Boivin Gabrielle , Uzunovic Adnan , Kus Stacey , Ruddick John N. R.
Published: December 2020

Wood is vulnerable to significant color changes when used in exterior applications. Some copper-based wood preservatives use colorants to minimize this color change. This paper examines the ability of a peroxide post-treatment to turn wood impregnated with micronized basic copper carbonate (CuCO3·Cu(OH)2) (MBCC) a stable brown color. MBCC-treated wood, with and without peroxide post-treatment, along with associated controls were evaluated for color change, erosion and black-stain fungal resistance after exposure to artificial photo-degradation. The impact of the peroxide treatment on copper leaching was assessed in a laboratory experiment, and the impact on copper reactivity was assessed by electron parametric resonance (EPR) spectroscopy. Peroxide post-treatment of wood pressure impregnated with MBCC was shown to reduce color change by more than 50% compared to controls. Erosion due to photo-degradation and colonization by black-stain fungi were lower in samples treated with MBCC than in untreated controls and were relatively unaffected by peroxide post-treatment. The peroxide post-treatment was associated with increased amounts of mobile copper. This led to increased susceptibility to leaching and to a more than 60% increase in the amount of copper than had reacted with the wood.
Molecular Dynamics Study of Anti-Wear Erosion and Corrosion Protection of PTFE/Al2O3 (010) Coating Composite in Water Hydraulic Valves
Authors: Mlela Masoud Kamoleka , Xu He , Wang Haihang
Published: December 2020

Cavitation erosion and corrosion commonly occur on the surface of fluid dynamic system components, mostly water hydraulic valves, causing the failure of metal parts. Coating of polytetrafluoroethylene (PTFE) on Al2O3 (010) was created by varying the chain length of polytetrafluoroethylene. Calculations were conducted by molecular dynamic (MD) simulations. This study shows that the K10 and K20 chain lengths’ mechanical properties possess negative elastic, shear, and bulk modulus values. We have found that the K10 chain length composition shows the high results of binding energy and negative bulk modulus of 6267.16 kJ/mol and −3709.54 GPa, respectively. The K10 chain length was observed to possess a higher cohesive energy density (CED) and solubility parameter of (6.885 ± 0.00076) × 109 J/m3 and (82.974 ± 0.005) (J/cm3)0.5, respectively. It was also found that increasing the chain length contributes to decreasing the binding energy and solubility parameter of PTFE/Al2O3 (010) composition. These results are vital for overcoming the repetitive regime of high compressive strength of water microjets on the valves’ material surface. Improved values of the cohesive energy density and solubility parameters imply the water’s superior hydrophobic effect.
Toward Smart Lockdown: A Novel Approach for COVID-19 Hotspots Prediction Using a Deep Hybrid Neural Network
Authors: Khan Sultan Daud , Alarabi Louai , Basalamah Saleh
Published: December 2020

COVID-19 caused the largest economic recession in the history by placing more than one third of world’s population in lockdown. The prolonged restrictions on economic and business activities caused huge economic turmoil that significantly affected the financial markets. To ease the growing pressure on the economy, scientists proposed intermittent lockdowns commonly known as “smart lockdowns”. Under smart lockdown, areas that contain infected clusters of population, namely hotspots, are placed on lockdown, while economic activities are allowed to operate in un-infected areas. In this study, we proposed a novel deep learning prediction framework for the accurate prediction of hotpots. We exploit the benefits of two deep learning models, i.e., Convolutional Neural Network (CNN) and Long Short-Term Memory (LSTM) and propose a hybrid framework that has the ability to extract multi time-scale features from convolutional layers of CNN. The multi time-scale features are then concatenated and provide as input to 2-layers LSTM model. The LSTM model identifies short, medium and long-term dependencies by learning the representation of time-series data. We perform a series of experiments and compare the proposed framework with other state-of-the-art statistical and machine learning based prediction models. From the experimental results, we demonstrate that the proposed framework beats other existing methods with a clear margin.
Structural Phase Diagram of LaO1−xFxBiSSe: Suppression of the Structural Phase Transition by Partial F Substitutions
Authors: Hoshi Kazuhisa , Sakuragi Shunsuke , Yajima Takeshi , Goto Yosuke , Miura Akira , Moriyoshi Chikako , Kuroiwa Yoshihiro , Mizuguchi Yoshikazu
Published: December 2020

Recently, the anomalous two-fold-symmetric in-plane anisotropy of superconducting states has been observed in a layered superconductor system, LaO1−xFxBiSSe (x = 0.1 and 0.5), with a tetragonal (four-fold symmetric) in-plane structure. To understand the origin of the phenomena observed in LaO1−xFxBiSSe, clarification of the low-temperature structural phase diagram is needed. In this study, we have investigated the low-temperature crystal structure of LaO1−xFxBiSSe (x = 0, 0.01, 0.02, 0.03, and 0.5). From synchrotron X-ray diffraction experiments, a structural transition from tetragonal to monoclinic was observed for x = 0 and 0.01 at 340 and 240 K, respectively. For x = 0.03, a structural transition and broadening of the diffraction peak were not observed down to 100 K. These facts suggest that the structural transition could be suppressed by 3% F substitution in LaO1−xFxBiSSe. Furthermore, the crystal structure for x = 0.5 at 4 K was examined by low-temperature laboratory X-ray diffraction, which confirmed that the tetragonal structure is maintained at 4 K for x = 0.5. Our structural investigation suggests that the two-fold-symmetric in-plane anisotropy of superconducting states observed in LaO1−xFxBiSSe was not originated from structural symmetry lowering in its average structure. To evaluate the possibility of the local structural modification like nanoscale puddles in the average tetragonal structure, further experiments are desired.
Cobalt(II) Complexes Based on Benzylmalonate Anions Exhibiting Field-Induced Single-Ion Magnet Slow Relaxation Behavior
Authors: Zorina-Tikhonova Ekaterina , Matyukhina Anna , Skabitskiy Ivan , Shmelev Maksim , Korchagin Denis , Babeshkin Konstantin , Efimov Nikolay , Kiskin Mikhail , Eremenko Igor
Published: December 2020

The reaction of (NBu4)2Bzmal (where Bzmal2− is benzylmalonate dianion) with Co(OAc)2∙4H2O gives the [Co(Bzmal)(EtOH)(H2O)]n 2D-polymer (1). The addition of 2,2′-bipyridine (bpy) to the starting system results in the [Co(Bzmal)(bpy)2]·H2O·EtOH molecular complex (2). Their molecular and crystal structures were analyzed by single-crystal X-ray crystallography. An analysis of the static magnetic data supported by the SA-CASSCF/NEVPT2 calculations revealed the presence of easy-plane magnetic anisotropy in both complexes. The AC susceptibility data confirm that both complexes show a slow field-induced (HDC = 1000 Oe) magnetic relaxation behavior.
“Free of Base” Sulfa-Michael Addition for Novel o-Carboranyl-DL-Cysteine Synthesis
Authors: Laskova Julia , Kosenko Irina , Ananyev Ivan , Stogniy Marina , Sivaev Igor , Bregadze Vladimir
Published: December 2020

The sulfa-Michael addition reaction was applied for the two-step synthesis of o-carboranyl cysteine 1-HOOCCH(NH2)CH2S-1,2-C2B10H11 from the trimethylammonium salt of 1-mercapto-o-carborane and methyl 2-acetamidoacrylate. To avoid the decapitation of o-carborane into its nido-form, the “free of base” method under mild conditions in a system of two immiscible solvents toluene-H2O was developed. The replacement of H2O by 2H2O resulted in carboranyl-cysteine containing a deuterium label at the α-position of the amino acid 1-HOOCCD(NH2)CH2S-1,2-C2B10H11. The structure of the protected o-carboranyl cysteine was determined by single-crystal X-ray diffraction. The obtained compounds can be considered as potential agents for the Boron Neutron Capture Therapy of cancer.
Consumption of Carnivores by Wolves: A Worldwide Analysis of Patterns and Drivers
Authors: Martins Inês , Krofel Miha , Mota Paulo G. , Álvares Francisco
Published: December 2020

The occurrence of carnivore species in wolf diet has been overlooked and poorly studied despite the potential implications for wolf ecology and wildlife management. We conducted an extensive literature review, focusing on 120 wolf diet studies worldwide to assess global patterns of carnivore consumption by wolves and their ecological and human-related determinants. We used a total of 143 sampling sites with data on the consumption of carnivores by wolves. In total, 35 carnivore species were reported to be consumed by wolves, comprising members of all taxonomic carnivore families represented within the gray wolf range. The carnivores were mostly limited to occasional consumption (<5% of wolf diet) but could account for as much as 25% in some study areas. The most frequently consumed carnivore species were those with reported scavenging behavior, belonging to medium-sized generalist canids. Generalized linear model (GLM) analysis revealed that higher magnitudes of carnivore consumption were related to nonprotected areas as well as lower occurrences of wild ungulates, domestic ungulates, and small mammals in wolf diet, while higher numbers of consumed carnivore species were related to nonprotected areas with low vegetation productivity and lower occurrences of domestic ungulates and small mammals in wolf diet. Our results suggest that carnivore consumption by wolves is driven by altered ecosystems and human-dominated landscapes, where mesopredator densities are often increased and prey densities decreased, which intensify competition and the need for alternative food sources.
The Influence of Calcification Factors and Endothelial-Dysfunction Factors on the Development of Unstable Atherosclerotic Plaques
Authors: Polonskaya Yana V. , Kashtanova Elena V. , Murashov Ivan S. , Kurguzov Aleksei V. , Sadovski Evgeny V. , Maslatsov Nikolay A. , Stakhneva Ekaterina M. , Chernyavskii Alexander M. , Ragino Yuliya I.
Published: December 2020

Background: This study aimed to evaluate changes in markers of calcification and of endothelial dysfunction during the development of calcification and instability of atherosclerotic plaques and to identify associations of calcification factors with the formation of unstable plaques. Methods: We analyzed 44 male patients with coronary atherosclerosis who underwent endarterectomy in coronary arteries during coronary bypass surgery. The endarterectomy material (intima/media) was examined using histological and biochemical methods, and the stability and calcification degree of atherosclerotic plaques were assessed. In homogenates of the tissue samples and in blood, concentrations of osteoprotegerin, osteocalcin, osteopontin, osteonectin, monocyte-chemoattractant protein type 1 (MCP-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin were determined by enzyme immunoassays. Results: Unstable atherosclerotic plaques proved to be calcified more frequently (80.4% of plaques) than stable ones (45.0%). Osteonectin, E-selectin, and sVCAM-1 levels were lower in unstable plaques and plaques with large calcification deposits. Osteocalcin content increased with the increasing size of the calcification deposits in plaque. Blood osteocalcin concentration directly correlated with osteocalcin concentration in atherosclerotic plaques and was higher in the blood of patients with calcified plaques in coronary arteries. Conclusions: The results provide the basis for further research on the suitability of osteocalcin as a potential biomarker of an unstable calcified atherosclerotic plaque in a coronary artery.
Retrospective Definition of Clostridioides difficile PCR Ribotypes on the Basis of Whole Genome Polymorphisms: A Proof of Principle Study
Authors: Goyal Manisha , Hauben Lysiane , Pouseele Hannes , Jaillard Magali , De Bruyne Katrien , van Belkum Alex , Goering Richard
Published: December 2020

Clostridioides difficile is a cause of health care-associated infections. The epidemiological study of C. difficile infection (CDI) traditionally involves PCR ribotyping. However, ribotyping will be increasingly replaced by whole genome sequencing (WGS). This implies that WGS types need correlation with classical ribotypes (RTs) in order to perform retrospective clinical studies. Here, we selected genomes of hyper-virulent C. difficile strains of RT001, RT017, RT027, RT078, and RT106 to try and identify new discriminatory markers using in silico ribotyping PCR and De Bruijn graph-based Genome Wide Association Studies (DBGWAS). First, in silico ribotyping PCR was performed using reference primer sequences and 30 C. difficile genomes of the five different RTs identified above. Second, discriminatory genomic markers were sought with DBGWAS using a set of 160 independent C. difficile genomes (14 ribotypes). RT-specific genetic polymorphisms were annotated and validated for their specificity and sensitivity against a larger dataset of 2425 C. difficile genomes covering 132 different RTs. In silico PCR ribotyping was unsuccessful due to non-specific or missing theoretical RT PCR fragments. More successfully, DBGWAS discovered a total of 47 new markers (13 in RT017, 12 in RT078, 9 in RT106, 7 in RT027, and 6 in RT001) with minimum q-values of 0 to 7.40 × 10−5, indicating excellent marker selectivity. The specificity and sensitivity of individual markers ranged between 0.92 and 1.0 but increased to 1 by combining two markers, hence providing undisputed RT identification based on a single genome sequence. Markers were scattered throughout the C. difficile genome in intra- and intergenic regions. We propose here a set of new genomic polymorphisms that efficiently identify five hyper-virulent RTs utilizing WGS data only. Further studies need to show whether this initial proof-of-principle observation can be extended to all 600 existing RTs.