bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized Pilot Clinical and Microbiological Study Comparing Laser Microtextured Implants with and without Platform Switching
Authors: Carrigy James , Perrotti Vittoria , Franciotti Raffaella , Sharma Ajay , Quaranta Alessandro
Published: April 2021

Minimising marginal bone loss around dental implants is of paramount importance. The success of methods such as platform switching (PS) and laser-micro-texturing (LM) are well documented. Whether or not a combination of these designs will further improve outcomes has not been studied previously. Hence, this prospective, randomized controlled single-centre pilot study compared the clinical and microbiological outcomes of implants with both PS and LM (test) to implants with only LM (control). A test and control implant were placed in thirteen patients totalling 26 implants. The primary investigated outcome was marginal bone level (MBL); secondary outcomes were peri-implant probing depths (PPD), bleeding on probing (BOP) and marginal tissue height (MTH). Additionally, the presence of five putative periodontal pathogens were assessed using real-time polymerized chain reaction. At 12 months the overall implant survival rate was 95.8%. MBL change was not found to be different between test and control at any time points, but a significant change was detected within the test implants at 6 months compared to baseline (p = 0.006). No differences were found in the secondary outcomes. Average PPD at 12 months was 2.68 ± 0.73 mm and 2.30 ± 0.46 mm and average change in MTH was 0.05 ± 0.72 mm and −0.24 ± 0.59 mm at tests and controls. No differences were reported in BOP frequency. Total periodontal pathogens count revealed no significant difference among control, test implants and adjacent tooth sites. Within the limitations of this study, it can be concluded that the addition of PS to LM implants does not significantly alter either short-term clinical outcomes or the vulnerability to pathogenic microflora colonization.
Polarimetric Radar Characteristics of Tornadogenesis Failure in Supercell Thunderstorms
Authors: Van Den Broeke Matthew
Published: April 2021

Many nontornadic supercell storms have times when they appear to be moving toward tornadogenesis, including the development of a strong low-level vortex, but never end up producing a tornado. These tornadogenesis failure (TGF) episodes can be a substantial challenge to operational meteorologists. In this study, a sample of 32 pre-tornadic and 36 pre-TGF supercells is examined in the 30 min pre-tornadogenesis or pre-TGF period to explore the feasibility of using polarimetric radar metrics to highlight storms with larger tornadogenesis potential in the near-term. Overall the results indicate few strong distinguishers of pre-tornadic storms. Differential reflectivity (ZDR) arc size and intensity were the most promising metrics examined, with ZDR arc size potentially exhibiting large enough differences between the two storm subsets to be operationally useful. Change in the radar metrics leading up to tornadogenesis or TGF did not exhibit large differences, though most findings were consistent with hypotheses based on prior findings in the literature.
Calendar Aging of Li-Ion Cells—Experimental Investigation and Empirical Correlation
Authors: Werner Daniel , Paarmann Sabine , Wetzel Thomas
Published: April 2021

The lifetime of the battery significantly influences the acceptance of electric vehicles. Calendar aging contributes to the limited operating lifetime of lithium-ion batteries. Therefore, its consideration in addition to cyclical aging is essential to understand battery degradation. This study consequently examines the same graphite/NCA pouch cell that was the subject of previously published cyclic aging tests. The cells were aged at different temperatures and states of charge. The self-discharge was continuously monitored, and after each storage period, the remaining capacity and the impedance were measured. The focus of this publication is on the correlation of the measurements. An aging correlation is obtained that is valid for a wide range of temperatures and states of charge. The results show an accelerated capacity fade and impedance rise with increasing temperature, following the law of Arrhenius. However, the obtained data do also indicate that there is no path dependency, i.e., earlier periods at different temperature levels do not affect the present degradation rate. A large impact of the storage state of charge at 100% is evident, whereas the influence is small below 80%. Instead of the commonly applied square root of the time function, our results are in excellent agreement with an exponential function.
Green Production of Cladribine by Using Immobilized 2′-Deoxyribosyltransferase from Lactobacillus delbrueckii Stabilized through a Double Covalent/Entrapment Technology
Authors: Rivero Cintia Wanda , García Natalia Soledad , Fernández-Lucas Jesús , Betancor Lorena , Romanelli Gustavo Pablo , Trelles Jorge Abel
Published: April 2021

Nowadays, enzyme-mediated processes offer an eco-friendly and efficient alternative to the traditional multistep and environmentally harmful chemical processes. Herein we report the enzymatic synthesis of cladribine by a novel 2′-deoxyribosyltransferase (NDT)-based combined biocatalyst. To this end, Lactobacillus delbrueckii NDT (LdNDT) was successfully immobilized through a two-step immobilization methodology, including a covalent immobilization onto glutaraldehyde-activated biomimetic silica nanoparticles followed by biocatalyst entrapment in calcium alginate. The resulting immobilized derivative, SiGPEI 25000-LdNDT-Alg, displayed 98% retained activity and was shown to be active and stable in a broad range of pH (5–9) and temperature (30–60 °C), but also displayed an extremely high reusability (up to 2100 reuses without negligible loss of activity) in the enzymatic production of cladribine. Finally, as a proof of concept, SiGPEI 25000-LdNDT-Alg was successfully employed in the green production of cladribine at mg scale.
Cardiac Glycosides as Immune System Modulators
Authors: Škubník Jan , Pavlíčková Vladimíra , Rimpelová Silvie
Published: April 2021

Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na+/K+-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds.
Investigation of Mitochondrial Adaptations to Modulation of Carbohydrate Supply during Adipogenesis of 3T3-L1 Cells by Targeted 1H-NMR Spectroscopy
Authors: Delcourt Manon , Delsinne Virginie , Colet Jean-Marie , Declèves Anne-Emilie , Tagliatti Vanessa
Published: April 2021

(1) Background: White adipose tissue (WAT) is a dynamic and plastic tissue showing high sensitivity to carbohydrate supply. In such a context, the WAT may accordingly modulate its mitochondrial metabolic activity. We previously demonstrated that a partial replacement of glucose by galactose in a culture medium of 3T3-L1 cells leads to a poorer adipogenic yield and improved global mitochondrial health. In the present study, we investigate key mitochondrial metabolic actors reflecting mitochondrial adaptation in response to different carbohydrate supplies. (2) Methods: The metabolome of 3T3-L1 cells was investigated during the differentiation process using different glucose/galactose ratios and by a targeted approach using 1H-NMR (Proton nuclear magnetic resonance) spectroscopy; (3) Results: Our findings indicate a reduction of adipogenic and metabolic overload markers under the low glucose/galactose condition. In addition, a remodeling of the mitochondrial function triggers the secretion of metabolites with signaling and systemic energetical homeostasis functions. Finally, this study also sheds light on a new way to consider the mitochondrial metabolic function by considering noncarbohydrates related pathways reflecting both healthier cellular and mitochondrial adaptation mechanisms; (4) Conclusions: Different carbohydrates supplies induce deep mitochondrial metabolic and function adaptations leading to overall adipocytes function and profile remodeling during the adipogenesis.
Neuropilin 1 Regulation of Vascular Permeability Signaling
Authors: Domingues Alison , Fantin Alessandro
Published: April 2021

The vascular endothelium acts as a selective barrier to regulate macromolecule exchange between the blood and tissues. However, the integrity of the endothelium barrier is compromised in an array of pathological settings, including ischemic disease and cancer, which are the leading causes of death worldwide. The resulting vascular hyperpermeability to plasma molecules as well as leukocytes then leads to tissue damaging edema formation and inflammation. The vascular endothelial growth factor A (VEGFA) is a potent permeability factor, and therefore a desirable target for impeding vascular hyperpermeability. However, VEGFA also promotes angiogenesis, the growth of new blood vessels, which is required for reperfusion of ischemic tissues. Moreover, edema increases interstitial pressure in poorly perfused tumors, thereby affecting the delivery of therapeutics, which could be counteracted by stimulating the growth of new functional blood vessels. Thus, targets must be identified to accurately modulate the barrier function of blood vessels without affecting angiogenesis, as well as to develop more effective pro- or anti-angiogenic therapies. Recent studies have shown that the VEGFA co-receptor neuropilin 1 (NRP1) could be playing a fundamental role in steering VEGFA-induced responses of vascular endothelial cells towards angiogenesis or vascular permeability. Moreover, NRP1 is involved in mediating permeability signals induced by ligands other than VEGFA. This review therefore focuses on current knowledge on the role of NRP1 in the regulation of vascular permeability signaling in the endothelium to provide an up-to-date landscape of the current knowledge in this field.
The Act of Controlling Adult Stem Cell Dynamics: Insights from Animal Models
Authors: Krishnan Meera , Kumar Sahil , Kangale Luis Johnson , Ghigo Eric , Abnave Prasad
Published: April 2021

Adult stem cells (ASCs) are the undifferentiated cells that possess self-renewal and differentiation abilities. They are present in all major organ systems of the body and are uniquely reserved there during development for tissue maintenance during homeostasis, injury, and infection. They do so by promptly modulating the dynamics of proliferation, differentiation, survival, and migration. Any imbalance in these processes may result in regeneration failure or developing cancer. Hence, the dynamics of these various behaviors of ASCs need to always be precisely controlled. Several genetic and epigenetic factors have been demonstrated to be involved in tightly regulating the proliferation, differentiation, and self-renewal of ASCs. Understanding these mechanisms is of great importance, given the role of stem cells in regenerative medicine. Investigations on various animal models have played a significant part in enriching our knowledge and giving In Vivo in-sight into such ASCs regulatory mechanisms. In this review, we have discussed the recent In Vivo studies demonstrating the role of various genetic factors in regulating dynamics of different ASCs viz. intestinal stem cells (ISCs), neural stem cells (NSCs), hematopoietic stem cells (HSCs), and epidermal stem cells (Ep-SCs).
CSN5A Subunit of COP9 Signalosome Is Required for Resetting Transcriptional Stress Memory after Recurrent Heat Stress in Arabidopsis
Authors: Singh Amit Kumar , Dhanapal Shanmuhapreya , Finkelshtein Alin , Chamovitz Daniel A.
Published: April 2021

In nature, plants are exposed to several environmental stresses that can be continuous or recurring. Continuous stress can be lethal, but stress after priming can increase the tolerance of a plant to better prepare for future stresses. Reports have suggested that transcription factors are involved in stress memory after recurrent stress; however, less is known about the factors that regulate the resetting of stress memory. Here, we uncovered a role for Constitutive Photomorphogenesis 5A (CSN5A) in the regulation of stress memory for resetting transcriptional memory genes (APX2 and HSP22) and H3K4me3 following recurrent heat stress. Furthermore, CSN5A is also required for the deposition of H3K4me3 following recurrent heat stress. Thus, CSN5A plays an important role in the regulation of histone methylation and transcriptional stress memory after recurrent heat stress.
Modulation of the EMT/MET Process by E-Cadherin in Airway Epithelia Stress Injury
Authors: Han Li , Luo Huaiqing , Huang Wenjie , Zhang Jiang , Wu Di , Wang Jinmei , Pi Jiao , Liu Chi , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Xiang Yang
Published: April 2021

Persistent injury and the following improper repair in bronchial epithelial cells are involved in the pathogenesis of airway inflammation and airway remodeling of asthma. E-cadherin (ECAD) has been shown to be involved in airway epithelium injury repair, but its underlying mechanisms to this process is poorly understood. Here, we describe a previously undetected function of ECAD in regulating the balance of EMT and MET during injury repair. Injury in mice and human bronchial epithelial cells (HBECs) was induced by successive ozone stress for 4 days at 30 min per day. ECAD overexpression in HBECs was induced by stable transfection. EMT features, transforming growth factor beta1 (TGF-β1) secretion, transcriptional repressor Snail expression, and β-catenin expression were assayed. Ozone exposure and then removal successfully induced airway epithelium injury repair during which EMT and MET occurred. The levels of TGF-β1 secretion and Snail expression increased in EMT process and decreased in MET process. While ECAD overexpression repressed EMT features; enhanced MET features; and decreased TGF-β1 secretion, Snail mRNA level, and β-catenin protein expression. Moreover, activating β-catenin blocked the effects of ECAD on EMT, MET and TGF-β1 signaling. Our results demonstrate that ECAD regulates the balance between EMT and MET, by preventing β-catenin to inhibit TGFβ1 and its target genes, and finally facilitates airway epithelia repair.
Unravelling the Molecular Mechanisms Underlying the Protective Effect of Lactate on the High-Pressure Resistance of Listeria monocytogenes
Authors: Serra-Castelló Cristina , Ferrocino Ilario , Jofré Anna , Cocolin Luca , Bover-Cid Sara , Rantsiou Kalliopi
Published: April 2021

Formulations with lactate as an antimicrobial and high-pressure processing (HPP) as a lethal treatment are combined strategies used to control L. monocytogenes in cooked meat products. Previous studies have shown that when HPP is applied in products with lactate, the inactivation of L. monocytogenes is lower than that without lactate. The purpose of the present work was to identify the molecular mechanisms underlying the piezo-protection effect of lactate. Two L. monocytogenes strains (CTC1034 and EGDe) were independently inoculated in a cooked ham model medium without and with 2.8% potassium lactate. Samples were pressurized at 400 MPa for 10 min at 10 °C. Samples were subjected to RNA extraction, and a shotgun transcriptome sequencing was performed. The short exposure of L. monocytogenes cells to lactate through its inoculation in a cooked ham model with lactate 1h before HPP promoted a shift in the pathogen’s central metabolism, favoring the metabolism of propanediol and ethanolamine together with the synthesis of the B12 cofactor. Moreover, the results suggest an activated methyl cycle that would promote modifications in membrane properties resulting in an enhanced resistance of the pathogen to HPP. This study provides insights on the mechanisms developed by L. monocytogenes in response to lactate and/or HPP and sheds light on the understanding of the piezo-protective effect of lactate.
Identification and Characterization of a Novel, Cold-Adapted d-Xylobiose- and d-Xylose-Releasing Endo-β-1,4-Xylanase from an Antarctic Soil Bacterium, Duganella sp. PAMC 27433
Authors: Kim Do Young , Kim Jonghoon , Lee Yung Mi , Lee Jong Suk , Shin Dong-Ha , Ku Bon-Hwan , Son Kwang-Hee , Park Ho-Yong
Published: April 2021

Endo-β-1,4-xylanase is a key enzyme in the degradation of β-1,4-d-xylan polysaccharides through hydrolysis. A glycoside hydrolase family 10 (GH10) endo-β-1,4-xylanase (XylR) from Duganella sp. PAMC 27433, an Antarctic soil bacterium, was identified and functionally characterized. The XylR gene (1122-bp) encoded an acidic protein containing a single catalytic GH10 domain that was 86% identical to that of an uncultured bacterium BLR13 endo-β-1,4-xylanase (ACN58881). The recombinant enzyme (rXylR: 42.0 kDa) showed the highest beechwood xylan-degrading activity at pH 5.5 and 40 °C, and displayed 12% of its maximum activity even at 4 °C. rXylR was not only almost completely inhibited by 5 mM N-bromosuccinimide or metal ions (each 1 mM) including Hg2+, Ca2+, or Cu2+ but also significantly suppressed by 1 mM Ni2+, Zn2+, or Fe2+. However, its enzyme activity was upregulated (>1.4-fold) in the presence of 0.5% Triton X-100 or Tween 80. The specific activities of rXylR toward beechwood xylan, birchwood xylan, oat spelts xylan, and p-nitrophenyl-β-d-cellobioside were 274.7, 103.2, 35.6, and 365.1 U/mg, respectively. Enzymatic hydrolysis of birchwood xylan and d-xylooligosaccharides yielded d-xylose and d-xylobiose as the end products. The results of the present study suggest that rXylR is a novel cold-adapted d-xylobiose- and d-xylose-releasing endo-β-1,4-xylanase.
Intra-Brain Connectivity vs. Inter-Brain Connectivity in Gestures Reproduction: What Relationship?
Authors: Balconi Michela , Fronda Giulia
Published: April 2021

Recently, the neurosciences have become interested in the investigation of neural responses associated with the use of gestures. This study focuses on the relationship between the intra-brain and inter-brain connectivity mechanisms underlying the execution of different categories of gestures (positive and negative affective, social, and informative) characterizing non-verbal interactions between thirteen couples of subjects, each composed of an encoder and a decoder. The study results underline a similar modulation of intra- and inter-brain connectivity for alpha, delta, and theta frequency bands in specific areas (frontal or posterior regions) depending on the type of gesture. Moreover, taking into account the gestures’ valence (positive or negative), a similar modulation of intra- and inter-brain connectivity in the left and right sides was observed. This study showed congruence in the intra-brain and inter-brain connectivity trend during the execution of different gestures, underlining how non-verbal exchanges might be characterized by intra-brain phase alignment and implicit mechanisms of mirroring and synchronization between the two individuals involved in the social exchange.
Mutations and Protein Interaction Landscape Reveal Key Cellular Events Perturbed in Upper Motor Neurons with HSP and PLS
Authors: Gozutok Oge , Helmold Benjamin Ryan , Ozdinler P. Hande
Published: April 2021

Hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS) are rare motor neuron diseases, which affect mostly the upper motor neurons (UMNs) in patients. The UMNs display early vulnerability and progressive degeneration, while other cortical neurons mostly remain functional. Identification of numerous mutations either directly linked or associated with HSP and PLS begins to reveal the genetic component of UMN diseases. Since each of these mutations are identified on genes that code for a protein, and because cellular functions mostly depend on protein-protein interactions, we hypothesized that the mutations detected in patients and the alterations in protein interaction domains would hold the key to unravel the underlying causes of their vulnerability. In an effort to bring a mechanistic insight, we utilized computational analyses to identify interaction partners of proteins and developed the protein-protein interaction landscape with respect to HSP and PLS. Protein-protein interaction domains, upstream regulators and canonical pathways begin to highlight key cellular events. Here we report that proteins involved in maintaining lipid homeostasis and cytoarchitectural dynamics and their interactions are of great importance for UMN health and stability. Their perturbation may result in neuronal vulnerability, and thus maintaining their balance could offer therapeutic interventions.
COVID-19, Isolation, Quarantine: On the Efficacy of Internet-Based Eye Movement Desensitization and Reprocessing (EMDR) and Cognitive-Behavioral Therapy (CBT) for Ongoing Trauma
Authors: Perri Rinaldo , Castelli Paola , La Rosa Cecilia , Zucchi Teresa , Onofri Antonio
Published: April 2021

Literature points to cognitive-behavioural therapy (CBT) and eye movement desensitization and reprocessing (EMDR) as evidence-based therapies for trauma-related disorders. Treatments are typically administered in a vis-à-vis setting with patients reporting symptoms of a previously experienced trauma. Conversely, online-therapies and ongoing trauma have not received adequate attention. This study aimed to compare the efficacy of two brief treatments for health professionals and individuals suffering from the circumstances imposed by the coronavirus disease 2019 (COVID-19) pandemic. The EMDR and the trauma focused-CBT were administered online during the earliest stage of distress to manage the ongoing trauma associated to quarantine or disease. Thirty-eight patients satisfying the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for acute stress disorder were randomly assigned to the EMDR or CBT treatment. Both groups received a 7-session therapy, and psychometric tests were administered before, after the treatment and at one-month follow-up to assess traumatic symptoms, depression and anxiety. Results revealed that both treatments reduced anxiety by 30%, and traumatic and depressive symptoms by 55%. Present findings indicate the internet-based EMDR and CBT as equally effective brief treatments, also suggesting a maintenance of the effects as indicated by the follow-up evaluation. The EMDR and CBT might be considered as first line therapies to treat the ongoing trauma and to prevent the sensitization and accumulation of trauma memories.
Sensory Attenuation in Sport and Rehabilitation: Perspective from Research in Parkinson’s Disease
Authors: Kearney Joshua , Brittain John-Stuart
Published: April 2021

People with Parkinson’s disease (PD) experience motor symptoms that are affected by sensory information in the environment. Sensory attenuation describes the modulation of sensory input caused by motor intent. This appears to be altered in PD and may index important sensorimotor processes underpinning PD symptoms. We review recent findings investigating sensory attenuation and reconcile seemingly disparate results with an emphasis on task-relevance in the modulation of sensory input. Sensory attenuation paradigms, across different sensory modalities, capture how two identical stimuli can elicit markedly different perceptual experiences depending on our predictions of the event, but also the context in which the event occurs. In particular, it appears as though contextual information may be used to suppress or facilitate a response to a stimulus on the basis of task-relevance. We support this viewpoint by considering the role of the basal ganglia in task-relevant sensory filtering and the use of contextual signals in complex environments to shape action and perception. This perspective highlights the dual effect of basal ganglia dysfunction in PD, whereby a reduced capacity to filter task-relevant signals harms the ability to integrate contextual cues, just when such cues are required to effectively navigate and interact with our environment. Finally, we suggest how this framework might be used to establish principles for effective rehabilitation in the treatment of PD.
Immuno-PET Molecular Imaging of RANKL in Cancer
Authors: Dewulf Jonatan , Vangestel Christel , Verhoeven Yannick , De Waele Jorrit , Zwaenepoel Karen , van Dam Peter A. , Elvas Filipe , Van den Wyngaert Tim
Published: April 2021

Purpose: The involvement of RANK/RANKL signaling in the tumor microenvironment (TME) in driving response or resistance to immunotherapy has only very recently been recognized. Current quantification methods of RANKL expression suffer from issues such as sensitivity, variability, and uncertainty on the spatial heterogeneity within the TME, resulting in conflicting reports on its reliability and limited use in clinical practice. Non-invasive molecular imaging using immuno-PET is a promising approach combining superior targeting specificity of monoclonal antibodies (mAb) and spatial, temporal and functional information of PET. Here, we evaluated radiolabeled anti-RANKL mAbs as a non-invasive biomarker of RANKL expression in the TME. Experimental design: Anti-human RANKL mAbs (AMG161 and AMG162) were radiolabeled with 89Zr using the bifunctional chelator DFO in high yield, purity and with intact binding affinity. After assessing the biodistribution in healthy CD-1 nude mice, [89Zr]Zr-DFO-AMG162 was selected for further evaluation in ME-180 (RANKL-transduced), UM-SCC-22B (RANKL-positive) and HCT-116 (RANKL-negative) human cancer xenografts to assess the feasibility of in vivo immuno-PET imaging of RANKL. Results: [89Zr]Zr-DFO-AMG162 was selected as the most promising tracer for further validation based on biodistribution experiments. We demonstrated specific accumulation of [89Zr]Zr-DFO-AMG162 in RANKL transduced ME-180 xenografts. In UM-SCC-22B xenograft models expressing physiological RANKL levels, [89Zr]Zr-DFO-AMG162 imaging detected significantly higher signal compared to control [89Zr]Zr-DFO-IgG2 and to RANKL negative HCT-116 xenografts. There was good visual agreement with tumor autoradiography and immunohistochemistry on adjacent slides, confirming these findings. Conclusions: [89Zr]Zr-DFO-AMG162 can detect heterogeneous RANKL expression in the TME of human cancer xenografts, supporting further translation of RANKL immuno-PET to evaluate tumor RANKL distribution in patients.
Temporal Quantitative Proteomics Reveals Proteomic and Phosphoproteomic Alterations Associated with Adaptive Response to Hypoxia in Melanoma Cells
Authors: Datta Keshava K. , Periasamy Parthiban , Mohan Sonali V. , Ziegman Rebekah , Gowda Harsha
Published: April 2021

Hypoxia is a common feature in various solid tumours, including melanoma. Cancer cells in hypoxic environments are resistant to both chemotherapy and radiation. Hypoxia is also associated with immune suppression. Identification of proteins and pathways that regulate cancer cell survival in hypoxic environments can reveal potential vulnerabilities that can be exploited to improve the efficacy of anticancer therapies. We carried out temporal proteomic and phosphoproteomic profiling in melanoma cell lines to identify hypoxia-induced protein expression and phosphorylation changes. By employing a TMT-based quantitative proteomics strategy, we report the identification and quantitation of >7000 proteins and >10,000 phosphosites in melanoma cell lines grown in hypoxia. Proteomics data show metabolic reprogramming as one of the prominent adaptive responses in hypoxia. We identify several novel hypoxia-mediated phosphorylation changes that have not been reported before. They reveal kinase signalling pathways that are potentially involved in modulating cellular response to hypoxia. In addition to known protein expression changes, we identify several novel proteomic alterations associated with adaptive response to hypoxia. We show that cancer cells require the ubiquitin–proteasome system to survive in both normoxia and hypoxia. Inhibition of proteasome activity affects cell survival and may provide a novel therapeutic avenue to target cancer cells in hypoxia. Our study can serve as a valuable resource to pursue novel candidates to target hypoxia in cancers and improve the efficacy of anticancer therapies.
Highly Selective Vapor and Liquid Phase Transfer Hydrogenation of Diaryl and Polycyclic Ketones with Secondary Alcohols in the Presence of Magnesium Oxide as Catalyst
Authors: Gliński Marek , Markowska Anna , Wrońska Laura , Jerzak Anna , Tarkowska Magdalena
Published: April 2021

MgO has been shown to catalyze an almost quantitative hydrogen transfer from 2-octanol as the hydrogen donor to benzophenone to form benzhydrol, a useful intermediate product in the pharmaceutical industry. The hydrogen transfer from a series of alcohols to the carbonyl group of benzophenone, its ten derivatives, four polycyclic ketones, and 2-naphthyl phenyl ketone was carried out in liquid (LP) or vapor phase (VP). The dependence of reactivity on the structure of the hydrogen donor, reaction temperature, donor-acceptor ratio, amount of catalyst, and the type and position of substituents has been established. For both reaction modes, optimal conditions for selective synthesis of the alcohols were determined and side reactions were investigated. The results indicate that the reactivity of the ketone is suppressed by the presence of a methyl substituent in the ortho position to a much greater extent in LP mode. A scale-up was demonstrated in the liquid phase mode.
Hollow-Shell-Structured Mesoporous Silica-Supported Palladium Catalyst for an Efficient Suzuki-Miyaura Cross-Coupling Reaction
Authors: Mohammed Abdulelah Taher Ali , Wang Lijian , Jin Ronghua , Liu Guohua , Tan Chunxia
Published: April 2021

The construction of a high stability heterogeneous catalyst for privileged common catalysis is a benefit in regard to reuse and separation. Herein, a palladium diphenylphosphine-based hollow-shell-structured mesoporous catalyst (HS@PdPPh2@MSN) was prepared by immobilizing bis((diphenylphosphino)ethyltriethoxysilane)palladium acetate onto the inner wall of a mesoporous organicsilicane hollow shell, whose surface was protected by a –Si(Me)3 group. Electron microscopies confirmed its hollow-shell-structure, and structural analyses and characterizations revealed its well-defined single-site active species within the silicate network. As presented in this study, the newly constructed HS@PdPPh2@MSN enabled an efficient Suzuki-Miyaura cross-coupling reaction for varieties of substrates with up to 95% yield in mild conditions. Meanwhile, it could be reused at least five times with good activity, indicating its excellent stability and recyclability. Furthermore, the cost-effective and easily synthesized HS@PdPPh2@MSN made it a good candidate for employment in fine chemical engineering.
Metabolite Biomarkers of Leishmania Antimony Resistance
Authors: Gutierrez Guarnizo Sneider Alexander , Karamysheva Zemfira N. , Galeano Elkin , Muskus Carlos E.
Published: April 2021

Leishmania parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. Leishmania exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis. Nevertheless, even though antimony resistance has been widely documented, the mechanisms involved are not completely understood. In this study, we aimed to identify potential metabolite biomarkers of antimony resistance that could improve leishmaniasis treatment. Here, using L. tropica promastigotes as the biological model, we showed that the level of response to antimony can be potentially predicted using 1H-NMR-based metabolomic profiling. Antimony-resistant parasites exhibited differences in metabolite composition at the intracellular and extracellular levels, suggesting that a metabolic remodeling is required to combat the drug. Simple and time-saving exometabolomic analysis can be efficiently used for the differentiation of sensitive and resistant parasites. Our findings suggest that changes in metabolite composition are associated with an optimized response to the osmotic/oxidative stress and a rearrangement of carbon-energy metabolism. The activation of energy metabolism can be linked to the high energy requirement during the antioxidant stress response. We also found that metabolites such as proline and lactate change linearly with the level of resistance to antimony, showing a close relationship with the parasite’s efficiency of drug resistance. A list of potential metabolite biomarkers is described and discussed.
Cancer Stem Cells and Neovascularization
Authors: Li Fengkai , Xu Jiahui , Liu Suling
Published: April 2021

Cancer stem cells (CSCs) refer to a subpopulation of cancer cells responsible for tumorigenesis, metastasis, and drug resistance. Increasing evidence suggests that CSC-associated tumor neovascularization partially contributes to the failure of cancer treatment. In this review, we discuss the roles of CSCs on tumor-associated angiogenesis via trans-differentiation or forming the capillary-like vasculogenic mimicry, as well as the roles of CSCs on facilitating endothelial cell-involved angiogenesis to support tumor progression and metastasis. Furthermore, we discuss the underlying regulation mechanisms, including the intrinsic signals of CSCs and the extrinsic signals such as cytokines from the tumor microenvironment. Further research is required to identify and verify some novel targets to develop efficient therapeutic approaches for more efficient cancer treatment through interfering CSC-mediated neovascularization.
Myeloid-Derived Suppressor Cells as Therapeutic Targets in Uterine Cervical and Endometrial Cancers
Authors: Mabuchi Seiji , Sasano Tomoyuki
Published: April 2021

Uterine cervical and endometrial cancers are the two most common gynecological malignancies. As demonstrated in other types of solid malignancies, an increased number of circulating or tumor-infiltrating myeloid-derived suppressor cells (MDSCs) have also been observed in uterine cervical and endometrial cancers, and increased MDSCs are associated with an advanced stage, a short survival, or a poor response to chemotherapy or radiotherapy. In murine models of uterine cervical and endometrial cancers, MDSCs have been shown to play important roles in the progression of cancer. In this review, we have introduced the definition of MDSCs and their functions, discussed the roles of MDSCs in uterine cervical and endometrial cancer progression, and reviewed treatment strategies targeting MDSCs, which may exhibit growth-inhibitory effects and enhance the efficacy of existing anticancer treatments.
Erdmann’s Anion—An Inexpensive and Useful Species for the Crystallization of Illicit Drugs after Street Confiscations
Authors: Wood Matthew R. , Mikhael Sandra , Bernal Ivan , Lalancette Roger A.
Published: April 2021

Erdmann’s anion [1,6-diammino tetranitrocobaltate(III)] is useful in the isolation and crystallization of recently confiscated street drugs needing to be identified and catalogued. The protonated form of such drugs forms excellent crystals with that anion; moreover, Erdmann’s salts are considerably less expensive than the classically used AuCl4− anion to isolate them, while preparation of high-quality crystals is equally easy in both cases. We describe the preparation and structures of the K+CoH6N6O8− and NH4+CoH6N7O8−, salts of Erdmann’s. In addition, herein are described the preparations of this anion’s salts with cocaine (C17H28CoN7O12), with methamphetamine (C10H22CoN7O8), and with methylone (C22H34CoN8O14), whose preparation and stereochemistry had been characterized by the old AuCl4− salts methodology. For all species in this report, the space groups and cell constants were determined at 296 and 100 K, looking for possible thermally induced polymorphism—none was found. Since the structures were essentially identical at the two temperatures studied, we discuss only the 100 K results. Complete spheres of data accessible to a Bruker ApexII diffractometer with Cu–Kα radiation, λ = 1.54178 Å, were recorded and used in the refinements. Using the refined single crystal structural data for the street drugs, we computed their X-ray powder diffraction patterns, which are beneficial as quick identification standards in law enforcement work.
Subtalar Arthroereisis for Flexible Flatfoot in Children—Clinical, Radiographic and Pedobarographic Outcome Comparing Three Different Methods
Authors: Vogt Bjoern , Toporowski Gregor , Gosheger Georg , Rölfing Jan Duedal , Rosenbaum Dieter , Schiedel Frank , Laufer Andrea , Kleine-Koenig Marie-Theres , Theil Christoph , Roedl Robert , Frommer Adrien
Published: April 2021

Subtalar arthroereises (STA) is a minimally invasive and reversible surgery to correct symptomatic flexible flatfoot (FFF) in children. Various techniques were described either applying expandable sinus tarsi implants or lateral calcaneus stop screws. Studies comparing the outcome of STA with different devices are rare. This retrospective single-center cohort study analyzes the results of STA using three different implants. 113 STA were performed in 73 consecutive patients (28 females). Mean age at surgery was 10.8 years (range 5–16). Mean follow-up was 29.0 months (range 1–111). In 21 feet the non-absorbable Kalix® endorthesis and in 56 feet the absorbable Giannini endorthesis were applied. Subtalar extraarticular screw arthroereises (SESA) was conducted in 36 feet. Clinical, radiographic and pedobarographic parameters were analyzed. No intraoperative complications were observed. All three procedures achieved comparable improvements of the clinical, radiographic and pedobarographic parameters. The mean foot function index (FFI) improved from 36.4 (range 12–63) to 22.8 (range 2–55). The mean preoperative calcaneal inclination angle and the lateral talocalcaneal angle improved from 9.5° (range 0–22) and 42.3° (range 21–62) to 12.8° (range 0–26) and 37.6° (range 15–56), respectively. Pedobarographically determined values of the arch index, the medial midfoot contact area and the medial forefoot peak pressure decreased. In contrast to SESA (1/36, 3%), a higher incidence of implant-related complications was observed using Kalix® (6/21, 29%) and Giannini (10/56, 8%) sinus tarsi implants. Peroneal muscle contractures only occurred in the SESA group (4/36, 11%). Premature removal due to treatment-related complications was necessary in 6/21 Kalix® implants (29%), 4/56 Giannini implants (7%) and 4/36 SESA implants (11%). Implant choice for treatment of painful FFF in children with STA seems to play a subordinate role. Clinical, radiographic and pedobarographic outcomes are comparable between the applied implants. Surgeons and patients should be aware of the different spectrum of implant-related complications. Treatment can be reliably monitored by radiation-free pedobarography providing dynamic information about the deformity.
Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination as a Control Strategy
Authors: Kayesh Mohammad , Hashem Md , Tsukiyama-Kohara Kyoko
Published: April 2021

Koala populations are currently declining and under threat from koala retrovirus (KoRV) infection both in the wild and in captivity. KoRV is assumed to cause immunosuppression and neoplastic diseases, favoring chlamydiosis in koalas. Currently, 10 KoRV subtypes have been identified, including an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). The host’s immune response acts as a safeguard against pathogens. Therefore, a proper understanding of the immune response mechanisms against infection is of great importance for the host’s survival, as well as for the development of therapeutic and prophylactic interventions. A vaccine is an important protective as well as being a therapeutic tool against infectious disease, and several studies have shown promise for the development of an effective vaccine against KoRV. Moreover, CRISPR/Cas9-based genome editing has opened a new window for gene therapy, and it appears to be a potential therapeutic tool in many viral infections, which could also be investigated for the treatment of KoRV infection. Here, we discuss the recent advances made in the understanding of the immune response in KoRV infection, as well as the progress towards vaccine development against KoRV infection in koalas.
The Microstructure and Conductivity Evolution of Plasma-Sprayed (Mn, Co)3O4 Spinel Coatings during Conductivity Measurements at Elevated Temperature
Authors: Zou Jianbo , Song Chen , Wen Kui , Liu Taikai , Deng Chunming , Liu Min , Yang Chenghao
Published: April 2021

(Mn, Co)3O4 spinel is widely used to protect the metallic interconnect of solid oxide fuel cells while it suffers deoxidization during the preparation by plasma spray. This work was proposed to study the effect of spray parameters on the microstructure and conductivity of spinel coatings. In this work, spinel coatings were prepared by the atmospheric plasma spray. The prepared coatings were heated up to 700 °C and held on for 15 h to allow the conductivity evolution. The microstructure and composition of coatings were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectrum (XPS). The results show that all coatings were evidently densified in two hours of heating while the measured conductivities were continuously evolved. The phase composition was found contributed more to the conductivity evolutions than the densification. The conversion of CoO to MnCo2O4 was observed and thus endowed the coatings a conductivity of 40 S/cm. A high fraction of Co3+ diffraction peaks, a high amount of Mn2+ and a low content of Co2+ jointly showed that more Co3+ occupied the B site of AB2O4 phase and more Mn2+ stood at the A site, indicating a stoichiometric composition of MnCo2O4. Annealing twins were detected by TEM and EBSD for the heated coatings but only a limited contribution to the evolution of the conductivity was considered. Finally, we suggest a high flowrate of plasma gas and a high input energy to prepare spinel coatings with designed conductivity.
Indoor and Outdoor Performance Study of Metallic Zinc Particles in Black Paint to Improve Solar Absorption for Solar Still Application
Authors: Ahmad Muhammad Shakeel , Han Shwe Sin , Zafar Amad , Ghafoor Usman , Rahim Nasrudin Abd , Ali Muhammad Umair , Rim You Seung
Published: April 2021

In this study, the effects of metallic zinc (Zn) particles were studied to increase surface temperature on a solar-still absorber, which is a major component of increased production. Various concentrations of Zn particles were mixed in black paint and applied to the absorber plate. SEM and XRD were used to examine and confirm the surface morphology and phase identification of as-received powder. UV-Vis spectroscopy was used to examine light-absorption properties. Finally, extensive indoor testing (using an improvised solar emulator) and outdoor testing were conducted to optimize the concentration. The specimens containing 10 wt% Zn in black paint showed the highest increase in temperature, i.e., 103.53 °C in indoor conditions at 1000 W/m2 irradiation, which is 59.17% higher than a bare aluminum plate and 17.57% higher than an only black-paint-coated aluminum plate. On the other hand, specimens containing 10 wt% Zn reached just 87.53 °C, compared to 80.00 °C for an only black-paint-coated aluminum plate and 60.62 °C for bare aluminum.
Critical Temperature in the BCS-BEC Crossover with Spin-Orbit Coupling
Authors: Dell’Anna Luca , Grava Stefano
Published: April 2021

We review the study of the superfluid phase transition in a system of fermions whose interaction can be tuned continuously along the crossover from Bardeen–Cooper–Schrieffer (BCS) superconducting phase to a Bose–Einstein condensate (BEC), also in the presence of a spin–orbit coupling. Below a critical temperature the system is characterized by an order parameter. Generally a mean field approximation cannot reproduce the correct behavior of the critical temperature Tc over the whole crossover. We analyze the crucial role of quantum fluctuations beyond the mean-field approach useful to find Tc along the crossover in the presence of a spin–orbit coupling, within a path integral approach. A formal and detailed derivation for the set of equations useful to derive Tc is performed in the presence of Rashba, Dresselhaus and Zeeman couplings. In particular in the case of only Rashba coupling, for which the spin–orbit effects are more relevant, the two-body bound state exists for any value of the interaction, namely in the full crossover. As a result the effective masses of the emerging bosonic excitations are finite also in the BCS regime.
Leaching Kinetics of Secondary Zinc Oxide in a NH3–NH4HCO3–H2O System
Authors: Li Hui , Zhao Linfei , Wang Le , Liang Jinglong , Yan Hongyan , Liu Jinrui
Published: April 2021

Secondary zinc oxide (SZO), which comes from the zinc industry, is an important secondary resource of zinc and other valuable metals. In this study, the production feasibility and rationality of a cleaner zinc recovery process using SZO and a hydrometallurgical method were described. Zinc extraction is promoted by the addition of ammonium bicarbonate to a NH3–H2O system, and the maximum recovery of zinc could be close to 80% at the optimum leaching conditions of a stirring rate of 400 rpm, an ammonia/ammonium ratio of 7:3, a total ammonia concentration of 4 mol/L, and a liquid/solid ratio of 7 mL/g for 30 min at 35 °C. The kinetics of leaching were modeled using the shrinking core model of constant-size particles, and the rate-controlling step was determined to be the diffusion through the product layer. The apparent activation energy of the reaction was estimated to be 11.04 KJ·mol−1, while the order of reaction with respect to total ammonia concentration was 1.53 and the liquid/solid ratio was 2.26. The analysis results of the initial residue and the leached residue indicated that lead was transferred from PbCl2 to PbCO3 and that ZnFe2O4 was not leached in the NH3-NH4HCO3-H2O system.