bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Control Applied to Oenological Management of Red Wine Fermentative Macerations
Authors: Luna Ricardo , Lima Bruno M. , Cuevas-Valenzuela José , Normey-Rico Julio E. , Pérez-Correa José R.
Published: June 2021

The management of wineries for industrial red winemaking is limited by the capacity and availability of fermentation tanks over the harvest season. The winemakers aim to optimize the wine quality, the fermentative maceration length, and the fermentation tank’s productive cycle simultaneously. Maceration in varietal wine production is carried out until a specific sugar content (digging-out point) is attained, finishing before alcoholic fermentation. Winemakers have found that by trial and error handling of the digging-out point, they can improve the winery capacity and production cost. In this work, we develop an optimal control problem for managing the digging-out point considering two objectives associated with process efficiency and costs. A good compromise between these objectives was found by applying multi-criteria decision-making (MCDM) techniques and the knee point. Two control strategies were compared: free nutrition and traditional nutrition. TOPSIS and LINMAP algorithms were used to choose the most suitable strategy that coincided with the knee point. The preferred option was nitrogen addition only at the beginning of fermentation (6.6–10.6 g/hL of DAP) and a high fermentation temperature (30 °C), yielding the desired digging-out point with a small error (6–9 g/L).
Improvement of Enantiomeric l-Lactic Acid Production from Mixed Hexose-Pentose Sugars by Coculture of Enterococcus mundtii WX1 and Lactobacillus rhamnosus SCJ9
Authors: Klongklaew Augchararat , Unban Kridsada , Kanpiengjai Apinun , Wongputtisin Pairote , Pamueangmun Punnita , Shetty Kalidas , Khanongnuch Chartchai
Published: June 2021

Among 39 pentose-utilizing lactic acid bacteria (LAB) selected from acid-forming bacteria from the midgut of Eri silkworm, the isolate WX1 was selected with the highest capability to produce optically pure l-lactic acid (l-LA) from glucose, xylose and arabinose with furfural-tolerant properties. The isolate WX1 was identified as Enterococcus mundtii based on 16S rDNA sequence analysis. The conversion yields of l-LA from glucose and xylose by E. mundtii WX1 were 0.97 and 0.68 g/g substrate, respectively. Furthermore, l-LA production by E. mundtii WX1 in various glucose-xylose mixtures indicated glucose repression effect on xylose consumption. The coculture of E. mundtii WX1 and Lactobacillus rhamnosus SCJ9, a homofermentative LAB capable of producing l-LA from glucose clearly showed an improvement of l-LA production from 30 g/L total glucose-xylose (6:4). The results from Plackett–Burman design (PBD) indicated that Tween 80, MnSO4 and yeast extract (YE) were three medium components that significantly influenced (p < 0.05) l-LA production using the coculture strategy in the presence of 2 g/L furfural. Optimal concentrations of these variables revealed by central composite design (CCD) and response surface methodology (RSM) were 20.61 g/L YE, 1.44 g/L Tween 80 and 1.27 g/L MnSO4. Based on the optimized medium with 30 g/L total glucose-xylose (6:4), the maximum experimental l-LA value of 23.59 g/L reflecting 0.76 g/g substrate were achieved from 48 h fermentation at 37 °C. l-LA produced by coculture cultivated under standard MRS medium and new optimized conditions were 1.28 and 1.53 times higher than that obtained from single culture by E. mundtii WX1, respectively. This study provides the foundations for practical applications of coculture in bioconversion of lignocellulose particularly glucose-xylose-rich corn stover to l-LA.
Effect of Superheated Steam Treatment on the Lipid Stability of Dried Whole Wheat Noodles during Storage
Authors: Jia Wan-Ting , Yang Zhen , Guo Xiao-Na , Zhu Ke-Xue
Published: June 2021

Dried whole wheat noodles (DWWN) are a kind of nutritious convenience food with broad market prospects. However, due to the presence of high content of unsaturated fatty acids (UFAs) and lipid degrading enzymes, the shelf life and edible quality of DWWN are easily affected. This study explored the effect of superheated steam treatment (SST-155 °C-10 s, SST-170 °C-10 s, SST-190 °C-5 s) on the lipid stability of DWWN. The lipase, lipoxygenase and peroxidase of the DWWN treated with superheated steam were completely passivated during storage. After 12 weeks of storage, the fatty acid value of DWWN increased by 35.1, 17.9, 15.9, 24.6 mg NaOH/100 g in the groups of control, SST-155 °C-10 s, SST-170 °C-10 s, SST-190 °C-5 s, respectively; whereas the content of UFAs decreased by 13.5%, 6.8%, 5.4%, and 2.7%, respectively. The content of 2-pentylfuran in the SST-155 °C-10 s, SST-170 °C-10 s, SST-190 °C-5 s group was 0.7, 0.6, and 0.4-fold than that of the control group, respectively. In addition, the total tocopherol and total volatile compounds of the SST-190 °C-5 s group were 2.4 and 0.7-fold than that of the control group, respectively. Therefore, SST should be a new technology that can improve the lipid stability of DWWN.
Lacticaseibacillus rhamnosus Impedes Growth of Listeria spp. in Cottage Cheese through Manganese Limitation
Authors: van Gijtenbeek Lieke A. , Singer Quinn , Steffensen Louise E. , Neuens Shannon , Guldager Helle S. , Bidstrup Susanne , Høgholm Tina , Madsen Mikkel G. , Glass Kathleen , Siedler Solvej
Published: June 2021

Acidification and nutrient depletion by dairy starter cultures is often sufficient to prevent outgrowth of pathogens during post-processing of cultured dairy products. In the case of cottage cheese, however, the addition of cream dressing to the curd and subsequent cooling procedures can create environments that may be hospitable for the growth of Listeria monocytogenes. We report on a non-bacterio-cinogenic Lacticaseibacillus rhamnosus strain that severely limits the growth potential of L. monocytogenes in creamed cottage cheese. The main mechanism underlying Listeria spp. inhibition was found to be caused by depletion of manganese (Mn), thus through competitive exclusion of a trace element essential for the growth of many microorganisms. Growth of Streptococcus thermophilus and Lactococcus lactis that constitute the starter culture, on the other hand, were not influenced by reduced Mn levels. Addition of L. rhamnosus with Mn-based bioprotective properties during cottage cheese production therefore offers a solution to inhibit undesired bacteria in a bacteriocin-independent fashion.
Potential Contribution of Climate Change to the Protein Haze of White Wines from the French Southwest Region
Authors: Pasquier Grégory , Feilhes Carole , Dufourcq Thierry , Geffroy Olivier
Published: June 2021

The aim of this study was to evaluate the role played by climatic conditions during grape ripening in the protein instability of white wines produced in the French southwest region. For this purpose, basic wine analyses were carried out on 268 musts and the corresponding wines, all produced during the 2016, 2017, 2018, and 2019 vintages, with distinctive climatic conditions. Qualitative and quantitative variables were correlated with levels of protein haze determined by heat test (80 °C/2 h) in the wines using analysis of covariance (ANCOVA), principal component analysis (PCA), and classification and regression trees (CART). Our results show that the climatic change, with the increase in temperatures, and the decrease in precipitation during the grape ripening phase, tends to enhance the risk of protein instability in wines. Indeed, the values of pH, titratable acidity, and malic acid concentrations of the musts, which are good indicators of the conditions in which the grapes ripened and of the level of ripeness of the grapes, were also the variables that correlated best with the protein haze. By measuring these parameters at harvest before alcoholic fermentation, it may be possible to predict the risk of protein haze, and thus early and precisely adapt the stabilization treatment to be applied.
Changes in Physical and Oral Function after a Long-Term Care Prevention Program in Community-Dwelling Japanese Older Adults: A 12-Month Follow-Up Study
Authors: Iwao-Kawamura Yoshimi , Shigeishi Hideo , Uchida Shino , Kawano Shirou , Maehara Tomoko , Sugiyama Masaru , Ohta Kouji
Published: June 2021

Background: The aim of this prospective cohort study was to clarify changes in physical and oral function in older adults after completing a 3-month health program combining physical and oral exercise, oral health instruction, and nutritional guidance. Methods: Subjects were 34 women aged at least 70 years (mean age 79.2 years) in Bungotakada City, Oita Prefecture, Japan. Physical and oral function was investigated on the first day (baseline), at the end of the program, and 6 and 12 months after completing the health program. Physical function was measured using handgrip strength test, timed up and go (TUG) test and one-leg standing time test. Oral diadochokinesis test and repetitive saliva swallowing test (RSST) were employed to assess oral function. Results: TUG scores were significantly lower at 6 and 12 months than at baseline in participants aged ≥70 and <80 years. The repetition rate of the monosyllables /pa/, /ta/, and /ka/ was improved at the end of program in participants aged ≥70 and <80 years and increased to more than 6 times/second at 12 months. Conclusions: Our 3-month health program maintained improvements in oral and physical function in older women 1 year after completing the program.
Introducing an Open-Source Regional Water Quality Data Viewer Tool to Support Research Data Access
Authors: Dolder Danisa , Williams Gustavious P. , Miller A. Woodruff , Nelson Everett James , Jones Norman L. , Ames Daniel P.
Published: June 2021

Water quality data collection, storage, and access is a difficult task and significant work has gone into methods to store and disseminate these data. We present a tool to disseminate research in a simple method that does not replace but extends and leverages these tools. The tool is not geo-graphically limited and works with any spatially-referenced data. In most regions, government agencies maintain central repositories for water quality data. In the United States, the federal government maintains two systems to fill that role for hydrological data: the U.S. Geological Survey (USGS) National Water Information System (NWIS) and the U.S. Environmental Protection Agency (EPA) Storage and Retrieval System (STORET), since superseded by the Water Quality Portal (WQP). The Consortium of the Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) has developed the Hydrologic Information System (HIS) to standardize the search and discovery of these data as well as other observational time series datasets. Additionally, CUAHSI developed and maintains HydroShare.org (5 May 2021) as a web portal for researchers to store and share hydrology data in a variety of formats including spatial geographic information system data. We present the Tethys Platform based Water Quality Data Viewer (WQDV) web application that uses these systems to provide researchers and local monitoring organizations with a simple method to archive, view, analyze, and distribute water quality data. WQDV provides an archive for non-official or preliminary research data and access to those data that have been collected but need to be distributed prior to review or inclusion in the state database. WQDV can also accept subsets of data downloaded from other sources, such as the EPA WQP. WQDV helps users understand what local data are available and how they relate to the data in larger databases. WQDV presents data in spatial (maps) and temporal (time series graphs) forms to help the users analyze and potentially screen the data sources before export for additional analysis. WQDV provides a convenient method for interim data to be widely disseminated and easily accessible in the context of a subset of official data. We present WQDV using a case study of data from Utah Lake, Utah, United States of America.
Pollution, Inflammation, and Vaccines: A Complex Crosstalk
Authors: Franza Laura , Cianci Rossella
Published: June 2021

The importance of pollution in determining human health is becoming increasingly clear, also given the dramatic consequences it has had on recent geopolitical events. Yet, the consequences of contamination are not always straightforward. In this paper, we will discuss the effects of different pollutants on different aspects of human health, in particular on the immune system and inflammation. Different environmental pollutants can have different effects on the immune system, which can then promote complex pathologies, such as autoimmune disorders and cancer. The interaction with the microbiota also further helps to determine the consequences of contamination on wellbeing. The pollution can affect vaccination efficacy, given the widespread effects of vaccination on immunity. At the same time, some vaccinations also can exert protective effects against some forms of pollution.
Protecting Nurses from Mistreatment by Patients: A Cross-Sectional Study on the Roles of Emotional Contagion Susceptibility and Emotional Regulation Ability
Authors: Liu Bing , Zhu Naixin , Wang Huijuan , Li Fengyu , Men Chenghao
Published: June 2021

In recent years, patient mistreatment of healthcare workers, especially nurses, has been frequent, endangering the interests of organizations while also threatening nurses’ own development. This study aims to examine from the perspective of nurses’ personal interests whether mistreatment by patients decreases nurses’ workplace well-being and career commitment, and how their susceptibility to emotional contagion and emotional regulation ability might mitigate these negative effects. This study adopted a cross-sectional study design (data were collected through self-reported questionnaires with a two-month time lag between the months of August–October 2017). A total of 289 nurses from three hospitals in Shandong province, China, were recruited to participate in our study. The results reveal that mistreatment by patients is negatively related to nurses’ workplace well-being and career commitment. Emotional contagion susceptibility moderates the relationships between mistreatment by patients and career commitment, while there is no significant buffering effect of mistreatment by patients on workplace well-being. Emotional regulation ability moderates the relationships between mistreatment by patients and both workplace well-being and career commitment. These results suggest that improvements in nurses’ emotional regulation ability and susceptibility to emotional contagion can alleviate the harmful impacts of mistreatment by patients.
Special Issue on “Advances in Socio-Economic Research on Ageing”
Authors: Gagliardi Cristina , Lamura Giovanni
Published: June 2021

This Special Issue provides the readers of the International Journal of Environmental Research and Public Health a multidimensional overview of recent developments in the field of socio-economic gerontological research [...]
Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort
Authors: Navarro-Lafuente Fuensanta , Arense-Gonzalo Julián , Adoamnei Evdochia , Prieto-Sánchez María , Sánchez-Ferrer María , García-Marcos Luis , Morales Eva , Mendiola Jaime , Torres-Cantero Alberto ,   the NELA Study Group
Published: June 2021

Paracetamol is the one of the most commonly used medications during pregnancy. However, its potential antiandrogenic effect has been suggested. The objective of this study was to evaluate associations between maternal paracetamol use during pregnancy and anogenital distance (AGD) in male newborns from a Spanish birth cohort. The study included two hundred and seventy-seven mother-male child pairs with self-reported paracetamol use and frequency during each trimester of pregnancy. AGD measurements were taken employing standardized methods. The associations between maternal paracetamol use and AGD measures were evaluated using linear regression models, adjusting for potential confounders and covariates. Overall, 61.7% of pregnant women consumed paracetamol at any time of pregnancy with an average of 9.43 (SD = 15.33) days throughout pregnancy. No associations between the maternal use of paracetamol or its frequency and AGD measures among different trimesters or during the whole pregnancy were found in the adjusted final models. A non-differential misclassification error may have occurred—the recall of paracetamol intake independent of AGD measurements—introducing bias towards the null hypothesis. Nevertheless, the current evidence suggests that paracetamol might have a potential antiandrogenic effect especially in the early stages of fetal development. Thus, it would be highly recommendable to pursue further studies to elucidate the potential effects of paracetamol in human perinatal health and its use among pregnant women.
Equation for Tooth Size Prediction from Mixed Dentition Analysis for Taiwanese Population: A Pilot Study
Authors: Chong See Yen , Aung Lwin Moe , Pan Yu-Hwa , Chang Wei-Jen , Tsai Chi-Yang
Published: June 2021

Background: In mixed dentition analysis, estimation of the mesiodistal width of unerupted permanent canines and premolars is essential for successful diagnosis and treatment planning. The present study aimed to develop a simple linear equation to predict permanent tooth sizes from mixed dentition analysis for Taiwanese people. Methods: The sample comprised 200 dental casts, derived from Taiwanese patients (100 males and 100 females; age, 12–35 years). Mesial distal tooth widths were measured in dental casts with a digital caliper. A student’s t-test was conducted to detect tooth size correlations with gender-specific differences, as well as intra-arch counterparts. Standard linear regression was conducted to develop a simple equation representing predictions of canine-premolar relationships. Results: All teeth were not significantly different between the left and right sides, regardless of gender and upper or lower arches. In terms of types of teeth, males had larger tooth dimensions in both arches than females. New regression equations for estimating the dimensions of the unerupted canines and premolars in the Taiwanese population were developed. Conclusions: Using a sample of Taiwanese people, new models derived for females and males separately were developed, which should provide highly accurate predictions for unerupted canines and premolars in the Taiwanese population.
Evaluation of Implementing TOM: A Group-Based Fall Prevention Programme among Community-Dwelling Older Adults in The Netherlands
Authors: Frazer Sanne W. T. , van der Veen Rozan , Baan Anneloes , Hermans Mariëlle E. W. , Olij Branko F.
Published: June 2021

There is strong evidence that effective fall prevention elements exist, but the implementation into society remains difficult. The aim of the current study is to describe and evaluate the implementation of the fall prevention programme “Thuis Onbezorgd Mobiel” (TOM). This novel approach combines effective components into a multidisciplinary group-based programme for adults aged 65 years or older with an increased risk of falling. To investigate the impact on several health-related outcomes such as subjective health, quality of life, physical functioning, and falls, we applied a quasi-experimental pre–post design including a follow-up period. A total of 164 older adults subscribed to the programme: 80 were eligible to start and 73 completed it. The impact analysis revealed a significant improvement in subjective health, physical functioning, and quality of life directly after participating in the programme. The impact on subjective health and quality of life persisted six months after the programme. Important facilitators for the implementation of the programme were social contact and clear communication. Lack of a concrete follow-up was seen as an important barrier. The results of the current research help guide further implementation of effective fall prevention interventions in practice.
Profiles of Risky Driving Behaviors in Adolescent Drivers: A Cluster Analysis of a Representative Sample from Tuscany Region (Italy)
Authors: Lastrucci Vieri , Innocenti Francesco , Lorini Chiara , Berti Alice , Silvestri Caterina , Lazzeretti Marco , Voller Fabio , Bonaccorsi Guglielmo
Published: June 2021

(1) Background: Research on patterns of risky driving behaviors (RDBs) in adolescents is scarce. This study aims to identify distinctive patterns of RDBs and to explore their characteristics in a representative sample of adolescents. (2) Methods: this is a cross-sectional study of a representative sample of Tuscany Region students aged 14–19 years (n = 2162). The prevalence of 11 RDBs was assessed and a cluster analysis was conducted to identify patterns of RDBs. ANOVA, post hoc pairwise comparisons and multivariate logistic regression models were used to characterize cluster membership. (3) Results: four distinct clusters of drivers were identified based on patterns of RDBs; in particular, two clusters—the Reckless Drivers (11.2%) and the Careless Drivers (21.5%)—showed high-risk patterns of engagement in RDBs. These high-risk clusters exhibited the weakest social bonds, the highest psychological distress, the most frequent participation in health compromising and risky behaviors, and the highest risk of a road traffic accident. (4) Conclusion: findings suggest that it is possible to identify typical profiles of RDBs in adolescents and that risky driving profiles are positively interrelated with other risky behaviors. This clustering suggests the need to develop multicomponent prevention strategies rather than addressing specific RDBs in isolation.
Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing
Authors: Anurogo Dito , Yuli Prasetyo Budi Nova , Thi Ngo Mai-Huong , Huang Yen-Hua , Pawitan Jeanne Adiwinata
Published: June 2021

Hereditary anemia has various manifestations, such as sickle cell disease (SCD), Fanconi anemia, glucose-6-phosphate dehydrogenase deficiency (G6PDD), and thalassemia. The available management strategies for these disorders are still unsatisfactory and do not eliminate the main causes. As genetic aberrations are the main causes of all forms of hereditary anemia, the optimal approach involves repairing the defective gene, possibly through the transplantation of normal hematopoietic stem cells (HSCs) from a normal matching donor or through gene therapy approaches (either in vivo or ex vivo) to correct the patient’s HSCs. To clearly illustrate the importance of cell and gene therapy in hereditary anemia, this paper provides a review of the genetic aberration, epidemiology, clinical features, current management, and cell and gene therapy endeavors related to SCD, thalassemia, Fanconi anemia, and G6PDD. Moreover, we expound the future research direction of HSC derivation from induced pluripotent stem cells (iPSCs), strategies to edit HSCs, gene therapy risk mitigation, and their clinical perspectives. In conclusion, gene-corrected hematopoietic stem cell transplantation has promising outcomes for SCD, Fanconi anemia, and thalassemia, and it may overcome the limitation of the source of allogenic bone marrow transplantation.
Bioaccumulation, Biodistribution, Toxicology and Biomonitoring of Organofluorine Compounds in Aquatic Organisms
Authors: Savoca Dario , Pace Andrea
Published: June 2021

This review is a survey of recent advances in studies concerning the impact of poly- and perfluorinated organic compounds in aquatic organisms. After a brief introduction on poly- and perfluorinated compounds (PFCs) features, an overview of recent monitoring studies is reported illustrating ranges of recorded concentrations in water, sediments, and species. Besides presenting general concepts defining bioaccumulative potential and its indicators, the biodistribution of PFCs is described taking in consideration different tissues/organs of the investigated species as well as differences between studies in the wild or under controlled laboratory conditions. The potential use of species as bioindicators for biomonitoring studies are discussed and data are summarized in a table reporting the number of monitored PFCs and their total concentration as a function of investigated species. Moreover, biomolecular effects on taxonomically different species are illustrated. In the final paragraph, main findings have been summarized and possible solutions to environmental threats posed by PFCs in the aquatic environment are discussed.
Sex and Age-Related Differences in Neuroinflammation and Apoptosis in Balb/c Mice Retina Involve Resolvin D1
Authors: Trotta Maria Consiglia , Gharbia Sami , Herman Hildegard , Mladin Bianca , Hermenean Andrei , Balta Cornel , Cotoraci Coralia , Peteu Victor Eduard , Gesualdo Carlo , Petrillo Francesco , Galdiero Marilena , Alfano Roberto , Gherghiceanu Mihaela , D’Amico Michele , Rossi Settimio , Hermenean Anca
Published: June 2021

(1) Background: The pro-resolving lipid mediator Resolvin D1 (RvD1) has already shown protective effects in animal models of diabetic retinopathy. This study aimed to investigate the retinal levels of RvD1 in aged (24 months) and younger (3 months) Balb/c mice, along with the activation of macro- and microglia, apoptosis, and neuroinflammation. (2) Methods: Retinas from male and female mice were used for immunohistochemistry, immunofluorescence, transmission electron microscopy, Western blotting, and enzyme-linked immunosorbent assays. (3) Results: Endogenous retinal levels of RvD1 were reduced in aged mice. While RvD1 levels were similar in younger males and females, they were markedly decreased in aged males but less reduced in aged females. Both aged males and females showed a significant increase in retinal microglia activation compared to younger mice, with a more marked reactivity in aged males than in aged females. The same trend was shown by astrocyte activation, neuroinflammation, apoptosis, and nitrosative stress, in line with the microglia and Müller cell hypertrophy evidenced in aged retinas by electron microscopy. (4) Conclusions: Aged mice had sex-related differences in neuroinflammation and apoptosis and low retinal levels of endogenous RvD1.
In Vitro Evaluation of the Individual and Combined Cytotoxic and Estrogenic Effects of Zearalenone, Its Reduced Metabolites, Alternariol, and Genistein
Authors: Balázs Adrienn , Faisal Zelma , Csepregi Rita , Kőszegi Tamás , Kriszt Balázs , Szabó István , Poór Miklós
Published: June 2021

Mycotoxins are toxic metabolites of filamentous fungi. Previous studies demonstrated the co-occurrence of Fusarium and Alternaria toxins, including zearalenone (ZEN), ZEN metabolites, and alternariol (AOH). These xenoestrogenic mycotoxins appear in soy-based meals and dietary supplements, resulting in the co-exposure to ZEN and AOH with the phytoestrogen genistein (GEN). In this study, the cytotoxic and estrogenic effects of ZEN, reduced ZEN metabolites, AOH, and GEN are examined to evaluate their individual and combined impacts. Our results demonstrate that reduced ZEN metabolites, AOH, and GEN can aggravate ZEN-induced toxicity; in addition, the compounds tested exerted mostly synergism or additive combined effects regarding cytotoxicity and/or estrogenicity. Therefore, these observations underline the importance and the considerable risk of mycotoxin co-exposure and the combined effects of mycoestrogens with phytoestrogens.
Towards a Treatment for Neuroinflammation in Epilepsy: Interleukin-1 Receptor Antagonist, Anakinra, as a Potential Treatment in Intractable Epilepsy
Authors: Yamanaka Gaku , Ishida Yu , Kanou Kanako , Suzuki Shinji , Watanabe Yusuke , Takamatsu Tomoko , Morichi Shinichiro , Go Soken , Oana Shingo , Yamazaki Takashi , Kawashima Hisashi
Published: June 2021

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a unique catastrophic epilepsy syndrome, and the development of drug-resistant epilepsy (DRE) is inevitable. Recently, anakinra, an interleukin-1 receptor antagonist (IL-1RA), has been increasingly used to treat DRE due to its potent anticonvulsant activity. We here summarized its effects in 38 patients (32 patients with FIRES and six with DRE). Of the 22 patients with FIRES, 16 (73%) had at least short-term seizure control 1 week after starting anakinra, while the remaining six suspected anakinra-refractory cases were male and had poor prognoses. Due to the small sample size, an explanation for anakinra refractoriness was not evident. In all DRE patients, seizures disappeared or improved, and cognitive function improved in five of the six patients following treatment. Patients showed no serious side effects, although drug reactions with eosinophilia and systemic symptoms, cytopenia, and infections were observed. Thus, anakinra has led to a marked improvement in some cases, and functional deficiency of IL-1RA was indicated, supporting a direct mechanism for its therapeutic effect. This review first discusses the effectiveness of anakinra for intractable epileptic syndromes. Anakinra could become a new tool for intractable epilepsy treatment. However, it does not currently have a solid evidence base.
NXP031 Improves Cognitive Impairment in a Chronic Cerebral Hypoperfusion-Induced Vascular Dementia Rat Model through Nrf2 Signaling
Authors: Lee Jae-Min , Lee Joo-Hee , Song Min-Kyung , Kim Youn-Jung
Published: June 2021

Vascular dementia (VaD) is a progressive cognitive impairment caused by a reduced blood supply to the brain. Chronic cerebral hypoperfusion (CCH) is one cause of VaD; it induces oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, damaging several brain regions. Vitamin C plays a vital role in preventing oxidative stress-related diseases induced by reactive oxygen species, but it is easily oxidized and loses its antioxidant activity. To overcome this weakness, we have developed a vitamin C/DNA aptamer complex (NXP031) that increases vitamin C’s antioxidant efficacy. Aptamers are short single-stranded nucleic acid polymers (DNA or RNA) that can interact with their corresponding target with high affinity. We established an animal model of VaD by permanent bilateral common carotid artery occlusion (BCCAO) in 12 week old Wistar rats. Twelve weeks after BCCAO, we injected NXP031 into the rats intraperitoneally for two weeks at moderate (200 mg/4 mg/kg) and high concentrations (200 mg/20 mg/kg). NXP031 administration alleviates cognitive impairment, microglial activity, and oxidative stress after CCH. NXP031 increased the expression of basal lamina (laminin), endothelial cell (RECA-1, PECAM-1), and pericyte (PDGFRβ); these markers maintain the BBB integrity. We found that NXP031 administration activated the Nrf2-ARE pathway and increased the expression of SOD-1 and GSTO1/2. These results suggest that this new aptamer complex, NXP031, could be a therapeutic intervention in CCH-induced VaD.
Arabidopsis thaliana G3BP Ortholog Rescues Mammalian Stress Granule Phenotype across Kingdoms
Authors: Reuper Hendrik , Götte Benjamin , Williams Lucy , Tan Timothy J. C. , McInerney Gerald M. , Panas Marc D. , Krenz Björn
Published: June 2021

Stress granules (SGs) are dynamic RNA–protein complexes localized in the cytoplasm that rapidly form under stress conditions and disperse when normal conditions are restored. The formation of SGs depends on the Ras-GAP SH3 domain-binding protein (G3BP). Formations, interactions and functions of plant and human SGs are strikingly similar, suggesting a conserved mechanism. However, functional analyses of plant G3BPs are missing. Thus, members of the Arabidopsis thaliana G3BP (AtG3BP) protein family were investigated in a complementation assay in a human G3BP knock-out cell line. It was shown that two out of seven AtG3BPs were able to complement the function of their human homolog. GFP-AtG3BP fusion proteins co-localized with human SG marker proteins Caprin-1 and eIF4G1 and restored SG formation in G3BP double KO cells. Interaction between AtG3BP-1 and -7 and known human G3BP interaction partners such as Caprin-1 and USP10 was also demonstrated by co-immunoprecipitation. In addition, an RG/RGG domain exchange from Arabidopsis G3BP into the human G3BP background showed the ability for complementation. In summary, our results support a conserved mechanism of SG function over the kingdoms, which will help to further elucidate the biological function of the Arabidopsis G3BP protein family.
Functional Analysis of the Promoter Regions of Two Apoptosis-Related Genes (Bcl-2 and Cycs) and Their Regulation by Zn in Yellow Catfish
Authors: He Yang , Zhao Tao , Chen Fang , Song Changchun , Zhong Chongchao , Luo Zhi
Published: June 2021

B-cell lymphoma 2 (Bcl-2) and cytochrome c (Cycs) are two important proteins relevant to cellular apoptosis. In this study, we characterized the functions of the promoter regions of two apoptosis-related genes, Bcl-2 and Cycs, in yellow catfish Pelteobagrus fulvidraco. We obtained a 1989 bp Bcl-2 promoter and an 1830 bp Cycs promoter and predicted several key transcription factor binding sites (TFBSs) on the promoters, such as Kruppel-like factor 4 (KLF4), signal transducer and activator of transcription factor 3 (STAT3), forkhead box O (FOXO), metal-responsive element (MRE) and hepatocyte nuclear factor 1α (HNF-1α). Zinc (Zn) increased the activities of the Bcl-2 promoter but decreased the activities of the Cycs promoter. Metal-responsive transcription factor 1 (MTF-1) and HNF-1α directly bound with Bcl-2 and Cycs promoters, and they positively regulated the activity of the Bcl-2 promoter but negatively regulated the activity of the Cycs promoter. Zn promoted the binding ability of HNF-1α to the Bcl-2 promoter but decreased its binding ability to the Cycs promoter. However, Zn had no significant effect on the binding capability of MTF-1 to the regions of Bcl-2 and Cycs promoters. Zn upregulated the mRNA and total protein expression of Bcl-2 but downregulated the mRNA and total protein expression of Cycs. At the same time, Annexin V–FITC/PI staining showed that Zn significantly reduced the apoptosis of primary hepatocytes. For the first time, our study provides evidence for the MRE and HNF-1α response elements on the Bcl-2 and Cycs promoters, offering new insight into the mechanism by which Zn affects apoptosis in vertebrates.
Analysis of Both Lipid Metabolism and Endocannabinoid Signaling Reveals a New Role for Hypothalamic Astrocytes in Maternal Caloric Restriction-Induced Perinatal Programming
Authors: Tovar Rubén , Vargas Antonio , Aranda Jesús , Sánchez-Salido Lourdes , González-González Laura , Chowen Julie A. , Rodríguez de Fonseca Fernando , Suárez Juan , Rivera Patricia
Published: June 2021

Maternal malnutrition in critical periods of development increases the risk of developing short- and long-term diseases in the offspring. The alterations induced by this nutritional programming in the hypothalamus of the offspring are of special relevance due to its role in energy homeostasis, especially in the endocannabinoid system (ECS), which is involved in metabolic functions. Since astrocytes are essential for neuronal energy efficiency and are implicated in brain endocannabinoid signaling, here we have used a rat model to investigate whether a moderate caloric restriction (R) spanning from two weeks prior to the start of gestation to its end induced changes in offspring hypothalamic (a) ECS, (b) lipid metabolism (LM) and/or (c) hypothalamic astrocytes. Monitorization was performed by analyzing both the gene and protein expression of proteins involved in LM and ECS signaling. Offspring born from caloric-restricted mothers presented hypothalamic alterations in both the main enzymes involved in LM and endocannabinoids synthesis/degradation. Furthermore, most of these changes were similar to those observed in hypothalamic offspring astrocytes in culture. In conclusion, a maternal low caloric intake altered LM and ECS in both the hypothalamus and its astrocytes, pointing to these glial cells as responsible for a large part of the alterations seen in the total hypothalamus and suggesting a high degree of involvement of astrocytes in nutritional programming.
Assessment of Paroxetine Molecular Interactions with Selected Monoamine and γ-Aminobutyric Acid Transporters
Authors: Kowalska Magdalena , Fijałkowski Łukasz , Nowaczyk Alicja
Published: June 2021

Thus far, many hypotheses have been proposed explaining the cause of depression. Among the most popular of these are: monoamine, neurogenesis, neurobiology, inflammation and stress hypotheses. Many studies have proven that neurogenesis in the brains of adult mammals occurs throughout life. The generation of new neurons persists throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells. For this reason, the search for drugs acting in this mechanism seems to be a priority for modern pharmacotherapy. Paroxetine is one of the most commonly used antidepressants. However, the exact mechanism of its action is not fully understood. The fact that the therapeutic effect after the administration of paroxetine occurs after a few weeks, even if the levels of monoamine are rapidly increased (within a few minutes), allows us to assume a neurogenic mechanism of action. Due to the confirmed dependence of depression on serotonin, norepinephrine, dopamine and γ-aminobutyric acid levels, studies have been undertaken into paroxetine interactions with these primary neurotransmitters using in silico and in vitro methods. We confirmed that paroxetine interacts most strongly with monoamine transporters and shows some interaction with γ-aminobutyric acid transporters. However, studies of the potency inhibitors and binding affinity values indicate that the neurogenic mechanism of paroxetine’s action may be determined mainly by its interactions with serotonin transporters.
ITGB6-Knockout Suppresses Cholangiocarcinoma Cell Migration and Invasion with Declining PODXL2 Expression
Authors: Soejima Yurie , Takeuchi Miho , Miyamoto Nao , Sawabe Motoji , Fukusato Toshio
Published: June 2021

Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous bile duct cancer with a poor prognosis. Integrin αvβ6 (β6) has been shown to be upregulated in iCCA and is associated with its subclassification and clinicopathological features. In the present study, two ITGB6-knockout HuCCT1 CCA cell lines (ITGB6-ko cells) were established using the clustered regulatory interspaced short palindromic repeats (CRISPR), an associated nuclease 9 (Cas9) system, and single-cell cloning. RNA sequencing analysis, real-time polymerase chain reaction (PCR), and immunofluorescent methods were applied to explore possible downstream factors. ITGB6-ko cells showed significantly decreased expression of integrin β6 on flow cytometric analysis. Both cell lines exhibited significant inhibition of cell migration and invasion, decreased wound-healing capability, decreased colony formation ability, and cell cycle dysregulation. RNA sequencing and real-time PCR analysis revealed a remarkable decrease in podocalyxin-like protein 2 (PODXL2) expression in ITGB6-ko cells. Colocalization of PODXL2 and integrin β6 was also observed. S100 calcium-binding protein P and mucin 1, which are associated with CCA subclassification, were downregulated in ITGB6-ko cells. These results describe the successful generation of ITGB6-ko CCA cell clones with decreased migration and invasion and downregulation of PODXL2, suggesting the utility of integrin β6 as a possible therapeutic target or diagnostic marker candidate.
Ozone Induced Stomatal Regulations, MAPK and Phytohormone Signaling in Plants
Authors: Hasan Md. Mahadi , Rahman Md. Atikur , Skalicky Milan , Alabdallah Nadiyah M. , Waseem Muhammad , Jahan Mohammad Shah , Ahammed Golam Jalal , El-Mogy Mohamed M. , El-Yazied Ahmed Abou , Ibrahim Mohamed F. M. , Fang Xiang-Wen
Published: June 2021

Ozone (O3) is a gaseous environmental pollutant that can enter leaves through stomatal pores and cause damage to foliage. It can induce oxidative stress through the generation of reactive oxygen species (ROS) like hydrogen peroxide (H2O2) that can actively participate in stomatal closing or opening in plants. A number of phytohormones, including abscisic acid (ABA), ethylene (ET), salicylic acid (SA), and jasmonic acid (JA) are involved in stomatal regulation in plants. The effects of ozone on these phytohormones’ ability to regulate the guard cells of stomata have been little studied, however, and the goal of this paper is to explore and understand the effects of ozone on stomatal regulation through guard cell signaling by phytohormones. In this review, we updated the existing knowledge by considering several physiological mechanisms related to stomatal regulation after response to ozone. The collected information should deepen our understanding of the molecular pathways associated with response to ozone stress, in particular, how it influences stomatal regulation, mitogen-activated protein kinase (MAPK) activity, and phytohormone signaling. After summarizing the findings and noting the gaps in the literature, we present some ideas for future research on ozone stress in plants
Pioglitazone Ameliorates Lipopolysaccharide-Induced Behavioral Impairment, Brain Inflammation, White Matter Injury and Mitochondrial Dysfunction in Neonatal Rats
Authors: Yeh Jiann-Horng , Wang Kuo-Ching , Kaizaki Asuka , Lee Jonathan W. , Wei Han-Chi , Tucci Michelle A. , Ojeda Norma B. , Fan Lir-Wan , Tien Lu-Tai
Published: June 2021

Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 2 mg/kg) was administered to Sprague–Dawley rat pups on postnatal day 5 (P5), and i.p. administration of pioglitazone (20 mg/kg) or vehicle was performed 5 min after LPS injection. Sensorimotor behavioral tests were performed 24 h after LPS exposure, and changes in biochemistry of the brain was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, reduction of oligodendrocytes and mitochondrial activity, and increases in lipid peroxidation and brain inflammation, as indicated by the increment of interleukin-1β (IL-1β) levels and number of activated microglia in the neonatal rat brain. Pioglitazone treatment significantly improved LPS-induced neurobehavioral and physiological disturbances including the loss of body weight, hypothermia, righting reflex, wire-hanging maneuver, negative geotaxis, and hind-limb suspension in neonatal rats. The neuroprotective effect of pioglitazone against the loss of oligodendrocytes and mitochondrial activity was associated with attenuation of LPS-induced increment of thiobarbituric acid reactive substances (TBARS) content, IL-1β levels and number of activated microglia in neonatal rats. Our results show that pioglitazone prevents neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on microglial activation, IL-1β induction, lipid peroxidation, oligodendrocyte production and mitochondrial activity.
Resistance in the Genus Spodoptera: Key Insect Detoxification Genes
Authors: Hilliou Frédérique , Chertemps Thomas , Maïbèche Martine , Le Goff Gaëlle
Published: June 2021

The genus Spodoptera (Lepidoptera: Noctuidae) includes species that are among the most important crop pests in the world. These polyphagous species are able to feed on many plants, including corn, rice and cotton. In addition to their ability to adapt to toxic compounds produced by plants, they have developed resistance to the chemical insecticides used for their control. One of the main mechanisms developed by insects to become resistant involves detoxification enzymes. In this review, we illustrate some examples of the role of major families of detoxification enzymes such as cytochromes P450, carboxyl/cholinesterases, glutathione S-transferases (GST) and transporters such as ATP-binding cassette (ABC) transporters in insecticide resistance. We compare available data for four species, Spodoptera exigua, S. frugiperda, S. littoralis and S. litura. Molecular mechanisms underlying the involvement of these genes in resistance will be described, including the duplication of the CYP9A cluster, over-expression of GST epsilon or point mutations in acetylcholinesterase and ABCC2. This review is not intended to be exhaustive but to highlight the key roles of certain genes.
The Effectiveness of Rehabilitation of Occupational Voice Disorders in a Health Resort Hospital Environment
Authors: Sinkiewicz Anna , Garstecka Agnieszka , Mackiewicz-Nartowicz Hanna , Nawrocka Lidia , Wojciechowska Wioletta , Szkiełkowska Agata
Published: June 2021

Background: The aim of this study was to present a rehabilitation program of occupational voice disorders for teachers, conducted in the form of health resort stays, and evaluate its effectiveness depending on job seniority. Methods: The study included 420 teachers who participated in a complex vocal prophylactic and rehabilitation program carried out during a 24-day stay at a health resort hospital. Employment time varied from 4 to 45 years (mean 28.3 years). The participants were divided into three groups: employment time < 21 years (57 teachers), 21–30 years (182 teachers) and > 30 years (181 teachers). All of the subjects underwent maximum phonation time assessment as well as jitter, shimmer and NHR (noise to harmonic ratio) parameters assessment before and after the program; they also underwent perceptual evaluation using the GRBAS scale and voice self-assessment using the VHI-30 scale. Results: The perceptual evaluation using the GRBAS scale and self-report measures of voice function assessed using the VHI scale revealed improvement (p < 0.001). The parameters of jitter, shimmer and NHR improved significantly: jitter p < 0.001, shimmer p < 0.001 and NHR p < 0.003. Maximum phonation time increased slightly but significantly (p < 0.001). For all of the studied groups regardless of their employment time, maximum phonation time increased (p < 0.001). Initially, the lowest values of maximum phonation time were observed in teachers with longer job seniority, which improved after the rehabilitation but remained <15 s. Conclusions: Voice care for teachers is crucial regardless of their job seniority. Early prophylaxis for voice disorders is effective, as the results of rehabilitation are better in teachers with a shorter employment time.
Influence of Cultural Background on Visitor Segments’ Tourist Destination Image: A Case Study of Barcelona and Chinese Tourists
Authors: Tian Mingge , Cànoves Gemma , Chu Yujing , Font-Garolera Jaume , Prat Forga José María
Published: June 2021

Tourists from different cultural backgrounds have different perceptions of the image of a tourist destination. This paper aims to investigate tourist destination image (TDI) from a national cultural perspective and to see whether there exists the influence of culture on a visitor segment’s destination image as well as their travel behavior and satisfaction. Barcelona as the destination and the Chinese market are utilized to present an empirical discussion of the study. Based on the results of the qualitative method previously conducted by the authors, a questionnaire was designed in this paper. The SPSS 22 program was used for data management and analysis. This study first demonstrates that TDI perceived by the Chinese visitors is influenced by their pro-social cultural background and, second, that the visitors greatly value prestige and social networking during the visitation. This study further discusses the reasons why the visitors greatly value prestige and social networking and how “facework” influences their travel behavior based on the concept of culture value orientation. Overall, this study contributes to the existing knowledge on the formation of perception of TDI by analyzing the influence of the tourist cultural background on their TDI.