bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Outdoor Particulate Matter PM2.5 on Indoor Air Quality: The Implementation of a New Assessment Method
Authors: Bekierski Dominik , Kostyrko Krystyna Barbara
Published: September 2021

Epidemiological research has shown that there is a positive correlation between the incidence of disease and mortality in humans and the mass concentration of particulate matter. An average 1 g of suspended dust emitted in a room results in the same exposure as 1 kg emitted to the outside air. In this study, the authors described the state of knowledge on dust pollution inside and outside buildings (I/O ratios), and methods of testing the PM infiltration process parameters. According to the law of indoor–outdoor particle mass balance and the physical basis of aerosol penetration theory, a relatively simple but new method for estimating the penetration factor P was tested. On the basis of the curve of dynamic changes of internal dust concentration in the process of particle concentration decay and next of the followed curve of dynamic rebound of particle concentration, authors measured penetration factor of ambient PM2.5 through building envelope. Authors modification of the method is to be used for determining the value of the particle deposition rate k not from the course of the characteristics in the transient state (the so-called particle concentration decay curves) but from the concentration rebound course, stimulated by natural particle infiltration process. Recognition measurements of the mass concentration of suspended PM2.5 and PM10 particles inside the rooms were carried out. In this study, the choice of the prediction particle penetration factor P calculation method was supported by the exemplary calculation of the p value for a room polluted by PM2.5. The preliminary results of the penetration factors determined by this method P = 0.61 are consistent with the P factor values from the literature obtained so far for this dimensional group of dusts.
Data-Targeted Prior Distribution for Variational AutoEncoder
Authors: Akkari Nissrine , Casenave Fabien , Daniel Thomas , Ryckelynck David
Published: September 2021

Bayesian methods were studied in this paper using deep neural networks. We are interested in variational autoencoders, where an encoder approaches the true posterior and the decoder approaches the direct probability. Specifically, we applied these autoencoders for unsteady and compressible fluid flows in aircraft engines. We used inferential methods to compute a sharp approximation of the posterior probability of these parameters with the transient dynamics of the training velocity fields and to generate plausible velocity fields. An important application is the initialization of transient numerical simulations of unsteady fluid flows and large eddy simulations in fluid dynamics. It is known by the Bayes theorem that the choice of the prior distribution is very important for the computation of the posterior probability, proportional to the product of likelihood with the prior probability. Hence, we propose a new inference model based on a new prior defined by the density estimate with the realizations of the kernel proper orthogonal decomposition coefficients of the available training data. We numerically show that this inference model improves the results obtained with the usual standard normal prior distribution. This inference model was constructed using a new algorithm improving the convergence of the parametric optimization of the encoder probability distribution that approaches the posterior. This latter probability distribution is data-targeted, similarly to the prior distribution. This new generative approach can also be seen as an improvement of the kernel proper orthogonal decomposition method, for which we do not usually have a robust technique for expressing the pre-image in the input physical space of the stochastic reduced field in the feature high-dimensional space with a kernel inner product.
Evaluation of Vortex Generators in the Heat Transfer Improvement of Airflow through an In-Line Heated Tube Arrangement
Authors: Syaiful  , Wahyuni Tri , Yunianto Bambang , Sinaga Nazaruddin
Published: September 2021

Improving heat transfer from surface to airflow is a current research concern for enhancing energy efficiency. The use of vortex generators for improving heat transfer from the surface to the airflow is very effective. Therefore, this study focuses on applying flat and concave vortex generators with and without holes in order to improve heat transfer. In this study, the number of pairs of vortex generators was varied from one to three pairs at a certain angle of attack for various forms of vortex generators. The airflow velocity through the duct was varied in the range of 0.4 to 2.0 m/s at 0.2 m/s intervals. From the investigation results, we observed that the highest thermal performance was found with the use of concave delta winglets without holes for various pairs of vortex generators in terms of the overall Reynolds number. The highest thermal enhancement factor was found to be around 1.42 at a Reynolds number of approximately 9000. From this study, it was also shown that the lowest cost–benefit ratio was about 1.75 at a Reynolds number of approximately 3500 for three pairs of vortex generators.
Oxidative Quality of Dairy Powders: Influencing Factors and Analysis
Authors: Clarke Holly J. , McCarthy William P. , O’Sullivan Maurice G. , Kerry Joseph P. , Kilcawley Kieran N.
Published: September 2021

Lipid oxidation (LO) is a primary cause of quality deterioration in fat-containing dairy powders and is often used as an estimation of a products shelf-life and consumer acceptability. The LO process produces numerous volatile organic compounds (VOC) including aldehydes, ketones and alcohols, which are known to contribute to the development of off-flavours in dairy powders. The main factors influencing the oxidative state of dairy powders and the various analytical techniques used to detect VOC as indicators of LO in dairy powders are outlined. As the ability to identify and quantify specific VOC associated with LO improves this review highlights how these techniques can be used in conjunction with olfactory and sensory analysis to better understand product specific LO processes with the aim of maximizing shelf-life without compromising quality.
Blockchain Technology for Trustworthy Operations in the Management of Strategic Grain Reserves
Authors: Iftekhar Adnan , Cui Xiaohui , Yang Yiping
Published: September 2021

Food is a daily requirement for everyone, while production patterns are seasonal. Producing sufficient nutrients is becoming more difficult because water and soil resources are already stressed and are becoming increasingly strained by climate change. Improving food security requires expertise in various areas, including sophisticated climate models, genetics research, market and household behaviour modelling, political shock modelling, and comprehensive environmental research. Additionally, governments stockpile grains to enhance national food security. These reserves should engage in markets only according to clear and transparent regulations and within defined price ranges to facilitate market functioning. It increases the demand for better technology in public administration to boost the management and distribution capacity while concentrating on improved controls and transparent governance systems. Blockchain technology emerges as a promising technology to enhance visibility, transparency, and data integrity with an immutable distributed ledger to increase trust in the parties’ business transactions. This paper discusses blockchain technology and its potential role in strategic grain reserve management.
Food Texture Acceptance, Sensory Sensitivity, and Food Neophobia in Children and Their Parents
Authors: Cappellotto Maddalena , Olsen Annemarie
Published: September 2021

This study aims to explore whether children’s food texture preferences are associated with different levels of sensory sensitivity and food neophobia, as well as with other variables, such as parental texture preferences. An online questionnaire was completed by 70 children aged 6–13 years old, alongside one of their parents. Generic texture preferences of children and parents were investigated with the Child Food Texture Preference Questionnaire (CFTPQ). Parents provided background information about their children by completing the Food Neophobia Scale (FNS), the Short Sensory Profile (SSP) and a Food Frequency Questionnaire (FFQ). The results showed that children who differed in their texture-liker status also differed in their levels of food neophobia and sensory information processing: children who preferred softer and non-particulate versions of foods were found to be more neophobic and sensory sensitive across all sensory domains. No relationship was found between parental and children’s texture preferences.
Nutraceutical Chewing Candy Formulations Based on Acetic, Alcoholic, and Lactofermented Apple Juice Products
Authors: Bartkiene Elena , Zokaityte Egle , Zavistanaviciute Paulina , Mockus Ernestas , Cernauskas Darius , Ruzauskas Modestas , Tolpeznikaite Ernesta , Guiné Raquel P. F.
Published: September 2021

The aim of this study was to develop nutraceutical chewing candy (NCC) formulations based on acetic, alcoholic, and lactofermented apple juice (AJ) products. In addition, different texture-forming (gelatin, pectin) and sweetening (stevia, xylitol) agents were tested. To implement the aim of this study, combinations based on AJ, prepared from fresh and frozen apples, apple cider (C) samples (No.1, No.2, No.3, and No.4), and apple vinegar (V) were used. First, the most appropriate combination was selected by evaluating overall acceptability (OA) and emotions induced for consumers (EIC). In addition, the volatile compound (VC) profile, and physicochemical and antimicrobial characteristics of the developed combinations were analyzed. For AJ fermentation, lactic acid bacteria (LAB) strains possessing antimicrobial properties (LUHS122—L. plantarum and LUHS210—L. casei) were used. AJ prepared from frozen apples had 11.1% higher OA and 45.9%, 50.4%, and 33.3% higher fructose, glucose, and saccharose concentrations, respectively. All the tested C samples inhibited Bacillus subtilis and had an average OA of 6.6 points. Very strong positive correlations were found between AJ and C OA and the emotion ‘happy’; comparing lactofermented AJ, the highest OA was obtained for AJ fermented for 48 h with LUHS122, and a moderate positive correlation was found between AJ OA and the emotion ‘happy’ (r = 0.7617). This sample also showed the highest viable LAB count (7.59 log10 CFU mL−1) and the broadest spectrum of pathogen inhibition (inhibited 6 out of 10 tested pathogens). Further, acetic, alcoholic, and lactofermented AJ product combinations were tested. For the preparation of NCC, the combination consisting of 50 mL of AJ fermented with LUHS122 for 48 h + 50 mL C-No.3 + 2 mL V was selected because it showed the highest OA, induced a high intensity of the emotion ‘happy’ for the judges, and inhibited 8 out of 10 tested pathogens. Finally, the OA of the prepared NCC was, on average, 9.03 points. The combination of acetic, alcoholic, and lactofermented AJ products leads to the formation of a specific VC profile and increases the OA and antimicrobial activity of the products which could be successfully applied in the food and nutraceutical industries.
Determinants and Prevention Strategies for Household Food Waste: An Exploratory Study in Taiwan
Authors: Teng Chih-Ching , Chih Chueh , Yang Wen-Ju , Chien Chia-Hui
Published: September 2021

Given the large amount of food waste coming from households, reducing household food waste is essential to the mitigation of overall food waste and the provision of multi-faceted benefits for both people and the planet. This study identifies factors and management strategies for the reduction of household food waste in the Taiwanese household setting. Using snowball sampling, semi-structured interviews are conducted to collect data from 27 household food providers in Taipei. The research findings identify four critical motivators and four barriers to minimizing household food waste in Taiwan. The most frequently mentioned motivator for the reduction of food waste is a convenient shopping environment, and the most important barrier is lack of knowledge for assessing the edibility of food. Additionally, four major prevention strategies are identified to help reduce household food waste: (1) planned purchase schedule; (2) skills to keep food fresh and longer; (3) understanding family preferences and leftover management, and (4) sharing additional food and co-procurement and cooking. The results of this study not only help improve the understanding and application of Chinese household food waste reduction, but also demonstrate the significance of its socio-cultural impacts in future studies.
Cocoa (Theobroma cacao L.) Seed-Derived Peptides Reduce Blood Pressure by Interacting with the Catalytic Site of the Angiotensin-Converting Enzyme
Authors: Coronado-Cáceres Luis Jorge , Hernández-Ledesma Blanca , Mojica Luis , Quevedo-Corona Lucía , Rabadán-Chávez Griselda , Castillo-Herrera Gustavo Adolfo , Lugo Cervantes Eugenia
Published: September 2021

This study aimed at determining the effect of cocoa proteins (CP) on the blood pressure, using in silico, in vitro and in vivo approaches. The in silico assay showed 26 Criollo cocoa peptides with alignment in the Blast® analysis. Peptide sequences ranged from 6 to 16 amino acids, with molecular weight ranging from 560.31 to 1548.76 Da. The peptide sequences LSPGGAAV, TSVSGAGGPGAGR, and TLGNPAAAGPF showed the highest theoretical affinity with −8.6, −5.0, and −10.2 kcal/mol, for the angiotensin-converting enzyme (ACE), renin, and angiotensin II type 1 receptor (AT1-R), respectively. The Criollo CP hydrolysates (CPH) presented in vitro ACE inhibitory activity with an IC50 value of 0.49 mg/mL. Furthermore, the orogastric administration of 150 mg CP/kg/day in rats fed a high-fat (HF) diet (HF + CP group) showed a significant decrease in systolic blood pressure (SBP) by 5% (p < 0.001) and diastolic blood pressure (DBP) by 7% (p < 0.001) compared with the HF group. The human equivalent dose (HED) of CP for an adult (60 kg) is 1.45 g per day. These results suggest that the consumption of CP could reduce blood pressure by blocking ACE, and could be used as an ingredient in the elaboration of antihypertensive functional foods.
Enrichment Free qPCR for Rapid Identification and Quantification of Campylobacter jejuni, C. coli, C. lari, and C. upsaliensis in Chicken Meat Samples by a New Couple of Primers
Authors: Vizzini Priya , Vidic Jasmina , Manzano Marisa
Published: September 2021

Campylobacter is the main cause of bacterial foodborne disease and poultry meat is the principal source of human infections. Rapid methods for Campylobacter detection are urgently needed to decrease high bacterial prevalence in poultry products. In this study, we developed new primers, CampyPFw and CampyPRv, that target the 16S-23S rRNA genes of Campylobacter jejuni, C. coli, C. lari and C. upsaliensis. The primers were tested on positive and negative reference strains in pure cultures and in inoculated poultry meat samples before their application in real-time PCR (qPCR) protocol for analyzing chicken meat samples. In parallel, the samples were tested by using the ISO 10272-1:2006 method. The qPCR protocol based on CampyPFw and CampyPRv showed good sensitivity, with the limit of detection of 4.6 × 102 cells/mL in chicken samples without enrichment steps.
The Application of Projection Word Embeddings on Medical Records Scoring System
Authors: Lin Chin , Lee Yung-Tsai , Wu Feng-Jen , Lin Shing-An , Hsu Chia-Jung , Lee Chia-Cheng , Tsai Dung-Jang , Fang Wen-Hui
Published: September 2021

Medical records scoring is important in a health care system. Artificial intelligence (AI) with projection word embeddings has been validated in its performance disease coding tasks, which maintain the vocabulary diversity of open internet databases and the medical terminology understanding of electronic health records (EHRs). We considered that an AI-enhanced system might be also applied to automatically score medical records. This study aimed to develop a series of deep learning models (DLMs) and validated their performance in medical records scoring task. We also analyzed the practical value of the best model. We used the admission medical records from the Tri-Services General Hospital during January 2016 to May 2020, which were scored by our visiting staffs with different levels from different departments. The medical records were scored ranged 0 to 10. All samples were divided into a training set (n = 74,959) and testing set (n = 152,730) based on time, which were used to train and validate the DLMs, respectively. The mean absolute error (MAE) was used to evaluate each DLM performance. In original AI medical record scoring, the predicted score by BERT architecture is closer to the actual reviewer score than the projection word embedding and LSTM architecture. The original MAE is 0.84 ± 0.27 using the BERT model, and the MAE is 1.00 ± 0.32 using the LSTM model. Linear mixed model can be used to improve the model performance, and the adjusted predicted score was closer compared to the original score. However, the project word embedding with the LSTM model (0.66 ± 0.39) provided better performance compared to BERT (0.70 ± 0.33) after linear mixed model enhancement (p < 0.001). In addition to comparing different architectures to score the medical records, this study further uses a mixed linear model to successfully adjust the AI medical record score to make it closer to the actual physician’s score.
Association between Subjective Body Image, Body Mass Index and Psychological Symptoms in Chinese Adolescents: A Nationwide Cross-Sectional Study
Authors: Zhang Yueyun , Liu Baozhong , Sun Long
Published: September 2021

Background: Conflicting findings were reported about the associations between subjective body image (SBI), body mass index (BMI) and psychological symptoms in China and other countries in the world. In this study, we aim to explore the associations between SBI, BMI, and psychological symptoms based on a large-scale, national wide survey among Chinese adolescents. Methods: The 2014–2015 China Education Panel Survey (CEPS) database, with 8134 middle school students (4137 boys and 3997 girls), was analyzed to explore the association between SBI, BMI and psychological symptoms. SBI was assessed by one question about the perception of own body shape with options “very thin”, “slightly thin”, “average”, “weak heavy”, and “very heavy”. BMI was calculated by the self-reported body weight and height. Psychological symptoms were evaluated by 10 items involving both aspects of depression and anxiety. Results: The results indicated that both boys and girls who perceived weak or very heavy weight were positively associated with psychological symptoms (p < 0.05). For boys, perceiving very thin body image was also in higher risk of psychological symptoms (p < 0.05), after controlling social-demographic variables and BMI. Comparing with normal weight boys or girls, obese boys (β = −2.22, 95% CI −3.37~−1.07) and overweight girls (β = −1.03, 95% CI −2.01~−0.06) were in lower levels of psychological symptoms after controlling for SBI. Other factors associated with psychological symptoms were family economic status, academic performance, and self-rated health status. Conclusions: A deviation from an “average” SBI was positively associated with psychological symptoms, which should be scanned when evaluating the Chinese adolescents’ mental health. These findings provide epidemiological evidence for the association between SBI and psychological symptoms in non-western social contexts.
Can Studying Genetically Predisposed Individuals Inform Prevention Strategies for RA?
Authors: Fowler-Woods Amanda , Smolik Irene , Anaparti Vidyanand , O’Neil Liam , El-Gabalawy Hani
Published: September 2021

Rheumatoid arthritis (RA) is a prevalent autoimmune disorder in which complex genetic predisposition interacts with multiple environmental factors to precipitate chronic and progressive immune-mediated joint inflammation. Currently, in most affected individuals, ongoing suppression of the inflammation is required to prevent irreversible damage and functional loss. The delineation of a protracted preclinical period in which autoimmunity is initially established and then evolves to become pathogenic provides unprecedented opportunities for interventions that have the potential to prevent the onset of this lifelong disease. Clinical trials aimed at assessing the impact of specific prevention strategies require the identification of individuals who are at high risk of future RA development. Currently, these risk factors include a strong family history of RA, and the detection of circulating RA-associated autoantibodies, particularly anti-citrullinated protein antibodies (ACPA). Yet, even in such individuals, there remains considerable uncertainty about the likelihood and the timeframe for future disease development. Thus, individuals who are approached to participate in such clinical trials are left weighing the risks and benefits of the prevention measures, while having large gaps in our current understanding. To address this challenge, we have undertaken longitudinal studies of the family members of Indigenous North American RA patients, this population being known to have a high prevalence of RA, early age of onset, and familial clustering of cases. Our studies have indicated that the concepts of “risk” and “prevention” need to be communicated in a culturally relevant manner, and proposed prevention interventions need to have an appropriate balance of effectiveness, safety, convenience, and cultural acceptability. We have focused our proposed prevention studies on immunomodulatory/anti-inflammatory nutritional supplements that appear to strike such a complex balance.
Combination of PD98059 and TGF-β1 Efficiently Differentiates Human Urine-Derived Stem Cells into Smooth Muscle Cells
Authors: Hwang Yongha , Cha Seon-Heui , Kim Donghee , Jun Hee-Sook
Published: September 2021

Pluripotent adult stem cells have potential applications in cell therapy and tissue engineering. Urine-derived stem cells (UDSCs) differentiate into various cell types. Here, we attempted to differentiate human UDSCs (hUDSCs) into smooth muscle cells (SMCs) using transforming growth factor-beta 1 (TGF-β1) and/or PD98059, an extracellular signal-regulated kinase (ERK) inhibitor. Both quantitative polymerase chain reaction (qPCR) and Western blot analysis showed that the expression of messenger ribonucleic acid (mRNA) and proteins for alpha-smooth muscle actin (α-SMA), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC), which are specific markers for SMCs, increased on day 9 after differentiation and again on day 14. The differentiated cells from human UDSCs (hUDSCs) with a combination of TGF-β1 and PD98059 showed the highest expression of SMC marker proteins. Immunocytochemical staining performed to assess the molecular expression revealed CNN and α-SMA colocalizing in the cytoplasm. The cells that differentiated from hUDSCs with a combination of TGF-β1 and PD98059 showed the strongest expression for CNN1, α-SMA, and SM-MHC. Functional testing of the differentiated cells revealed a stronger contractile capacity for the cells differentiated with a combination of PD98059 and TGF-β1 than those differentiated with a single factor. These results suggest the combination of PD98059 and TGF-β1 to be a more effective differentiation method and that differentiated SMCs could be used for restoring the functions of the sphincter muscle or bladder.
Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty
Authors: Mahindran Elancheleyen , Law Jia Xian , Ng Min Hwei , Nordin Fazlina
Published: September 2021

Projected life expectancy continues to grow worldwide owing to the advancement of new treatments and technologies leading to rapid growth of geriatric population. Thus, age-associated diseases especially in the musculoskeletal system are becoming more common. Loss of bone (osteoporosis) and muscle (sarcopenia) mass are conditions whose prevalence is increasing because of the change in population distribution in the world towards an older mean age. The deterioration in the bone and muscle functions can cause severe disability and seriously affects the patients’ quality of life. Currently, there is no treatment to prevent and reverse age-related musculoskeletal frailty. Existing interventions are mainly to slow down and control the signs and symptoms. Mesenchymal stem cell (MSC) transplantation is a promising approach to attenuate age-related musculoskeletal frailty. This review compiles the present knowledge of the causes and changes of the musculoskeletal frailty and the potential of MSC transplantation as a regenerative therapy for age-related musculoskeletal frailty.
Comparative Phosphoproteomic Analysis Reveals the Response of Starch Metabolism to High-Temperature Stress in Rice Endosperm
Authors: Pang Yuehan , Hu Yaqi , Bao Jinsong
Published: September 2021

High-temperature stress severely affects rice grain quality. While extensive research has been conducted at the physiological, transcriptional, and protein levels, it is still unknown how protein phosphorylation regulates seed development in high-temperature environments. Here, we explore the impact of high-temperature stress on the phosphoproteome of developing grains from two indica rice varieties, 9311 and Guangluai4 (GLA4), with different starch qualities. A total of 9994 phosphosites from 3216 phosphoproteins were identified in all endosperm samples. We identified several consensus phosphorylation motifs ([sP], [LxRxxs], [Rxxs], [tP]) induced by high-temperature treatment and revealed a core set of protein kinases, splicing factors, and regulatory factors in response to high-temperature stress, especially those involved in starch metabolism. A detailed phosphorylation scenario in the regulation of starch biosynthesis (AGPase, GBSSI, SSIIa, SSIIIa, BEI, BEIIb, ISA1, PUL, PHO1, PTST) in rice endosperm was proposed. Furthermore, the dynamic changes in phosphorylated enzymes related to starch synthesis (SSIIIa-Ser94, BEI-Ser562, BEI-Ser620, BEI-Ser821, BEIIb-Ser685, BEIIb-Ser715) were confirmed by Western blot analysis, which revealed that phosphorylation might play specific roles in amylopectin biosynthesis in response to high-temperature stress. The link between phosphorylation-mediated regulation and starch metabolism will provide new insights into the mechanism underlying grain quality development in response to high-temperature stress.
β-Caryophyllene Induces Apoptosis and Inhibits Angiogenesis in Colorectal Cancer Models
Authors: Dahham Saad S. , Tabana Yasser , Asif Muhammad , Ahmed Marawan , Babu Dinesh , Hassan Loiy E. , Ahamed Mohamed B. Khadeer , Sandai Doblin , Barakat Khaled , Siraki Arno , Majid Amin M. S. A.
Published: September 2021

Beta-Caryophyllene (BCP), a naturally occurring sesquiterpene abundantly found in cloves, hops, and cannabis, is the active candidate of a relatively new group of vascular-inhibiting compounds that aim to block existing tumor blood vessels. Previously, we have reported the anti-cancer properties of BCP by utilizing a series of in-vitro anti-tumor-related assays using human colorectal carcinoma cells. The present study aimed to investigate the effects of BCP on in-vitro, ex-vivo, and in-vivo models of anti-angiogenic assays and evaluate its anti-cancer activity in xenograft tumor (both ectopic and orthotopic) mice models of human colorectal cancer. Computational structural analysis and an apoptosis antibody array were also performed to understand the molecular players underlying this effect. BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF) secretion from human umbilical vein endothelial cells and sprouting of rat aorta microvessels. BCP has a probable binding at Site#0 on the surface of VEGFR2. Moreover, BCP significantly deformed the vascularization architecture compared to the negative control in a chick embryo chorioallantoic membrane assay. BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively. The histological analysis of the tumor from BCP-treated mice revealed a clear reduction of the density of vascularization. In addition, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions. These results suggest that BCP acts at multiple stages of angiogenesis and could be used as a promising therapeutic candidate to halt the growth of colorectal tumor cells.
A Fast and Reliable Process to Fabricate Regenerated Silk Fibroin Solution from Degummed Silk in 4 Hours
Authors: Wöltje Michael , Kölbel Arthur , Aibibu Dilbar , Cherif Chokri
Published: September 2021

Silk fibroin has a high potential for use in several approaches for technological and biomedical applications. However, industrial production has been difficult to date due to the lengthy manufacturing process. Thus, this work investigates a novel procedure for the isolation of non-degraded regenerated silk fibroin that significantly reduces the processing time from 52 h for the standard methods to only 4 h. The replacement of the standard degumming protocol by repeated short-term microwave treatments enabled the generation of non-degraded degummed silk fibroin. Subsequently, a ZnCl2 solution was used to completely solubilize the degummed fibroin at only 45 °C with an incubation time of only 1 h. Desalting was performed by gel filtration. Based on these modifications, it was possible to generate a cytocompatible aqueous silk fibroin solution from degummed silk within only 4 h, thus shortening the total process time by 48 h without degrading the quality of the isolated silk fibroin solution.
Programmed Non-Apoptotic Cell Death in Hereditary Retinal Degeneration: Crosstalk between cGMP-Dependent Pathways and PARthanatos?
Authors: Yan Jie , Chen Yiyi , Zhu Yu , Paquet-Durand François
Published: September 2021

Programmed cell death (PCD) is a highly regulated process that results in the orderly destruction of a cell. Many different forms of PCD may be distinguished, including apoptosis, PARthanatos, and cGMP-dependent cell death. Misregulation of PCD mechanisms may be the underlying cause of neurodegenerative diseases of the retina, including hereditary retinal degeneration (RD). RD relates to a group of diseases that affect photoreceptors and that are triggered by gene mutations that are often well known nowadays. Nevertheless, the cellular mechanisms of PCD triggered by disease-causing mutations are still poorly understood, and RD is mostly still untreatable. While investigations into the neurodegenerative mechanisms of RD have focused on apoptosis in the past two decades, recent evidence suggests a predominance of non-apoptotic processes as causative mechanisms. Research into these mechanisms carries the hope that the knowledge created can eventually be used to design targeted treatments to prevent photoreceptor loss. Hence, in this review, we summarize studies on PCD in RD, including on apoptosis, PARthanatos, and cGMP-dependent cell death. Then, we focus on a possible interplay between these mechanisms, covering cGMP-signaling targets, overactivation of poly(ADP-ribose)polymerase (PARP), energy depletion, Ca2+-permeable channels, and Ca2+-dependent proteases. Finally, an outlook is given into how specific features of cGMP-signaling and PARthanatos may be targeted by therapeutic interventions.
Adenovirus Vectors Expressing Eight Multiplex Guide RNAs of CRISPR/Cas9 Efficiently Disrupted Diverse Hepatitis B Virus Gene Derived from Heterogeneous Patient
Authors: Kato Yuya , Tabata Hirotaka , Sato Kumiko , Nakamura Mariko , Saito Izumu , Nakanishi Tomoko
Published: September 2021

Hepatitis B virus (HBV) chronically infects more than 240 million people worldwide, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Genome editing using CRISPR/Cas9 could provide new therapies because it can directly disrupt HBV genomes. However, because HBV genome sequences are highly diverse, the identical target sequence of guide RNA (gRNA), 20 nucleotides in length, is not necessarily present intact in the target HBV DNA in heterogeneous patients. Consequently, possible genome-editing drugs would be effective only for limited numbers of patients. Here, we show that an adenovirus vector (AdV) bearing eight multiplex gRNA expression units could be constructed in one step and amplified to a level sufficient for in vivo study with lack of deletion. Using this AdV, HBV X gene integrated in HepG2 cell chromosome derived from a heterogeneous patient was cleaved at multiple sites and disrupted. Indeed, four targets out of eight could not be cleaved due to sequence mismatches, but the remaining four targets were cleaved, producing irreversible deletions. Accordingly, the diverse X gene was disrupted at more than 90% efficiency. AdV containing eight multiplex gRNA units not only offers multiple knockouts of genes, but could also solve the problems of heterogeneous targets and escape mutants in genome-editing therapy.
The PPARα and PPARγ Epigenetic Landscape in Cancer and Immune and Metabolic Disorders
Authors: Porcuna Jesús , Mínguez-Martínez Jorge , Ricote Mercedes
Published: September 2021

Peroxisome proliferator-activated receptors (PPARs) are ligand-modulated nuclear receptors that play pivotal roles in nutrient sensing, metabolism, and lipid-related processes. Correct control of their target genes requires tight regulation of the expression of different PPAR isoforms in each tissue, and the dysregulation of PPAR-dependent transcriptional programs is linked to disorders, such as metabolic and immune diseases or cancer. Several PPAR regulators and PPAR-regulated factors are epigenetic effectors, including non-coding RNAs, epigenetic enzymes, histone modifiers, and DNA methyltransferases. In this review, we examine advances in PPARα and PPARγ-related epigenetic regulation in metabolic disorders, including obesity and diabetes, immune disorders, such as sclerosis and lupus, and a variety of cancers, providing new insights into the possible therapeutic exploitation of PPAR epigenetic modulation.
Glycan–Lectin Interactions in Cancer and Viral Infections and How to Disrupt Them
Authors: Kremsreiter Stefanie Maria , Kroell Ann-Sophie Helene , Weinberger Katharina , Boehm Heike
Published: September 2021

Glycan–lectin interactions play an essential role in different cellular processes. One of their main functions is involvement in the immune response to pathogens or inflammation. However, cancer cells and viruses have adapted to avail themselves of these interactions. By displaying specific glycosylation structures, they are able to bind to lectins, thus promoting pathogenesis. While glycan–lectin interactions promote tumor progression, metastasis, and/or chemoresistance in cancer, in viral infections they are important for viral entry, release, and/or immune escape. For several years now, a growing number of investigations have been devoted to clarifying the role of glycan–lectin interactions in cancer and viral infections. Various overviews have already summarized and highlighted their findings. In this review, we consider the interactions of the lectins MGL, DC-SIGN, selectins, and galectins in both cancer and viral infections together. A possible transfer of ways to target and disrupt them might lead to new therapeutic approaches in different pathological backgrounds.
Dependence of Graphene Oxide (GO) Toxicity on Oxidation Level, Elemental Composition, and Size
Authors: Jiang Tao , Amadei Carlo Alberto , Lin Yishan , Gou Na , Rahman Sheikh Mokhlesur , Lan Jiaqi , Vecitis Chad D. , Gu April Z.
Published: September 2021

The mass production of graphene oxide (GO) unavoidably elevates the chance of human exposure, as well as the possibility of release into the environment with high stability, raising public concern as to its potential toxicological risks and the implications for humans and ecosystems. Therefore, a thorough assessment of GO toxicity, including its potential reliance on key physicochemical factors, which is lacking in the literature, is of high significance and importance. In this study, GO toxicity, and its dependence on oxidation level, elemental composition, and size, were comprehensively assessed. A newly established quantitative toxicogenomic-based toxicity testing approach, combined with conventional phenotypic bioassays, were employed. The toxicogenomic assay utilized a GFP-fused yeast reporter library covering key cellular toxicity pathways. The results reveal that, indeed, the elemental composition and size do exert impacts on GO toxicity, while the oxidation level exhibits no significant effects. The UV-treated GO, with significantly higher carbon-carbon groups and carboxyl groups, showed a higher toxicity level, especially in the protein and chemical stress categories. With the decrease in size, the toxicity level of the sonicated GOs tended to increase. It is proposed that the covering and subsequent internalization of GO sheets might be the main mode of action in yeast cells.
MicroRNAs and Calcium Signaling in Heart Disease
Authors: Park Jae-Ho , Kho Changwon
Published: September 2021

In hearts, calcium (Ca2+) signaling is a crucial regulatory mechanism of muscle contraction and electrical signals that determine heart rhythm and control cell growth. Ca2+ signals must be tightly controlled for a healthy heart, and the impairment of Ca2+ handling proteins is a key hallmark of heart disease. The discovery of microRNA (miRNAs) as a new class of gene regulators has greatly expanded our understanding of the controlling module of cardiac Ca2+ cycling. Furthermore, many studies have explored the involvement of miRNAs in heart diseases. In this review, we aim to summarize cardiac Ca2+ signaling and Ca2+-related miRNAs in pathological conditions, including cardiac hypertrophy, heart failure, myocardial infarction, and atrial fibrillation. We also discuss the therapeutic potential of Ca2+-related miRNAs as a new target for the treatment of heart diseases.
MERTK+/hi M2c Macrophages Induced by Baicalin Alleviate Non-Alcoholic Fatty Liver Disease
Authors: Junior  , Lai Yin-Siew , Nguyen Huyen Thi , Salmanida Farrah P. , Chang Ko-Tung
Published: September 2021

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. An accumulation of fat, followed by inflammation, is the major cause of NAFLD progression. During inflammation, macrophages are the most abundant immune cells recruited to the site of injury. Macrophages are classified into “proinflammatory” M1 macrophages, and “anti-inflammatory” M2 macrophages. In NAFLD, M1 macrophages are the most prominent macrophages that lead to an excessive inflammatory response. Previously, we found that baicalin could polarize macrophages into anti-inflammatory M2c subtype macrophages with an increased level of MERTK expression. Several studies have also shown a strong correlation between MERTK expression and cholesterol efflux, efferocytosis, as well as phagocytosis capability. Therefore, in this study, we aim to elucidate the potential and efficacy of mononuclear-cell (MNC)-derived MERTK+/hi M2c macrophages induced by baicalin as a cell-based therapy for NAFLD treatment. In our results, we have demonstrated that a MERTK+/hi M2c macrophage injection to NAFLD mice contributes to an increased level of serum HDL secretion in the liver, a decline in the circulating CD4+CD25− and CD8+CD25− T cells and lowers the total NAFLD pathological score by lessening the inflammation, necrosis, and fibrosis. In the liver, profibrotic COL1A1 and FN, proinflammation TNFα, as well as the regulator of lipid metabolism PPARɣ expression, were also downregulated after injection. In parallel, the transcriptomic profiles of the injected MERTK+/hi M2c macrophages showed that the various genes directly or indirectly involved in NAFLD progression (e.g., SERPINE1, FADS2) were also suppressed. Downregulation of cytokines and inflammation-associated genes, such as CCR5, may promote a pro-resolving milieu in the NAFLD liver. Altogether, cell-based therapy using MERTK+/hi M2c macrophages is promising, as it ameliorates NAFLD in mice.
Antitumor Effect of Morusin via G1 Arrest and Antiglycolysis by AMPK Activation in Hepatocellular Cancer
Authors: Cho Ah-Reum , Park Woon-Yi , Lee Hyo-Jung , Sim Deok-Yong , Im Eunji , Park Ji-Eon , Ahn Chi-Hoon , Shim Bum-Sang , Kim Sung-Hoon
Published: September 2021

Though Morusin isolated from the root of Morus alba was known to have antioxidant, anti-inflammatory, antiangiogenic, antimigratory, and apoptotic effects, the underlying antitumor effect of Morusin is not fully understood on the glycolysis of liver cancers. Hence, in the current study, the antitumor mechanism of Morusin was explored in Hep3B and Huh7 hepatocellular carcninomas (HCC) in association with glycolysis and G1 arrest. Herein, Morusin significantly reduced the viability and the number of colonies in Hep3B and Huh7 cells. Moreover, Morusin significantly increased G1 arrest, attenuated the expression of cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) and upregulated p21 and p27 in Hep3B and Huh7 cells. Interestingly, Morusin significantly activated phosphorylation of the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) but attenuated the expression of the p-mammalian target of protein kinase B (AKT), rapamycin (mTOR), c-Myc, hexokinase 2(HK2), pyruvate kinases type M2 (PKM2), and lactate dehydrogenase (LDH) in Hep3B and Huh7 cells. Consistently, Morusin suppressed lactate, glucose, and adenosine triphosphate (ATP) in Hep3B and Huh7 cells. Conversely, the AMPK inhibitor compound C reduced the ability of Morusin to activate AMPK and attenuate the expression of p-mTOR, HK2, PKM2, and LDH-A and suppressed G1 arrest induced by Morusin in Hep3B cells. Overall, these findings suggest that Morusin exerts an antitumor effect in HCCs via AMPK mediated G1 arrest and antiglycolysis as a potent dietary anticancer candidate.
Coronary Heart Disease (CHD) in Elderly Patients: Which Drug to Choose, Ticagrelor and Clopidogrel? A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Akkaif Mohammed Ahmed , Sha’aban Abubakar , Daud Nur Aizati Athirah , Yunusa Ismaeel , Ng Mei Li , Sk Abdul Kader Muhamad Ali , Noor Dzul Azri Mohamed , Ibrahim Baharudin
Published: September 2021

Background: A new generation P2Y12 receptor inhibitor (ticagrelor) is recommended in current therapeutic guidelines to treat patients with coronary heart disease (CHD). However, it is unknown if ticagrelor is more effective than clopidogrel in elderly patients. Therefore, a systematic review was done to assess the effectiveness and safety of ticagrelor and clopidogrel in older patients with CHD to determine the appropriate antiplatelet treatment plan. Methodology: We performed a systematic review of randomized controlled trials (RCTs) to compare the effectiveness and safety of ticagrelor vs. clopidogrel in elderly patients with CHD. We selected eligible RCTs based on specified study criteria following a systematic search of PubMed and Scopus databases from January 2007 to May 2021. Primary efficacy outcomes assessed were major adverse cardiovascular events (MACEs), myocardial infarction (MI), stent thrombosis (ST), and all-cause death. The secondary outcome assessed was major bleeding events. We used RevMan 5.3 software to conduct a random-effects meta-analysis and estimated the pooled incidence and risk ratios (RRs) with 95% confidence intervals (CIs) for ticagrelor and clopidogrel. Results: Data from 6 RCTs comprising 21,827 elderly patients were extracted according to the eligibility criteria. There was no significant difference in the MACE outcome (incidence: 9.23% vs. 10.57%; RR = 0.95, 95% CI = 0.70–1.28, p = 0.72), MI (incidence: 5.40% vs. 6.23%; RR = 0.94, 95% CI= 0.69–1.27, p = 0.67), ST (incidence: 2.33% vs. 3.17%; RR = 0.61, 95% CI= 0.32–1.17, p = 0.13), and all-cause death (4.29% vs. 5.33%; RR = 0.86, 95% CI = 0.65–1.12, p = 0.25) for ticagrelor vs. clopidogrel, respectively. In addition, ticagrelor was not associated with a significant increase in the rate of major bleeding (incidence: 9.98% vs. 9.33%: RR = 1.37, 95% CI = 0.97–1.94, p = 0.07) vs. clopidogrel. Conclusions: This study did not find evidence that ticagrelor is significantly more effective or safer than clopidogrel in elderly patients with CHD.
Three-Dimensional Surface Texture Analysis of Fluoride’s Effect on Enamel Erosion
Authors: Habashi Waseem , Bader-Farraj Amal , Shpack Nir , Beitlitum Ilan , May Hila , Sarig Rachel
Published: September 2021

Enamel erosion has become a common clinical finding that often impairs dental esthetics and function. In the current study, we aimed to implement the three-dimensional surface texture analysis (3DST) method to explore the protective effect of fluoride on surface texture prior to erosive conditions. For each of the 50 teeth used in this study, the polished buccal enamel surface was divided into three separate areas: the first area was untouched polished enamel, the two other surfaces were immersed in 0.3% citric acid for 30 s. One was treated with high-concentration (19,000 ppm) sodium fluoride (NaF) solution prior to acid attack, and the other had no treatment prior to acid exposure. Enamel surface texture and step height measurements were obtained using a high-resolution disk scanning confocal microscope, and SEM images were also acquired. Surfaces treated with fluoride showed fewer variations in 3-D surface texture parameters than the eroded surface compared to the control group (p = 0.001). This was in accordance with the SEM descriptive images. The findings indicate that pre-fluoridated enamel areas were less affected by the acid and showed similar features to the untouched enamel. Moreover, a protective effect of the fluoride treatment against irreversible enamel damage was noted as the surface loss (step-height) was significantly reduced (p = 0.03). The study showed that 3DST analysis is a valuable methodology for detecting and quantifying subtle differences between the surfaces. When exploring the combination of all surface texture parameters, it was revealed that the pre-fluoridated eroded enamel surfaces showed considerable similarity to the untouched enamel.