bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Variability of the Color of Beech Wood in the Color Space CIE L*a*b*
Authors: Dzurenda Ladislav
Published: May 2023

In this contribution, the color of dry beech wood from the zone, sapwood, mature wood and false heartwood of Fagus sylvatica L. trees was analyzed, and the measurement values were statistically processed in relation to the lightness coordinate L* as well as the chromatic coordinates of red color a* and yellow color b* in the color space CIE L*a*b*. The dispersion of color (color dispersion) ∆EuC of beech wood in coreless zones and the color of the wood of false heartwood were evaluated through the combined standard uncertainties of the individual coordinates of the color space. The visual color differences between the color of sapwood beech wood and the color of mature wood as well as between the color of sapwood and false heartwood are numerically documented through the values of total color differences ∆E* = 3.5 and ∆E* = 18.1. Within the framework of the categorization, the color difference between mature wood and sapwood belongs to the category of visible changes, and the difference between the color of the wood of the false heartwood and the color of the sapwood belongs to the category of significant color changes. By defining the boundaries of the color of beech wood for the color of sapwood, mature wood and false heartwood in the color space CIE L*a*b*, space is created to sort it into color groups in case of customer requests. At the same time, designers are expanding the possibilities of applying beech wood to color compositions, depending on the darkness and color of the beech wood identified by the values of the color space coordinates.
Human Chorionic Gonadotropin Enhancement of Early Maturation and Consequences for Reproductive Success of Feminized European Eel (Anguilla anguilla)
Authors: Palstra Arjan P. , van de Ven Ida , Jéhannet Pauline , Kruijt Leo , Schipper Henk , Swinkels William , Heinsbroek Leon T. N.
Published: May 2023

To induce oocyte development, eels are weekly injected with salmon or carp pituitary extract (CPE). The weekly handling and hormone peaks result in inferior oocyte quality; therefore, alternative treatments that improve oocyte quality and reproductive success require investigation. The enhancement of early sexual maturation by a single injection with human chorionic gonadotropin (hCG), administered prior to CPE treatment, was investigated. Fifty feminized eels were subjected to simulated migration, after which eels received either a hCG or a sham injection. After two months, the hCG-treated eels showed an increase in eye size, gonadosomatic index (GSI), and plasma 11-ketotestosterone concentration, when compared with the sham-injected controls. The hCG-treated eels showed increases in oocyte diameter and lipid area, and in ovarian expression of aromatase (cyp19), follicle stimulating hormone receptor (fshr) and lipoprotein lipase (lpl). Yolk was present in the oocytes of the hCG-treated eels, not yet in the oocytes of the controls. The hCG-induced deposition of yolk may relate to early-life treatment with 17β-estradiol during feminization. hCG-treated eels required four CPE injections less to mature than the controls. hCG treatment may benefit reproductive success in feminized eels by initiating vitellogenesis and reducing the hypophysation period, although larvae were obtained from most females in both groups.
Effect of Drying Process on the Formation of the Characteristic Flavor of Oyster (Crassostrea hongkongensis)
Authors: Wang Zhijun , Li Hanqi , Cao Wenhong , Chen Zhongqin , Gao Jialong , Zheng Huina , Lin Haisheng , Qin Xiaoming
Published: May 2023

Oysters are nutritious and tasty but difficult to store. Drying can extend the storage period of oysters and give them a unique flavor. In this study, the effects of four drying procedures, namely, vacuum freeze drying (VFD), vacuum drying (VD), natural sun-drying (NSD), and hot air drying (HAD), on the flavor characteristics of oysters (Crassostrea hongkongensis) were investigated using blanched oysters as a control (CK). Results showed that HAD produced more free amino acids than the other methods, but VFD retained the most flavor nucleotides. Compared with cold drying (VFD), hot drying (VD, NSD, and HAD) increased the abundance of organic acids, betaine, and aroma substances. Glutamic acid, alanine, AMP, hexanal, octanal, heptanal, (E, E)-2,4-heptadienal, (E)-2-decenal, nonanal, etc., are defined as the characteristic flavor compounds of dried oysters, with umami, sweet, green, fatty, and fruity aromas being the main organoleptic attributes of dried oysters. Glutamic acid, glycine, betaine, IMP, pentanal, ethyl heptanoate, (E, Z)-2,4-nonadienal, 1-octen-3-one, 2-hexenal, 2-octenal, hexanal, decanal were defined as markers to distinguish different drying methods. Overall, HAD showed improved flavor qualities and characteristics and was better suited for the highly commercialized production of dried oysters.
Study on the Changes in Volatile Flavor Compounds in Whole Highland Barley Flour during Accelerated Storage after Different Processing Methods
Authors: Zhang Wengang , Yang Xijuan , Zhang Jie , Lan Yongli , Dang Bin
Published: May 2023

The effect of heat processing on the flavor characteristics of highland barley flour (HBF) in storage was revealed by analyzing differences in volatile compounds associated with flavor deterioration in HBF using GC-MS identification and relative odor activity values (ROAVs). Hydrocarbons were the most abundant in untreated and extrusion puffed HBFs, while heterocycles were found to be the most abundant in explosion puffed, baked, and fried HBFs. The major contributors to the deterioration of flavor in different HBFs were hexanal, hexanoic acid, 2-pentylfuran, 1-pentanol, pentanal, 1-octen-3-ol, octanal, 2-butyl-2-octanal, and (E,E)-2,4-decadienal. Amino acid and fatty acid metabolism was ascribed to the main formation pathways of these compounds. Baking slowed down the flavor deterioration in HBF, while extrusion puffing accelerated the flavor deterioration in HBF. The screened key compounds could predict the quality of HBF. This study provides a theoretical basis for the regulation of the flavor quality of barley and its products.
Functionality of Puff Pastry Olive Pomace Oil-Based Margarines and Their Baking Performance
Authors: Álvarez María Dolores , Herranz Beatriz , Saiz Arancha , Cofrades Susana
Published: May 2023

Designing healthier lipids is a current approach to developing potential functional foods. Olive pomace oil (OPO) has beneficial effects on human health, attributed to its high oleic acid content and unique bioactive compounds. Four puff pastry margarines (PP-M), based on OPO (M1, M2 at 40.8%, and M3, M4 at 30.8%, and cocoa butter at 10%) combined with low molecular weight organogelators, were prepared using two initial cooling rates (M1, M3 at 0.144 °C/min and M2, M4 at 0.380 °C/min) and compared to both commercial puff pastry (PP) butter (CB) and fatty preparation (CFP). Subsequently, six baked PP counterparts were elaborated. Physical-chemical, mechanical properties, and lipid profiles were analyzed in M1–M4 and PP, while thermal properties were determined in M1–M4. Sensory analysis was carried out in PP-M1 and PP-M3 counterparts. Elasticity (G′) of M1–M4 samples was between that of controls CB and CFP, although a higher OPO content reduced viscous modulus (G″). The initial cooling rate did not affect the melting behavior of M1–M4. The firmness of PP-M1 was similar to that of PP-CB and PP-CFP, and the better spreadability and plasticity of M1 positively favored PP puffing. In addition, PP-M1 had 36.8% less SFA content than baked PP-CB, and its overall acceptability was similar. For the first time, a new margarine with high OPO content, showing adequate firmness, spreadability, and plasticity, was formulated, which gave rise to PP with appropriate performance and sensory quality and a healthy lipid profile.
Incidental Findings in Forensic Investigations: A Narrative Review
Authors: Fasani Giulia , Gino Sarah , Sguazzi Giulia
Published: May 2023

Incidental findings (IFs) are unexpected disclosures that do not fall within the aim of a test and have a potential impact on an individual’s life. In the forensic field, IFs can be considered information that is not related to the cause of death, the dynamic of the event, or the scope of the investigation. Questions regarding how forensic professionals should consider, address, and report IFs form the focus of our study. This narrative review was performing following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with the aim of defining and summarizing evidence about IFs, analyzing their ethical and legal management, and emphasizing the importance of adequate informed consent. The current state of the art regarding IFs has revealed the need for guidelines with the purpose of making the best decisions for the parties involved since the circumstances are extremely delicate, and therefore, forensic geneticists require protection and support. For this reason, elaboration of informed consent, which considers the possibility of making accidental discoveries, could operate as an immediate solution to fill the current gaps. However, the development of clear international recommendations is the best solution to such a complex issue.
Multiplicity of Positive Solutions to Hadamard-Type Fractional Relativistic Oscillator Equation with p-Laplacian Operator
Authors: Shen Tengfei
Published: May 2023

The purpose of this paper is to investigate the initial value problem of Hadamard-type fractional relativistic oscillator equation with p-Laplacian operator. By overcoming the perturbation of singularity to fractional relativistic oscillator equation, the multiplicity of positive solutions to the problem were proved via the methods of reducing and topological degree in cone, which extend and enrich some previous results.
Experimental Study on the Distribution and Height of Spontaneous Imbibition Water of Chang 7 Continental Shale Oil
Authors: Zhu Jianhong , Chen Junbin , Duanmu Xiaoliang , Wang Xiaoming , Gong Diguang , Nie Xiangrong
Published: May 2023

After multi-stage volume hydraulic fracturing in a shale oil reservoir, massive amounts of water can be imbibed into the matrix pores. One of the key imbibition characteristics of a shale reservoir is the imbibition water and its height distribution. Based on high pressure mercury injection (HPMI) experiments and nuclear magnetic resonance (NMR) analyses, this study quantitatively evaluated the pore-size distribution of Chang 7 continental shale oil reservoirs in Yanchang Formation, Ordos Basin. The pores could be divided into three types as micropores (≤0.1 μm), mesopores (0.1–1.0 μm), and macropores (>1.0 μm), while the volume of micropores and mesopores accounted for more than 90%. This demonstrated that there were strong heterogeneity and micro–nano characteristics. According to the spontaneous imbibition (SI) experiments, the cumulative proportion of imbibition water content was the largest in micropores, exceeding 43%, followed by mesopores around 30%, and that of macropores was the lowest, and basically less than 20%. The negative values of stage water content in the macropore or mesopore indicated that these pores became a water supply channel for other dominant imbibition pores. Additionally, combining the fractal theory with the NMR T2 spectrum, the relative imbibition water and actual height were calculated in different pores, while the height distribution varied with cores and shale oil. The shorter the core, the higher was the relative height, while the radius of macropores filled with imbibition water was reduced. This indicates that the height distribution was affected by the pore structure, oil viscosity, and core length.
Topological Subordination in Quantum Mechanics
Authors: Iomin Alexander , Metzler Ralf , Sandev Trifce
Published: May 2023

An example of non-Markovian quantum dynamics is considered in the framework of a geometrical (topological) subordination approach. The specific property of the model is that it coincides exactly with the fractional diffusion equation, which describes the geometric Brownian motion on combs. Both classical diffusion and quantum dynamics are described using the dilatation operator xddx. Two examples of geometrical subordinators are considered. The first one is the Gaussian function, which is due to the comb geometry. For the quantum consideration with a specific choice of the initial conditions, it corresponds to the integral representation of the Mittag–Leffler function by means of the subordination integral. The second subordinator is the Dirac delta function, which results from the memory kernels that define the fractional time derivatives in the fractional diffusion equation.
Associations between Green Space Surrounding Kindergartens and Hyperactivity Behaviors among Chinese Preschool Children
Authors: Ai Baozhuo , Zhang Shiyu , Fu Jiaying , Yin Xiaona , Wen Guomin , Sun Dengli , Xian Danxia , Zhao Yafen , Lin Hualiang , Chen Weiqing , Yang Weikang , Zhang Zilong
Published: May 2023

Background: Attention deficit hyperactivity disorder (ADHD) affects approximately 2–7% of children worldwide and has become a global public health concern. The health effects of green space on ADHD in young children are unclear. We investigated associations between school-surrounding greenness and hyperactivity behaviors in preschool children. Methods: We performed a cross-sectional analysis using data of 66,678 preschool children (mean age: 3.53 years) from an on-going cohort in Shenzhen, China. The greenness surrounding kindergartens was measured using satellite-derived Normalized Difference Vegetation Index (NDVI) values at buffers of 250 m, 500 m, and 1000 m. Children’s hyperactivity behaviors were measured using the validated Conners’ Parent Rating Scale-Revised. We used generalized linear mixed models to assess the associations of greenness exposure with hyperactivity behaviors with adjustment for a variety of covariates. Results: Exposure to higher school-surrounding greenness was associated with lower prevalence of hyperactivity behaviors. In fully adjusted models, the odds ratio of hyperactivity behaviors in relation to an IQR (0.1) increase in NDVI at the 250 m buffer was 0.91 [confidence interval (CI): 0.84,0.98]. Consistent results were observed for greenness at the 500 m and 1000 m buffers. The negative association between greenness and hyperactivity behaviors was more pronounced in boys than in girls. Conclusions: Our findings suggest that higher levels of school-surrounding green spaces are associated with a lower risk of hyperactivity behaviors in preschool children.
Latinx and Asian Engagement/Complicity in Anti-Blackness
Authors: Aronson Brittany , Stohry Hannah R.
Published: May 2023

We live in a world that desperately wishes to ignore centuries of racial divisions and hierarchies by positioning multiracial people as a declaration of a post-racial society. The latest U.S. 2020 Census results show that the U.S. population has grown in racial and ethnic diversity in the last ten years, with the white population decreasing. Our U.S. systems of policies, economy, and well-being are based upon “scientific” constructions of racial difference, hierarchy, Blackness, and fearmongering around miscegenation (racial mixing) that condemn proximity to Blackness. Driven by our respective multiracial Latinx and Asian experiences and entry points to anti-Blackness, this project explores the history of Latinx and Asian racialization and engagement with anti-Blackness. Racial hierarchy positions our communities as honorary whites and employs tactics to complicate solidarity and coalition. This project invites engagement in consciousness-raising in borderlands as sites of transformation as possible methods of addressing structural anti-Blackness.
Complete Chloroplast Genome Determination of Ranunculus sceleratus from Republic of Korea (Ranunculaceae) and Comparative Chloroplast Genomes of the Members of the Ranunculus Genus
Authors: Kim Kang-Rae , Park So Young , Kim Heesoo , Hong Jeong Min , Kim Sun-Yu , Yu Jeong-Nam
Published: May 2023

Ranunculus sceleratus (family: Ranunculaceae) is a medicinally and economically important plant; however, gaps in taxonomic and species identification limit its practical applicability. This study aimed to sequence the chloroplast genome of R. sceleratus from Republic of Korea. Chloroplast sequences were compared and analyzed among Ranunculus species. The chloroplast genome was assembled from Illumina HiSeq 2500 sequencing raw data. The genome was 156,329 bp and had a typical quadripartite structure comprising a small single-copy region, a large single-copy region, and two inverted repeats. Fifty-three simple sequence repeats were identified in the four quadrant structural regions. The region between the ndhC and trnV-UAC genes could be useful as a genetic marker to distinguish between R. sceleratus populations from Republic of Korea and China. The Ranunculus species formed a single lineage. To differentiate between Ranunculus species, we identified 16 hotspot regions and confirmed their potential using specific barcodes based on phylogenetic tree and BLAST-based analyses. The ndhE, ndhF, rpl23, atpF, rps4, and rpoA genes had a high posterior probability of codon sites in positive selection, while the amino acid site varied between Ranunculus species and other genera. Comparison of the Ranunculus genomes provides useful information regarding species identification and evolution that could guide future phylogenetic analyses.
Evaluating the Differential Response of Transcription Factors in Diploid versus Autotetraploid Rice Leaves Subjected to Diverse Saline–Alkali Stresses
Authors: Wang Ningning , Wang Yingkai , Wang Chenxi , Leng Zitian , Qi Fan , Wang Shiyan , Zhou Yiming , Meng Weilong , Liu Keyan , Zhang Chunying , Ma Jian
Published: May 2023

Saline–alkali stress is a significant abiotic stress factor that impacts plant growth, development, and crop yield. Consistent with the notion that genome-wide replication events can enhance plant stress resistance, autotetraploid rice exhibited a higher level of tolerance to saline–alkali stress than its donor counterparts, which is reflected by differential gene expression between autotetraploid and diploid rice in response to salt, alkali, and saline–alkali stress. In this study, we investigated the expression of the transcription factors (TFs) in the leaf tissues of autotetraploid and diploid rice under different types of saline–alkali stress. Transcriptome analysis identified a total of 1040 genes from 55 TF families that were altered in response to these stresses, with a significantly higher number in autotetraploid rice compared to diploid rice. Contrarily, under these stresses, the number of expressed TF genes in autotetraploid rice was greater than that in diploid rice for all three types of stress. In addition to the different numbers, the differentially expressed TF genes were found to be from significantly distinct TF families between autotetraploid and diploid rice genotypes. The GO enrichment analysis unraveled that all the DEGs were distributed with differentially biological functions in rice, in particular those that were enriched in the pathways of phytohormones and salt resistance, signal transduction, and physiological and biochemical metabolism in autotetraploid rice compared to its diploid counterpart. This may provide useful guidance for studying the biological roles of polyploidization in plant resilience in response to saline–alkali stress.
Dynamically Changing Mental Stress Parameters of First-Year Medical Students over the Three-Year Course of the COVID-19 Pandemic: A Repeated Cross-Sectional Study
Authors: Gellisch Morris , Bablok Martin , Morosan-Puopolo Gabriela , Schäfer Thorsten , Brand-Saberi Beate
Published: May 2023

Numerous research results have already pointed towards the negative influence of increased mental stress on educational processes and motivational criteria. It has also been shown that the global public health crisis induced by COVID-19 was related to anxiety symptoms and elevated levels of distress. To holistically elucidate the dynamics of the pandemic-related mental stress of first-year medical students, the associated parameters of three different cohorts were measured at the beginning of the pandemic-related restrictions on university life in Germany (20/21), at the peak of the COVID-19-related restrictions (21/22) and during the easing of the restrictions in the winter term 22/23. In a repeated cross-sectional study design, the constructs of worries, tension, demands and joy were collected from first-year medical students (n = 578) using the Perceived Stress Questionnaire. The results demonstrate significantly increased values of the constructs worries (p < 0.001), tension (p < 0.001) and demands (p < 0.001) at the peak of the pandemic related restrictions compared to the previous and following year as well as significantly decreasing values of general joy of life during the observed period of 3 years (all p-values < 0.001). A confirmatory factor analysis was performed to verify the questionnaire’s factor structure regarding the addressed target group during the pandemic (CFI: 0.908, RMSEA: 0.071, SRMR: 0.052). These data, collected over a period of three years, provide information regarding dynamically manifesting mental stress during the COVID-19 pandemic, and refer to new areas of responsibility for the faculties to adequately counteract future crisis situations.
Identification of Heat-Resistant Varieties of Non-Headed Chinese Cabbage and Discovery of Heat-Resistant Physiological Mechanisms
Authors: Yu Jing , Li Pengli , Tu Song , Feng Ningxiao , Chang Liying , Niu Qingliang
Published: May 2023

Affected by global warming, continuous high temperature has a negative impact on plant growth and development and become a major constraint to crop production. Germplasm resource identification has become a research hotspot in many fields, and it is also necessary to establish effective identification methods. In this study, twenty Brassica rapa varieties were selected to investigate the physiological and biochemical characteristics under heat stress, explore the relationship between physiological response and the heat resistance mechanism, and select some typical heat-resistant and heat-sensitive varieties. The effects of photosynthetic electron transfer and antioxidant pathway on the heat resistance of Brassica rapa were identified. These findings will provide important guidance for the physiological regulation and identification method of heat stress in plants.
The Epidemiological Surveillance of Mesothelioma Mortality in Italy as a Tool for the Prevention of Asbestos Exposure
Authors: Fazzo Lucia , Minelli Giada , De Santis Marco , Ceccarelli Emiliano , Iavarone Ivano , Zona Amerigo
Published: May 2023

As part of a surveillance plan active since the early 1990s, this study evaluates malignant mesothelioma (MM) mortality for the time-window 2010–2019 in Italy, a country that banned asbestos in 1992. National and regional mortality rates for MM, and municipal standardized mortality ratios (all mesotheliomas, pleural (MPM) and peritoneal (MPeM)), by gender and age group were calculated. A municipal clustering analysis was also performed. There were 15,446 deaths from MM (11,161 males, 3.8 × 100,000; 4285 females, 1.1 × 100,000), of which 12,496 were MPM and 661 were MPeM. In the study period, 266 people ≤50 years died from MM. A slightly decreasing rate among males since 2014 was observed. The areas at major risk hosted asbestos-cement plants, asbestos mines (chrysotile in Balangero), shipyards, petrochemical and chemical plants, and refineries. Female mortality excesses particularly were found in municipalities with a fluoro-edenite-contaminated mine (Biancavilla) and textile facilities. Excesses were also found in a region with the presence of natural asbestos fibres and in males living in two small islands. The Italian National Prevention Plan stated recommendations to eliminate asbestos exposures and to implement health surveillance and healthcare for people exposed to asbestos.
Education Level and Self-Reported Cardiovascular Disease in Norway—The Tromsø Study, 1994–2016
Authors: Cathro Celina Janene , Brenn Tormod , Chen Sairah Lai Fa
Published: May 2023

Background: Cardiovascular disease (CVD) is a leading source of morbidity and mortality, and research has shown education level to be a risk factor for the disease. The aim of this study was to investigate the association between education level and self-reported CVD in Tromsø, Norway. Methods: This prospective cohort study included 12,400 participants enrolled in the fourth and seventh surveys of the Tromsø Study (Tromsø4 and Tromsø7) in 1994–1995 and 2015–2016, respectively. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Results: For every 1-level increase in education, the age-adjusted risk of self-reported CVD decreased by 9% (OR = 0.91, 95% CI: 0.87–0.96), but after adjustment for covariates, the association was weaker (OR = 0.96, 95% CI: 0.92–1.01). The association was stronger for women (OR = 0.86, 95% CI: 0.79–0.94) than men (OR = 0.91, 95% CI: 0.86–0.97) in age-adjusted models. After adjustment for covariates, the associations for women and men were similarly weak (women: OR = 0.95, 95% CI: 0.87–1.04; men: OR = 0.97, 95% CI: 0.91–1.03). In age-adjusted-models, higher education level was associated with a lower risk of self-reported heart attack (OR = 0.90, 95% CI: 0.84–0.96), but not stroke (OR = 0.97, 95% CI: 0.90–1.05) or angina (OR = 0.98, 95% CI: 0.90–1.07). There were no clear associations observed in the multivariable models for CVD components (heart attack: OR = 0.97, 95% CI: 0.91–1.05; stroke: OR = 1.01, 95% CI: 0.93–1.09; angina: OR = 1.04, 95% CI: 0.95–1.14). Conclusions: Norwegian adults with a higher education level were at lower risk of self-reported CVD. The association was present in both genders, with a lower risk observed in women than men. After accounting for lifestyle factors, there was no clear association between education level and self-reported CVD, likely due to covariates acting as mediators.
Alu-Mediated Insertions in the DMD Gene: A Difficult Puzzle to Interpret Clinically
Authors: Torella Annalaura , Budillon Alberto , Zanobio Mariateresa , Del Vecchio Blanco Francesca , Picillo Esther , Politano Luisa , Nigro Vincenzo , Piluso Giulio
Published: May 2023

Disrupting variants in the DMD gene are associated with Duchenne or Becker muscular dystrophy (DMD/BMD) or with hyperCKemia, all of which present very different degrees of clinical severity. The clinical phenotypes of these disorders could not be distinguished in infancy or early childhood. Accurate phenotype prediction based on DNA variants may therefore be required in addition to invasive tests, such as muscle biopsy. Transposon insertion is one of the rarest mutation types. Depending on their position and characteristics, transposon insertions may affect the quality and/or quantity of dystrophin mRNA, leading to unpredictable alterations in gene products. Here, we report the case of a three-year-old boy showing initial skeletal muscle involvement in whom we characterized a transposon insertion (Alu sequence) in exon 15 of the DMD gene. In similar cases, the generation of a null allele is predicted, resulting in a DMD phenotype. However, mRNA analysis of muscle biopsy tissue revealed skipping of exon 15, which restored the reading frame, thus predicting a milder phenotype. This case is similar to very few others already described in the literature. This case further enriches our knowledge of the mechanisms perturbing splicing and causing exon skipping in DMD, helping to properly guide clinical diagnosis.
JAK Signaling Is Critically Important in Cytokine-Induced Viral Susceptibility of Keratinocytes
Authors: Arnold Kimberly A. , Peterson Liam F. , Beck Lisa A. , Brewer Matthew G.
Published: May 2023

Little is known about whether type 1 (IFNγ), 2 (IL-4/IL-13), or 3 (IL-17A/IL-22) cytokines affect the susceptibility of keratinocytes (KC) to viruses. These immune pathways predominate in various skin diseases: lupus, atopic dermatitis (AD), and psoriasis, respectively. Janus kinase inhibitors (JAKi) are approved to treat both AD and psoriasis, and are in clinical development for lupus. We evaluated whether these cytokines alter viral susceptibility of KC and determined if this effect is modulated by treatment with JAKi. Viral susceptibility to vaccinia virus (VV) or herpes simplex virus-1 (HSV-1) ± JAKi was assessed in immortalized and primary human KC pretreated with cytokines. Exposure to type 2 (IL-4 + IL-13) or the type 3 (IL-22) cytokines significantly increased KC viral susceptibility. Specifically, there was a peak increase of 12.2 ± 3.1-fold (IL-4 + IL-13) or 7.7 ± 2.8-fold (IL-22) in VV infection as measured by plaque number. Conversely, IFNγ significantly reduced susceptibility to VV (63.1 ± 64.4-fold). The IL-4 + IL-13-induced viral susceptibility was reduced (44 ± 16%) by JAK1 inhibition, while the IL-22-enhanced viral susceptibility was diminished (76 ± 19%) by TYK2 inhibition. IFNγ-mediated resistance to viral infection was reversed by JAK2 inhibition (366 ± 294% increase in infection). Cytokines expressed in AD skin (IL-4, IL-13, IL-22) increase KC viral susceptibility while IFNγ is protective. JAKi that target JAK1 or TYK2 reversed cytokine-enhanced viral susceptibility, while JAK2 inhibition reduced the protective effects of IFNγ.
Antidepressant Effects of Essential Oils: A Review of the Past Decade (2012–2022) and Molecular Docking Study of Their Major Chemical Components
Authors: Fonseca Emily Christie M. , Ferreira Lanalice R. , Figueiredo Pablo Luis B. , Maia Cristiane do Socorro F. , Setzer William N. , Da Silva Joyce Kelly R.
Published: May 2023

Depression is a mental disorder that affects more than 300 million people worldwide. The medications available for treatment take a long time to exhibit therapeutic results and present several side effects. Furthermore, there is a decrease in the quality of life of people suffering from this affliction. Essential oils are traditionally used to relieve the symptoms of depression due to the properties of the constituents of these oils to cross the blood–brain barrier acting on depression-related biological receptors associated with reduced toxicity and side effects. In addition, compared to traditional drugs, they have several administration forms. This review provides a comprehensive assessment of studies on plants whose essential oil has exhibit antidepressant activity in the past decade and the mechanism of action of the major components and models tested. An additional in silico study was conducted with the frequent compounds in the composition of these essential oils, providing a molecular approach to the mechanism of action that has been reported in the past decade. This review is valuable for the development of potential antidepressant medications in addition to providing a molecular approach to the antidepressant mechanism of action of the major volatile compounds that have been reported in the past decade.
Plasma-Induced Oxygen Vacancies in N-Doped Hollow NiCoPBA Nanocages Derived from Prussian Blue Analogue for Efficient OER in Alkaline Media
Authors: Le Huu Tuan , Lee Ji Eon , Yun So Yeon , Kwon Ohyung , Park Jin Kuen , Jeong Young Kyu
Published: May 2023

Although water splitting is a promising method to produce clean hydrogen energy, it requires efficient and low-cost catalysts for the oxygen evolution reaction (OER). This study focused on plasma treatment’s significance of surface oxygen vacancies in improving OER electrocatalytic activity. For this, we directly grew hollow NiCoPBA nanocages using a Prussian blue analogue (PBA) on nickel foam (NF). The material was treated with N plasma, followed by a thermal reduction process for inducing oxygen vacancies and N doping on the structure of NiCoPBA. These oxygen defects were found to play an essential role as a catalyst center for the OER in enhancing the charge transfer efficiency of NiCoPBA. The N-doped hollow NiCoPBA/NF showed excellent OER performance in an alkaline medium, with a low overpotential of 289 mV at 10 mA cm−2 and a high stability for 24 h. The catalyst also outperformed a commercial RuO2 (350 mV). We believe that using plasma-induced oxygen vacancies with simultaneous N doping will provide a novel insight into the design of low-priced NiCoPBA electrocatalysts.
Further Insights into the Gut Microbiota of Cow’s Milk Allergic Infants: Analysis of Microbial Functionality and Its Correlation with Three Fecal Biomarkers
Authors: Zubeldia-Varela Elisa , Barker-Tejeda Tomás Clive , Mera-Berriatua Leticia , Bazire Raphaëlle , Cabrera-Freitag Paula , Ubeda Carles , Barber Domingo , Francino María Pilar , Rojo David , Ibáñez-Sandín María Dolores , Pérez-Gordo Marina
Published: May 2023

Cow’s milk allergy (CMA) is one of the most prevalent food allergies in children. Several studies have demonstrated that gut microbiota influences the acquisition of oral tolerance to food antigens at initial stages of life. Changes in the gut microbiota composition and/or functionality (i.e., dysbiosis) have been linked to inadequate immune system regulation and the emergence of pathologies. Moreover, omic sciences have become an essential tool for the analysis of the gut microbiota. On the other hand, the use of fecal biomarkers for the diagnosis of CMA has recently been reviewed, with fecal calprotectin, α-1 antitrypsin, and lactoferrin being the most relevant. This study aimed at evaluating functional changes in the gut microbiota in the feces of cow’s milk allergic infants (AI) compared to control infants (CI) by metagenomic shotgun sequencing and at correlating these findings with the levels of fecal biomarkers (α-1 antitrypsin, lactoferrin, and calprotectin) by an integrative approach. We have observed differences between AI and CI groups in terms of fecal protein levels and metagenomic analysis. Our findings suggest that AI have altered glycerophospholipid metabolism as well as higher levels of lactoferrin and calprotectin that could be explained by their allergic status.
Quality and Agronomic Trait Analyses of Pyramids Composed of Wheat Genes NGli-D2, Sec-1s and 1Dx5+1Dy10
Authors: Bu Zhimu , Fang Gongyan , Yu Haixia , Kong Dewei , Huo Yanbing , Ma Xinyu , Chong Hui , Guan Xin , Liu Daxin , Fan Kexin , Yan Min , Ma Wujun , Chen Jiansheng
Published: May 2023

Due to rising living standards, it is important to improve wheat’s quality traits by adjusting its storage protein genes. The introduction or locus deletion of high molecular weight subunits could provide new options for improving wheat quality and food safety. In this study, digenic and trigenic wheat lines were identified, in which the 1Dx5+1Dy10 subunit, and NGli-D2 and Sec-1s genes were successfully polymerized to determine the role of gene pyramiding in wheat quality. In addition, the effects of ω-rye alkaloids during 1BL/1RS translocation on quality were eliminated by introducing and utilizing 1Dx5+1Dy10 subunits through gene pyramiding. Additionally, the content of alcohol-soluble proteins was reduced, the Glu/Gli ratio was increased and high-quality wheat lines were obtained. The sedimentation values and mixograph parameters of the gene pyramids under different genetic backgrounds were significantly increased. Among all the pyramids, the trigenic lines in Zhengmai 7698, which was the genetic background, had the highest sedimentation value. The mixograph parameters of the midline peak time (MPT), midline peak value (MPV), midline peak width (MPW), curve tail value (CTV), curve tail width (CTW), midline value at 8 min (MTxV), midline width at 8 min (MTxW) and midline integral at 8 min (MTxI) of the gene pyramids were markedly enhanced, especially in the trigenic lines. Therefore, the pyramiding processes of the 1Dx5+1Dy10, Sec-1S and NGli-D2 genes improved dough elasticity. The overall protein composition of the modified gene pyramids was better than that of the wild type. The Glu/Gli ratios of the type I digenic line and trigenic lines containing the NGli-D2 locus were higher than that of the type II digenic line without the NGli-D2 locus. The trigenic lines with Hengguan 35 as the genetic background had the highest Glu/Gli ratio among the specimens. The unextractable polymeric protein (UPP%) and Glu/Gli ratios of the type II digenic line and trigenic lines were significantly higher than those of the wild type. The UPP% of the type II digenic line was higher than that of the trigenic lines, while the Glu/Gli ratio was slightly lower than that of the trigenic lines. In addition, the celiac disease (CD) epitopes’ level of the gene pyramids significantly decreased. The strategy and information reported in this study could be very useful for improving wheat processing quality and reducing wheat CD epitopes.
Reversal of Tau-Dependent Cognitive Decay by Blocking Adenosine A1 Receptors: Comparison of Transgenic Mouse Models with Different Levels of Tauopathy
Authors: Anglada-Huguet Marta , Endepols Heike , Sydow Astrid , Hilgers Ronja , Neumaier Bernd , Drzezga Alexander , Kaniyappan Senthilvelrajan , Mandelkow Eckhard , Mandelkow Eva-Maria
Published: May 2023

The accumulation of tau is a hallmark of several neurodegenerative diseases and is associated with neuronal hypoactivity and presynaptic dysfunction. Oral administration of the adenosine A1 receptor antagonist rolofylline (KW-3902) has previously been shown to reverse spatial memory deficits and to normalize the basic synaptic transmission in a mouse line expressing full-length pro-aggregant tau (TauΔK) at low levels, with late onset of disease. However, the efficacy of treatment remained to be explored for cases of more aggressive tauopathy. Using a combination of behavioral assays, imaging with several PET-tracers, and analysis of brain tissue, we compared the curative reversal of tau pathology by blocking adenosine A1 receptors in three mouse models expressing different types and levels of tau and tau mutants. We show through positron emission tomography using the tracer [18F]CPFPX (a selective A1 receptor ligand) that intravenous injection of rolofylline effectively blocks A1 receptors in the brain. Moreover, when administered to TauΔK mice, rolofylline can reverse tau pathology and synaptic decay. The beneficial effects are also observed in a line with more aggressive tau pathology, expressing the amyloidogenic repeat domain of tau (TauRDΔK) with higher aggregation propensity. Both models develop a progressive tau pathology with missorting, phosphorylation, accumulation of tau, loss of synapses, and cognitive decline. TauRDΔK causes pronounced neurofibrillary tangle assembly concomitant with neuronal death, whereas TauΔK accumulates only to tau pretangles without overt neuronal loss. A third model tested, the rTg4510 line, has a high expression of mutant TauP301L and hence a very aggressive phenotype starting at ~3 months of age. This line failed to reverse pathology upon rolofylline treatment, consistent with a higher accumulation of tau-specific PET tracers and inflammation. In conclusion, blocking adenosine A1 receptors by rolofylline can reverse pathology if the pathological potential of tau remains below a threshold value that depends on concentration and aggregation propensity.
The Blood–Brain Barrier in Health and Disease
Authors: Al Rihani Sweilem B. , Batarseh Yazan S. , Kaddoumi Amal
Published: May 2023

The blood–brain barrier (BBB) is a complex network of tightly regulated cells and transport proteins that separate the circulating blood from the brain tissue [...]
An Optimized/Scale Up-Ready Protocol for Extraction of Bacterially Produced dsRNA at Good Yield and Low Costs
Authors: Figueiredo Prates Lucas Henrique , Merlau Maximilian , Rühl-Teichner Johanna , Schetelig Marc F. , Häcker Irina
Published: May 2023

Double-stranded RNA (dsRNA) can trigger RNA interference (RNAi) and lead to directed silencing of specific genes. This natural defense mechanism and RNA-based products have been explored for their potential as a sustainable and ecofriendly alternative for pest control of species of agricultural importance and disease vectors. Yet, further research, development of new products and possible applications require a cost-efficient production of dsRNA. In vivo transcription of dsRNA in bacterial cells has been widely used as a versatile and inducible system for production of dsRNA combined with a purification step required to extract the dsRNA. Here, we optimized an acidic phenol-based protocol for extraction of bacterially produced dsRNA at low cost and good yield. In this protocol, bacterial cells are efficiently lysed, with no viable bacterial cells present in the downstream steps of the purification. Furthermore, we performed a comparative dsRNA quality and yield assessment of our optimized protocol and other protocols available in the literature and confirmed the cost-efficiency of our optimized protocol by comparing the cost of extraction and yields of each extraction method.
Chelator PBT2 Forms a Ternary Cu2+ Complex with β-Amyloid That Has High Stability but Low Specificity
Authors: Drew Simon C.
Published: May 2023

The metal chelator PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) acts as a terdentate ligand capable of forming binary and ternary Cu2+ complexes. It was clinically trialed as an Alzheimer’s disease (AD) therapy but failed to progress beyond phase II. The β-amyloid (Aβ) peptide associated with AD was recently concluded to form a unique Cu(Aβ) complex that is inaccessible to PBT2. Herein, it is shown that the species ascribed to this binary Cu(Aβ) complex in fact corresponds to ternary Cu(PBT2)NImAβ complexes formed by the anchoring of Cu(PBT2) on imine nitrogen (NIm) donors of His side chains. The primary site of ternary complex formation is His6, with a conditional stepwise formation constant at pH 7.4 (Kc [M−1]) of logKc = 6.4 ± 0.1, and a second site is supplied by His13 or His14 (logKc = 4.4 ± 0.1). The stability of Cu(PBT2)NImH13/14 is comparable with that of the simplest Cu(PBT2)NIm complexes involving the NIm coordination of free imidazole (logKc = 4.22 ± 0.09) and histamine (logKc = 4.00 ± 0.05). The 100-fold larger formation constant for Cu(PBT2)NImH6 indicates that outer-sphere ligand–peptide interactions strongly stabilize its structure. Despite the relatively high stability of Cu(PBT2)NImH6, PBT2 is a promiscuous chelator capable of forming a ternary Cu(PBT2)NIm complex with any ligand containing an NIm donor. These ligands include histamine, L-His, and ubiquitous His side chains of peptides and proteins in the extracellular milieu, whose combined effect should outweigh that of a single Cu(PBT2)NImH6 complex regardless of its stability. We therefore conclude that PBT2 is capable of accessing Cu(Aβ) complexes with high stability but low specificity. The results have implications for future AD therapeutic strategies and understanding the role of PBT2 in the bulk transport of transition metal ions. Given the repurposing of PBT2 as a drug for breaking antibiotic resistance, ternary Cu(PBT2)NIm and analogous Zn(PBT2)NIm complexes may be relevant to its antimicrobial properties.
Recent Mechanisms of Neurodegeneration and Photobiomodulation in the Context of Alzheimer’s Disease
Authors: Su Matthew , Nizamutdinov Damir , Liu Hanli , Huang Jason H.
Published: May 2023

Alzheimer’s disease (AD) is a neurodegenerative disease and the world’s primary cause of dementia, a condition characterized by significant progressive declines in memory and intellectual capacities. While dementia is the main symptom of Alzheimer’s, the disease presents with many other debilitating symptoms, and currently, there is no known treatment exists to stop its irreversible progression or cure the disease. Photobiomodulation has emerged as a very promising treatment for improving brain function, using light in the range from red to the near-infrared spectrum depending on the application, tissue penetration, and density of the target area. The goal of this comprehensive review is to discuss the most recent achievements in and mechanisms of AD pathogenesis with respect to neurodegeneration. It also provides an overview of the mechanisms of photobiomodulation associated with AD pathology and the benefits of transcranial near-infrared light treatment as a potential therapeutic solution. This review also discusses the older reports and hypotheses associated with the development of AD, as well as some other approved AD drugs.
Effects of Phosphorylation on the Activity, Inhibition and Stability of Carbonic Anhydrases
Authors: Huang Xiaojing , Winter Daniel , Glover Dominic J. , Supuran Claudiu T. , Donald William A.
Published: May 2023

Carbonic anhydrases (CAs) are a metalloenzyme family that have important roles in cellular processes including pH homeostasis and have been implicated in multiple pathological conditions. Small molecule inhibitors have been developed to target carbonic anhydrases, but the effects of post-translational modifications (PTMs) on the activity and inhibition profiles of these enzymes remain unclear. Here, we investigate the effects of phosphorylation, the most prevalent carbonic anhydrase PTM, on the activities and drug-binding affinities of human CAI and CAII, two heavily modified active isozymes. Using serine to glutamic acid (S > E) mutations to mimic the effect of phosphorylation, we demonstrate that phosphomimics at a single site can significantly increase or decrease the catalytic efficiencies of CAs, depending on both the position of the modification and the CA isoform. We also show that the S > E mutation at Ser50 of hCAII decreases the binding affinities of hCAII with well-characterized sulphonamide inhibitors including by over 800-fold for acetazolamide. Our findings suggest that CA phosphorylation may serve as a regulatory mechanism for enzymatic activity, and affect the binding affinity and specificity of small, drug and drug-like molecules. This work should motivate future studies examining the PTM-modification forms of CAs and their distributions, which should provide insights into CA physiopathological functions and facilitate the development of ‘modform-specific’ carbonic anhydrase inhibitors.
Expression Analysis of Lipocalin 2 (LCN2) in Reproductive and Non-Reproductive Tissues of Esr1-Deficient Mice
Authors: Kessel Jan C. , Weiskirchen Ralf , Schröder Sarah K.
Published: May 2023

Estrogen receptor alpha (ERα) is widely expressed in reproductive organs, but also in non-reproductive tissues of females and males. There is evidence that lipocalin 2 (LCN2), which has diverse immunological and metabolic functions, is regulated by ERα in adipose tissue. However, in many other tissues, the impact of ERα on LCN2 expression has not been studied yet. Therefore, we used an Esr1-deficient mouse strain and analyzed LCN2 expression in reproductive (ovary, testes) and non-reproductive tissues (kidney, spleen, liver, lung) of both sexes. Tissues collected from adult wild-type (WT) and Esr1-deficient animals were analyzed by immunohistochemistry, Western blot analysis, and RT-qPCR for Lcn2 expression. In non-reproductive tissues, only minor genotype- or sex-specific differences in LCN2 expression were detected. In contrast, significant differences in LCN2 expression were observed in reproductive tissues. Particularly, there was a strong increase in LCN2 in Esr1-deficient ovaries when compared to WTs. In summary, we found an inverse correlation between the presence of ERα and the expression of LCN2 in testes and ovaries. Our results provide an important basis to better understand LCN2 regulation in the context of hormones and in health and disease.