bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumoral administration of the antisecretory peptide AF16 cures murine gliomas and modulates macrophage functions
Authors: Kopecky Jan , Pérez Julio Enríquez , Eriksson Håkan , Visse Edward , Siesjö Peter , Darabi Anna 
Published: March 2022

AbstractGlioblastoma has remained the deadliest primary brain tumor while its current therapy offers only modest survival prolongation. Immunotherapy has failed to record notable benefits in routine glioblastoma treatment. Conventionally, immunotherapy relies on T cells as tumor-killing agents; however, T cells are outnumbered by macrophages in glioblastoma microenvironment. In this study, we explore the effect of AF16, a peptide from the endogenous antisecretory factor protein, on the survival of glioma-bearing mice, the tumor size, and characteristics of the tumor microenvironment with specific focus on macrophages. We elucidate the effect of AF16 on the inflammation-related secretome of human and murine macrophages, as well as human glioblastoma cells. In our results, AF16 alone and in combination with temozolomide leads to cure in immunocompetent mice with orthotopic GL261 gliomas, as well as prolonged survival in immunocompromised mice. We recorded decreased tumor size and changes in infiltration of macrophages and T cells in the murine glioma microenvironment. Human and murine macrophages increased expression of proinflammatory markers in response to AF16 treatment and the same effect was seen in human primary glioblastoma cells. In summary, we present AF16 as an immunomodulatory factor stimulating pro-inflammatory macrophages with a potential to be implemented in glioblastoma treatment protocols.
Hyaluronic acid functionalized ZnO nanoparticles co-deliver AS and GOD for synergistic cancer starvation and oxidative damage
Authors: Ren Zhenkun , Han Xibin , Wang Lixin , Wang Yi 
Published: March 2022

AbstractArtesunate was reported to have inhibition effect on tumors via amplified oxidative stress while the lack of intratumoral ferrous ions supply greatly hinders its efficacy. Herein, the AS/GOD@HAZnO NPs we proposed could be efficiently taken in by the affinity between hyaluronic acid and the CD44 receptors. DLS and TEM results manifested the nano-size (~ 160 nm) and circular shape of AS/GOD@HAZnO NPs. Due to the acid-responsive degradation, AS/GOD@HAZnO NPs realized responsive release (up to 80%) in acid environment while only 20% was released in neutral medium. The cellular and in vivo experiment showed that co-delivery of AS and GOD via HAZnO NPs could effectively induce the overproduction of ROS and cut the glucose supply of tumor cells, and thus result in efficient cell apoptosis and tumor inhibition.
Effects of a reduction of the number of electrodes in the EEG montage on the number of identified seizure patterns
Authors: Tacke Moritz , Janson Katharina , Vill Katharina , Heinen Florian , Gerstl Lucia , Reiter Karl , Borggraefe Ingo 
Published: March 2022

AbstractContinuous EEG monitoring (cEEG) is frequently used in neurocritical care. The detection of seizures is one of the main objectives. The placement of the EEG electrodes is time consuming, therefore a reduced montage might lead to an increased availability in the ICU setting. It is unknown whether such a reduction of electrodes reduces the number of seizure patterns that are detected. A total of 95 seizure and 95 control EEG sequences from a pediatric epilepsy monitoring unit (EMU) were anonymized and reduced to an eight-lead montage. Two experts evaluated the recordings and the seizure detection rates using the reduced and the full montage were compared. Sensitivity and specificity for the seizure detection were calculated using the original EMU findings as gold standard. The sensitivity to detect seizures was 0.65 for the reduced montage compared to 0.76 for the full montage (p = 0.031). The specificities (0.97 and 0.96) were comparable (p = 1). A total of 4/9 (44%) of the generalized, 12/44 (27%) of the frontal, 6/14 (43%) of the central, 0/1 (0%) of the occipital, 6/20 (30%) of the temporal, and 5/7 (71%) of the parietal seizure patterns were not detected using the reduced montage. The median time difference between the onset of the seizure pattern in the full and reduced montage was 0.026s (IQR 5.651s). In this study the reduction of the EEG montage from 21 to eight electrodes reduced the sensitivity to detect seizure patterns from 0.76 to 0.65. The specificity remained virtually unchanged.
In vivo competition assays between Vip3 proteins confirm the occurrence of shared binding sites in Spodoptera littoralis
Authors: Lázaro-Berenguer María , Quan Yudong , Hernández-Martínez Patricia , Ferré Juan 
Published: March 2022

AbstractDue to their different specificity, the use of Vip3 proteins from Bacillus thuringiensis in combination with the conventionally used Cry proteins in crop protection is being essential to counteract the appearance of insect resistance. Therefore, understanding the mode of action of Vip3 proteins is crucial for their better application, with special interest on the binding to membrane receptors as the main step for specificity. Derived from in vitro heterologous competition binding assays using 125I-Vip3A and other Vip3 proteins as competitors, it has been shown that Vip3 proteins share receptors in Spodoptera frugiperda and Spodoptera exigua brush border membrane vesicles (BBMV). In this study, using 125I-Vip3Aa, we have first extended the in vitro competition binding site model of Vip3 proteins to Spodoptera littoralis. With the aim to understand the relevance (in terms of toxicity) of the binding to the midgut sites observed in vitro on the insecticidal activity of these proteins, we have performed in vivo competition assays with S. littoralis larvae, using disabled mutant (non-toxic) Vip3 proteins as competitors for blocking the toxicity of Vip3Aa and Vip3Af. The results of the in vivo competition assays confirm the occurrence of shared binding sites among Vip3 proteins and help understand the functional role of the shared binding sites as revealed in vitro.
The NSAID glafenine rescues class 2 CFTR mutants via cyclooxygenase 2 inhibition of the arachidonic acid pathway
Authors: Carlile Graeme W. , Yang Qi , Matthes Elizabeth , Liao Jie , Birault Véronique , Sneddon Helen F. , Poole Darren L. , Hall Callum J. , Hanrahan John W. , Thomas David Y. 
Published: March 2022

AbstractMost cases of cystic fibrosis (CF) are caused by class 2 mutations in the cystic fibrosis transmembrane regulator (CFTR). These proteins preserve some channel function but are retained in the endoplasmic reticulum (ER). Partial rescue of the most common CFTR class 2 mutant, F508del-CFTR, has been achieved through the development of pharmacological chaperones (Tezacaftor and Elexacaftor) that bind CFTR directly. However, it is not clear whether these drugs will rescue all class 2 CFTR mutants to a medically relevant level. We have previously shown that the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen can correct F508del-CFTR trafficking. Here, we utilized RNAi and pharmacological inhibitors to determine the mechanism of action of the NSAID glafenine. Using cellular thermal stability assays (CETSAs), we show that it is a proteostasis modulator. Using medicinal chemistry, we identified a derivative with a fourfold increase in CFTR corrector potency. Furthermore, we show that these novel arachidonic acid pathway inhibitors can rescue difficult-to-correct class 2 mutants, such as G85E-CFTR > 13%, that of non-CF cells in well-differentiated HBE cells. Thus, the results suggest that targeting the arachidonic acid pathway may be a profitable way of developing correctors of certain previously hard-to-correct class 2 CFTR mutations.
Agrivoltaic systems have the potential to meet energy demands of electric vehicles in rural Oregon, US
Authors: Steadman Casey L. , Higgins Chad W. 
Published: March 2022

AbstractElectrification of the transportation industry is necessary; however, range anxiety has proven to be a major hindrance to individuals adopting electric vehicles (EVs). Agrivoltaic systems (AVS) can facilitate the transition to EVs by powering EV charging stations along major rural roadways, increasing their density and mitigating range anxiety. Here we conduct case study analyses of future EV power needs for Oregon, USA, and identify 174 kha of AVS viable agricultural land outside urban boundaries that is south facing and does not have prohibitive attributes (designated wetland, forested land, or otherwise protected lands). 86% highway access points have sufficient available land to supply EV charging stations with AVS. These AVS installations would occupy less than 3% (5 kha) of the identified available land area. Installing EV charging stations at these 86% highway access points would yield 231 EV charging stations with a median range of 5.9 km (3.6 mi), a distance comparable to driver expectations, suggesting that this approach would serve to mitigate range anxiety. AVS powered rural charging stations in Oregon could support the equivalent of 673,915 electric vehicles yr−1, reducing carbon emissions due to vehicle use in OR by 3.1 mil MTCO2 yr−1, or 21%.
High-performance freestanding supercapacitor electrode based on polypyrrole coated nickel cobalt sulfide nanostructures
Authors: Barazandeh Mohammad , Kazemi Sayed Habib 
Published: March 2022

AbstractIn the present work, we report the successful fabrication of dandelion-like Nickel–Cobalt Sulfide@Polypyrrole microspheres through the hydrothermal method and its possible application as a binder-free electrode in supercapacitors. This electrode exhibited low charge transfer resistance with a remarkable specific capacitance of 2554.9 F g−1 at 2.54 A g−1, in addition to considerable cycle life stability. Also, an asymmetric device was prepared using NiCo2S4@PPy/NF as positive and rGO/NF as negative electrodes. This asymmetric supercapacitor exhibited a specific capacitance of 98.9 F g−1 at 1.84 A g−1 and delivered an energy density of 35.17 Wh kg−1 at a power density of 1472 W kg−1. Such a remarkable performance can be originated from the synergy effect of NiCo2S4 and PPy and the direct deposition of the composite on the current collector. Our findings suggest the dandelion-like NiCo2S4@PPy as a promising material for making high-performance supercapacitors.
Neuroimaging reveals distinct brain glucose metabolism patterns associated with morphine consumption in Lewis and Fischer 344 rat strains
Authors: Soto-Montenegro Mª Luisa , García-Vázquez Verónica , Lamanna-Rama Nicolás , López-Montoya Gonzalo , Desco Manuel , Ambrosio Emilio 
Published: March 2022

AbstractVulnerability to addiction may be given by the individual's risk of developing an addiction during their lifetime. A challenge in the neurobiology of drug addiction is understanding why some people become addicted to drugs. Here, we used positron emission tomography (PET) and statistical parametric mapping (SPM) to evaluate changes in brain glucose metabolism in response to chronic morphine self-administration (MSA) in two rat strains with different vulnerability to drug abuse, Lewis (LEW) and Fischer 344 (F344). Four groups of animals were trained to self-administer morphine or saline for 15 days. 2-deoxy-2-[18F]-fluoro-d-glucose (FDG)-PET studies were performed on the last day of MSA (acquisition phase) and after 15 days of withdrawal. PET data were analyzed using SPM12. LEW-animals self-administered more morphine injections per session than F344-animals. We found significant brain metabolic differences between LEW and F344 strains in the cortex, hypothalamus, brainstem, and cerebellum. In addition, the different brain metabolic patterns observed after the MSA study between these rat strains indicate differences in the efficiency of neural substrates to translate the drug effects, which could explain the differences in predisposition to morphine abuse between one individual and another. These findings have important implications for the use of these rat strains in translational morphine and opiate research.
New insights into real-time detection of tephra grainsize, settling velocity and sedimentation rate
Authors: Freret-Lorgeril V. , Bonadonna C. , Rossi E. , Poulidis A. P. , Iguchi M. 
Published: March 2022

AbstractCharacterizing the size and settling velocity of pyroclastic fragments injected into the atmosphere during volcanic eruptions (i.e., tephra) is crucial to the forecasting of plume and cloud dispersal. Optical disdrometers have been integrated into volcano monitoring networks worldwide in order to best constrain these parameters in real time. Nonetheless, their accuracy during tephra fallout still needs to be assessed. A significant complication is the occurrence of particle aggregates that modify size and velocity distributions of falling tephra. We made the first use of the Thies Clima Laser Precipitation Monitor (LPM) for tephra-fallout detection at Sakurajima volcano (Japan), which is characterized by a lower size detection window with respect to more commonly used disdrometers (e.g., Parsivel2) and can more easily distinguish different falling objects. For the first time, individual particles have been distinguished from most aggregates based on disdrometer data, with the potential to provide useful grain-size information in real time. In case of negligible aggregation, LPM and collected sample-based estimates are in agreement for both grain-size and sedimentation rate. In case of significant aggregation, particle shape analyses and a dedicated drag equation are used to filter out aggregates from LPM data that also provide good agreement with collected tephra samples.
Identification of the C-terminal region in Amelogenesis Imperfecta causative protein WDR72 required for Golgi localization
Authors: Husein Dina , Alamoudi Ahmed , Ohyama Yoshio , Mochida Hanna , Ritter Brigitte , Mochida Yoshiyuki 
Published: March 2022

AbstractAmelogenesis Imperfecta (AI) represents a group of hereditary conditions that manifest tooth enamel defects. Several causative mutations in the WDR72 gene have been identified and patients with WDR72 mutations have brown (or orange-brown) discolored enamel, rough enamel surface, early loss of enamel after tooth eruption, and severe attrition. Although the molecular function of WDR72 is not yet fully understood, a recent study suggested that WDR72 could be a facilitator of endocytic vesicle trafficking, which appears inconsistent with the previously reported cytoplasmic localization of WDR72. Therefore, the aims of our study were to investigate the tissues and cell lines in which WDR72 was expressed and to further determine the sub-cellular localization of WDR72. The expression of Wdr72 gene was investigated in mouse tissues and cell lines. Endogenous WDR72 protein was detected in the membranous fraction of ameloblast cell lines in addition to the cytosolic fraction. Sub-cellular localization studies supported our fractionation data, showing WDR72 at the Golgi apparatus, and to a lesser extent, in the cytoplasmic area. In contrast, a WDR72 AI mutant form that lacks its C-terminal region was exclusively detected in the cytoplasm. In addition, our studies identified a putative prenylation/CAAX motif within the last four amino acids of human WDR72 and generated a WDR72 variant, called CS mutant, in which the putative motif was ablated by a point mutation. Interestingly, mutation of the putative CAAX motif impaired WDR72 recruitment to the Golgi. Cell fractionation assays confirmed subcellular distribution of wild-type WDR72 in both cytosolic and membranous fractions, while the WDR72 AI mutant and CS mutant forms were predominantly detected in the cytosolic fraction. Our studies provide new insights into the subcellular localization of WDR72 and demonstrate a critical role for the C-terminal CAAX motif in regulating WDR72 recruitment to the Golgi. In accordance with structural modelling studies that classified WDR72 as a potential vesicle transport protein, our findings suggest a role for WDR72 in vesicular Golgi transport that may be key to understanding the underlying cause of AI.
Identifying metabolic reprogramming phenotypes with glycolysis-lipid metabolism discoordination and intercellular communication for lung adenocarcinoma metastasis
Authors: Li Xin , Tang Lefan , Deng Jiaxing , Qi Xiuying , Zhang Juxuan , Qi Haitao , Li Mengyue , Liu Yixin , Zhao Wenyuan , Gu Yunyan , Qi Lishuang , Li Xia 
Published: March 2022

AbstractTumor metastasis imposes metabolic requirements for escaping from primary tissues, producing vulnerability in treatment. This study aimed to explore the metabolic reprogramming relevant to lung adenocarcinoma (LUAD) metastasis and decode the underlying intercellular alterations. Using the gene expression profiles of 394 LUAD samples derived from The Cancer Genome Atlas (TCGA), we identified 11 metastasis-related metabolic genes involved in glycolysis and lipid metabolism, and defined three metabolic reprogramming phenotypes (MP-I, -II, and -III) using unsupervised clustering. MP-III with the highest glycolytic and lowest lipid metabolic levels exhibited the highest metastatic potency and poorest survival in TCGA and six independent cohorts totaling 1,235 samples. Genomic analyses showed that mutations in TP53 and KEAP1, and deletions in SETD2 and PBRM1 might drive metabolic reprogramming in MP-III. Single-cell RNA-sequencing data from LUAD validated a metabolic evolutionary trajectory from normal to MP-II and MP-III, through MP-I. The further intercellular communications revealed that MP-III interacted uniquely with endothelial cells and fibroblasts in the ANGPTL pathway, and had stronger interactions with endothelial cells in the VEGF pathway. Herein, glycolysis-lipid dysregulation patterns suggested metabolic reprogramming phenotypes relevant to metastasis. Further insights into the oncogenic drivers and microenvironmental interactions would facilitate the treatment of LUAD metastasis in the future.
Diversity of Antibiotic Resistance genes and Transfer Elements-Quantitative Monitoring (DARTE-QM): a method for detection of antimicrobial resistance in environmental samples
Authors: Smith Schuyler D. , Choi Jinlyung , Ricker Nicole , Yang Fan , Hinsa-Leasure Shannon , Soupir Michelle L. , Allen Heather K. , Howe Adina 
Published: March 2022

AbstractEffective monitoring of antibiotic resistance genes and their dissemination in environmental ecosystems has been hindered by the cost and efficiency of methods available for the task. We developed the Diversity of Antibiotic Resistance genes and Transfer Elements-Quantitative Monitoring (DARTE-QM), a method implementing TruSeq high-throughput sequencing to simultaneously sequence thousands of antibiotic resistant gene targets representing a full-spectrum of antibiotic resistance classes common to environmental systems. In this study, we demonstrated DARTE-QM by screening 662 antibiotic resistance genes within complex environmental samples originated from manure, soil, and livestock feces, in addition to a mock-community reference to assess sensitivity and specificity. DARTE-QM offers a new approach to studying antibiotic resistance in environmental microbiomes, showing advantages in efficiency and the ability to scale for many samples. This method provides a means of data acquisition that will alleviate some of the obstacles that many researchers in this area currently face.
Structure-based design of a dual-warhead covalent inhibitor of FGFR4
Authors: Chen Xiaojuan , Li Huiliang , Lin Qianmeng , Dai Shuyan , Yue Sitong , Qu Lingzhi , Li Maoyu , Guo Ming , Wei Hudie , Li Jun , Jiang Longying , Xu Guangyu , Chen Yongheng 
Published: March 2022

AbstractThe fibroblast growth factor 19 (FGF19)/fibroblast growth factor receptor 4 (FGFR4) signaling pathways play critical roles in a variety of cancers, such as hepatocellular carcinoma (HCC). FGFR4 is recognized as a promising target to treat HCC. Currently, all FGFR covalent inhibitors target one of the two cysteines (Cys477 and Cys552). Here, we designed and synthesized a dual-warhead covalent FGFR4 inhibitor, CXF-009, targeting Cys477 and Cys552 of FGFR4. We report the cocrystal structure of FGFR4 with CXF-009, which exhibits a dual-warhead covalent binding mode. CXF-009 exhibited stronger selectivity for FGFR4 than FGFR1-3 and other kinases. CXF-009 can also potently inhibit the single cystine mutants, FGFR4(C477A) and FGFR4(C552A), of FGFR4. In summary, our study provides a dual-warhead covalent FGFR4 inhibitor that can covalently target two cysteines of FGFR4. CXF-009, to our knowledge, is the first reported inhibitor that forms dual-warhead covalent bonds with two cysteine residues in FGFR4. CXF-009 also has the potential to overcome drug induced resistant FGFR4 mutations and might serve as a lead compound for future anticancer drug discovery.
Planar microplasma optical emission gas spectroscopy based on selective growth of ZnO nanowires
Authors: Ramezannezhad Mohammad , Nikfarjam Alireza , Sichani Soroush Bakhshi , Akram Mohammad Makhdoumi 
Published: March 2022

AbstractThe present study demonstrates a novel miniature planar device by the selective growth of ZnO nanowires for microplasma optical emission gas spectroscopy. Gold electrodes are fabricated on the silicon substrate by thermal evaporation and photolithography process with a 15 μm gap size. Zinc oxide (ZnO) nanowires, are selectively grown on the electrodes without using a seeding layer by a hydrothermal method which is a cost‐effective approach. Growth of vertically aligned ZnO nanowires on electrodes with sharp tips reinforce the field emission enhancement factor which results in lower microplasma generation voltage. The SEM characterizations reveals that ZnO nanowires are grown on electrodes, selectively. The diameter range and length of nanowires vary between 50 and 250 nm and 3 and 5 μm, respectively. Also, the gap distance between electrodes decreases from 15 μm to about 4–10 μm due to the growth of vertically aligned nanowires. The experimental tests are implemented for helium, nitrogen, and carbon dioxide gases at room temperature and atmospheric pressure. The results successfully exhibit the characteristic peaks and repeatable responses for all the samples. In addition, the required working voltage for microplasma formation of He, N2, and CO2 reduce 32%, 22%, and 20%, respectively, after ZnO nanowires growth. Besides, the electrodes sputtering rate significantly decreases during the tests due to the thermal stability of ZnO nanowires. According to the device performance, the proposed structure could be a promising candidate for relative low voltage, highly selective and stable optical emission spectroscopy for gas detection applications.