bluuebunny/crossref_metadata_2025 huggingface dataset:
Geoheritage Value of Three Localities from Kislovodsk in the Southern Central Ciscaucasus: A Resource of Large Resort Area
Authors: Yashalova Natalia N. , Ruban Dmitry A.
Published: May 2024

Many geographical domains possess notable geological and geomorphological features, which are yet to be characterized comprehensively in terms of geoheritage. The present study focuses on the Kislovodsk area, which is situated in the southern part of the Central Ciscaucasus (post-Paleozoic platform), where the latter joins to the Greater Caucasus (late Cenozoic orogen). Three geosites are reported from there, and their qualitative description and semi-quantitative, score-based assessment are offered. The Honey Waterfalls represent an example of river erosion affecting Carboniferous granitoids with uppermost Jurassic weathering horizon and overlain by Lower Cretaceous carbonates. The Ring Mountain is a natural arch formed as result of wind erosion. The Little Saddle is a viewpoint offering a spectacular, panoramic view toward the Elbrus Mountain that is the highest peak of Russia and Europe and an impressive dormant stratovolcano. The Honey Waterfalls and the Ring Mountain are ranked nationally (the latter receives the highest total scores), and the Little Saddle is ranked regionally. These geosites are diverse in several aspects, and, particularly, different geoheritage types and forms are established. The Kislovodsk area bearing the reported geoheritage objects is a part of the Mineralnye Vody resort area, which is large and important for the national tourism and recreation industry. The related opportunities and challenges for geoheritage resource management have to be considered.
Association between Height-Changing Scores and Risk of Sarcopenia Estimated from Anthropometric Measurements in Older Adults: A Cross-Sectional Study
Authors: Srikrajang Siwaluk , Komolsuradej Narucha
Published: May 2024

Anthropometric assessments are commonly used to diagnose sarcopenia in older adults. However, the ongoing exploration of novel approaches aims to improve the early detection of sarcopenia. This study investigated the association between the height-changing score (HCS) and the risk of sarcopenia defined by anthropometric measurements in 340 older adults (mean age: 66.2 years). The HCS derived from the difference in height and demi-span equivalent height (DEH) was used as an indicator of declining height in the older adults. Multivariate logistic regression analysis revealed a significant association between the HCS and the risk of sarcopenia in both male and female older adults (OR = 1.146, 95% CI [1.021, 1.286], p = 0.021). In addition, income, BMI, and nutritional status were significantly associated with the risk of sarcopenia (OR = −1.933, 95% CI [0.271, 0.986], p = 0.045; OR = −2.099, 95% CI [0.386, 0.587], p < 0.001; OR = −1.443, 95% CI [0.555, 0.866], p = 0.001, respectively). The white blood cell count, lymphocyte count, and HDL cholesterol were blood biomarkers significantly correlated with calf circumference. It can be suggested that the HCS acts as an indicator and screening tool for sarcopenia risk in older adults, highlighting the potential impact of decreased height on muscle mass loss. Encouraging nutritional support can help mitigate the risk of sarcopenia.
Assessment of Dietary and Lifestyle Quality among the Romanian Population in the Post-Pandemic Period
Authors: Mititelu Magdalena , Popovici Violeta , Neacșu Sorinel Marius , Musuc Adina Magdalena , Busnatu Ștefan Sebastian , Oprea Eliza , Boroghină Steluța Constanța , Mihai Andreea , Streba Costin Teodor , Lupuliasa Dumitru , Gheorghe Emma , Kebbewar Nadin , Lupu Carmen Elena
Published: May 2024

Background: The pandemic caused by the SARS-CoV-2 virus demonstrated the importance of prevention through a healthy diet and lifestyle, the most vulnerable people being those with severe chronic conditions, those who are overweight, and those with an unbalanced immune system. This study aims to examine the nutritional status and lifestyle behaviors of the Romanian population. Methods: The evaluation of the eating habits and lifestyle of the Romanian population in the post-pandemic period was carried out based on a cross-sectional observational study with the help of a questionnaire. Results: A total of 4704 valid answers were registered (3136 female and 1568 male respondents). Among the respondents, most of them belong to the young population, 2892 between the ages of 18 and 40, i.e., 61.5%. Most male respondents are overweight (1400) and obese (780). Most respondents indicated a tendency to consume 1–2 meals per day irregularly (p = 0.617). Only 974 respondents adopted a healthy diet, and 578 a healthy lifestyle. Conclusions: The present study reports low adherence to a healthy diet (20.7%) and healthy lifestyle (12.28%), especially among the young population (<30 years). In the current context, it reports a reduced tendency to consume vegetables and fruits among the population, below the daily average recommended by the nutrition guidelines, a tendency towards sedentary behavior, and even deficient hydration of some of the respondents; these negative aspects can create a long-term series of nutritional and psycho-emotional imbalances. Our results evidence that complex surveys among the population are regularly required to investigate nutritional or lifestyle deficiencies; moreover, it could be helpful in further educational measures in nutrition, food, and environmental safety.
Caregiver Employees’ Mental Well-Being in Hong Kong
Authors: Lee Maggie Man-Sin , Yeoh Eng-Kiong , Wang Kailu , Wong Eliza Lai-Yi
Published: May 2024

Background: The rapidly aging global population has increased the demand for caregivers. Many caregivers simultaneously engage in paid employment, and the dual role makes the needs of caregiver employees conceivably more remarkable. However, there is a gap in the literature about the specific needs of caregiver employees. Method: Caregiver employees (n = 1205) across Hong Kong caring for those ≥65 years were recruited for a cross-sectional face-to-face survey from December 2021 to January 2022, to evaluate mental well-being measured by the Short Warwick –Edinburgh Mental Well-being Scale. Univariate and multivariate analyses were conducted; significant variables (p < 0.05) were included in multiple linear regression, along with caregiver-friendly workplace policies’ availability, to understand their association with their mental well-being. Findings: The mean score of the Short Warwick–Edinburgh Mental Well-being Scale among caregiver employees in this study was 24.9, with 7.2% indicative of probable clinical depression and 10.0% possible mild depression. In addition, the current study showed that 30.2% of the caregiver employees felt distressed about the caregiving role. Among external factors, family support (measured by the Lubben Social Network Scale) and workplace culture (measured by the Marshall Supervision Subscale) positively correlated with mental well-being with regression coefficients of 0.252 (p < 0.001) and 0.482 (p < 0.001), respectively. In the fully adjusted model, a negative regression coefficient was observed for overall spillover (−0.050, p < 0.001) and Short Warwick–Edinburgh Mental Well-being Scale scores, while positive regression coefficients were observed for overall self-rate (0.041, p < 0.001), Lubben (0.124, p < 0.001), and corporate culture (0.365, p < 0.001). Better Short Warwick–Edinburgh Mental Well-being Scale scores were observed when caregiver-friendly workplace policies were clearly stated than when they were made on a case-by-case discretionary basis. Conclusions: Caregiver-friendly workplace policies may be critical to Hong Kong’s sustainable future, both economically and socially, as they ensure a healthy and productive workforce to support an aging population.
Efficacy and Safety of Bojungikgi-Tang for Persistent Allergic Rhinitis: A Randomized, Double-Blinded, Placebo-Controlled, Phase II Trial
Authors: Lee Su Won , Woo Seong-Cheon , Lyu Yee Ran , Yang Won-Kyung , Kim Seung-Hyung , Kim Je Hyun , Kim Si Yeon , Kang Weechang , Jung In Chul , Kim Taesoo , Park Yang Chun
Published: May 2024

Conventional treatments for allergic rhinitis (AR) exhibit insufficiency and long-term use-related side effects. Considering the reported anti-inflammatory and immunoregulatory effects of Bojungikgi-tang (BJIGT), we aimed to assess its efficacy on persistent AR (PAR). Patients with PAR were randomly assigned in a 1:1:1 ratio into high-dose BJIGT, standard-dose BJIGT, and placebo groups, followed by 1-week run-in and 4-week treatment periods. The primary outcome included the mean change in Total Nasal Symptom Score (TNSS), with secondary outcomes encompassing the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, biomarkers, overall assessment, TNSS by AR pattern identification, and the Sasang constitution. The mean TNSS change was more improved in the BJIGT group than in the placebo group; however, no statistically significant differences were observed. Additional interaction effect analysis revealed a statistically significant improvement in the high-dose BJIGT group compared with the placebo group from weeks 1–2 to weeks 3–4. Regarding secondary outcomes, the BJIGT group exhibited similar or improved results compared with the placebo group, showing no statistically significant differences. No serious adverse effects or clinically significant changes in safety assessments were observed. Given that this study validated clinical improvement and safety, it serves as potential groundwork for pertinent future studies.
Water Extracts of Cruciferous Vegetable Seeds Inhibit Enzymic Browning of Fresh-Cut Mid Ribs of Romaine Lettuce
Authors: Androudis Efstratios , Gerasopoulos Athanasios , Koukounaras Athanasios , Siomos Anastasios S. , Gerasopoulos Dimitrios
Published: May 2024

Enzymatic browning, occurring on the cut surfaces of many popular fresh-cut fruit and vegetables due to wounding and the activity of endogenous polyphenyloxidase enzymes, is considered as the main reason for their rejection by consumers. In this study, water extracts were obtained from seeds of cabbage, sinapis, and wild rocket at 10 and 20% w/w seed:water ratios (SWE) and analyzed for total phenolic compounds (TPC) and antioxidant capacity (AC). The extract was then applied on cut surfaces of mid rib segments of lettuce leaves for 1 or 3 min. The segments were stored at 7 °C for 14 days. The SWE’s inhibitory capacity on enzymatic browning were measured by CIELAB color coordinates L* a* and b* and expressed as second derivatives, their % inhibition and different indices. An additional visual acceptance measurement and calculation of shelf life was also performed. The seed extracts of cabbage at 10–20% and wild rocket at 20% showed the highest anti-browning efficacy (comparable to 25 mM potassium metabisulfite control) along with TPC and AC. A high % of seed:water extract and increased exposure time led to a considerable increase in shelf life, visual score, % inhibition of browning or whitening index of the extracts of all seed sources. Chromatometric outcome data clearly showed that the visual data were more accurate than the chromatometric procedure (L*, a*, b* values, their derives ΔE, h°, C, Δh° and ΔC or calculated indices), although the latter could detect the differing degrees of browning development or its inhibition in treated and control segments during storage.
Insights into the PYR/PYL/RCAR Gene Family in Pomegranates (Punica granatum L.): A Genome-Wide Study on Identification, Evolution, and Expression Analysis
Authors: Yin Ke , Cheng Fan , Ren Hongfang , Huang Jingyi , Zhao Xueqing , Yuan Zhaohe
Published: May 2024

The response of plants to abiotic stress is intricately mediated by PYR/PYL/RCARs, key components within the ABA signal transduction pathway. Despite the widespread identification of PYL genes across diverse plant species, the evolutionary history and structural characteristics of these genes within the pomegranate (Punica granatum L.) remained unexplored. In this study, we uncovered, for the first time, 12 PgPYLs from the whole genome dataset of ‘Tunisia’, mapping them onto five chromosomes and categorizing them into three distinct subgroups (Group I, Group II, and Group III) through phylogenetic analysis. Detailed examination of the composition of these genes revealed similar conserved motifs and exon–intron structures among genes within the same subgroup. Fragment duplication emerged as the primary mechanism driving the amplification of the PYL gene family, as evidenced by intra-species collinearity analysis. Furthermore, inter-species collinearity analysis provided insights into potential evolutionary relationships among the identified PgPYL genes. Cis-acting element analysis revealed a rich repertoire of stress and hormone response elements within the promoter region of PgPYLs, emphasizing their putative roles in diverse signaling pathways. Upon treatment with 100 μmol/L ABA, we investigated the expression patterns of the PgPYL gene family, and the qRT-PCR data indicated a significant up-regulation in the majority of PYL genes. This suggested an active involvement of PgPYL genes in the plant’s response to exogenous ABA. Among them, PgPYL1 was chosen as a candidate gene to explore the function of the gene family, and the CDS sequence of PgPYL1 was cloned from pomegranate leaves with a full length of 657 bp, encoding 218 amino acids. Tobacco transient expression analysis demonstrated a consistent trend in the expression levels of pBI121-PgPYL1 and the related genes of the ABA signaling pathway, both of which increased initially before declining. This study not only contributes to the elucidation of the genomic and structural attributes of PgPYL genes but also provides a foundation for understanding their potential functions in stress responses. The identified conserved motifs, evolutionary relationships, and expression patterns under ABA treatment pave the way for further research into the PgPYL gene family’s role in pomegranate biology, offering valuable insights for future studies on genetic improvement and stress resilience in pomegranate cultivation.
Sustainable Characterization of Some Extracts of Origanum vulgare L. and Biosafety Evaluation Using Allium cepa Assay
Authors: Nicuță Daniela , Grosu Luminița , Alexa Irina-Claudia , Fînaru Adriana-Luminița
Published: May 2024

Origanum vulgare L. is ethnomedicinally valuable against various diseases. In Romania, attention for the oregano extracts such as infusions, decoctions, or tinctures, which are very popular among consumers, is constantly increasing, mainly as an important therapeutic alternative. Therefore, this study was undertaken to evaluate the comparative cytotoxic and genotoxic effects of aqueous and hydroalcoholic extracts of local oregano using a sustainable method such as the Allium cepa assay. Two aqueous oregano extracts obtained by infusion (I01) and decoction (D02) and two hydroalcoholic extracts (E03—water/ethanol 80:20 v/v; E04—water/ethanol 60:40 v/v) were used in this study. Before performing the Allium cepa test, a phytochemical screening carried out using fast and efficient analytical methods (electrometry, colorimetry, UV-Vis spectrometry, and high-performance thin-layer chromatography/HPTLC) allowed the qualitative differences in the chemical profile of the investigated oregano extracts to be highlighted. The aqueous and hydroalcoholic oregano extracts were tested on root meristems of Allium cepa and the cytotoxicity and genotoxicity parameters evaluated were the mitotic index (MI) and chromosomal aberration (CA). The results revealed a decrease in MI for each analyzed sample, with hydroethanolic extract E04 showing the most significant effect on MI (9.66%, 3 times less than that of the control sample), followed by the D02 sample obtained by decoction. Chromosomal aberrations such as the ana-telophase with bridges, expelled chromosomes, or delayed chromosomes were observed in all four extracts. The frequency of cells with CA was higher in the case of samples treated with hydroalcoholic extracts compared to aqueous extracts. The experimental extraction conditions influenced the mitotic index, the varieties of identified chromosomal aberrations, and their frequency. Therefore, based on the result obtained in this study, it may be concluded that the Oregano vulgare L. extracts present cytotoxic and genotoxic effects on onion cells. The Allium cepa assay proves to be an easy-to-handle method, with reliable results, minimal cost, and environmental friendliness for the evaluation of the cytotoxic and genotoxic effects of oregano extracts.
Determinants of Remuneration Committee Chairman’s Pay: Evidence from the UK
Authors: Shiyyab Fadi Shehab
Published: May 2024

This study investigates the association between the compensation of Remuneration Committee Chairpersons (RCCs) and their characteristics. Utilizing data from firms listed on the UK FTSE350 index between 2010 and 2020, the research unveils that RCC remuneration is influenced by factors such as observable efforts, time commitment, and accumulated experience. Notably, the analysis reveals a substantial gender gap in RCCs’ pay. The results suggest that the contractual pricing of individual director-level attributes plays a role in explaining disparities in compensation for roles with similar responsibilities. Furthermore, the study sheds light on the intricate process of determining compensation within the directorial hierarchy. It delves into how differences in pay among individuals occupying similar positions across various companies can be elucidated by the distinct attributes and qualifications of each individual. Ultimately, the findings advocate for a nuanced examination of directorial roles, highlighting the necessity of distinguishing between different director roles rather than treating them as a homogeneous entity.
Peripheral Blood Gene Expression Profiling Reveals Molecular Pathways Associated with Cervical Artery Dissection
Authors: Shlapakova Polina S. , Dobrynina Larisa A. , Kalashnikova Ludmila A. , Gubanova Mariia V. , Danilova Maria S. , Gnedovskaya Elena V. , Grigorenko Anastasia P. , Gusev Fedor E. , Manakhov Andrey D. , Rogaev Evgeny I.
Published: May 2024

Cervical artery dissection (CeAD) is the primary cause of ischemic stroke in young adults. Monogenic heritable connective tissue diseases account for fewer than 5% of cases of CeAD. The remaining sporadic cases have known risk factors. The clinical, radiological, and histological characteristics of systemic vasculopathy and undifferentiated connective tissue dysplasia are present in up to 70% of individuals with sporadic CeAD. Genome-wide association studies identified CeAD-associated genetic variants in the non-coding genomic regions that may impact the gene transcription and RNA processing. However, global gene expression profile analysis has not yet been carried out for CeAD patients. We conducted bulk RNA sequencing and differential gene expression analysis to investigate the expression profile of protein-coding genes in the peripheral blood of 19 CeAD patients and 18 healthy volunteers. This was followed by functional annotation, heatmap clustering, reports on gene–disease associations and protein–protein interactions, as well as gene set enrichment analysis. We found potential correlations between CeAD and the dysregulation of genes linked to nucleolar stress, senescence-associated secretory phenotype, mitochondrial malfunction, and epithelial–mesenchymal plasticity.
MEF2D Functions as a Tumor Suppressor in Breast Cancer
Authors: Wang Xiaoxia , Shen He , Chen Yanmin , Zhang Yali , Wang Jianmin , Liu Song , Xu Bo , Wang Hai , Frangou Costa , Zhang Jianmin
Published: May 2024

The myocyte enhancer factor 2 (MEF2) gene family play fundamental roles in the genetic programs that control cell differentiation, morphogenesis, proliferation, and survival in a wide range of cell types. More recently, these genes have also been implicated as drivers of carcinogenesis, by acting as oncogenes or tumor suppressors depending on the biological context. Nonetheless, the molecular programs they regulate and their roles in tumor development and progression remain incompletely understood. The present study evaluated whether the MEF2D transcription factor functions as a tumor suppressor in breast cancer. The knockout of the MEF2D gene in mouse mammary epithelial cells resulted in phenotypic changes characteristic of neoplastic transformation. These changes included enhanced cell proliferation, a loss of contact inhibition, and anchorage-independent growth in soft agar, as well as the capacity for tumor development in mice. Mechanistically, the knockout of MEF2D induced the epithelial-to-mesenchymal transition (EMT) and activated several oncogenic signaling pathways, including AKT, ERK, and Hippo-YAP. Correspondingly, a reduced expression of MEF2D was observed in human triple-negative breast cancer cell lines, and a low MEF2D expression in tissue samples was found to be correlated with a worse overall survival and relapse-free survival in breast cancer patients. MEF2D may, thus, be a putative tumor suppressor, acting through selective gene regulatory programs that have clinical and therapeutic significance.
Tumor versus Tumor Cell Targeting in Metal-Based Nanoparticles for Cancer Theranostics
Authors: Urbano-Gámez Jesús David , Guzzi Cinzia , Bernal Manuel , Solivera Juan , Martínez-Zubiaurre Iñigo , Caro Carlos , García-Martín María Luisa
Published: May 2024

The application of metal-based nanoparticles (mNPs) in cancer therapy and diagnostics (theranostics) has been a hot research topic since the early days of nanotechnology, becoming even more relevant in recent years. However, the clinical translation of this technology has been notably poor, with one of the main reasons being a lack of understanding of the disease and conceptual errors in the design of mNPs. Strikingly, throughout the reported studies to date on in vivo experiments, the concepts of “tumor targeting” and “tumor cell targeting” are often intertwined, particularly in the context of active targeting. These misconceptions may lead to design flaws, resulting in failed theranostic strategies. In the context of mNPs, tumor targeting can be described as the process by which mNPs reach the tumor mass (as a tissue), while tumor cell targeting refers to the specific interaction of mNPs with tumor cells once they have reached the tumor tissue. In this review, we conduct a critical analysis of key challenges that must be addressed for the successful targeting of either tumor tissue or cancer cells within the tumor tissue. Additionally, we explore essential features necessary for the smart design of theranostic mNPs, where ‘smart design’ refers to the process involving advanced consideration of the physicochemical features of the mNPs, targeting motifs, and physiological barriers that must be overcome for successful tumor targeting and/or tumor cell targeting.
Extracellular Vesicles Generated by Mesenchymal Stem Cells in Stirred Suspension Bioreactors Promote Angiogenesis in Human-Brain-Derived Endothelial Cells
Authors: Phelps Jolene , Hart David A. , Mitha Alim P. , Duncan Neil A. , Sen Arindom
Published: May 2024

Interrupted blood flow in the brain due to ischemic injuries such as ischemic stroke or traumatic brain injury results in irreversible brain damage, leading to cognitive impairment associated with inflammation, disruption of the blood–brain barrier (BBB), and cell death. Since the BBB only allows entry to a small class of drugs, many drugs used to treat ischemia in other tissues have failed in brain-related disorders. The administration of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) has shown promise in improving the functional recovery of the brain following cerebral ischemia by inducing blood vessel formation. To facilitate such a treatment approach, it is necessary to develop bioprocesses that can produce therapeutically relevant MSC-EVs in a reproducible and scalable manner. This study evaluated the feasibility of using stirred suspension bioreactors (SSBs) to scale-up the serum-free production of pro-angiogenic MSC-EVs under clinically relevant physioxic conditions. It was found that MSCs grown in SSBs generated EVs that stimulated angiogenesis in cerebral microvascular endothelial cells, supporting the use of SSBs to produce MSC-EVs for application in cerebral ischemia. These properties were impaired at higher cell confluency, outlining the importance of considering the time of harvest when developing bioprocesses to manufacture EV populations.
Interaction between Enrofloxacin and Three Essential Oils (Cinnamon Bark, Clove Bud and Lavender Flower)—A Study on Multidrug-Resistant Escherichia coli Strains Isolated from 1-Day-Old Broiler Chickens
Authors: Zych Sławomir , Adaszyńska-Skwirzyńska Michalina , Szewczuk Małgorzata Anna , Szczerbińska Danuta
Published: May 2024

Avian pathogenic Escherichia coli (APEC) causes a variety of infections outside the intestine. The treatment of these infections is becoming increasingly difficult due to the emergence of multi-drug resistant (MDR) strains, which can also be a direct or indirect threat to humans as consumers of poultry products. Therefore, alternative antimicrobial agents are being sought, which could be essential oils, either administered individually or in interaction with antibiotics. Sixteen field isolates of E. coli (originating from 1-day-old broilers) and the ATCC 25922 reference strain were tested. Commercial cinnamon bark, clove bud, lavender flower essential oils (EOs) and enrofloxacin were selected to assess the sensitivity of the selected E. coli strains to antimicrobial agents. The checkerboard method was used to estimate the individual minimum inhibitory concentration (MIC) for each antimicrobial agent as well as to determine the interactions between the selected essential oil and enrofloxacin. In the case of enrofloxacin, ten isolates were resistant at MIC ≥ 2 μg/mL, three were classified as intermediate (0.5–1 μg/mL) and three as sensitive at ≤0.25 μg/mL. Regardless of the sensitivity to enrofloxacin, the MIC for cinnamon EO was 0.25% v/v and for clove EO was 0.125% v/v. All MDR strains had MIC values for lavender EO of 1% v/v, while drug-sensitive isolates had MIC of 0.5% v/v. Synergism between enrofloxacin and EO was noted more frequently in lavender EO (82.35%), followed by cinnamon EO (64.7%), than in clove EO (47.1%). The remaining cases exhibited additive effects. Owing to synergy, the isolates became susceptible to enrofloxacin at an MIC of ≤8 µg/mL. A time–kill study supports these observations. Cinnamon and clove EOs required for up to 1 h and lavender EO for up to 4 h to completely kill a multidrug-resistant strain as well as the ATCC 25922 reference strain of E. coli. Through synergistic or additive effects, blends with a lower than MIC concentration of enrofloxacin mixed with a lower EO content required 6 ± 2 h to achieve a similar effect.
Molecular Mechanisms of Fetal and Neonatal Lupus: A Narrative Review of an Autoimmune Disease Transferal across the Placenta
Authors: Di Ludovico Armando , Rinaldi Marta , Mainieri Francesca , Di Michele Stefano , Girlando Virginia , Ciarelli Francesca , La Bella Saverio , Chiarelli Francesco , Attanasi Marina , Mauro Angela , Bizzi Emanuele , Brucato Antonio , Breda Luciana
Published: May 2024

This study, conducted by searching keywords such as “maternal lupus”, “neonatal lupus”, and “congenital heart block” in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.
Fine Mapping of Candidate Gene Controlling Anthocyanin Biosynthesis for Purple Peel in Solanum melongena L.
Authors: Xiao Kai , Tan Feng , Zhang Aidong , Zhou Yaru , Zhu Weimin , Bao Chonglai , Zha Dingshi , Wu Xuexia
Published: May 2024

Fruit color is an intuitive quality of horticultural crops that can be used as an evaluation criterion for fruit ripening and is an important factor affecting consumers’ purchase choices. In this study, a genetic population from the cross of green peel ‘Qidong’ and purple peel ‘8 guo’ revealed that the purple to green color of eggplant peel is dominant and controlled by a pair of alleles. Bulked segregant analysis (BSA), SNP haplotyping, and fine genetic mapping delimited candidate genes to a 350 kb region of eggplant chromosome 10 flanked by markers KA2381 and CA8828. One ANS gene (EGP22363) was predicted to be a candidate gene based on gene annotation and sequence alignment of the 350-kb region. Sequence analysis revealed that a single base mutation of ‘T’ to ‘C’ on the exon green peel, which caused hydrophobicity to become hydrophilic serine, led to a change in the three-level spatial structure. Additionally, EGP22363 was more highly expressed in purple peels than in green peels. Collectively, EGP22363 is a strong candidate gene for anthocyanin biosynthesis in purple eggplant peels. These results provide important information for molecular marker-assisted selection in eggplants, and a basis for analyzing the regulatory pathways responsible for anthocyanin biosynthesis in eggplants.
The CpG Island Methylator Phenotype Status in Synchronous and Solitary Primary Colorectal Cancers: Prognosis and Effective Therapeutic Drug Prediction
Authors: Weng Yun-Yun , Huang Ming-Yii
Published: May 2024

Synchronous colorectal cancer (sCRC) is characterized by the occurrence of more than one tumor within six months of detecting the first tumor. Evidence suggests that sCRC might be more common in the serrated neoplasia pathway, marked by the CpG island methylator phenotype (CIMP), than in the chromosomal instability pathway (CIN). An increasing number of studies propose that CIMP could serve as a potential epigenetic predictor or prognostic biomarker of sCRC. Therapeutic drugs already used for treating CIMP-positive colorectal cancers (CRCs) are reviewed and drug selections for sCRC patients are discussed.
A Review of Resistance Mechanisms to Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia
Authors: Wiśniewski Kamil , Puła Bartosz
Published: May 2024

Bruton’s Tyrosine Kinase (BTK) inhibitors have become one of the most vital drugs in the therapy of chronic lymphocytic leukemia (CLL). Inactivation of BTK disrupts the B-cell antigen receptor (BCR) signaling pathway, which leads to the inhibition of the proliferation and survival of CLL cells. BTK inhibitors (BTKi) are established as leading drugs in the treatment of both treatment-naïve (TN) and relapsed or refractory (R/R) CLL. Furthermore, BTKi demonstrate outstanding efficacy in high-risk CLL, including patients with chromosome 17p deletion, TP53 mutations, and unmutated status of the immunoglobulin heavy-chain variable region (IGHV) gene. Ibrutinib is the first-in-class BTKi which has changed the treatment landscape of CLL. Over the last few years, novel, covalent (acalabrutinib, zanubrutinib), and non-covalent (pirtobrutinib) BTKi have been approved for the treatment of CLL. Unfortunately, continuous therapy with BTKi contributes to the acquisition of secondary resistance leading to clinical relapse. In recent years, it has been demonstrated that the predominant mechanisms of resistance to BTKi are mutations in BTK or phospholipase Cγ2 (PLCG2). Some differences in the mechanisms of resistance to covalent BTKi have been identified despite their similar mechanism of action. Moreover, novel mutations resulting in resistance to non-covalent BTKi have been recently suggested. This article summarizes the clinical efficacy and the latest data regarding resistance to all of the registered BTKi.
Comprehensive Management of Stroke: From Mechanisms to Therapeutic Approaches
Authors: Arnalich-Montiel Ana , Burgos-Santamaría Alba , Pazó-Sayós Laia , Quintana-Villamandos Begoña
Published: May 2024

Acute ischemic stroke (AIS) is a challenging disease, which needs urgent comprehensive management. Endovascular thrombectomy (EVT), alone or combined with iv thrombolysis, is currently the most effective therapy for patients with acute ischemic stroke (AIS). However, only a limited number of patients are eligible for this time-sensitive treatment. Even though there is still significant room for improvement in the management of this group of patients, up until now there have been no alternative therapies approved for use in clinical practice. However, there is still hope, as clinical research with novel emerging therapies is now generating promising results. These drugs happen to stop or palliate some of the underlying molecular mechanisms involved in cerebral ischemia and secondary brain damage. The aim of this review is to provide a deep understanding of these mechanisms and the pathogenesis of AIS. Later, we will discuss the potential therapies that have already demonstrated, in preclinical or clinical studies, to improve the outcomes of patients with AIS.
Genome-Wide Epistatic Network Analyses of Semantic Fluency in Older Adults
Authors: Tan Qihua , Li Weilong , Nygaard Marianne , An Ping , Feitosa Mary , Wojczynski Mary K. , Zmuda Joseph , Arbeev Konstantin , Ukraintseva Svetlana , Yashin Anatoliy , Christensen Kaare , Mengel-From Jonas
Published: May 2024

Semantic fluency impairment has been attributed to a wide range of neurocognitive and psychiatric conditions, especially in the older population. Moderate heritability estimates on semantic fluency were obtained from both twin and family-based studies suggesting genetic contributions to the observed variation across individuals. Currently, effort in identifying the genetic variants underlying the heritability estimates for this complex trait remains scarce. Using the semantic fluency scale and genome-wide SNP genotype data from the Long Life Family Study (LLFS), we performed a genome-wide association study (GWAS) and epistasis network analysis on semantic fluency in 2289 individuals aged over 60 years from the American LLFS cohorts and replicated the findings in 1129 individuals aged over 50 years from the Danish LLFS cohort. In the GWAS, two SNPs with genome-wide significance (rs3749683, p = 2.52 × 10−8; rs880179, p = 4.83 × 10−8) mapped to the CMYAS gene on chromosome 5 were detected. The epistasis network analysis identified five modules as significant (4.16 × 10−5 < p < 7.35 × 10−3), of which two were replicated (p < 3.10 × 10−3). These two modules revealed significant enrichment of tissue-specific gene expression in brain tissues and high enrichment of GWAS catalog traits, e.g., obesity-related traits, blood pressure, chronotype, sleep duration, and brain structure, that have been reported to associate with verbal performance in epidemiological studies. Our results suggest high tissue specificity of genetic regulation of gene expression in brain tissues with epistatic SNP networks functioning jointly in modifying individual verbal ability and cognitive performance.
Unburned Tobacco Smoke Affects Neuroinflammation-Related Pathways in the Rat Mesolimbic System
Authors: Morosini Camilla , Vivarelli Fabio , Rullo Laura , Volino Emilia , Losapio Loredana Maria , Paolini Moreno , Romualdi Patrizia , Canistro Donatella , Candeletti Sanzio
Published: May 2024

Tobacco use disorder represents a significant public health challenge due to its association with various diseases. Despite awareness efforts, smoking rates remain high, partly due to ineffective cessation methods and the spread of new electronic devices. This study investigated the impact of prolonged nicotine exposure via a heat-not-burn (HnB) device on selected genes and signaling proteins involved in inflammatory processes in the rat ventral tegmental area (VTA) and nucleus accumbens (NAc), two brain regions associated with addiction to different drugs, including nicotine. The results showed a reduction in mRNA levels for PPARα and PPARγ, two nuclear receptors and anti-inflammatory transcription factors, along with the dysregulation of gene expression of the epigenetic modulator KDM6s, in both investigated brain areas. Moreover, decreased PTEN mRNA levels and higher AKT phosphorylation were detected in the VTA of HnB-exposed rats with respect to their control counterparts. Finally, significant alterations in ERK 1/2 phosphorylation were observed in both mesolimbic areas, with VTA decrease and NAc increase, respectively. Overall, the results suggest that HnB aerosol exposure disrupts intracellular pathways potentially involved in the development and maintenance of the neuroinflammatory state. Moreover, these data highlight that, similar to conventional cigarettes, HnB devices use affects specific signaling pathways shaping neuroinflammatory process in the VTA and NAc, thus triggering mechanisms that are currently considered as potentially relevant for the development of addictive behavior.
N-Terminal Amino Acid Affects the Translation Efficiency at Lower Temperatures in a Reconstituted Protein Synthesis System
Authors: Fuse-Murakami Tomoe , Matsumoto Rena , Kanamori Takashi
Published: May 2024

The Escherichia coli (E. coli)-based protein synthesis using recombinant elements (PURE) system is a cell-free protein synthesis system reconstituted from purified factors essential for E. coli translation. The PURE system is widely used for basic and synthetic biology applications. One of the major challenges associated with the PURE system is that the protein yield of the system varies depending on the protein. Studies have reported that the efficiency of translation is significantly affected by nucleotide and amino acid sequences, especially in the N-terminal region. Here, we investigated the inherent effect of various N-terminal sequences on protein synthesis using the PURE system. We found that a single amino acid substitution in the N-terminal region significantly altered translation efficiency in the PURE system, especially at low temperatures. This result gives us useful suggestions for the expression of the protein of interest in vitro and in vivo.
Puerarin Modulates Hepatic Farnesoid X Receptor and Gut Microbiota in High-Fat Diet-Induced Obese Mice
Authors: Yang Ching-Wei , Liu Hsuan-Miao , Chang Zi-Yu , Liu Geng-Hao , Chang Hen-Hong , Huang Po-Yu , Lee Tzung-Yan
Published: May 2024

Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver triglyceride, liver free fatty acid (FFA), and improved gut microbiota dysbiosis in obese mice. Puerarin’s beneficial metabolic effects were attenuated when farnesoid X receptor (FXR) was antagonized, suggesting FXR-mediated mechanisms. In hepatocytes, puerarin ameliorated high FFA-induced sterol regulatory element-binding protein (SREBP) 1 signaling, inflammation, and mitochondrial dysfunction in an FXR-dependent manner. In obese mice, puerarin reduced liver damage, regulated hepatic lipogenesis, decreased inflammation, improved mitochondrial function, and modulated mitophagy and ubiquitin-proteasome pathways, but was less effective in FXR knockout mice. Puerarin upregulated hepatic expression of FXR, bile salt export pump (BSEP), and downregulated cytochrome P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP), indicating modulation of bile acid synthesis and transport. Puerarin also restored gut microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila. This study demonstrates that puerarin effectively ameliorates metabolic disturbances and gut microbiota dysbiosis in obese mice, predominantly through FXR-dependent pathways. These findings underscore puerarin’s potential as a therapeutic agent for managing obesity and enhancing gut health, highlighting its dual role in improving metabolic functions and modulating microbial communities.
Experimental and Computational Studies on the Interaction of DNA with Hesperetin Schiff Base CuII Complexes
Authors: Pisanu Federico , Sykula Anna , Sciortino Giuseppe , Maseras Feliu , Lodyga-Chruscinska Elzbieta , Garribba Eugenio
Published: May 2024

The interactions with calf thymus DNA (CT-DNA) of three Schiff bases formed by the condensation of hesperetin with benzohydrazide (HHSB or L1H3), isoniazid (HIN or L2H3), or thiosemicarbazide (HTSC or L3H3) and their CuII complexes (CuHHSB, CuHIN, and CuHTSC with the general formula [CuLnH2(AcO)]) were evaluated in aqueous solution both experimentally and theoretically. UV–Vis studies indicate that the ligands and complexes exhibit hypochromism, which suggests helical ordering in the DNA helix. The intrinsic binding constants (Kb) of the Cu compounds with CT-DNA, in the range (2.3–9.2) × 106, from CuHTSC to CuHHSB, were higher than other copper-based potential drugs, suggesting that π–π stacking interaction due to the presence of the aromatic rings favors the binding. Thiazole orange (TO) assays confirmed that ligands and Cu complexes displace TO from the DNA binding site, quenching the fluorescence emission. DFT calculations allow for an assessment of the equilibrium between [Cu(LnH2)(AcO)] and [Cu(LnH2)(H2O)]+, the tautomer that binds CuII, amido (am) and not imido (im), and the coordination mode of HTSC (O−, N, S), instead of (O−, N, NH2). The docking studies indicate that the intercalative is preferred over the minor groove binding to CT-DNA with the order [Cu(L1H2am)(AcO)] > [Cu(L2H2am)(AcO)] ≈ TO ≈ L1H3 > [Cu(L3H2am)(AcO)], in line with the experimental Kb constants, obtained from the UV–Vis spectroscopy. Moreover, dockings predict that the binding strength of [Cu(L1H2am)(AcO)] is larger than [Cu(L1H2am)(H2O)]+. Overall, the results suggest that when different enantiomers, tautomers, and donor sets are possible for a metal complex, a computational approach should be recommended to predict the type and strength of binding to DNA and, in general, to macromolecules.
Is Cardiac Transplantation Still a Contraindication in Patients with Muscular Dystrophy-Related End-Stage Dilated Cardiomyopathy? A Systematic Review
Authors: Politano Luisa
Published: May 2024

Inherited muscular diseases (MDs) are genetic degenerative disorders typically caused by mutations in a single gene that affect striated muscle and result in progressive weakness and wasting in affected individuals. Cardiac muscle can also be involved with some variability that depends on the genetic basis of the MD (Muscular Dystrophy) phenotype. Heart involvement can manifest with two main clinical pictures: left ventricular systolic dysfunction with evolution towards dilated cardiomyopathy and refractory heart failure, or the presence of conduction system defects and serious life-threatening ventricular arrhythmias. The two pictures can coexist. In these cases, heart transplantation (HTx) is considered the most appropriate option in patients who are not responders to the optimized standard therapeutic protocols. However, cardiac transplant is still considered a relative contraindication in patients with inherited muscle disorders and end-stage cardiomyopathies. High operative risk related to muscle impairment and potential graft involvement secondary to the underlying myopathy have been the two main reasons implicated in the generalized reluctance to consider cardiac transplant as a viable option. We report an overview of cardiac involvement in MDs and its possible association with the underlying molecular defect, as well as a systematic review of HTx outcomes in patients with MD-related end-stage dilated cardiomyopathy, published so far in the literature.
Voltage Sensors Embedded in G Protein-Coupled Receptors
Authors: Tauber Merav , Ben-Chaim Yair
Published: May 2024

Some signaling processes mediated by G protein-coupled receptors (GPCRs) are modulated by membrane potential. In recent years, increasing evidence that GPCRs are intrinsically voltage-dependent has accumulated. A recent publication challenged the view that voltage sensors are embedded in muscarinic receptors. Herein, we briefly discuss the evidence that supports the notion that GPCRs themselves are voltage-sensitive proteins and an alternative mechanism that suggests that voltage-gated sodium channels are the voltage-sensing molecules involved in such processes.
AFB1 Toxicity in Human Food and Animal Feed Consumption: A Review of Experimental Treatments and Preventive Measures
Authors: Pożarska Agnieszka , Karpiesiuk Krzysztof , Kozera Wojciech , Czarnik Urszula , Dąbrowski Michał , Zielonka Łukasz
Published: May 2024

Aims: The current review aims to outline and summarize the latest research on aflatoxin, with research studies describing natural, herbal and chemical compound applications in animal (pig) models and in vitro cellular studies. Aflatoxin, a carcinogenic toxin metabolite, is produced by Aspergillus flavus in humid environments, posing a threat to human health and crop production. The current treatment involves the prevention of exposure to aflatoxin and counteracting its harmful toxic effects, enabling survival and research studies on an antidote for aflatoxin. Objectives: To summarize current research prospects and to outline the influence of aflatoxin on animal forage in farm production, food and crop processing. The research application of remedies to treat aflatoxin is undergoing development to pinpoint biochemical pathways responsible for aflatoxin effects transmission and actions of treatment. Significance: To underline the environmental stress of aflatoxin on meat and dairy products; to describe clinical syndromes associated with aflatoxicosis on human health that are counteracted with proposed treatment and preventive interventions. To understand how to improve the health of farm animals with feed conditions.
The Synthesis and Analysis of the Cytotoxicity of Al2O3-Supported Silver Nanoparticles Prepared by the Plasma Chemical Process Initiated by Pulsed MW Radiation in the Al2O3–Ag Powder Mixtures
Authors: Skvortsova Nina N. , Akhmadullina Nailya S. , Vafin Ildar Yu. , Obraztsova Ekaterina A. , Hrytseniuk Yanislav S. , Nikandrova Arina A. , A. Lukianov Dmitrii , Gayanova Tatiana E. , Voronova Elena V. , Shishilov Oleg N. , Stepakhin Vladimir D.
Published: May 2024

An original plasma chemical process initiated by microwave discharge in a mixture of metal and dielectric powders was applied to prepare specific materials, which consisted of microsized spherical particles of aluminum oxide covered with silver nanoparticles. The prepared materials are highly uniform in shape, size distribution, and composition. Their cytotoxicity was investigated using the human cell lines MCF7, HEK293T, A549, and VA-13 and the bacterial strains E. coli JW5503 (ΔtolC) and E. coli K12. Their cytotoxicity was found not to exceed the cytotoxicity of the starting materials. Thus, the prepared materials can be considered highly promising for catalysis and biotechnology applications.