bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Evaluation of CFTR Gene Expression: A Comparison between Relative Quantification by Real-Time PCR and Absolute Quantification by Droplet Digital PCR
Authors: Bruno Sabina Maria , Blaconà Giovanna , Lo Cicero Stefania , Castelli Germana , Virgulti Mariarita , Testino Giancarlo , Pierandrei Silvia , Fuso Andrea , Cimino Giuseppe , Ferraguti Giampiero , Eramo Adriana , Lucarelli Marco
Published: September 2023

In the precision medicine era of cystic fibrosis (CF), therapeutic interventions, by the so-called modulators, target the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The levels of targetable CFTR proteins are a main variable in the success of patient-specific therapy. In turn, the CFTR protein level depends, at least in part, on the level of CFTR mRNA. Many mechanisms can modulate the CFTR mRNA level, for example, transcriptional rate, stability of the mRNA, epigenetics, and pathogenic variants that can affect mRNA production and degradation. Independently from the causes of variable CFTR mRNA levels, their exact quantitative assessment is of great importance in CF. Methods with high analytical sensitivity, precision, and accuracy are mandatory for the quantitative evaluation aimed at the amelioration of the diagnostic, prognostic, and therapeutic aspects. This paper compares, for the first time, two CFTR gene expression quantification methods: a well-established method for the relative quantification of CFTR mRNA using a real-time PCR and an innovative method for its absolute quantification using a droplet digital PCR. No comprehensive methods for absolute CFTR quantification via droplet digital PCR have been published so far. The accurate quantification of CFTR expression at the mRNA level is a critical step for the personalized therapeutic approaches of CF.
Comparative Genomics Reveals Novel Species and Insights into the Biotechnological Potential, Virulence, and Resistance of Alcaligenes
Authors: Pedrosa-Silva Francisnei , Venancio Thiago M.
Published: September 2023

Alcaligenes is a cosmopolitan bacterial genus that exhibits diverse properties which are beneficial to plants. However, the genomic versatility of Alcaligenes has also been associated with the ability to cause opportunistic infections in humans, raising concerns about the safety of these microorganisms in biotechnological applications. Here, we report an in-depth comparative analysis of Alcaligenes species using all publicly available genomes to investigate genes associated with species, biotechnological potential, virulence, and resistance to multiple antibiotics. Phylogenomic analysis revealed that Alcaligenes consists of at least seven species, including three novel species. Pan-GWAS analysis uncovered 389 species-associated genes, including cold shock proteins (e.g., cspA) and aquaporins (e.g., aqpZ) found exclusively in the water-isolated species, Alcaligenes aquatilis. Functional annotation of plant-growth-promoting traits revealed enrichment of genes for auxin biosynthesis, siderophores, and organic acids. Genes involved in xenobiotic degradation and toxic metal tolerance were also identified. Virulome and resistome profiles provide insights into selective pressures exerted in clinical settings. Taken together, the results presented here provide the grounds for more detailed clinical and ecological studies of the genus Alcaligenes.
Searching for Effective Methods of Diagnosing Nervous System Lesions in Patients with Alström and Bardet–Biedl Syndromes
Authors: Waszczykowska Arleta , Jeziorny Krzysztof , Barańska Dobromiła , Matera Katarzyna , Pyziak-Skupien Aleksandra , Ciborowski Michał , Zmysłowska Agnieszka
Published: September 2023

Bardet–Biedl syndrome (BBS) and Alström syndrome (ALMS) are rare multisystem diseases with an autosomal recessive mode of inheritance and genetic heterogeneity, characterized by visual impairment, hearing impairment, cardiomyopathy, childhood obesity, and insulin resistance. The purpose of our study was to evaluate the indicators of nervous system changes occurring in patients with ALMS and BBS using optical coherence tomography (OCT) and magnetic resonance spectroscopy (MRS) methods compared to a group of healthy subjects. The OCT results showed significantly lower macular thickness in the patient group compared to the control group (p = 0.002). The MRS study observed differences in metabolite levels between the study and control groups in brain areas such as the cerebellum, thalamus, and white matter. After summing the concentrations from all areas, statistically significant results were obtained for N-acetylaspartate, total N-acetylaspartate, and total creatine. Concentrations of these metabolites were reduced in ALMS/BBS patients by 38% (p = 0.0004), 35% (p = 0.0008), and 28% (p = 0.0005), respectively. Our results may help to understand the pathophysiology of these rare diseases and identify strategies for new therapies.
Transcriptome and Physiological Analysis Highlight Lignin Metabolism of the Fruit Dots Disordering during Postharvest Cold Storage in ‘Danxiahong’ Pear
Authors: Duan Ruiwei , Zhang Xiangzhan , Liu Yudong , Wang Lei , Yang Jian , Wang Long , Wang Suke , Su Yanli , Xue Huabai
Published: September 2023

Pear (Pyrus L.) is one of the most important fruits in the world. Fruit dots are an important trait that affects pear quality. Abnormal fruit dots usually reduce the merchantability of pears. In this research, during cold storage, ‘Danxiahong’ pear fruit exhibited protrudent fruit dots on the peels. Microscopy system measurement showed that fruit dots size and height on the abnormal fruit peel were bigger and higher than the normal ones. Likewise, scanning electron microscopy observations indicated that the abnormal fruit peel, in contrast to the normal pear peel, exhibited an abnormal cell structure and fruit dots. Physiological analysis showed that the lignin content in abnormal fruit peel was significantly higher than in normal fruit peel. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the top-enriched pathways were mainly associated with lignin synthesis and metabolism. The transcripts of lignin biosynthesis-associated genes were analyzed, and the results showed that the expression of a cascade of structural genes, including PpyPAL, PpyCCR, PpyC3H, PpyC4H, PpyHCT, PpyCAD, PpyLAC, and PpyPOD, was significantly induced in the protrudent peels. Furthermore, the expression of regulatory genes involved in lignin biosynthesis, especially the NAC-MYB-based gene regulatory network, was significantly upregulated in the abnormal peels. Real-time quantitative PCR (RT-qPCR) analysis confirmed the induction of lignin biosynthesis genes. Overall, this research revealed that the abnormal fruit surface was caused by fruit dots disorder during cold storage. This research provides insights into the fine regulation pathways in the prevention of fruit dots protrusion, especially in modulating lignin synthesis and metabolism during postharvest storage.
Characterization and Comparison of the Two Mitochondrial Genomes in the Genus Rana
Authors: Wang Yan-Mei , Zhang Chi-Ying , Luo Si-Te , Ding Guo-Hua , Qiao Fen
Published: September 2023

The mitochondrial genome (mitogenome) possesses several invaluable attributes, including limited recombination, maternal inheritance, a fast evolutionary rate, compact size, and relatively conserved gene arrangement, all of which make it particularly useful for applications in phylogenetic reconstruction, population genetics, and evolutionary research. In this study, we aimed to determine the complete mitogenomes of two morphologically similar Rana species (Rana hanluica and Rana longicrus) using next-generation sequencing. The entire circular mitogenome was successfully identified, with a length of 19,395 bp for R. hanluica and 17,833 bp for R. longicrus. The mitogenomes of both species contained 37 genes, including 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 transfer RNA genes, and one control region; mitogenome size varied predominantly with the length of the control region. The two synonymous codon usages in 13 PCGs showed that T and A were used more frequently than G and C. The ratios of non-synonymous to synonymous substitutions of all 13 PCGs were <1 in the Rana species, indicating that the PCGs were under purifying selection. Finally, phylogenetic relationship analyses suggested that R. hanluica and R. longicrus were classified in the R. japonica group. Our study provides valuable reference material for the taxonomy of the genus Rana.
Exploring the Deuterium Excess of Cretaceous Arctic Paleoprecipitation Using Stable Isotope Composition of Clay Minerals from the Prince Creek Formation (Maastrichtian) in Northern Alaska
Authors: Andrzejewski Kate , Ludvigson Greg , Suarez Marina , McCarthy Paul , Flaig Peter
Published: September 2023

We report estimated stable isotope compositions of Artic paleoprecipitation using phyllosilicates sampled from three paleosols and two bentonites in the Prince Creek Formation (Maastrichtian) in northern Alaska. Previous studies reported a deuterium excess in estimates of Arctic paleoprecipitation from the Late Cretaceous by combining hydrogen and oxygen proxy sources, including pedogenic minerals, dinosaurian tooth enamel phosphates, pedogenic siderites, and n-alkane biomarkers. The new dataset produced in this study removes uncertainty on possible explanations (photosynthetic and transpiration) of the deuterium excess by producing stable hydrogen and oxygen isotopic signatures from the same source material. The δD of the phyllosilicates range from −171‰ to −72‰ VSMOW and δ18O ranges from 5.0 to 11.8‰ VSMOW. By assuming a MAT of 6.3 °C and calculating uniquely derived fractionation equations for each phyllosilicate, we report estimated isotopic composition of Late Cretaceous paleoprecipitation with an average δD value of −133‰ VSMOW, corresponding to an average δ18O value of −20.3‰ VSMOW. The estimates of Late Cretaceous paleoprecipitation do not intersect the Global Meteoric Water Line and reveal a reported deuterium excess ranging from 7 to 46 per mil. These results confirm the presence of a deuterium excess in Late Cretaceous Arctic paleoprecipitation and provide new insight to assessing possible explanations for this phenomenon.
Does Monosodium Urate Crystal Vascular Deposition Exist? Review of the Evidence
Authors: Pascart Tristan , Budzik Jean-François
Published: September 2023

Cardiovascular disease in gout is a central issue, but the underlying mechanisms linking the two are unclear. The existence of monosodium (MSU) crystal deposition directly inflaming vessel walls has been recurrently suggested and challenged since the 1950s and is again a matter of active debate since recent studies using dual-energy computed tomography (DECT) suggested a higher prevalence of plaques considered to be containing MSU crystals in patients with gout. The objective of this review is to critically cover the evidence gathered on MSU crystal deposition in the cardiovascular system. In patients affected with gout, histological evidence of MSU crystals in arteries lacks a biochemical characterization supporting the observation in polarized light microscopy, while current knowledge on vascular lesions identified in DECT as containing MSU crystals suggests that they may be only artifacts, including in cadaveric and phantom studies. In individuals without gout, MSU crystal deposition in vessel walls have not been demonstrated, despite higher urate local plaque concentrations and increased xanthine oxidase activity. Gout is associated with increased arterial calcification and atherosclerosis, both being potential confounders of suspected MSU crystal deposition for the analysis of DECT scans and histopathology, respectively. In summary, the reality of the presence of MSU crystals in vascular plaques has not been demonstrated so far, and needs further investigation as it represents a potential outcome for cardiovascular complications of gout.
A Pilot Fuzzy System with Virtual Reality for Mild Cognitive Impairment (MCI) Assessment
Authors: Liu Cheng-Li , Chuang Che-Jen , Chou Chin-Mei
Published: September 2023

Mild cognitive impairment (MCI) is when brain function declines. MCI is the gray area transitioning from normal aging to the AD stage. Currently, the majority of early MCI diagnoses are processed through comprehensive neuropsychological tests. These tests may take the form of interviews, paper-and-pencil tests, or computer-based tests. There may be resistance from the subject if he/she has to undergo many screening tests simultaneously for multiple evaluation information, resulting in execution difficulty. The objectives of this study are to use 3D virtual reality to create an entertaining test scenario integrating the Mini-Cog, SPMSQ, MMSE, SLUMS, CDR, and CASI for middle-aged to older adults, furthermore, to employ fuzzy logic control (FLC) technology to develop a “MCI assessment system” for obtaining some pilot information for MCI assessment. There were 24 middle-aged to older adults aged from 50 to 65 years who participated in the evaluation experiment. The results showed that the MCI assessment system developed in this study is highly correlated with the traditional screening tests, including the Mini-Cog, SPMSQ, MMSE, SLUMS, and CASI. The assessment system can provide an integrated reference score for clinic workers in making judgments. In addition, the distribution of the System Usability Scale (SUS) evaluation scores for the MCI assessment system revealed that 87.5% were grade C (good to use) or above and 29.2% were grade B (extremely good to use) or above. The assessment system received positive feedback from the subjects.
An Examination of Subjective and Objective Measures of Stress in Tactical Populations: A Scoping Review
Authors: Tramel Whitney , Schram Ben , Canetti Elisa , Orr Robin
Published: September 2023

Persons working in tactical occupations are often exposed to high-stress situations. If this stress is to be measured, an understanding of the stress outcomes used in these occupations is needed. The aim of this review was to capture and critically appraise research investigating subjective and objective outcome measures of physiological stress in tactical occupations. Several literature databases (PubMed, EMBASE, EBsco) were searched using key search words and terms. Studies meeting inclusion criteria were critically evaluated and scored by two authors using the Joanne Briggs Institute (JBI) critical appraisal tool. Of 17,171 articles, 42 studies were retained. The Cohen’s Kappa agreement between authors was 0.829 with a mean JBI Score of included studies of 8.1/9 ± 0.37 points. Multiple subjective and objective measures were assessed during a variety of high-stress tasks and environments across different occupations, including police officers, emergency service personnel, firefighters, and soldiers in the military. Common objective outcomes measures were heart rate, cortisol, and body temperature, and subjective measures were ratings of perceived exertion, and the Self Trait Anxiety Inventory. Often used in combination (i.e., subjective and objective), these outcome measures can be used to monitor stressors faced by tactical personnel undergoing on-the-job training.
Non-Destructive Testing of Dalle de Verre Windows by Fernand Léger and Alexandre Cingria in Switzerland
Authors: Hugenschmidt Johannes , Wolf Sophie , Gosselin Christophe
Published: September 2023

Dalle de verre windows consist of thick slabs of coloured glass set in a matrix of reinforced concrete. The invention of this special art form is closely linked to the developments in modern architecture in the first half of the 20th century that are characterized by using new technologies such as steel-frame construction, reinforced concrete and the increasing use of glass. Many of these windows are showing damage, some of it severe. Until now, the causes of damage have hardly been investigated and there is still no practical and suitable approach to the analysis of the state of conservation of dalle de verre glazings. One of the main objectives of an interdisciplinary project (2019–2021) was therefore to evaluate the potential of non-destructive techniques for the characterisation of and identification of damage of dalle the verre windows in their structural, physical and climatic context. Various non-destructive methods (Ground-Penetrating Radar, Electric resistivity, Half-cell potential, Ultrasonics, Induction, Magnet and Thermography) have been tested on two prominent dalle de verre examples: the windows created by Fernand Léger for the church of Saint-Germain d’Auxerre in Courfaivre (Swiss Jura mountains) and the large tripartite by Alexandre Cingria once decorating the choir window church of the Franciscan monastery at Fribourg, Switzerland. The results of the analyses presented in this paper provide valuable information on the advantages and limitations as well as the costs of the methods used.
Exogenous Selenium Enhances Cadmium Stress Tolerance by Improving Physiological Characteristics of Cabbage (Brassica oleracea L. var. capitata) Seedlings
Authors: Jia Kaiyue , Zhan Zhipeng , Wang Bingqian , Wang Wuhong , Wei Wenjing , Li Dawei , Huang Wei , Xu Zhongmin
Published: September 2023

In recent years, the levels of cadmium (Cd) in agricultural soils have been increasing. Cd is highly toxic and can enter the human body through the food chain, threatening human health, therefore, reducing the Cd content in vegetables and producing green and non-polluting food has become a common concern in society. However, the physiological properties of exogenous selenium in alleviating Cd stress in cabbage seedlings have not been thoroughly investigated. In this study, exogenous Se (10 μMol/L) was applied under Cd (25 μMol/L) stress and the physiological characteristics such as biomass, photosynthetic fluorescence parameters, Se and Cd contents, chloroplast ultrastructure, leaf membrane esterification, and antioxidant enzyme activities were determined. The results showed that the exogenous application of Se could effectively alleviate the decrease in growth, photosynthetic pigment, and the gas exchange characteristics of the cabbage seedlings under Cd stress, improve cabbage root vitality, reduce root leaf Cd content, and alleviate the Cd stress-induced damage. Ultrastructural observation showed that the Cd stress caused the disruption to the chloroplasts’ internal structure in the cabbage leaves, while an exogenous Se treatment alleviated the chloroplast damage to some extent, improved the stability of the inner capsule membrane, and alleviated the Cd stress-induced damage to the photosynthetic organs. Cd stress also caused oxidative damage and the excessive accumulation of reactive oxygen species (ROS) in the leaves of cabbage seedlings, as evidenced by the significant accumulation of superoxide anion (O2−), hydrogen peroxide (H2O2), malondialdehyde (MDA), and electrolyte leakage. On the other hand, after the exogenous Se treatment, the Cd stress-induced oxidative damage could be reduced by up-regulating the activities of the antioxidant enzymes, such as superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX). At the same time, Cd stress significantly increased glutathione (GSH) levels, and the exogenous Se treatment further increased the GSH levels, thereby increasing the tolerance of the cabbage to Cd stress. In conclusion, exogenous Se can further improve the Cd tolerance of the cabbage seedlings by protecting the photosynthetic system, eliminating excessive accumulation of reactive oxygen species under Cd stress, alleviating oxidative stress, and reducing Cd levels in plants, among other physiological properties.
Treating Garlic Seed Cloves with Negative Temperatures Increases the Productivity of Noble Garlic in the Brazilian Semi-Arid Region
Authors: Morais Éric George , Grangeiro Leilson Costa , Resende Francisco Vilela , Negreiros Maria Zuleide de , Oliveira Renata Ramayane Torquato , Pereira Dalbert de Freitas , Santos Elidayane da Nóbrega , Costa Romualdo Medeiros Cortez , Queiroz Gabriela Carvalho Maia de , Carmo Luiz Henrique de Araujo
Published: September 2023

The treatment with low temperatures, for a certain period, stimulates the accumulation of phytohormones in garlic seed cloves, which influence the growth and development of the plants. Thus, this work aimed to evaluate the effects of garlic seed cloves under negative temperatures for different periods on the development and productivity of noble garlic cultivated in the Brazilian semi-arid region. Two experiments were carried out and analyzed separately in the municipalities of Mossoró and São Miguel, RN, Brazil, in which three temperature ranges (−5 to −3 °C, −2 to 0 °C and 1 to 3 °C) and three periods (50, 55, and 60 days) were tested. Low-temperature conditioning of the garlic seed cloves was carried out in a temperature-controlled freezer. Relative humidity during treatment ranged from 60 to 70%. Seed cloves submitted to temperatures below zero provided the differentiation of cloves, even in unfavorable edaphoclimatic conditions for cultivating noble garlic. Seed cloves conditioned with negative temperatures increased the productivity of garlic grown in Mossoró, but with a lower average yield than garlic produced in São Miguel. Garlic seed cloves treated at negative temperatures in São Miguel provided garlic productivity equivalent to the yield of garlic grown in the states of the southern region. In addition, it produced class 6 and 7 bulbs, which have greater commercial value and acceptance by consumers. The results demonstrated the potential of garlic seed cloves treated with temperatures below zero to increase the production of noble garlic in the semi-arid region of the country.
Identification and Expression Analysis of Adenylate Kinase Gene Family in Potato
Authors: Li Xiang , Lyu Chengcheng , Song Jun , Lu Yifei , Zeng Fuchun , Lu Liming , Li Liqin
Published: September 2023

Adenylate kinase (ADK) is a key enzyme that is widely distributed in animals and plants. It plays an important role in growth and stress response. However, ADK genes in potato (StADK) have been little reported. It is of great significance to identify ADK members and understand the molecular mechanism of stress response and tolerance. Based on the potato genome data, 23 StADK genes were identified at a genome-wide level. We then performed a comprehensive study using a bioinformatics method. The results of the evolutionary tree showed that StADK proteins were divided into four groups, and they were highly homologous to the Arabidopsis thaliana ADK members. Meanwhile, our study found that they existed on eight chromosomes, and we obtained three pairs of fragment duplications. Furthermore, we detected the six selected StADK genes using qRT-PCR, and the results confirmed that the genes are involved in the regulation of cold, ABA, salt, H2O2 and drought stresses. Our study provides a theoretical basis for studying the function of the potato ADK genes and lays a solid foundation for further understanding the molecular mechanism of the potato ADK genes under various environmental stresses.
Comparison of hs-CRP in Adult Obesity and Central Obesity in Indonesia Based on Omega-3 Fatty Acids Intake: Indonesian Family Life Survey 5 (IFLS 5) Study
Authors: Megawati Ginna , Indraswari Noormarina , Johansyah Alexandra Aurelia , Kezia Capella , Herawati Dewi Marhaeni Diah , Gurnida Dida Achmad , Musfiroh Ida
Published: September 2023

Obesity and central obesity are associated with dire conditions, such as metabolic syndrome, in which low-grade inflammation plays a part. C-reactive protein (CRP) is an inflammatory marker found to be elevated in those conditions. Omega-3 fatty acids work against inflammation and lower CRP levels in obese individuals. This study compared high-sensitivity CRP (hs-CRP) in adult obesity and central obesity in Indonesia based on omega-3 fatty acid intake using Indonesian Family Life Survey (IFLS) 5 data. Secondary data from household questionnaires were obtained from the IFLS 5 online database. Data from 3152 subjects were used; 76.65% of the subjects were female, with a mean age of 45.27 ± 15.77 years. Subjects were classified into five modified categories of obesity and central obesity based on body mass index (BMI) and waist circumference (WC). Omega-3 fatty acid intake was categorized into “low” and “adequate” based on dietary recommendations from the Mediterranean Diet Foundation (2011). There is a significant difference in hs-CRP based on modified obesity categories (p < 0.05). There was no significant difference in hs-CRP between low and adequate omega-3 intake (p > 0.05). These data suggest that hs-CRP is related to overweight, obesity, and central obesity. Meanwhile, omega-3 fatty acids are unrelated to hs-CRP. Further studies are needed to confirm these results.
The MothersBabies Study, an Australian Prospective Cohort Study Analyzing the Microbiome in the Preconception and Perinatal Period to Determine Risk of Adverse Pregnancy, Postpartum, and Child-Related Health Outcomes: Study Protocol
Authors: Strout Naomi , Pasic Lana , Hicks Chloe , Chua Xin-Yi , Tashvighi Niki , Butler Phoebe , Liu Zhixin , El-Assaad Fatima , Holmes Elaine , Susic Daniella , Samaras Katherine , Craig Maria E. , Davis Gregory K. , Henry Amanda , Ledger William L. , El-Omar Emad M.
Published: September 2023

The microbiome has emerged as a key determinant of human health and reproduction, with recent evidence suggesting a dysbiotic microbiome is implicated in adverse perinatal health outcomes. The existing research has been limited by the sample collection and timing, cohort design, sample design, and lack of data on the preconception microbiome. This prospective, longitudinal cohort study will recruit 2000 Australian women, in order to fully explore the role of the microbiome in the development of adverse perinatal outcomes. Participants are enrolled for a maximum of 7 years, from 1 year preconception, through to 5 years postpartum. Assessment occurs every three months until pregnancy occurs, then during Trimester 1 (5 + 0–12 + 6 weeks gestation), Trimester 2 (20 + 0–24 + 6 weeks gestation), Trimester 3 (32 + 0–36 + 6 weeks gestation), and postpartum at 1 week, 2 months, 6 months, and then annually from 1 to 5 years. At each assessment, maternal participants self-collect oral, skin, vaginal, urine, and stool samples. Oral, skin, urine, and stool samples will be collected from children. Blood samples will be obtained from maternal participants who can access a study collection center. The measurements taken will include anthropometric, blood pressure, heart rate, and serum hormonal and metabolic parameters. Validated self-report questionnaires will be administered to assess diet, physical activity, mental health, and child developmental milestones. Medications, medical, surgical, obstetric history, the impact of COVID-19, living environments, and pregnancy and child health outcomes will be recorded. Multiomic bioinformatic and statistical analyses will assess the association between participants who developed high-risk and low-risk pregnancies, adverse postnatal conditions, and/or childhood disease, and their microbiome for the different sample types.
Autistic Traits Related to the Importance of Interpersonal Touch and Appreciation of Observed Touch during COVID-19 Social Distancing
Authors: de Jong Jutta R. , Dijkerman Hendrik Christiaan , Keizer Anouk
Published: September 2023

Studies have confirmed the significance of touch for psychological wellbeing. Social distancing regulations during the COVID-19 pandemic reduced people’s ability to engage in interpersonal touch and caused increased an appreciation for observed touch, as well as a longing for touch within the neurotypical population. Yet, while the impact of social distancing and the importance of touch are evident in neurotypical individuals, it remains unclear how these factors manifest in autistic individuals. Previous research has related high levels of autistic traits to reduced levels of perceived pleasantness of touch and a reduced interest in interpersonal touch. Our study aimed to examine the differences in the appreciation of observed touch and longing for touch during social distancing between individuals with low and high levels of autistic traits. We conducted an online survey on autistic traits, the appreciation of observed CT-optimal touch and longing for touch. Consistent with our predictions, our results confirmed that individuals with high levels of autistic traits evaluated videos depicting CT-optimal touch less favorably compared to those with lower scores on autistic traits. Additionally, only the group with low levels of autistic traits exhibited a longing for touch during social distancing, whereas the group with high levels of autistic traits did not. The results provide insights in the appreciation of touch in relation to autistic traits during the unique circumstances of the COVID-19 pandemic.
Expert Perspectives on the Effectiveness of Psychotherapy
Authors: Löffler-Stastka Henriette , Ronge-Toloraya Andreas , Hassemer Simeon , Krajic Karl
Published: September 2023

The effectiveness of psychotherapeutic care, as well as the implementation of adequate improvements, are in question. A qualitative interview study was carried out in a cyclical research design with a comparative analysis on the basis of thematic coding using Grounded Theory Methodology. An overview of the design, sampling procedure, and data analysis is given. A variety of critical perspectives emerged concerning the state of psychotherapeutic care in Austria. Two perspectives are presented in this paper as interim results: a health care administration perspective states a general lack of knowledge and a possible unmet need, problematizes the underutilized benefit of psychotherapists and describes a shift in regard to the issue of effectiveness of care to the topic of access to psychotherapeutic care and to a problem with the care and work ethics of professionals. In this perspective, one solution may be to implement intermediary organizations, clearinghouses with multi-professional teams, comprehensive documentation and an indication-oriented approach. The health insurance perspective also claims the organization-specific action problem and the lack of rules for clearing in such intermediary organizations, as well as the relevance of regulated, limited access to psychotherapy.
Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts
Authors: Inoue Sho , Inahashi Yuki , Itakura Makoto , Inoue Gen , Muneshige Kyoko , Hirose Tomoyasu , Iwatsuki Masato , Takaso Masashi , Miyagi Masayuki , Uchida Kentaro
Published: September 2023

Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease.
Non-Targeted Screening of Metabolites in Aqueous-Ethanol Extract from Spiraea hypericifolia (Rosaceae) Using LC-HRMS
Authors: Kostikova Vera A. , Petrova Natalia V. , Shaldaeva Tatiana M. , Koval Vladimir V. , Chernonosov Alexander A.
Published: September 2023

By means of liquid chromatography combined with high-resolution mass spectrometry, metabolite profiling was performed on an aqueous-ethanol extract from Spiraea hypericifolia (Rosaceae) collected in Siberia (Russia). Up to 140 compounds were found in the extract, of which 47 were tentatively identified. The identified compounds were amino acids, sugars, phenylpropanoids, fatty acids and their derivatives, triterpenoids, flavonoids, and others. A quantitative analysis showed the predominance of phenolcarboxylic acids and flavonoids in the studied extract, but a qualitative analysis revealed the higher structural diversity of flavonoids. Of the 23 identified flavonoids, 13 were flavonols: quercetin, hyperoside, isoquercitrin, reynoutrin, avicularin, rutin, quercetin-3-O-(6″-O-malonyl)-β-D-glucoside, 3-O-methylquercetin-3′-O-β-D-glucopyranoside, isorhamnetin, rhamnetin-3-O-β-D-xylopyranosyl-β-D-glucopyranoside, kaempferol, tiliroside, and trifolin; six were catechins: catechin, (−)-epicatechin, (+)-epicatechin, (+)-catechin-7-O-β-D-xyloside, (2S,3R)-3,5-dihydroxy-2-(4-hydroxyphenyl)-3,4-dihydro-2H-chromen-7-yl-β-D-glucopyranoside, and catechin 7-O-apiofuranoside; two are isoflavones: genistin and genistein; and one was a flavone (luteolin-4′-O-β-D-glucopyranoside) and another was an anthocyanidin (pelargonidin). The aqueous-ethanol extract from S. hypericifolia showed antioxidant activity (half-maximal inhibitory concentration 102.95 μg/mL), which was likely related to the high concentrations of phenolcarboxylic acids (229.6 mg/g), flavonoids (118.3 mg/g), and tannins (62.9 mg/g).
Milk-Derived Small Extracellular Vesicles Promote Osteogenic Differentiation and Inhibit Inflammation via microRNA-21
Authors: Liu Runyuan , Liu Shuo , Wu Saixuan , Xia Meng , Liu Wanqing , Wang Lina , Dong Ming , Niu Weidong
Published: September 2023

Chronic apical periodontitis (CAP) is a disease with characteristics of inflammation and bone loss. In this study, our objective was to examine the function of small extracellular vesicles (sEVs) obtained from milk in encouraging osteogenic differentiation and inhibiting inflammation by miR-21 in CAP. The expression of miR-21 was detected using qRT-PCR in human CAP samples. The impact of miR-21 on the process of osteogenic differentiation was investigated using CCK-8, qRT-PCR, immunofluorescence staining, and Western blot analysis. The evaluation of RAW 264.7 cell polarization and the assessment of inflammatory factor expression were conducted through qRT-PCR. The influence of sEVs on MC3T3-E1 cells and RAW 264.7 cells was examined, with a particular emphasis on the involvement of miR-21. In human CAP samples, a decrease in miR-21 expression was observed. MiR-21 increased the expression of osteogenesis-related genes and M2 polarization genes while decreasing the expression of M1 polarization genes and inflammatory cytokines. Treatment with milk-derived sEVs also promoted osteogenesis and M2 polarization while inhibiting M1 polarization and inflammation. Conversely, the addition of miR-21 inhibitors resulted in opposite effects. Our results indicated that sEVs derived from milk had a positive effect on bone formation and activation of anti-inflammatory (M2) macrophages and simultaneously reduced inflammation by regulating miR-21 in CAP.
Prospective Evaluation of the BD MAX StaphSR Assay for the Screening of Methicillin-Susceptible and -Resistant Staphylococcus aureus from Nasal Swabs Taken in Intensive Care Unit Patients
Authors: Fayolle Martin , Epercieux Amélie , Haddar Cyrille H. , Pillet Sylvie , Berthelot Philippe , Pozzetto Bruno , Carricajo Anne , Grattard Florence , Verhoeven Paul O.
Published: September 2023

Screening patients for S. aureus nasal carriage has proved effective in preventing cross-contamination and endogenous infection with this bacterium. The aim of this study was to assess the performance of the BD MAX StaphSR assay with liquid Amies elution swabs, taken during routine care of intensive care unit patients. Direct and pre-enriched cultures were used as reference methods to screen for S. aureus and methicillin-resistant S. aureus (MRSA). Discrepant results between the BD MAX StaphSR assay and cultures were resolved by using the Xpert SA Nasal Complete assay. A total of 607 nasal swabs taken from 409 patients were included in this study. Compared to culture methods, the sensitivity and specificity of the BD MAX StaphSR assay were 92.5% and 91.7% for S. aureus screening, and 94.7% and 98.3% for MRSA screening, respectively. In 52 (8.6%) specimens, there was a discrepancy between the results of cultures and the BD MAX StaphSR assay, including 13 (25%) where the results of the BD MAX StaphSR assay were confirmed by the Xpert SA Nasal Complete test. This prospective study showed that the BD MAX StaphSR assay is reliable for S. aureus and MRSA detection from nasal samples taken with liquid Amies elution swabs.
Characterization and Functional Analysis of Chalcone Synthase Genes in Highbush Blueberry (Vaccinium corymbosum)
Authors: Zhang Zening , Qu Pengyan , Hao Siyi , Li Ruide , Zhang Yongyan , Zhao Qi , Wen Pengfei , Cheng Chunzhen
Published: September 2023

Chalcone synthase (CHS) is the first key enzyme-catalyzing plant flavonoid biosynthesis. Until now, however, the blueberry CHS gene family has not been systematically characterized and studied. In this study, we identified 22 CHS genes that could be further classified into four subfamilies from the highbush blueberry (Vaccinium corymbosum) genome. This classification was well supported by the high nucleotide and protein sequence similarities and similar gene structure and conserved motifs among VcCHS members from the same subfamily. Gene duplication analysis revealed that the expansion of the blueberry CHS gene family was mainly caused by segmental duplications. Promoter analysis revealed that the promoter regions of VcCHSs contained numerous cis-acting elements responsive to light, phytohormone and stress, along with binding sites for 36 different types of transcription factors. Gene expression analysis revealed that Subfamily I VcCHSs highly expressed in fruits at late ripening stages. Through transient overexpression, we found that three VcCHSs (VcCHS13 from subfamily II; VcCHS8 and VcCHS21 from subfamily I) could significantly enhance the anthocyanin accumulation and up-regulate the expression of flavonoid biosynthetic structural genes in blueberry leaves and apple fruits. Notably, the promoting effect of the Subfamily I member VcCHS21 was the best. The promoter of VcCHS21 contains a G-box (CACGTG) and an E-box sequence, as well as a bHLH binding site. A yeast one hybridization (Y1H) assay revealed that three anthocyanin biosynthesis regulatory bHLHs (VcAN1, VcbHLH1-1 and VcbHLH1-2) could specifically bind to the G-box sequence (CACGTG) in the VcCHS21 promoter, indicating that the expression of VcCHS21 was regulated by bHLHs. Our study will be helpful for understanding the characteristics and functions of blueberry CHSs.
Paying Comprehensive Attention to the Temperature-Dependent Dual-Channel Excited-State Intramolecular Proton Transfer Mechanism of Fluorescence Ratio Probe BZ-DAM
Authors: Gao Jiaan , Zhang Yifu , Mu Hongyan , Yang Min , Guan Xiaotong , Jin Guangyong , Li Hui
Published: September 2023

The mechanism of fluorescence detection of diethyl chlorophosphate (DCP) based on 2-substituted benzothiazole (BZ-DAM) was studied by a theoretical calculation method. It should not be ignored that both the BZ-DAM and the detection product BZ-CHO have two excited-state intramolecular proton transfer (ESIPT) channels. Density functional theory (DFT) and time-dependent DFT (TDDFT) theory were used to study the photophysical mechanism of two compounds in two channels in (acetonitrile) ACN solvent, and the temperature dependence of the two channels was given. Channel 1 is more likely to exist at low temperatures and channel 2 is more likely to exist at high temperatures. By theoretical analysis of the constructed potential energy curve, the hydrogen bond energy and electron-hole analysis, we confirmed that both molecules undergo ESIPT and intramolecular charge transfer (ICT) processes in channel 1 and ESIPT and twisted intramolecular charge transfer (TICT) coupling processes in channel 2. The formation of product BZ-CHO molecules led to a significant fluorescence blue-shift phenomenon and inhibited the ICT process, which confirmed that BZ-DAM could be used as a fluorescence probe for fluorescence detection. We sincerely hope that this work will not only help to clarify the excited-state dynamics behavior of the BZ-DAM probe but also provide a new idea for designing and optimizing a new chemical dosimeter.
Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies
Authors: Buccellato Francesca R. , D’Anca Marianna , Tartaglia Gianluca Martino , Del Fabbro Massimo , Scarpini Elio , Galimberti Daniela
Published: September 2023

In an ever-increasing aged world, Alzheimer’s disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55 million people affected, the WHO considers AD to be a disease with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies are aimed to mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) and the N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, the best approaches for managing the disease seem to combine pharmacological and non-pharmacological therapies to stimulate cognitive reserve. Over the last twenty years, a number of drugs have been discovered acting on the well-established biological hallmarks of AD, deposition of β-amyloid aggregates and accumulation of hyperphosphorylated tau protein in cells. Although previous efforts disappointed expectations, a new era in treating AD has been working its way recently. The Food and Drug Administration (FDA) gave conditional approval of the first disease-modifying therapy (DMT) for the treatment of AD, aducanumab, a monoclonal antibody (mAb) designed against Aβ plaques and oligomers in 2021, and in January 2023, the FDA granted accelerated approval for a second monoclonal antibody, Lecanemab. This review describes ongoing clinical trials with DMTs and non-pharmacological therapies. We will also present a future scenario based on new biomarkers that can detect AD in preclinical or prodromal stages, identify people at risk of developing AD, and allow an early and curative treatment.
Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes
Authors: Weawsiangsang Sattaporn , Rattanachak Nontaporn , Jongjitvimol Touchkanin , Jaifoo Theerasak , Charoensit Pensri , Viyoch Jarupa , Ross Sukunya , Ross Gareth M. , Baldock Robert A. , Jongjitwimol Jirapas
Published: September 2023

Hydroquinine has antimicrobial potential with demonstrated activity against several bacteria, including multidrug-resistant (MDR) P. aeruginosa reference strains. Despite this, there is limited evidence confirming the antibacterial activity of hydroquinine against clinical isolates and the underlying mechanism of action. Here, we aimed to investigate the antibacterial effect of hydroquinine in clinical P. aeruginosa strains using phenotypic antimicrobial susceptibility testing and synergistic testing. In addition, we examined the potential inhibitory mechanisms against MDR P. aeruginosa isolates using informatic-driven molecular docking analysis in combination with RT-qPCR. We uncovered that hydroquinine inhibits and kills clinical P. aeruginosa at 2.50 mg/mL (MIC) and 5.00 mg/mL (MBC), respectively. Hydroquinine also showed partial synergistic effects with ceftazidime against clinical MDR P. aeruginosa strains. Using SwissDock, we identified potential interactions between arginine deiminase (ADI)-pathway-related proteins and hydroquinine. Furthermore, using RT-qPCR, we found that hydroquinine directly affects the mRNA expression of arc operon. We demonstrated that the ADI-related genes, including the arginine/ornithine antiporter (arcD) and the three enzymes (arginine deiminase (arcA), ornithine transcarbamylase (arcB), and carbamate kinase (arcC)), were significantly downregulated at a half MIC of hydroquinine. This study is the first report that the ADI-related proteins are potential molecular targets for the inhibitory effect of hydroquinine against clinically isolated MDR P. aeruginosa strains.
Association between the Cytosine Hydroxymethylation and the Expression of microRNA in Multiple Sclerosis in Polish Population
Authors: Basak Justyna , Piotrzkowska Danuta , Kucharska-Lusina Aleksandra , Majsterek Ireneusz
Published: September 2023

Multiple sclerosis is a chronic demyelinating disorder with an unclear etiology. A key role is thought to be played by Th17 cells and microRNAs associated with Th17, such as miR-155, miR-326 and miR-223. The present study compared the methylation and hydroxymethylation levels of CpG sites within promoters of these microRNA between MS patients and controls using PBMCs and analyzed their relationship with microRNA expression. Significant intergroup differences were found between the levels of 5-hmC within the CpG-1 miR-155 promoter and CpG within the miR-326 promoter; in addition, miR-155-5p and miR-223-3p expression was elevated in MS patients. Correlation analysis showed a positive relationship between the level of 5-hmC of CpG-2 in the miR-223 promoter and miR-223-3p level. As it is possible to pharmacologically modulate the level of epigenetic modifications, our findings cast light on the etiology of MS and support the development of more effective therapies.
In Silico Analysis Reveals the Modulation of Ion Transmembrane Transporters in the Cerebellum of Alzheimer’s Disease Patients
Authors: D’Angiolini Simone , Basile Maria Sofia , Mazzon Emanuela , Gugliandolo Agnese
Published: September 2023

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. AD hallmarks are extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles in the brain. It is interesting to notice that Aβ plaques appear in the cerebellum only in late stages of the disease, and then it was hypothesized that it can be resistant to specific neurodegenerative mechanisms. However, the role of cerebellum in AD pathogenesis is not clear yet. In this study, we performed an in silico analysis to evaluate the transcriptional profile of cerebellum in AD patients and non-AD subjects in order to deepen the knowledge on its role in AD. The analysis evidenced that only the molecular function (MF) “active ion transmembrane transporter activity” was overrepresented. Regarding the 21 differentially expressed genes included in this MF, some of them may be involved in the ion dyshomeostasis reported in AD, while others assumed, in the cerebellum, an opposite regulation compared to those reported in other brain regions in AD patients. They might be associated to a protective phenotype, that may explain the initial resistance of cerebellum to neurodegeneration in AD. Of note, this MF was not overrepresented in prefrontal cortex and visual cortex indicating that it is a peculiarity of the cerebellum.