bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas Diffusion and Flow in Shale Nanopores with Bound Water Films
Authors: Zhao Tianyi , Ji Yuan
Published: June 2022

Shale reservoirs are rich in nanoscale pore-microfractures, and generally contain water (especially inorganic pores) under reservoir conditions. Therefore, evaluating gas flow capacity under water-bearing conditions is of great significance for analyzing reservoir capacity and forecasting production. Based on the single-phase gas transfer theory in nanopores, we established a gas transport model in both circular pores and slit pores by considering pore-fracture patterns of actual samples. As will be shown, inorganic pore fractures are mostly slit-type, while organic pores are mostly circular. This gas transport model also uses weighting coefficients superimposed on slip flow and molecular free flow. Further, the effect of water saturation on gas flow is quantified by considering the distribution characteristics of inorganic and organic pores in shale and also by combining the pore distribution characteristics of actual samples. The flow characteristics of gas in organic and inorganic pores under water-bearing conditions in the reservoir are further compared. The study lays a theoretical foundation for the reasonable evaluation and prediction of shale gas well capacity under reservoir water conditions.
New Developments in the Production and Research of Actinide Elements
Authors: Laatiaoui Mustapha , Raeder Sebastian
Published: June 2022

This article briefly reviews topics related to actinide research discussed at the virtual workshop Atomic Structure of Actinides & Related Topics organized by the University of Mainz, the Helmholtz Institute Mainz, and the GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany, and held on the 26–28 May 2021. It includes references to recent theoretical and experimental work on atomic structure and related topics, such as element production, access to nuclear properties, trace analysis, and medical applications.
Super Connected Direct Product of Graphs and Cycles
Authors: Yin Jiaqiong , Tian Yingzhi
Published: June 2022

The topology of an interconnection network can be modeled by a graph G=(V(G),E(G)). The connectivity of graph G is a parameter used to measure the reliability of a corresponding network. The direct product is an important graph product. This paper mainly focuses on the super connectedness of the direct product of graphs and cycles. The connectivity of G, denoted by κ(G), is the size of a minimum vertex set S⊆V(G) such that G−S is not connected or has only one vertex. The graph G is said to be super connected, simply super-κ, if every minimum vertex cut is the neighborhood of a vertex with minimum degree. The direct product of two graphs G and H, denoted by G×H, is the graph with vertex set V(G×H)=V(G)×V(H) and edge set E(G×H)={(u1,v1)(u2,v2)|u1u2∈E(G),v1v2∈E(H)}. In this paper, we give some sufficient conditions for the direct product G×Cn to be super connected, where Cn is the cycle on n vertices. Furthermore, those sufficient conditions are the best possible.
On the Laplacian, the Kirchhoff Index, and the Number of Spanning Trees of the Linear Pentagonal Derivation Chain
Authors: Tu Yue , Ma Xiaoling , Zhang Yuqing , Ren Junyu
Published: June 2022

Let Pn be a pentagonal chain with 2n pentagons in which two pentagons with two edges in common can be regarded as adding one vertex and two edges to a hexagon. Thus, the linear pentagonal derivation chains QPn represent the graph obtained by attaching four-membered rings to every two pentagons of Pn. In this article, the Laplacian spectrum of QPn consisting of the eigenvalues of two symmetric matrices is determined. Next, the formulas for two graph invariants that can be represented by the Laplacian spectrum, namely, the Kirchhoff index and the number of spanning trees, are studied. Surprisingly, the Kirchhoff index is almost one half of the Wiener index of a linear pentagonal derivation chain QPn.
Lab-It Is Taking Molecular Genetics to School
Authors: Simão Márcio , Conceição Natércia , Imaginário Susana , Amaro João , Cancela Maria Leonor
Published: June 2022

The Molecular Genetics Mobile Lab or “Laboratório itinerante de Genética Molecular” (Lab-it) was funded in 2008 by Leonor Cancela to promote the learning of molecular genetics which had been introduced at that time into high school biology programms. The project aimed to introduce hands-on laboratory activities in molecular genetics to complement the theoretical concepts taught in school. These included the development of experimental protocols based on theoretical scenarios focusing on themes of forensics sciences, biomedical applications, diagnostic methods, and ecological research using basic molecular biology techniques, such as DNA extraction, polymerase chain reaction (PCR), electrophoresis, and restriction enzyme application. In these scenarios, the students execute all the procedures with the help of the Lab-it instructor and using the Lab-it equipment, followed by a discussion of the results with all the participants and the school teacher. These approaches help the students to consolidate the concepts of molecular biology and simultaneously promote discussions on new advances in the area and choices for university careers. In addition to practical sessions, Lab-it also promotes seminars on topics of interest to the students and teachers. Since 2008, 18 high schools have participated in the region of Algarve, averaging each year about 400 students participating in practical activities. In 2021, despite the COVID pandemic, 9 schools and 379 students were involved in Lab-it practical sessions and 99% of them considered the activity to contribute to better understanding the molecular biology methods approached in theoretical classes and expressed high interest in those sessions.
Possible Event-Related Potential Correlates of Voluntary Attention and Reflexive Attention in the Emei Music Frog
Authors: Niu Wenjun , Shen Di , Sun Ruolei , Fan Yanzhu , Yang Jing , Zhang Baowei , Fang Guangzhan
Published: June 2022

Attention, referring to selective processing of task-related information, is central to cognition. It has been proposed that voluntary attention (driven by current goals or tasks and under top-down control) and reflexive attention (driven by stimulus salience and under bottom-up control) struggle to control the focus of attention with interaction in a push–pull fashion for everyday perception in higher vertebrates. However, how auditory attention engages in auditory perception in lower vertebrates remains unclear. In this study, each component of auditory event-related potentials (ERP) related to attention was measured for the telencephalon, diencephalon and mesencephalon in the Emei music frog (Nidirana daunchina), during the broadcasting of acoustic stimuli invoking voluntary attention (using binary playback paradigm with silence replacement) and reflexive attention (using equiprobably random playback paradigm), respectively. Results showed that (1) when the sequence of acoustic stimuli could be predicted, the amplitudes of stimulus preceding negativity (SPN) evoked by silence replacement in the forebrain were significantly greater than that in the mesencephalon, suggesting voluntary attention may engage in auditory perception in this species because of the correlation between the SPN component and top-down control such as expectation and/or prediction; (2) alternately, when the sequence of acoustic stimuli could not be predicted, the N1 amplitudes evoked in the mesencephalon were significantly greater than those in other brain areas, implying that reflexive attention may be involved in auditory signal processing because the N1 components relate to selective attention; and (3) both SPN and N1 components could be evoked by the predicted stimuli, suggesting auditory perception of the music frogs might invoke the two kind of attention resources simultaneously. The present results show that human-like ERP components related to voluntary attention and reflexive attention exist in the lower vertebrates also.
MTBP and MYC: A Dynamic Duo in Proliferation, Cancer, and Aging
Authors: Grieb Brian C. , Eischen Christine M.
Published: June 2022

The oncogenic transcription factor c-MYC (MYC) is highly conserved across species and is frequently overexpressed or dysregulated in human cancers. MYC regulates a wide range of critical cellular and oncogenic activities including proliferation, metabolism, metastasis, apoptosis, and differentiation by transcriptionally activating or repressing the expression of a large number of genes. This activity of MYC is not carried out in isolation, instead relying on its association with a myriad of protein cofactors. We determined that MDM Two Binding Protein (MTBP) indirectly binds MYC and is a novel MYC transcriptional cofactor. MTBP promotes MYC-mediated transcriptional activity, proliferation, and cellular transformation by binding in a protein complex with MYC at MYC-bound promoters. This discovery provided critical context for data linking MTBP to aging as well as a rapidly expanding body of evidence demonstrating MTBP is overexpressed in many human malignancies, is often linked to poor patient outcomes, and is necessary for cancer cell survival. As such, MTBP represents a novel and potentially broad reaching oncologic drug target, particularly when MYC is dysregulated. Here we have reviewed the discovery of MTBP and the initial controversy with its function as well as its associations with proliferation, MYC, DNA replication, aging, and human cancer.
Odonate Diversity Patterns in Italy Disclose Intricate Colonization Pathways
Authors: Fattorini Simone
Published: June 2022

As a natural bridge between Europe and Africa, Italy occupies a prominent position to understand the biogeography of Europe. The influence of climatic, spatial, and historical factors on current patterns of species richness and turnover (i.e., inter-regional biogeographical differences) has been analyzed for 88 species occurring in 17 Italian natural regions. Use of multimodel inference showed that odonate richness decreased southwards in response to decreasing rainfall, as expected for animals that depend on freshwater for their development. Use of Mantel tests indicated that patterns of inter-regional similarities were influenced by both climate and geographical distances. These patterns, as highlighted using Non-Metric Multidimensional Scaling, indicate a role for historical factors. Biogeographical similarities between Italian regions and adjacent areas revealed multiple colonization pathways. These results, coupled with the overall southward decrease in species richness, suggest that, after serving as a Pleistocene refuge from which odonates may have colonized medio-European areas, Italy was in turn subject to colonization from north to south. This resulted in Italian odonate fauna being less species rich compared to faunas in the medio-European territories, but also being biogeographically very complex.
Temperature- and Nutrients-Induced Phenotypic Changes of Antarctic Green Snow Bacteria Probed by High-Throughput FTIR Spectroscopy
Authors: Smirnova Margarita , Tafintseva Valeria , Kohler Achim , Miamin Uladzislau , Shapaval Volha
Published: June 2022

Temperature fluctuations and nutrient composition are the main parameters influencing green snow microbiome. In this study we investigated the influence of temperature and nutrient conditions on the growth and cellular chemical profile of bacteria isolated from green snow. Chemical profiling of the green snow bacteria was done by high-throughput FTIR spectroscopy combined with multivariate data analysis. We showed that temperature and nutrients fluctuations strongly affect growth ability and chemical profile of the green snow bacteria. The size of colonies for green snow bacteria grown at higher (25 °C) and lower (4 °C and 10 °C) than optimal temperature (18 °C) was smaller. All isolates grew on rich medium, and only 19 isolates were able to grow on synthetic minimal media. Lipid and mixed spectral regions showed to be phylogeny related. FTIR fingerprinting indicates that lipids are often affected by the temperature fluctuations. Growth on different media resulted in the change of the whole chemical profile, where lipids showed to be more affected than proteins and polysaccharides. Correlation analysis showed that nutrient composition is clearly strongly influencing chemical changes in the cells, followed by temperature.
The Landscape of Noncoding RNA in Pulmonary Hypertension
Authors: Deng Lin , Han Xiaofeng , Wang Ziping , Nie Xiaowei , Bian Jinsong
Published: June 2022

The transcriptome of pulmonary hypertension (PH) is complex and highly genetically heterogeneous, with noncoding RNA transcripts playing crucial roles. The majority of RNAs in the noncoding transcriptome are long noncoding RNAs (lncRNAs) with less circular RNAs (circRNAs), which are two characteristics gaining increasing attention in the forefront of RNA research field. These noncoding transcripts (especially lncRNAs and circRNAs) exert important regulatory functions in PH and emerge as potential disease biomarkers and therapeutic targets. Recent technological advancements have established great momentum for discovery and functional characterization of ncRNAs, which include broad transcriptome sequencing such as bulk RNA-sequence, single-cell and spatial transcriptomics, and RNA-protein/RNA interactions. In this review, we summarize the current research on the classification, biogenesis, and the biological functions and molecular mechanisms of these noncoding RNAs (ncRNAs) involved in the pulmonary vascular remodeling in PH. Furthermore, we highlight the utility and challenges of using these ncRNAs as biomarkers and therapeutics in PH.
Characterization of DAG Binding to TRPC Channels by Target-Dependent cis–trans Isomerization of OptoDArG
Authors: Erkan-Candag Hazel , Krivic Denis , Gsell Mathias A. F. , Aleksanyan Mina , Stockner Thomas , Dimova Rumiana , Tiapko Oleksandra , Groschner Klaus
Published: June 2022

Azobenzene-based photochromic lipids are valuable probes for the analysis of ion channel–lipid interactions. Rapid photoisomerization of these molecules enables the analysis of lipid gating kinetics and provides information on lipid sensing. Thermal relaxation of the metastable cis conformation to the trans conformation of azobenzene photolipids is rather slow in the dark and may be modified by ligand–protein interactions. Cis photolipid-induced changes in pure lipid membranes as visualized from the morphological response of giant unilamellar vesicles indicated that thermal cis–trans isomerization of both PhoDAG-1 and OptoDArG is essentially slow in the lipid bilayer environment. While the currents activated by cis PhoDAG remained stable upon termination of UV light exposure (dark, UV-OFF), cis OptoDArG-induced TRPC3/6/7 activity displayed a striking isoform-dependent exponential decay. The deactivation kinetics of cis OptoDArG-induced currents in the dark was sensitive to mutations in the L2 lipid coordination site of TRPC channels. We conclude that the binding of cis OptoDArG to TRPC channels promotes transition of cis OptoDArG to the trans conformation. This process is suggested to provide valuable information on DAG–ion channel interactions and may enable highly selective photopharmacological interventions.
The Translational Regulation in mTOR Pathway
Authors: Yang Miaomiao , Lu Yanming , Piao Weilan , Jin Hua
Published: June 2022

The mechanistic/mammalian target of rapamycin (mTOR) plays a master role in cell proliferation and growth in response to insulin, amino acids, energy levels, and oxygen. mTOR can coordinate upstream signals with downstream effectors, including transcriptional and translational apparatuses to regulate fundamental cellular processes such as energy utilization, protein synthesis, autophagy, cell growth, and proliferation. Of the above, protein synthesis is highly energy-consuming; thus, mRNA translation is under the tight and immediate control of mTOR signaling. The translational regulation driven by mTOR signaling mainly relies on eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP), ribosomal protein S6 kinase (S6K), and its downstream players, which are significant in rapid cellular response to environmental change. mTOR signaling not only controls the general mRNA translation, but preferential mRNA translation as well. This means that mTOR signaling shows the stronger selectivity to particular target mRNAs. Some evidence has supported the contribution of 4E-BP and La-related proteins 1 (LARP1) to such translational regulation. In this review, we summarize the mTOR pathway and mainly focus on mTOR-mediated mRNA translational regulation. We introduce the major components of mTOR signaling and their functions in translational control in a general or particular manner, and describe how the specificity of regulation is coordinated. Furthermore, we summarize recent research progress and propose additional ideas for reference. Because the mTOR pathway is on the center of cell growth and metabolism, comprehensively understanding this pathway will contribute to the therapy of related diseases, including cancers, type 2 diabetes, obesity, and neurodegeneration.
Blood Cell-Derived Microvesicles in Hematological Diseases and beyond
Authors: Georgatzakou Hara T. , Fortis Sotirios P. , Papageorgiou Effie G. , Antonelou Marianna H. , Kriebardis Anastasios G.
Published: June 2022

Microvesicles or ectosomes represent a major type of extracellular vesicles that are formed by outward budding of the plasma membrane. Typically, they are bigger than exosomes but smaller than apoptotic vesicles, although they may overlap with both in size and content. Their release by cells is a means to dispose redundant, damaged, or dangerous material; to repair membrane lesions; and, primarily, to mediate intercellular communication. By participating in these vital activities, microvesicles may impact a wide array of cell processes and, consequently, changes in their concentration or components have been associated with several pathologies. Of note, microvesicles released by leukocytes, red blood cells, and platelets, which constitute the vast majority of plasma microvesicles, change under a plethora of diseases affecting not only the hematological, but also the nervous, cardiovascular, and urinary systems, among others. In fact, there is evidence that microvesicles released by blood cells are significant contributors towards pathophysiological states, having inflammatory and/or coagulation and/or immunomodulatory arms, by either promoting or inhibiting the relative disease phenotypes. Consequently, even though microvesicles are typically considered to have adverse links with disease prognosis, progression, or outcomes, not infrequently, they exert protective roles in the affected cells. Based on these functional relations, microvesicles might represent promising disease biomarkers with diagnostic, monitoring, and therapeutic applications, equally to the more thoroughly studied exosomes. In the current review, we provide a summary of the features of microvesicles released by blood cells and their potential implication in hematological and non-hematological diseases.
Slug Mediates MRP2 Expression in Non-Small Cell Lung Cancer Cells
Authors: Zhang Xieyi , Liu Wangyang , Edaki Kazue , Nakazawa Yuta , Takahashi Saori , Sunakawa Hiroki , Mizoi Kenta , Ogihara Takuo
Published: June 2022

Transcriptional factors, such as Snail, Slug, and Smuc, that cause epithelial-mesenchymal transition are thought to regulate the expression of Ezrin, Radixin, and Moesin (ERM proteins), which serve as anchors for efflux transporters on the plasma membrane surface. Our previous results using lung cancer clinical samples indicated a correlation between Slug and efflux transporter MRP2. In the current study, we aimed to evaluate the relationships between MRP2, ERM proteins, and Slug in lung cancer cells. HCC827 cells were transfected by Mock and Slug plasmid. Both mRNA expression levels and protein expression levels were measured. Then, the activity of MRP2 was evaluated using CDCF and SN-38 (MRP2 substrates). HCC827 cells transfected with the Slug plasmid showed significantly higher mRNA expression levels of MRP2 than the Mock-transfected cells. However, the mRNA expression levels of ERM proteins did not show a significant difference between Slug-transfected cells and Mock-transfected cells. Protein expression of MRP2 was increased in Slug-transfected cells. The uptake of both CDCF and SN-38 was significantly decreased after transfection with Slug. This change was abrogated by treatment with MK571, an MRP2 inhibitor. The viability of Slug-transfected cells, compared to Mock cells, significantly increased after incubation with SN-38. Thus, Slug may increase the mRNA and protein expression of MRP2 without regulation by ERM proteins in HCC827 cells, thereby enhancing MRP2 activity. Inhibition of Slug may reduce the efficacy of multidrug resistance in lung cancer.
The Applicability of Current Turbidimetric Approaches for Analyzing Fibrin Fibers and Other Filamentous Networks
Authors: Belcher Heather A. , Litwa Karen , Guthold Martin , Hudson Nathan E.
Published: June 2022

Turbidimetry is an experimental technique often used to study the structure of filamentous networks. To extract structural properties such as filament diameter from turbidimetric data, simplifications to light scattering theory must be employed. In this work, we evaluate the applicability of three commonly utilized turbidimetric analysis approaches, each using slightly different simplifications. We make a specific application towards analyzing fibrin fibers, which form the structural scaffold of blood clots, but the results are generalizable. Numerical simulations were utilized to assess the applicability of each approach across a range of fiber lengths and diameters. Simulation results indicated that all three turbidimetric approaches commonly underestimate fiber diameter, and that the “Carr-Hermans” approach, utilizing wavelengths in the range of 500–800 nm, provided <10% error for the largest number of diameter/length combinations. These theoretical results were confirmed, under select conditions, via the comparison of fiber diameters extracted from experimental turbidimetric data, with diameters obtained using super-resolution microscopy.
COVID-19 and the Importance of Being Prepared: A Multidisciplinary Strategy for the Discovery of Antivirals to Combat Pandemics
Authors: Galvez-Llompart Maria , Zanni Riccardo , Galvez Jorge , Basak Subhash C. , Goyal Sagar M.
Published: June 2022

During an emergency, such as a pandemic in which time and resources are extremely scarce, it is important to find effective and rapid solutions when searching for possible treatments. One possibility in this regard is the repurposing of available “on the market” drugs. This is a proof of the concept study showing the potential of a collaboration between two research groups, engaged in computer-aided drug design and control of viral infections, for the development of early strategies to combat future pandemics. We describe a QSAR (quantitative structure activity relationship) based repurposing study on molecular topology and molecular docking for identifying inhibitors of the main protease (Mpro) of SARS-CoV-2, the causative agent of COVID-19. The aim of this computational strategy was to create an agile, rapid, and efficient way to enable the selection of molecules capable of inhibiting SARS-CoV-2 protease. Molecules selected through in silico method were tested in vitro using human coronavirus 229E as a surrogate for SARS-CoV-2. Three strategies were used to screen the antiviral activity of these molecules against human coronavirus 229E in cell cultures, e.g., pre-treatment, co-treatment, and post-treatment. We found >99% of virus inhibition during pre-treatment and co-treatment and 90–99% inhibition when the molecules were applied post-treatment (after infection with the virus). From all tested compounds, Molport-046-067-769 and Molport-046-568-802 are here reported for the first time as potential anti-SARS-CoV-2 compounds.
Comprehensive Analysis of Disease Pathology in Immunocompetent and Immunocompromised Hosts following Pulmonary SARS-CoV-2 Infection
Authors: Ramasamy Santhamani , Kolloli Afsal , Kumar Ranjeet , Husain Seema , Soteropoulos Patricia , Chang Theresa L. , Subbian Selvakumar
Published: June 2022

The Coronavirus disease 2019 (COVID-19) pandemic disproportionately affects immunocompetent and immunocompromised individuals, with the latter group being more vulnerable to severe disease and death. However, the differential pathogenesis of SARS-CoV-2 in the context of a specific immunological niche remains unknown. Similarly, systematic analysis of disease pathology in various extrapulmonary organs in immunocompetent and immunocompromised hosts during SARS-CoV-2 infection is not fully understood. We used a hamster model of SARS-CoV-2 infection, which recapitulates the pathophysiology of patients with mild-to-moderate COVID-19, to determine the dynamics of SARS-CoV-2 replication and histopathology at organ-level niches and map how COVID-19 symptoms vary in different immune contexts. Hamsters were intranasally infected with low (LD) or high (HD) inoculums of SARS-CoV-2, and the kinetics of disease pathology and viral load in multiple organs, antibody response, inflammatory cytokine expression, and genome-wide lung transcriptome by RNAseq analysis were determined and compared against corresponding responses from chemically induced immunocompromised hamsters. We observed transient body weight loss proportional to the SARS-CoV-2 infectious dose in immunocompetent hamsters. The kinetics of viral replication and peak viral loads were similar between LD and HD groups, although the latter developed more severe disease pathology in organs. Both groups generated a robust serum antibody response. In contrast, infected immunocompromised animals showed more prolonged body weight loss and mounted an inadequate SARS-CoV-2-neutralizing antibody response. The live virus was detected in the pulmonary and extrapulmonary organs for extended periods. These hamsters also had persistent inflammation with severe bronchiolar-alveolar hyperplasia/metaplasia. Consistent with the differential disease presentation, distinct changes in inflammation and immune cell response pathways and network gene expression were seen in the lungs of SARS-CoV-2-infected immunocompetent and immunocompromised animals.
Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation
Authors: Lee Chien-Hsing , Tsai Hsin-Yi , Chen Chun-Lin , Chen Jen-Lung , Lu Chao-Chun , Fang Yi-Ping , Wu Deng-Chyang , Huang Yaw-Bin , Lin Ming-Wei
Published: June 2022

Chemotherapy is the treatment of choice for gastric cancer; however, the currently available therapeutic drugs for treatment have limited efficacy. Cancer stemness and the tumor microenvironment may play crucial roles in tumor growth and chemoresistance. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum chaperone facilitating protein folding and cell homeostasis during stress and may participate in chemoresistance. Isoliquiritigenin (ISL) is a bioactive flavonoid found in licorice. In this study, we demonstrated the role of GRP78 in gastric cancer stemness and evaluated GRP78-mediated stemness inhibition, tumor microenvironment regulation, and chemosensitivity promotion by ISL. ISL not only suppressed GRP78-mediated gastric cancer stem cell–like characteristics, stemness-related protein expression, and cancer-associated fibroblast activation but also gastric tumor growth in xenograft animal studies. The findings indicated that ISL is a promising candidate for clinical use in combination chemotherapy.
High Level Expression and Purification of Cecropin-like Antimicrobial Peptides in Escherichia coli
Authors: Wu Chih-Lung , Chih Ya-Han , Hsieh Hsin-Ying , Peng Kuang-Li , Lee Yi-Zong , Yip Bak-Sau , Sue Shih-Che , Cheng Jya-Wei
Published: June 2022

Cecropins are a family of antimicrobial peptides (AMPs) that are widely found in the innate immune system of Cecropia moths. Cecropins exhibit a broad spectrum of antimicrobial and anticancer activities. The structures of Cecropins are composed of 34–39 amino acids with an N-terminal amphipathic α-helix, an AGP hinge and a hydrophobic C-terminal α-helix. KR12AGPWR6 was designed based on the Cecropin-like structural feature. In addition to its antimicrobial activities, KR12AGPWR6 also possesses enhanced salt resistance, antiendotoxin and anticancer properties. Herein, we have developed a strategy to produce recombinant KR12AGPWR6 through a salt-sensitive, pH and temperature dependent intein self-cleavage system. The His6-Intein-KR12AGPWR6 was expressed by E. coli and KR12AGPWR6 was released by the self-cleavage of intein under optimized ionic strength, pH and temperature conditions. The molecular weight and structural feature of the recombinant KR12AGPWR6 was determined by MALDI-TOF mass, CD, and NMR spectroscopy. The recombinant KR12AGPWR6 exhibited similar antimicrobial activities compared to the chemically synthesized KR12AGPWR6. Our results provide a potential strategy to obtain large quantities of AMPs and this method is feasible and easy to scale up for commercial production.
Citrus limon L.-Derived Nanovesicles Show an Inhibitory Effect on Cell Growth in p53-Inactivated Colorectal Cancer Cells via the Macropinocytosis Pathway
Authors: Takakura Hideki , Nakao Toshimasa , Narita Takumi , Horinaka Mano , Nakao-Ise Yukako , Yamamoto Tetsushi , Iizumi Yosuke , Watanabe Motoki , Sowa Yoshihiro , Oda Keisuke , Mori Nobuhiro , Sakai Toshiyuki , Mutoh Michihiro
Published: June 2022

Edible plant-derived nanovesicles have been explored as effective materials for preventing colorectal cancer (CRC) incidence, dependent on gene status, as a K-Ras-activating mutation via the macropinocytosis pathway. Approximately 70% of CRC harbors the p53 mutation, which is strongly associated with a poor prognosis for CRC. However, it has not been revealed whether p53 inactivation activates the macropinocytosis pathway or not. In this study, we investigated parental cells, wild-type or null for p53 treated with Citrus limon L.-derived nanovesicles, as potential materials for CRC prevention. Using ultracentrifugation, we obtained C. limon L.-derived nanovesicles, the diameters of which were approximately 100 nm, similar to that of the exosomes derived from mammalian cells. C. limon L.-derived nanovesicles showed inhibitory effects on cell growth in not p53-wild, but also in p53-inactivated CRC cells. Furthermore, we revealed that the macropinocytosis pathway is activated by p53 inactivation and C. limon L.-derived nanovesicles were up taken via the macropinocytosis pathway. Notably, although C. limon L.-derived nanovesicles contained citrate, the inhibitory effects of citrate were not dependent on the p53 status. We thus provide a novel mechanism for the growth inhibition of C. limon L.-derived nanovesicles via macropinocytosis and expect to develop a functional food product containing them for preventing p53-inactivation CRC incidence.
In Vitro Anticancer Activity of Two Ferrocene-Containing Camphor Sulfonamides as Promising Agents against Lung Cancer Cells
Authors: Schröder Maria , Petrova Maria , Vlahova Zlatina , Dobrikov Georgi M. , Slavchev Ivaylo , Pasheva Evdokia , Ugrinova Iva
Published: June 2022

The successful design of antitumour drugs often combines in one molecule different biologically active subunits that can affect various regulatory pathways in the cell and thus achieve higher efficacy. Two ferrocene derivatives, DK-164 and CC-78, with different residues were tested for cytotoxic potential on non-small lung cancer cell lines, A549 and H1299, and non-cancerous MRC5. DK-164 demonstrated remarkable selectivity toward cancer cells and more pronounced cytotoxicity against A549. The cytotoxicity of CC-78 toward H1299 was even higher than that of the well-established anticancer drugs cisplatin and tamoxifen, but it did not reveal any noticeable selective effect. DK-164 showed predominantly pro-apoptotic activity in non-small cell lung carcinoma (NSCLC) cells, while CC-78 caused accidental cell death with features characteristic of necrosis. The level of induced autophagy was similar for both substances in cancer cells. DK-164 treatment of A549, H1299, and MRC5 cells for 48 h significantly increased the fluorescence signal of the NFkB (nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells) protein in the nucleus in all three cell lines, while CC-78 did not provoke NFkB translocation in any of the tested cell lines. Both compounds caused a significant transfer of the p53 protein in the nucleus of A549 cells but not in non-cancerous MRC5 cells. In A549, DK-164 generated oxidative stress close to the positive control after 48 h, while CC-78 had a moderate effect on the cellular redox status. In the non-cancerous cells, MRC5, both compounds produced ROS similar to the positive control for the same incubation period. The different results related to the cytotoxic potential of DK-164 and CC-78 associated with the examined cellular mechanisms induced in lung cancer cells might be used to conclude the specific functions of the various functional groups in the ferrocene compounds, which can offer new perspectives for the design of antitumour drugs.
Chronic Rhinosinusitis, S. aureus Biofilm and Secreted Products, Inflammatory Responses, and Disease Severity
Authors: Shaghayegh Gohar , Cooksley Clare , Ramezanpour Mahnaz , Wormald Peter-John , Psaltis Alkis James , Vreugde Sarah
Published: June 2022

Chronic rhinosinusitis (CRS) is a persistent inflammation of the nasal cavity and paranasal sinuses associated with tissue remodelling, dysfunction of the sinuses’ natural defence mechanisms, and induction of different inflammatory clusters. The etiopathogenesis of CRS remains elusive, and both environmental factors, such as bacterial biofilms and the host’s general condition, are thought to play a role. Bacterial biofilms have significant clinical relevance due to their potential to cause resistance to antimicrobial therapy and host defenses. Despite substantial medical advances, some CRS patients suffer from recalcitrant disease that is unresponsive to medical and surgical treatments. Those patients often have nasal polyps with tissue eosinophilia, S. aureus-dominant mucosal biofilm, comorbid asthma, and a severely compromised quality of life. This review aims to summarise the contemporary knowledge of inflammatory cells/pathways in CRS, the role of bacterial biofilm, and their impact on the severity of the disease. Here, an emphasis is placed on S. aureus biofilm and its secreted products. A better understanding of these factors might offer important diagnostic and therapeutic perceptions for recalcitrant disease.
Exploring Anatomo-Morphometric Characteristics of Infrapatellar, Suprapatellar Fat Pad, and Knee Ligaments in Osteoarthritis Compared to Post-Traumatic Lesions
Authors: Fontanella Chiara Giulia , Belluzzi Elisa , Pozzuoli Assunta , Scioni Manuela , Olivotto Eleonora , Reale Davide , Ruggieri Pietro , De Caro Raffaele , Ramonda Roberta , Carniel Emanuele Luigi , Favero Marta , Macchi Veronica
Published: June 2022

Several studies have investigated cartilage degeneration and inflammatory subchondral bone and synovial membrane changes using magnetic resonance (MR) in osteoarthritis (OA) patients. Conversely, there is a paucity of data exploring the role of knee ligaments, infrapatellar fat pad (IFP), and suprapatellar fat pad (SFP) in knee OA compared to post-traumatic cohorts of patients. Therefore, the aim of this study was to analyze the volumetric and morphometric characteristics of the following joint tissues: IFP (volume, surface, depth, femoral and tibial arch lengths), SFP (volume, surface, oblique, antero–posterior, and cranio–caudal lengths), anterior (ACL) and posterior cruciate ligament (PCL) (volume, surface, and length), and patellar ligament (PL) (volume, surface, arc, depth, and length). Eighty-nine MR images were collected in the following three groups: (a) 32 patients with meniscal tears, (b) 29 patients with ACL rupture (ACLR), and (c) 28 patients affected by end-stage OA. Volume, surface, and length of both ACL and PCL were determined in groups a and c. A statistical decrease of IFP volume, surface, depth, femoral and tibial arch lengths was found in end-stage OA compared to patients with meniscal tear (p = 0.002, p = 0.008, p < 0.0001, p = 0.028 and p < 0.001, respectively) and patients with ACLR (p < 0.0001, p < 0.0001, p = 0.008 and p = 0.011, respectively). An increment of volume and surface SFP was observed in group b compared to both groups a and c, while no differences were found in oblique, antero–posterior, and cranio–caudal lengths of SFP among the groups. No statistical differences were highlighted comparing volume, surface, arc, and length of PL between the groups, while PL depth was observed to be decreased in end-OA patients compared with meniscal tear patients (p = 0.023). No statistical differences were observed comparing ACL and PCL lengths between patients undergoing meniscectomy and TKR. Our study confirms that IFP MR morphometric characteristics are different between controls and OA, supporting an important role of IFP in OA pathology and progression in accordance with previously published studies. In addition, PL depth changes seem to be associated with OA pathology. Multivariate analysis confirmed that OA patients had a smaller IFP compared to patients with meniscal tears, confirming its involvement in OA.
The Amyloidogenic Peptide Amyloid Beta(16–22) Displays Facet Dependent Conformation on Metal Surfaces
Authors: Somers Kieran P. , Cheung David L.
Published: June 2022

Currently, it is not understood how metal nanoparticles influence the formation of protein fibrils, although recent literature highlights that the shape and chemical composition of such nanoparticles can strongly influence the process. Understanding this process at a fundamental level can potentially unlock routes to the development of new therapeutics, as well as novel materials for technological applications. This requires a microscopic picture of the behaviour of amyloidogenic proteins on metal surfaces. Using replica exchange molecular dynamics simulations, we investigate the conformation of the model amyloidogenic peptide, Aβ(16–22), on different gold and silver surfaces. The conformation of the peptide on gold surfaces also shows a strong facet dependence, with fibril-like conformations being promoted in the 100 surface and inhibited on the 111 surface. A smaller degree of facet dependence is seen for silver with the peptide behaving similar on both of these. The difference in the facet dependence can be related to the difference between direct adsorption onto the gold 111 surface, with a preference towards indirect (water mediated) adsorption onto the other surfaces. This new information on the behaviour of an amyloidogenic peptide on metal surfaces can give insight into the size-dependent effect of nanoparticles on fibril formation and the use of surfaces to control fibrillation.
Towards Highly Loaded and Finely Dispersed CuO Catalysts via ADP: Effect of the Alumina Support
Authors: Van Everbroeck Tim , Papavasiliou Aggeliki , Ciocarlan Radu-George , Poulakis Evangelos , Philippopoulos Constantine J. , Jardim Erika O. , Silvestre-Albero Joaquin , Sakellis Elias , Cool Pegie , Katsaros Fotios K.
Published: June 2022

To meet current economic demands enforcing the replacement of platinum-group metals, extensively used in three-way-catalytic converters (TWC), research is driven towards low-cost and widely available base metals. However, to cope with their lower activity, high metal loadings must be coupled with increased dispersion. Herein, a series of CuO/Al2O3 samples is produced and the effect of different alumina supports’ properties on CuO dispersion, speciation and eventually on the TWC performance is studied. The alumina samples are synthesized via different methods, including soft-templating routes and flame spray pyrolysis, and compared with a commercial one, while CuO used as the catalytic active phase is added through ammonia-driven deposition–precipitation. As found, the large surface area and low crystallinity of the aluminas produced by soft-templating routes favor strong metal–support interaction, generating highly dispersed and strongly bonded CuO species at low loading and copper-aluminate phases at high loading. Notably, the use of amorphous mesoporous alumina completely prevents the formation of crystalline CuO even at 15 wt% Cu. Such high metal loading and dispersion capacity without the application of elevated calcination temperatures is one of the best reported for nonreducible supports. Catalytic evaluation of this material reveals a pronounced enhancement of oxidation activity with metal loading increase.
BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells
Authors: Zhang Qianru , Grunberger Jason William , Khurana Nitish , Zhou Xin , Xu Xianyu , Ghandehari Hamidreza , Chen Fenglei
Published: June 2022

Accumulation of silica nanoparticles (SNPs) in the testes leads to male reproductive toxicity. However, little is known about the effect and mechanistic insights of SNP-induced autophagy on apoptosis in Leydig cells. In this study, we aimed to verify the role of SNP-induced autophagy in apoptosis and explore the possible underlying mechanism in mouse primary Leydig cells (PLCs). H&E staining showed that SNPs changed the histological structures of the testes, including a reduction in the Leydig cell populations in vivo. CCK-8 assay showed that SNPs decreased cell viability, and flow cytometry showed that SNPs increased cell apoptosis, both in a dose-dependent manner in vitro. Additionally, Western blotting further found that SNPs activated autophagy by an increase in BECLIN-1, ATG16L, and LC3-II levels and promoted the intrinsic pathway of apoptosis by an increase in the BAX/BCL-2 ratio, cleaved the caspase 8 and caspase 3 levels. Furthermore, autophagy decreased SNP-induced apoptosis via regulation of the caspase 8 level combined with rapamycin, 3-methyladenine, and chloroquine. BECLIN-1 depletion increased the caspase 8 level, leading to an increase in SNP-induced cell apoptosis. Collectively, this evidence demonstrates that SNPs activated BECLIN-1-mediated autophagy, which prevented SNP-induced testicular toxicity via the inhibition of caspase 8-mediated cell apoptosis in Leydig cells.
Obesity: The Fat Tissue Disease Version of Cancer
Authors: Boubertakh Besma , Silvestri Cristoforo , Di Marzo Vincenzo
Published: June 2022

Obesity is a disease with high potential for fatality. It perfectly fits the disease definition, as cancer does. This is because it damages body structure and functions, both mechanically and biologically, and alters physical, mental, and social health. In addition, it shares many common morbid characteristics with the most feared disease, cancer. For example, it is influenced by a sophisticated interaction between a person’s genetics, the environment, and an increasing number of other backgrounds. Furthermore, it displays abnormal cell growth and proliferation events, only limited to white fat, resulting in adipose tissue taking up an increasing amount of space within the body. This occurs through fat “metastases” and via altered signaling that further aggravates the pathology of obesity by inducing ubiquitous dishomeostasis. These metastases can be made graver by angiogenesis, which might boost diseased tissue growth. More common features with cancer include its progressive escalation through different levels of severity and its possibility of re-onset after recovery. Despite all these similarities with cancer, obesity is substantially less agitating for most people. Thus, the ideas proposed herein could have utility to sensitize the public opinion about the hard reality of obesity. This is increasingly needed, as the obesity pandemic has waged a fierce war against our bodies and society in general, while there is still doubt about whether it is a real disease or not. Hence, raising public consciousness to properly face health issues is crucial to improving our health instead of gaining weight unhealthily. It is obviously illogical to fight cancer extremely seriously on the one hand and to consider dying with obesity as self-inflicted on the other. In fact, obesity merits a top position among the most lethal diseases besides cancer.
Detection of Acetoin and Diacetyl by a Tobacco Mosaic Virus-Assisted Field-Effect Biosensor
Authors: Welden Melanie , Severins Robin , Poghossian Arshak , Wege Christina , Bongaerts Johannes , Siegert Petra , Keusgen Michael , Schöning Michael J.
Published: June 2022

Acetoin and diacetyl have a major impact on the flavor of alcoholic beverages such as wine or beer. Therefore, their measurement is important during the fermentation process. Until now, gas chromatographic techniques have typically been applied; however, these require expensive laboratory equipment and trained staff, and do not allow for online monitoring. In this work, a capacitive electrolyte–insulator–semiconductor sensor modified with tobacco mosaic virus (TMV) particles as enzyme nanocarriers for the detection of acetoin and diacetyl is presented. The enzyme acetoin reductase from Alkalihalobacillus clausii DSM 8716T is immobilized via biotin–streptavidin affinity, binding to the surface of the TMV particles. The TMV-assisted biosensor is electrochemically characterized by means of leakage–current, capacitance–voltage, and constant capacitance measurements. In this paper, the novel biosensor is studied regarding its sensitivity and long-term stability in buffer solution. Moreover, the TMV-assisted capacitive field-effect sensor is applied for the detection of diacetyl for the first time. The measurement of acetoin and diacetyl with the same sensor setup is demonstrated. Finally, the successive detection of acetoin and diacetyl in buffer and in diluted beer is studied by tuning the sensitivity of the biosensor using the pH value of the measurement solution.
Scoping Review of Yoga in Schools: Mental Health and Cognitive Outcomes in Both Neurotypical and Neurodiverse Youth Populations
Authors: Hart Niamh , Fawkner Samantha , Niven Ailsa , Booth Josie
Published: June 2022

Yoga is used widely as a therapeutic tool for physical and mental well-being. The mind-body activity could be an inclusive and cost-effective intervention used within schools to help tackle the mental health crisis in youth populations. To date, research has focused on mainly neurotypical youth populations. However, greater acknowledgement of the impact for neurodiverse youth populations is warranted. Therefore, the aim of this scoping review is to understand what is known about the relationships between yoga in schools and mental health and cognition in neurotypical and neurodiverse youth populations. Methods: This review followed O’Malley and Arskey’s methodological framework. A comprehensive database search using fundamental keywords and index terms was conducted. Screening was carried out in CovidenceTM software. Results: Substantial evidence to support the use of school-based yoga programmes for the improvement of anxiety, self-concept, resilience, depression, self-esteem, subjective and psychological well-being, executive function, inhibition, working memory, attention and academic performance in neurotypical populations was found. Evidence to support school-based yoga programmes in neurodiverse populations with improvements in self-concept, subjective well-being, executive function, academic performance and attention was also found. Conclusions: The findings support the provision of yoga in schools to improve mental health and cognition whilst also creating clear pathways for future research and school-based yoga intervention development.
COVID-19 Lockdown, Sedentarism, Metabolic Alterations, Obesity: Can We Reverse the Domino Effect in Children?
Authors: Sforza Chiarella
Published: June 2022

Some diseases impact more on our personal and social life than other ones depending on various aspects [...]