bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure Assessment of Silver and Gold Nanoparticles Generated During the Synthesis Process in a South African Research Laboratory
Authors: Masekameni Masilu D. , Andraos Charlene , Yu Il Je , Gulumian Mary
Published: May 2022

During the synthesis of engineered nanomaterials (ENMs), various occupational exposures occur, leading to health consequences. To date, there is paucity of studies focused on modeling the deposition of nanoparticles emitted from ENMs synthesis processes. This study aimed to characterise and assess exposure to gold (AuNPs) and silver nanoparticles (AgNPs) during a synthesis process in a research laboratory in South Africa. AuNPs and AgNPs synthesis processes were monitored for an hour in a laboratory using a Scanning Mobility Particle Sizer. The monitoring was conducted at a height of 1.2–1.5 m (m) and 1.5 m away from the hood, assuming a 30 cm (cm) breathing circumference zone. Each synthesis process was monitored thrice to generate reliable point estimates, which were used to assess exposure over 8 hours. A time-weighted average concentration was calculated and compared to the derived 8-h occupational exposure limit (OEL) for AgNPs (0.19 μg/m3) and the proposed provisional nano reference value for AuNPs (20,000 particles/cm3). The Multiple-Path Particle Dosimetry model was used to calculate the deposition and retention of both AuNPs and AgNPs. NPs emitted during the synthesis process were dominant in the nuclei (79% for AuNPs and 54% for AgNPs), followed by the Aitken (12% for AuNPs and 29% for AgNPs), with fewer particles in the accumulation mode (9.2% for AuNPs and 17% for AgNPs). AuNPs and AgNPs generated during the synthesis process were determined at 1617.3 ± 102 cm3 (0.046 μg/m3) and 2,687 cm3 ± 620 (0.077 μg/m3), respectively. For the three exposure scenarios, none exceeded the occupational exposure limit for both AuNPs (provisional) and AgNPs (OEL). Workers in the synthesis laboratory are exposed to a concentration below the recommended occupational exposure limit for silver and the proposed provisional nano reference value for gold. Although, the concentrations to which laboratory workers are exposed to are below safe levels, the assessment of the lung deposition patterns indicate a high particle lung retention which raise concerns about long term safety of workers.
Recognition of Cattle's Feeding Behaviors Using Noseband Pressure Sensor With Machine Learning
Authors: Chen Guipeng , Li Cong , Guo Yang , Shu Hang , Cao Zhen , Xu Beibei
Published: May 2022

Automatic monitoring of feeding behavior especially rumination and eating in cattle is important to keep track of animal health and growth condition and disease warnings. The noseband pressure sensor is not only able to accurately sense the pressure change of the cattle's jaw movements, which can directly reflect the cattle's chewing behavior, but also has strong resistance to interference. However, it is difficult to keep the same initial pressure while wearing the pressure sensor, and this will pose a challenge to process the feeding behavior data. This article proposed a machine learning approach aiming at eliminating the influence of initial pressure on the identification of rumination and eating behaviors. The method mainly used the local slope to obtain the local data variation and combined Fast Fourier Transform (FFT) to extract the frequency-domain features. Extreme Gradient Boosting Algorithm (XGB) was performed to classify the features of rumination and eating behaviors. Experimental results showed that the local slope in combination with frequency-domain features achieved an F1 score of 0.96, and recognition accuracy of 0.966 in both rumination and eating behaviors. Combined with the commonly used data processing algorithms and time-domain feature extraction method, the proposed approach improved the behavior recognition accuracy. This work will contribute to the standardized application and promotion of the noseband pressure sensors.
Trim Flap System Design for Improving Ballistic-Lifting Entry Performance of the Tianwen-1 Mars Probe
Authors: Li Xinli , Li Yansong , Hu Dayong , Rao Wei , Qi Yufeng , Yang Qiang , Wang Gang
Published: May 2022

The trim flap is an aerodynamic control surface capable of allowing Mars entry vehicles to improve landing performance during the most dangerous entry, descent, and landing (EDL) phase. In present work, a deployable trim flap system was proposed to meet the aerodynamical trim requirement of the Tianwen-1 Mars probe, which provided a mass-saving alternative to the conventional use of the center-of-gravity (CG) offset of ballast mass. In order to guide the trim flap design, theoretical and finite element (FE) models were established to predict and evaluate the deployment performance. Then, a full-scale physical prototype was manufactured for deployment experiments to verify the design effectiveness as well as validate the theoretical and FE models. Results predicted by theoretical and FE models were in good agreement with deployment experiments. Furthermore, the effects of three factors on the deployment performance were investigated, including the non-linear behavior of the damping, acceleration environment, and backshell flexibility. The manufactured prototype was installed on the Tianwen-1 Mars probe, saving more than 300 kg when compared to the conventional use of ballast mass CG offset, and assisted Tianwen-1 in achieving a successful landing, making China the first country in the world to utilize the trim flap technology for Mars EDL.
Rice for Food Security: Revisiting Its Production, Diversity, Rice Milling Process and Nutrient Content
Authors: Mohidem Nur Atikah , Hashim Norhashila , Shamsudin Rosnah , Che Man Hasfalina
Published: May 2022

Rice is food consumed regularly and is vital for the food security of over half the world’s population. Rice production on a global scale is predicted to rise by 58 to 567 million tonnes (Mt) by 2030. Rice contains a significant number of calories and a wide variety of essential vitamins, minerals, and other nutritional values. Its nutrients are superior to those found in maize, wheat, and potatoes. It is also recognised as a great source of vitamin E and B5 as well as carbohydrates, thiamine, calcium, folate, and iron. Phytic acid and phenols are among the phenolic compounds found in rice, alongside sterols, flavonoids, terpenoids, anthocyanins, tocopherols, tocotrienols, and oryzanol. These compounds have been positively linked to antioxidant properties and have been shown to help prevent cardiovascular disease and diabetes. This review examines recent global rice production, selected varieties, consumption, ending stocks, and the composition of rice grains and their nutritional values. This review also includes a new method of paddy storage, drying, and grading of rice. Finally, the environmental impacts concerning rice cultivation are discussed, along with the obstacles that must be overcome and the current policy directions of rice-producing countries.
Territorial Social Innovation and Alternative Food Networks: The Case of a New Farmers’ Cooperative on the Island of Ibiza (Spain)
Authors: Vercher Néstor
Published: May 2022

Social innovation is gaining attention as a perspective that stresses the relevance of transforming social relations to promote sustainable territorial development. This paper adopts the social innovation approach to examine Alternative Food Networks. The main aim of the study is to identify key factors in the emergence and development of social innovation processes that give rise to new organisational formulas among farmers, which contribute to the coordination and efficiency of food supply in Alternative Food Networks. The article provides an original conceptual framework on territorial social innovation (TerriSI), which is empirically tested in a case study in Ibiza (Spain). Through a mixed methods approach, the study analyses the emergence and development of a new agricultural cooperative that involves producers participating in Alternative Food Networks in Ibiza. This is considered a socially innovative initiative since it comprises novel social reconfigurations within the local context. The findings underline key factors of territorial social innovation linked to the particular conditions of territories, triggers, leadership, coordination mechanisms, and the capacity to disseminate innovation through the territory.
Radiation Use Efficiency and Agronomic Performance of Biomass Sorghum under Different Sowing Dates
Authors: Chavez Jose C. , Ganjegunte Girisha K. , Jeong Jaehak , Rajan Nithya , Zapata Samuel D. , Ruiz-Alvarez Osias , Enciso Juan
Published: May 2022

Accurate estimation of radiation use efficiency (RUE) at variable timed sowing dates will enhance the prediction of plant dry matter accumulation. The objectives of this study were to (1) determine the impact of three sowing dates on the productivity, performance, and economic feasibility of three biomass sorghum hybrids and (2) evaluate the variability of RUE in the production of biomass sorghum under the effects of variable timed sowing dates. Over a two-year experiment, biomass sorghum hybrids were grown and monitored at different sowing seasons under optimal growth conditions. Average dry biomass (DB) productivity at harvest ranged from 22.71 to 32.77 Mg ha−1. Higher leaf area index (LAI) values (>4.0) represented an intercept of over 95% of incident photosynthetically active radiation (PAR). RUE obtained from the slope of the linear relationship between DB produced and accumulated intercepted photosynthetically active radiation (IPAR) ranged from 2.92 to 4.157 g MJ−1 across growing seasons. Higher RUE values were observed for the energy hybrids in the early and mid-season. They converted IPAR efficiently into DB. Lastly, the economic feasibility of each sorghum hybrid and sowing date was evaluated in terms of their expected net returns. Economic results suggest that the sorghum hybrids considered could be a viable source of biomass season long, with net returns ranging from USD 560.55 ha−1 to USD 1255.06 ha−1.
The Effect of Tomato Waste Compost on Yield of Tomato and Some Biological Properties of Soil
Authors: Durmuş Murat , Kızılkaya Rıdvan
Published: May 2022

Turkey ranks third in the world in terms of tomato production, and approximately 12.5 million tons of tomatoes are produced annually. Especially in greenhouse cultivation, tomato wastes do not stay in the soil and are taken out of the greenhouse. Ten million tons of tomato waste is generated annually in Turkey. Compost is a very important organic material containing plant nutrients such as nitrogen, phosphorus, potassium, magnesium, and microelements. Tomato waste compost is a good organic fertilizer that increases both tomato yield and biological activities in soil. The aim of this study is to determine the effect of tomato compost (TC) on tomato yield and biological properties of soils. For this purpose, a pot experiment was established in the greenhouse and TC was applied in four different doses (TC1—1%, TC2—2%, TC3—4%, TC4—6%) to pots containing 3.5 kg of soil, these doses were also applied with chemical fertilizer (CF) (CF, TC1 + CF, TC + CF, TC3 + CF, TC4 + CF), and then tomato plants were grown. Each application was applied as three replications. Among the compost applications, the highest tomato yield was obtained with the TC4 (0.96 kg/pot, 14.4 t/ha) application: 15.66% higher yield was obtained compared to chemical fertilizers. Among all treatments, TC1 + CF (1.07 kg/pot, 16.10 t/ha), which increased the tomato yield by 28.9%, had the highest yield. All applications have increased CO2 production in the soil; the highest CO2 production was determined in the last harvest period with TC3 + CF and TC4 + CF (0.27 mgCO2 1 gr−1 24 h−1). The maximum microbial biomass carbon content was determined in the first harvest period. Among the applications, the most microbial biomass carbon was determined after the TC4 + CF (114.42 mgMBC 100 gr−1) application. Catalase enzyme activity was obtained the most with TC4 + CF (601.56 mlO2 1 gr−1) application in first florescence. Dehydrogenase enzyme activity was obtained the most with TC3 (55.96 μg TPF g−1) application in end of harvest. After compost application, tomato yield increased and biological properties of soil improved.
Transcriptomics Analysis on Fertility Conversion in Thermosensitive Genetic Male Sterility Line Zhu1S under High Temperature
Authors: Chen Yan , Chen Yi , Xiang Zhipan , Li Jiaxin , Chen Huiling , Mao Dandan , Chen Liangbi
Published: May 2022

Zhu1S is a thermosensitive genic male-sterile (TGMS) line of rice possessing outstanding combining ability and low critical temperature, which has been extensively utilized as a female parent in two-line hybrid ricebreeding. However, the fertility of Zhu 1S during hybrid seed production is frequently affected by high temperature, thus leading to its fertility alteration and aborted hybrid seed production. To understand its fertility conversion mechanism under high temperature, we employed transcriptomics analyses on the anthers of young panicles of Zhu 1S during the fertility alternation sensitivity stage under high (Zhu 1S-H) and low (Zhu 1S-L) temperatures. The results showed that a total of 1119 differentially expressed genes (DEGs) were identified between Zhu 1S-H and Zhu1S-L anthers, including 680 up-regulated and 439 down-regulated genes. Bioinformatics analysis of these DEGs revealed that the high temperature induction caused fertility-sterility conversion in Zhu1S, mainly by decreasing the mRNA abundances of important genes closely related to plant hormone and MAPK signal pathway and transcriptional regulation factors, thereby impeding the growth and development of the anther of Zhu 1S, which ultimately affected the fertility transition of Zhu 1S under high temperature. The protein–protein interaction network analysis indicates that transcription factor OsTIFY11C possibility plays a central role in the fertility transition of Zhu 1S under high temperature.The present studies offer a theoretical foundation for further research into the molecular mechanism underlying fertility conversion in TGMS line Zhu 1S.
Growth Response and Dry Matter Partitioning of Quality Protein Maize (Zea mays L.) Genotypes under Aluminum Toxicity
Authors: Zishiri Rutendo M. , Mutengwa Charles S. , Tandzi Liliane N. , Manyevere Alen
Published: May 2022

In this work, 75 quality protein maize (QPM) inbred lines were evaluated for aluminum tolerance using a nutrient solution assay in a laboratory and a soil-based technique in a greenhouse tunnel. The experiment was set up in a completely randomized design with three replications in the laboratory, and a randomized complete block design was used in the greenhouse. Aluminum toxicity was generated by amending a nutrient solution with 600 µM of aluminum sulfate (Al2 [SO4]3) in the laboratory, and Al2 [SO4]3 was applied at a rate of 24 mg kg−1 of soil in the greenhouse experiment. Relative root length (RRL) and hematoxylin staining (HS) scores were used to identify tolerant genotypes in the laboratory. According to RRL, 94.7% of genotypes were tolerant and 5.3% were sensitive, while Hematoxylin (HS) classified 77.9% of the genotypes as tolerant, and 22.1% as sensitive. RRL and HS presented a very strong negative association (−0.788). In the soil-based method, the experiments were conducted twice in successive summer seasons of 2019 and 2020. Several growth traits were measured and most genotypes that exhibited tolerance in the nutrient solution also had similar tolerance in the soil-based screening technique. Genetic variability for tolerance was identified, revealing potentially useful donors of tolerance genes in breeding programs.
Genomic and Transcriptomic Dissection of the Large-Effect Loci Controlling Drought-Responsive Agronomic Traits in Wheat
Authors: Cao Liangjing , Lyu Mingjie , Wang Jingyi , Wang Xuan , Li Xinchang , Jing Ruilian , Liu Jun , Hu Xinwen
Published: May 2022

Drought tolerance is one of the most important targets for wheat breeding. Previous population genetics studies have uncovered 20 large-effect quantitative trait loci (QTLs) that contribute to stress-responsive agronomic traits. Here, we identified 19,035,814 single nucleotide polymorphisms and 719,049 insertion/deletion variations in the genomes of two popular winter wheat cultivars, Lu-Mai 14 and Han-Xuan 10, using a whole-genome re-sequencing assay. There were 4972 loss-of-function mutations carried by protein-coding genes, such as CCA1/LHY, AGO1, ABI3/VP1, EIN3, TPP, and ARFs. We carried out a time-course abscisic acid (ABA)-treatment experiment and profiled 61,251 expressed genes in the roots using a strand-specific RNA sequencing approach. A large number of genes showed time-point specific and/or cultivar-preferential responsive expression patterns. Gene ontology enrichment analysis revealed that ABA-responsive genes were associated with stress-related functions. Among the 20 QTLs, we uncovered 306 expressed genes with high- and/or moderate-effect variations and 472 differentially expressed genes. Detailed analysis and verification of the homozygous genomic variations in the candidate genes encoding sulfotransferase, proteinase, kinase, nitrate transporter, and transcription factors suggested previously unexpected pathways associated with abiotic stress responses in wheat.
Morphological Relationships between the Cholinergic and Somatostatin-28(1-12) Systems in the Alpaca (Lama pacos) Brainstem
Authors: Marcos Pilar , Coveñas Rafael
Published: May 2022

In the alpaca brainstem, the distribution of the cholinergic system by the immunohistochemical detection of the enzyme choline acetyltransferase (ChAT) has been described, and its relationship with the distribution of somatostatin-28(1-12) is analyzed by double-immunostaining techniques. Overlapping distribution patterns for both substances were observed in many brainstem regions, suggesting that interactions between them may occur in the reticular formation, nucleus ambiguus or laterodorsal tegmental nucleus. Colocalization of the two substances in the same cell bodies was only observed in restricted areas, such as the nucleus of the solitary tract, reticular formation and nucleus ambiguus. In addition, in several regions, an apparent high innervation of the peptidergic fibers on cholinergic neurons has been observed. The results suggest that chemospecific interactions could be crucial for the control of specific cardiorespiratory and/or digestive functions in alpacas. These interactions may represent brain-adaptive mechanisms to particular environments and have a potential therapeutic use in respiratory disorders.
A Retrospective Study on the Effectiveness and Safety of Vancomycin versus Daptomycin in Hemodialysis Patients
Authors: Kato Hideo , Hagihara Mao , Kato Mariko , Yamagishi Yuka , Umemura Takumi , Asai Nobuhiro , Hirai Jun , Iwamoto Takuya , Mikamo Hiroshige
Published: May 2022

Vancomycin or daptomycin is administered to hemodialysis patients infected with methicillin-resistant Staphylococcus and Enterococcus species. Although serious concerns regarding nephrotoxicity due to vancomycin have been raised, it might not be a critical issue in hemodialysis patients. Moreover, very few studies have investigated the effectiveness of vancomycin versus daptomycin in patients undergoing hemodialysis. Hence, we retrospectively evaluated the effectiveness and safety of vancomycin and daptomycin in patients undergoing hemodialysis. We investigated the following measures: mortality, clinical and microbiological effectiveness, and incidence of adverse events in hemodialysis patients who received vancomycin or daptomycin from 2014 to 2019. Moreover, we evaluated the covariates related to 30-day mortality. We found that 73 patients received vancomycin, while 34 received daptomycin for the treatment of infections due to methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative Staphylococci, and Enterococcus faecium. Mortality after vancomycin treatment was significantly lower than daptomycin treatment (4.1% vs. 26.5%, p < 0.01). The clinical and microbiological effectiveness as well as the safety were not significantly different between the two treatments. Although daptomycin treatment with a loading dose was associated with lower mortality, the mortality of the treatment (8.3%) did not differ significantly compared to that of the vancomycin treatment (4.1%). Therefore, our findings suggest that vancomycin remains the first-line treatment for hemodialysis patients; however, a loading dose may be beneficial for patients receiving daptomycin.
Experimental Evolution of Copper Resistance in Escherichia coli Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and Sulfonamide
Authors: Boyd Sada M. , Rhinehardt Kristen L. , Ewunkem Akamu J. , Harrison Scott H. , Thomas Misty D. , Graves Joseph L.
Published: May 2022

The rise in antimicrobial resistant bacteria have prompted the need for antibiotic alternatives. To address this problem, significant attention has been given to the antimicrobial use and novel applications of copper. As novel applications of antimicrobial copper increase, it is important to investigate how bacteria may adapt to copper over time. Here, we used experimental evolution with re-sequencing (EER-seq) and RNA-sequencing to study the evolution of copper resistance in Escherichia coli. Subsequently, we tested whether copper resistance led to rifampicin, chloramphenicol, bacitracin, and/or sulfonamide resistance. Our results demonstrate that E. coli is capable of rapidly evolving resistance to CuSO4 after 37 days of selection. We also identified multiple de novo mutations and differential gene expression patterns associated with copper, most notably those mutations identified in the cpx gene. Furthermore, we found that the copper resistant bacteria had decreased sensitivity when compared to the ancestors in the presence of chloramphenicol, bacitracin, and sulfonamide. Our data suggest that the selection of copper resistance may inhibit growth in the antimicrobials tested, resulting in evolutionary trade-offs. The results of our study may have important implications as we consider the antimicrobial use of copper and how bacteria may respond to increased use over time.
Limited Heme Oxygenase Contribution to Modulating the Severity of Salmonella enterica serovar Typhimurium Infection
Authors: Sebastián Valentina P. , Moreno-Tapia Daniela , Melo-González Felipe , Hernández-Cáceres María P. , Salazar Geraldyne A. , Pardo-Roa Catalina , Farías Mónica A. , Vallejos Omar P. , Schultz Bárbara M. , Morselli Eugenia , Álvarez-Lobos Manuel M. , González Pablo A. , Kalergis Alexis M. , Bueno Susan M.
Published: May 2022

An important virulence trait of Salmonella enterica serovar Typhimurium (S. Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe2+, biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during S. Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent S. Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of S. Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of S. Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled S. Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to Salmonella infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner.
High-Yield Production of a Rich-in-Hydroxytyrosol Extract from Olive (Olea europaea) Leaves
Authors: Papageorgiou Costas S. , Lyri Paraskevi , Xintaropoulou Ioanna , Diamantopoulos Ioannis , Zagklis Dimitris P. , Paraskeva Christakis A.
Published: May 2022

The aim of the present study was to explore the high-yield production of hydroxytyrosol, a phenolic compound with very high antioxidant capacity. Olea europaea leaves were chosen as feedstock as they contain significant amounts of oleuropein, which can be hydrolyzed to hydroxytyrosol. The chosen techniques are widely used in the industry and can be easily scaled up. Olive leaves underwent drying and mechanical pretreatment and extractives were transported to a solvent by solid–liquid extraction using water–ethanol mixtures. The use of approximately 60–80% ethanol showed an almost 2-fold increase in extracted phenolics compared to pure water, to approximately 45 g/kg of dry leaves. Extracted oleuropein was hydrolyzed with hydrochloric acid and the hydrolysate was extracted with ethyl acetate after pH adjustment. This step led to a hydroxytorosol content increase from less than 4% to approximately 60% w/w of dry extract, or 10–15 g of hydroxytyrosol recovery per kg of dry leaves.
Peroxygenase-Catalyzed Selective Synthesis of Calcitriol Starting from Alfacalcidol
Authors: Li Yuanying , Zhang Pengpeng , Sun Zhoutong , Li Huanhuan , Ge Ran , Sheng Xiang , Zhang Wuyuan
Published: May 2022

Calcitriol is an active analog of vitamin D3 and has excellent physiological activities in regulating healthy immune function. To synthesize the calcitriol compound, the concept of total synthesis is often adopted, which typically involves multiple steps and results in an overall low yield. Herein, we envisioned an enzymatic approach for the synthesis of calcitriol. Peroxygenase from Agrocybe aegerita (AaeUPO) was used as a catalyst to hydroxylate the C-H bond at the C-25 position of alfacalcidol and yielded the calcitriol in a single step. The enzymatic reaction yielded 80.3% product formation in excellent selectivity, with a turnover number up to 4000. In a semi-preparative scale synthesis, 72% isolated yield was obtained. It was also found that AaeUPO is capable of hydroxylating the C-H bond at the C-1 position of vitamin D3, thereby enabling the calcitriol synthesis directly from vitamin D3.
Local and Systemic Oxidative Stress Biomarkers for Male Infertility: The ORION Study
Authors: Bergsma Anna T. , Li Hui Ting , Eliveld Jitske , Bulthuis Marian L. C. , Hoek Annemieke , van Goor Harry , Bourgonje Arno R. , Cantineau Astrid E. P.
Published: May 2022

Infertility problems occur in around 10% of all couples worldwide, with male-factor infertility as the sole contributor in 20–30% of these cases. Oxidative stress (OS) is suggested to be associated with the pathophysiology of male infertility. In spermatozoa, OS can lead to damage to the cell membrane, resulting in disruption of DNA integrity and a decrease in motility. Established biomarkers for OS include free thiols and malondialdehyde (MDA), both representing different components of the reactive species interactome (RSI). This exploratory study aimed to investigate seminal plasma-free thiol and MDA levels in relation to semen parameters as defined by the World Health Organization (WHO) to determine if these markers are adequate to define local OS status. Furthermore, this study investigated if there is a relation between systemic and local OS status by comparing seminal concentrations of free thiol (R-SH, sulfhydryl groups, representing the extracellular redox status) and MDA (lipid peroxidation product) levels to those measured in serum. Free thiol and MDA measurements in both serum and semen plasma were performed in 50 males (18–55 y) of couples seeking fertility treatment. A significant positive correlation was found between seminal plasma-free thiol levels and sperm concentration and progressive motility (r = 0.383, p = 0.008 and r = 0.333, p = 0.022, respectively). In addition, a significant positive correlation was found between MDA levels in seminal plasma and sperm concentration (r = 0.314, p = 0.031). This study supports that seminal plasma-free thiols may be promising as local OS biomarkers. No associations were observed between local and systemic OS biomarker concentrations.
5-Methyltetrahydrofolate Attenuates Oxidative Stress and Improves Kidney Function in Acute Kidney Injury through Activation of Nrf2 and Antioxidant Defense
Authors: Wijerathne Charith U. B. , Au-Yeung Kathy K. W. , Siow Yaw L. , O Karmin
Published: May 2022

Oxidative stress is a major mediator of adverse outcomes in acute kidney injury (AKI). Deficiency of micronutrients, such as folate, is common in AKI. Our previous study reported that AKI impaired kidney reabsorption of folate and decreased plasma folate level in rats. The present study investigated the effect of 5-methyltetrahydrofolate (5-MTHF), a biologically active form of folate/folic acid, on AKI-impaired kidney function and oxidative stress. Sprague-Dawley rats developed AKI after kidney ischemia (45 min) and reperfusion (24 h). Injection of 5-MTHF (3 µg/kg body weight) improved kidney function and attenuated oxidative stress with a restoration of glutathione and a reduction of lipid peroxidation in the kidney. Injection of 5-MTHF activated transcription factor Nrf2 and increased the expression of glutathione synthesizing enzymes, superoxide dismutase-1 and heme oxygenase-1 in the kidney. Simulated ischemia-reperfusion through hypoxia-reoxygenation increased oxidative stress in proximal tubular cells. Incubation of cells with 5-MTHF alleviated cell injury and increased antioxidant enzyme expression and intracellular glutathione levels. Inhibition of Nrf2 expression through siRNA transfection abolished the effect of 5-MTHF against oxidative stress. These results suggest that low-dose folic acid can improve kidney function through activation of Nrf2 and restoration of antioxidant defence. Micronutrient supplements may improve clinical outcomes in AKI.
The Optimization of Civil Aircraft Product Option Selection Considering the Economy Response with an Improved Non-Dominated Sorting Genetic Algorithm
Authors: Feng Yunwen , Song Zhicen , Lu Cheng
Published: May 2022

To serve customized option selection for civil aircraft, a mathematical product option selection optimization model combined with an Improved Non-dominated Sorting Genetic Algorithm for decreasing aircraft fleet maintenance cost was investigated. For airlines, considering the economy and reliability in customized option selection is the most intuitive way to improve aircraft performance to generate the optimal formation configuration. Product option selection usually takes certain indicators as constraints (reliability and economy) to meet and maximize performance through equipment selection (the selected parameters include mean time between failures, price, etc.). To describe the customization needs of airlines by a mathematical model and find the optimal decision through an algorithm, a multi-objective, mathematical product option selection optimization model response with reliability parameters as a decision variable, maintainability as a link, and aircraft fleet maintenance and availability as an objective function is established to serve aircraft option selection in this paper. Next, the multi-objective genetic algorithm is used to solve the model, and the convergence, distribution and fitting accuracy of the objective functions are analyzed. Eventually, the landing gear system is used to verify the effectiveness of the model and method. After optimization, the aircraft fleet maintenance cost is reduced by 20.71%, and the availability is increased by 2.576%. Through the mathematical optimization model, the product configuration is provided for the development of the customization option selection project.
A Convolution-Neural-Network Feedforward Active-Noise-Cancellation System on FPGA for In-Ear Headphone
Authors: Jang Young-Jae , Park Jaehyun , Lee Won-Cheol , Park Hong-June
Published: May 2022

A real-time streaming feedforward active-noise-cancellation (ANC) system for an in-ear headphone was demonstrated in a real application scenario, by implementing a 10-layer dilated convolutional-neural-network (CNN) on a field programmable gate array (FPGA). A 16 × 16 systolic array was used in the FPGA, to speed up the model computation. The system latency was 170.6 μs, at the system clock frequency of 120 MHz. The CNN model used 3232 parameters. Due to the large input receptive field, of 327 ms, this work achieved total power reduction, of 14.8 dB and 14.3 dB at the noise incident direction of 0∘ and 90∘, respectively, and the noise attenuation bandwidth was 2000 Hz at both angles; all results were superior to those of the conventional FxLMS algorithm.
Area-Time Efficient Hardware Architecture for CRYSTALS-Kyber
Authors: Nguyen Tuy Tan , Kim Sungjae , Eom Yongjun , Lee Hanho
Published: May 2022

This paper presents a novel area-time efficient hardware architecture of the lattice-based CRYSTALS-Kyber, which has entered the third round of the post-quantum cryptography standardization competition hosted by the National Institute of Standards and Technology. By developing a dual-path delay feedback number theoretic transform multiplier dedicating for Kyber parameter set and deploying this multiplier in the Kyber architecture, the key generation, encryption, and decryption operations are accelerated substantially. Furthermore, the proposed architecture offers the best value of area-time product in comparison with existing approaches. The implementation results on Xilinx Vivado targeted for Virtex-7 FPGA board demonstrate that the proposed Kyber cryptoprocessor completes encryption and decryption operations in approximately 57.5 μs at the highest frequency of 226 MHz. Furthermore, the area-time product value when using the proposed Kyber architecture is improved by at least twofold compared with existing architectures.
Structural Heart Valve Disease in the Era of Change and Innovation: The Crosstalk between Medical Sciences and Engineering
Authors: Nappi Francesco , Nenna Antonio , Chello Massimo
Published: May 2022

In recent years, both cardiology and cardiovascular surgery have witnessed an era of consistently evolving changes which have dramatically transformed the course and management of cardiovascular disease [...]
The Role of Selenoproteins SELENOM and SELENOT in the Regulation of Apoptosis, ER Stress, and Calcium Homeostasis in the A-172 Human Glioblastoma Cell Line
Authors: Varlamova Elena G. , Goltyaev Michael V. , Turovsky Egor A.
Published: May 2022

It is known that seven mammalian selenoproteins are localized in the endoplasmic reticulum: SELENOM, SELENOT, SELENOF, SELENOK, SELENOS, SELENON, and DIO2. Among them, SELENOM and SELENOT are the least studied; therefore, the study of their function using the widespread method of suppressing the expression of genes encoding these proteins and the activity of the enzymes themselves by RNA interference is of great interest. We have shown that a decrease in the expression of SELENOM and SELENOT mRNA in the A-172 human glioblastoma cell line by more than 10 times and the quantitative content of enzymes by more than 3 times leads to ER stress, expressed as a decrease in the ER capacity for storing Ca2+ ions. At the level of regulation of apoptotic processes, SELENOM knockdown leads to an increase in the expression of pro-apoptotic CHOP, GADD34, PUMA, and BIM genes, but a compensatory increase in the levels of SELENOT and antioxidant genes from the group of glutathione peroxidases and thioredoxins did not induce cell death. Knockdown of SELENOT had the opposite effect, reducing the expression of pro-apoptotic proteins and regulating the level of a smaller number of genes encoding antioxidant enzymes, which also did not affect the baseline level of apoptosis in the studied cells. At the same time, ER stress induced by MSA or SeNPs induced a more pronounced pro-apoptotic effect in SELENOT knockdown cells through suppression of the expression of selenium-containing antioxidant proteins. Thus, in this work, for the first time, the mechanisms of fine regulation of the processes of apoptosis, cell proliferation, and ER stress by two ER resident proteins, SELENOM and SELENOT, are touched upon, which is not only fundamental but also applied to clinical importance due to the close relationship between the calcium signaling system of cells, folding proteins-regulators of apoptosis and cell survival pathways.
Early Forms of α-Synuclein Pathology Are Associated with Neuronal Complex I Deficiency in the Substantia Nigra of Individuals with Parkinson’s Disease
Authors: Flønes Irene Hana , Nyland Harald , Sandnes Dagny-Ann , Alves Guido Werner , Tysnes Ole-Bjørn , Tzoulis Charalampos
Published: May 2022

Idiopathic Parkinson’s disease (iPD) is characterized by degeneration of the dopaminergic substantia nigra pars compacta (SNc), typically in the presence of Lewy pathology (LP) and mitochondrial respiratory complex I (CI) deficiency. LP is driven by α-synuclein aggregation, morphologically evolving from early punctate inclusions to Lewy bodies (LBs). The relationship between α-synuclein aggregation and CI deficiency in iPD is poorly understood. While studies in models suggest they are causally linked, observations in human SNc show that LBs preferentially occur in CI intact neurons. Since LBs are end-results of α-synuclein aggregation, we hypothesized that the relationship between LP and CI deficiency may be better reflected in neurons with early-stage α-synuclein pathology. Using quadruple immunofluorescence in SNc tissue from eight iPD subjects, we assessed the relationship between neuronal CI or CIV deficiency and early or late forms of LP. In agreement with previous findings, we did not observe CI-negative neurons with late LP. In contrast, early LP showed a significant predilection for CI-negative neurons (p = 6.3 × 10−5). CIV deficiency was not associated with LP. Our findings indicate that early α-syn aggregation is associated with CI deficiency in iPD, and suggest a double-hit mechanism, where neurons exhibiting both these pathologies are selectively lost.
Macrophages in Health and Non-Infectious Disease 2.0
Authors: Bezsonov Evgeny E. , Gratchev Alexei , Orekhov Alexander N.
Published: May 2022

This Special Issue (SI) has collected the most recent publications on the mechanisms that macrophages use to regulate homeostasis and their involvement in the pathogenesis of various non-infectious diseases [...]
Antitumor Properties of a New Macrocyclic Tetranuclear Oxidovanadium(V) Complex with 3-Methoxysalicylidenvaline Ligand
Authors: Turtoi Mihaela , Anghelache Maria , Patrascu Andrei A. , Deleanu Mariana , Voicu Geanina , Raduca Mihai , Safciuc Florentina , Manduteanu Ileana , Calin Manuela , Popescu Delia-Laura
Published: May 2022

A wide variety of metal-based compounds have been obtained and studied for their antitumor activity since the intensely used cytostatic drugs (e.g., cisplatin) failed to accomplish their expected pharmacological properties. Thus, we aimed to develop a new vanadium-based drug and assess its antitumor properties using the human hepatocarcinoma (HepG2) cell line. The compound was synthesized from vanadyl sulfate, DL-valine, and o-vanillin and was spectrally and structurally characterized (UV-Vis, IR, CD, and single-crystal/powder-XRD). Compound stability in biological media, cell uptake, and the interaction with albumin were assessed. The mechanisms of its antitumor activity were determined compared to cisplatin by performing cytotoxicity, oxidative and mitochondrial status, DNA fragmentation, β-Tubulin synthesis investigation, and cell cycle studies. Herein, we developed a macrocyclic tetranuclear oxidovanadium(V) compound, [(VVO)(L)(CH3O)]4, having coordinated four Schiff base (H2L) ligands, 3-methoxysalicylidenvaline. We showed that [(VVO)(L)(CH3O)]4: (i) has pH-dependent stability in biological media, (ii) binds to albumin in a dose-dependent manner, (iii) is taken up by cells in a time-dependent way, (iv) has a higher capacity to induce cell death compared to cisplatin (IC50 = 6 μM vs. 10 μM), by altering the oxidative and mitochondrial status in HepG2 cells. Unlike cisplatin, which blocks the cell cycle in the S-phase, the new vanadium-based compound arrests it in S and G2/M-phase, whereas no differences in the induction of DNA fragmentation and reduction of β-Tubulin synthesis between the two were determined. Thus, the [(VVO)(L)(CH3O)]4 antitumor mechanism involved corroboration between the generation of oxidative species, mitochondrial dysfunction, degradation of DNA, cell cycle arrest in the S and G2/M-phase, and β-Tubulin synthesis reduction. Our studies demonstrate the potent antitumor activity of [(VVO)(L)(CH3O)]4 and propose it as an attractive candidate for anticancer therapy.
Comparison of CD3e Antibody and CD3e-sZAP Immunotoxin Treatment in Mice Identifies sZAP as the Main Driver of Vascular Leakage
Authors: Kim Shihyoung , Shukla Rajni Kant , Kim Eunsoo , Cressman Sophie G. , Yu Hannah , Baek Alice , Choi Hyewon , Kim Alan , Sharma Amit , Wang Zhirui , Huang Christene A. , Reneau John C. , Boyaka Prosper N. , Liyanage Namal P. M. , Kim Sanggu
Published: May 2022

Anti-CD3-epsilon (CD3e) monoclonal antibodies (mAbs) and CD3e immunotoxins (ITs) are promising targeted therapy options for various T-cell disorders. Despite significant advances in mAb and IT engineering, vascular leakage syndrome (VLS) remains a major dose-limiting toxicity for ITs and has been poorly characterized for recent “engineered” mAbs. This study undertakes a direct comparison of non-mitogenic CD3e-mAb (145-2C11 with Fc-silentTM murine IgG1: S-CD3e-mAb) and a new murine-version CD3e-IT (saporin–streptavidin (sZAP) conjugated with S-CD3e-mAb: S-CD3e-IT) and identifies their distinct toxicity profiles in mice. As expected, the two agents showed different modes of action on T cells, with S-CD3e-mAb inducing nearly complete modulation of CD3e on the cell surface, while S-CD3e-IT depleted the cells. S-CD3e-IT significantly increased the infiltration of polymorphonuclear leukocytes (PMNs) into the tissue parenchyma of the spleen and lungs, a sign of increased vascular permeability. By contrast, S-CD3e-mAbs-treated mice showed no notable signs of vascular leakage. Treatment with control ITs (sZAP conjugated with Fc-silent isotype antibodies) induced significant vascular leakage without causing T-cell deaths. These results demonstrate that the toxin portion of S-CD3e-IT, not the CD3e-binding portion (S-CD3e-mAb), is the main driver of vascular leakage, thus clarifying the molecular target for improving safety profiles in CD3e-IT therapy.
Physiological Roles of the Autoantibodies to the 78-Kilodalton Glucose-Regulated Protein (GRP78) in Cancer and Autoimmune Diseases
Authors: Gonzalez-Gronow Mario , Pizzo Salvatore Vincent
Published: May 2022

The 78 kDa glucose-regulated protein (GRP78), a member of the 70 kDa heat-shock family of molecular chaperones (HSP70), is essential for the regulation of the unfolded protein response (UPR) resulting from cellular endoplasmic reticulum (ER) stress. During ER stress, GRP78 evades retention mechanisms and is translocated to the cell surface (csGRP78) where it functions as an autoantigen. Autoantibodies to GRP78 appear in prostate, ovarian, gastric, malignant melanoma, and colorectal cancers. They are also found in autoimmune pathologies such as rheumatoid arthritis (RA), neuromyelitis optica (NMO), anti-myelin oligodendrocyte glycoprotein antibody-associated disorder (AMOGAD), Lambert-Eaton myasthenic syndrome (LEMS), multiple sclerosis (MS), neuropsychiatric systemic lupus erythematosus (NPSLE) and type 1 diabetes (T1D). In NMO, MS, and NPSLE these autoantibodies disrupt and move across the blood-brain barrier (BBB), facilitating their entry and that of other pathogenic antibodies to the brain. Although csGRP78 is common in both cancer and autoimmune diseases, there are major differences in the specificity of its autoantibodies. Here, we discuss how ER mechanisms modulate csGRP78 antigenicity and the production of autoantibodies, permitting this chaperone to function as a dual compartmentalized receptor with independent signaling pathways that promote either pro-proliferative or apoptotic signaling, depending on whether the autoantibodies bind csGRP78 N- or C-terminal regions.
Antigen Load and T Cell Function: A Challenging Interaction in HBV Infection
Authors: Montali Ilaria , Vecchi Andrea , Rossi Marzia , Tiezzi Camilla , Penna Amalia , Reverberi Valentina , Laccabue Diletta , Missale Gabriele , Boni Carolina , Fisicaro Paola
Published: May 2022

Current treatment for chronic HBV infection is mainly based on nucleos(t)ide analogues, that in most cases need to be administered for a patient’s lifetime. There is therefore a pressing need to develop new therapeutic strategies to shorten antiviral treatments. A severe dysfunction of virus-specific T cell responses contributes to virus persistence; hence, immune-modulation to reconstitute an efficient host antiviral response is considered a potential approach for HBV cure. In this perspective, a detailed understanding of the different causes of T cell exhaustion is essential for the design of successful functional T cell correction strategies. Among many different mechanisms which are widely believed to play a role in T cell dysfunction, persistent T cell exposure to high antigen burden, in particular HBsAg, is expected to influence T cell differentiation and function. Definitive evidence of the possibility to improve anti-viral T cell functions by antigen decline is, however, still lacking. This review aims at recapitulating what we have learned so far on the complex T cell–viral antigen interplay in chronic HBV infection.
Mechanisms Underlying Antipsychotic-Induced NAFLD and Iron Dysregulation: A Multi-Omic Approach
Authors: May Meghan , Barlow Deborah , Ibrahim Radwa , Houseknecht Karen L.
Published: May 2022

Atypical antipsychotic (AA) medications are widely prescribed for the treatment of psychiatric disorders, including schizophrenia, bipolar disorder and treatment-resistant depression. AA are associated with myriad metabolic and endocrine side effects, including systemic inflammation, weight gain, dyslipidemia and insulin resistance, all of which are associated with increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is highly prevalent in patients with mental illness, and AA have been shown to increase incidence of NAFLD pre-clinically and clinically. However, the underlying mechanisms have not been described. We mined multi-omic datasets from preclinical murine models of sub-chronic risperidone or olanzapine treatment, in vitro exposure of human cells to risperidone and psychiatric patients following onset of aripiprazole therapy focused on pathways associated with the pathophysiology of NAFLD, including iron accumulation, systemic inflammation and dyslipidemia. We identified numerous differentially expressed traits affecting these pathways conserved across study systems and AA medications. We used these findings to propose mechanisms for AA-associated development of NAFLD and dysregulated iron homeostasis.