bluuebunny/crossref_metadata_2025 huggingface dataset:
Carrier-Free Cellular Transport of CRISPR/Cas9 Ribonucleoprotein for Genome Editing by Cold Atmospheric Plasma
Authors: Cui Haodong , Jiang Min , Zhou Wenhua , Gao Ming , He Rui , Huang Yifan , Chu Paul K. , Yu Xue-Feng
Published: October 2021

A carrier-free CRISPR/Cas9 ribonucleoprotein delivery strategy for genome editing mediated by a cold atmospheric plasma (CAP) is described. The CAP is promising in many biomedical applications due to efficient production of bioactive ionized species. The MCF-7 cancer cells after CAP exposure exhibit increased extracellular reactive oxygen and nitrogen species (RONS) and altered membrane potential and permeability. Hence, transmembrane transport of Ca2+ into the cells increases and accelerates ATP hydrolysis, resulting in enhanced ATP-dependent endocytosis. Afterwards, the increased Ca2+ and ATP contents promote the release of cargo into cytoplasm due to the enhanced endosomal escape. The increased membrane permeability also facilitates passive diffusion of foreign species across the membrane into the cytosol. After CAP exposure, the MCF-7 cells incubated with Cas9 ribonucleoprotein (Cas9-sgRNA complex, Cas9sg) with a size of about 15 nm show 88.9% uptake efficiency and 65.9% nuclear import efficiency via passive diffusion and ATP-dependent endocytosis pathways. The efficient transportation of active Cas9sg after the CAP treatment leads to 21.7% and 30.2% indel efficiencies in HEK293T and MCF-7 cells, respectively. This CAP-mediated transportation process provides a simple and robust alternative for the delivery of active CRISPR/Cas9 ribonucleoprotein. Additionally, the technique can be extended to other macro-biomolecules and nanomaterials to cater to different biomedical applications.
A Multidisciplinary Approach to Evaluate the Effects of Contaminants of Emerging Concern on Natural Freshwater and Brackish Water Phytoplankton Communities
Authors: Pastorino Paolo , Broccoli Andrea , Bagolin Elisa , Anselmi Serena , Cavallo Andrea , Prearo Marino , Renzi Monia
Published: October 2021

Ecotoxicological assays on monospecific phytoplankton have limited application for detecting the effects of environmental pollutants on multiple species communities. With this study, we took an ecotoxicological, ecological, and biochemical approach to evaluate the effects of two contaminants of emerging concern (zinc oxide nanoparticles, ZnO NPs, and potassium dichromate, K2Cr2O7) at different concentrations (K2Cr2O7 5.6–18–50 mg/L; ZnO NPs 10–100–300 mg/L) on natural freshwater and brackish water phytoplankton communities. Cell density and absorbance values decreased in freshwater and brackish water phytoplankton communities after exposure to ZnO NPs (100 mg/L and 300 mg/L only for freshwater), whereas growth rate was increased in both freshwater and brackish water phytoplankton communities after exposure to ZnO NPs 10 mg/L. Differently, there was no clear relationship between concentration and inhibition growth after exposure to K2Cr2O7: the lowest cell density was recorded after exposure to 18 mg/L. Moreover, the evenness index value was lower compared to the other concentrations, indicating the growth of a few, albeit resistant species to higher K2Cr2O7 concentrations. Generally, Bacillariophyceae and Dinoficee were prevalent in phytoplankton cultures after exposure to ZnO NPs and K2Cr2O7. The Shannon-Wiener index was slightly higher in the negative than the positive controls, but diversity was low after all treatments in both ecotoxicological assays. The evenness index was always very close to zero, indicating the numerical predominance of one or very few species. Finally, the decrease in chlorophyll-a and pheophytin-a in both ecotoxicological assays indicated a change in photosynthetic activity. Our findings provide evidence for alterations in natural phytoplankton after exposure to emerging contaminants that can disrupt an entire ecosystem’s integrity.
Effects of Molecular Iodine/Chemotherapy in the Immune Component of Breast Cancer Tumoral Microenvironment
Authors: Cuenca-Micó Olga , Delgado-González Evangelina , Anguiano Brenda , Vaca-Paniagua Felipe , Medina-Rivera Alejandra , Rodríguez-Dorantes Mauricio , Aceves Carmen
Published: October 2021

Molecular iodine (I2) induces apoptotic, antiangiogenic, and antiproliferative effects in breast cancer cells. Little is known about its effects on the tumor immune microenvironment. We studied the effect of oral (5 mg/day) I2 supplementation alone (I2) or together with conventional chemotherapy (Cht+I2) on the immune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I2 and Cht+I2 samples showed significant increases in the expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I2 groups. Real-time RT-PCR showed that I2 tumors overexpress T-BET (p = 0.019) and interferon-gamma (IFNγ; p = 0.020) and silence tumor growth factor-beta (TGFβ; p = 0.049), whereas in Cht+I2 tumors, GATA3 is silenced (p = 0.014). Preliminary methylation analysis shows that I2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFβ in Cht+I2. In conclusion, our data showed that I2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also participate.
Mutually Exclusive Expression of Closely Related Odorant-Binding Proteins 9A and 9B in the Antenna of the Red Flour Beetle Tribolium castaneum
Authors: Montino Alice , Balakrishnan Karthi , Dippel Stefan , Trebels Björn , Neumann Piotr , Wimmer Ernst A.
Published: October 2021

Olfaction is crucial for insects to find food sources, mates, and oviposition sites. One of the initial steps in olfaction is facilitated by odorant-binding proteins (OBPs) that translocate hydrophobic odorants through the aqueous olfactory sensilla lymph to the odorant receptor complexes embedded in the dendritic membrane of olfactory sensory neurons. The Tribolium castaneum (Coleoptera, Tenebrionidae) OBPs encoded by the gene pair TcasOBP9A and TcasOBP9B represent the closest homologs to the well-studied Drosophila melanogaster OBP Lush (DmelOBP76a), which mediates pheromone reception. By an electroantennographic analysis, we can show that these two OBPs are not pheromone-specific but rather enhance the detection of a broad spectrum of organic volatiles. Both OBPs are expressed in the antenna but in a mutually exclusive pattern, despite their homology and gene pair character by chromosomal location. A phylogenetic analysis indicates that this gene pair arose at the base of the Cucujiformia, which dates the gene duplication event to about 200 Mio years ago. Therefore, this gene pair is not the result of a recent gene duplication event and the high sequence conservation in spite of their expression in different sensilla is potentially the result of a common function as co-OBPs.
Quantitative Super-Resolution Imaging for the Analysis of GPCR Oligomerization
Authors: Joseph Megan D. , Tomas Bort Elena , Grose Richard P. , McCormick Peter J. , Simoncelli Sabrina
Published: October 2021

G-protein coupled receptors (GPCRs) are known to form homo- and hetero- oligomers which are considered critical to modulate their function. However, studying the existence and functional implication of these complexes is not straightforward as controversial results are obtained depending on the method of analysis employed. Here, we use a quantitative single molecule super-resolution imaging technique named qPAINT to quantify complex formation within an example GPCR. qPAINT, based upon DNA-PAINT, takes advantage of the binding kinetics between fluorescently labelled DNA imager strands to complementary DNA docking strands coupled to protein targeting antibodies to quantify the protein copy number in nanoscale dimensions. We demonstrate qPAINT analysis via a novel pipeline to study the oligomerization of the purinergic receptor Y2 (P2Y2), a rhodopsin-like GPCR, highly expressed in the pancreatic cancer cell line AsPC-1, under control, agonistic and antagonistic conditions. Results reveal that whilst the density of P2Y2 receptors remained unchanged, antagonistic conditions displayed reduced percentage of oligomers, and smaller numbers of receptors in complexes. Yet, the oligomeric state of the receptors was not affected by agonist treatment, in line with previous reports. Understanding P2Y2 oligomerization under agonistic and antagonistic conditions will contribute to unravelling P2Y2 mechanistic action and therapeutic targeting.
Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts
Authors: Salvadori Laura , Chiappalupi Sara , Arato Iva , Mancuso Francesca , Calvitti Mario , Marchetti Maria Cristina , Riuzzi Francesca , Calafiore Riccardo , Luca Giovanni , Sorci Guglielmo
Published: October 2021

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in DMD gene translating in lack of functional dystrophin and resulting in susceptibility of myofibers to rupture during contraction. Inflammation and fibrosis are critical hallmarks of DMD muscles, which undergo progressive degeneration leading to loss of independent ambulation in childhood and death by early adulthood. We reported that intraperitoneal injection of microencapsulated Sertoli cells (SeC) in dystrophic mice translates into recovery of muscle morphology and performance thanks to anti-inflammatory effects and induction of the dystrophin paralogue, utrophin at the muscle level, opening new avenues in the treatment of DMD. The aim of this study is to obtain information about the direct effects of SeC on myoblasts/myotubes, as a necessary step in view of a translational application of SeC-based approaches to DMD. We show that (i) SeC-derived factors stimulate cell proliferation in the early phase of differentiation in C2C12, and human healthy and DMD myoblasts; (ii) SeC delay the expression of differentiation markers in the early phase nevertheless stimulating terminal differentiation in DMD myoblasts; (iii) SeC restrain the fibrogenic potential of fibroblasts, and inhibit myoblast-myofibroblast transdifferentiation; and, (iv) SeC provide functional replacement of dystrophin in preformed DMD myotubes regardless of the mutation by inducing heregulin β1/ErbB2/ERK1/2-dependent utrophin expression. Altogether, these results show that SeC are endowed with promyogenic and antifibrotic effects on dystrophic myoblasts, further supporting their potential use in the treatment of DMD patients. Our data also suggest that SeC-based approaches might be useful in improving the early phase of muscle regeneration, during which myoblasts have to adequately proliferate to replace the damaged muscle mass.
Dynamic Properties and Energy Dissipation Study of Sandwich Viscoelastic Damper Considering Temperature Influence
Authors: Xu Yeshou , Xu Zhaodong , Guo Yingqing , Huang Xinghuai , Dong Yaorong , Li Qiangqiang
Published: October 2021

Viscoelastic dampers are a kind of classical passive energy dissipation and vibration control devices which are widely utilized in engineering fields. The mechanical properties and energy dissipation capacity of the viscoelastic damper are significantly affected by ambient temperature. In this work, dynamic properties tests of the sandwich type viscoelastic damper at different environmental temperatures are carried out. The equivalent fractional Kelvin model which can characterize the mechanical behavior of the viscoelastic damper with varying frequencies and temperatures is introduced to describe the dynamic properties and energy dissipation capability of the sandwich viscoelastic damper. The self-heating phenomenon of the sandwich viscoelastic damper is studied with a numerical simulation, and the dynamic properties and energy dissipation variation of the viscoelastic damper with self-heating processes are also analyzed. The results show that the dynamic properties of the viscoelastic damper are significantly affected by temperature, excitation frequency and the internal self-generated heating.
Opposite Incidence Trends for Differentiated and Medullary Thyroid Cancer in Young Dutch Patients over a 30-Year Time Span
Authors: Lebbink Chantal , van den Broek Medard , Kwast Annemiek , Derikx Joep , Dierselhuis Miranda , Kruijff Schelto , Links Thera , van Trotsenburg A. , Valk Gerlof , Vriens Menno , Verrijn Stuart Annemarie , van Santen Hanneke , Karim-Kos Henrike
Published: October 2021

Thyroid cancer is the most common endocrine malignancy in children. A rising incidence has been reported worldwide. Possible explanations include the increased use of enhanced imaging (leading to incidentalomas) and an increased prevalence of risk factors. We aimed to evaluate the incidence and survival trends of thyroid cancer in Dutch children, adolescents, and young adults (0–24 years) between 1990 and 2019. The age-standardized incidence rates of differentiated thyroid cancer (DTC, including papillary and follicular thyroid cancer (PTC and FTC, respectively)) and medullary thyroid cancer (MTC), the average annual percentage changes (AAPC) in incidence rates, and 10-year overall survival (OS) were calculated based on data obtained from the nationwide cancer registry (Netherlands Cancer Registry). A total of 839 patients aged 0–24 years had been diagnosed with thyroid carcinoma (PTC: 594 (71%), FTC: 128 (15%), MTC: 114 (14%)) between 1990 and 2019. The incidence of PTC increased significantly over time (AAPC +3.6%; 95%CI +2.3 to +4.8), the incidence rate of FTC showed a stable trend ((AAPC −1.1%; 95%CI −3.4 to +1.1), while the incidence of MTC decreased significantly (AAPC: −4.4% (95%CI −7.3 to −1.5). The 10-year OS was 99.5% (1990–1999) and 98.6% (2000–2009) in patients with DTC and 92.4% (1990–1999) and 96.0% (2000–2009) in patients with MTC. In this nationwide study, a rising incidence of PTC and decreasing incidence of MTC were observed. For both groups, in spite of the high proportion of patients with lymph node involvement at diagnosis for DTC and the limited treatment options for MTC, 10-year OS was high.
Neoadjuvant Concurrent Radiotherapy and Chemotherapy in Early Breast Cancer Patients: Long-Term Results of a Prospective Phase II Trial
Authors: Jornet Diane , Loap Pierre , Pierga Jean-Yves , Laki Fatima , Vincent-Salomon Anne , Kirova Youlia M. , Fourquet Alain
Published: October 2021

Background: Neoadjuvant concurrent radiochemotherapy makes it possible to increase the breast conservation rate. This study reports the long term outcome of this treatment. Methods: From 2001 to 2003, 59 women with T2–3 N0–2 M0 invasive breast cancer (BC) not amenable to upfront breast conserving treatment (BCS) were included in this prospective, non-randomized phase II study. Chemotherapy (CT) consisted of four cycles of continuous 5-FU infusion and Vinorelbine. Starting concurrently with the second CT cycle, normofractionated RT was delivered to the breast and LN. Breast surgery was then performed. Results: Median follow-up (FU) was 13 years [3–18]. BCS was performed in 41 (69%) patients and mastectomy in 18 patients, with pathological complete response rate of 27%. Overall and distant-disease free survivals rates at 13 years were 70.9% [95% CI 59.6–84.2] and 71.5% [95% CI 60.5–84.5] respectively. Loco regional and local controls rates were 83.4% [95% CI 73.2–95.0] and 92.1% [95% CI 83.7–100], respectively. Late toxicity (CTCAE-V3) was assessed in 51 patients (86%) with a median follow-up of 13 years. Fifteen presented grade 2 fibrosis (29.4%), 8 (15.7%) had telangiectasia, and 1 had radiodermatitis. Conclusions: This combined treatment provided high long-term local control rates with limited side-effects.
Identification and Comprehensive Co-Detection of Necrotic and Viable Aneuploid Cancer Cells in Peripheral Blood
Authors: Lin Alexander Y. , Wang Daisy Dandan , Li Linda , Lin Peter Ping
Published: October 2021

Aneuploid circulating tumor cells (CTCs, CD31−) and circulating tumor endothelial cells (CTECs, CD31+) exhibit an active interplay in peripheral blood, and play an essential role in tumorigenesis, neoangiogenesis, disease progression, therapy-resistant minimal residual disease (MRD), cancer metastasis and relapse. Currently, most CTC detection techniques are restricted to the indistinguishable quantification of circulating rare cells, including both necrotic and viable cells in cancer patients. Clinically imperative demands to distinguish and detect live and/or dead non-hematological aneuploid cancer cells in peripheral blood, which will assist in the rapid evaluation of therapeutic effects, real-time monitoring of treatment resistance longitudinally developed along with therapy and the effective detection of post-therapeutic MRD, have not yet been achieved. The integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH)-derived novel strategy was developed in this study, aiming to precisely identify and detect live and necrotic cancer cells (NC) enriched from carcinoma patients’ biofluids. The innovative SE-iFISH (NC) provides a meaningful and practical approach to co-detect various viable and necrotic aneuploid CTCs and CTECs. The detected circulating rare cells can be characterized and categorized into diverse subtypes based upon cell viability, morphology, multiple tumor markers’ expression, and the degree of aneuploidy relevant to both malignancy and therapeutic resistance. Each subtype of live or necrotic CTCs and CTECs possesses distinct utility in anti-cancer drug development, translational research, and clinical practice.
Pancreatic Neuroendocrine Tumors: Molecular Mechanisms and Therapeutic Targets
Authors: Maharjan Chandra , Ear Po , Tran Catherine , Howe James , Chandrasekharan Chandrikha , Quelle Dawn
Published: October 2021

Pancreatic neuroendocrine tumors (pNETs) are unique, slow-growing malignancies whose molecular pathogenesis is incompletely understood. With rising incidence of pNETs over the last four decades, larger and more comprehensive ‘omic’ analyses of patient tumors have led to a clearer picture of the pNET genomic landscape and transcriptional profiles for both primary and metastatic lesions. In pNET patients with advanced disease, those insights have guided the use of targeted therapies that inhibit activated mTOR and receptor tyrosine kinase (RTK) pathways or stimulate somatostatin receptor signaling. Such treatments have significantly benefited patients, but intrinsic or acquired drug resistance in the tumors remains a major problem that leaves few to no effective treatment options for advanced cases. This demands a better understanding of essential molecular and biological events underlying pNET growth, metastasis, and drug resistance. This review examines the known molecular alterations associated with pNET pathogenesis, identifying which changes may be drivers of the disease and, as such, relevant therapeutic targets. We also highlight areas that warrant further investigation at the biological level and discuss available model systems for pNET research. The paucity of pNET models has hampered research efforts over the years, although recently developed cell line, animal, patient-derived xenograft, and patient-derived organoid models have significantly expanded the available platforms for pNET investigations. Advancements in pNET research and understanding are expected to guide improved patient treatments.
Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)
Authors: Es Hamidreza Aboulkheyr , Cox Thomas R , Sarafraz-Yazdi Ehsan , Thiery Jean Paul , Warkiani Majid Ebrahimi
Published: October 2021

The aim of this study was to assess the effects of pirfenidone (PFD) on promoting epithelial–mesenchymal-transition (EMT) and stemness features in breast carcinoma cells through targeting cancer-associated-fibroblasts (CAFs). Using The Cancer Genome Atlas (TCGA) database, we analyzed the association between stromal index, EMT, and stemness-related genes across 1084 breast cancer patients, identifying positive correlation between YAP1, EMT, and stemness genes in samples with a high-stromal index. We monitored carcinoma cell invasion and spheroid formation co-cultured with CAFs in a 3D microfluidic device, followed by exposing carcinoma cells, spheroids, and CAFs with PFD. We depicted a positive association between the high-stromal index and the expression of EMT and stemness genes. High YAP1 expression in samples correlated with more advanced EMT status and stromal index. Additionally, we found that CAFs promoted spheroid formation and induced the expression of YAP1, VIM, and CD44 in spheroids. Treatment with PFD reduced carcinoma cell migration and decreased the expression of these genes at the protein level. The cytokine profiling showed significant depletion of various EMT- and stemness-regulated cytokines, particularly IL8, CCL17, and TNF-beta. These data highlight the potential application of PFD on inhibiting EMT and stemness in carcinoma cells through the targeting of critical cytokines.
The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis
Authors: Bai Yuchen , Boath Jarryd , White Gabrielle R. , Kariyawasam Uluvitike G. I. U. , Farah Camile S. , Darido Charbel
Published: October 2021

The oral epithelium is one of the fastest repairing and continuously renewing tissues. Stem cell activation within the basal layer of the oral epithelium fuels the rapid proliferation of multipotent progenitors. Stem cells first undergo asymmetric cell division that requires tightly controlled and orchestrated differentiation networks to maintain the pool of stem cells while producing progenitors fated for differentiation. Rapidly expanding progenitors subsequently commit to advanced differentiation programs towards terminal differentiation, a process that regulates the structural integrity and homeostasis of the oral epithelium. Therefore, the balance between differentiation and terminal differentiation of stem cells and their progeny ensures progenitors commitment to terminal differentiation and prevents epithelial transformation and oral squamous cell carcinoma (OSCC). A recent comprehensive molecular characterization of OSCC revealed that a disruption of terminal differentiation factors is indeed a common OSCC event and is superior to oncogenic activation. Here, we discuss the role of differentiation and terminal differentiation in maintaining oral epithelial homeostasis and define terminal differentiation as a critical tumour suppressive mechanism. We further highlight factors with crucial terminal differentiation functions and detail the underlying consequences of their loss. Switching on terminal differentiation in differentiated progenitors is likely to represent an extremely promising novel avenue that may improve therapeutic interventions against OSCC.
Targeting the Redox Balance Pathway Using Ascorbic Acid in sdhb Zebrafish Mutant Larvae
Authors: Dona Margo , Lamers Maaike , Rohde Svenja , Gorissen Marnix , Timmers Henri J. L. M.
Published: October 2021

Patients with mutations in the β-subunit of the succinate dehydrogenase (SDHB) have the highest risk to develop incurable malignant phaeochromocytomas and paragangliomas (PPGLs). Therapy development is hindered by limited possibilities to test new therapeutic strategies in vivo. One possible molecular mechanism of SDHB-associated tumorigenesis originates in an overproduction of reactive oxygen species (ROS) due to mitochondrial dysfunction. Ascorbic acid (Vitamin C) has already been shown to act as anti-cancer agent in several clinical trials for various types of cancer. In this study, the potential of the sdhbrmc200 zebrafish model to study SDHB-associated PPGLs using a drug screening approach was investigated. First, we identified increased basal ROS levels in homozygous sdhb larvae compared to heterozygous and wild-type siblings. Using a semi high-throughput drug screening, the effectiveness of different dosages of anti- and pro-oxidant Vitamin C were assessed to evaluate differences in survival, ROS levels, and locomotor activity. Low-dosage levels of Vitamin C induced a decrease of ROS levels but no significant effects on lifespan. In contrast, high-dosage levels of Vitamin C shortened the lifespan of the homozygous sdhbrmc200 larvae while not affecting the lifespan of heterozygous and wild-type siblings. These results validated the sdhbrmc200 zebrafish model as a powerful drug screening tool that may be used to identify novel therapeutic targets for SDHB-associated PPGLs.
Therapeutic Values of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma: Facts and Hopes
Authors: Wang Yijun , Zhang Tongyue , Sun Mengyu , Ji Xiaoyu , Xie Meng , Huang Wenjie , Xia Limin
Published: October 2021

One of the major challenges in hepatocellular carcinoma (HCC) treatment is drug resistance and low responsiveness to systemic therapies, partly due to insufficient T cell infiltration. Myeloid-derived suppressor cells (MDSCs) are immature marrow-derived cell populations with heterogeneity and immunosuppression characteristics and are essential components of the suppressive tumor immune microenvironment (TIME). Increasing evidence has demonstrated that MDSCs are indispensable contributing factors to HCC development in a T cell-dependent or non-dependent manner. Clinically, the frequency of MDSCs is firmly linked to HCC clinical outcomes and the effectiveness of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Furthermore, MDSCs can also be used as prognostic and predictive biomarkers for patients with HCC. Therefore, treatments reprograming MDSCs may offer potential therapeutic opportunities in HCC. Here, we recapitulated the dynamic relevance of MDSCs in the initiation and development of HCC and paid special attention to the effect of MDSCs on T cells infiltration in HCC. Finally, we pointed out the potential therapeutic effect of targeting MDSCs alone or in combination, hoping to provide new insights into HCC treatment.
Optimizing MgO Content for Boosting γ-Al2O3-Supported Ni Catalyst in Dry Reforming of Methane
Authors: Bagabas Abdulaziz , Al-Fatesh Ahmed Sadeq , Kasim Samsudeen Olajide , Arasheed Rasheed , Ibrahim Ahmed Aidid , Ashamari Rawan , Anojaidi Khalid , Fakeeha Anis Hamza , Abu-Dahrieh Jehad K. , Abasaeed Ahmed Elhag
Published: October 2021

The dry reforming of methane (DRM) process has attracted research interest because of its ability to mitigate the detrimental impacts of greenhouse gases such as methane (CH4) and carbon dioxide (CO2) and produce alcohols and clean fuel. In view of this importance of DRM, we disclosed the efficiency of a new nickel-based catalyst, which was promoted with magnesia (MgO) and supported over gamma-alumina (γ-Al2O3) doped with silica (SiO2), toward DRM. The synthesized catalysts were characterized by H2 temperature-programmed reduction (H2-TPR), X-ray diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Thermogravimetric analysis (TGA), and Transmission electron microscopy (TEM) techniques. The effect of MgO weight percent loading (0.0, 1.0, 2.0, and 3.0 wt. %) was examined because the catalytic performance was found to be a function of this parameter. An optimum loading of 2.0 wt. % of MgO was obtained, where the conversion of CH4 and CO2 at 800 °C were 86% and 91%, respectively, while the syngas (H2/CO) ratios relied on temperature and were in the range of 0.85 to 0.95. The TGA measurement of the best catalyst, which was operated over a 15-h reaction time, displayed negligible weight loss (<9.0 wt. %) due to carbon deposition, indicating the good resistance of our catalyst system to the deposition of carbon owing to the dopant and the modifier. TEM images showed the presence of multiwalled carbon nanotubes, confirming the TGA.
The Role of AhR in the Hallmarks of Brain Aging: Friend and Foe
Authors: Ojo Emmanuel S. , Tischkau Shelley A.
Published: October 2021

In recent years, aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered to be involved in aging phenotypes across several species. This receptor is a highly conserved biosensor that is activated by numerous exogenous and endogenous molecules, including microbiota metabolites, to mediate several physiological and toxicological functions. Brain aging hallmarks, which include glial cell activation and inflammation, increased oxidative stress, mitochondrial dysfunction, and cellular senescence, increase the vulnerability of humans to various neurodegenerative diseases. Interestingly, many studies have implicated AhR signaling pathways in the aging process and longevity across several species. This review provides an overview of the impact of AhR pathways on various aging hallmarks in the brain and the implications for AhR signaling as a mechanism in regulating aging-related diseases of the brain. We also explore how the nature of AhR ligands determines the outcomes of several signaling pathways in brain aging processes.
Chaperone-Mediated Autophagy Markers LAMP2A and HSPA8 in Advanced Non-Small Cell Lung Cancer after Neoadjuvant Therapy
Authors: Losmanova Tereza , Zens Philipp , Scherz Amina , Schmid Ralph A. , Tschan Mario P. , Berezowska Sabina
Published: October 2021

In recent years autophagy has attracted the attention of researchers from many medical fields, including cancer research, and certain anti-macroautophagy drugs in combination with cytotoxic or targeted therapies have entered clinical trials. In the present study, we focused on a less explored subtype of autophagy, i.e., chaperone-mediated autophagy (CMA), with the key proteins LAMP2A and HSPA8 (HSC70), and their immunohistochemical evaluation with previously extensively validated antibodies. We were interested in whether the marker expression is influenced by the antecedent therapy, and its correlation with survival on a cohort of patients with non-small cell lung cancer (NSCLC) after neoadjuvant therapy and matched primary resected tumors. In concordance with our previous study, we did not find any intratumoral heterogeneity, nor correlation between the two parameters, nor correlation between the markers and any included pathological parameters. Surprisingly, the expression of both markers was also independent to tumor response or administered neoadjuvant treatment. In the survival analysis, the results were only significant for LAMP2A, where higher levels were associated with longer 5-year overall survival and disease-free survival for the mixed group of adenocarcinomas and squamous cell carcinomas (p < 0.0001 and p = 0.0019 respectively) as well as the squamous cell carcinoma subgroup (p = 0.0001 and p = 0.0001 respectively). LAMP2A was also an independent prognostic marker in univariate and multivariate analysis.
DC Nanogrids for Integration of Demand Response and Electric Vehicle Charging Infrastructures: Appraisal, Optimal Scheduling and Analysis
Authors: Habeeb Salwan Ali , Tostado-Véliz Marcos , Hasanien Hany M. , Turky Rania A. , Meteab Wisam Kaream , Jurado Francisco
Published: October 2021

With the development of electronic infrastructures and communication technologies and protocols, electric grids have evolved towards the concept of Smart Grids, which enable the communication of the different agents involved in their operation, thus notably increasing their efficiency. In this context, microgrids and nanogrids have emerged as invaluable frameworks for optimal integration of renewable sources, electric mobility, energy storage facilities and demand response programs. This paper discusses a DC isolated nanogrid layout for the integration of renewable generators, battery energy storage, demand response activities and electric vehicle charging infrastructures. Moreover, a stochastic optimal scheduling tool is developed for the studied nanogrid, suitable for operators integrated into local service entities along with the energy retailer. A stochastic model is developed for fast charging stations in particular. A case study serves to validate the developed tool and analyze the economical and operational implications of demand response programs and charging infrastructures. Results evidence the importance of demand response initiatives in the economic profit of the retailer.
Studies on the Effects of NH3 in H2 and Air on the Performance of PEMFC
Authors: Hu Kefeng , Yang Daijun
Published: October 2021

The effect of NH3 in H2 and in air was investigated at various concentrations ranging from 1.0 ppm to 100 ppm in air and ranging from 0.25 ppm to 10 ppm in fuel. The effect of NH3 on cathode caused an instantaneous decrease in cell voltage which dropped from 0.734 V to 0.712 V in 30 h and drop rates was 0.73 mV/h for 1 ppm; however, the cell voltage dropped to 0.415 V in 1 h for 100 ppm of NH3. The voltage could not be recovered after the polarization test (V-I test) but could be recovered to 84.4% after operation with neat air for 1.5 h and 98.4% after cycle voltammogram (CV). It was found that the voltage drop was obvious, and the drop rate increased with the NH3 concentration in H2. The voltage drop rates at 500 mA/cm2 were 0.54 mV/h for 0.5 ppm of NH3, 0.8 mV/h for 1 ppm, and 2 mV/h for 10 ppm. The voltage could be recovered from 70.6% to 77.3% after discharged with high purity H2 for 24 h, to 92.8% after being purged with clean air for 10 h and to 98.4% after CV scan. The tolerance concentration of NH3 in H2 for 1000 h was 40 ppb, for 2000 h was 20 ppb, and for 5000 h was 9 ppb.
A Method for Assessing the Stability of Digital Automatic Control Systems (ACS) with Discrete Elements. Hypothesis and Simulation Results
Authors: Kodkin Vladimir , Baldenkov Alexander , Anikin Alexander
Published: October 2021

The article presents a new approach to the analysis of the stability of automatic systems with discrete links. In almost all modern automatic control systems (ACS), there are links that break signals in time. These are power controlled switches—transistors or thyristors operating in a pulsed mode and digital links in regulators. Time discretization significantly affects the stability of processes in the automatic control system. The theoretical analysis of such systems is rather complicated and requires a significant change in engineering approaches to analysis. With the improvement of digital controllers and a significant increase in their performance, this problem has practically been forgotten. However, its mathematical “content” has not changed since the 1980s when discreteness began to play a major role in hindering the transition to digital automatic control systems. In this paper, we propose a new approach that consists of interpreting the sampling operation by a link with the proposed frequency characteristic, which determines the suppression of input high-frequency signals. This link greatly simplifies engineering calculations and demonstrates the new capabilities of sampling systems. These possibilities include the rational distribution of digitalization resources—the number of bits and the sampling interval between the regulator channels, depending on the frequency range of the efficiency of these channels. We verify and confirm our theoretical statements through simulations and show how this approach makes it possible to formulate new principles of construction of seemingly well-known controllers—PID (Proportional Integral Differential) controllers and variable structure systems (VSS).
The Multi-Advective Water Mixing Approach for Transport through Heterogeneous Media
Authors: Soler-Sagarra Joaquim , Hakoun Vivien , Dentz Marco , Carrera Jesus
Published: October 2021

Finding a numerical method to model solute transport in porous media with high heterogeneity is crucial, especially when chemical reactions are involved. The phase space formulation termed the multi-advective water mixing approach (MAWMA) was proposed to address this issue. The water parcel method (WP) may be obtained by discretizing MAWMA in space, time, and velocity. WP needs two transition matrices of velocity to reproduce advection (Markovian in space) and mixing (Markovian in time), separately. The matrices express the transition probability of water instead of individual solute concentration. This entails a change in concept, since the entire transport phenomenon is defined by the water phase. Concentration is reduced to a chemical attribute. The water transition matrix is obtained and is demonstrated to be constant in time. Moreover, the WP method is compared with the classic random walk method (RW) in a high heterogeneous domain. Results show that the WP adequately reproduces advection and dispersion, but overestimates mixing because mixing is a sub-velocity phase process. The WP method must, therefore, be extended to take into account incomplete mixing within velocity classes.
Interpretable Forecasting of Energy Demand in the Residential Sector
Authors: Sakkas Nikos , Yfanti Sofia , Daskalakis Costas , Barbu Eduard , Domnich Marharyta
Published: October 2021

Energy demand forecasting is practiced in several time frames; different explanatory variables are used in each case to serve different decision support mandates. For example, in the short, daily, term building level, forecasting may serve as a performance baseline. On the other end, we have long-term, policy-oriented forecasting exercises. TIMES (an acronym for The Integrated Markal Efom System) allows us to model supply and anticipated technology shifts over a long-term horizon, often extending as far away in time as 2100. Between these two time frames, we also have a mid-term forecasting time frame, that of a few years ahead. Investigations here are aimed at policy support, although in a more mid-term horizon, we address issues such as investment planning and pricing. In this paper, we develop and evaluate statistical and neural network approaches for this mid-term forecasting of final energy and electricity for the residential sector in six EU countries (Germany, the Netherlands, Sweden, Spain, Portugal and Greece). Various possible approaches to model the explanatory variables used are presented, discussed, and assessed as to their suitability. Our end goal extends beyond model accuracy; we also include interpretability and counterfactual concepts and analysis, aiming at the development of a modelling approach that can provide decision support for strategies aimed at influencing energy demand.
Types and Composition of Biomass in Biocoke Synthesis with the Coal Blending Method
Authors: Yustanti Erlina , Wardhono Endarto Yudo , Mursito Anggoro Tri , Alhamidi Ali
Published: October 2021

The steelmaking industry requires coke as a reducing agent, as an energy source, and for its ability to hold slag in a blast furnace. Coking coal as raw coke material is very limited. Studying the use of biomass as a mixture of coking coal in the synthesis of biocoke is necessary to reduce greenhouse gas coal emissions. This research focuses on biomass and heating temperature through the coal blending method to produce biocoke with optimal mechanical properties for the blast-furnace standard. The heating temperature of biomass to biochar was evaluated at 400, 500, and 600 °C. The blending of coking coal with biochar was in the compositions of 95:5, 85:15, and 75:25 wt.%. A compacting force of 20 MPa was employed to produce biocoke that was 50 mm in diameter and 27 mm thick using a hot cylinder dye. The green sample was heated at 1100 °C for 4 h, followed by quenching with a water medium, resulting in dense samples. Increasing heating temperature is generally directly proportional to an increase in fixed carbon and calorific value. Biocoke that meets several blast-furnace criteria is a coal mixture with coconut-shell charcoal of 85:15 wt.%. Carbonization at 500 °C, yielding fixed carbon, calorific value, and compressive strength, was achieved at 89.02 ± 0.11%; 29.681 ± 0.46 MJ/kg, and 6.53 ± 0.4 MPa, respectively. This product meets several criteria for blast-furnace applications, with CRI 29.8 and CSR 55.1.
Structural Modeling and Failure Assessment of Spar-Type Substructure for 5 MW Floating Offshore Wind Turbine under Extreme Conditions in the East Sea
Authors: Ha Kwangtae , Kim Jun-Bae , Yu Youngjae , Seo Hyoung-Seock
Published: October 2021

Not only the driving for offshore wind energy capacity of 12 GW by Korea’s Renewable Energy 2030 plan but also the need for the rejuvenation of existing world-class shipbuilders’ infrastructures is drawing much attention to offshore wind energy in Korea, especially to the diverse substructures. Considering the deep-sea environment in the East Sea, this paper presents detailed modeling and analysis of spar-type substructure for a 5 MW floating offshore wind turbine (FOWT). This process uses a fully coupled integrated load analysis, which was carried out using FAST, a widely used integrated load analysis software developed by NREL, coupled with an in-house hydrodynamic code (UOU code). The environmental design loads were calculated from data recorded over three years at the Ulsan Marine buoy point according to the ABS and DNVGL standards. The total 12 maximum cases from DLC 6.1 were selected to evaluate the structural integrity of the spar-type substructure under the three co-directional conditions (45°, 135°, and 315°) of wind and wave. A three-dimensional (3D) structural finite element (FE) model incorporating the wind turbine tower and floating structure bolted joint connection was constructed in FEGate (pre/post-structural analysis module based on MSC NASTRAN for ship and offshore structures). The FEM analysis applied the external loads such as the structural loads due to the inertial acceleration, buoyancy, and gravity, and the environmental loads due to the wind, wave, and current. The three-dimensional FE analysis results from the MSC Nastran software showed that the designed spar-type substructure had enough strength to endure the extreme limitation in the East Sea based on the von Mises criteria. The current process of this study would be applicable to the other substructures such as the submersible type.
Classroom Temperature and Learner Absenteeism in Public Primary Schools in the Eastern Cape, South Africa
Authors: Pule Vicky , Mathee Angela , Melariri Paula , Kapwata Thandi , Abdelatif Nada , Balakrishna Yusentha , Kunene Zamantimande , Mogotsi Mirriam , Wernecke Bianca , Wright Caradee Yael
Published: October 2021

Children spend a significant proportion of their time at school and in school buildings. A healthy learning environment that supports children should be thermally conducive for learning and working. Here, we aimed to study the relations between indoor classroom temperatures and learner absenteeism as a proxy for children’s health and well-being. This one-year prospective study that spanned two calendar years (from June 2017 to May 2018) entailed measurement of indoor classroom temperature and relative humidity, calculated as apparent temperature (Tapp) and collection of daily absenteeism records for each classroom in schools in and around King Williams Town, Eastern Cape province, South Africa. Classroom characteristics were collected using a standardized observation checklist. Mean indoor classroom temperature ranged from 11 to 30 °C, while mean outdoor temperature ranged from 6 °C to 31 °C during the sample period. Indoor classroom temperatures typically exceeded outdoor temperatures by 5 °C for 90% of the study period. While multiple factors may influence absenteeism, we found absenteeism was highest at low indoor classroom Tapp (i.e., below 15 °C). Absenteeism decreased as indoor Tapp increased to about 25 °C before showing another increase in absenteeism. Classroom characteristics differed among schools. Analyses of indoor classroom temperature and absenteeism in relation to classroom characteristics showed few statistically significant relations—although not exceptionally strong ones—likely because of the multiple factors that influence absenteeism. However, given the possible relationship between indoor temperature and absenteeism, there is a learning imperative to consider thermal comfort as a fundamental element of school planning and design. Furthermore, additional research on factors besides temperature that affect learner absenteeism is needed, especially in rural areas.
Susceptibility to COVID-19 after High Exposure to Perfluoroalkyl Substances from Contaminated Drinking Water: An Ecological Study from Ronneby, Sweden
Authors: Nielsen Christel , Jöud Anna
Published: October 2021

There is concern that immunotoxic environmental contaminants, particularly perfluoroalkyl substances (PFAS), may play a role in the clinical course of COVID-19 and epidemiologic studies are needed to answer if high-exposed populations are especially vulnerable in light of the ongoing pandemic. The objective was, therefore, to determine if exposure to highly PFAS-contaminated drinking water was associated with an increased incidence of COVID-19 in Ronneby, Sweden, during the first year of the pandemic. We conducted an ecological study determining the sex- and age-standardized incidence ratio (SIR) in the adult population relative to a neighboring reference town with similar demographic characteristics but with only background levels of exposure. In Sweden, COVID-19 is subject to mandatory reporting, and we retrieved aggregated data on all verified cases until 3 March 2021 from the Public Health Agency of Sweden. The SIR in Ronneby was estimated at 1.19 (95% CI: 1.12; 1.27). The results suggest a potential link between high PFAS exposure and susceptibility to COVID-19 that warrants further research to clarify causality.
Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review
Authors: Du Preez Stanley , Cabanas Helene , Staines Donald , Marshall-Gradisnik Sonya
Published: October 2021

The transient receptor potential (TRP) superfamily of ion channels is involved in the molecular mechanisms that mediate neuroimmune interactions and activities. Recent advancements in neuroimmunology have identified a role for TRP cation channels in several neuroimmune disorders including amyotropic lateral sclerosis, multiple sclerosis, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating disorder with an obscure aetiology, hence considerable examination of its pathobiology is warranted. Dysregulation of TRP melastatin (TRPM) subfamily members and calcium signalling processes are implicated in the neurological, immunological, cardiovascular, and metabolic impairments inherent in ME/CFS. In this review, we present TRPM7 as a potential candidate in the pathomechanism of ME/CFS, as TRPM7 is increasingly recognized as a key mediator of physiological and pathophysiological mechanisms affecting neurological, immunological, cardiovascular, and metabolic processes. A focused examination of the biochemistry of TRPM7, the role of this protein in the aforementioned systems, and the potential of TRPM7 as a molecular mechanism in the pathophysiology of ME/CFS will be discussed in this review. TRPM7 is a compelling candidate to examine in the pathobiology of ME/CFS as TRPM7 fulfils several key roles in multiple organ systems, and there is a paucity of literature reporting on its role in ME/CFS.