bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival of HT29 Cancer Cells Is Affected by IGF1R Inhibition via Modulation of Self-DNA-Triggered TLR9 Signaling and the Autophagy Response
Authors: Sipos Ferenc , Bohusné Barta Bettina , Simon Ágnes , Nagy Lőrinc , Dankó Titanilla , Raffay Regina Eszter , Petővári Gábor , Zsiros Viktória , Wichmann Barnabás , Sebestyén Anna , Műzes Györgyi
Published: May 2022

Purpose: In HT29 colon cancer cells, a close interplay between self-DNA-induced TLR9 signaling and autophagy response was found, with remarkable effects on cell survival and differentiation. IGF1R activation drives the development and malignant progression of colorectal cancer. IGF1R inhibition displays a controversial effect on autophagy. The interrelated roles of IGF1R inhibition and TLR9/autophagy signaling in HT29 cancer cells have not yet been clarified. In our study, we aimed to investigate the complex interplay of IGF1R inhibition and TLR9/autophagy signaling in HT29 cells.

Methods: HT29 cells were incubated with tumor-originated self-DNA with or without inhibitors of IGF1R (picropodophyllin), autophagy (chloroquine), and TLR9 (ODN2088), respectively. Cell proliferation and metabolic activity measurements, direct cell counting, NanoString and Taqman gene expression analyses, immunocytochemistry, WES Simple Western blot, and transmission electron microscopy investigations were performed.

Results: The concomitant use of tumor-derived self-DNA and IGF1R inhibitors displays anti-proliferative potential, which can be reversed by parallel TLR9 signaling inhibition. The distinct effects of picropodophyllin, ODN2088, and chloroquine per se or in combination on HT29 cell proliferation and autophagy suggest that either the IGF1R-associated or non-associated autophagy machinery is “Janus-faced” regarding its actions on cell proliferation. Autophagy, induced by different combinations of self-DNA and inhibitors is not sufficient to rescue HT29 cells from death but results in the survival of some CD133-positive stem-like HT29 cells.

Conclusion: The creation of new types of combined IGF1R, autophagy, and/or TLR9 signaling inhibitors would play a significant role in the development of more personalized anti-tumor therapies for colorectal cancer.
Experimental Investigation of a Cylindrical Air-Breathing Continuous Rotating Detonation Engine with Different Nozzle Throat Diameters
Authors: Wang Guangyu , Liu Shijie , Peng Haoyang , Liu Weidong
Published: May 2022

A continuous detonation engine with various exhaust nozzles, analogous to typical scramjet cavity combustors with variable rear-wall heights, was adopted to perform a succession of cylindrical air-breathing continuous rotating detonation experiments fueled by a non-premixed ethylene/air mixture. The results show that the detonation combustion was observed to self-sustain in the combustor through simultaneous high-speed imaging covering the combustor and isolator. A long test, lasting more than three seconds, was performed in this unique configuration, indicating that the cylindrical isolator–combustor engine exhibits potential for practical applications. Three distinct combustion modes were revealed with varied equivalent ratios (hybrid mode, sawtooth wave mode, and deflagration mode). The diameter of the nozzle throat was critical in the formation of rotating detonation waves. When the nozzle throat diameter was larger than the specific value, the detonation wave could not form and self-sustain. The upstream boundary of the shock train was supposed to be close to the isolator entrance in conditions of a high equivalence ratio and small nozzle throat diameter. In addition, it was verified that periodic high-frequency pressure oscillation could cause substantial impacts on the incoming flow as compared with the steady deflagration with the same combustor pressure.
Status of Essential Elements in Soil and Grain of Organically Produced Maize, Spelt, and Soybean
Authors: Dragicevic Vesna , Stoiljkovic Milovan , Brankov Milan , Tolimir Miodrag , Tabaković Marijenka , Dodevska Margarita S. , Simić Milena
Published: May 2022

Organic agriculture offers many benefits through the increased nutritional quality of produced crops, agro-ecosystem preservation, and climate change mitigation. The development of an efficient nutrient management strategy in low-input systems, such as organic agriculture, which supports soil fertility and essential nutrients absorption by crops, is continually exploring. Thus, a study with maize–spelt–soybean rotation during a 5-year period in organic production was established to evaluate the variability in soil organic matter (SOM) and the status of available elements: N, P, K, Ca, Mg, Fe, Cu, Mn, Zn, and Si from the soil, as well as grain yield (GY) and the content of protein, P, K, Ca, Mg, Fe, Cu, Mn, Zn, and Si concentration in the grain of spelt, maize, and soybean. Significant variations in mineral elements in the soil, GY, and grain composition were detected. Spelt achieved the highest average GY, while soybean grain was the richest in a majority of examined nutrients. The soil Ca content was important for GY, while the protein level in grain was generally tied to the Mn level in the soil. It was recognized that soil–crop crosstalk is an important strategy for macro- and micro-nutrients management in the soil and grain of organically produced spelt, maize, and soybean. While a reduction in the GY and protein concentration in grain was present over time, it was established that a low-input system under dry-farming conditions supports nutrient availability and accumulation in grain, under semi-arid agro-ecological conditions of central Serbia.
Assessment of Soil Contamination Using GIS and Multi-Variate Analysis: A Case Study in El-Minia Governorate, Egypt
Authors: Hammam Amr A. , Mohamed Wagih S. , Sayed Safa Essam-Eldeen , Kucher Dmitry E. , Mohamed Elsayed Said
Published: May 2022

The issue of soil contamination is one of the most important subjects that interests decision-makers all over the world. It is also related to soil fertility and food security. The soils adjacent to the drains in Egypt suffer from increasing concentration of heavy metals, which negatively affects soil and crop quality. Precise spatial distribution maps of heavy metals are an essential key to mitigating the negative impacts on the ecosystem. Sixty random soil locations adjacent to the El-Moheet drainage were chosen on the west side of the Nile River, El-Minia governorate, Egypt. Six heavy metals (Cr, Co, Cu, Cd, Pb, and Zn) were selected to generate their spatial pattern maps using ordinary Kriging (OK). Principal component analysis (PCA) and contamination factors (CF) were applied to evaluate soil contamination levels in the study area. The results showed that the Gaussiang model was a high fit for soil pH, and Pb, the Exponential model was fit for EC, Stable model was fit for OC, Co, Cu, and Cd. In addition, the Spherical model was fit for both Cr and Zn. The MSE values were close to zero in all selected metals, while the values of RMSSE were close to one. The results showed that the soil heavy metal concentrations were grouped into two clusters using PCA. Furthermore, three contamination degrees were obtained (moderate, considerable, and very high), with about 70.7% of the study area characterized by considerable heavy metals concentration, where the average heavy metals concentration (mg kg−1) in this degree was 91.23 ± 19.5, 29.44 ± 5.2, 53.83 ± 10.2, 1.12 ± 0.3, 36.04 ± 18.0, and 101.29 ± 35 for Cr, Co, Cu, Cd, Pb, and Zn, respectively. The current results reflect the mismanagement and use of low-quality water for irrigation in the study area, which increased the toxic element concentration in soil surface layers. In the end, the results of spatial distribution maps of pollutants and their degrees could support decision-makers as a basis for developing appropriate mitigation plans for heavy metals.
Effects of Agricultural Management Practices on the Temporal Variability of Soil Temperature under Different Crop Rotations in Bad Lauchstaedt-Germany
Authors: Jarrah Mahboube , Mayel Sonia , Franko Uwe , Kuka Katrin
Published: May 2022

To investigate the effects of management practices on the dynamics of soil temperature, during 2014–2017, a field experiment was carried out in Bad Lauchstaedt, Germany. In this study, four management systems are compared for determining management-induced changes in soil temperature at different depths: (i) conventional tillage (TC) with the standard rate of N fertilizer (P1N1), (ii) conventional tillage with the half-standard rate of N fertilizer (P1N0), (iii) reduced tillage (TR) with the standard rate of N fertilizer (P0N1), and iv) reduced tillage with the half-standard rate of N fertilizer (P0N0). Temporal analysis of soil temperature is assessed to examine data observed at a specific time to achieve a better understanding of the soil temperature dynamic that occurs at different time scales. The results showed that the soil temperature has decreasing amplitudes and increasing phase shifts with increasing soil depth, i.e., the deeper the measurement depth, the smoother the soil temperature changes cycle and the smaller the variability. Results showed that the diurnal temperature variation is found up to 45 cm depth of soil whereas annual temperature variation is up to a depth of 180 cm. The results, moreover, revealed that soil temperature dynamic was affected by tillage systems and fertilization and a time lag is observed between the temperature fluctuations at the surface and deeper layers, due to induced management effects on plant cover, residues, and soil properties. Although higher soil temperature at the sowing stage under TR is contributed to higher amounts of surface crop residues in crop rotations, the effect of residues on soil temperature variation reduces with an increase in percent plant cover and shading of soil, which happens in the last stage of plant growth. At the last stage of crop development regardless of tillage systems, applying more N fertilization increased crop yield, resulting in cooling soil temperature.
Short Communication: Use of Infrared Thermometers for Cutaneous Temperature Recording: Agreement with the Rectal Temperature in Felis catus
Authors: Giannetto Claudia , Acri Giuseppe , Pennisi Melissa , Piccione Giuseppe , Arfuso Francesca , Falcone Annastella , Giudice Elisabetta , Di Pietro Simona
Published: May 2022

In veterinary medicine, the gold standard for assessing body temperature is rectal temperature assessment. Considering that this procedure is stressful for many species, in particular for cats, it could be clinically important to consider an alternative approach for the monitoring of core body temperature. The aim of this study was to test if cutaneous temperature measurements by means of different infrared thermometers are in agreement with the most commonly used method for body temperature measurement in cats. The cutaneous temperature was recorded in the jugular, shoulder, rib, flank, and inner thigh, using three different non-contact infrared thermometers (IR1, IR2, and IR3) in 20 cats. The cutaneous temperature was then compared to the rectal temperature, recorded by means of a digital thermometer. The obtained data indicated that the cutaneous temperature recorded by the infrared thermometers was not in agreement with the data recorded by the digital thermometer in the rectum. In cats, the use of non-contact infrared thermometers gave no reproducible or constant data to justify their application for the recording of body temperature instead of rectal temperature recording. In addition, the infrared temperature measurement devices generated results that were not in good agreement among themselves, providing a novel result of clinical importance.
Public Health Interventions to Improve Antimicrobial Resistance Awareness and Behavioural Change Associated with Antimicrobial Use: A Systematic Review Exploring the Use of Social Media
Authors: Parveen Sana , Garzon-Orjuela Nathaly , Amin Doaa , McHugh Patricia , Vellinga Akke
Published: May 2022

Introduction: Over the years there have been several interventions targeted at the public to increase their knowledge and awareness about Antimicrobial Resistance (AMR). In this work, we updated a previously published review by Price et al. (2018), on effectiveness of interventions to improve the public’s antimicrobial resistance awareness and behaviours associated with prudent use of antimicrobials to identify which interventions work best in influencing public behaviour. Methods: Five databases—Medline (OVID), CINAHL (EBSCO), Embase, PsycINFO, and Cochrane Central Register of Controlled Trials (CENTRAL-OVID)—were searched for AMR interventions between 2017 and 2021 targeting the public. All studies which had a before and after assessment of the intervention were considered for inclusion. Results: In total, 17 studies were found to be eligible for inclusion in the review. Since there was a variety in the study interventions and in particular outcomes, a narrative synthesis approach was adopted for analysis. Whereas each study showed some impact on awareness and knowledge, none measured long-term impact on behaviours towards antibiotic use, awareness, or knowledge. Engagement was higher in interventions which included interactive elements such as games or videos. Social media was not used for recruitment of participants or as a mode of communication in any AMR interventions included in this review.
Modulation of Oxidative Stress-Induced Senescence during Non-Alcoholic Fatty Liver Disease
Authors: Pedroza-Diaz Johanna , Arroyave-Ospina Johanna C. , Serna Salas Sandra , Moshage Han
Published: May 2022

Non-alcoholic fatty liver disease is characterized by disturbed lipid metabolism and increased oxidative stress. These conditions lead to the activation of different cellular response mechanisms, including senescence. Cellular senescence constitutes an important response to injury in the liver. Recent findings show that chronic oxidative stress can induce senescence, and this might be a driving mechanism for NAFLD progression, aggravating the disturbance of lipid metabolism, organelle dysfunction, pro-inflammatory response and hepatocellular damage. In this context, the modulation of cellular senescence can be beneficial to ameliorate oxidative stress-related damage during NAFLD progression. This review focuses on the role of oxidative stress and senescence in the mechanisms leading to NAFLD and discusses the possibilities to modulate senescence as a therapeutic strategy in the treatment of NAFLD.
Passenger Flow-Oriented Metro Operation without Timetables
Authors: He Li , Chen Lei , Liu Jin , Roberts Clive , Yu Saijun , Feng Xujie
Published: May 2022

Unpredictable fluctuant passenger flow usually exists in urban metro operations. In this situation, traditional predetermined metro timetables cannot always meet the variation of passenger flow, and thus the service quality of the metro system could be affected profoundly. In this paper, by introducing an innovative metro operation method without timetables, we develop a nonlinear integer programming model to continually optimise the train operation to deal with detected real-time passenger flow variations. We aim to minimise the total passenger waiting time in the research time horizon under the vehicle number constraint. A modified genetic algorithm integrated with a macroscopic metro simulator is adopted to solve the proposed model. A case study based on the Beijing Metro Line 19 is implemented to provide a quantitative result for evaluating the proposed passenger flow-oriented metro operation method without timetables. Compared to traditional timetable-based metro operation, the method could significantly improve the metro operation’s flexibility and the quality of services.
On Modeling Cancer and Tuberculosis Data Using the Birnbaum–Saunders Lifetime Model Established on a Logistic Kernel
Authors: Alam Farouq Mohammad A. , Almalki Abeer Mansour
Published: May 2022

Due to their importance in representing, explaining, and analyzing phenomena, statistical lifetime distributions are widely used in science. As a result, this paper discusses a modern lifetime model called Birnbaum–Saunders logistic distribution. This distribution extends the Birnbaum–Saunders distribution, as it has proven to be characterized by great flexibility in data modeling in practice. Different features of this distribution have been discussed. The parameters of the model are estimated using the maximum likelihood and modified moment estimation methods. To evaluate the performance of the methods, a simulation study with data contamination scenarios is presented. Finally, the new model’s flexibility is tested using real datasets.
Optimization of Shingled-Type Lightweight Glass-Free Solar Modules for Building Integrated Photovoltaics
Authors: Park Min-Joon , Youn Sungmin , Jeon Kiseok , Lee Soo Ho , Jeong Chaehwan
Published: May 2022

High-power and lightweight photovoltaic (PV) modules are suitable for building-integrated photovoltaic (BIPV) systems. Due to the characteristics of the installation sites, the BIPV solar modules are limited by weight and installation area. In this study, we fabricated glass-free and shingled-type PV modules with an area of 1040 mm × 965 mm, which provide more conversion power compared to conventional PV modules at the same installed area. Further, we employed an ethylene tetrafluoroethylene sheet instead of a front cover glass and added an Al honeycomb sandwich structure to enhance the mechanical stability of lightweight PV modules. To optimize the conversion power of the PV module, we adjusted the amount of dispensed electrically conductive adhesives between the solar cells. Finally, we achieved a conversion power of 195.84 W at an area of 1.004 m2, and we performed standard reliability tests using a PV module that weighed only 9 kg/m2.
Short-Term Canyon Wind Speed Prediction Based on CNN—GRU Transfer Learning
Authors: Ji Lipeng , Fu Chenqi , Ju Zheng , Shi Yicheng , Wu Shun , Tao Li
Published: May 2022

Due to the particularity of the site selection of hydropower stations, the canyon wind with large fluctuations often occurs during the construction of the hydropower station, which will seriously affect the safety of construction personnel. Especially in the early stage of the construction of the hydropower station, the historical data and information on the canyon wind are scarce. Short-term forecasting of canyon wind speed has become extremely important. The main innovation of this paper is to propose a time series prediction method based on transfer learning. This method can achieve short-term prediction when there are few wind speed sample data, and the model is relatively simple while ensuring the accuracy of prediction. Considering the temporal and nonlinear characteristics of canyon wind speed data, a hybrid transfer learning model based on a convolutional neural network (CNN) and gated recurrent neural network (GRU) is proposed to predict short-term canyon wind speed with fewer observation data. In this method, the time sliding window is used to extract time series from historical wind speed data and temperature data of adjacent cities as the input of the neural network. Next, CNN is used to extract the feature vector from the input, and the feature vector can form time series. Then, the GRU network is used for short-term wind speed prediction by the time series. Experimental results show that the proposed method improves MAE and RMSE by nearly 20%, which will provide new ideas for the application of wind speed forecasting in canyons under complex terrain. The research contents of this paper contribute to the actual construction of hydropower stations.
Cancer-Associated Microbiota: From Mechanisms of Disease Causation to Microbiota-Centric Anti-Cancer Approaches
Authors: Dey Priyankar , Ray Chaudhuri Saumya
Published: May 2022

Helicobacter pylori infection is the only well-established bacterial cause of cancer. However, due to the integral role of tissue-resident commensals in maintaining tissue-specific immunometabolic homeostasis, accumulated evidence suggests that an imbalance of tissue-resident microbiota that are otherwise considered as commensals, can also promote various types of cancers. Therefore, the present review discusses compelling evidence linking tissue-resident microbiota (especially gut bacteria) with cancer initiation and progression. Experimental evidence supporting the cancer-causing role of gut commensal through the modulation of host-specific processes (e.g., bile acid metabolism, hormonal effects) or by direct DNA damage and toxicity has been discussed. The opportunistic role of commensal through pathoadaptive mutation and overcoming colonization resistance is discussed, and how chronic inflammation triggered by microbiota could be an intermediate in cancer-causing infections has been discussed. Finally, we discuss microbiota-centric strategies, including fecal microbiota transplantation, proven to be beneficial in preventing and treating cancers. Collectively, this review provides a comprehensive understanding of the role of tissue-resident microbiota, their cancer-promoting potentials, and how beneficial bacteria can be used against cancers.
Downregulated ADAMTS1 Incorporating A2M Contributes to Tumorigenesis and Alters Tumor Immune Microenvironment in Lung Adenocarcinoma
Authors: Lee Hsiao-Chen , Chang Chao-Yuan , Huang Yung-Chi , Wu Kuan-Li , Chiang Hung-Hsing , Chang Yung-Yun , Liu Lian-Xiu , Hung Jen-Yu , Hsu Ya-Ling , Wu Yu-Yuan , Tsai Ying-Ming
Published: May 2022

Lung adenocarcinoma (LUAD) still holds the most dreadful clinical outcomes worldwide. Despite advanced treatment strategies, there are still some unmet needs. Next-generation sequencing of large-scale cancer genomics discovery projects combined with bioinformatics provides the opportunity to take a step forward in meeting clinical conditions. Based on in-house and The Cancer Genome Atlas (TCGA) cohorts, the results showed decreased levels of ADAMTS1 conferred poor survival compared with normal parts. Gene set enrichment analyses (GSEA) indicated the negative correlation between ADAMTS1 and the potential roles of epithelial–mesenchymal transition (EMT), metastasis, and poor prognosis in LUAD patients. With the knockdown of ADAMTS1, A549 lung cancer cells exhibited more aggressive behaviors such as EMT and increased migration, resulting in cancer metastasis in a mouse model. The pathway interaction network disclosed the linkage of downregulated α2-macroglobulin (A2M), which regulates EMT and metastasis. Furthermore, immune components analysis indicated a positive relationship between ADAMTS1 and the infiltrating levels of multiple immune cells, especially anticancer CD4+ T cells in LUAD. Notably, ADAMTS1 expression was also inversely correlated with the accumulation of immunosuppressive myeloid-derived suppressor cells and regulatory T cells, implying the downregulated ADAMTS1 mediated immune adjustment to fit the tumor survival disadvantages in LUAD patients. In conclusion, our study indicates that ADAMTS1 interacts with A2M in regulating EMT and metastasis in LUAD. Additionally, ADAMTS1 contributes to poor prognosis and immune infiltration in LUAD patients
Increase in Serum MMP-9 and TIMP-1 Concentrations during Alcohol Intoxication in Adolescents—A Preliminary Study
Authors: Zdanowicz Katarzyna , Kowalczuk-Kryston Monika , Olanski Witold , Werpachowska Irena , Mielech Wlodzimierz , Lebensztejn Dariusz Marek
Published: May 2022

Background: Alcohol consumption by adolescents is responsible for a number of adverse health and social outcomes. Despite the well-established effect of alcohol use on the development of alcoholic liver disease, the relationship between the pattern of alcohol consumption and liver fibrosis is still unclear. This study is a follow-up to work on liver damage from alcohol intoxication. The aim of our study was to explore the early effects of alcohol intoxication on liver fibrosis in adolescents. Methods: The prospective study included 57 adolescents aged 14–17 years admitted to the emergency department (ED) from February 2017 to June 2018 due to acute alcohol intoxication. Serum levels of amino terminal propeptide of type III procollagen (PIIINP), type IV collagen, matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were determined by enzyme-linked immunosorbent assays. Results: There were significant differences in MMP-9 (p = 0.02) and TIMP-1 (p = 0.007) levels between the study and control groups. Liver parameters and selected markers of fibrosis were similar in groups in terms of blood alcohol concentrations (BAC). MMP-9 was positively correlated with alanine aminotransferase (ALT) (r = 0.38; p = 0.004) and total bilirubin (r = 0.39; p = 0.004). Positive significant correlations were also found between TIMP-1 and ALT (r = 0.47; p < 0.001), AST (r = 0.29; p = 0.03) and total bilirubin (r = 0.32; p = 0.02). In receiver operating characteristic (ROC) analysis, MMP-9 (AUC = 0.67, p = 0.02) and TIMP-1 (AUC = 0.69, p = 0.003) allowed for the differentiation of patients with and without alcohol intoxication. Conclusion: Our results show that even a single episode of alcohol intoxication in adolescents can lead to imbalance in markers of fibrosis.
Fluorescent Anti-CEA Nanobody for Rapid Tumor-Targeting and Imaging in Mouse Models of Pancreatic Cancer
Authors: Lwin Thinzar M. , Turner Michael A. , Nishino Hiroto , Amirfakhri Siamak , Hernot Sophie , Hoffman Robert M. , Bouvet Michael
Published: May 2022

Tumor-specific targeting with fluorescent probes can enhance contrast for identification of cancer during surgical resection and visualize otherwise invisible tumor margins. Nanobodies are the smallest naturally-occurring antigen-binding molecules with rapid pharmacokinetics. The present work demonstrates the efficacy of a fluorescent anti-CEA nanobody conjugated to an IR800 dye to target and label patient derived pancreatic cancer xenografts. After intravenous administration, the probe rapidly localized to the pancreatic cancer tumors within an hour and had a tumor-to-background ratio of 2.0 by 3 h. The fluorescence signal was durable over a prolonged period of time. With the rapid kinetics afforded by fluorescent nanobodies, both targeting and imaging can be performed on the same day as surgery.
The STING Ligand and Delivery System Synergistically Enhance the Immunogenicity of an Intranasal Spike SARS-CoV-2 Vaccine Candidate
Authors: Jearanaiwitayakul Tuksin , Limthongkul Jitra , Kaofai Chernkhwan , Apichirapokey Suttikarn , Chawengkirttikul Runglawan , Sapsutthipas Sompong , Sunintaboon Panya , Ubol Sukathida
Published: May 2022

The respiratory organ serves as a primary target site for SARS-CoV-2. Thus, the vaccine-stimulating immune response of the respiratory tract is significant in controlling SARS-CoV-2 transmission and disease development. In this study, mucoadhesive nanoparticles were used to deliver SARS-CoV-2 spike proteins (S-NPs) into the nasal tracts of mice. The responses in the respiratory organ and the systemic responses were monitored. The administration of S-NPs along with cGAMP conferred a robust stimulation of antibody responses in the respiratory tract, as demonstrated by an increase of IgA and IgG antibodies toward the spike proteins in bronchoalveolar lavages (BALs) and the lungs. Interestingly, the elicited antibodies were able to neutralize both the wild-type and Delta variant strains of SARS-CoV-2. Significantly, the intranasal immunization also stimulated systemic responses. This is evidenced by the increased production of circulating IgG and IgA, which were able to neutralize and bind specifically to the SARS-CoV-2 virion and spike protein. Additionally, this intranasal administration potently activated a splenic T cell response and the production of Th-1 cytokines, suggesting that this vaccine may well activate a cellular response in the respiratory tract. The results demonstrate that STING agonist strongly acts as an adjuvant to the immunogenicity of S-NPs. This platform may be an ideal vaccine against SARS-CoV-2.
Enhancing the Bioactivity of Bicyclic Peptides Targeted to Grb7-SH2 by Restoring Cell Permeability
Authors: Sturre Natasha P. , Colson Rhys N. , Shah Neelam , Watson Gabrielle M. , Yang Xue , Wilce Matthew C. J. , Price John T. , Wilce Jacqueline A.
Published: May 2022

The development of peptide inhibitors against intracellular targets depends upon the dual challenge of achieving a high affinity and specificity for the target and maintaining cellular permeability for biological activity. Previous efforts to develop bicyclic peptides targeted to the Grb7 signalling protein implicated in HER2+ve cancer progression have resulted in improved affinity. However, these same peptides demonstrated a lowered activity due to their decreased ability to penetrate cell membranes. Here, we report the testing of a new series of bicyclic G7 peptides designed to possess improved bioactivity. We discovered that the incorporation of two amino acids (Phe-Pro, Phe-Trp or Phe-Arg) within the bicyclic peptide framework maintains an enhanced binding affinity for the Grb7-SH2 domain compared to that of the first-generation monocyclic peptide G7-18NATE. Structure determination using X-ray crystallography revealed that the mode of binding by the expanded bicyclic G7 peptide is analogous to that of G7-18NATE. Interestingly, while the bicyclic peptide containing Phe-Trp did not display the highest affinity for Grb7-SH2 in the series, it was the most potent inhibitor of HER2+ve SKBR3 breast cancer cell migration when coupled to Penetratin. Together, this demonstrates that peptide flexibility as well as the amino acid tryptophan can play important roles in the uptake of peptides into the cell.
A New Kind of Chemical Nanosensors for Discrimination of Espresso Coffee
Authors: Greco Giuseppe , Carmona Estefanía Núñez , Sberveglieri Giorgio , Genzardi Dario , Sberveglieri Veronica
Published: May 2022

There are different methods to extract and brew coffee, therefore, coffee processing is an important factor and should be studied in detail. Herein, coffee was brewed by means of a new espresso professional coffee machine, using coffee powder or portioned coffee (capsule). Four different kinds of coffees (Biologico, Dolce, Deciso, Guatemala) were investigated with and without capsules and the goal was to classify the volatiloma of each one by Small Sensor System (S3). The response of the semiconductor metal oxide sensors (MOX) of S3 where recorded, for all 288 replicates and after normalization ∆R/R0 was extracted as a feature. PCA analysis was used to compare and differentiate the same kind of coffee sample with and without a capsule. It could be concluded that the coffee capsules affect the quality, changing on the flavor profile of espresso coffee when extracted different methods confirming the use of s3 device as a rapid and user-friendly tool in the food quality control chain.
Measurement of Pulsating Flow Using a Self-Attachable Flexible Strain Sensor Based on Adhesive PDMS and CNT
Authors: Ryu Chaehyun , Park Jeonhyeong , Jung Soon In , Jang Il Ryu , Kim Hoe Joon
Published: May 2022

Accurate monitoring is needed for pulsating flow in many healthcare and bio applications. Specifically, real-time monitoring of pulsating blood flow provides rich information regarding a patient’s health conditions. This paper proposes a flexible strain sensor capable of detecting the pulsating fluid flow by directly measuring the circumferential strain induced by a rapid change in the flow rate. The thin and flexible strain sensor consists of a polydimethylsiloxane (PDMS) with a Triton-X treatment to enhance the adhesive property and multi-walled carbon nanotubes (MWCNT) as the piezoresistive sensing layer. MWCNT integration implements a simple spray-coating method. The adhesive PDMS/CNT strain sensor exhibits a highly adhesive nature and can be attached to a silicone tube’s curved surface. By analyzing the theoretical modeling based on fluid energy equation and solid mechanics, strains induced on the soft tube by the change in flow rate, viscosity, and fluid density can be predicted. We performed the flow rate measurement at varying fluid-flow rates and liquid viscosities, and the results match our prediction. The sensitivity and limit of detection of the presented strain sensor are about 0.55 %min/L and 0.4 L/min, respectively. Both the calculation and experiment confirm that the sensor resistance is most sensitive to the fluid-flow rate, thus, enabling the accurate tracking of pulsating fluids’ flow rate, regardless of the viscosity or density.
“A Head Start or a Pain in the Neck?”—Establishment and Evaluation of a Video-Based “Hands-On” Head and Neck Ultrasound Course
Authors: Pillong Lukas , Bozzato Alessandro , Hecker Dietmar , Bozzato Victoria , Schick Bernhard , Kulas Philipp
Published: May 2022

The COVID-19 pandemic has strongly highlighted the need for more digitalization in healthcare. Teaching ultrasound skills in online courses is a key challenge in this context. The aim of this study was to establish an online video-based head and neck ultrasound course with an evaluation of the quality, effectiveness, and feasibility of this teaching method compared to in-person teaching. Twenty-two medical students were taught head and neck ultrasound in two groups: one group in an in-person course and the other one in a video-based course. Learning success was analyzed using self-evaluation forms and external assessment by an experienced ultrasonographer. Comparing pre- and post-training self-evaluation, all participants showed statistically significant learning progress. In the external assessment, the overall scores in both groups did not differ significantly. The courses themselves were positively evaluated by all participants. Herein, we present the first feasibility study of a web-based head and neck-ultrasound course for medical students. The methodology provides the potential for future changes in telemedical education and sustainable improvements in telemedical teaching and global intra-clinical and interdisciplinary patient care.
Kaposi Sarcoma, a Trifecta of Pathogenic Mechanisms
Authors: Rusu-Zota Gabriela , Manole Oana Mădălina , Galeș Cristina , Porumb-Andrese Elena , Obadă Otilia , Mocanu Cezar Valentin
Published: May 2022

Kaposi’s sarcoma is a rare disease with four known variants: classic, epidemic, endemic and iatrogenic (transplant-related), all caused by an oncogenic virus named Human Herpes Virus 8. The viral infection in itself, along with the oncogenic properties of HHV8 and with immune system dysfunction, forms the grounds on which Kaposi’s Sarcoma may develop. Infection with HHV8 occurs through saliva via close contacts, blood, blood products, solid organ donation and, rarely, vertical transmission. Chronic inflammation and oncogenesis are promoted by a mix of viral genes that directly promote cell survival and transformation or interfere with the regular cell cycle and cell signaling (of particular note: LANA-1, v-IL6, vBCL-2, vIAP, vIRF3, vGPCR, gB, K1, K8.1, K15). The most common development sites for Kaposi’s sarcoma are the skin, mucocutaneous zones, lymph nodes and visceral organs, but it can also rarely appear in the musculoskeletal system, urinary system, endocrine organs, heart or eye. Histopathologically, spindle cell proliferation with slit-like vascular spaces, plasma cell and lymphocyte infiltrate are characteristic. The clinical presentation is heterogenic depending on the variant; some patients have indolent disease and others have aggressive disease. The treatment options include highly active antiretroviral therapy, surgery, radiation therapy, chemotherapy, and immunotherapy. A literature search was carried out using the MEDLINE/PubMed, SCOPUS and Google Scholar databases with a combination of keywords with the aim to provide critical, concise, and comprehensive insights into advances in the pathogenic mechanism of Kaposi’s sarcoma.
Smile Aesthetic Evaluation on Videographs: An Intra-Rater and Inter-Rater Agreement Study
Authors: Faure-Brac Mathias , Antezack Angéline , Melloul Sebastien , Hadj Saïd Mehdi Hadj , Raskin Anne , Monnet-Corti Virginie
Published: May 2022

The aim of this study was to assess on videographs the intra- and inter-rater reproducibility of the Smile Esthetic Index (SEI) that has been previously validated on photographs. Smile videographs were obtained using a smartphone associated with the Smile Lite MDP mounted on a tripod. They were then randomized and evaluated twice consecutively at a 1-week interval by three periodontists according to the SEI based on 10 variables. Cohen’s Kappa and Fleiss’ Kappa tests were performed to measure intra- and inter-rater agreement. Sixty-five smile videographs of 24 men and 41 women (mean age 33 ± 11.3 years) were scored. A mean intra-rater agreement of 0.68 (0.64–0.73) was obtained, representing substantial agreement. The inter-rater agreement calculated for each variable ranged from 0.31 for the variable “absence of visible excessive gingiva” to 0.90 for the variable “absence of diastema and/or missing inter-dental papilla.” Within the limits of this study, we have demonstrated that it was possible to use videographs to reproducibly evaluate an aesthetic score (SEI) previously validated on photographs.
Walking through Algebraic Thinking with Theme-Based (Mobile) Math Trails
Authors: Barbosa Ana , Vale Isabel , Jablonski Simone , Ludwig Matthias
Published: May 2022

Tasks are a key resource in the process of teaching and learning mathematics, which is why task design continues to be one of the main research issues in mathematics education. Different settings can influence the principles underlying the formulation of tasks, and so does the outdoor context. Specifically, a math trail can be a privileged context, known to promote positive attitudes and additional engagement for the learning of mathematics, confronting students with a sequence of real-life tasks, related to a particular mathematical theme. Recently, mobile devices and apps, i.e., MathCityMap, have been recognized as an important resource to facilitate the extension of the classroom to the outdoors. The study reported in this paper intends to identify the principles of design for mobile theme-based math trails (TBT) that result in rich learning experiences in early algebraic thinking. A designed-based research is used, through a qualitative approach, to develop and refine design principles for TBT about Sequences and Patterns. The iterative approach is described by cycles with the intervention of the researchers, pre-service and in-service teachers and students of the targeted school levels. The results are discussed taking into account previous research and data collected along the cycles, conducing to the development of general design principles for TBT tasks.
Impact of an Active Learning Methodology on Students’ Emotions and Self-Efficacy Beliefs towards the Learning of Chemical Reactions—The Case of Secondary Education Students
Authors: Dávila-Acedo Maria Antonia , Sánchez-Martín Jesús , Airado-Rodríguez Diego , Cañada-Cañada Florentina
Published: May 2022

The main goal of this article was to analyse the impact of the implementation of an active methodology, namely inquiry-based learning, on the emotions experienced by students and their self-efficacy beliefs toward the curricular content in relation to chemical reactions. A sample of 56 students at the third level of compulsory secondary education (K-9) was considered. It was found that the use of an active methodology had on the one hand, a statistically significant effect on the promotion of positive emotions and a decrease in negative emotions and on the other hand a positive effect on the improvement of students’ self-efficacy beliefs towards learning the curricular content related to chemical reactions. The implementation of practical activities in the classroom might lead to better learning of scientific content; at least, the results presented in the current article point in that direction.
Integration of Single-Port Memory (ISPM) for Multiprecision Computation in Systolic-Array-Based Accelerators
Authors: Yang Renyu , Shen Junzhong , Wen Mei , Cao Yasong , Li Yuhang
Published: May 2022

On-chip memory is one of the core components of deep learning accelerators. In general, the area used by the on-chip memory accounts for around 30% of the total chip area. With the increasing complexity of deep learning algorithms, it will become a challenge for the accelerators to integrate much larger on-chip memory responding to algorithm needs, whereas the on-chip memory for multiprecision computation is required by the different precision (such as FP32, FP16) computations in training and inference. To solve it, this paper explores the use of single-port memory (SPM) in systolic-array-based deep learning accelerators. We propose transformation methods for multiple precision computation scenarios, respectively, to avoid the conflict of simultaneous read and write requests on the SPM. Then, we prove that the two methods are feasible and can be implemented on hardware without affecting the computation efficiency of the accelerator. Experimental results show that both methods have about 30% and 25% improvement in terms of area cost when accelerator integrates SPM without affecting the throughput of the accelerator, while the hardware cost is almost negligible.
A New Approach for Quantifying Purpurogallin in Brewed Beverages Using LC-MS in Combination with Solid Phase Extraction
Authors: Liao Yu-Chen , Kim Taejo , Silva Juan L. , Chen Bang-Yuan
Published: May 2022

Purpurogallin (PPG) is a phenolic compound known for its high antioxidant properties in plant-based food materials. However, there is no easy and reliable method for direct determination of PPG in brewed beverages owing to its hydrophobicity, which makes it hard to separate from the background hydrophobic components. Therefore, a method employing solid-phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS) was developed for detection and quantification of PPG in brewed beverages, and PPG content was quantified in commercial coffee, cocoa, and tea samples. The limits of detection and quantification were 71.8 and 155.6 ng/g dry weight (dw), respectively. The recovery with SPE was 26.6%. When combined with acetonitrile extraction (ANE), the recovery was 6.8%, higher than 2.6% with water extraction (WTE). Test tube extractions were better than moka pot brewing (MPB) for PPG quantification. Total PPG content of ground coffees prepared by ANE, WTE, and MPB ranged between 635 and 770, 455 and 630, and 85 and 135 ng/g dw, respectively. PPG was detected in two English breakfast tea samples (335–360 ng/g dw) using WTE, but not in cocoa samples. ANE showed higher (p < 0.05) PPG levels, but WTE (r = 0.55, p < 0.01) correlated better with MPB than ANE (r = 0.43, p < 0.01). The result indicated that WTE is the best method to determine PPG in brewed beverages. This work demonstrated that PPG was significant in brewed coffee, and our pioneer study in developing the method for beverage sample preparation and LC-MS analysis has made possible industrial applications and provided new perspectives for future research.
Removal of Ochratoxin A from Grape Juice by Clarification: A Response Surface Methodology Study
Authors: Behfar Majid , Heshmati Ali , Mehri Freshteh , Khaneghah Amin Mousavi
Published: May 2022

This study achieved maximum removal of ochratoxin A (OTA) during the grape juice clarification process with minimal reduction in antioxidant compounds (phenolic acid, flavonoids, and antioxidant capacity by FRAP) by the RSM method. Independent variables included three types of clarifiers—gelatin, bentonite, and diatomite (diatomaceous earth)—at a concentration level of 0.25–0.75% and clarification time of 1–3 h. OTA was measured by high-performance liquid chromatography with fluorescence detection. Clarifying agent concentration and clarification time affected the reduction amount of OTA and antioxidant compounds in grape juice. There was a direct linear correlation between the reduction amounts of OTA and antioxidant compounds and capacity with the concentration of bentonite, gelatin, and diatomite, and the clarification time. The reduction amount of OTA and antioxidant capacity followed the linear mode. However, the decreased phenolic acid and flavonoid values followed the quadratic model. The study results showed that if the concentrations of bentonite, gelatin, and diatomite and clarification time were 0.45, 0.62, 0.25%, and 1 h, respectively, the maximum amount of OTA reduction (41.67%) occurred. Furthermore, the phenolic acid, flavonoid, and antioxidant activity decrease amounts were at their lowest levels, i.e., 23.86, 7.20, and 17.27%, respectively.
Saccharomyces cerevisiae I4 Showed Alleviating Effects on Dextran Sulfate Sodium-Induced Colitis of Balb/c Mice
Authors: Meng Yuan , Zhang Lijuan , Li Panpan , Yu Jiang , Mu Guangqing , Li Xinling , Tuo Yanfeng
Published: May 2022

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The purpose of this study was to investigate the ameliorating effects of three yeast strains, Saccharomyces cerevisiae I4, Clavispora lusitaniae 30 and Pichia kudriavzevii 11, isolated from traditional fermented dairy food in Xinjiang, China, on the ulcerative colitis symptoms of Balb/c mice treated by dextran sulfate sodium (DSS). Among which, S. cerevisiae I4 had good tolerance to simulated gastrointestinal juice and strong adhesion to HT–29 cells monolayers. Furthermore, the three yeast strains were oral administered to Balb/c mice with DSS induced colitis. The weight loss, colon shortening and histological injury of colitis mice were ameliorated. Then, oral administration of S. cerevisiae I4 improved the immune state by reducing the contents of TNF–α, IL–6 and IL–1β and increasing immunoglobulin. The relative expression of intestinal barrier proteins Claudin–1, Occludin and Zonula Occludins–1 (ZO–1) of the mice enhanced, and the short chain fatty acids (SCFAs) content such as Propionic acid, Butyric acid, Isobutyric acid and Isovaleric acid in the feces of the mice increased to varying degrees, after S. cerevisiae I4 treatment compared with the model group of drinking 3% DSS water without yeast treatment. Moreover, S. cerevisiae I4 treatment lifted the proportion of beneficial bacteria such as Muribaculaceae, Lactobacillaceae and Rikenellaceae in the intestinal tract of the mice, the abundance of harmful bacteria such as Staphylococcus aureus and Turicibacter was decreased. These results suggested that S. cerevisiae I4 could alleviate DSS induced colitis in mice by enhancing intestinal barrier function and regulating intestinal flora balance.
Effects of Konjac Glucomannan on Oil Absorption and Safety Hazard Factor Formation of Fried Battered Fish Nuggets
Authors: Sun Jingwen , Wu Runlin , Hu Benlun , Jia Caihua , Rong Jianhua , Xiong Shanbai , Liu Ru
Published: May 2022

The purpose of this study was to investigate the effects of konjac glucomannan (KGM) on oil absorption and the formation of safety hazard factors in fried battered fish nuggets by measuring advanced glycation end products (AGEs) and acrylamide contents. Other physicochemical properties were determined to explore the reason for oil absorption and formation of safety hazard factors. The acrylamide was found mainly in the crust. The addition of 0.8% KGM could significantly reduce the acrylamide content (p < 0.05). For the battered sample, the AGEs content was far lower than the unbattered. The addition of 0.8% KGM could significantly reduce the AGEs content in the inner layer (p < 0.05). The microstructure showed that the sample with 0.8% KGM had the most compact crust. The compact crust reduced oil and malondialdehyde contents. Combined with the other indicators, the inhibitory effect of 0.8% KGM on acrylamide was closely related with the decreased extent of oil oxidation and Maillard reaction in the samples with 0.8% KGM. The inhibitory effect of 0.8% KGM on AGEs might originate from its lower oil content.