bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio-Inspired Design of an Underwater Robot Exploiting Fin Undulation Propulsion
Authors: Bianchi Giovanni , Cinquemani Simone , Resta Ferruccio
Published: March 2021

Interest in autonomous underwater vehicles is constantly increasing following the emerging needs of underwater exploration and military purposes. Thus, several new propulsion mechanisms are studied and developed. Fish swimming is a promising source of inspiration because they outperform conventional propellers in terms of energy efficiency and maneuvrability. Their advantages are not only due to the streamlined shape and their low-drag skin but also, above all, due to the particular fin motion, which makes thrust generation possible with small energy dissipation. This paper analyses the motion of batoid fishes that are considered highly efficient by biologists. Their motion is reproduced by different linkage mechanisms optimized to fit underwater robots. A bioinspired robot mimicking cownose ray locomotion is, then, designed and built. Numerical analysis of its dynamics allows us to measure the size of actuators and to estimate the robot behavior. Finally, the control algorithm that maintains the mechanism synchronization according to different strategies is described and some experimental results are presented.
Preliminary Analysis of a Lightweight and Deployable Soft Robot for Space Applications
Authors: Troise Mario , Gaidano Matteo , Palmieri Pierpaolo , Mauro Stefano
Published: March 2021

The rising interest in soft robotics, combined to the increasing applications in the space industry, leads to the development of novel lightweight and deployable robotic systems, that could be easily contained in a relatively small package to be deployed when required. The main challenges for soft robotic systems are the low force exertion and the control complexity. In this manuscript, a soft manipulator concept, having inflatable links, is introduced to face these issues. A prototype of the inflatable link is manufactured and statically characterized using a pseudo-rigid body model on varying inflation pressure. Moreover, the full robot model and algorithms for the load and pose estimation are presented. Finally, a control strategy, using inverse kinematics and an elastostatic approach, is developed. Experimental results provide input data for the control algorithm, and its validity domain is discussed on the basis of a simulation model. This preliminary analysis puts the basis of future advancements in building the robot prototype and developing dynamic models and robust control.
Current Progress in Femtosecond Laser Ablation/Ionisation Time-of-Flight Mass Spectrometry
Authors: Tulej Marek , Ligterink Niels F.W. , de Koning Coenraad , Grimaudo Valentine , Lukmanov Rustam , Keresztes Schmidt Peter , Riedo Andreas , Wurz Peter
Published: March 2021

The last decade witnessed considerable progress in the development of laser ablation/ionisation time-of-flight mass spectrometry (LI-TOFMS). The improvement of both the laser ablation ion sources employing femtosecond lasers and the method of ion coupling with the mass analyser led to highly sensitive element and isotope measurements, minimisation of matrix effects, and reduction of various fractionation effects. This improvement of instrumental performance can be attributed to the progress in laser technology and accompanying commercialisation of fs-laser systems, as well as the availability of fast electronics and data acquisition systems. Application of femtosecond laser radiation to ablate the sample causes negligible thermal effects, which in turn allows for improved resolution of chemical surface imaging and depth profiling. Following in the footsteps of its predecessor ns-LIMS, fs-LIMS, which employs fs-laser ablation ion sources, has been developed in the last two decades as an important method of chemical analysis and will continue to improve its performance in subsequent decades. This review discusses the background of fs-laser ablation, overviews the most relevant instrumentation and emphasises their performance figures, and summarizes the studies on several applications, including geochemical, semiconductor, and bio-relevant materials. Improving the chemical analysis is expected by the implementation of laser pulse sequences or pulse shaping methods and shorter laser wavelengths providing current progress in mass resolution achieved in fs-LIMS. In parallel, advancing the methods of data analysis has the potential of making this technique very attractive for 3D chemical analysis with micrometre lateral and sub-micrometre vertical resolution.
The Caribbean and 1.5 °C: Is SRM an Option?
Authors: Clarke Leonardo A. , Taylor Michael A. , Centella-Artola Abel , Williams Matthew St. M. , Campbell Jayaka D. , Bezanilla-Morlot Arnoldo , Stephenson Tannecia S.
Published: March 2021

The Caribbean, along with other small island developing states (SIDS), have advocated for restricting global warming to 1.5 °C above pre-industrial levels by the end of the current century. Solar radiation management (SRM) may be one way to achieve this goal. This paper examines the mean Caribbean climate under various scenarios of an SRM-altered versus an SRM-unaltered world for three global warming targets, namely, 1.5, 2.0 and 2.5 °C above pre-industrial levels. Data from the Geoengineering Model Intercomparison Project Phase 1 (GeoMIP1) were examined for two SRM scenarios: the G3 experiment where there is a gradual injection of sulfur dioxide (SO2) into the tropical lower stratosphere starting in 2020 and terminating after 50 years, and the G4 experiment where a fixed 5 Teragram (Tg) of SO2 per year is injected into the atmosphere starting in 2020 and ending after 50 years. The results show that SRM has the potential to delay attainment of the 1.5, 2.0 and 2.5 °C global warming targets. The extent of the delay varies depending on the SRM methodology but may be beyond mid-century for the 1.5 °C goal. In comparison, however, the higher temperature thresholds are both still attained before the end of century once SRM is ceased, raising questions about the value of the initial delay. The application of SRM also significantly alters mean Caribbean climate during the global warming target years (determined for a representative concentration pathway 4.5 (RCP4.5) world without SRM). The Caribbean is generally cooler but drier during the 1.5 °C years and similarly cool but less dry for years corresponding to the higher temperature targets. Finally, the mean Caribbean climate at 1.5 °C differs if the global warming target is achieved under SRM versus RCP4.5. The same is true for the higher warming targets. The implications of all the results are discussed as a background for determining whether SRM represents a viable consideration for Caribbean SIDS to achieve their “1.5 to stay alive” goal.
Determination of Dose–Response Relationship to Derive Odor Impact Criteria for a Wastewater Treatment Plant
Authors: Zhang Yan , Yang Weihua , Schauberger Günther , Wang Jianzhuang , Geng Jing , Wang Gen , Meng Jie
Published: March 2021

Municipal wastewater treatment plants (WWTPs) inside cities have been the major complained sources of odor pollution in China, whereas there is little knowledge about the dose–response relationship to describe the resident complaints caused by odor exposure. This study explored a dose–response relationship between the modelled exposure and the annoyance surveyed by questionnaires. Firstly, the time series of odor concentrations were preliminarily simulated by a dispersion model. Secondly, the perception-related odor exposures were further calculated by combining with the peak to mean factors (constant value 4 (Germany) and 2.3 (Italy)), different time periods of “a whole year”, “summer”, and “nighttime of summer”, and two approaches of odor impact criterion (OIC) (“odor-hour” and “odor concentration”). Thirdly, binomial logistic regression models were used to compare kinds of perception-related odor exposures and odor annoyance by odds ratio, goodness of fit and predictive ability. All perception-related odor exposures were positively associated with odor annoyance. The best goodness of fit was found when using “nighttime of summer” in predicting odor-annoyance responses, which highlights the importance of the time of the day and the time of the year weighting. The best predictive performance for odor perception was determined when the OIC was 4 ou/m3 at the 99th percentile for the odor exposure over time periods of nighttime of summer. The study of dose–response relationship could be useful for the odor management and control of WWTP to maximize the satisfaction of air quality for the residents inside city.
Fixed-Point Study of Generalized Rational Type Multivalued Contractive Mappings on Metric Spaces with a Graph
Authors: Choudhury Binayak , Metiya Nikhilesh , Khatua Debashis , de la Sen Manuel
Published: March 2021

The main result of this paper is a fixed-point theorem for multivalued contractions obtained through an inequality with rational terms. The contraction is an F-type contraction. The results are obtained in a metric space endowed with a graph. The main theorem is supported by illustrative examples. Several results as special cases are obtained by specific choices of the control functions involved in the inequality. The study is broadly in the domain of setvalued analysis. The methodology of the paper is a blending of both graph theoretic and analytic methods.
A Cellular Potts Model for Analyzing Cell Migration across Constraining Pillar Arrays
Authors: Scianna Marco , Preziosi Luigi
Published: March 2021

Cell migration in highly constrained environments is fundamental in a wide variety of physiological and pathological phenomena. In particular, it has been experimentally shown that the migratory capacity of most cell lines depends on their ability to transmigrate through narrow constrictions, which in turn relies on their deformation capacity. In this respect, the nucleus, which occupies a large fraction of the cell volume and is substantially stiffer than the surrounding cytoplasm, imposes a major obstacle. This aspect has also been investigated with the use of microfluidic devices formed by dozens of arrays of aligned polymeric pillars that limit the available space for cell movement. Such experimental systems, in particular, in the designs developed by the groups of Denais and of Davidson, were here reproduced with a tailored version of the Cellular Potts model, a grid-based stochastic approach where cell dynamics are established by a Metropolis algorithm for energy minimization. The proposed model allowed quantitatively analyzing selected cell migratory determinants (e.g., the cell and nuclear speed and deformation, and forces acting at the nuclear membrane) in the case of different experimental setups. Most of the numerical results show a remarkable agreement with the corresponding empirical data.
Synthetic Scaffold Systems for Increasing the Efficiency of Metabolic Pathways in Microorganisms
Authors: Geraldi Almando , Khairunnisa Fatiha , Farah Nadya , Bui Le , Rahman Ziaur
Published: March 2021

Microbes have been the preferred hosts for producing high-value chemicals from cheap raw materials. However, metabolic flux imbalance, the presence of competing pathways, and toxic intermediates often lead to low production efficiency. The spatial organization of the substrates, intermediates, and enzymes is critical to ensuring efficient metabolic activity by microorganisms. One of the most common approaches for bringing the key components of biosynthetic pathways together is through molecular scaffolds, which involves the clustering of pathway enzymes on engineered molecules via different interacting mechanisms. In particular, synthetic scaffold systems have been applied to improve the efficiency of various heterologous and synthetic pathways in Escherichia coli and Saccharomyces cerevisiae, with varying degrees of success. Herein, we review the recent developments and applications of protein-based and nucleic acid-based scaffold systems and discuss current challenges and future directions in the use of such approaches.
Arginine Metabolites as Biomarkers of Myocardial Ischaemia, Assessed with Cardiac Magnetic Resonance Imaging in Chronic Kidney Disease
Authors: Shah Ranjit J. , Tommasi Sara , Faull Randall , Gleadle Jonathan M. , Mangoni Arduino A. , Selvanayagam Joseph B.
Published: March 2021

(1) Background: Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Myocardial oxygenation and perfusion response to stress, using oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) and stress T1 mapping respectively, are impaired in CKD patients with and without known coronary artery disease (CAD). Endothelial dysfunction, assessed by circulating levels of asymmetric dimethylarginine (ADMA) and homoarginine (HMA), promotes atherosclerosis. We hypothesized that in CKD patients, worsening endothelial dysfunction is associated with worsening myocardial oxygenation and perfusion as assessed by change in OS-CMR signal intensity (Δ OS-CMR SI) and stress T1 (ΔT1) values. (2) Methods: 38 patients with advanced CKD underwent cardiovascular magnetic resonance (CMR) scanning at 3 Tesla. OS-CMR and T1 mapping images were acquired both at rest and after adenosine stress and analyzed semi-quantitatively. Serum ADMA and HMA concentrations were assessed using mass spectrometry. (3) Results: There was no significant correlation between Δ OS-CMR SI and ADMA or HMA. Interestingly, there was a significant negative correlation seen between Δ T1 and ADMA (r = −0.419, p = 0.037, n = 30) but not between Δ T1 and HMA. (4) Conclusions: Stress T1 response is impaired in CKD patients and is independently associated with higher circulating ADMA concentrations.
Lipidomic Signatures for Colorectal Cancer Diagnosis and Progression Using UPLC-QTOF-ESI+MS
Authors: Răchieriu Claudiu , Eniu Dan Tudor , Moiş Emil , Graur Florin , Socaciu Carmen , Socaciu Mihai Adrian , Hajjar Nadim Al
Published: March 2021

Metabolomics coupled with bioinformatics may identify relevant biomolecules such as putative biomarkers of specific metabolic pathways related to colorectal diagnosis, classification and prognosis. This study performed an integrated metabolomic profiling of blood serum from 25 colorectal cancer (CRC) cases previously classified (Stage I to IV) compared with 16 controls (disease-free, non-CRC patients), using high-performance liquid chromatography and mass spectrometry (UPLC-QTOF-ESI+ MS). More than 400 metabolites were separated and identified, then all data were processed by the advanced Metaboanalyst 5.0 online software, using multi- and univariate analysis, including specificity/sensitivity relationships (area under the curve (AUC) values), enrichment and pathway analysis, identifying the specific pathways affected by cancer progression in the different stages. Several sub-classes of lipids including phosphatidylglycerols (phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and PAs), fatty acids and sterol esters as well as ceramides confirmed the “lipogenic phenotype” specific to CRC development, namely the upregulated lipogenesis associated with tumor progression. Both multivariate and univariate bioinformatics confirmed the relevance of some putative lipid biomarkers to be responsible for the altered metabolic pathways in colorectal cancer.
Assessment of Occupational Exposure to Indium Dust for Indium-Tin-Oxide Manufacturing Workers
Authors: Kim Boo Wook , Cha Wonseok , Choi Sungwon , Shin Jungah , Choi Byung-Soon , Kim Miyeon
Published: March 2021

According to recent research, indium nanoparticles (NPs) are more toxic than micro-sized particles. While cases of indium lung disease have been reported worldwide, very little research has been conducted on the occupational exposure to indium NPs. Recently, an indium-related lung disease was reported in Korea, a global powerhouse for display manufacturing. In this study, we conducted an assessment ofoccupational exposure at an indium tin oxide (ITO) powder manufacturing plant, where the first case of indium lung disease in Korea occurred. Airborne dustwas obtained from a worker’s breathing zone, and area sampling in the workplace environment was conducted using real-time monitoring devices. Personal samples were analyzed for the indium concentrations in total dust, respirable dust fraction, and NPs using personal NPs respiratory deposition samplers. The total indium concentration of the personal samples was lower than the threshold limit value recommended by the American Conference of Governmental Industrial Hygienists (ACGIH TLV), which was set as occupational exposure limit (OEL). However, the respirable indium concentration exceeded the recently set ACGIH TLV for the respirable fraction of indium dust. The concentration of indium NPs ranged between 0.003 and 0.010 × 10−2 mg/m3, accounting for only 0.4% of the total and 2.7% of the respirable indium particles. This was attributed to the aggregating of NPs at the µm sub-level. Given the extremely low fraction of indium NPs in the total and respirable dust, the current OEL values, set as the total and respirable indium concentrations, do not holistically represent the occupational exposure to indium NPs or prevent health hazards. Therefore, it is necessary to set separate OEL values for indium NPs. This study covers only the process of handling ITO powder. Therefore, follow-up studies need to be conducted on other ITO sputtering target polishing and milling processes, which typically generate more airborne NPs, to further investigate the effects of indium on workers and facilitate the necessary implementation of indium-reducing technologies.
Visual Side Effects Linked to Sildenafil Consumption: An Update
Authors: Ausó Eva , Gómez-Vicente Violeta , Esquiva Gema
Published: March 2021

Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra® (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. It also exerts minor inhibitory action against PDE6, which is present exclusively in rod and cone photoreceptors. The effects of sildenafil on the visual system have been investigated in a wide variety of clinical and preclinical studies due to the fact that a high dose of sildenafil may cause mild and transient visual symptoms in some patients. A literature review was performed using PubMed, Cochrane Library and Clinical Trials databases from 1990 up to 2020, focusing on the pathophysiology of visual disorders induced by sildenafil. The aim of this review was not only to gather and summarize the information available on sildenafil clinical trials (CTs), but also to spot subpopulations with increased risk of developing undesirable visual side effects. This PDE inhibitor has been associated with transient and reversible ocular side effects, including changes in color vision and light perception, blurred vision, photophobia, conjunctival hyperemia and keratitis, and alterations in the electroretinogram (ERG). Sildenafil may induce a reversible increase in intraocular pressure (IOP) and a few case reports suggest it is involved in the development of nonarteritic ischemic optic neuropathy (NAION). Reversible idiopathic serous macular detachment, central serous retinopathy and ERG disturbances have been related to the significant impact of sildenafil on retinal perfusion. So far, sildenafil does not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors as long as the therapeutic dose is not exceeded and is taken under a physician’s direction to treat a medical condition. However, the recreational use of sildenafil can lead to harmful side effects, including vision changes.
Chromatin-Spliceosome Mutations in Acute Myeloid Leukemia
Authors: Ochi Yotaro , Ogawa Seishi
Published: March 2021

Recent genetic studies on large patient cohorts with acute myeloid leukemia (AML) have cataloged a comprehensive list of driver mutations, resulting in the classification of AML into distinct genomic subgroups. Among these subgroups, chromatin-spliceosome (CS)-AML is characterized by mutations in the spliceosome, cohesin complex, transcription factors, and chromatin modifiers. Class-defining mutations of CS-AML are also frequently identified in myelodysplastic syndrome (MDS) and secondary AML, indicating the molecular similarity among these diseases. CS-AML is associated with myelodysplasia-related changes in hematopoietic cells and poor prognosis, and, thus, can be treated using novel therapeutic strategies and allogeneic stem cell transplantation. Functional studies of CS-mutations in mice have revealed that CS-mutations typically cause MDS-like phenotypes by altering the epigenetic regulation of target genes. Moreover, multiple CS-mutations often synergistically induce more severe phenotypes, such as the development of lethal MDS/AML, suggesting that the accumulation of many CS-mutations plays a crucial role in the progression of MDS/AML. Indeed, the presence of multiple CS-mutations is a stronger indicator of CS-AML than a single mutation. This review summarizes the current understanding of the genetic and clinical features of CS-AML and the functional roles of driver mutations characterizing this unique category of AML.
Mast Cell-Derived SAMD14 Is a Novel Regulator of the Human Prostate Tumor Microenvironment
Authors: Teng Linda K. H. , Pereira Brooke A. , Keerthikumar Shivakumar , Huang Cheng , Niranjan Birunthi , Lee Sophie N. , Richards Michelle , Schittenhelm Ralf B. , Furic Luc , Goode David L. , Lawrence Mitchell G. , Taylor Renea A. , Ellem Stuart J. , Risbridger Gail P. , Lister Natalie L.
Published: March 2021

Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs), which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remain poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed that overexpression of SAMD14 in HMC-1 altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data present the first profile of human MCs derived from prostate cancer patient specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.
Gold-Based Nanoplataform for the Treatment of Anaplastic Thyroid Carcinoma: A Step Forward
Authors: Amaral Mariana , Charmier Adília J. , Afonso Ricardo A. , Catarino José , Faísca Pedro , Carvalho Lina , Ascensão Lia , Coelho João M. P. , Gaspar M. Manuela , Reis Catarina Pinto
Published: March 2021

Anaplastic thyroid carcinoma (ATC) is a very rare subtype of thyroid carcinoma and one of the most lethal malignancies. Poor prognosis is mainly associated with its undifferentiated nature, inoperability, and failing to respond to the typically used therapies for thyroid cancer. Photothermal Therapy (PTT) entails using light to increase tissues’ temperature, leading to hyperthermia-mediated cell death. Tumours are more susceptible to heat as they are unable to dissipate it. By using functionalized gold nanoparticles (AuNPs) that transform light energy into heat, it is possible to target the heat to the tumour. This study aims to formulate ATC-targeted AuNPs able to convert near-infrared light into heat, for PTT of ATC. Different AuNPs were synthetized and coated. Size, morphology, and surface plasmon resonances band were determined. The optimized coated-AuNPs were then functionalized with ligands to assess ATC’s specificity. Safety, efficacy, and selectivity were assessed in vitro. The formulations were deemed safe when not irradiated (>70% cell viability) and selective for ATC. However, when irradiated, holo-transferrin-AuNPs were the most cytotoxic (22% of cell viability). The biodistribution and safety of this formulation was assessed in vivo. Overall, this novel formulation appears to be a highly promising approach to evaluate in a very near future.
Modulating the Heat Stress Response to Improve Hyperthermia-Based Anticancer Treatments
Authors: Scutigliani Enzo M. , Liang Yongxin , Crezee Hans , Kanaar Roland , Krawczyk Przemek M.
Published: March 2021

Cancer treatments based on mild hyperthermia (39–43 °C, HT) are applied to a widening range of cancer types, but several factors limit their efficacy and slow down more widespread adoption. These factors include difficulties in adequate heat delivery, a short therapeutic window and the acquisition of thermotolerance by cancer cells. Here, we explore the biological effects of HT, the cellular responses to these effects and their clinically-relevant consequences. We then identify the heat stress response—the cellular defense mechanism that detects and counteracts the effects of heat—as one of the major forces limiting the efficacy of HT-based therapies and propose targeting this mechanism as a potentially universal strategy for improving their efficacy.
3D Pharmacophore-Based Discovery of Novel KV10.1 Inhibitors with Antiproliferative Activity
Authors: Toplak Žan , Hendrickx Louise Antonia , Gubič Špela , Možina Štefan , Žegura Bojana , Štern Alja , Novak Matjaž , Shi Xiaoyi , Peigneur Steve , Tytgat Jan , Tomašič Tihomir , Pardo Luis A. , Mašič Lucija Peterlin
Published: March 2021

(1) Background: The voltage-gated potassium channel KV10.1 (Eag1) is considered a near- universal tumour marker and represents a promising new target for the discovery of novel anticancer drugs. (2) Methods: We utilized the ligand-based drug discovery methodology using 3D pharmacophore modelling and medicinal chemistry approaches to prepare a novel structural class of KV10.1 inhibitors. Whole-cell patch clamp experiments were used to investigate potency, selectivity, kinetics and mode of inhibition. Anticancer activity was determined using 2D and 3D cell-based models. (3) Results: The virtual screening hit compound ZVS-08 discovered by 3D pharmacophore modelling exhibited an IC50 value of 3.70 µM against KV10.1 and inhibited the channel in a voltage-dependent manner consistent with the action of a gating modifier. Structural optimization resulted in the most potent KV10.1 inhibitor of the series with an IC50 value of 740 nM, which was potent on the MCF-7 cell line expressing high KV10.1 levels and low hERG levels, induced significant apoptosis in tumour spheroids of Colo-357 cells and was not mutagenic. (4) Conclusions: Computational ligand-based drug design methods can be successful in the discovery of new potent KV10.1 inhibitors. The main problem in the field of KV10.1 inhibitors remains selectivity against the hERG channel, which needs to be addressed in the future also with target-based drug design methods.
Plasminogen Activator Inhibitor-1 Secretion by Autophagy Contributes to Melanoma Resistance to Chemotherapy through Tumor Microenvironment Modulation
Authors: Tzeng Hong-Tai , Yang Jenq-Lin , Tseng Yu-Ju , Lee Chih-Hung , Chen Wei-Ju , Chyuan I-Tsu
Published: March 2021

Autophagy plays a crucial role in maintenance of cellular homeostasis via intracellular signaling pathways, lysosomal degradation of selective cargo and mediating protein secretion. Dysregulation of autophagy has been implicated in tumorigenesis, tumor progression, and resistance to therapy. However, the mechanism of autophagy-dependent secretion involved in the responsiveness to chemotherapy is poorly understood. In this study, we showed that mitoxantrone (MitoX), a chemotherapeutic agent used for treating various cancers but not melanoma, induced autophagy in melanoma cells in vitro and in vivo. We also found that plasminogen activator inhibitor (PAI)-1 secretion by MitoX-induced autophagy modulated the pro-tumoral microenvironment. Attenuation of PAI-1 activity using a specific inhibitor, tiplaxtinin (TPX), or by targeting the autophagy gene, Becn1, induced efficient antitumor immunity, thereby overcoming the resistance to MitoX in vivo. Of note, the therapeutic efficacy of TPX was abolished in MitoX-treated Becn1-defective tumors. Collectively, our results demonstrate that tumor autophagy-dependent PAI-1 secretion impairs the therapeutic efficacy of MitoX and highlight targeting of tumor autophagy or its secretory cargo, PAI-1, as a novel strategy to repurpose MitoX-based chemotherapy for melanoma treatment.
Comprehensive Genomic Characterization of Fifteen Early-Onset Lynch-Like Syndrome Colorectal Cancers
Authors: Golubicki Mariano , Díaz-Gay Marcos , Bonjoch Laia , Franch-Expósito Sebastià , Muñoz Jenifer , Cuatrecasas Miriam , Ocaña Teresa , Iseas Soledad , Mendez Guillermo , Carballido Marcela , Robbio Juan , Cisterna Daniel , Roca Enrique , Castells Antoni , Balaguer Francesc , Castellví-Bel Sergi , Antelo Marina
Published: March 2021

Lynch-like syndrome (LLS) is an increasingly common clinical challenge with an underlying molecular basis mostly unknown. To shed light onto it, we focused on a very young LLS early-onset colorectal cancer (CRC) cohort (diagnosis ≤ 40 y.o.), performing germline and tumor whole-exome sequencing (WES) of 15 patients, and additionally analyzing their corresponding tumor mutational burden (TMB) and mutational signatures. We identified four cases (27%) with double somatic putative variants in mismatch repair (MMR) core genes, as well as three additional cases (20%) with double MSH3 somatic alterations in tumors with unexplained MSH2/MSH6 loss of expression, and two cases (13%) with POLD1 potential biallelic alterations. Average TMB was significantly higher for LLS cases with double somatic alterations. Lastly, nine predicted deleterious variants in genes involved in the DNA repair functions and/or previously associated with CRC were found in nine probands, four of which also showed MMR biallelic somatic inactivation. In conclusion, we contribute new insights into LLS CRC, postulating MSH3 and POLD1 double somatic alterations as an underlying cause of a microsatellite instability (MSI) phenotype, proposing intrinsic biological differences between LLS with and without somatic alterations, and suggesting new predisposing candidate genes in this scenario.
Catalyst Heating Characteristics in the Traveling-Wave Microwave Reactor
Authors: Martínez González Alberto , Stankiewicz Andrzej , Nigar Hakan
Published: March 2021

Traveling-Wave Microwave Reactor (TMR) presents a novel heterogeneous catalytic reactor concept based on a coaxial waveguide structure. In the current paper, both modeling and experimental studies of catalyst heating in the TMR are presented. The developed 3D multiphysics model was validated from the electromagnetic and heat transfer points of view. Extrudes of silicon carbide (SiC) were selected as catalyst supports and microwave absorbing media in a packed-bed configuration. The packed-bed temperature evolution was in good agreement with experimental data, with an average deviation of less than 10%. Both experimental and simulation results show that the homogeneous temperature distribution is possible in the TMR system. It is envisioned that the TMR concept may facilitate process scale-up while providing temperature homogeneity beyond the intrinsic restrictions of microwave cavity systems.
Effect of Operating Conditions on the Performance of Rh/TiO2 Catalyst for the Reaction of LPG Steam Reforming
Authors: Kokka Aliki , Ramantani Theodora , Panagiotopoulou Paraskevi
Published: March 2021

The catalytic performance of Rh/TiO2 catalyst was investigated for the reaction of Liquefied Petroleum Gas (LPG) steam reforming with respect to the operating conditions employed. The impacts of reaction temperature, steam/C ratio, Gas Hourly Space Velocity (GHSV), and time were examined and discussed both in the absence and presence of butane in the feed. It was found that the catalytic performance is improved by increasing the reaction temperature, steam content in the feed, and/or by decreasing GHSV. In the presence of butane in the feed, the effect of H2O/C ratio on catalytic performance is prominent, whereas the opposite was observed for the effect of GHSV. The propane conversion curve decreases by adding butane in the feed, indicating that the presence of butane retards propane steam reforming. The investigation of the dynamic response of Rh/TiO2 catalyst to variations of H2O/C ratio showed that neither catalytic activity nor product selectivity is varied with time following abrupt changes of the steam/C ratio between 2 and 7. The catalyst exhibited excellent stability with time-on-stream at 500 and 650 °C. However, a reversible catalyst deactivation seems to be operable when the reaction occurs at 600 °C, resulting in a progressive decrease of propane conversion, which, however, can be completely restored by increasing the temperature to 650 °C in He flow, respectively. The long-term stability of Rh/TiO2 catalyst in the form of pellets showed that this catalyst is not only active and selective but also stable, and therefore, it is a promising catalyst for the reaction of LPG steam reforming.
Spermatogenic Activity and Sperm Traits in Post-Pubertal and Adult Tomcats (Felis catus): Implication of Intra-Male Variation in Sperm Size
Authors: Pintus Eliana , Kadlec Martin , Karlasová Barbora , Popelka Marek , Ros-Santaella José Luis
Published: March 2021

Tomcats are considered to be adults at 1 year of age, although many reach sexual maturity at an earlier age. Nevertheless, we still know little about whether the spermatogenic activity and sperm quality of mature under one-year-old tomcats differ from those of tomcats that are over one-year-old. This study aims to evaluate the spermatogenic activity, sperm traits, and their relationships in mature tomcats at two different ages. Sixteen tomcats showing complete spermatogenesis and spermatozoa in their epididymal caudae were used and classified according to their age as post-pubertal (<1 year old) or adult (˃1 year old). Our results show that adult cats have higher epididymal sperm concentration and lower coefficient of variation in sperm head width and ellipticity than post-pubertal cats. However, they do not differ in their testicular and epididymal mass, spermatogenesis, and sperm traits such as motility, mitochondrial activity, morphology, morphometry, as well as plasma membrane, acrosome, and DNA integrity. Reduced intra-male variation of sperm head ellipticity is associated with higher testis mass, epididymis mass, and sperm concentration. Interestingly, low intra-male variation in sperm head size is associated with increased Sertoli cell function and reduced post-meiotic germ cell loss. These findings increase our knowledge about feline reproductive physiology and provide new insights into the functional significance of low intra-male variation in sperm size and shape in tomcats.
Beyond Self-Recycling: Cell-Specific Role of Autophagy in Atherosclerosis
Authors: Henderson James M. , Weber Christian , Santovito Donato
Published: March 2021

Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall and underlies the development of cardiovascular diseases, such as myocardial infarction and ischemic stroke. As such, atherosclerosis stands as the leading cause of death and disability worldwide and intensive scientific efforts are made to investigate its complex pathophysiology, which involves the deregulation of crucial intracellular pathways and intricate interactions between diverse cell types. A growing body of evidence, including in vitro and in vivo studies involving cell-specific deletion of autophagy-related genes (ATGs), has unveiled the mechanistic relevance of cell-specific (endothelial, smooth-muscle, and myeloid cells) defective autophagy in the processes of atherogenesis. In this review, we underscore the recent insights on autophagy’s cell-type-dependent role in atherosclerosis development and progression, featuring the relevance of canonical catabolic functions and emerging noncanonical mechanisms, and highlighting the potential therapeutic implications for prevention and treatment of atherosclerosis and its complications.
Hydrogen Nano-Bubble Water Suppresses ROS Generation, Adipogenesis, and Interleukin-6 Secretion in Hydrogen-Peroxide- or PMA-Stimulated Adipocytes and Three-Dimensional Subcutaneous Adipose Equivalents
Authors: Xiao Li , Miwa Nobuhiko
Published: March 2021

Reactive oxygen species (ROS)-induced oxidative stress in adipose tissue is associated with inflammation and the development of obesity-related metabolic disorders. The aim of this study is to investigate the effects of hydrogen nano-bubble water (HW) on ROS generation, adipogenesis, and interleukin-6 (IL-6) secretion in hydrogen peroxide (H2O2) or phorbol 12-myristate 13-acetate (PMA)-stimulated OP9 adipocytes, and three-dimensional (3D) subcutaneous adipose equivalents. Nanoparticle tracking analysis showed that fresh HW contains 1.17 × 108/mL of nano-sized hydrogen bubbles. Even after 8 to 13 months of storage, approximately half of the bubbles still remained in the water. CellROX® staining showed that HW could diminish H2O2- or PMA-induced intracellular ROS generation in human keratinocytes HaCaT and OP9 cells. We discovered that PMA could markedly increase lipid accumulation to 180% and IL-6 secretion 2.7-fold in OP9 adipocytes. Similarly, H2O2 (5 µM) also significantly stimulated lipid accumulation in OP9 cells and the 3D adipose equivalents. HW treatment significantly repressed H2O2- or PMA-induced lipid accumulation and IL-6 secretion in OP9 adipocytes and the 3D adipose equivalents. In conclusion, HW showed a possibility of repressing oxidative stress, inflammatory response, and adipogenesis at cellular/tissue levels. It can be used for preventing the development of metabolic disorders amongst obese people.
Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge
Authors: Gutiérrez-Cuevas Jorge , Sandoval-Rodriguez Ana , Meza-Rios Alejandra , Monroy-Ramírez Hugo Christian , Galicia-Moreno Marina , García-Bañuelos Jesús , Santos Arturo , Armendariz-Borunda Juan
Published: March 2021

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.
TRPM4 Participates in Aldosterone-Salt-Induced Electrical Atrial Remodeling in Mice
Authors: Simard Christophe , Ferchaud Virginie , Sallé Laurent , Milliez Paul , Manrique Alain , Alexandre Joachim , Guinamard Romain
Published: March 2021

Aldosterone plays a major role in atrial structural and electrical remodeling, in particular through Ca2+-transient perturbations and shortening of the action potential. The Ca2+-activated non-selective cation channel Transient Receptor Potential Melastatin 4 (TRPM4) participates in atrial action potential. The aim of our study was to elucidate the interactions between aldosterone and TRPM4 in atrial remodeling and arrhythmias susceptibility. Hyperaldosteronemia, combined with a high salt diet, was induced in mice by subcutaneously implanted osmotic pumps during 4 weeks, delivering aldosterone or physiological serum for control animals. The experiments were conducted in wild type animals (Trpm4+/+) as well as Trpm4 knock-out animals (Trpm4-/-). The atrial diameter measured by echocardiography was higher in Trpm4-/- compared to Trpm4+/+ animals, and hyperaldosteronemia-salt produced a dilatation in both groups. Action potentials duration and triggered arrhythmias were measured using intracellular microelectrodes on the isolated left atrium. Hyperaldosteronemia-salt prolong action potential in Trpm4-/- mice but had no effect on Trpm4+/+ mice. In the control group (no aldosterone-salt treatment), no triggered arrythmias were recorded in Trpm4+/+ mice, but a high level was detected in Trpm4-/- mice. Hyperaldosteronemia-salt enhanced the occurrence of arrhythmias (early as well as delayed-afterdepolarization) in Trpm4+/+ mice but decreased it in Trpm4-/- animals. Atrial connexin43 immunolabelling indicated their disorganization at the intercalated disks and a redistribution at the lateral side induced by hyperaldosteronemia-salt but also by Trpm4 disruption. In addition, hyperaldosteronemia-salt produced pronounced atrial endothelial thickening in both groups. Altogether, our results indicated that hyperaldosteronemia-salt and TRPM4 participate in atrial electrical and structural remodeling. It appears that TRPM4 is involved in aldosterone-induced atrial action potential shortening. In addition, TRPM4 may promote aldosterone-induced atrial arrhythmias, however, the underlying mechanisms remain to be explored.
Climate Services for Renewable Energy in the Nordic Electricity Market
Authors: Halsnæs Kirsten , Bay Lisa , Kaspersen Per Skougaard , Drews Martin , Larsen Morten Andreas Dahl
Published: March 2021

To limit global warming to less than 2 °C requires a low-carbon transition with very large shares of renewables. Options such as wind, solar and hydro are influenced by both short and longer-term weather and climate variability. While still subject to natural and anthropogenic climate forcing and fluctuating energy prices, water reservoirs can dually operate as storage and production facilities and serve to balance the more volatile production capacity from solar and wind. This paper assesses the dynamics and demands of the hydro-dominated Nordic electricity system and market and identifies untapped potential for climate services based on a combination of literature-based research, documented stakeholder needs and data sources on historical and future conditions. A critical need for both improving the appropriateness and reliability of existing climate services and for developing new tailored solutions for a broader group of stakeholders from the renewable energy sector in the Nordics is observed. The quantification of uncertainties related to short-term weather forecasts and longer-term climate predictions is also found to be important for minimizing the financial risk in relation to systems management and to overall investments in renewable energy.
Exploration of the Effect of Oxygen on Superconductivity in MgB2 Bulk by Using Boron Powder with Different Particle and Purification
Authors: Yang Liangqun , Suo Hongli , Ma Lin , Liu Min , Zhao Wanli , Liu Jianhua , Wang Lei , Zhang Zili , Wang Qiuliang
Published: March 2021

In this study, boron powder with different particle sizes was purified by both chemical and heat treatment methods. The reduction in the particle size can improve the chemical purification with no effort on the heat treatment. The superconducting properties of the powder drastically changed even with only a partial elimination of oxygen. On the one hand, less oxygen content resulted in high Tc and Jc values under the low magnetic field, and most importantly, a significant improvement in the superconducting connectivity (Af value). On the other hand, the degradation of Jc under a high field and a change in the pinning mechanism were also found, along with decreasing oxygen. This result indicated that oxygen, probably MgO, might act as the pinning center and as an obstacle for the supercurrent in MgB2 at the same time. This work paves the way for obtaining pure oxygen-free MgB2 and understanding the real effect of oxygen in MgB2.
Color Glass by Layered Nitride Films for Building Integrated Photovoltaic (BIPV) System
Authors: Gasonoo Akpeko , Ahn Hyeon-Sik , Lim Seongmin , Lee Jae-Hyun , Choi Yoonseuk
Published: March 2021

We investigated layered titanium nitride (TiN) and aluminum nitride (AlN) for color glasses in building integrated photovoltaic (BIPV) systems. AlN and TiN are among suitable and cost-effective optical materials to be used as thin multilayer films, owing to the significant difference in their refractive index. To fabricate the structure, we used radio frequency magnetron deposition method to achieve the target thickness uniformly. A simple, fast, and cheap fabrication method is achieved by depositing the multilayer films in a single sputtering chamber. It is demonstrated that a multilayer stack that allows light to be transmitted from a low refractive index layer to a high refractive index layer or vice-versa can effectively create various distinct color reflections for different film thicknesses and multilayer structures. It is investigated from simulation based on wave optics that TiN/AlN multilayer offers better color design freedom and a cheaper fabrication process as compared to AlN/TiN multilayer films. Blue, green, and yellow color glasses with optical transmittance of more than 80% was achieved by indium tin oxide (ITO)-coated glass/TiN/AlN multilayer films. This technology exhibits good potential in commercial BIPV system applications.