bluuebunny/crossref_metadata_2025 huggingface dataset:
TLR4 Deficiency Exacerbates Biliary Injuries and Peribiliary Fibrosis Caused by Clonorchis sinensis in a Resistant Mouse Strain
Authors: Yan Chao , Wu Jing , Xu Na , Li Jing , Zhou Qian-Yang , Yang Hui-Min , Cheng Xiao-Dan , Liu Ji-Xin , Dong Xin , Koda Stephane , Zhang Bei-Bei , Yu Qian , Chen Jia-Xu , Tang Ren-Xian , Zheng Kui-Yang
Published: January 2021

Mice with different genetic backgrounds have various susceptibilities to infection with Clonorchis sinensis, although the mechanisms underlying are largely unknown. Toll-like receptor 4 (TLR4) as one of the most important pattern recognition receptors (PPRs) is essential for the invasion, survival, pathogenesis, and elimination of worms. The roles played by TLR4 in C. sinensis infection may vary due to the different genetic backgrounds of mice. In the present study, a relatively resistant mouse strain-C57BL/10 to C. sinensis was used for investigation on the possible roles of TLR4 in the biliary injuries and peribiliary fibrosis. TLR4 wild type (TLR4wild) and TLR4 defective (TLR4def) mice were orally infected with 45 metacercariae of C. sinensis, and all C. sinensis-infected mice and non-infected groups were anesthetized on day 28 post-infection. The liver and serum from each mouse were collected for assessment of the biliary injuries and biliary fibrosis. Meanwhile, hepatic leukocytes were isolated and detected for the activation of M1 or M2 macrophage using flow cytometry. The hepatic type 1 immune response and type 2 immune responses -relative molecules were also evaluated using ELISA and quantitative PCR. The data showed that TLR4def aggravated liver inflammatory cell infiltrations, bile duct proliferation, biliary and hepatocellular injuries, and ECM deposition in C. sinensis-infected mice, compared with TLR4wild mice when they were intragastrically administered with the same amounts of C. sinensis metacercaria. Furthermore, the M2-like macrophages and type 2 immune responses were significantly predominant induced in TLR4def mice, compared with that of TLR4wild mice following C. sinensis infection. But the type 1 immune response were significantly decreased in TLR4def mice, compared with TLR4wild mice after C. sinensis infection. These data demonstrate that TLR4 deficiency exacerbates biliary injuries and peribiliary fibrosis caused by C. sinensis in C57BL/10 strain mice, which is contributed by augments of type 2 immune responses and decrease pro-inflammatory responses.
Gender-Related Differences in Heart Failure Biomarkers
Authors: Cediel Germán , Codina Pau , Spitaleri Giosafat , Domingo Mar , Santiago-Vacas Evelyn , Lupón Josep , Bayes-Genis Antoni
Published: January 2021

Important differences in comorbidities and clinical characteristics exist between women and men with heart failure (HF). In particular, differences in the kinetics of biological circulating biomarkers—a critical component of cardiovascular care—are highly relevant. Most circulating HF biomarkers are assessed daily by clinicians without taking sex into account, despite the multiple gender-related differences observed in plasma concentrations. Even in health, compared to men, women tend to exhibit higher levels of natriuretic peptides and galectin-3 and lower levels of cardiac troponins and the cardiac stress marker, soluble ST2. Many biological factors can provide a reliable explanation for these differences, like body composition, fat distribution, or menopausal status. Notwithstanding, these sex-specific differences in biomarker levels do not reflect different pathobiological mechanisms in HF between women and men, and they do not necessarily imply a need to use different diagnostic cut-off levels in clinical practice. To date, the sex-specific prognostic value of HF biomarkers for risk stratification is an unresolved issue that future research must elucidate. This review outlines current evidence regarding gender-related differences in circulating biomarkers widely used in HF, the pathophysiological mechanisms underlying these differences, and their clinical relevance.
Radiation Exposure to the Thyroid After the Chernobyl Accident
Authors: Drozdovitch Vladimir
Published: January 2021

Introduction

The Chernobyl accident resulted in a considerable release of radioactivity to the atmosphere, particularly of Iodine-131 (131I), with the greatest contamination occurring in Belarus, Ukraine, and western part of Russia.

Material and Methods

Increase in thyroid cancer and other thyroid diseases incidence in population exposed to Chernobyl fallout in these counties was the major health effect of the accident. Therefore, a lot of attention was paid to the thyroid doses, mainly, the 131I intake during two months after the accident. This paper reviews thyroid doses, both the individual for the subjects of radiation epidemiological studies and population-average doses. Exposure to 131I intake and other exposure pathways to population of affected regions and the Chernobyl cleanup workers (liquidators) are considered.

Results

Individual thyroid doses due to 131I intake varied up to 42 Gy and depended on the age of the person, the region where a person was exposed, and their cow’s milk consumption habits. Population-average thyroid doses among children of youngest age reached up to 0.75 Gy in the most contaminated area, the Gomel Oblast, in Belarus. Intake of 131I was the main pathway of exposure to the thyroid gland; its mean contribution to the thyroid dose in affected regions was more than 90%. The mean thyroid dose from inhalation of 131I for early Chernobyl cleanup workers was estimated to be 0.18 Gy. Individual thyroid doses due to different exposure pathways varied among 1,137 cleanup workers included in the epidemiological studies up to 9 Gy. Uncertainties associated with dose estimates, in terms of mean geometric standard deviation of individual stochastic doses, varied in range from 1.6 for doses based on individual-radiation measurements to 2.6 for “modelled” doses.

Conclusion

The 131I was the most radiologically important radionuclide that resulted in radiation exposure to the thyroid gland and cause an increase in the of rate of thyroid cancer and other thyroid diseases in population exposed after the Chernobyl accident.
New Insights Into the Role of Autoreactive CD8 T Cells and Cytokines in Human Type 1 Diabetes
Authors: Bender Christine , Rajendran Sakthi , von Herrath Matthias G.
Published: January 2021

Since the establishment of the network for pancreatic organ donors with diabetes (nPOD), we have gained unprecedented insight into the pathology of human type 1 diabetes. Many of the pre-existing “dogmas”, mostly derived from studies of animal models and sometimes limited human samples, have to be revised now. For example, we have learned that autoreactive CD8 T cells are present even in healthy individuals within the exocrine pancreas. Furthermore, their “attraction” to islets probably relies on beta-cell intrinsic events, such as the over-expression of MHC class I and resulting presentation of autoantigens such as (prepro)insulin. In addition, we are discovering other signs of beta-cell dysfunction, possibly at least in part due to stress, such as the over-expression of certain cytokines. This review summarizes the latest developments focusing on cytokines and autoreactive CD8 T cells in human type 1 diabetes pathogenesis.
An Investigation of ZZ/ZW and XX/XY Sex Determination Systems in North African Catfish (Clarias gariepinus, Burchell, 1822)
Authors: Nguyen Dung Ho My , Panthum Thitipong , Ponjarat Jatupong , Laopichienpong Nararat , Kraichak Ekaphan , Singchat Worapong , Ahmad Syed Farhan , Muangmai Narongrit , Peyachoknagul Surin , Na-Nakorn Uthairat , Srikulnath Kornsorn
Published: January 2021

An investigation of sex-specific loci may provide important insights into fish sex determination strategies. This may be useful for biotechnological purposes, for example, to produce all-male or all-female fish for commercial breeding. The North African catfish species, Clarias gariepinus, has been widely adopted for aquaculture because its superior growth and disease resistance render the species suitable for hybridization with other catfish to improve the productivity and quality of fish meat. This species has either a ZZ/ZW or XX/XY sex determination system. Here, we investigate and characterize these systems using high-throughput genome complexity reduction sequencing as Diversity Arrays Technology. This approach was effective in identifying moderately sex-linked loci with both single-nucleotide polymorphisms (SNPs) and restriction fragment presence/absence (PA) markers in 30 perfectly sexed individuals of C. gariepinus. However, SNPs based markers were not found in this study. In total, 41 loci met the criteria for being moderately male-linked (with male vs. female ratios 80:20 and 70:30), while 25 loci were found to be moderately linked to female sex. No strictly male- or female-linked loci were detected. Seven moderately male-linked loci were partially homologous to some classes of transposable elements and three moderately male-linked loci were partially homologous to functional genes. Our data showed that the male heterogametic XX/XY sex determination system should co-exist with the ZZ/ZW system in C. gariepinus. Our finding of the co-existence of XX/XY and ZZ/ZW systems can be applied to benefit commercial breeding of this species in Thailand. This approach using moderately sex-linked loci provides a solid baseline for revealing sex determination mechanisms and identify potential sex determination regions in catfish, allowing further investigation of genetic improvements in breeding programs.
Label-Free Comparative Proteomics Analysis Revealed Heat Stress Responsive Mechanism in Hypsizygus marmoreus
Authors: Xu Lili , Guo Lizhong , Yu Hao
Published: January 2021

Heat stress is an important adverse environmental stress that influences the growth and development of Hypsizygus marmoreus (white var.). However, the molecular basis of heat stress response in H. marmoreus remains poorly understood. In this study, label-free comparative proteomic technique was applied to investigate global protein expression profile of H. marmoreus mycelia under heat stress. Confocal laser scanning microscope observation revealed that mycelia underwent autolysis and apoptosis under heat stress. Autolysis was mediated by upregulating the expression of cell wall degradation enzymes and inhibiting cell wall synthesis enzymes, and apoptosis might be induced by ROS and activation of caspases. TBARS analysis indicated that ROS was accumulated in H. marmoreus mycelia under heat stress. H. marmoreus induced antioxidant defense system by upregulating the expression of catalases, superoxide dismutases and peroxidases to prevent oxidative damage. MAPK cascade was found to be involved in heat stress signal transduction. The stress signal induced a ubiquitous defense response: inducible expression of different kinds of heat shock proteins. Trehalose synthesis enzymes were also upregulated, suggesting the accumulation of stress protector trehalose under heat stress. Besides, upregulated proteasome was identified, which could prevented the accumulation of non-functional misfolding proteins. To satisfy ATP depletion in heat response cellular processes, such as ROS scavenging, and protein folding and synthesis, enzymes involved in energy production (carbon metabolism and ATP synthesis) system were upregulated under heat stress. Taken together, these findings improve our understanding of the molecular mechanisms underlying the response of heat stress in H. marmoreus.
Transcriptome Profiling Revealed Multiple rquA Genes in the Species of Spirostomum (Protozoa: Ciliophora: Heterotrichea)
Authors: Mukhtar Irum , Wu Siyi , Wei Shurong , Chen Ruanni , Cheng Yunying , Liang Chen , Chen Jianming
Published: January 2021

Adaptation to life at different oxygen tensions plays a role in protozoan ecology and controls the distribution of different species in anoxic habitats. The ciliate genusSpirostomuminhabiting fresh or low salinity water globally where these species are considered as bioindicators. Under anaerobic or low oxygen conditions, the rhodoquinol-dependent pathway has been reported in the species from the class Heterotrichea. With the help of RNA sequencing (RNAseq) data,Spirostomumspp., are suitable for deep molecular investigations onrquAfor rhodoquinone (RQ) biosynthesis. In this study,Spirostomum ambiguum,Spirostomum subtilis, andSpirostomum terescollected from densely vegetated freshwater habitat in Fuzhou, China, explored the evidence ofrquA. Based on transcriptome analysis, two to three RquA proteins were identified inS. ambiguum,S. teres, andS. subtilis, respectively. The presence of a key Motif-I of RquA and mitochondrial targeting signals (MTS), also confirmed the identity of these as RquA. Furthermore,SpirostomumRquA proteins could be sorted into two groups based on their conserved amino acid (CAA) residues. Phylogenetic analysis also exhibited RquA division into two subclades contained RquA1 and RquA2/RquA3 and supports two to three paralogs ofrquAgenes in the genomesSpirostomumspp. Additional transcriptomes and genomes analysis ofBlepharismaspp., andStentorspp., respectively, also revealed at least two paralogs ofrquAin members of the class Heterotrichea. The present study provides evidence for the presence of RquA and rhodoquinol dependent fumarate reduction pathway inSpirostomumspecies potentially use to respire in the oxygen-depleted habitats and two to three diverserquAgenes.
A Light-Inducible Split-dCas9 System for Inhibiting the Progression of Bladder Cancer Cells by Activating p53 and E-cadherin
Authors: Huang Xinbo , Zhou Qun , Wang Mingxia , Cao Congcong , Ma Qian , Ye Jing , Gui Yaoting
Published: January 2021

Optogenetic systems have been increasingly investigated in the field of biomedicine. Previous studies had found the inhibitory effect of the light-inducible genetic circuits on cancer cell growth. In our study, we applied an AND logic gates to the light-inducible genetic circuits to inhibit the cancer cells more specifically. The circuit would only be activated in the presence of both the human telomerase reverse transcriptase (hTERT) and the human uroplakin II (hUPII) promoter. The activated logic gate led to the expression of the p53 or E-cadherin protein, which could inhibit the biological function of tumor cells. In addition, we split the dCas9 protein to reduce the size of the synthetic circuit compared to the full-length dCas9. This light-inducible system provides a potential therapeutic strategy for future bladder cancer.
NOTCH3 is a Prognostic Factor and Is Correlated With Immune Tolerance in Gastric Cancer
Authors: Cui Yuehong , Li Qian , Li Wei , Wang Yan , Lv Fang , Shi Xinying , Tang Zhaoqing , Shen Zhenbin , Hou Yingyong , Zhang Henghui , Mao Beibei , Liu Tianshu
Published: January 2021

Introduction

Although traditional treatments confer survival benefits to patients with gastric cancer (GC), many patients experience relapse soon after postoperative adjuvant therapy. Immune-related mechanisms play an important role in GC, and immunotherapeutic strategies are considered to be a promising direction for the treatment of GC. Thus, our study aimed to investigate the expression and prognostic significance of immune-related genes in GC.

Methods

Formalin-fixed, paraffin-embedded samples were collected from 48 resectable GC patients. The transcriptome data of the tumor immune microenvironment were assessed using an immuno-oncology 395-gene panel RNA sequencing platform. The prognostic value of the 395 genes was analyzed and validated in the KM plotter and GEPIA databases. The data from The Cancer Genome Atlas (TCGA, downloaded from UCSC Xena repository) and Tumor IMmune Estimation Resource (TIMER) were used to evaluate the correlations between prognostic factors and immune signatures.

Results

Among the 395 genes, NOTCH3 was identified as a good prognostic factor for GC patients. Its prognostic value was also suggested in both our GC cohort from Zhongshan Hospital and the public databases (KM plotter and GEPIA database). Mechanistically, high NOTCH3 expression correlated with a lower infiltration of activated CD8+ T cells and a higher infiltration of immunosuppressive cells including Tregs and M2 macrophages in the tumor microenvironment. Moreover, high NOTCH3 expression was accompanied by the increased expression of a series of immune checkpoint inhibitors, resulting in a dampened immune response. Interestingly, NOTCH3 expression had a negative association with well-documented predictive biomarkers of immune checkpoint blockade (ICB) immunotherapy, including tumor mutation burden (TMB), gene expression profiling (GEP) score and innate anti-PD-1 resistance (IPRES) signature.

Conclusion

These findings uncovered a new mechanism by which NOTCH3 participates in the immune tolerance of GC, implying the potential of NOTCH3 as a therapeutic target or predictive marker for GC patients.
Intricacies of Radiographic Assessment in Testicular Germ Cell Tumors
Authors: Makovník Marek , Rejleková Katarína , Uhrin Ivan , Mego Michal , Chovanec Michal
Published: January 2021

Testicular germ cell tumors (GCTs) are malignancies with a unique biology, pathology, clinical appearance, and excellent outcomes. A correct radiographic assessment of GCTs is extremely important for the clinical management in several typical scenarios. Advancements in the field of diagnostic medicine bring an increasing number of sophisticated imaging methods to increase the performance of imaging studies. The conventional computed tomography (CT) remains the mainstay of diagnostic imaging in the management of GCTs. While certain improvements in the sensitivity and specificity are suggested with magnetic resonance (MR) imaging with lymphotrophic nanoparticles in evaluating retroperitoneal lymph nodes during the staging procedure, further exploration in larger prospective studies is needed. A common diagnostic dilemma is assessing the post-chemotherapy residual disease in GCTs. Several studies have consistently shown advantages in the utility of positron emission tomography (PET) scanning in post-chemotherapy residual retroperitoneal lymph nodes in patients with seminoma, but not with non-seminoma. Recommendations suggest that seminoma patients with a residual disease in the retroperitoneum larger than 3 cm should be subjected for PET scanning with 18-fluorodeoxyglucose. Relatively high sensitivity, specificity and a negative predictive value (80–95%) may guide clinical decision to spare these patients of high morbidity of an unnecessary surgery. However, a positive predictive value of around 50% renders PET scanning difficult to interpret in the case of positive finding. These patients often require extremely difficult surgical procedures with the high risk of post-operative morbidity. Therefore, seminoma patients with PET positive residual masses larger than 3 cm still remain a serious challenge in the decision making of nuclear medicine specialist, oncologists, and urologic surgeons. In this article, we aim to summarize data on controversial dilemmas in staging procedures, active surveillance, and post-chemotherapy assessment of GCTs based on the available published literature.
A Decision-Making Supporting Prediction Method for Breast Cancer Neoadjuvant Chemotherapy
Authors: Song Dong , Man Xiaxia , Jin Meng , Li Qian , Wang Han , Du Ye
Published: January 2021

Neoadjuvant chemotherapy (NAC) may increase the resection rate of breast cancer and shows promising effects on patient prognosis. It has become a necessary treatment choice and is widely used in the clinical setting. Benefitting from the clinical information obtained during NAC treatment, computational methods can improve decision-making by evaluating and predicting treatment responses using a multidisciplinary approach, as there are no uniformly accepted protocols for all institutions for adopting different treatment regiments. In this study, 166 Chinese breast cancer cases were collected from patients who received NAC treatment at the First Bethune Hospital of Jilin University. The Miller–Payne grading system was used to evaluate the treatment response. Four machine learning multiple classifiers were constructed to predict the treatment response against the 26 features extracted from the patients’ clinical data, including Random Forest (RF) model, Convolution Neural Network (CNN) model, Support Vector Machine (SVM) model, and Logistic Regression (LR) model, where the RF model achieved the best performance using our data. To allow a more general application, the models were reconstructed using only six selected features, and the RF model achieved the highest performance with 54.26% accuracy. This work can efficiently guide optimal treatment planning for breast cancer patients.
A Novel Blockade CD47 Antibody With Therapeutic Potential for Cancer
Authors: Lin Fangzhen , Xiong Mengshang , Hao Wei , Song Yuewen , Liu Ruoqi , Yang Yuanyuan , Yuan Xiangfei , Fan Dongmei , Zhang Yizi , Hao Mu , Ye Zhou , Lu Yang , Zhang Yanjun , Wang Jianxiang , Xiong Dongsheng
Published: January 2021

Macrophages as components of the innate immune system play a critical role in antitumor responses. Strategies for targeting CD47 are becoming a hot spot for cancer therapy. The expression of CD47 is exercised by macrophages to make a distinction between “self” or “nonself.” Anti-CD47 antibodies block the interaction between macrophage signal regulatory protein-α (SIRPα) and tumor surface CD47. In this study, we report and assess a novel anti-CD47 blocking antibody named 2C8, which exhibits high affinity and tremendous anticancer effects. More concretely, 2C8 significantly induces macrophages, including protumorigenic subtype M2 macrophages killing tumor cells in vitro, and is revealed to be more effective than commercially available anti-CD47 mAb B6H12.2. In vivo, 2C8 controls tumor growth and extends survival of xenograft mice. The antitumor ability of 2C8 might be applicable to many other cancers. The generation of a novel CD47 antibody contributes to consolidating clinical interest in targeting macrophages for the treatment of malignancy and, moreover, as a supplement therapy when patients are resistant or refractory to other checkpoint therapies or relapse after such treatments.
Decompression of Multimorbidity Along the Disease Trajectories of Diabetes Mellitus Patients
Authors: Haug Nils , Sorger Johannes , Gisinger Teresa , Gyimesi Michael , Kautzky-Willer Alexandra , Thurner Stefan , Klimek Peter
Published: January 2021

Multimorbidity, the presence of two or more diseases in a patient, is maybe the greatest health challenge for the aging populations of many high-income countries. One of the main drivers of multimorbidity is diabetes mellitus (DM) due to its large number of risk factors and complications. Yet, we currently have very limited understanding of how to quantify multimorbidity beyond a simple counting of diseases and thereby inform prevention and intervention strategies tailored to the needs of elderly DM patients. Here, we conceptualize multimorbidity as typical temporal progression patterns of multiple diseases, so-called trajectories, and develop a framework to perform a matched and sex-specific comparison between DM and non-diabetic patients. We find that these disease trajectories can be organized into a multi-level hierarchy in which DM patients progress from relatively healthy states with low mortality to high-mortality states characterized by cardiovascular diseases, chronic lower respiratory diseases, renal failure, and different combinations thereof. The same disease trajectories can be observed in non-diabetic patients, however, we find that DM patients typically progress at much higher rates along their trajectories. Comparing male and female DM patients, we find a general tendency that females progress faster toward high multimorbidity states than males, in particular along trajectories that involve obesity. Males, on the other hand, appear to progress faster in trajectories that combine heart diseases with cerebrovascular diseases. Our results show that prevention and efficient management of DM are key to achieve a compression of morbidity into higher patient ages. Multidisciplinary efforts involving clinicians as well as experts in machine learning and data visualization are needed to better understand the identified disease trajectories and thereby contribute to solving the current multimorbidity crisis in healthcare.
Complex Inferential Processes Are Needed for Implicature Comprehension, but Not for Implicature Production
Authors: Mognon Irene , Sprenger Simone A. , Kuijper Sanne J. M. , Hendriks Petra
Published: January 2021

Upon hearing “Some of Michelangelo’s sculptures are in Rome,” adults can easily generate a scalar implicature and infer that the intended meaning of the utterance corresponds to “Some but not all Michelangelo’s sculptures are in Rome.” Comprehension experiments show that preschoolers struggle with this kind of inference until at least 5 years of age. Surprisingly, the few studies having investigated children’s production of scalar expressions like some and all suggest that production is adult-like already in their third year of life. Thus, children’s production of implicatures seems to develop at least 2 years before their comprehension of implicatures. In this paper, we present a novel account of scalar implicature generation in the framework of Bidirectional Optimality Theory: the Asymmetry Account. We show that the production–comprehension asymmetry is predicted to emerge because the comprehension of some requires the hearer to consider the speaker’s perspective, but the production of some does not require the speaker to consider the hearer’s perspective. Hence, children’s comprehension of scalar expressions, but not their production of scalar expressions, is predicted to be related to their theory of mind development. Not possessing fully developed theory of mind abilities yet, children thus have difficulty in comprehending scalar expressions such as some in an adult-like way. Our account also explains why variable performance is found in experimental studies testing children’s ability to generate scalar implicatures; moreover, it describes the differences between children’s and adults’ implicature generation in terms of their ability to recursively apply theory of mind; finally, it sheds new light on the question why the interpretation of numerals does not require implicature generation.
Applying Deep Learning Techniques to Estimate Patterns of Musical Gesture
Authors: Dalmazzo David , Waddell George , Ramírez Rafael
Published: January 2021

Repetitive practice is one of the most important factors in improving the performance of motor skills. This paper focuses on the analysis and classification of forearm gestures in the context of violin playing. We recorded five experts and three students performing eight traditional classical violin bow-strokes: martelé, staccato, detaché, ricochet, legato, trémolo, collé, and col legno. To record inertial motion information, we utilized the Myo sensor, which reports a multidimensional time-series signal. We synchronized inertial motion recordings with audio data to extract the spatiotemporal dynamics of each gesture. Applying state-of-the-art deep neural networks, we implemented and compared different architectures where convolutional neural networks (CNN) models demonstrated recognition rates of 97.147%, 3DMultiHeaded_CNN models showed rates of 98.553%, and rates of 99.234% were demonstrated by CNN_LSTM models. The collected data (quaternion of the bowing arm of a violinist) contained sufficient information to distinguish the bowing techniques studied, and deep learning methods were capable of learning the movement patterns that distinguish these techniques. Each of the learning algorithms investigated (CNN, 3DMultiHeaded_CNN, and CNN_LSTM) produced high classification accuracies which supported the feasibility of training classifiers. The resulting classifiers may provide the foundation of a digital assistant to enhance musicians' time spent practicing alone, providing real-time feedback on the accuracy and consistency of their musical gestures in performance.
Exogenous Application of Nitric Oxide Mitigates Water Stress and Reduces Natural Viral Disease Incidence of Tomato Plants Subjected to Deficit Irrigation
Authors: Elkelish Amr , Ibrahim Mohamed F. M. , Ashour Hatem , Bondok Ahmed , Mukherjee Soumya , Aftab Tariq , Hikal Mohamed , El-Yazied Ahmed Abou , Azab Ehab , Gobouri Adil A. , Moustafa-Farag Mohamed , Metwally Amr A. , El-Gawad Hany G. Abd
Published: January 2021

The present work reveals the beneficial role of sodium nitroprusside (SNP; NO donor concentration: 50 and 100 µM) in mitigation of water stress accompanied by a reduction in viral disease incidence in tomato plants subjected to deficit irrigation. The plants were grown under two irrigation regimes: well-watered (WW; irrigated after the depletion of 55–60% of available soil water) and water deficit (WD; irrigated after the depletion of 85–90% of available soil water) in two seasons of 2018 and 2019. The results indicated that under water stress conditions, plant growth, chlorophyll, relative water content (RWC), and fruit yield were decreased. Conversely, water stress significantly increased the MDA, proline, soluble sugars, and antioxidant enzymes’ activities. Moreover, it was obvious a negligible increase in the fruit content from NO2 and NO3. Water-deficit stress, however, had a positive impact on reducing the percentage of viral disease (TMV and TYLCV) incidence on tomato plants. Similarly, SNP application in the form of foliar spray significantly reduced the disease incidence, the severity, and the relative concentrations of TMV and TYLCV in tomato plants raised under both WW and WD conditions. The treatment of SNP at 100 µM achieved better results and could be recommended to induce tomato plant tolerance to water stress. Thus, the present work highlights the role of NO (SNP) in the alleviation of water stress in tomato plants and subsequent reduction in viral disease incidence during deficit irrigation.
A Simple Technique for Studying Chaos Using Jerk Equation with Discrete Time Sine Map
Authors: Arshad Muhammad Haseeb , Kassas Mahmoud , Hussein Alaa E. , Abido Mohammad A.
Published: January 2021

Over the past decade, chaotic systems have found their immense application in different fields, which has led to various generalized, novel, and modified chaotic systems. In this paper, the general jerk equation is combined with a scaled sine map, which has been approximated in terms of a polynomial using Taylor series expansion for exhibiting chaotic behavior. The paper is based on numerical simulation and experimental verification of the system with four control parameters. The proposed system’s chaotic behavior is verified by calculating different chaotic invariants using MATLAB, such as bifurcation diagram, 2-D attractor, Fourier spectra, correlation dimension, and Maximum Lyapunov Exponent. Experimental verification of the system was carried out using Op-Amps with analog multipliers.
Antioxidant and Antibacterial Activity of Nepeta × faassenii Bergmans ex Stearn Essential Oil
Authors: Jianu Călin , Moleriu Radu , Stoin Daniela , Cocan Ileana , Bujancă Gabriel , Pop Georgeta , Lukinich-Gruia Alexandra Teodora , Muntean Delia , Rusu Laura-Cristina , Horhat Delia Ioana
Published: January 2021

This study was designed to evaluate, for the first time, the antioxidant and antimicrobial activities of Nepeta × faassenii essential oil (NEO). Twenty-six compounds were identified by gas chromatography and mass spectrometry analysis, of which 4a alpha,7alpha,7a alpha-nepetalactone (34.12%), elemol (23.23%), spiro(5,6)dodecane (13.73%), and 3,4 alpha-dihydro-4a alpha, 7 alpha, 7a alpha-nepetalactone (7.93%) were the major compounds. The NEO exhibited broad-spectrum antibacterial effects, and possesses potent antifungal activity on Candida albicans and Candida parapsilosis. NEO’s antioxidant activity was evaluated against cold-pressed sunflowers oil by peroxide, thiobarbituric acid, 1,1-diphenyl- 2-picrylhydrazyl radical, and β-carotene/linoleic acid bleaching methods. The NEO showed strong scavenging (IC50: 0.032 ± 0.005 mg/mL) and relative antioxidative activity (RAA%: 92.31 ± 0.17%) in 1,1-diphenyl- 2-picrylhydrazyl radical and β-carotene/linoleic acid bleaching assays, respectively. Moreover, during 24 days of the incubation period, the oil inhibits the primary lipid oxidation significantly better (p < 0.05) than butylated hydroxyanisole (BHA). In the case of secondary lipid oxidation, the oil performed significantly better (p < 0.001) than BHA from day 8 to day 12 of the incubation period. The biological activities recorded suggest that NEO may represent an antioxidant and antimicrobial agent with applications in medicine or the food industry.
Fast Sound Source Localization Based on SRP-PHAT Using Density Peaks Clustering
Authors: Zhuo De-Bing , Cao Hui
Published: January 2021

Sound source localization has been increasingly used recently. Among the existing techniques of sound source localization, the steered response power–phase transform (SRP-PHAT) exhibits considerable advantages regarding anti-noise and anti-reverberation. When applied in real-time situations, however, the heavy computational load makes it impossible to localize the sound source in a reasonable time since SRP-PHAT employs a grid search scheme. To solve the problem, an improved procedure called ODB-SRP-PHAT, i.e., steered response power and phase transformation with an offline database (ODB), was proposed by the authors. The basic idea of ODB-SRP-PHAT is to determine the possible sound source positions using SRP-PHAT and density peak clustering before real-time localization and store the identified positions in an ODB. Then, at the online positioning stage, only the power values of the positions in the ODB will be calculated. When used in real-time monitoring, e.g., locating the speaker in a video conference, the computational load of ODB-SRP-PHAT is significantly smaller than that of SRP-PHAT. Simulations and experiments under a real environment verified the high localization accuracy with a small computational load of ODB-SRP-PHAT. In addition, the advantages of anti-noise and anti-reverberation remained. The suggested procedure displayed good applicability in a real environment.
A Computer Simulation Research of Two Types of Cardiac Physiological Pacing
Authors: Zhu Honglei , Jin Lian , Huang Yanqi , Wu Xiaomei
Published: January 2021

This manuscript adopted the cardiac modeling and simulation method to study the problems of physiological pacing in clinical application. A multiscale rabbit ventricular electrophysiological model was constructed. We simulated His-bundle pacing (HBP) treatment for left bundle branch block (LBBB) and atrioventricular block (AVB), and left bundle branch pacing (LBBP) treatment for LBBB by setting various moments of the stimulus. The synthetic ECGs and detailed electrical activities were analyzed. Our electrophysiological model accurately simulated the normal state, HBP, and LBBP. The synthetic ECG showed that QRS duration was narrowed by 30% after HBP correction for LBBB. For LBBB correction with LBBP, the synthetic ECGs of LBBP starting before 30 ms (if the end of atrial excitation is set as 0 ms) presented right bundle branch block (RBBB), and those of LBBP starting at 30–38 ms were synchronous, while those of LBBP starting after 42 ms possessed LBBB morphologies. The best pacing results were obtained when LBBP started at 34 ms. This manuscript verified the feasibility of the constructed ventricular model, and studied the physiological pacing mechanism. The results showed that HBP realized correction for AVB and high LBBB. The performance of LBBP can be improved by applying the stimulus within a specific period of time (0–8 ms) after atrial excitation.
Methodology for Complex Efficiency Evaluation of Machinery Safety Measures in a Production Organization
Authors: Pačaiová Hana , Andrejiová Miriam , Balažiková Michaela , Tomašková Marianna , Gazda Tomáš , Chomová Katarína , Hijj Ján , Salaj Lukáš
Published: January 2021

Even though the rules for the free circulation of machinery within the European Union (EU) market have existed for more than 30 years, accidents related to their activities have constantly been reaching significant value. When designing a machine, the design must stem from a risk assessment, where all stages of its life cycle and the ways to use it must be taken into consideration. In industrial operations with old machinery, despite fulfilling its function reliably, the safety level is below the developing requirements for safe operations. The proposed methodology to assess machinery safety conditions comes from the assumption of the proper application of risk assessment steps and their effectiveness in risk reduction mainly through implementing both effective and efficient preventive measures. The objective of the research applied in three operations was to verify the methods concerning machinery safety and its management. The created methodology, based on 19 requirements for safety, evaluates the level of current measures using a criterion of the current safety status and the total effectiveness of safety measures. Its output is the assessment of the efficiency level of the implemented safety measures of each machine as well as of the whole operation.
Optimization of Lignin Recovery from the Pre-Hydrolysate of Kraft-Based Dissolving Pulp Production Processes
Authors: Mazar Adil , Jemaa Naceur , Wafa Al Dajani Waleed , Marinova Mariya , Perrier Michel
Published: January 2021

A pre-hydrolysate is an aqueous stream obtained during the production of hardwood kraft dissolving pulp. It is rich in sugars and contains dissolved organic matters. The purpose of this study is to investigate the optimization of lignin recovery from wood pre-hydrolysates and to characterize the extracted lignin. The optimal conditions for lignin extraction have been determined to be (a) a filtration temperature of 40 °C, (b) a sulfuric acid concentration of 8.5 kg·m−3, and (c) a coagulation time of 180 min. Using these conditions, high filtration rates have been obtained and the extracted lignin has a low content of impurities (8.3%), a low molecular weight (1270 Da), and a very low polydispersity (Mw/Mn = 1.22). Compared to kraft lignin, the pre-hydrolysate lignin has a much lower molecular weight and could be a potential candidate for niche applications. A high lignin recovery rate is possible (52% of the total lignin content in the pre-hydrolysate).
Alcohol-and-HIV-Induced Lysosomal Dysfunction Regulates Extracellular Vesicles Secretion in Vitro and in Liver-Humanized Mice
Authors: Dagur Raghubendra Singh , New-Aaron Moses , Ganesan Murali , Wang Weimin , Romanova Svetlana , Kidambi Srivatsan , Kharbanda Kusum K. , Poluektova Larisa Y. , Osna Natalia A.
Published: January 2021

Background: Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress and lysosomaldysfunction in the liver cells. We hypothesize that the increased release of extracellular vesicles(EVs) in hepatocytes and liver humanized mouse model is linked to lysosome dysfunction. Methods:The study was performed on primary human hepatocytes and human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected with CYP2E1 and XPack-GFP) cells and validated on ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-, Rag2-/-, common cytokine receptor gamma chainknockout (FRG-KO) mice. Cells and mice were infected with HIV-1ADA virus. Results: We observedan increase in the secretion of EVs associated with a decrease in lysosomal activity and expressionof lysosomal-associated membrane protein 1. Next-generation RNA sequencing of primary humanhepatocytes revealed 63 differentially expressed genes, with 13 downregulated and 50 upregulatedgenes in the alcohol–HIV-treated group. Upstream regulator analysis of differentially expressedgenes through Ingenuity Pathway Analysis identified transcriptional regulators affecting downstreamgenes associated with increased oxidative stress, lysosomal associated disease, and function andEVs biogenesis. Our in vitro findings were corroborated by in vivo studies on human hepatocytetransplantedhumanized mice, indicating that intensive EVs’ generation by human hepatocytes andtheir secretion to serum was associated with increased oxidative stress and reduction in lysosomalactivities triggered by HIV infection and ethanol diet. Conclusion: HIV-and-ethanol-metabolisminducedEVs release is tightly controlled by lysosome status in hepatocytes and participates in thedevelopment of double-insult-induced liver injury.
Neuroprotective Effects of Extracts from Tiger Milk Mushroom Lignosus rhinocerus Against Glutamate-Induced Toxicity in HT22 Hippocampal Neuronal Cells and Neurodegenerative Diseases in Caenorhabditis elegans
Authors: Kittimongkolsuk Parinee , Pattarachotanant Nattaporn , Chuchawankul Siriporn , Wink Michael , Tencomnao Tewin
Published: January 2021

Despite the Tiger Milk Mushroom Lignosus rhinocerus (LR) having been used as a traditional medicine, little is known about the neuroprotective effects of LR extracts. This study aims to investigate the neuroprotective effect of three extracts of LR against glutamate-induced oxidative stress in mouse hippocampal (HT22) cells as well as to determine their effect in Caenorhabditis elegans. In vitro, we assessed the toxicity of three LR extracts (ethanol extract (LRE), cold-water extract (LRC) and hot-water extract (LRH)) and their protective activity by MTT assay, Annexin V-FITC/propidium iodide staining, Mitochondrial Membrane Potential (MMP) and intracellular ROS accumulation. Furthermore, we determined the expression of antioxidant genes (catalase (CAT), superoxide dismutase (SOD1 and SOD2) and glutathione peroxidase (GPx)) by qRT-PCR. In vivo, we investigated the neuroprotective effect of LRE, not only against an Aβ-induced deficit in chemotaxis behavior (Alzheimer model) but also against PolyQ40 formation (model for Morbus Huntington) in transgenic C. elegans. Only LRE significantly reduced both apoptosis and intracellular ROS levels and significantly increased the expression of antioxidant genes after glutamate-induced oxidative stress in HT22 cells. In addition, LRE significantly improved the Chemotaxis Index (CI) in C. elegans and significantly decreased PolyQ40 aggregation. Altogether, the LRE exhibited neuroprotective properties both in vitro and in vivo.
Design, Synthesis and In Vitro Investigation of Novel Basic Celastrol Carboxamides as Bio-Inspired Leishmanicidal Agents Endowed with Inhibitory Activity against Leishmania Hsp90
Authors: Bassanini Ivan , Parapini Silvia , Ferrandi Erica E. , Gabriele Elena , Basilico Nicoletta , Taramelli Donatella , Sparatore Anna
Published: January 2021

The natural triterpene celastrol (CE) is here used as lead compound for the design and synthesis of a panel of eleven CE carboxamides that were tested in vitro for their growth inhibitory activity against Leishmania infantum and L.tropica parasites. Among them, in vitro screening identified four basic CE carboxamides endowed with nanomolar leishmanicidal activity, against both the promastigotes and the intramacrophage Leishmania amastigotes forms. These compounds also showed low toxicity toward two human (HMEC-1 and THP-1) and one murine (BMDM) cell lines. Interestingly, the most selective CE analogue (compound 3) was also endowed with the ability to inhibit the ATPase activity of the Leishmania protein chaperone Hsp90 as demonstrated by the in vitro assay conducted on a purified, full-length recombinant protein. Preliminary investigations by comparing it with the naturally occurring Hsp90 active site inhibitor Geldanamycin (GA) in two different in vitro experiments were performed. These promising results set the basis for a future biochemical investigation of the mode of interaction of celastrol and CE-inspired compounds with Leishmania Hsp90.
A New Look at the Purported Health Benefits of Commercial and Natural Clays
Authors: Incledion Alexander , Boseley Megan , Moses Rachael L. , Moseley Ryan , Hill Katja E. , Thomas David W. , Adams Rachel A. , Jones Tim P. , BéruBé Kelly A.
Published: January 2021

Clays attributed to have medicinal properties have been used since prehistoric times and are still used today as complementary medicines, which has given rise to unregulated “bioceutical” clays to treat skin conditions. Recently, clays with antibacterial characteristics have been proposed as alternatives to antibiotics, potentially overcoming modern day antibiotic resistance. Clays with suggested antibacterial properties were examined to establish their effects on common wound-infecting bacteria. Geochemical, microscopical, and toxicological characterization of clay particulates, their suspensions and filtered leachates was performed on THP-1 and HaCaT cell lines. Cytoskeletal toxicity, cell proliferation/viability (MTT assays), and migration (scratch wounds) were further evaluated. Clays were assayed for antibacterial efficacy using minimum inhibitory concentration assays. All clays possessed a mineral content with antibacterial potential; however, clay leachates contained insufficient ions to have any antibacterial effects. All clay leachates displayed toxicity towards THP-1 monocytes, while clay suspensions showed less toxicity, suggesting immunogenicity. Reduced clay cytotoxicity on HaCaTs was shown, as many leachates stimulated wound-healing responses. The “Green” clay exhibited antibacterial effects and only in suspension, which was lost upon neutralization. pH and its interaction with clay particle surface charge is more significant than previously understood to emphasize dangers of unregulated marketing and unsubstantiated bioceutical claims.
Musical Training and Brain Volume in Older Adults
Authors: Chaddock-Heyman Laura , Loui Psyche , Weng Timothy B. , Weisshappel Robert , McAuley Edward , Kramer Arthur F.
Published: January 2021

Musical practice, including musical training and musical performance, has been found to benefit cognitive function in older adults. Less is known about the role of musical experiences on brain structure in older adults. The present study examined the role of different types of musical behaviors on brain structure in older adults. We administered the Goldsmiths Musical Sophistication Index, a questionnaire that includes questions about a variety of musical behaviors, including performance on an instrument, musical practice, allocation of time to music, musical listening expertise, and emotional responses to music. We demonstrated that musical training, defined as the extent of musical training, musical practice, and musicianship, was positively and significantly associated with the volume of the inferior frontal cortex and parahippocampus. In addition, musical training was positively associated with volume of the posterior cingulate cortex, insula, and medial orbitofrontal cortex. Together, the present study suggests that musical behaviors relate to a circuit of brain regions involved in executive function, memory, language, and emotion. As gray matter often declines with age, our study has promising implications for the positive role of musical practice on aging brain health.